User login
Longitudinal Erythronychia Manifesting With Pain and Cold Sensitivity
The Diagnosis: Glomangiomyoma
The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.1 They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.2 Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.7
Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.8 With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.11,12
There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.13
While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.16 The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.18 One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.13 On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.20
A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.2 It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.2 The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.21 In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.22 Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.21 In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.8 Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.23
Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.25 On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.26
Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.28 Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.28 Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.27 They typically are positive for α-smooth muscle actin and caldesmon on immunostaining.
Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.31 These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.31 On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.31,32
- Gombos Z, Zhang PJ. Glomus tumor. Arch Pathol Lab Med. 2008;132: 1448-1452. doi:10.5858/2008-132-1448-gt
- Hare AQ, Rich P. Nail tumors. Dermatol Clin. 2021;39:281-292. doi:10.1016/j.det.2020.12.007
- Hazani R, Houle JM, Kasdan ML, et al. Glomus tumors of the hand. Eplasty. 2008;8:E48.
- Hwang JK, Lipner SR. Blue nail discoloration: literature review and diagnostic algorithms. Am J Clin Dermatol. 2023;24:419-441. doi:10.1007/s40257-023-00768-6
- Lipner SR, Scher RK. Longitudinal erythronychia of the fingernail. JAMA Dermatol. 2016;152:1271-1272. doi:10.1001/jamadermatol.2016.2747
- Jellinek NJ, Lipner SR. Longitudinal erythronychia: retrospective single-center study evaluating differential diagnosis and the likelihood of malignancy. Dermatol Surg. 2016;42:310-319. doi:10.1097 /DSS.0000000000000594
- Lipner SR, Scher RK. Subungual glomus tumors: underrecognized clinical findings in neurofibromatosis 1. J Am Acad Dermatol. 2021;84:E269. doi:10.1016/j.jaad.2020.08.129
- Dhami A, Vale SM, Richardson ML, et al. Comparing ultrasound with magnetic resonance imaging in the evaluation of subungual glomus tumors and subungual myxoid cysts. Skin Appendage Disord. 2023;9:262-267. doi:10.1159/000530397
- Baek HJ, Lee SJ, Cho KH, et al. Subungual tumors: clinicopathologic correlation with US and MR imaging findings. Radiographics. 2010;30:1621-1636. doi:10.1148/rg.306105514
- Patel T, Meena V, Meena P. Hand and foot glomus tumors: significance of MRI diagnosis followed by histopathological assessment. Cureus. 2022;14:E30038. doi:10.7759/cureus.30038
- Mravic M, LaChaud G, Nguyen A, et al. Clinical and histopathological diagnosis of glomus tumor: an institutional experience of 138 cases. Int J Surg Pathol. 2015;23:181-188. doi:10.1177/1066896914567330
- Folpe AL, Fanburg-Smith JC, Miettinen M, et al. Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors. Am J Surg Pathol. 2001;25:1-12. doi:10.1097/00000478-200101000-00001
- Calduch L, Monteagudo C, Martínez-Ruiz E, et al. Familial generalized multiple glomangiomyoma: report of a new family, with immunohistochemical and ultrastructural studies and review of the literature. Pediatr Dermatol. 2002;19:402-408. doi:10.1046/j.1525-1470.2002.00114.x
- Mentzel T, Hügel H, Kutzner H. CD34-positive glomus tumor: clinicopathologic and immunohistochemical analysis of six cases with myxoid stromal changes. J Cutan Pathol. 2002;29:421-425. doi:10.1034 /j.1600-0560.2002.290706.x
- Kang TW, Lee KH, Park CJ. A case of subungual glomangiomyoma with myxoid stromal change. Korean J Dermatol. 2008;46:550-553.
- Wollstein A, Wollstein R. Subungual glomangiomyoma—a case report. Hand Surg. 2012;17:271-273. doi:10.1142/S021881041272032X
- Aqil N, Gallouj S, Moustaide K, et al. Painful tumors in a patient with neurofibromatosis type 1: a case report. J Med Case Rep. 2018;12:319. doi:10.1186/s13256-018-1847-0
- Demirdag HG, Akay BN, Kirmizi A, et al. Subungual glomangiomyoma. J Am Podiatr Med Assoc. 2020;110:Article_13. doi:10.7547/19-051
- Vega SML, Ruiz SJA, Ramírez CS, et al. Subungual glomangiomyoma: a case report. Dermatol Cosmet Med Quir. 2022;20:258-262.
- Chalise S, Jha A, Neupane PR. Glomangiomyoma of uncertain malignant potential in the urinary bladder: a case report. JNMA J Nepal Med Assoc. 2021;59:719-722. doi:10.31729/jnma.5388
- de Berker D, Goettman S, Baran R. Subungual myxoid cysts: clinical manifestations and response to therapy. J Am Acad Dermatol. 2002;46:394-398. doi:10.1067/mjd.2002.119652
- Gupta MK, Lipner SR. Transillumination for improved diagnosis of digital myxoid cysts. Cutis. 2020;105:82.
- Fernandez-Flores A, Saeb-Lima M. Mucin as a diagnostic clue in dermatopathology. J Cutan Pathol. 2016;43:1005-1016. doi:10.1111/cup.12782
- Choi R, Kim SR, Glusac EJ, et al. Subungual neuroma masquerading as green nail syndrome. JAAD Case Rep. 2022;20:17-19. doi:10.1016 /j.jdcr.2021.11.025
- Rashid RM, Rashid RM, Thomas V. Subungal traumatic neuroma. J Am Acad Dermatol. 2010;63:E7-E8. doi:10.1016/j.jaad.2010.01.028
- Whitehouse HJ, Urwin R, Stables G. Traumatic subungual neuroma. Clin Exp Dermatol. 2018;43:65-66. doi:10.1111/ced.13247
- Lipner SR, Ko D, Husain S. Subungual leiyomyoma presenting as erythronychia: case report and review of the literature. J Drugs Dermatol. 2019;18:465-467.
- Taleb E, Saldías C, Gonzalez S, et al. Sonographic characteristics of leiomyomatous tumors of skin and nail: a case series. Dermatol Pract Concept. 2022;12:e2022082. doi:10.5826/dpc.1203a82
- Baran R, Requena L, Drapé JL. Subungual angioleiomyoma masquerading as a glomus tumour. Br J Dermatol. 2000;142:1239-1241. doi:10.1046/ j.1365-2133.2000.03560.x
- Watabe D, Sakurai E, Mori S, et al. Subungual angioleiomyoma. Indian J Dermatol Venereol Leprol. 2017;83:74-75. doi:10.4103/0378-6323 .185045
- Jha AK, Sinha R, Kumar A, et al. Spiradenoma causing longitudinal splitting of the nail. Clin Exp Dermatol. 2016;41:754-756. doi:10.1111 /ced.12886
- Leach BC, Graham BS. Papular lesion of the proximal nail fold. eccrine spiradenoma. Arch Dermatol. 2004;140:1003-1008. doi:10.1001 /archderm.140.8.1003-a
The Diagnosis: Glomangiomyoma
The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.1 They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.2 Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.7
Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.8 With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.11,12
There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.13
While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.16 The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.18 One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.13 On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.20
A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.2 It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.2 The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.21 In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.22 Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.21 In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.8 Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.23
Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.25 On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.26
Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.28 Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.28 Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.27 They typically are positive for α-smooth muscle actin and caldesmon on immunostaining.
Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.31 These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.31 On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.31,32
The Diagnosis: Glomangiomyoma
The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.1 They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.2 Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.7
Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.8 With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.11,12
There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.13
While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.16 The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.18 One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.13 On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.20
A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.2 It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.2 The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.21 In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.22 Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.21 In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.8 Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.23
Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.25 On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.26
Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.28 Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.28 Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.27 They typically are positive for α-smooth muscle actin and caldesmon on immunostaining.
Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.31 These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.31 On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.31,32
- Gombos Z, Zhang PJ. Glomus tumor. Arch Pathol Lab Med. 2008;132: 1448-1452. doi:10.5858/2008-132-1448-gt
- Hare AQ, Rich P. Nail tumors. Dermatol Clin. 2021;39:281-292. doi:10.1016/j.det.2020.12.007
- Hazani R, Houle JM, Kasdan ML, et al. Glomus tumors of the hand. Eplasty. 2008;8:E48.
- Hwang JK, Lipner SR. Blue nail discoloration: literature review and diagnostic algorithms. Am J Clin Dermatol. 2023;24:419-441. doi:10.1007/s40257-023-00768-6
- Lipner SR, Scher RK. Longitudinal erythronychia of the fingernail. JAMA Dermatol. 2016;152:1271-1272. doi:10.1001/jamadermatol.2016.2747
- Jellinek NJ, Lipner SR. Longitudinal erythronychia: retrospective single-center study evaluating differential diagnosis and the likelihood of malignancy. Dermatol Surg. 2016;42:310-319. doi:10.1097 /DSS.0000000000000594
- Lipner SR, Scher RK. Subungual glomus tumors: underrecognized clinical findings in neurofibromatosis 1. J Am Acad Dermatol. 2021;84:E269. doi:10.1016/j.jaad.2020.08.129
- Dhami A, Vale SM, Richardson ML, et al. Comparing ultrasound with magnetic resonance imaging in the evaluation of subungual glomus tumors and subungual myxoid cysts. Skin Appendage Disord. 2023;9:262-267. doi:10.1159/000530397
- Baek HJ, Lee SJ, Cho KH, et al. Subungual tumors: clinicopathologic correlation with US and MR imaging findings. Radiographics. 2010;30:1621-1636. doi:10.1148/rg.306105514
- Patel T, Meena V, Meena P. Hand and foot glomus tumors: significance of MRI diagnosis followed by histopathological assessment. Cureus. 2022;14:E30038. doi:10.7759/cureus.30038
- Mravic M, LaChaud G, Nguyen A, et al. Clinical and histopathological diagnosis of glomus tumor: an institutional experience of 138 cases. Int J Surg Pathol. 2015;23:181-188. doi:10.1177/1066896914567330
- Folpe AL, Fanburg-Smith JC, Miettinen M, et al. Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors. Am J Surg Pathol. 2001;25:1-12. doi:10.1097/00000478-200101000-00001
- Calduch L, Monteagudo C, Martínez-Ruiz E, et al. Familial generalized multiple glomangiomyoma: report of a new family, with immunohistochemical and ultrastructural studies and review of the literature. Pediatr Dermatol. 2002;19:402-408. doi:10.1046/j.1525-1470.2002.00114.x
- Mentzel T, Hügel H, Kutzner H. CD34-positive glomus tumor: clinicopathologic and immunohistochemical analysis of six cases with myxoid stromal changes. J Cutan Pathol. 2002;29:421-425. doi:10.1034 /j.1600-0560.2002.290706.x
- Kang TW, Lee KH, Park CJ. A case of subungual glomangiomyoma with myxoid stromal change. Korean J Dermatol. 2008;46:550-553.
- Wollstein A, Wollstein R. Subungual glomangiomyoma—a case report. Hand Surg. 2012;17:271-273. doi:10.1142/S021881041272032X
- Aqil N, Gallouj S, Moustaide K, et al. Painful tumors in a patient with neurofibromatosis type 1: a case report. J Med Case Rep. 2018;12:319. doi:10.1186/s13256-018-1847-0
- Demirdag HG, Akay BN, Kirmizi A, et al. Subungual glomangiomyoma. J Am Podiatr Med Assoc. 2020;110:Article_13. doi:10.7547/19-051
- Vega SML, Ruiz SJA, Ramírez CS, et al. Subungual glomangiomyoma: a case report. Dermatol Cosmet Med Quir. 2022;20:258-262.
- Chalise S, Jha A, Neupane PR. Glomangiomyoma of uncertain malignant potential in the urinary bladder: a case report. JNMA J Nepal Med Assoc. 2021;59:719-722. doi:10.31729/jnma.5388
- de Berker D, Goettman S, Baran R. Subungual myxoid cysts: clinical manifestations and response to therapy. J Am Acad Dermatol. 2002;46:394-398. doi:10.1067/mjd.2002.119652
- Gupta MK, Lipner SR. Transillumination for improved diagnosis of digital myxoid cysts. Cutis. 2020;105:82.
- Fernandez-Flores A, Saeb-Lima M. Mucin as a diagnostic clue in dermatopathology. J Cutan Pathol. 2016;43:1005-1016. doi:10.1111/cup.12782
- Choi R, Kim SR, Glusac EJ, et al. Subungual neuroma masquerading as green nail syndrome. JAAD Case Rep. 2022;20:17-19. doi:10.1016 /j.jdcr.2021.11.025
- Rashid RM, Rashid RM, Thomas V. Subungal traumatic neuroma. J Am Acad Dermatol. 2010;63:E7-E8. doi:10.1016/j.jaad.2010.01.028
- Whitehouse HJ, Urwin R, Stables G. Traumatic subungual neuroma. Clin Exp Dermatol. 2018;43:65-66. doi:10.1111/ced.13247
- Lipner SR, Ko D, Husain S. Subungual leiyomyoma presenting as erythronychia: case report and review of the literature. J Drugs Dermatol. 2019;18:465-467.
- Taleb E, Saldías C, Gonzalez S, et al. Sonographic characteristics of leiomyomatous tumors of skin and nail: a case series. Dermatol Pract Concept. 2022;12:e2022082. doi:10.5826/dpc.1203a82
- Baran R, Requena L, Drapé JL. Subungual angioleiomyoma masquerading as a glomus tumour. Br J Dermatol. 2000;142:1239-1241. doi:10.1046/ j.1365-2133.2000.03560.x
- Watabe D, Sakurai E, Mori S, et al. Subungual angioleiomyoma. Indian J Dermatol Venereol Leprol. 2017;83:74-75. doi:10.4103/0378-6323 .185045
- Jha AK, Sinha R, Kumar A, et al. Spiradenoma causing longitudinal splitting of the nail. Clin Exp Dermatol. 2016;41:754-756. doi:10.1111 /ced.12886
- Leach BC, Graham BS. Papular lesion of the proximal nail fold. eccrine spiradenoma. Arch Dermatol. 2004;140:1003-1008. doi:10.1001 /archderm.140.8.1003-a
- Gombos Z, Zhang PJ. Glomus tumor. Arch Pathol Lab Med. 2008;132: 1448-1452. doi:10.5858/2008-132-1448-gt
- Hare AQ, Rich P. Nail tumors. Dermatol Clin. 2021;39:281-292. doi:10.1016/j.det.2020.12.007
- Hazani R, Houle JM, Kasdan ML, et al. Glomus tumors of the hand. Eplasty. 2008;8:E48.
- Hwang JK, Lipner SR. Blue nail discoloration: literature review and diagnostic algorithms. Am J Clin Dermatol. 2023;24:419-441. doi:10.1007/s40257-023-00768-6
- Lipner SR, Scher RK. Longitudinal erythronychia of the fingernail. JAMA Dermatol. 2016;152:1271-1272. doi:10.1001/jamadermatol.2016.2747
- Jellinek NJ, Lipner SR. Longitudinal erythronychia: retrospective single-center study evaluating differential diagnosis and the likelihood of malignancy. Dermatol Surg. 2016;42:310-319. doi:10.1097 /DSS.0000000000000594
- Lipner SR, Scher RK. Subungual glomus tumors: underrecognized clinical findings in neurofibromatosis 1. J Am Acad Dermatol. 2021;84:E269. doi:10.1016/j.jaad.2020.08.129
- Dhami A, Vale SM, Richardson ML, et al. Comparing ultrasound with magnetic resonance imaging in the evaluation of subungual glomus tumors and subungual myxoid cysts. Skin Appendage Disord. 2023;9:262-267. doi:10.1159/000530397
- Baek HJ, Lee SJ, Cho KH, et al. Subungual tumors: clinicopathologic correlation with US and MR imaging findings. Radiographics. 2010;30:1621-1636. doi:10.1148/rg.306105514
- Patel T, Meena V, Meena P. Hand and foot glomus tumors: significance of MRI diagnosis followed by histopathological assessment. Cureus. 2022;14:E30038. doi:10.7759/cureus.30038
- Mravic M, LaChaud G, Nguyen A, et al. Clinical and histopathological diagnosis of glomus tumor: an institutional experience of 138 cases. Int J Surg Pathol. 2015;23:181-188. doi:10.1177/1066896914567330
- Folpe AL, Fanburg-Smith JC, Miettinen M, et al. Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors. Am J Surg Pathol. 2001;25:1-12. doi:10.1097/00000478-200101000-00001
- Calduch L, Monteagudo C, Martínez-Ruiz E, et al. Familial generalized multiple glomangiomyoma: report of a new family, with immunohistochemical and ultrastructural studies and review of the literature. Pediatr Dermatol. 2002;19:402-408. doi:10.1046/j.1525-1470.2002.00114.x
- Mentzel T, Hügel H, Kutzner H. CD34-positive glomus tumor: clinicopathologic and immunohistochemical analysis of six cases with myxoid stromal changes. J Cutan Pathol. 2002;29:421-425. doi:10.1034 /j.1600-0560.2002.290706.x
- Kang TW, Lee KH, Park CJ. A case of subungual glomangiomyoma with myxoid stromal change. Korean J Dermatol. 2008;46:550-553.
- Wollstein A, Wollstein R. Subungual glomangiomyoma—a case report. Hand Surg. 2012;17:271-273. doi:10.1142/S021881041272032X
- Aqil N, Gallouj S, Moustaide K, et al. Painful tumors in a patient with neurofibromatosis type 1: a case report. J Med Case Rep. 2018;12:319. doi:10.1186/s13256-018-1847-0
- Demirdag HG, Akay BN, Kirmizi A, et al. Subungual glomangiomyoma. J Am Podiatr Med Assoc. 2020;110:Article_13. doi:10.7547/19-051
- Vega SML, Ruiz SJA, Ramírez CS, et al. Subungual glomangiomyoma: a case report. Dermatol Cosmet Med Quir. 2022;20:258-262.
- Chalise S, Jha A, Neupane PR. Glomangiomyoma of uncertain malignant potential in the urinary bladder: a case report. JNMA J Nepal Med Assoc. 2021;59:719-722. doi:10.31729/jnma.5388
- de Berker D, Goettman S, Baran R. Subungual myxoid cysts: clinical manifestations and response to therapy. J Am Acad Dermatol. 2002;46:394-398. doi:10.1067/mjd.2002.119652
- Gupta MK, Lipner SR. Transillumination for improved diagnosis of digital myxoid cysts. Cutis. 2020;105:82.
- Fernandez-Flores A, Saeb-Lima M. Mucin as a diagnostic clue in dermatopathology. J Cutan Pathol. 2016;43:1005-1016. doi:10.1111/cup.12782
- Choi R, Kim SR, Glusac EJ, et al. Subungual neuroma masquerading as green nail syndrome. JAAD Case Rep. 2022;20:17-19. doi:10.1016 /j.jdcr.2021.11.025
- Rashid RM, Rashid RM, Thomas V. Subungal traumatic neuroma. J Am Acad Dermatol. 2010;63:E7-E8. doi:10.1016/j.jaad.2010.01.028
- Whitehouse HJ, Urwin R, Stables G. Traumatic subungual neuroma. Clin Exp Dermatol. 2018;43:65-66. doi:10.1111/ced.13247
- Lipner SR, Ko D, Husain S. Subungual leiyomyoma presenting as erythronychia: case report and review of the literature. J Drugs Dermatol. 2019;18:465-467.
- Taleb E, Saldías C, Gonzalez S, et al. Sonographic characteristics of leiomyomatous tumors of skin and nail: a case series. Dermatol Pract Concept. 2022;12:e2022082. doi:10.5826/dpc.1203a82
- Baran R, Requena L, Drapé JL. Subungual angioleiomyoma masquerading as a glomus tumour. Br J Dermatol. 2000;142:1239-1241. doi:10.1046/ j.1365-2133.2000.03560.x
- Watabe D, Sakurai E, Mori S, et al. Subungual angioleiomyoma. Indian J Dermatol Venereol Leprol. 2017;83:74-75. doi:10.4103/0378-6323 .185045
- Jha AK, Sinha R, Kumar A, et al. Spiradenoma causing longitudinal splitting of the nail. Clin Exp Dermatol. 2016;41:754-756. doi:10.1111 /ced.12886
- Leach BC, Graham BS. Papular lesion of the proximal nail fold. eccrine spiradenoma. Arch Dermatol. 2004;140:1003-1008. doi:10.1001 /archderm.140.8.1003-a
A 38-year-old woman presented to our nail specialty clinic with a red line and associated pain on the left fourth fingernail of 2 and 3 years’ duration, respectively. The patient described the pain as throbbing, with sensitivity to pressure and cold. She noted that the nail grew slowly and would sometimes split at the distal edge. She did not recall any discrete trauma to the digit or nail. The patient was right-handed, making the symptoms less likely to be due to overuse from daily activities. She had received no prior treatment for these symptoms.
The patient’s medical history included iron deficiency as well as acne and eczema. She had no personal or family history of skin cancer. Physical examination of the affected digit and nail revealed a longitudinal red line and distal onycholysis. With contact dermoscopy, the red line blanched. Pressure applied using a #11 scalpel blade elicited pinpoint tenderness (positive Love test), and application of an ice pack caused pain (positive cold test). A radiograph of the left hand was negative for bone erosions, and magnetic resonance imaging showed a 0.3-cm subungual lesion at the level of the fourth distal phalanx. An excision of the nail unit was performed.
American Hunger Games: Food Insecurity Among the Military and Veterans
American Hunger Games: Food Insecurity Among the Military and Veterans
The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.
Analects by Confucius1
From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.
The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.2 The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.3
The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”4
As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.5
Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.5 US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.6 The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.7
Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.8
Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members.
I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive.
As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.1
Dawson MM. The Wisdom of Confucius: A Collection of the Ethical Sayings of Confucius and of his disciples. International Pocket Library; 1932.
National Defense Authorization Act for Fiscal Year 2020. 116th Cong (2019), Public Law 116-92. U.S. Government Printing Office. https://www.govinfo.gov/content/pkg/PLAW-116publ92/html/PLAW-116publ92.htm
Asch BJ, Rennane S, Trail TE, et al. Food insecurity among members of the armed forces and their dependents. RAND Corporation. January 3, 2023. Accessed September 22, 2025. https://www.rand.org/pubs/research_reports/RRA1230-1.html
US Department of Agriculture Economic Research Service. Food Security in the U.S.—Definitions of Food Security. US Department of Agriculture Economic Research Service. January 10, 2025. https://www.ers.usda.gov/topics/food-nutrition-assistance/food-security-in-the-us/definitions-of-food-security
Active military and veteran food insecurity. Feeding America. Accessed September 22, 2025. https://www.feedingamerica.org/hunger-in-america/food-insecurity-in-veterans
Pradun S. Find access to stop food insecurity in your community. VA News. September 19, 2025. Accessed September 22, 2025. https://news.va.gov/142733/find-access-stop-food-insecurity-your-community/
Cohen AJ, Dosa DM, Rudolph JL, et al. Risk factors for veteran food insecurity: findings from a National US Department of Veterans Affairs Food Insecurity Screener. Public Health Nutr. 2022;25:819-828. doi:10.1017/S1368980021004584
Chen C. VA and Rockefeller Foundation collaborate to access food for Veterans. VA News. September 5, 2023. Accessed September 22, 2025. https://news.va.gov/123228/va-rockefeller-foundation-expand-access-to-food/
The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.
Analects by Confucius1
From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.
The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.2 The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.3
The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”4
As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.5
Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.5 US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.6 The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.7
Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.8
Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members.
I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive.
As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.1
The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.
Analects by Confucius1
From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.
The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.2 The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.3
The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”4
As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.5
Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.5 US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.6 The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.7
Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.8
Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members.
I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive.
As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.1
Dawson MM. The Wisdom of Confucius: A Collection of the Ethical Sayings of Confucius and of his disciples. International Pocket Library; 1932.
National Defense Authorization Act for Fiscal Year 2020. 116th Cong (2019), Public Law 116-92. U.S. Government Printing Office. https://www.govinfo.gov/content/pkg/PLAW-116publ92/html/PLAW-116publ92.htm
Asch BJ, Rennane S, Trail TE, et al. Food insecurity among members of the armed forces and their dependents. RAND Corporation. January 3, 2023. Accessed September 22, 2025. https://www.rand.org/pubs/research_reports/RRA1230-1.html
US Department of Agriculture Economic Research Service. Food Security in the U.S.—Definitions of Food Security. US Department of Agriculture Economic Research Service. January 10, 2025. https://www.ers.usda.gov/topics/food-nutrition-assistance/food-security-in-the-us/definitions-of-food-security
Active military and veteran food insecurity. Feeding America. Accessed September 22, 2025. https://www.feedingamerica.org/hunger-in-america/food-insecurity-in-veterans
Pradun S. Find access to stop food insecurity in your community. VA News. September 19, 2025. Accessed September 22, 2025. https://news.va.gov/142733/find-access-stop-food-insecurity-your-community/
Cohen AJ, Dosa DM, Rudolph JL, et al. Risk factors for veteran food insecurity: findings from a National US Department of Veterans Affairs Food Insecurity Screener. Public Health Nutr. 2022;25:819-828. doi:10.1017/S1368980021004584
Chen C. VA and Rockefeller Foundation collaborate to access food for Veterans. VA News. September 5, 2023. Accessed September 22, 2025. https://news.va.gov/123228/va-rockefeller-foundation-expand-access-to-food/
Dawson MM. The Wisdom of Confucius: A Collection of the Ethical Sayings of Confucius and of his disciples. International Pocket Library; 1932.
National Defense Authorization Act for Fiscal Year 2020. 116th Cong (2019), Public Law 116-92. U.S. Government Printing Office. https://www.govinfo.gov/content/pkg/PLAW-116publ92/html/PLAW-116publ92.htm
Asch BJ, Rennane S, Trail TE, et al. Food insecurity among members of the armed forces and their dependents. RAND Corporation. January 3, 2023. Accessed September 22, 2025. https://www.rand.org/pubs/research_reports/RRA1230-1.html
US Department of Agriculture Economic Research Service. Food Security in the U.S.—Definitions of Food Security. US Department of Agriculture Economic Research Service. January 10, 2025. https://www.ers.usda.gov/topics/food-nutrition-assistance/food-security-in-the-us/definitions-of-food-security
Active military and veteran food insecurity. Feeding America. Accessed September 22, 2025. https://www.feedingamerica.org/hunger-in-america/food-insecurity-in-veterans
Pradun S. Find access to stop food insecurity in your community. VA News. September 19, 2025. Accessed September 22, 2025. https://news.va.gov/142733/find-access-stop-food-insecurity-your-community/
Cohen AJ, Dosa DM, Rudolph JL, et al. Risk factors for veteran food insecurity: findings from a National US Department of Veterans Affairs Food Insecurity Screener. Public Health Nutr. 2022;25:819-828. doi:10.1017/S1368980021004584
Chen C. VA and Rockefeller Foundation collaborate to access food for Veterans. VA News. September 5, 2023. Accessed September 22, 2025. https://news.va.gov/123228/va-rockefeller-foundation-expand-access-to-food/
American Hunger Games: Food Insecurity Among the Military and Veterans
American Hunger Games: Food Insecurity Among the Military and Veterans
Updates in Multiple Sclerosis Imaging
Updates in Multiple Sclerosis Imaging
Multiple sclerosis (MS) is a complex, chronic immune-mediated disease of the central nervous system characterized by focal inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI), first incorporated into the McDonald Criteria for the diagnosis of MS in 2001, is an integral tool in the diagnosis, prognosis, and therapeutic monitoring of people with MS (PwMS).1
MRI research in MS is rapidly expanding and offers insights into the pathophysiology of MS with important implications for the routine clinical care of PwMS. At the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting, the US Department of Veterans Affairs (VA) MS Centers of Excellence hosted an educational symposium highlighting MRI biomarkers in MS, including T2-lesions, chronic black holes (cBHs), brain atrophy, paramagnetic rim lesions (PRLs), and the central vein sign (CVS). The symposium also provided a brief overview of quantitative MRI techniques used to characterize MS lesion severity and research applications of these techniques. This clinical review summarizes the main points of that symposium with the goal of introducing key concepts to federal health care practitioners caring for PwMS.
MRI Biomarkers in MS
T2-lesions, Chronic Black Holes, and Brain Atrophy
Focal immune-mediated inflammation and demyelination in MS may be detected by MRI as hyperintense foci on T2-weighted (T2-w) imaging (eg, T2-w turbo spin echo or T2-w fluid attenuated inversion recovery sequences). These T2-lesions, critical for diagnosing MS, are typically ovoid and occur in the periventricular, juxtacortical, infratentorial spinal cord white matter (Figure 1A). T2-lesion number and volume show some association with disability and optic nerve.
Wattjes et al highlight 2 cases to demonstrate this point: a man aged 52 years with MS for 23 years and a woman aged 50 years with MS for 11 years. Despite having MS for a much shorter duration, the woman had worse disability due to a higher lesion number and volume.2 T2-lesion volume also impacts disability progression in PwMS. Gauthier et al compared the probability of progression in 3 women, all of whom were aged 39 years and had MS for 6 years. The profile with highest probability of disability progression had the highest quartile of T2-lesion volume.3 T2-lesion volume over 2 years correlates with worse scores on disability metrics such as the MS functional composite, paced auditory serial addition task, and brain volume.4 A 2024 systematic review and meta-analysis demonstrated that T2-lesion volume is significantly correlated with clinical disability in PwMS.5
Select T2-lesions are also hypointense on T1-w spin echo images and are known as cBHs (Figure 1B). Histologically, T2-lesions with cBHs have more severe architectural disruption than those without cBHs.6 cBH number and volume are significantly correlated with disability, regardless of the degree of hypointensity on T1-w imaging.5,7 A 10-year longitudinal study demonstrated that cBHs were associated with disease progression after 5 years while T2-lesion volume was not, indicating that cBHs may be a more accurate predictor of disability.8
Brain atrophy, another imaging biomarker of MS, affects both the cerebral white and gray matter. White matter fraction (the volume of white matter relative to the intracranial compartment volume) and gray matter fraction (the volume of gray matter relative to the intracranial compartment) are significantly lower among PwMS compared with healthy controls. In addition, gray matter fraction is lower among patients with primary and secondary progressive MS compared with those with relapsing-remitting MS, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS). Gray matter fraction is also correlated with several motor and cognitive disability indices.9
Paramagnetic Rim Lesions
Neurologic worsening in PwMS occurs by 2 distinct mechanisms: relapse-associated worsening, a stepwise worsening of symptoms due to incomplete recovery following a relapse; and progression independent of relapse activity (PIRA), which is an irreversible neurologic deterioration in the absence of clinical or radiological relapses.10 PIRA is associated with neurodegeneration and predominates in both primary and secondary progressive MS. However, recent data demonstrated that PIRA may contribute to as much as 50% of disability worsening in relapsing MS and occurs early in the RMS disease course.10,11 Current high-efficacy disease modifying therapy, such as ocrelizumab, are extraordinarily successful at preventing focal inflammation and relapses but are less effective for preventing the slow march of disability progression characterizing PIRA.12,13 The prevention of PIRA is therefore an unmet treatment need.
Chronic active lesions (CALs) are an important driver of PIRA. When an acute gadolinium-enhancing lesion develops in PwMS, there are 3 possible fates of this lesion. The lesion may become chronically inactive, remyelinate, or transition to CALs.14 The histopathologic signature of CALs is compartmentalized, low-grade inflammation behind an intact blood-brain barrier with evidence of both active and chronic components.15 CALs may be found not only in cerebral white matter but also in the cerebral cortex and spinal cord.16,17 Combined MRI and histopathological studies have shown that iron-laden microglia/macrophages can be detected by susceptibility-based MRI as a rim of paramagnetic signal surrounding select T2-lesions.19 These PRLs represent an in vivo imaging biomarker of CAL (Figure 1C). According to the North American Imaging in MS Cooperative (NAIMS) consensus criteria, a PRL must surround at least two-thirds of the outer edge of a T2-lesion, be visible in ≥ 2 consecutive MRI slices, and cannot be contrast enhancing.20
PRLs can be visualized on multiple susceptibility-based imaging methods, including multiecho derived R2*/T2*, phase maps, susceptibility-weighted imaging, and quantitative susceptibility mapping.21-23 Retrospective analyses have shown no significant differences in sensitivity across these imaging modalities.24 Although first visualized with 7T MRI, PRLs may also be detected by 1.5T and 3T MRI with comparable sensitivities.25-27 However, there remains a significant knowledge gap regarding the accuracy of each imaging modality. Systematic, prospectively designed studies are needed to ascertain the comparative value of each method.
The presence of PRL is a poor prognostic indicator. PwMS without PRLs have higher levels of disability, are more likely to progress, and demonstrate greater gray matter atrophy and cognitive dysfunction when compared with PwMS with PRLs.27-29 Lesions with PRL tend to slowly expand, exhibit greater demyelination, and have diminished white matter integrity.21,22,30
PRLs may also be used as a diagnostic tool. PRLs are highly specific for MS/CIS with a 99.7% specificity and 98.4% positive predictive value, although the sensitivity is limited to 24%.31 Taken together, these data indicate that the presence of a PRL substantially increases the likelihood of an MS/CIS diagnosis, whereas the absence of a PRL does not exclude these diagnoses.
Several unanswered questions remain: Why do select acute MS lesions transition to CALs? How may investigators utilize PRLs as outcome measures in future clinical trials? How should PRLs be incorporated into the routine care of PwMS? As the role of this imaging biomarker is clarified both in the research and clinical settings, clinicians caring for PwMS can expect to increasingly encounter the topic of PRLs in the near future.
Central Vein Sign
A CVS is defined by the presence of a central vessel within a demyelinating plaque (Figure 1D). As early as the 1820s, MS plaques on gross pathology were noted to follow the course of a vessel. Early histological studies reported that up to 91% of MS plaques had a central vessel present.32 Lesion formation is dependent on the movement of lymphocytes and other inflammatory cells from the systemic circulation across the blood brain barrier into the perivascular space, a privileged site where immune cells interact with antigen presenting cells to launch an inflammatory cascade and eventual demyelinating lesion.33
CVS can be visualized on 1.5T, 3T and 7T MRI. However, 7T MRI is superior to 3T in the detection of CVS, with 85% of MS lesions having CVS visible compared with 45% on 3T.34 With advances in 7T MRI, fluid attenuated inversion recovery and T2* susceptibility, weighted sequences can be overlaid, allowing simultaneous visualization of the vessel and the demyelinating lesion. With higher density of parenchymal veins in the periventricular regions, the CVS is most seen in lesions of this territory but can also be present in juxtacortical, thalamic and infratentorial lesions with decreasing prevalence as these approach the cortex.35
MS lesions are more likely to have CVS than T2 hyperintense white matter lesions of other causes, with a large study reporting 78% of MS lesions were CVS positive. Further, CVS positive lesions can be found across all MS phenotypes including relapsing remitting, primary progressive, and secondary progressive.35 The CVS is also specific to MS lesions and is an effective tool for differentiating MS lesions from other common causes of T2 hyperintense lesions including chronic ischemic white matter disease,36 migraines,37 neuromyelitis optica spectrum disorders,38,39 Susac syndrome,40 and systemic autoimmune diseases (Behcet disease, systemic lupus erythematosus, and antiphospholipid syndrome).41
With CVS emerging as a promising radiographic biomarker for MS, NAIMS issued a consensus statement on necessary properties of a CVS. These criteria included appearance of a thin hypointense line or small dot, visualized in ≥ 2 perpendicular planes, with diameter < 2 mm, and running partially or entirely through the center of the lesion. They also clarified that lesions < 3 mm, confluent lesions, lesions with multiple vessels present or poorly visualized lesions were excluded.42
A shared CVS definition was a necessary step toward routine use of CVS as a radiographic biomarker and its incorporation in the 2024 revised McDonald criteria.43 Remaining limitations including 7T MRI is primarily available in research settings and the lack of consensus on a diagnostic threshold. There have been many proposed methods, including a 40% cut off,44 60% cut off,45 and Select 3* or Select 6* methods.46 The goal of each method is to optimize sensitivity and specificity while not compromising efficiency of MRI review for both neurologists and radiologists.
The CVS has significant potential as a radiographic biomarker for MS and may allow the early stages of MS to be differentiated from other common causes of white matter lesions on MRI. However, it remains unclear whether CVS holds prognostic value for patients, if CVS is suggestive of differing underlying pathology, or if the presence of a CVS is dynamic over time. Progress in these areas is anticipated as CVS is incorporated into routine clinical practice.
Quantitative MRI Techniques
In the research setting, several imaging modalities can be used to quantify the degree of microstructural injury in PwMS. The goal of these methods is to identify and quantify myelin and axonal damage, the major drivers of neurodegeneration. Among these methods, diffusion-based imaging is a measure of the amount of diffusion or fluid mobility across the tissues of the brain.47 Diffusion-weighted imaging (DWI) yields several parametric maps including axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (Figure 2 A, B, and C). These parametric maps provide information on different directions of water molecules’ movements. Myelin surrounds the axons preventing water molecules diffusion perpendicular to axons (RD) while axonal content prevents water diffusion horizontal to the axons (AD).Thus, AD is considered more specific to axonal injury, whereas RD is specific to myelin content.48 A higher value of any of these metrics is associated with a higher degree of tissue injury.
Although sensitive to axonal and myelin injury, AD and RD computed from single b-shell DWI experience several limitations including being affected by nonpathologic factors such as fiber orientation, distribution, and crossing, and by various nonmyelin specific pathologies including fluid accumulation during inflammation, myelin sheath thickness, and axonal intactness.48 Several multi b-shell methods have been developed to overcome diffusion imaging limitations. For example, work at the Nashville VA MS Center of Excellence has focused on the use of the multicompartment diffusion MRI with spherical mean technique (SMT). This method removes the orientation dependency of the diffusion MRI signal, increasing the signal-to-noise ratio and reducing biases from fiber undulation, crossing, and dispersion.49 SMT generates the apparent axonal volume fraction (Vax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). Vax was previously validated in MS as a measure of axonal integrity.49
In terms of myelin, several other specific measures have been developed. Magnetization transfer ratio (MTR) is another measure of tissue integrity that has been validated as a measure of tissue injury in MS (Figure 2E).50,51 Zheng et al found that the percentage of lesions with low MTR was significantly higher among patients whose disease disability progressed compared with patients who did not.52Selective inversion recovery with quantitative magnetization transfer (SIR-qMT) was developed to account for the limitations of MTR, including its sensitivity to edema and axonal density.52 Germane to myelin measurements, SIR-qMT generates the macromolecular to free size ratio (PSR). PSR represents the ratio of protons bound to macromolecules (myelin) to free protons (Figure 2F). PSR is considered a marker of myelin integrity, with lower values correlating with disability severity and indicating higher tissue damage and lower myelin content. Previous studies from the Nashville VA MS Center of Excellence validated the use of SIR-qMT among patients with MS, CIS, RIS, and healthy controls.53
Quantitative MRI has several research applications in the field of MS. We demonstrated that PRL harbor a higher degree of myelin injury indicated by PSR compared with rimless lesions.54 These MRI techniques are also helpful to investigate tissues surrounding the lesions, called normal appearing white matter (NAWM). Using quantitative MRI techniques such as MTR,52 PSR,53 and Vax,49 investigators have demonstrated that NAWM is injured in PwMS, and proximal NAWM may have higher degree of tissue damage compared with distant NAWM.55
Anticipated Innovations and Challenges
In the field of quantitative MRI, several new techniques are being adopted. Researchers are developing techniques such as myelin water fraction which evaluates the interaction between water and protons to measure myelin content. This is considered an advancement as it takes into account edema resulting from MS injury.56 Another example is multicompartment diffusion imaging, such as standard model imaging,57 and neurite orientation dispersion and density imaging,58 which considers water as an additional compartment compared with the SMT derived Vax. For PRL identification, more advanced methodologic techniques are developing such quantitative susceptibility mapping (QSM), which can detect iron deposits that surround the lesions with relatively high sensitivity and specificity of identifying PRL.59
Despite these innovations, several challenges remain before possible incorporation into the clinical setting. These limitations include longer scan time, familiarity of clinicians in using these maps, higher financial cost, and the necessity of advanced imaging processing skills. Artificial intelligence is a promising tool that may overcome these challenges through creating automated processing pipelines and developing synthetic maps without the need for additional acquisition.60
Conclusions
MRI is the most important tool for diagnosing and treating PwMS. Imaging biomarkers such as T2-lesions, cBHs, brain atrophy, PRLs, and CVS provide insight into the disease’s pathogenesis and are invaluable for the accurate diagnosis and prognostication of MS. Quantitative MRI techniques, while not available in the clinical setting, are important tools for translational research that may help direct the development of future therapeutics. In the near future, clinicians caring for PwMS should expect to encounter these imaging biomarkers more frequently in the clinical setting, especially with the inclusion of PRLs and CVS in the next iteration of the McDonald diagnostic criteria.
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127. doi:10.1002/ana.1032
Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and monitoring of multiple sclerosis: an update. Clin Neuroradiol. 2015;25:157-165. doi:10.1007/s00062-015-0430-y
Gauthier SA, Mandel M, Guttmann CR, et al. Predicting short-term disability in multiple sclerosis. Neurology. 2007;68:2059-2065.doi:10.1212/01.wnl.0000264890.97479.b1
Rudick RA, Lee JC, Simon J, Fisher E. Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study. Ann Neurol. 2006;60:236-242. doi:10.1002/ana.20883
Nabizadeh F, Zafari R, Mohamadi M, et al. MRI features and disability in multiple sclerosis: a systematic review and meta-analysis. J Neuroradiol. 2024;51:24-37. doi:10.1016/j.neurad.2023.11.007
Bagnato F, Jeffries N, Richert ND, et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003;126:1782-1789. doi:10.1093/brain/awg182
Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014;85:1109-1115. doi:10.1136/jnnp-2013-306906
Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology. 2005;65:1526-1532. doi:10.1212/01.wnl.0000184471.83948.e0
Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64:247-254. doi:10.1002/ana.21423
Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145:3147-3161. doi:10.1093/brain/awac016
Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1132-1140. doi:10.1001/jamaneurol.2020.1568
Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. doi:10.1056/NEJMoa1601277
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220. doi:10.1056/NEJMoa1606468
Prineas JW, Kwon EE, Cho ES, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50:646-657. doi:10.1002/ana.1255
Kuhlmann T, Ludwin S, Prat A, Antel J, Brück W, Lassmann H. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 2017;133:13-24. doi:10.1007/s00401-016-1653-y
Pitt D, Boster A, Pei W, et al. Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging. Arch Neurol. 2010;67:812-818. doi:10.1001/archneurol.2010.148
Gilmore CP, Geurts JJ, Evangelou N, et al. Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Mult Scler. 2009;15:180-188. doi:10.1177/1352458508096876
Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210-218. doi:10.1111/j.1750-3639.2007.00064.x
Bagnato F, Hametner S, Yao B, et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134:3602-3615. doi:10.1093/brain/awr278
Bagnato F, Sati P, Hemond CC, et al. Imaging chronic active lesions in multiple sclerosis: a consensus statement. Brain. 2024;147:2913-2933. doi:10.1093/brain/awae013
Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017;133:25-42. doi:10.1007/s00401-016-1636-z
Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016;126:2597-2609. doi:10.1172/JCI86198
Gillen KM, Mubarak M, Park C, et al. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021;8:877-886. doi:10.1002/acn3.51338
Ng Kee Kwong KC, Mollison D, Meijboom R, et al. The prevalence of paramagnetic rim lesions in multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2021;16:e0256845. doi:10.1371/journal.pone.0256845
Absinta M, Sati P, Fechner A, et al. Identification of chronic active multiple sclerosis lesions on 3T MRI. AJNR Am J Neuroradiol. 2018;39:1233-1238. doi:10.3174/ajnr.A5660
Hemond CC, Reich DS, Dundamadappa SK. Paramagnetic rim lesions in multiple sclerosis: comparison of visualization at 1.5-T and 3-T MRI. AJR Am J Roentgenol. 2022;219:120-131. doi:10.2214/AJR.21.26777
Altokhis AI, Hibbert AM, Allen CM, et al. Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis. Mult Scler. 2022;28:2202-2211. doi:10.1177/13524585221114750
Choi S, Lake S, Harrison DM. Evaluation of the blood-brain barrier, demyelination, and neurodegeneration in paramagnetic rim lesions in multiple sclerosis on 7 tesla MRI. J Magn Reson Imaging. 2024;59:941-951. doi:10.1002/jmri.28847
Kazimuddin HF, Wang J, Hernandez B, et al. Paramagnetic rim lesions and their relationship with neurodegeneration and clinical disability at the time of multiple sclerosis diagnosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.
Rohm Z, Koch C, Kazimuddin H, et al. Longitudinal characterization of paramagnetic rim lesions in early multiple sclerosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.
Meaton I, Altokhis A, Allen CM, et al. Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis. Mult Scler. 2022;28:2212-2220. doi:10.1177/13524585221118677
Fog T. On the vessel-plaque relationships in the brain in multiple sclerosis. Acta Neurol Scand Suppl. 1964;40:9-15.
Ineichen BV, Okar SV, Proulx ST, et al. Perivascular spaces and their role in neuroinflammation. Neuron. 2022;110:3566-3581. doi:10.1016/j.neuron.2022.10.024
Tallantyre EC, Morgan PS, Dixon JE, et al. A comparison of 3T and 7T in the detection of small parenchymal veins within MS lesions. Invest Radiol. 2009;44:491-494. doi:10.1097/RLI.0b013e3181b4c144
Kilsdonk ID, Lopez-Soriano A, Kuijer JP, et al. Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics. J Neurol. 2014;261:1356-1364. doi:10.1007/s00415-014-7351-6
Tallantyre EC, Dixon JE, Donaldson I, et al. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011;76:534-539. doi:10.1212/WNL.0b013e31820b7630
Solomon AJ, Schindler MK, Howard DB, et al. “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol. 2015;3:82-87. doi:10.1002/acn3.273
Sinnecker T, Dörr J, Pfueller CF, et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012;79:708-714. doi:10.1212/WNL.0b013e3182648bc8
Kister I, Herbert J, Zhou Y, Ge Y. Ultrahigh-field MR (7 T) imaging of brain lesions in neuromyelitis optica. Mult Scler Int. 2013;2013:398259. doi:10.1155/2013/398259
Wuerfel J, Sinnecker T, Ringelstein EB, et al. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler. 2012;18:1592-1599. doi:10.1177/1352458512441270
Massacesi L. Perivenular distribution of white matter lesions evaluated by MRI can differentiate MS lesions from inflammatory small vessel diseases. Eur J Neurol. 2016;23:86. doi:10.1212/WNL.86.16_supplement.P6.121
Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12:714-722. doi:10.1038/nrneurol.2016.166
Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24:850-865. doi:10.1016/S1474-4422(25)00270-4
Mistry N, Dixon J, Tallantyre E, et al. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013;70:623-628. doi:10.1001/jamaneurol.2013.1405
Campion T, Smith RJP, Altmann DR, et al. FLAIR* to visualize veins in white matter lesions: a new tool for the diagnosis of multiple sclerosis? Eur Radiol. 2017;27:4257-4263. doi:10.1007/s00330-017-4822-z
Solomon AJ, Watts R, Ontaneda D, et al. Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm. Mult Scler. 2018;24:750-757. doi:10.1177/1352458517726383
Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI. J Neurol. 2002;249:875-883. doi:10.1007/s00415-002-0752-y
Song SK, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005;26:132-140. doi:10.1016/j.neuroimage.2005.01.028
Bagnato F, Franco G, Li H, et al. Probing axons using multi-compartmental diffusion in multiple sclerosis. Ann Clin Transl Neurol. 2019;6:1595-1605. doi:10.1002/acn3.50836
Filippi M, Cercignani M, Inglese M, et al. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology. 2001;56:304-311. doi:10.1212/wnl.56.3.304
Bagnato F. Clinical application of magnetization transfer imaging. In: Advanced Neuro MR Techniques and Applications. Elsevier; 2022:403-417. doi:10.1016/B978-0-12-822479-3.00041-5
Zheng Y, Lee JC, Rudick R, Fisher E. Long-term magnetization transfer ratio evolution in multiple sclerosis white matter lesions. J Neuroimaging. 2018;28:191-198. doi:10.1111/jon.12480
Bagnato F, Hametner S, Franco G, et al. Selective inversion recovery quantitative magnetization transfer brain MRI at 7T: clinical and postmortem validation in multiple sclerosis. J Neuroimaging. 2018;28:380-388. doi:10.1111/jon.12511
Clarke MA, Cheek R, Hernandez B, et al. Paramagnetic rim lesions and the central vein sign: characterizing multiple sclerosis imaging markers. J Neuroimaging. 2024;34:86-94. doi:10.1111/jon.13173
Clarke MA, Lakhani DA, Wen S, et al. Perilesional neurodegenerative injury in multiple sclerosis: relation to focal lesions and impact on disability. Mult Scler Relat Disord. 2021;49:102738. doi:10.1016/j.msard.2021.102738
Laule C, Moore GRW. Myelin water imaging to detect demyelination and remyelination and its validation in pathology. Brain Pathol. 2018;28:750-764. doi:10.1111/bpa.12645
Coelho S, Baete SH, Lemberskiy G, et al. Reproducibility of the standard model of diffusion in white matter on clinical MRI systems. Neuroimage. 2022;257:119290. doi:10.1016/j.neuroimage.2022.119290
Novikov DS, Veraart J, Jelescu IO, et al. Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI. Neuroimage. 2018;174:518-538. doi:10.1016/j.neuroimage.2018.03.006
Langkammer C, Liu T, Khalil M, et al. Quantitative susceptibility mapping in multiple sclerosis. Radiology. 2013;267:551-559. doi:10.1148/radiol.12120707
Collorone S, Coll L, Lorenzi M, et al. Artificial intelligence applied to MRI data to tackle key challenges in multiple sclerosis. Mult Scler. 2024;30:767-784. doi:10.1177/13524585241249422
Multiple sclerosis (MS) is a complex, chronic immune-mediated disease of the central nervous system characterized by focal inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI), first incorporated into the McDonald Criteria for the diagnosis of MS in 2001, is an integral tool in the diagnosis, prognosis, and therapeutic monitoring of people with MS (PwMS).1
MRI research in MS is rapidly expanding and offers insights into the pathophysiology of MS with important implications for the routine clinical care of PwMS. At the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting, the US Department of Veterans Affairs (VA) MS Centers of Excellence hosted an educational symposium highlighting MRI biomarkers in MS, including T2-lesions, chronic black holes (cBHs), brain atrophy, paramagnetic rim lesions (PRLs), and the central vein sign (CVS). The symposium also provided a brief overview of quantitative MRI techniques used to characterize MS lesion severity and research applications of these techniques. This clinical review summarizes the main points of that symposium with the goal of introducing key concepts to federal health care practitioners caring for PwMS.
MRI Biomarkers in MS
T2-lesions, Chronic Black Holes, and Brain Atrophy
Focal immune-mediated inflammation and demyelination in MS may be detected by MRI as hyperintense foci on T2-weighted (T2-w) imaging (eg, T2-w turbo spin echo or T2-w fluid attenuated inversion recovery sequences). These T2-lesions, critical for diagnosing MS, are typically ovoid and occur in the periventricular, juxtacortical, infratentorial spinal cord white matter (Figure 1A). T2-lesion number and volume show some association with disability and optic nerve.
Wattjes et al highlight 2 cases to demonstrate this point: a man aged 52 years with MS for 23 years and a woman aged 50 years with MS for 11 years. Despite having MS for a much shorter duration, the woman had worse disability due to a higher lesion number and volume.2 T2-lesion volume also impacts disability progression in PwMS. Gauthier et al compared the probability of progression in 3 women, all of whom were aged 39 years and had MS for 6 years. The profile with highest probability of disability progression had the highest quartile of T2-lesion volume.3 T2-lesion volume over 2 years correlates with worse scores on disability metrics such as the MS functional composite, paced auditory serial addition task, and brain volume.4 A 2024 systematic review and meta-analysis demonstrated that T2-lesion volume is significantly correlated with clinical disability in PwMS.5
Select T2-lesions are also hypointense on T1-w spin echo images and are known as cBHs (Figure 1B). Histologically, T2-lesions with cBHs have more severe architectural disruption than those without cBHs.6 cBH number and volume are significantly correlated with disability, regardless of the degree of hypointensity on T1-w imaging.5,7 A 10-year longitudinal study demonstrated that cBHs were associated with disease progression after 5 years while T2-lesion volume was not, indicating that cBHs may be a more accurate predictor of disability.8
Brain atrophy, another imaging biomarker of MS, affects both the cerebral white and gray matter. White matter fraction (the volume of white matter relative to the intracranial compartment volume) and gray matter fraction (the volume of gray matter relative to the intracranial compartment) are significantly lower among PwMS compared with healthy controls. In addition, gray matter fraction is lower among patients with primary and secondary progressive MS compared with those with relapsing-remitting MS, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS). Gray matter fraction is also correlated with several motor and cognitive disability indices.9
Paramagnetic Rim Lesions
Neurologic worsening in PwMS occurs by 2 distinct mechanisms: relapse-associated worsening, a stepwise worsening of symptoms due to incomplete recovery following a relapse; and progression independent of relapse activity (PIRA), which is an irreversible neurologic deterioration in the absence of clinical or radiological relapses.10 PIRA is associated with neurodegeneration and predominates in both primary and secondary progressive MS. However, recent data demonstrated that PIRA may contribute to as much as 50% of disability worsening in relapsing MS and occurs early in the RMS disease course.10,11 Current high-efficacy disease modifying therapy, such as ocrelizumab, are extraordinarily successful at preventing focal inflammation and relapses but are less effective for preventing the slow march of disability progression characterizing PIRA.12,13 The prevention of PIRA is therefore an unmet treatment need.
Chronic active lesions (CALs) are an important driver of PIRA. When an acute gadolinium-enhancing lesion develops in PwMS, there are 3 possible fates of this lesion. The lesion may become chronically inactive, remyelinate, or transition to CALs.14 The histopathologic signature of CALs is compartmentalized, low-grade inflammation behind an intact blood-brain barrier with evidence of both active and chronic components.15 CALs may be found not only in cerebral white matter but also in the cerebral cortex and spinal cord.16,17 Combined MRI and histopathological studies have shown that iron-laden microglia/macrophages can be detected by susceptibility-based MRI as a rim of paramagnetic signal surrounding select T2-lesions.19 These PRLs represent an in vivo imaging biomarker of CAL (Figure 1C). According to the North American Imaging in MS Cooperative (NAIMS) consensus criteria, a PRL must surround at least two-thirds of the outer edge of a T2-lesion, be visible in ≥ 2 consecutive MRI slices, and cannot be contrast enhancing.20
PRLs can be visualized on multiple susceptibility-based imaging methods, including multiecho derived R2*/T2*, phase maps, susceptibility-weighted imaging, and quantitative susceptibility mapping.21-23 Retrospective analyses have shown no significant differences in sensitivity across these imaging modalities.24 Although first visualized with 7T MRI, PRLs may also be detected by 1.5T and 3T MRI with comparable sensitivities.25-27 However, there remains a significant knowledge gap regarding the accuracy of each imaging modality. Systematic, prospectively designed studies are needed to ascertain the comparative value of each method.
The presence of PRL is a poor prognostic indicator. PwMS without PRLs have higher levels of disability, are more likely to progress, and demonstrate greater gray matter atrophy and cognitive dysfunction when compared with PwMS with PRLs.27-29 Lesions with PRL tend to slowly expand, exhibit greater demyelination, and have diminished white matter integrity.21,22,30
PRLs may also be used as a diagnostic tool. PRLs are highly specific for MS/CIS with a 99.7% specificity and 98.4% positive predictive value, although the sensitivity is limited to 24%.31 Taken together, these data indicate that the presence of a PRL substantially increases the likelihood of an MS/CIS diagnosis, whereas the absence of a PRL does not exclude these diagnoses.
Several unanswered questions remain: Why do select acute MS lesions transition to CALs? How may investigators utilize PRLs as outcome measures in future clinical trials? How should PRLs be incorporated into the routine care of PwMS? As the role of this imaging biomarker is clarified both in the research and clinical settings, clinicians caring for PwMS can expect to increasingly encounter the topic of PRLs in the near future.
Central Vein Sign
A CVS is defined by the presence of a central vessel within a demyelinating plaque (Figure 1D). As early as the 1820s, MS plaques on gross pathology were noted to follow the course of a vessel. Early histological studies reported that up to 91% of MS plaques had a central vessel present.32 Lesion formation is dependent on the movement of lymphocytes and other inflammatory cells from the systemic circulation across the blood brain barrier into the perivascular space, a privileged site where immune cells interact with antigen presenting cells to launch an inflammatory cascade and eventual demyelinating lesion.33
CVS can be visualized on 1.5T, 3T and 7T MRI. However, 7T MRI is superior to 3T in the detection of CVS, with 85% of MS lesions having CVS visible compared with 45% on 3T.34 With advances in 7T MRI, fluid attenuated inversion recovery and T2* susceptibility, weighted sequences can be overlaid, allowing simultaneous visualization of the vessel and the demyelinating lesion. With higher density of parenchymal veins in the periventricular regions, the CVS is most seen in lesions of this territory but can also be present in juxtacortical, thalamic and infratentorial lesions with decreasing prevalence as these approach the cortex.35
MS lesions are more likely to have CVS than T2 hyperintense white matter lesions of other causes, with a large study reporting 78% of MS lesions were CVS positive. Further, CVS positive lesions can be found across all MS phenotypes including relapsing remitting, primary progressive, and secondary progressive.35 The CVS is also specific to MS lesions and is an effective tool for differentiating MS lesions from other common causes of T2 hyperintense lesions including chronic ischemic white matter disease,36 migraines,37 neuromyelitis optica spectrum disorders,38,39 Susac syndrome,40 and systemic autoimmune diseases (Behcet disease, systemic lupus erythematosus, and antiphospholipid syndrome).41
With CVS emerging as a promising radiographic biomarker for MS, NAIMS issued a consensus statement on necessary properties of a CVS. These criteria included appearance of a thin hypointense line or small dot, visualized in ≥ 2 perpendicular planes, with diameter < 2 mm, and running partially or entirely through the center of the lesion. They also clarified that lesions < 3 mm, confluent lesions, lesions with multiple vessels present or poorly visualized lesions were excluded.42
A shared CVS definition was a necessary step toward routine use of CVS as a radiographic biomarker and its incorporation in the 2024 revised McDonald criteria.43 Remaining limitations including 7T MRI is primarily available in research settings and the lack of consensus on a diagnostic threshold. There have been many proposed methods, including a 40% cut off,44 60% cut off,45 and Select 3* or Select 6* methods.46 The goal of each method is to optimize sensitivity and specificity while not compromising efficiency of MRI review for both neurologists and radiologists.
The CVS has significant potential as a radiographic biomarker for MS and may allow the early stages of MS to be differentiated from other common causes of white matter lesions on MRI. However, it remains unclear whether CVS holds prognostic value for patients, if CVS is suggestive of differing underlying pathology, or if the presence of a CVS is dynamic over time. Progress in these areas is anticipated as CVS is incorporated into routine clinical practice.
Quantitative MRI Techniques
In the research setting, several imaging modalities can be used to quantify the degree of microstructural injury in PwMS. The goal of these methods is to identify and quantify myelin and axonal damage, the major drivers of neurodegeneration. Among these methods, diffusion-based imaging is a measure of the amount of diffusion or fluid mobility across the tissues of the brain.47 Diffusion-weighted imaging (DWI) yields several parametric maps including axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (Figure 2 A, B, and C). These parametric maps provide information on different directions of water molecules’ movements. Myelin surrounds the axons preventing water molecules diffusion perpendicular to axons (RD) while axonal content prevents water diffusion horizontal to the axons (AD).Thus, AD is considered more specific to axonal injury, whereas RD is specific to myelin content.48 A higher value of any of these metrics is associated with a higher degree of tissue injury.
Although sensitive to axonal and myelin injury, AD and RD computed from single b-shell DWI experience several limitations including being affected by nonpathologic factors such as fiber orientation, distribution, and crossing, and by various nonmyelin specific pathologies including fluid accumulation during inflammation, myelin sheath thickness, and axonal intactness.48 Several multi b-shell methods have been developed to overcome diffusion imaging limitations. For example, work at the Nashville VA MS Center of Excellence has focused on the use of the multicompartment diffusion MRI with spherical mean technique (SMT). This method removes the orientation dependency of the diffusion MRI signal, increasing the signal-to-noise ratio and reducing biases from fiber undulation, crossing, and dispersion.49 SMT generates the apparent axonal volume fraction (Vax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). Vax was previously validated in MS as a measure of axonal integrity.49
In terms of myelin, several other specific measures have been developed. Magnetization transfer ratio (MTR) is another measure of tissue integrity that has been validated as a measure of tissue injury in MS (Figure 2E).50,51 Zheng et al found that the percentage of lesions with low MTR was significantly higher among patients whose disease disability progressed compared with patients who did not.52Selective inversion recovery with quantitative magnetization transfer (SIR-qMT) was developed to account for the limitations of MTR, including its sensitivity to edema and axonal density.52 Germane to myelin measurements, SIR-qMT generates the macromolecular to free size ratio (PSR). PSR represents the ratio of protons bound to macromolecules (myelin) to free protons (Figure 2F). PSR is considered a marker of myelin integrity, with lower values correlating with disability severity and indicating higher tissue damage and lower myelin content. Previous studies from the Nashville VA MS Center of Excellence validated the use of SIR-qMT among patients with MS, CIS, RIS, and healthy controls.53
Quantitative MRI has several research applications in the field of MS. We demonstrated that PRL harbor a higher degree of myelin injury indicated by PSR compared with rimless lesions.54 These MRI techniques are also helpful to investigate tissues surrounding the lesions, called normal appearing white matter (NAWM). Using quantitative MRI techniques such as MTR,52 PSR,53 and Vax,49 investigators have demonstrated that NAWM is injured in PwMS, and proximal NAWM may have higher degree of tissue damage compared with distant NAWM.55
Anticipated Innovations and Challenges
In the field of quantitative MRI, several new techniques are being adopted. Researchers are developing techniques such as myelin water fraction which evaluates the interaction between water and protons to measure myelin content. This is considered an advancement as it takes into account edema resulting from MS injury.56 Another example is multicompartment diffusion imaging, such as standard model imaging,57 and neurite orientation dispersion and density imaging,58 which considers water as an additional compartment compared with the SMT derived Vax. For PRL identification, more advanced methodologic techniques are developing such quantitative susceptibility mapping (QSM), which can detect iron deposits that surround the lesions with relatively high sensitivity and specificity of identifying PRL.59
Despite these innovations, several challenges remain before possible incorporation into the clinical setting. These limitations include longer scan time, familiarity of clinicians in using these maps, higher financial cost, and the necessity of advanced imaging processing skills. Artificial intelligence is a promising tool that may overcome these challenges through creating automated processing pipelines and developing synthetic maps without the need for additional acquisition.60
Conclusions
MRI is the most important tool for diagnosing and treating PwMS. Imaging biomarkers such as T2-lesions, cBHs, brain atrophy, PRLs, and CVS provide insight into the disease’s pathogenesis and are invaluable for the accurate diagnosis and prognostication of MS. Quantitative MRI techniques, while not available in the clinical setting, are important tools for translational research that may help direct the development of future therapeutics. In the near future, clinicians caring for PwMS should expect to encounter these imaging biomarkers more frequently in the clinical setting, especially with the inclusion of PRLs and CVS in the next iteration of the McDonald diagnostic criteria.
Multiple sclerosis (MS) is a complex, chronic immune-mediated disease of the central nervous system characterized by focal inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI), first incorporated into the McDonald Criteria for the diagnosis of MS in 2001, is an integral tool in the diagnosis, prognosis, and therapeutic monitoring of people with MS (PwMS).1
MRI research in MS is rapidly expanding and offers insights into the pathophysiology of MS with important implications for the routine clinical care of PwMS. At the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting, the US Department of Veterans Affairs (VA) MS Centers of Excellence hosted an educational symposium highlighting MRI biomarkers in MS, including T2-lesions, chronic black holes (cBHs), brain atrophy, paramagnetic rim lesions (PRLs), and the central vein sign (CVS). The symposium also provided a brief overview of quantitative MRI techniques used to characterize MS lesion severity and research applications of these techniques. This clinical review summarizes the main points of that symposium with the goal of introducing key concepts to federal health care practitioners caring for PwMS.
MRI Biomarkers in MS
T2-lesions, Chronic Black Holes, and Brain Atrophy
Focal immune-mediated inflammation and demyelination in MS may be detected by MRI as hyperintense foci on T2-weighted (T2-w) imaging (eg, T2-w turbo spin echo or T2-w fluid attenuated inversion recovery sequences). These T2-lesions, critical for diagnosing MS, are typically ovoid and occur in the periventricular, juxtacortical, infratentorial spinal cord white matter (Figure 1A). T2-lesion number and volume show some association with disability and optic nerve.
Wattjes et al highlight 2 cases to demonstrate this point: a man aged 52 years with MS for 23 years and a woman aged 50 years with MS for 11 years. Despite having MS for a much shorter duration, the woman had worse disability due to a higher lesion number and volume.2 T2-lesion volume also impacts disability progression in PwMS. Gauthier et al compared the probability of progression in 3 women, all of whom were aged 39 years and had MS for 6 years. The profile with highest probability of disability progression had the highest quartile of T2-lesion volume.3 T2-lesion volume over 2 years correlates with worse scores on disability metrics such as the MS functional composite, paced auditory serial addition task, and brain volume.4 A 2024 systematic review and meta-analysis demonstrated that T2-lesion volume is significantly correlated with clinical disability in PwMS.5
Select T2-lesions are also hypointense on T1-w spin echo images and are known as cBHs (Figure 1B). Histologically, T2-lesions with cBHs have more severe architectural disruption than those without cBHs.6 cBH number and volume are significantly correlated with disability, regardless of the degree of hypointensity on T1-w imaging.5,7 A 10-year longitudinal study demonstrated that cBHs were associated with disease progression after 5 years while T2-lesion volume was not, indicating that cBHs may be a more accurate predictor of disability.8
Brain atrophy, another imaging biomarker of MS, affects both the cerebral white and gray matter. White matter fraction (the volume of white matter relative to the intracranial compartment volume) and gray matter fraction (the volume of gray matter relative to the intracranial compartment) are significantly lower among PwMS compared with healthy controls. In addition, gray matter fraction is lower among patients with primary and secondary progressive MS compared with those with relapsing-remitting MS, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS). Gray matter fraction is also correlated with several motor and cognitive disability indices.9
Paramagnetic Rim Lesions
Neurologic worsening in PwMS occurs by 2 distinct mechanisms: relapse-associated worsening, a stepwise worsening of symptoms due to incomplete recovery following a relapse; and progression independent of relapse activity (PIRA), which is an irreversible neurologic deterioration in the absence of clinical or radiological relapses.10 PIRA is associated with neurodegeneration and predominates in both primary and secondary progressive MS. However, recent data demonstrated that PIRA may contribute to as much as 50% of disability worsening in relapsing MS and occurs early in the RMS disease course.10,11 Current high-efficacy disease modifying therapy, such as ocrelizumab, are extraordinarily successful at preventing focal inflammation and relapses but are less effective for preventing the slow march of disability progression characterizing PIRA.12,13 The prevention of PIRA is therefore an unmet treatment need.
Chronic active lesions (CALs) are an important driver of PIRA. When an acute gadolinium-enhancing lesion develops in PwMS, there are 3 possible fates of this lesion. The lesion may become chronically inactive, remyelinate, or transition to CALs.14 The histopathologic signature of CALs is compartmentalized, low-grade inflammation behind an intact blood-brain barrier with evidence of both active and chronic components.15 CALs may be found not only in cerebral white matter but also in the cerebral cortex and spinal cord.16,17 Combined MRI and histopathological studies have shown that iron-laden microglia/macrophages can be detected by susceptibility-based MRI as a rim of paramagnetic signal surrounding select T2-lesions.19 These PRLs represent an in vivo imaging biomarker of CAL (Figure 1C). According to the North American Imaging in MS Cooperative (NAIMS) consensus criteria, a PRL must surround at least two-thirds of the outer edge of a T2-lesion, be visible in ≥ 2 consecutive MRI slices, and cannot be contrast enhancing.20
PRLs can be visualized on multiple susceptibility-based imaging methods, including multiecho derived R2*/T2*, phase maps, susceptibility-weighted imaging, and quantitative susceptibility mapping.21-23 Retrospective analyses have shown no significant differences in sensitivity across these imaging modalities.24 Although first visualized with 7T MRI, PRLs may also be detected by 1.5T and 3T MRI with comparable sensitivities.25-27 However, there remains a significant knowledge gap regarding the accuracy of each imaging modality. Systematic, prospectively designed studies are needed to ascertain the comparative value of each method.
The presence of PRL is a poor prognostic indicator. PwMS without PRLs have higher levels of disability, are more likely to progress, and demonstrate greater gray matter atrophy and cognitive dysfunction when compared with PwMS with PRLs.27-29 Lesions with PRL tend to slowly expand, exhibit greater demyelination, and have diminished white matter integrity.21,22,30
PRLs may also be used as a diagnostic tool. PRLs are highly specific for MS/CIS with a 99.7% specificity and 98.4% positive predictive value, although the sensitivity is limited to 24%.31 Taken together, these data indicate that the presence of a PRL substantially increases the likelihood of an MS/CIS diagnosis, whereas the absence of a PRL does not exclude these diagnoses.
Several unanswered questions remain: Why do select acute MS lesions transition to CALs? How may investigators utilize PRLs as outcome measures in future clinical trials? How should PRLs be incorporated into the routine care of PwMS? As the role of this imaging biomarker is clarified both in the research and clinical settings, clinicians caring for PwMS can expect to increasingly encounter the topic of PRLs in the near future.
Central Vein Sign
A CVS is defined by the presence of a central vessel within a demyelinating plaque (Figure 1D). As early as the 1820s, MS plaques on gross pathology were noted to follow the course of a vessel. Early histological studies reported that up to 91% of MS plaques had a central vessel present.32 Lesion formation is dependent on the movement of lymphocytes and other inflammatory cells from the systemic circulation across the blood brain barrier into the perivascular space, a privileged site where immune cells interact with antigen presenting cells to launch an inflammatory cascade and eventual demyelinating lesion.33
CVS can be visualized on 1.5T, 3T and 7T MRI. However, 7T MRI is superior to 3T in the detection of CVS, with 85% of MS lesions having CVS visible compared with 45% on 3T.34 With advances in 7T MRI, fluid attenuated inversion recovery and T2* susceptibility, weighted sequences can be overlaid, allowing simultaneous visualization of the vessel and the demyelinating lesion. With higher density of parenchymal veins in the periventricular regions, the CVS is most seen in lesions of this territory but can also be present in juxtacortical, thalamic and infratentorial lesions with decreasing prevalence as these approach the cortex.35
MS lesions are more likely to have CVS than T2 hyperintense white matter lesions of other causes, with a large study reporting 78% of MS lesions were CVS positive. Further, CVS positive lesions can be found across all MS phenotypes including relapsing remitting, primary progressive, and secondary progressive.35 The CVS is also specific to MS lesions and is an effective tool for differentiating MS lesions from other common causes of T2 hyperintense lesions including chronic ischemic white matter disease,36 migraines,37 neuromyelitis optica spectrum disorders,38,39 Susac syndrome,40 and systemic autoimmune diseases (Behcet disease, systemic lupus erythematosus, and antiphospholipid syndrome).41
With CVS emerging as a promising radiographic biomarker for MS, NAIMS issued a consensus statement on necessary properties of a CVS. These criteria included appearance of a thin hypointense line or small dot, visualized in ≥ 2 perpendicular planes, with diameter < 2 mm, and running partially or entirely through the center of the lesion. They also clarified that lesions < 3 mm, confluent lesions, lesions with multiple vessels present or poorly visualized lesions were excluded.42
A shared CVS definition was a necessary step toward routine use of CVS as a radiographic biomarker and its incorporation in the 2024 revised McDonald criteria.43 Remaining limitations including 7T MRI is primarily available in research settings and the lack of consensus on a diagnostic threshold. There have been many proposed methods, including a 40% cut off,44 60% cut off,45 and Select 3* or Select 6* methods.46 The goal of each method is to optimize sensitivity and specificity while not compromising efficiency of MRI review for both neurologists and radiologists.
The CVS has significant potential as a radiographic biomarker for MS and may allow the early stages of MS to be differentiated from other common causes of white matter lesions on MRI. However, it remains unclear whether CVS holds prognostic value for patients, if CVS is suggestive of differing underlying pathology, or if the presence of a CVS is dynamic over time. Progress in these areas is anticipated as CVS is incorporated into routine clinical practice.
Quantitative MRI Techniques
In the research setting, several imaging modalities can be used to quantify the degree of microstructural injury in PwMS. The goal of these methods is to identify and quantify myelin and axonal damage, the major drivers of neurodegeneration. Among these methods, diffusion-based imaging is a measure of the amount of diffusion or fluid mobility across the tissues of the brain.47 Diffusion-weighted imaging (DWI) yields several parametric maps including axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (Figure 2 A, B, and C). These parametric maps provide information on different directions of water molecules’ movements. Myelin surrounds the axons preventing water molecules diffusion perpendicular to axons (RD) while axonal content prevents water diffusion horizontal to the axons (AD).Thus, AD is considered more specific to axonal injury, whereas RD is specific to myelin content.48 A higher value of any of these metrics is associated with a higher degree of tissue injury.
Although sensitive to axonal and myelin injury, AD and RD computed from single b-shell DWI experience several limitations including being affected by nonpathologic factors such as fiber orientation, distribution, and crossing, and by various nonmyelin specific pathologies including fluid accumulation during inflammation, myelin sheath thickness, and axonal intactness.48 Several multi b-shell methods have been developed to overcome diffusion imaging limitations. For example, work at the Nashville VA MS Center of Excellence has focused on the use of the multicompartment diffusion MRI with spherical mean technique (SMT). This method removes the orientation dependency of the diffusion MRI signal, increasing the signal-to-noise ratio and reducing biases from fiber undulation, crossing, and dispersion.49 SMT generates the apparent axonal volume fraction (Vax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). Vax was previously validated in MS as a measure of axonal integrity.49
In terms of myelin, several other specific measures have been developed. Magnetization transfer ratio (MTR) is another measure of tissue integrity that has been validated as a measure of tissue injury in MS (Figure 2E).50,51 Zheng et al found that the percentage of lesions with low MTR was significantly higher among patients whose disease disability progressed compared with patients who did not.52Selective inversion recovery with quantitative magnetization transfer (SIR-qMT) was developed to account for the limitations of MTR, including its sensitivity to edema and axonal density.52 Germane to myelin measurements, SIR-qMT generates the macromolecular to free size ratio (PSR). PSR represents the ratio of protons bound to macromolecules (myelin) to free protons (Figure 2F). PSR is considered a marker of myelin integrity, with lower values correlating with disability severity and indicating higher tissue damage and lower myelin content. Previous studies from the Nashville VA MS Center of Excellence validated the use of SIR-qMT among patients with MS, CIS, RIS, and healthy controls.53
Quantitative MRI has several research applications in the field of MS. We demonstrated that PRL harbor a higher degree of myelin injury indicated by PSR compared with rimless lesions.54 These MRI techniques are also helpful to investigate tissues surrounding the lesions, called normal appearing white matter (NAWM). Using quantitative MRI techniques such as MTR,52 PSR,53 and Vax,49 investigators have demonstrated that NAWM is injured in PwMS, and proximal NAWM may have higher degree of tissue damage compared with distant NAWM.55
Anticipated Innovations and Challenges
In the field of quantitative MRI, several new techniques are being adopted. Researchers are developing techniques such as myelin water fraction which evaluates the interaction between water and protons to measure myelin content. This is considered an advancement as it takes into account edema resulting from MS injury.56 Another example is multicompartment diffusion imaging, such as standard model imaging,57 and neurite orientation dispersion and density imaging,58 which considers water as an additional compartment compared with the SMT derived Vax. For PRL identification, more advanced methodologic techniques are developing such quantitative susceptibility mapping (QSM), which can detect iron deposits that surround the lesions with relatively high sensitivity and specificity of identifying PRL.59
Despite these innovations, several challenges remain before possible incorporation into the clinical setting. These limitations include longer scan time, familiarity of clinicians in using these maps, higher financial cost, and the necessity of advanced imaging processing skills. Artificial intelligence is a promising tool that may overcome these challenges through creating automated processing pipelines and developing synthetic maps without the need for additional acquisition.60
Conclusions
MRI is the most important tool for diagnosing and treating PwMS. Imaging biomarkers such as T2-lesions, cBHs, brain atrophy, PRLs, and CVS provide insight into the disease’s pathogenesis and are invaluable for the accurate diagnosis and prognostication of MS. Quantitative MRI techniques, while not available in the clinical setting, are important tools for translational research that may help direct the development of future therapeutics. In the near future, clinicians caring for PwMS should expect to encounter these imaging biomarkers more frequently in the clinical setting, especially with the inclusion of PRLs and CVS in the next iteration of the McDonald diagnostic criteria.
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127. doi:10.1002/ana.1032
Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and monitoring of multiple sclerosis: an update. Clin Neuroradiol. 2015;25:157-165. doi:10.1007/s00062-015-0430-y
Gauthier SA, Mandel M, Guttmann CR, et al. Predicting short-term disability in multiple sclerosis. Neurology. 2007;68:2059-2065.doi:10.1212/01.wnl.0000264890.97479.b1
Rudick RA, Lee JC, Simon J, Fisher E. Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study. Ann Neurol. 2006;60:236-242. doi:10.1002/ana.20883
Nabizadeh F, Zafari R, Mohamadi M, et al. MRI features and disability in multiple sclerosis: a systematic review and meta-analysis. J Neuroradiol. 2024;51:24-37. doi:10.1016/j.neurad.2023.11.007
Bagnato F, Jeffries N, Richert ND, et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003;126:1782-1789. doi:10.1093/brain/awg182
Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014;85:1109-1115. doi:10.1136/jnnp-2013-306906
Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology. 2005;65:1526-1532. doi:10.1212/01.wnl.0000184471.83948.e0
Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64:247-254. doi:10.1002/ana.21423
Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145:3147-3161. doi:10.1093/brain/awac016
Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1132-1140. doi:10.1001/jamaneurol.2020.1568
Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. doi:10.1056/NEJMoa1601277
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220. doi:10.1056/NEJMoa1606468
Prineas JW, Kwon EE, Cho ES, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50:646-657. doi:10.1002/ana.1255
Kuhlmann T, Ludwin S, Prat A, Antel J, Brück W, Lassmann H. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 2017;133:13-24. doi:10.1007/s00401-016-1653-y
Pitt D, Boster A, Pei W, et al. Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging. Arch Neurol. 2010;67:812-818. doi:10.1001/archneurol.2010.148
Gilmore CP, Geurts JJ, Evangelou N, et al. Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Mult Scler. 2009;15:180-188. doi:10.1177/1352458508096876
Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210-218. doi:10.1111/j.1750-3639.2007.00064.x
Bagnato F, Hametner S, Yao B, et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134:3602-3615. doi:10.1093/brain/awr278
Bagnato F, Sati P, Hemond CC, et al. Imaging chronic active lesions in multiple sclerosis: a consensus statement. Brain. 2024;147:2913-2933. doi:10.1093/brain/awae013
Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017;133:25-42. doi:10.1007/s00401-016-1636-z
Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016;126:2597-2609. doi:10.1172/JCI86198
Gillen KM, Mubarak M, Park C, et al. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021;8:877-886. doi:10.1002/acn3.51338
Ng Kee Kwong KC, Mollison D, Meijboom R, et al. The prevalence of paramagnetic rim lesions in multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2021;16:e0256845. doi:10.1371/journal.pone.0256845
Absinta M, Sati P, Fechner A, et al. Identification of chronic active multiple sclerosis lesions on 3T MRI. AJNR Am J Neuroradiol. 2018;39:1233-1238. doi:10.3174/ajnr.A5660
Hemond CC, Reich DS, Dundamadappa SK. Paramagnetic rim lesions in multiple sclerosis: comparison of visualization at 1.5-T and 3-T MRI. AJR Am J Roentgenol. 2022;219:120-131. doi:10.2214/AJR.21.26777
Altokhis AI, Hibbert AM, Allen CM, et al. Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis. Mult Scler. 2022;28:2202-2211. doi:10.1177/13524585221114750
Choi S, Lake S, Harrison DM. Evaluation of the blood-brain barrier, demyelination, and neurodegeneration in paramagnetic rim lesions in multiple sclerosis on 7 tesla MRI. J Magn Reson Imaging. 2024;59:941-951. doi:10.1002/jmri.28847
Kazimuddin HF, Wang J, Hernandez B, et al. Paramagnetic rim lesions and their relationship with neurodegeneration and clinical disability at the time of multiple sclerosis diagnosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.
Rohm Z, Koch C, Kazimuddin H, et al. Longitudinal characterization of paramagnetic rim lesions in early multiple sclerosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.
Meaton I, Altokhis A, Allen CM, et al. Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis. Mult Scler. 2022;28:2212-2220. doi:10.1177/13524585221118677
Fog T. On the vessel-plaque relationships in the brain in multiple sclerosis. Acta Neurol Scand Suppl. 1964;40:9-15.
Ineichen BV, Okar SV, Proulx ST, et al. Perivascular spaces and their role in neuroinflammation. Neuron. 2022;110:3566-3581. doi:10.1016/j.neuron.2022.10.024
Tallantyre EC, Morgan PS, Dixon JE, et al. A comparison of 3T and 7T in the detection of small parenchymal veins within MS lesions. Invest Radiol. 2009;44:491-494. doi:10.1097/RLI.0b013e3181b4c144
Kilsdonk ID, Lopez-Soriano A, Kuijer JP, et al. Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics. J Neurol. 2014;261:1356-1364. doi:10.1007/s00415-014-7351-6
Tallantyre EC, Dixon JE, Donaldson I, et al. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011;76:534-539. doi:10.1212/WNL.0b013e31820b7630
Solomon AJ, Schindler MK, Howard DB, et al. “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol. 2015;3:82-87. doi:10.1002/acn3.273
Sinnecker T, Dörr J, Pfueller CF, et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012;79:708-714. doi:10.1212/WNL.0b013e3182648bc8
Kister I, Herbert J, Zhou Y, Ge Y. Ultrahigh-field MR (7 T) imaging of brain lesions in neuromyelitis optica. Mult Scler Int. 2013;2013:398259. doi:10.1155/2013/398259
Wuerfel J, Sinnecker T, Ringelstein EB, et al. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler. 2012;18:1592-1599. doi:10.1177/1352458512441270
Massacesi L. Perivenular distribution of white matter lesions evaluated by MRI can differentiate MS lesions from inflammatory small vessel diseases. Eur J Neurol. 2016;23:86. doi:10.1212/WNL.86.16_supplement.P6.121
Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12:714-722. doi:10.1038/nrneurol.2016.166
Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24:850-865. doi:10.1016/S1474-4422(25)00270-4
Mistry N, Dixon J, Tallantyre E, et al. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013;70:623-628. doi:10.1001/jamaneurol.2013.1405
Campion T, Smith RJP, Altmann DR, et al. FLAIR* to visualize veins in white matter lesions: a new tool for the diagnosis of multiple sclerosis? Eur Radiol. 2017;27:4257-4263. doi:10.1007/s00330-017-4822-z
Solomon AJ, Watts R, Ontaneda D, et al. Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm. Mult Scler. 2018;24:750-757. doi:10.1177/1352458517726383
Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI. J Neurol. 2002;249:875-883. doi:10.1007/s00415-002-0752-y
Song SK, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005;26:132-140. doi:10.1016/j.neuroimage.2005.01.028
Bagnato F, Franco G, Li H, et al. Probing axons using multi-compartmental diffusion in multiple sclerosis. Ann Clin Transl Neurol. 2019;6:1595-1605. doi:10.1002/acn3.50836
Filippi M, Cercignani M, Inglese M, et al. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology. 2001;56:304-311. doi:10.1212/wnl.56.3.304
Bagnato F. Clinical application of magnetization transfer imaging. In: Advanced Neuro MR Techniques and Applications. Elsevier; 2022:403-417. doi:10.1016/B978-0-12-822479-3.00041-5
Zheng Y, Lee JC, Rudick R, Fisher E. Long-term magnetization transfer ratio evolution in multiple sclerosis white matter lesions. J Neuroimaging. 2018;28:191-198. doi:10.1111/jon.12480
Bagnato F, Hametner S, Franco G, et al. Selective inversion recovery quantitative magnetization transfer brain MRI at 7T: clinical and postmortem validation in multiple sclerosis. J Neuroimaging. 2018;28:380-388. doi:10.1111/jon.12511
Clarke MA, Cheek R, Hernandez B, et al. Paramagnetic rim lesions and the central vein sign: characterizing multiple sclerosis imaging markers. J Neuroimaging. 2024;34:86-94. doi:10.1111/jon.13173
Clarke MA, Lakhani DA, Wen S, et al. Perilesional neurodegenerative injury in multiple sclerosis: relation to focal lesions and impact on disability. Mult Scler Relat Disord. 2021;49:102738. doi:10.1016/j.msard.2021.102738
Laule C, Moore GRW. Myelin water imaging to detect demyelination and remyelination and its validation in pathology. Brain Pathol. 2018;28:750-764. doi:10.1111/bpa.12645
Coelho S, Baete SH, Lemberskiy G, et al. Reproducibility of the standard model of diffusion in white matter on clinical MRI systems. Neuroimage. 2022;257:119290. doi:10.1016/j.neuroimage.2022.119290
Novikov DS, Veraart J, Jelescu IO, et al. Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI. Neuroimage. 2018;174:518-538. doi:10.1016/j.neuroimage.2018.03.006
Langkammer C, Liu T, Khalil M, et al. Quantitative susceptibility mapping in multiple sclerosis. Radiology. 2013;267:551-559. doi:10.1148/radiol.12120707
Collorone S, Coll L, Lorenzi M, et al. Artificial intelligence applied to MRI data to tackle key challenges in multiple sclerosis. Mult Scler. 2024;30:767-784. doi:10.1177/13524585241249422
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127. doi:10.1002/ana.1032
Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and monitoring of multiple sclerosis: an update. Clin Neuroradiol. 2015;25:157-165. doi:10.1007/s00062-015-0430-y
Gauthier SA, Mandel M, Guttmann CR, et al. Predicting short-term disability in multiple sclerosis. Neurology. 2007;68:2059-2065.doi:10.1212/01.wnl.0000264890.97479.b1
Rudick RA, Lee JC, Simon J, Fisher E. Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study. Ann Neurol. 2006;60:236-242. doi:10.1002/ana.20883
Nabizadeh F, Zafari R, Mohamadi M, et al. MRI features and disability in multiple sclerosis: a systematic review and meta-analysis. J Neuroradiol. 2024;51:24-37. doi:10.1016/j.neurad.2023.11.007
Bagnato F, Jeffries N, Richert ND, et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003;126:1782-1789. doi:10.1093/brain/awg182
Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014;85:1109-1115. doi:10.1136/jnnp-2013-306906
Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology. 2005;65:1526-1532. doi:10.1212/01.wnl.0000184471.83948.e0
Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64:247-254. doi:10.1002/ana.21423
Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145:3147-3161. doi:10.1093/brain/awac016
Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1132-1140. doi:10.1001/jamaneurol.2020.1568
Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. doi:10.1056/NEJMoa1601277
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220. doi:10.1056/NEJMoa1606468
Prineas JW, Kwon EE, Cho ES, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50:646-657. doi:10.1002/ana.1255
Kuhlmann T, Ludwin S, Prat A, Antel J, Brück W, Lassmann H. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 2017;133:13-24. doi:10.1007/s00401-016-1653-y
Pitt D, Boster A, Pei W, et al. Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging. Arch Neurol. 2010;67:812-818. doi:10.1001/archneurol.2010.148
Gilmore CP, Geurts JJ, Evangelou N, et al. Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Mult Scler. 2009;15:180-188. doi:10.1177/1352458508096876
Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210-218. doi:10.1111/j.1750-3639.2007.00064.x
Bagnato F, Hametner S, Yao B, et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134:3602-3615. doi:10.1093/brain/awr278
Bagnato F, Sati P, Hemond CC, et al. Imaging chronic active lesions in multiple sclerosis: a consensus statement. Brain. 2024;147:2913-2933. doi:10.1093/brain/awae013
Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017;133:25-42. doi:10.1007/s00401-016-1636-z
Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016;126:2597-2609. doi:10.1172/JCI86198
Gillen KM, Mubarak M, Park C, et al. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021;8:877-886. doi:10.1002/acn3.51338
Ng Kee Kwong KC, Mollison D, Meijboom R, et al. The prevalence of paramagnetic rim lesions in multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2021;16:e0256845. doi:10.1371/journal.pone.0256845
Absinta M, Sati P, Fechner A, et al. Identification of chronic active multiple sclerosis lesions on 3T MRI. AJNR Am J Neuroradiol. 2018;39:1233-1238. doi:10.3174/ajnr.A5660
Hemond CC, Reich DS, Dundamadappa SK. Paramagnetic rim lesions in multiple sclerosis: comparison of visualization at 1.5-T and 3-T MRI. AJR Am J Roentgenol. 2022;219:120-131. doi:10.2214/AJR.21.26777
Altokhis AI, Hibbert AM, Allen CM, et al. Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis. Mult Scler. 2022;28:2202-2211. doi:10.1177/13524585221114750
Choi S, Lake S, Harrison DM. Evaluation of the blood-brain barrier, demyelination, and neurodegeneration in paramagnetic rim lesions in multiple sclerosis on 7 tesla MRI. J Magn Reson Imaging. 2024;59:941-951. doi:10.1002/jmri.28847
Kazimuddin HF, Wang J, Hernandez B, et al. Paramagnetic rim lesions and their relationship with neurodegeneration and clinical disability at the time of multiple sclerosis diagnosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.
Rohm Z, Koch C, Kazimuddin H, et al. Longitudinal characterization of paramagnetic rim lesions in early multiple sclerosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.
Meaton I, Altokhis A, Allen CM, et al. Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis. Mult Scler. 2022;28:2212-2220. doi:10.1177/13524585221118677
Fog T. On the vessel-plaque relationships in the brain in multiple sclerosis. Acta Neurol Scand Suppl. 1964;40:9-15.
Ineichen BV, Okar SV, Proulx ST, et al. Perivascular spaces and their role in neuroinflammation. Neuron. 2022;110:3566-3581. doi:10.1016/j.neuron.2022.10.024
Tallantyre EC, Morgan PS, Dixon JE, et al. A comparison of 3T and 7T in the detection of small parenchymal veins within MS lesions. Invest Radiol. 2009;44:491-494. doi:10.1097/RLI.0b013e3181b4c144
Kilsdonk ID, Lopez-Soriano A, Kuijer JP, et al. Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics. J Neurol. 2014;261:1356-1364. doi:10.1007/s00415-014-7351-6
Tallantyre EC, Dixon JE, Donaldson I, et al. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011;76:534-539. doi:10.1212/WNL.0b013e31820b7630
Solomon AJ, Schindler MK, Howard DB, et al. “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol. 2015;3:82-87. doi:10.1002/acn3.273
Sinnecker T, Dörr J, Pfueller CF, et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012;79:708-714. doi:10.1212/WNL.0b013e3182648bc8
Kister I, Herbert J, Zhou Y, Ge Y. Ultrahigh-field MR (7 T) imaging of brain lesions in neuromyelitis optica. Mult Scler Int. 2013;2013:398259. doi:10.1155/2013/398259
Wuerfel J, Sinnecker T, Ringelstein EB, et al. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler. 2012;18:1592-1599. doi:10.1177/1352458512441270
Massacesi L. Perivenular distribution of white matter lesions evaluated by MRI can differentiate MS lesions from inflammatory small vessel diseases. Eur J Neurol. 2016;23:86. doi:10.1212/WNL.86.16_supplement.P6.121
Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12:714-722. doi:10.1038/nrneurol.2016.166
Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24:850-865. doi:10.1016/S1474-4422(25)00270-4
Mistry N, Dixon J, Tallantyre E, et al. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013;70:623-628. doi:10.1001/jamaneurol.2013.1405
Campion T, Smith RJP, Altmann DR, et al. FLAIR* to visualize veins in white matter lesions: a new tool for the diagnosis of multiple sclerosis? Eur Radiol. 2017;27:4257-4263. doi:10.1007/s00330-017-4822-z
Solomon AJ, Watts R, Ontaneda D, et al. Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm. Mult Scler. 2018;24:750-757. doi:10.1177/1352458517726383
Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI. J Neurol. 2002;249:875-883. doi:10.1007/s00415-002-0752-y
Song SK, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005;26:132-140. doi:10.1016/j.neuroimage.2005.01.028
Bagnato F, Franco G, Li H, et al. Probing axons using multi-compartmental diffusion in multiple sclerosis. Ann Clin Transl Neurol. 2019;6:1595-1605. doi:10.1002/acn3.50836
Filippi M, Cercignani M, Inglese M, et al. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology. 2001;56:304-311. doi:10.1212/wnl.56.3.304
Bagnato F. Clinical application of magnetization transfer imaging. In: Advanced Neuro MR Techniques and Applications. Elsevier; 2022:403-417. doi:10.1016/B978-0-12-822479-3.00041-5
Zheng Y, Lee JC, Rudick R, Fisher E. Long-term magnetization transfer ratio evolution in multiple sclerosis white matter lesions. J Neuroimaging. 2018;28:191-198. doi:10.1111/jon.12480
Bagnato F, Hametner S, Franco G, et al. Selective inversion recovery quantitative magnetization transfer brain MRI at 7T: clinical and postmortem validation in multiple sclerosis. J Neuroimaging. 2018;28:380-388. doi:10.1111/jon.12511
Clarke MA, Cheek R, Hernandez B, et al. Paramagnetic rim lesions and the central vein sign: characterizing multiple sclerosis imaging markers. J Neuroimaging. 2024;34:86-94. doi:10.1111/jon.13173
Clarke MA, Lakhani DA, Wen S, et al. Perilesional neurodegenerative injury in multiple sclerosis: relation to focal lesions and impact on disability. Mult Scler Relat Disord. 2021;49:102738. doi:10.1016/j.msard.2021.102738
Laule C, Moore GRW. Myelin water imaging to detect demyelination and remyelination and its validation in pathology. Brain Pathol. 2018;28:750-764. doi:10.1111/bpa.12645
Coelho S, Baete SH, Lemberskiy G, et al. Reproducibility of the standard model of diffusion in white matter on clinical MRI systems. Neuroimage. 2022;257:119290. doi:10.1016/j.neuroimage.2022.119290
Novikov DS, Veraart J, Jelescu IO, et al. Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI. Neuroimage. 2018;174:518-538. doi:10.1016/j.neuroimage.2018.03.006
Langkammer C, Liu T, Khalil M, et al. Quantitative susceptibility mapping in multiple sclerosis. Radiology. 2013;267:551-559. doi:10.1148/radiol.12120707
Collorone S, Coll L, Lorenzi M, et al. Artificial intelligence applied to MRI data to tackle key challenges in multiple sclerosis. Mult Scler. 2024;30:767-784. doi:10.1177/13524585241249422
Updates in Multiple Sclerosis Imaging
Updates in Multiple Sclerosis Imaging
Impact of Retroactive Application of Updated Surveillance Guidelines on Endoscopy Center Capacity at a Large VA Health Care System
Impact of Retroactive Application of Updated Surveillance Guidelines on Endoscopy Center Capacity at a Large VA Health Care System
In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.1 This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.4
As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.
Methods
VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.
Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.
Retroactive Interval Reclassification
Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.
Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.5 For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines.
This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.
Results
Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).
Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).
Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.
Discussion
With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.8 While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.9 This suggests the actual effect on capacity may be even lower than reported.
Limitations
The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.10 Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.11 Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.12,13
Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.14
Conclusions
Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.
Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2020;91:463-485. doi:10.1016/j.gie.2020.01.014
Dubé C, Yakubu M, McCurdy BR, et al. Risk of advanced adenoma, colorectal cancer, and colorectal cancer mortality in people with low-risk adenomas at baseline colonoscopy: a systematic review and meta-analysis. Am J Gastroenterol. 2017;112:1790-1801. doi:10.1038/ajg.2017.360
Click B, Pinsky PF, Hickey T, Doroudi M, Shoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319:2021-2031. doi:10.1001/jama.2018.5809
US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:1965-1977. doi:10.1001/jama.2021.6238
Djinbachian R, Dubé AJ, Durand M, et al. Adherence to post-polypectomy surveillance guidelines: a systematic review and meta-analysis. Endoscopy. 2019;51:673-683. doi:10.1055/a-0865-2082
Gawron AJ, Kaltenbach T, Dominitz JA. The impact of the coronavirus disease-19 pandemic on access to endoscopy procedures in the VA healthcare system. Gastroenterology. 2020;159:1216-1220.e1. doi:10.1053/j.gastro.2020.07.033
Xiao AH, Chang SY, Stevoff CG, Komanduri S, Pandolfino JE, Keswani RN. Adoption of multi-society guidelines facilitates value-based reduction in screening and surveillance colonoscopy volume during COVID-19 pandemic. Dig Dis Sci. 2021;66:2578-2584. doi:10.1007/s10620-020-06539-1
Dong J, Wang LF, Ardolino E, Feuerstein JD. Real-world compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer polypectomy surveillance guidelines: an observational study. Gastrointest Endosc. 2023;97:350-356.e3. doi:10.1016/j.gie.2022.08.020
Lee JK, Koripella PC, Jensen CD, et al. Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals. Clin Gastroenterol Hepatol. 2024;22:1315-1322.e7. doi:10.1016/j.cgh.2023.12.027
Veterans Access, Choice, and Accountability Act of 2014, HR 3230, 113th Cong (2014). Accessed September 8, 2025. https://www.congress.gov/bill/113th-congress/house-bill/3230
Dueker JM, Khalid A. Performance of the Veterans Choice Program for improving access to colonoscopy at a tertiary VA facility. Fed Pract. 2020;37:224-228.
Oliver A. The Veterans Health Administration: an American success story? Milbank Q. 2007;85:5-35. doi:10.1111/j.1468-0009.2007.00475.x
Furukawa MF, Machta RM, Barrett KA, et al. Landscape of health systems in the United States. Med Care Res Rev. 2020;77:357-366. doi:10.1177/1077558718823130
Petros V, Tsambikos E, Madhoun M, Tierney WM. Impact of community referral on colonoscopy quality metrics in a Veterans Affairs Medical Center. Clin Transl Gastroenterol. 2022;13:e00460. doi:10.14309/ctg.0000000000000460
In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.1 This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.4
As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.
Methods
VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.
Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.
Retroactive Interval Reclassification
Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.
Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.5 For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines.
This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.
Results
Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).
Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).
Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.
Discussion
With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.8 While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.9 This suggests the actual effect on capacity may be even lower than reported.
Limitations
The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.10 Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.11 Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.12,13
Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.14
Conclusions
Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.
In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.1 This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.4
As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.
Methods
VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.
Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.
Retroactive Interval Reclassification
Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.
Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.5 For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines.
This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.
Results
Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).
Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).
Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.
Discussion
With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.8 While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.9 This suggests the actual effect on capacity may be even lower than reported.
Limitations
The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.10 Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.11 Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.12,13
Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.14
Conclusions
Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.
Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2020;91:463-485. doi:10.1016/j.gie.2020.01.014
Dubé C, Yakubu M, McCurdy BR, et al. Risk of advanced adenoma, colorectal cancer, and colorectal cancer mortality in people with low-risk adenomas at baseline colonoscopy: a systematic review and meta-analysis. Am J Gastroenterol. 2017;112:1790-1801. doi:10.1038/ajg.2017.360
Click B, Pinsky PF, Hickey T, Doroudi M, Shoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319:2021-2031. doi:10.1001/jama.2018.5809
US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:1965-1977. doi:10.1001/jama.2021.6238
Djinbachian R, Dubé AJ, Durand M, et al. Adherence to post-polypectomy surveillance guidelines: a systematic review and meta-analysis. Endoscopy. 2019;51:673-683. doi:10.1055/a-0865-2082
Gawron AJ, Kaltenbach T, Dominitz JA. The impact of the coronavirus disease-19 pandemic on access to endoscopy procedures in the VA healthcare system. Gastroenterology. 2020;159:1216-1220.e1. doi:10.1053/j.gastro.2020.07.033
Xiao AH, Chang SY, Stevoff CG, Komanduri S, Pandolfino JE, Keswani RN. Adoption of multi-society guidelines facilitates value-based reduction in screening and surveillance colonoscopy volume during COVID-19 pandemic. Dig Dis Sci. 2021;66:2578-2584. doi:10.1007/s10620-020-06539-1
Dong J, Wang LF, Ardolino E, Feuerstein JD. Real-world compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer polypectomy surveillance guidelines: an observational study. Gastrointest Endosc. 2023;97:350-356.e3. doi:10.1016/j.gie.2022.08.020
Lee JK, Koripella PC, Jensen CD, et al. Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals. Clin Gastroenterol Hepatol. 2024;22:1315-1322.e7. doi:10.1016/j.cgh.2023.12.027
Veterans Access, Choice, and Accountability Act of 2014, HR 3230, 113th Cong (2014). Accessed September 8, 2025. https://www.congress.gov/bill/113th-congress/house-bill/3230
Dueker JM, Khalid A. Performance of the Veterans Choice Program for improving access to colonoscopy at a tertiary VA facility. Fed Pract. 2020;37:224-228.
Oliver A. The Veterans Health Administration: an American success story? Milbank Q. 2007;85:5-35. doi:10.1111/j.1468-0009.2007.00475.x
Furukawa MF, Machta RM, Barrett KA, et al. Landscape of health systems in the United States. Med Care Res Rev. 2020;77:357-366. doi:10.1177/1077558718823130
Petros V, Tsambikos E, Madhoun M, Tierney WM. Impact of community referral on colonoscopy quality metrics in a Veterans Affairs Medical Center. Clin Transl Gastroenterol. 2022;13:e00460. doi:10.14309/ctg.0000000000000460
Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2020;91:463-485. doi:10.1016/j.gie.2020.01.014
Dubé C, Yakubu M, McCurdy BR, et al. Risk of advanced adenoma, colorectal cancer, and colorectal cancer mortality in people with low-risk adenomas at baseline colonoscopy: a systematic review and meta-analysis. Am J Gastroenterol. 2017;112:1790-1801. doi:10.1038/ajg.2017.360
Click B, Pinsky PF, Hickey T, Doroudi M, Shoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319:2021-2031. doi:10.1001/jama.2018.5809
US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:1965-1977. doi:10.1001/jama.2021.6238
Djinbachian R, Dubé AJ, Durand M, et al. Adherence to post-polypectomy surveillance guidelines: a systematic review and meta-analysis. Endoscopy. 2019;51:673-683. doi:10.1055/a-0865-2082
Gawron AJ, Kaltenbach T, Dominitz JA. The impact of the coronavirus disease-19 pandemic on access to endoscopy procedures in the VA healthcare system. Gastroenterology. 2020;159:1216-1220.e1. doi:10.1053/j.gastro.2020.07.033
Xiao AH, Chang SY, Stevoff CG, Komanduri S, Pandolfino JE, Keswani RN. Adoption of multi-society guidelines facilitates value-based reduction in screening and surveillance colonoscopy volume during COVID-19 pandemic. Dig Dis Sci. 2021;66:2578-2584. doi:10.1007/s10620-020-06539-1
Dong J, Wang LF, Ardolino E, Feuerstein JD. Real-world compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer polypectomy surveillance guidelines: an observational study. Gastrointest Endosc. 2023;97:350-356.e3. doi:10.1016/j.gie.2022.08.020
Lee JK, Koripella PC, Jensen CD, et al. Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals. Clin Gastroenterol Hepatol. 2024;22:1315-1322.e7. doi:10.1016/j.cgh.2023.12.027
Veterans Access, Choice, and Accountability Act of 2014, HR 3230, 113th Cong (2014). Accessed September 8, 2025. https://www.congress.gov/bill/113th-congress/house-bill/3230
Dueker JM, Khalid A. Performance of the Veterans Choice Program for improving access to colonoscopy at a tertiary VA facility. Fed Pract. 2020;37:224-228.
Oliver A. The Veterans Health Administration: an American success story? Milbank Q. 2007;85:5-35. doi:10.1111/j.1468-0009.2007.00475.x
Furukawa MF, Machta RM, Barrett KA, et al. Landscape of health systems in the United States. Med Care Res Rev. 2020;77:357-366. doi:10.1177/1077558718823130
Petros V, Tsambikos E, Madhoun M, Tierney WM. Impact of community referral on colonoscopy quality metrics in a Veterans Affairs Medical Center. Clin Transl Gastroenterol. 2022;13:e00460. doi:10.14309/ctg.0000000000000460
Impact of Retroactive Application of Updated Surveillance Guidelines on Endoscopy Center Capacity at a Large VA Health Care System
Impact of Retroactive Application of Updated Surveillance Guidelines on Endoscopy Center Capacity at a Large VA Health Care System
A Case Report of Unanticipated Difficult Intubation Due to Posterior Tracheal Angulation
A Case Report of Unanticipated Difficult Intubation Due to Posterior Tracheal Angulation
Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,4 and kyphoscoliosis.5 These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.
Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.
Case Presentation
A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO2 monitoring. The ETT was secured at 22 cm measured at the teeth.
After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).
With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).
Discussion
Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.9 However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.10
In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.11 Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.11
This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning.
Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.12 Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.13 Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.6
Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.14 When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.
Conclusions
This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.
Creasy JD, Chiles C, Routh WD, et al. Overview of traumatic injury of the thoracic aorta. Radiogr Rev Publ Radiol Soc N Am Inc. 1997;17:27-45. doi:10.1148/radiographics.17.1.9017797
Yee AM, Christensen DN, Waterbrook AL, et al. Parapharyngeal abscess with tracheal deviation. Intern Emerg Med. 2017;12:1077-1078.doi:10.1007/s11739-017-1634-8
Querney J, Singh SI, Sebbag I. Tracheal deviation with phrenic nerve palsy after brachial plexus block. Anaesth Rep. 2021;9:41-43. doi:10.1002/anr3.12100
Geissler B, Wagner T, Dorn R, et al. Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel’s thyroiditis) caused by an occlusive vasculitis. J Endocrinol Invest. 2001;24:111-115. doi:10.1007/BF03343824
Kim HJ, Choi YS, Park SH, et al. Difficult endotracheal intubation secondary to tracheal deviation and stenosis in a patient with severe kyphoscoliosis: a case report. Korean J Anesthesiol. 2016;69:386-389. doi:10.4097/kjae.2016.69.4.386
Crabb IJ. Anterior deviation of the trachea. Anaesthesia. 2001;56:284-286.doi:10.1046/j.1365-2044.2001.01918-17.x
De Cassai A, Boscolo A, Rose K, et al. Predictive parameters of difficult intubation in thyroid surgery: a meta-analysis. Minerva Anestesiol. 2020;86:317-326. doi:10.23736/S0375-9393.19.14127-2
Davies R. Difficult tracheal intubation secondary to a tracheal diverticulum and a 90 degree deviation in the trachea. Anaesthesia. 2000;55:923-925. doi:10.1046/j.1365-2044.2000.01664-18.x
Cameron RB, Peacock WJ, Chang XG, et al. Double lumen endobronchial tube intubation: lessons learned from anatomy. BMC Anesthesiol. 2024;24:150. doi:10.1186/s12871-024-02517-6
Walls RM, Samuels-Kalow M, Perkins A. A new maneuver for endotracheal tube insertion during difficult GlideScope intubation. J Emerg Med. 2010;39:86-88. doi:10.1016/j.jemermed.2009.11.005
Buschmann CT, Tsokos M. Frequent and rare complications of resuscitation attempts. Intensive Care Med. 2009;35:397-404. doi:10.1007/s00134-008-1255-9
Greenland KB, Edwards MJ, Hutton NJ, et al. Changes in airway configuration with different head and neck positions using magnetic resonance imaging of normal airways: a new concept with possible clinical applications. Br J Anaesth. 2010;105:683-690. doi:10.1093/bja/aeq239
Takasugi Y, Futagawa K, Umeda T, et al. Thermophysical Properties of Thermosoftening Nasotracheal Tubes. Anesth Prog. 2018;65:100-105. doi:10.2344/anpr-65-02-06
Phelan MP. Use of the endotracheal bougie introducer for difficult intubations. Am J Emerg Med. 2004;22:479-482. doi:10.1016/j.ajem.2004.07.017
Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,4 and kyphoscoliosis.5 These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.
Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.
Case Presentation
A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO2 monitoring. The ETT was secured at 22 cm measured at the teeth.
After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).
With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).
Discussion
Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.9 However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.10
In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.11 Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.11
This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning.
Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.12 Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.13 Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.6
Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.14 When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.
Conclusions
This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.
Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,4 and kyphoscoliosis.5 These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.
Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.
Case Presentation
A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO2 monitoring. The ETT was secured at 22 cm measured at the teeth.
After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).
With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).
Discussion
Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.9 However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.10
In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.11 Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.11
This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning.
Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.12 Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.13 Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.6
Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.14 When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.
Conclusions
This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.
Creasy JD, Chiles C, Routh WD, et al. Overview of traumatic injury of the thoracic aorta. Radiogr Rev Publ Radiol Soc N Am Inc. 1997;17:27-45. doi:10.1148/radiographics.17.1.9017797
Yee AM, Christensen DN, Waterbrook AL, et al. Parapharyngeal abscess with tracheal deviation. Intern Emerg Med. 2017;12:1077-1078.doi:10.1007/s11739-017-1634-8
Querney J, Singh SI, Sebbag I. Tracheal deviation with phrenic nerve palsy after brachial plexus block. Anaesth Rep. 2021;9:41-43. doi:10.1002/anr3.12100
Geissler B, Wagner T, Dorn R, et al. Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel’s thyroiditis) caused by an occlusive vasculitis. J Endocrinol Invest. 2001;24:111-115. doi:10.1007/BF03343824
Kim HJ, Choi YS, Park SH, et al. Difficult endotracheal intubation secondary to tracheal deviation and stenosis in a patient with severe kyphoscoliosis: a case report. Korean J Anesthesiol. 2016;69:386-389. doi:10.4097/kjae.2016.69.4.386
Crabb IJ. Anterior deviation of the trachea. Anaesthesia. 2001;56:284-286.doi:10.1046/j.1365-2044.2001.01918-17.x
De Cassai A, Boscolo A, Rose K, et al. Predictive parameters of difficult intubation in thyroid surgery: a meta-analysis. Minerva Anestesiol. 2020;86:317-326. doi:10.23736/S0375-9393.19.14127-2
Davies R. Difficult tracheal intubation secondary to a tracheal diverticulum and a 90 degree deviation in the trachea. Anaesthesia. 2000;55:923-925. doi:10.1046/j.1365-2044.2000.01664-18.x
Cameron RB, Peacock WJ, Chang XG, et al. Double lumen endobronchial tube intubation: lessons learned from anatomy. BMC Anesthesiol. 2024;24:150. doi:10.1186/s12871-024-02517-6
Walls RM, Samuels-Kalow M, Perkins A. A new maneuver for endotracheal tube insertion during difficult GlideScope intubation. J Emerg Med. 2010;39:86-88. doi:10.1016/j.jemermed.2009.11.005
Buschmann CT, Tsokos M. Frequent and rare complications of resuscitation attempts. Intensive Care Med. 2009;35:397-404. doi:10.1007/s00134-008-1255-9
Greenland KB, Edwards MJ, Hutton NJ, et al. Changes in airway configuration with different head and neck positions using magnetic resonance imaging of normal airways: a new concept with possible clinical applications. Br J Anaesth. 2010;105:683-690. doi:10.1093/bja/aeq239
Takasugi Y, Futagawa K, Umeda T, et al. Thermophysical Properties of Thermosoftening Nasotracheal Tubes. Anesth Prog. 2018;65:100-105. doi:10.2344/anpr-65-02-06
Phelan MP. Use of the endotracheal bougie introducer for difficult intubations. Am J Emerg Med. 2004;22:479-482. doi:10.1016/j.ajem.2004.07.017
Creasy JD, Chiles C, Routh WD, et al. Overview of traumatic injury of the thoracic aorta. Radiogr Rev Publ Radiol Soc N Am Inc. 1997;17:27-45. doi:10.1148/radiographics.17.1.9017797
Yee AM, Christensen DN, Waterbrook AL, et al. Parapharyngeal abscess with tracheal deviation. Intern Emerg Med. 2017;12:1077-1078.doi:10.1007/s11739-017-1634-8
Querney J, Singh SI, Sebbag I. Tracheal deviation with phrenic nerve palsy after brachial plexus block. Anaesth Rep. 2021;9:41-43. doi:10.1002/anr3.12100
Geissler B, Wagner T, Dorn R, et al. Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel’s thyroiditis) caused by an occlusive vasculitis. J Endocrinol Invest. 2001;24:111-115. doi:10.1007/BF03343824
Kim HJ, Choi YS, Park SH, et al. Difficult endotracheal intubation secondary to tracheal deviation and stenosis in a patient with severe kyphoscoliosis: a case report. Korean J Anesthesiol. 2016;69:386-389. doi:10.4097/kjae.2016.69.4.386
Crabb IJ. Anterior deviation of the trachea. Anaesthesia. 2001;56:284-286.doi:10.1046/j.1365-2044.2001.01918-17.x
De Cassai A, Boscolo A, Rose K, et al. Predictive parameters of difficult intubation in thyroid surgery: a meta-analysis. Minerva Anestesiol. 2020;86:317-326. doi:10.23736/S0375-9393.19.14127-2
Davies R. Difficult tracheal intubation secondary to a tracheal diverticulum and a 90 degree deviation in the trachea. Anaesthesia. 2000;55:923-925. doi:10.1046/j.1365-2044.2000.01664-18.x
Cameron RB, Peacock WJ, Chang XG, et al. Double lumen endobronchial tube intubation: lessons learned from anatomy. BMC Anesthesiol. 2024;24:150. doi:10.1186/s12871-024-02517-6
Walls RM, Samuels-Kalow M, Perkins A. A new maneuver for endotracheal tube insertion during difficult GlideScope intubation. J Emerg Med. 2010;39:86-88. doi:10.1016/j.jemermed.2009.11.005
Buschmann CT, Tsokos M. Frequent and rare complications of resuscitation attempts. Intensive Care Med. 2009;35:397-404. doi:10.1007/s00134-008-1255-9
Greenland KB, Edwards MJ, Hutton NJ, et al. Changes in airway configuration with different head and neck positions using magnetic resonance imaging of normal airways: a new concept with possible clinical applications. Br J Anaesth. 2010;105:683-690. doi:10.1093/bja/aeq239
Takasugi Y, Futagawa K, Umeda T, et al. Thermophysical Properties of Thermosoftening Nasotracheal Tubes. Anesth Prog. 2018;65:100-105. doi:10.2344/anpr-65-02-06
Phelan MP. Use of the endotracheal bougie introducer for difficult intubations. Am J Emerg Med. 2004;22:479-482. doi:10.1016/j.ajem.2004.07.017
A Case Report of Unanticipated Difficult Intubation Due to Posterior Tracheal Angulation
A Case Report of Unanticipated Difficult Intubation Due to Posterior Tracheal Angulation
Rare Case of Necrobiotic Xanthogranuloma on the Scalp
Rare Case of Necrobiotic Xanthogranuloma on the Scalp
To the Editor:
Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.1 Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.2 In this article, we describe a rare presentation of NXG in location and skin type.
A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy.
We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.
Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.2 In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.2 In another study, paraproteinemia was detected in 82.1% of patients.3 The majority of case reports and systematic reviews detail periorbital or thoracic lesions.4 The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.
In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.3 The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care.
Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.
- Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672-2681.
- Spicknall KE, Mehregan DA. Necrobiotic xanthogranuloma. Int J Dermatol. 2009;48:1-10.
- Nelson CA, Zhong CS, Hashemi DA, et al. A multicenter cross-sectional study and systematic review of necrobiotic xanthogranuloma with proposed diagnostic criteria. JAMA Dermatol. 2020;156:270-279.
- Huynh KN, Nguyen BD. Histiocytosis and neoplasms of macrophagedendritic cell lineages: multimodality imaging with emphasis on PET/CT. Radiographics. 2021;41:576-594. doi: 10.1148/rg.2021200096
- Hilal T, DiCaudo DJ, Connolly SM, et al. Necrobiotic xanthogranuloma: a 30-year single-center experience. Ann Hematol. 2018;97:1471-1479.
- Oumeish OY, Oumeish I, Tarawneh M, et al. Necrobiotic xanthogranuloma associated with paraproteinemia and non- Hodgkin’s lymphoma developing into chronic lymphocytic leukemia: the first case reported in the literature and review of the literature. Int J Dermatol. 2006;45:306-310.
- Damsky W, Thakral D, McGeary MK, et al. Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare. J Am Acad Dermatol. 2020;82:612-621. doi:10.1016 /j.jaad.2019.05.098
- Wang A, Rahman NT, McGeary MK, et al. Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib. J Allergy Clin Immunol. 2021;147:1795-1809. doi:10.1016 /j.jaci.2020.10.012
- Stratman S, Amara S, Tan KJ, et al. Systemic Janus kinase inhibitors in the management of granuloma annulare. Arch Dermatol Res. 2025;317:743. doi:10.1007/s00403-025-04248-1
- McPhie ML, Swales WC, Gooderham MJ. Improvement of granulomatous skin conditions with tofacitinib in three patients: a case report. SAGE Open Med Case Rep. 2021;9:2050313X211039477. doi: 10.1177/2050313X211039477
- Sood S, Heung M, Georgakopoulos JR, et al. Use of Janus kinase inhibitors for granulomatous dermatoses: a systematic review. J Am Acad Dermatol. 2023;89:357-359. doi: 10.1016/j.jaad.2023.03.024
To the Editor:
Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.1 Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.2 In this article, we describe a rare presentation of NXG in location and skin type.
A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy.
We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.
Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.2 In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.2 In another study, paraproteinemia was detected in 82.1% of patients.3 The majority of case reports and systematic reviews detail periorbital or thoracic lesions.4 The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.
In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.3 The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care.
Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.
To the Editor:
Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.1 Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.2 In this article, we describe a rare presentation of NXG in location and skin type.
A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy.
We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.
Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.2 In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.2 In another study, paraproteinemia was detected in 82.1% of patients.3 The majority of case reports and systematic reviews detail periorbital or thoracic lesions.4 The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.
In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.3 The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care.
Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.
- Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672-2681.
- Spicknall KE, Mehregan DA. Necrobiotic xanthogranuloma. Int J Dermatol. 2009;48:1-10.
- Nelson CA, Zhong CS, Hashemi DA, et al. A multicenter cross-sectional study and systematic review of necrobiotic xanthogranuloma with proposed diagnostic criteria. JAMA Dermatol. 2020;156:270-279.
- Huynh KN, Nguyen BD. Histiocytosis and neoplasms of macrophagedendritic cell lineages: multimodality imaging with emphasis on PET/CT. Radiographics. 2021;41:576-594. doi: 10.1148/rg.2021200096
- Hilal T, DiCaudo DJ, Connolly SM, et al. Necrobiotic xanthogranuloma: a 30-year single-center experience. Ann Hematol. 2018;97:1471-1479.
- Oumeish OY, Oumeish I, Tarawneh M, et al. Necrobiotic xanthogranuloma associated with paraproteinemia and non- Hodgkin’s lymphoma developing into chronic lymphocytic leukemia: the first case reported in the literature and review of the literature. Int J Dermatol. 2006;45:306-310.
- Damsky W, Thakral D, McGeary MK, et al. Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare. J Am Acad Dermatol. 2020;82:612-621. doi:10.1016 /j.jaad.2019.05.098
- Wang A, Rahman NT, McGeary MK, et al. Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib. J Allergy Clin Immunol. 2021;147:1795-1809. doi:10.1016 /j.jaci.2020.10.012
- Stratman S, Amara S, Tan KJ, et al. Systemic Janus kinase inhibitors in the management of granuloma annulare. Arch Dermatol Res. 2025;317:743. doi:10.1007/s00403-025-04248-1
- McPhie ML, Swales WC, Gooderham MJ. Improvement of granulomatous skin conditions with tofacitinib in three patients: a case report. SAGE Open Med Case Rep. 2021;9:2050313X211039477. doi: 10.1177/2050313X211039477
- Sood S, Heung M, Georgakopoulos JR, et al. Use of Janus kinase inhibitors for granulomatous dermatoses: a systematic review. J Am Acad Dermatol. 2023;89:357-359. doi: 10.1016/j.jaad.2023.03.024
- Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672-2681.
- Spicknall KE, Mehregan DA. Necrobiotic xanthogranuloma. Int J Dermatol. 2009;48:1-10.
- Nelson CA, Zhong CS, Hashemi DA, et al. A multicenter cross-sectional study and systematic review of necrobiotic xanthogranuloma with proposed diagnostic criteria. JAMA Dermatol. 2020;156:270-279.
- Huynh KN, Nguyen BD. Histiocytosis and neoplasms of macrophagedendritic cell lineages: multimodality imaging with emphasis on PET/CT. Radiographics. 2021;41:576-594. doi: 10.1148/rg.2021200096
- Hilal T, DiCaudo DJ, Connolly SM, et al. Necrobiotic xanthogranuloma: a 30-year single-center experience. Ann Hematol. 2018;97:1471-1479.
- Oumeish OY, Oumeish I, Tarawneh M, et al. Necrobiotic xanthogranuloma associated with paraproteinemia and non- Hodgkin’s lymphoma developing into chronic lymphocytic leukemia: the first case reported in the literature and review of the literature. Int J Dermatol. 2006;45:306-310.
- Damsky W, Thakral D, McGeary MK, et al. Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare. J Am Acad Dermatol. 2020;82:612-621. doi:10.1016 /j.jaad.2019.05.098
- Wang A, Rahman NT, McGeary MK, et al. Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib. J Allergy Clin Immunol. 2021;147:1795-1809. doi:10.1016 /j.jaci.2020.10.012
- Stratman S, Amara S, Tan KJ, et al. Systemic Janus kinase inhibitors in the management of granuloma annulare. Arch Dermatol Res. 2025;317:743. doi:10.1007/s00403-025-04248-1
- McPhie ML, Swales WC, Gooderham MJ. Improvement of granulomatous skin conditions with tofacitinib in three patients: a case report. SAGE Open Med Case Rep. 2021;9:2050313X211039477. doi: 10.1177/2050313X211039477
- Sood S, Heung M, Georgakopoulos JR, et al. Use of Janus kinase inhibitors for granulomatous dermatoses: a systematic review. J Am Acad Dermatol. 2023;89:357-359. doi: 10.1016/j.jaad.2023.03.024
Rare Case of Necrobiotic Xanthogranuloma on the Scalp
Rare Case of Necrobiotic Xanthogranuloma on the Scalp
PRACTICE POINTS
- In skin of color, necrobiotic xanthogranuloma can appear orange or brown compared to its yellow appearance in lighter skin types.
- When necrobiotic xanthogranuloma is suspected, a thorough malignancy workup should be conducted.
Direct Care Dermatology: Weighing the Pros and Cons for the Early-Career Physician
Direct Care Dermatology: Weighing the Pros and Cons for the Early-Career Physician
As the health care landscape continues to shift, direct care (also known as direct pay) models have emerged as attractive alternatives to traditional insurance-based practice. For dermatology residents poised to enter the workforce, the direct care model offers potential advantages in autonomy, patient relationships, and work-life balance, but not without considerable risks and operational challenges. This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.
The transition from dermatology residency to clinical practice allows for a variety of paths, from large academic institutions to private practice to corporate entities (private equity–owned groups). In recent years, the direct care model has gained traction, particularly among physicians seeking greater autonomy and a more sustainable pace of practice.
Direct care dermatology practices operate outside the constraints of third-party payers, offering patients transparent pricing and direct access to care in exchange for fees paid out of pocket. By eliminating insurance companies as the middleman, it allows for less overhead, longer visits with patients, and increased access to care; however, though this model may seem appealing, direct care practices are not without their own set of challenges, especially amid rising concerns over physician burnout and administrative burden.
This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.
The Case for Direct Care Dermatology
The Challenges of Going Direct
Despite its appeal, starting a direct care practice is not without substantial risks and hurdles—particularly for residents just out of training. These challenges include financial risks and startup costs, market uncertainty, lack of mentorship or support, and limitations in treating complex dermatologic conditions.
Considerations for Residents
Before committing to practicing via a direct care model, dermatology residents should reflect on the following:
- Risk tolerance: Are you comfortable navigating the business and financial risk?
- Location: Does your target community have patients willing and able to pay out of pocket?
- Scope of interest: Will a direct care practice align with your clinical passions?
- Support systems: Do you have access to mentors, legal and financial advisors, and operational support?
- Long-term goals: Are you building a lifestyle practice, a scalable business, or a stepping stone to a future opportunity?
Ultimately, the decision to pursue a direct care model requires careful reflection on personal values, financial preparedness, and the unique needs of the community one intends to serve.
Final Thoughts
The direct care dermatology model offers an appealing alternative to traditional practice, especially for those prioritizing autonomy, patient connection, and work-life balance; however, it demands an entrepreneurial spirit as well as careful planning and an acceptance of financial uncertainty—factors that may pose challenges for new graduates. For dermatology residents, the decision to pursue direct care should be grounded in personal values, practical considerations, and a clear understanding of both the opportunities and limitations of this evolving practice model.
- Sinsky CA, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: a time and motion study in 4 specialties. Ann Intern Med.
- Dorrell DN, Feldman S, Wei-ting Huang W. The most common causes of burnout among US academic dermatologists based on a survey study. J Am Acad of Dermatol. 2019;81:269-270.
- Carlasare LE. Defining the place of direct primary care in a value-based care system. WMJ. 2018;117:106-110.
As the health care landscape continues to shift, direct care (also known as direct pay) models have emerged as attractive alternatives to traditional insurance-based practice. For dermatology residents poised to enter the workforce, the direct care model offers potential advantages in autonomy, patient relationships, and work-life balance, but not without considerable risks and operational challenges. This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.
The transition from dermatology residency to clinical practice allows for a variety of paths, from large academic institutions to private practice to corporate entities (private equity–owned groups). In recent years, the direct care model has gained traction, particularly among physicians seeking greater autonomy and a more sustainable pace of practice.
Direct care dermatology practices operate outside the constraints of third-party payers, offering patients transparent pricing and direct access to care in exchange for fees paid out of pocket. By eliminating insurance companies as the middleman, it allows for less overhead, longer visits with patients, and increased access to care; however, though this model may seem appealing, direct care practices are not without their own set of challenges, especially amid rising concerns over physician burnout and administrative burden.
This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.
The Case for Direct Care Dermatology
The Challenges of Going Direct
Despite its appeal, starting a direct care practice is not without substantial risks and hurdles—particularly for residents just out of training. These challenges include financial risks and startup costs, market uncertainty, lack of mentorship or support, and limitations in treating complex dermatologic conditions.
Considerations for Residents
Before committing to practicing via a direct care model, dermatology residents should reflect on the following:
- Risk tolerance: Are you comfortable navigating the business and financial risk?
- Location: Does your target community have patients willing and able to pay out of pocket?
- Scope of interest: Will a direct care practice align with your clinical passions?
- Support systems: Do you have access to mentors, legal and financial advisors, and operational support?
- Long-term goals: Are you building a lifestyle practice, a scalable business, or a stepping stone to a future opportunity?
Ultimately, the decision to pursue a direct care model requires careful reflection on personal values, financial preparedness, and the unique needs of the community one intends to serve.
Final Thoughts
The direct care dermatology model offers an appealing alternative to traditional practice, especially for those prioritizing autonomy, patient connection, and work-life balance; however, it demands an entrepreneurial spirit as well as careful planning and an acceptance of financial uncertainty—factors that may pose challenges for new graduates. For dermatology residents, the decision to pursue direct care should be grounded in personal values, practical considerations, and a clear understanding of both the opportunities and limitations of this evolving practice model.
As the health care landscape continues to shift, direct care (also known as direct pay) models have emerged as attractive alternatives to traditional insurance-based practice. For dermatology residents poised to enter the workforce, the direct care model offers potential advantages in autonomy, patient relationships, and work-life balance, but not without considerable risks and operational challenges. This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.
The transition from dermatology residency to clinical practice allows for a variety of paths, from large academic institutions to private practice to corporate entities (private equity–owned groups). In recent years, the direct care model has gained traction, particularly among physicians seeking greater autonomy and a more sustainable pace of practice.
Direct care dermatology practices operate outside the constraints of third-party payers, offering patients transparent pricing and direct access to care in exchange for fees paid out of pocket. By eliminating insurance companies as the middleman, it allows for less overhead, longer visits with patients, and increased access to care; however, though this model may seem appealing, direct care practices are not without their own set of challenges, especially amid rising concerns over physician burnout and administrative burden.
This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.
The Case for Direct Care Dermatology
The Challenges of Going Direct
Despite its appeal, starting a direct care practice is not without substantial risks and hurdles—particularly for residents just out of training. These challenges include financial risks and startup costs, market uncertainty, lack of mentorship or support, and limitations in treating complex dermatologic conditions.
Considerations for Residents
Before committing to practicing via a direct care model, dermatology residents should reflect on the following:
- Risk tolerance: Are you comfortable navigating the business and financial risk?
- Location: Does your target community have patients willing and able to pay out of pocket?
- Scope of interest: Will a direct care practice align with your clinical passions?
- Support systems: Do you have access to mentors, legal and financial advisors, and operational support?
- Long-term goals: Are you building a lifestyle practice, a scalable business, or a stepping stone to a future opportunity?
Ultimately, the decision to pursue a direct care model requires careful reflection on personal values, financial preparedness, and the unique needs of the community one intends to serve.
Final Thoughts
The direct care dermatology model offers an appealing alternative to traditional practice, especially for those prioritizing autonomy, patient connection, and work-life balance; however, it demands an entrepreneurial spirit as well as careful planning and an acceptance of financial uncertainty—factors that may pose challenges for new graduates. For dermatology residents, the decision to pursue direct care should be grounded in personal values, practical considerations, and a clear understanding of both the opportunities and limitations of this evolving practice model.
- Sinsky CA, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: a time and motion study in 4 specialties. Ann Intern Med.
- Dorrell DN, Feldman S, Wei-ting Huang W. The most common causes of burnout among US academic dermatologists based on a survey study. J Am Acad of Dermatol. 2019;81:269-270.
- Carlasare LE. Defining the place of direct primary care in a value-based care system. WMJ. 2018;117:106-110.
- Sinsky CA, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: a time and motion study in 4 specialties. Ann Intern Med.
- Dorrell DN, Feldman S, Wei-ting Huang W. The most common causes of burnout among US academic dermatologists based on a survey study. J Am Acad of Dermatol. 2019;81:269-270.
- Carlasare LE. Defining the place of direct primary care in a value-based care system. WMJ. 2018;117:106-110.
Direct Care Dermatology: Weighing the Pros and Cons for the Early-Career Physician
Direct Care Dermatology: Weighing the Pros and Cons for the Early-Career Physician
PRACTICE POINTS
- Direct care practices may be the new horizon of health care.
- Starting a direct care practice offers autonomy but demands entrepreneurial readiness.
- New dermatologists can enjoy control over scheduling, pricing, and patient care, but success requires business acumen, financial planning, and comfort with risk.
Streamlined Testosterone Order Template to Improve the Diagnosis and Evaluation of Hypogonadism in Veterans
Streamlined Testosterone Order Template to Improve the Diagnosis and Evaluation of Hypogonadism in Veterans
Testosterone therapy is administered following pragmatic diagnostic evaluation and workup to assess whether an adult male is hypogonadal, based on symptoms consistent with androgen deficiency and low morning serum testosterone concentrations on ≥ 2 occasions. Effects of testosterone administration include the development or maintenance of secondary sexual characteristics and increases in libido, muscle strength, fat-free mass, and bone density.
Testosterone prescriptions have markedly increased in the past 20 years, including within the US Department of Veterans Affairs (VA) health care system.1-3 This trend may be influenced by various factors, including patient perceptions of benefit, an increase in marketing, and the availability of more user-friendly formulations.
Since 2006, evidence-based clinical practice guidelines have recommended specific clinical and laboratory evaluation and counseling prior to starting testosterone replacement therapy (TRT).4-8 However, research has shown poor adherence to these recommendations, including at the VA, which raises concerns about inappropriate TRT initiation without proper diagnostic evaluation.9,10 Observational research has suggested a possible link between testosterone therapy and increased risk of cardiovascular (CV) events. The US Food and Drug Administration prescribing information includes boxed warnings about potential risks of high blood pressure, myocardial infarction, stroke, and CV-related mortality with testosterone treatment, contact transfer of transdermal testosterone, and pulmonary oil microembolism with testosterone undecanoate injections.11-15
A VA Office of Inspector General (OIG) review of VA clinician adherence to clinical and laboratory evaluation guidelines for testosterone deficiency found poor adherence among VA practitioners and made recommendations for improvement.4,15 These focused on establishing clinical signs and symptoms consistent with testosterone deficiency, confirming hypogonadism by repeated testosterone testing, determining the etiology of hypogonadism by measuring gonadotropins, initiating a discussion of risks and benefits of TRT, and assessing clinical improvement and obtaining an updated hematocrit test within 3 to 6 months of initiation.
The VA Puget Sound Health Care System (VAPSHCS) developed a local prior authorization template to assist health care practitioners (HCPs) to address the OIG recommendations. This testosterone order template (TOT) aimed to improve the diagnosis, evaluation, and monitoring of TRT in males with hypogonadism, combined with existing VA pharmacy criteria for the use of testosterone based on Endocrine Society guidelines. A version of the VAPSHCS TOT was approved as the national VA Computerized Patient Record System (CPRS) template.
Preliminary evaluation of the TOT suggested improved short-term adherence to guideline recommendations following implementation.16 This quality improvement study sought to assess the long-term effectiveness of the TOT with respect to clinical practice guideline adherence. The OIG did not address prostate-specific antigen (PSA) monitoring because understanding of the relationship between TRT and the risks of elevated PSA levels remains incomplete.6,17 This project hypothesized that implementation of a pharmacy-managed TOT incorporated into CPRS would result in higher adherence rates to guideline-recommended clinical and laboratory evaluation, in addition to counseling of men with hypogonadism prior to initiation of TRT.
Methods
Eligible participants were cisgender males who received a new testosterone prescription, had ≥ 2 clinic visits at VAPSHCS, and no previous testosterone prescription in the previous 2 years. Individuals were excluded if they had testosterone administered at VAPSHCS; were prescribed testosterone at another facility (VA or community-based); pilot tested an initial version of the TOT prior to November 30, 2019; or had an International Classification of Diseases, Tenth Revision codes for hypopituitarism, gender identity disorder, history of sexual assignment, or Klinefelter syndrome for which testosterone therapy was already approved. Patients who met the inclusion criteria were identified by an algorithm developed by the VAPSHCS pharmacoeconomist.
This quality improvement project used a retrospective, pre-post experimental design. Electronic chart review and systematic manual review of all eligible patient charts were performed for the pretemplate period (December 1, 2018, to November 30, 2019) and after the template implementation, (December 1, 2021, to November 30, 2022).
An initial version of the TOT was implemented on July 1, 2019, but was not fully integrated into CPRS until early 2020; individuals in whom the TOT was used prior to November 30, 2019, were excluded. Data from the initial period of the COVID-19 pandemic were avoided because of alterations in clinic and prescribing practices. As a quality improvement project, the TOT evaluation was exempt from formal review by the VAPSHCS Institutional Review Board, as determined by the Director of the Office of Transformation/Quality/Safety/Value.
Interventions
Testosterone is a Schedule III controlled substance with potential risks and a propensity for varied prescribing practices. It was designated as a restricted drug requiring a prior authorization drug request (PADR) for which a specific TOT was developed, approved by the VAPSHCS Pharmacy and Therapeutics Committee, and incorporated into CPRS. A team of pharmacists, primary care physicians, geriatricians, endocrinologists, and health informatics experts created and developed the TOT. Pharmacists managed and monitored its completion.
The process for prescribing testosterone via the TOT is outlined in the eAppendix. When an HCP orders testosterone in CPRS, reminders prompt them to use the TOT and indicate required laboratory measurements (an order set is provided). Completion of TOT is not necessary to order testosterone for patients with an existing diagnosis of an organic cause of hypogonadism (eg, Klinefelter syndrome or hypopituitarism) or transgender women (assigned male at birth). In the TOT, the prescriber must also indicate signs and symptoms of testosterone deficiency; required laboratory tests; and counseling regarding potential risks and benefits of TRT. A pharmacist reviews the TOT and either approves or rejects the testosterone prescription and provides follow-up guidance to the prescriber. The completed TOT serves as documentation of guideline adherence in CPRS. The TOT also includes sections for first renewal testosterone prescriptions, addressing guideline recommendations for follow-up laboratory evaluation and clinical response to TRT. Due to limited completion of this section in the posttemplate period, evaluating adherence to follow-up recommendations was not feasible.
Measures
This project assessed the percentage of patients in the posttemplate period vs pretemplate period with an approved PADR. Documentation of specific guideline-recommended measures was assessed: signs and symptoms of testosterone deficiency; ≥ 2 serum testosterone measurements (≥ 2 total, free and total, or 2 free testosterone levels, and ≥ 1 testosterone level before 10
The project also assessed the proportion of patients in the posttemplate period vs pretemplate period who had all hormone tests (≥ 2 serum testosterone and LH and FSH concentrations), all laboratory tests (hormone tests and hematocrit), and all 5 guideline-recommended measures.
Analysis
Statistical comparisons between the proportions of patients in the pretemplate and posttemplate periods for each measure were performed using a χ2 test, without correction for multiple comparisons. All analyses were conducted using Stata version 10.0. A P value < .05 was considered significant for all comparisons.
Results
Chart review identified 189 patients in the pretemplate period and 113 patients in the posttemplate period with a new testosterone prescription (Figure). After exclusions, 91 and 49 patients, respectively, met eligibility criteria (Table 1). Fifty-six patients (62%) pretemplate and 40 patients (82%) posttemplate (P = .015) had approved PADRs and comprised the groups that were analyzed (Table 2).



The mean age and body mass index were similar in the pretemplate and posttemplate periods, but there was variation in the proportions of patients aged < 70 years and those with a body mass index < 30 between the groups. The most common diagnosis in both groups was testicular hypofunction, and the most common comorbidity was type 2 diabetes mellitus. Concomitant use of opioids or glucocorticoids that can lower testosterone levels was rare. Most testosterone prescriptions originated from primary care clinics in both periods: 68 (75%) in the pretemplate period and 35 (71%) in the posttemplate period. Most testosterone treatment was delivered by intramuscular injection.
In the posttemplate period vs pretemplate period, the proportion of patients with an approved PADR (82% vs 62%, P = .02), and documentation of signs and symptoms of hypogonadism (93% vs 71%, P = .002) prior to starting TRT were higher, while the percentage of patients having ≥ 2 testosterone measurements (85% vs 89%, P = .53), ≥ 1 testosterone level before 10 AM (78% vs 75%, P = .70), and hematocrit measured (95% vs 91%, P = .47) were similar. Rates of LH and FSH testing were higher in the posttemplate period (80%) vs the pretemplate period (63%) but did not achieve statistical significance (P = .07), and discussion of the risks and benefits of TRT was higher in the posttemplate period (58%) vs the pretemplate period (34%) (P = .02). The percentage of patients who had all hormone measurements (total and/or free testosterone, LH, and FSH) was higher in the posttemplate period (78%) vs the pretemplate period (59%) but did not achieve statistical significance (P = .06). The rates of all guideline-recommended laboratory test orders were higher in the posttemplate period (78%) vs the pretemplate period (55%) (P = .03), and all 5 guideline-recommended clinical and laboratory measures were higher in the posttemplate period (45%) vs the pretemplate period (18%) (P = .004).
Discussion
The implementation of a pharmacy-managed TOT in CPRS demonstrated higher adherence to evidence-based guidelines for diagnosing and evaluating hypogonadism before TRT. After TOT implementation, a higher proportion of patients had documented signs and symptoms of testosterone deficiency, underwent all recommended laboratory tests, and had discussions about the risks and benefits of TRT. Adherence to 5 clinical and laboratory measures recommended by Endocrine Society guidelines was higher after TOT implementation, indicating improved prescribing practices.4
The requirement for TOT completion before testosterone prescription and its management by trained pharmacists likely contributed to higher adherence to guideline recommendations than previously reported. Integration of the TOT into CPRS with pharmacy oversight may have enhanced adherence by summarizing and codifying evidence-based guideline recommendations for clinical and biochemical evaluation prior to TRT initiation, offering relevant education to clinicians and pharmacists, automatically importing pertinent clinical information and laboratory results, and generating CPRS documentation to reduce clinician burden during patient care.
The proportion of patients with documented signs and symptoms of testosterone deficiency before TRT increased from the pretemplate period (71%) to the posttemplate period (93%), indicating that most patients receiving TRT had clinical manifestations of hypogonadism. This aligns with Endocrine Society guidelines, which define hypogonadism as a clinical disorder characterized by clinical manifestations of testosterone deficiency and persistently low serum testosterone levels on ≥ 2 separate occasions.4,6 However, recent trends in direct-to-consumer advertising for testosterone and the rise of “low T” clinics may contribute to increased testing, varied practices, and inappropriate testosterone therapy initiation (eg, in men with low testosterone levels who lack symptoms of hypogonadism).18 Improved adherence in documenting clinical hypogonadism with implementation of the TOT reinforces the value of incorporating educational material, as previously reported.11
Adherence to guideline recommendations following implementation of the TOT in this project was higher than those previously reported. In a study of 111,631 outpatient veterans prescribed testosterone from 2009 to 2012, only 18.3% had ≥ 2 testosterone prescriptions, and 3.5% had ≥ 2 testosterone, LH, and FSH levels measured prior to the initiation of a TRT.9 In a report of 63,534 insured patients who received TRT from 2010 to 2012, 40.3% had ≥ 2 testosterone prescriptions, and 12% had LH and/or FSH measured prior to the initiation.8
Low rates of guideline-recommended laboratory tests prior to initiation of testosterone treatment were reported in prior non-VA studies.19,20 Poor guideline adherence reinforces the need for clinician education or other methods to improve TRT and ensure appropriate prescribing practices across health care systems. The TOT described in this project is a sustainable clinical tool with the potential to improve testosterone prescribing practices.
The high rates of adherence to guideline recommendations at VAPSHCS likely stem from local endocrine expertise and ongoing educational initiatives, as well as the requirement for template completion before testosterone prescription. However, most testosterone prescriptions were initiated by primary care and monitored by pharmacists with varying degrees of training and clinical experience in hypogonadism and TRT.
However, adherence to guideline recommendations was modest, suggesting there is still an opportunity for improvement. The decision to initiate therapy should be made only after appropriate counseling with patients regarding its potential benefits and risks. Reports on the CV risk of TRT have been mixed. The 2023 TRAVERSE study found no increase in major adverse CV events among older men with hypogonadism and pre-existing CV risks undergoing TRT, but noted higher instances of pulmonary embolism, atrial fibrillation, and acute kidney injury.21 This highlights the need for clinicians to continue to engage in informed decision-making with patients. Effective pretreatment counseling is important but time-consuming; future TOT monitoring and modifications could consider mandatory checkboxes to document counseling on TRT risks and benefits.
The TOT described in this study could be adapted and incorporated into the prescribing process and electronic health record of larger health care systems. Use of an electronic template allows for automatic real-time dashboard monitoring of organization performance. The TOT described could be modified or simplified for specialty or primary care clinics or individual practitioners to improve adherence to evidence-based guideline recommendations and quality of care.
Strengths
A strength of this study is the multidisciplinary team (composed of stakeholders with experience in VA health care system and subject matter experts in hypogonadism) that developed and incorporated a user-friendly template for testosterone prescriptions; the use of evidence-based guideline recommendations; and the use of a structured chart review permitted accurate assessment of adherence to recommendations to document signs and symptoms of testosterone deficiency and a discussion of potential risks and benefits prior to TRT. To our knowledge, these recommendations have not been assessed in previous reports.
Limitations
The retrospective pre-post design of this study precludes a conclusion that implementation of the TOT caused the increase in adherence to guideline recommendations. Improved adherence could have resulted from the ongoing development of the preauthorization process for testosterone prescriptions or other changes over time. However, the preauthorization process had already been established for many years prior to template implementation. Forty-nine patients had new prescriptions for testosterone in the posttemplate period compared to 91 in the pretemplate period, but TRT was initiated in accordance with guideline recommendations more appropriately in the posttemplate period. The study’s sample size was small, and many eligible patients were excluded; however, exclusions were necessary to evaluate men who had new testosterone prescriptions for which the template was designed. Most men excluded were already taking testosterone.
Conclusions
The implementation of a CPRS-based TOT improved adherence to evidence-based guidelines for the diagnosis, evaluation, and counseling of patients with hypogonadism before starting TRT. While there were improvements in adherence with the TOT, the relatively low proportion of patients with documentation of TRT risks and benefits and all guideline recommendations highlights the need for additional efforts to further strengthen adherence to guideline recommendations and ensure appropriate evaluation, counseling, and prescribing practices before initiating TRT.
- Layton JB, Li D, Meier CR, et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J Clin Endocrinol Metab. 2014;99:835-842. doi:10.1210/jc.2013-3570
- Baillargeon J, Kuo YF, Westra JR, et al. Testosterone prescribing in the United States, 2002-2016. JAMA. 2018;320:200-202. doi:10.1001/jama.2018.7999
- Jasuja GK, Bhasin S, Rose AJ. Patterns of testosterone prescription overuse. Curr Opin Endocrinol Diabetes Obes. 2017;24:240-245. doi:10.1097/MED.0000000000000336
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2006;91:1995-2010. doi:10.1210/jc.2005-2847
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536-2559. doi:10.1210/jc.2009-2354
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:1715-1744. doi:10.1210/jc.2018-00229
- Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200:423-432. doi:10.1016/j.juro.2018.03.115
- Muram D, Zhang X, Cui Z, et al. Use of hormone testing for the diagnosis and evaluation of male hypogonadism and monitoring of testosterone therapy: application of hormone testing guideline recommendations in clinical practice. J Sex Med. 2015;12:1886-1894. doi:10.1111/jsm.12968
- Jasuja GK, Bhasin S, Reisman JI, et al. Ascertainment of testosterone prescribing practices in the VA. Med Care. 2015;53:746-752. doi:10.1097/MLR.0000000000000398?
- Jasuja GK, Bhasin S, Reisman JI, et al. Who gets testosterone? Patient characteristics associated with testosterone prescribing in the Veteran Affairs system: a cross-sectional study. J Gen Intern Med. 2017;32:304-311. doi:10.1007/s11606-016-3940-7
- Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109-122. doi:10.1056/NEJMoa1000485
- Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829-1836. doi:10.1001/jama.2013.280386
- Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9:e85805. doi:10.1371/journal.pone.0085805
- US Food and Drug Administration. FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. FDA.gov. March 3, 2015. Updated February 28, 2025. Accessed July 8, 2025. http://www.fda.gov/Drugs/DrugSafety/ucm436259.htm
- US Dept of Veterans Affairs, Office of Inspector General. Healthcare inspection – testosterone replacement therapy initiation and follow-up evaluation in VA male patients. April 11, 2018. Accessed July 8, 2025. https://www.vaoig.gov/reports/national-healthcare-review/healthcare-inspection-testosterone-replacement-therapy
- Narla R, Mobley D, Nguyen EHK, et al. Preliminary evaluation of an order template to improve diagnosis and testosterone therapy of hypogonadism in veterans. Fed Pract. 2021;38:121-127. doi:10.12788/fp.0103
- Bhasin S, Travison TG, Pencina KM, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Netw Open. 2023;6:e2348692. doi:10.1001/jamanetworkopen.2023.48692
- Dubin JM, Jesse E, Fantus RJ, et al. Guideline-discordant care among direct-to-consumer testosterone therapy platforms. JAMA Intern Med. 2022;182:1321-1323. doi:10.1001/jamainternmed.2022.4928
- Baillargeon J, Urban RJ, Ottenbacher KJ, et al. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med. 2013;173:1465-1466. doi:10.1001/jamainternmed.2013.6895
- Locke JA, Flannigan R, Günther OP, et al. Testosterone therapy: prescribing and monitoring patterns of practice in British Columbia. Can Urol Assoc J. 2021;15:e110-e117. doi:10.5489/cuaj.6586
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389:107-117. doi:10.1056/NEJMoa2215025
Testosterone therapy is administered following pragmatic diagnostic evaluation and workup to assess whether an adult male is hypogonadal, based on symptoms consistent with androgen deficiency and low morning serum testosterone concentrations on ≥ 2 occasions. Effects of testosterone administration include the development or maintenance of secondary sexual characteristics and increases in libido, muscle strength, fat-free mass, and bone density.
Testosterone prescriptions have markedly increased in the past 20 years, including within the US Department of Veterans Affairs (VA) health care system.1-3 This trend may be influenced by various factors, including patient perceptions of benefit, an increase in marketing, and the availability of more user-friendly formulations.
Since 2006, evidence-based clinical practice guidelines have recommended specific clinical and laboratory evaluation and counseling prior to starting testosterone replacement therapy (TRT).4-8 However, research has shown poor adherence to these recommendations, including at the VA, which raises concerns about inappropriate TRT initiation without proper diagnostic evaluation.9,10 Observational research has suggested a possible link between testosterone therapy and increased risk of cardiovascular (CV) events. The US Food and Drug Administration prescribing information includes boxed warnings about potential risks of high blood pressure, myocardial infarction, stroke, and CV-related mortality with testosterone treatment, contact transfer of transdermal testosterone, and pulmonary oil microembolism with testosterone undecanoate injections.11-15
A VA Office of Inspector General (OIG) review of VA clinician adherence to clinical and laboratory evaluation guidelines for testosterone deficiency found poor adherence among VA practitioners and made recommendations for improvement.4,15 These focused on establishing clinical signs and symptoms consistent with testosterone deficiency, confirming hypogonadism by repeated testosterone testing, determining the etiology of hypogonadism by measuring gonadotropins, initiating a discussion of risks and benefits of TRT, and assessing clinical improvement and obtaining an updated hematocrit test within 3 to 6 months of initiation.
The VA Puget Sound Health Care System (VAPSHCS) developed a local prior authorization template to assist health care practitioners (HCPs) to address the OIG recommendations. This testosterone order template (TOT) aimed to improve the diagnosis, evaluation, and monitoring of TRT in males with hypogonadism, combined with existing VA pharmacy criteria for the use of testosterone based on Endocrine Society guidelines. A version of the VAPSHCS TOT was approved as the national VA Computerized Patient Record System (CPRS) template.
Preliminary evaluation of the TOT suggested improved short-term adherence to guideline recommendations following implementation.16 This quality improvement study sought to assess the long-term effectiveness of the TOT with respect to clinical practice guideline adherence. The OIG did not address prostate-specific antigen (PSA) monitoring because understanding of the relationship between TRT and the risks of elevated PSA levels remains incomplete.6,17 This project hypothesized that implementation of a pharmacy-managed TOT incorporated into CPRS would result in higher adherence rates to guideline-recommended clinical and laboratory evaluation, in addition to counseling of men with hypogonadism prior to initiation of TRT.
Methods
Eligible participants were cisgender males who received a new testosterone prescription, had ≥ 2 clinic visits at VAPSHCS, and no previous testosterone prescription in the previous 2 years. Individuals were excluded if they had testosterone administered at VAPSHCS; were prescribed testosterone at another facility (VA or community-based); pilot tested an initial version of the TOT prior to November 30, 2019; or had an International Classification of Diseases, Tenth Revision codes for hypopituitarism, gender identity disorder, history of sexual assignment, or Klinefelter syndrome for which testosterone therapy was already approved. Patients who met the inclusion criteria were identified by an algorithm developed by the VAPSHCS pharmacoeconomist.
This quality improvement project used a retrospective, pre-post experimental design. Electronic chart review and systematic manual review of all eligible patient charts were performed for the pretemplate period (December 1, 2018, to November 30, 2019) and after the template implementation, (December 1, 2021, to November 30, 2022).
An initial version of the TOT was implemented on July 1, 2019, but was not fully integrated into CPRS until early 2020; individuals in whom the TOT was used prior to November 30, 2019, were excluded. Data from the initial period of the COVID-19 pandemic were avoided because of alterations in clinic and prescribing practices. As a quality improvement project, the TOT evaluation was exempt from formal review by the VAPSHCS Institutional Review Board, as determined by the Director of the Office of Transformation/Quality/Safety/Value.
Interventions
Testosterone is a Schedule III controlled substance with potential risks and a propensity for varied prescribing practices. It was designated as a restricted drug requiring a prior authorization drug request (PADR) for which a specific TOT was developed, approved by the VAPSHCS Pharmacy and Therapeutics Committee, and incorporated into CPRS. A team of pharmacists, primary care physicians, geriatricians, endocrinologists, and health informatics experts created and developed the TOT. Pharmacists managed and monitored its completion.
The process for prescribing testosterone via the TOT is outlined in the eAppendix. When an HCP orders testosterone in CPRS, reminders prompt them to use the TOT and indicate required laboratory measurements (an order set is provided). Completion of TOT is not necessary to order testosterone for patients with an existing diagnosis of an organic cause of hypogonadism (eg, Klinefelter syndrome or hypopituitarism) or transgender women (assigned male at birth). In the TOT, the prescriber must also indicate signs and symptoms of testosterone deficiency; required laboratory tests; and counseling regarding potential risks and benefits of TRT. A pharmacist reviews the TOT and either approves or rejects the testosterone prescription and provides follow-up guidance to the prescriber. The completed TOT serves as documentation of guideline adherence in CPRS. The TOT also includes sections for first renewal testosterone prescriptions, addressing guideline recommendations for follow-up laboratory evaluation and clinical response to TRT. Due to limited completion of this section in the posttemplate period, evaluating adherence to follow-up recommendations was not feasible.
Measures
This project assessed the percentage of patients in the posttemplate period vs pretemplate period with an approved PADR. Documentation of specific guideline-recommended measures was assessed: signs and symptoms of testosterone deficiency; ≥ 2 serum testosterone measurements (≥ 2 total, free and total, or 2 free testosterone levels, and ≥ 1 testosterone level before 10
The project also assessed the proportion of patients in the posttemplate period vs pretemplate period who had all hormone tests (≥ 2 serum testosterone and LH and FSH concentrations), all laboratory tests (hormone tests and hematocrit), and all 5 guideline-recommended measures.
Analysis
Statistical comparisons between the proportions of patients in the pretemplate and posttemplate periods for each measure were performed using a χ2 test, without correction for multiple comparisons. All analyses were conducted using Stata version 10.0. A P value < .05 was considered significant for all comparisons.
Results
Chart review identified 189 patients in the pretemplate period and 113 patients in the posttemplate period with a new testosterone prescription (Figure). After exclusions, 91 and 49 patients, respectively, met eligibility criteria (Table 1). Fifty-six patients (62%) pretemplate and 40 patients (82%) posttemplate (P = .015) had approved PADRs and comprised the groups that were analyzed (Table 2).



The mean age and body mass index were similar in the pretemplate and posttemplate periods, but there was variation in the proportions of patients aged < 70 years and those with a body mass index < 30 between the groups. The most common diagnosis in both groups was testicular hypofunction, and the most common comorbidity was type 2 diabetes mellitus. Concomitant use of opioids or glucocorticoids that can lower testosterone levels was rare. Most testosterone prescriptions originated from primary care clinics in both periods: 68 (75%) in the pretemplate period and 35 (71%) in the posttemplate period. Most testosterone treatment was delivered by intramuscular injection.
In the posttemplate period vs pretemplate period, the proportion of patients with an approved PADR (82% vs 62%, P = .02), and documentation of signs and symptoms of hypogonadism (93% vs 71%, P = .002) prior to starting TRT were higher, while the percentage of patients having ≥ 2 testosterone measurements (85% vs 89%, P = .53), ≥ 1 testosterone level before 10 AM (78% vs 75%, P = .70), and hematocrit measured (95% vs 91%, P = .47) were similar. Rates of LH and FSH testing were higher in the posttemplate period (80%) vs the pretemplate period (63%) but did not achieve statistical significance (P = .07), and discussion of the risks and benefits of TRT was higher in the posttemplate period (58%) vs the pretemplate period (34%) (P = .02). The percentage of patients who had all hormone measurements (total and/or free testosterone, LH, and FSH) was higher in the posttemplate period (78%) vs the pretemplate period (59%) but did not achieve statistical significance (P = .06). The rates of all guideline-recommended laboratory test orders were higher in the posttemplate period (78%) vs the pretemplate period (55%) (P = .03), and all 5 guideline-recommended clinical and laboratory measures were higher in the posttemplate period (45%) vs the pretemplate period (18%) (P = .004).
Discussion
The implementation of a pharmacy-managed TOT in CPRS demonstrated higher adherence to evidence-based guidelines for diagnosing and evaluating hypogonadism before TRT. After TOT implementation, a higher proportion of patients had documented signs and symptoms of testosterone deficiency, underwent all recommended laboratory tests, and had discussions about the risks and benefits of TRT. Adherence to 5 clinical and laboratory measures recommended by Endocrine Society guidelines was higher after TOT implementation, indicating improved prescribing practices.4
The requirement for TOT completion before testosterone prescription and its management by trained pharmacists likely contributed to higher adherence to guideline recommendations than previously reported. Integration of the TOT into CPRS with pharmacy oversight may have enhanced adherence by summarizing and codifying evidence-based guideline recommendations for clinical and biochemical evaluation prior to TRT initiation, offering relevant education to clinicians and pharmacists, automatically importing pertinent clinical information and laboratory results, and generating CPRS documentation to reduce clinician burden during patient care.
The proportion of patients with documented signs and symptoms of testosterone deficiency before TRT increased from the pretemplate period (71%) to the posttemplate period (93%), indicating that most patients receiving TRT had clinical manifestations of hypogonadism. This aligns with Endocrine Society guidelines, which define hypogonadism as a clinical disorder characterized by clinical manifestations of testosterone deficiency and persistently low serum testosterone levels on ≥ 2 separate occasions.4,6 However, recent trends in direct-to-consumer advertising for testosterone and the rise of “low T” clinics may contribute to increased testing, varied practices, and inappropriate testosterone therapy initiation (eg, in men with low testosterone levels who lack symptoms of hypogonadism).18 Improved adherence in documenting clinical hypogonadism with implementation of the TOT reinforces the value of incorporating educational material, as previously reported.11
Adherence to guideline recommendations following implementation of the TOT in this project was higher than those previously reported. In a study of 111,631 outpatient veterans prescribed testosterone from 2009 to 2012, only 18.3% had ≥ 2 testosterone prescriptions, and 3.5% had ≥ 2 testosterone, LH, and FSH levels measured prior to the initiation of a TRT.9 In a report of 63,534 insured patients who received TRT from 2010 to 2012, 40.3% had ≥ 2 testosterone prescriptions, and 12% had LH and/or FSH measured prior to the initiation.8
Low rates of guideline-recommended laboratory tests prior to initiation of testosterone treatment were reported in prior non-VA studies.19,20 Poor guideline adherence reinforces the need for clinician education or other methods to improve TRT and ensure appropriate prescribing practices across health care systems. The TOT described in this project is a sustainable clinical tool with the potential to improve testosterone prescribing practices.
The high rates of adherence to guideline recommendations at VAPSHCS likely stem from local endocrine expertise and ongoing educational initiatives, as well as the requirement for template completion before testosterone prescription. However, most testosterone prescriptions were initiated by primary care and monitored by pharmacists with varying degrees of training and clinical experience in hypogonadism and TRT.
However, adherence to guideline recommendations was modest, suggesting there is still an opportunity for improvement. The decision to initiate therapy should be made only after appropriate counseling with patients regarding its potential benefits and risks. Reports on the CV risk of TRT have been mixed. The 2023 TRAVERSE study found no increase in major adverse CV events among older men with hypogonadism and pre-existing CV risks undergoing TRT, but noted higher instances of pulmonary embolism, atrial fibrillation, and acute kidney injury.21 This highlights the need for clinicians to continue to engage in informed decision-making with patients. Effective pretreatment counseling is important but time-consuming; future TOT monitoring and modifications could consider mandatory checkboxes to document counseling on TRT risks and benefits.
The TOT described in this study could be adapted and incorporated into the prescribing process and electronic health record of larger health care systems. Use of an electronic template allows for automatic real-time dashboard monitoring of organization performance. The TOT described could be modified or simplified for specialty or primary care clinics or individual practitioners to improve adherence to evidence-based guideline recommendations and quality of care.
Strengths
A strength of this study is the multidisciplinary team (composed of stakeholders with experience in VA health care system and subject matter experts in hypogonadism) that developed and incorporated a user-friendly template for testosterone prescriptions; the use of evidence-based guideline recommendations; and the use of a structured chart review permitted accurate assessment of adherence to recommendations to document signs and symptoms of testosterone deficiency and a discussion of potential risks and benefits prior to TRT. To our knowledge, these recommendations have not been assessed in previous reports.
Limitations
The retrospective pre-post design of this study precludes a conclusion that implementation of the TOT caused the increase in adherence to guideline recommendations. Improved adherence could have resulted from the ongoing development of the preauthorization process for testosterone prescriptions or other changes over time. However, the preauthorization process had already been established for many years prior to template implementation. Forty-nine patients had new prescriptions for testosterone in the posttemplate period compared to 91 in the pretemplate period, but TRT was initiated in accordance with guideline recommendations more appropriately in the posttemplate period. The study’s sample size was small, and many eligible patients were excluded; however, exclusions were necessary to evaluate men who had new testosterone prescriptions for which the template was designed. Most men excluded were already taking testosterone.
Conclusions
The implementation of a CPRS-based TOT improved adherence to evidence-based guidelines for the diagnosis, evaluation, and counseling of patients with hypogonadism before starting TRT. While there were improvements in adherence with the TOT, the relatively low proportion of patients with documentation of TRT risks and benefits and all guideline recommendations highlights the need for additional efforts to further strengthen adherence to guideline recommendations and ensure appropriate evaluation, counseling, and prescribing practices before initiating TRT.
Testosterone therapy is administered following pragmatic diagnostic evaluation and workup to assess whether an adult male is hypogonadal, based on symptoms consistent with androgen deficiency and low morning serum testosterone concentrations on ≥ 2 occasions. Effects of testosterone administration include the development or maintenance of secondary sexual characteristics and increases in libido, muscle strength, fat-free mass, and bone density.
Testosterone prescriptions have markedly increased in the past 20 years, including within the US Department of Veterans Affairs (VA) health care system.1-3 This trend may be influenced by various factors, including patient perceptions of benefit, an increase in marketing, and the availability of more user-friendly formulations.
Since 2006, evidence-based clinical practice guidelines have recommended specific clinical and laboratory evaluation and counseling prior to starting testosterone replacement therapy (TRT).4-8 However, research has shown poor adherence to these recommendations, including at the VA, which raises concerns about inappropriate TRT initiation without proper diagnostic evaluation.9,10 Observational research has suggested a possible link between testosterone therapy and increased risk of cardiovascular (CV) events. The US Food and Drug Administration prescribing information includes boxed warnings about potential risks of high blood pressure, myocardial infarction, stroke, and CV-related mortality with testosterone treatment, contact transfer of transdermal testosterone, and pulmonary oil microembolism with testosterone undecanoate injections.11-15
A VA Office of Inspector General (OIG) review of VA clinician adherence to clinical and laboratory evaluation guidelines for testosterone deficiency found poor adherence among VA practitioners and made recommendations for improvement.4,15 These focused on establishing clinical signs and symptoms consistent with testosterone deficiency, confirming hypogonadism by repeated testosterone testing, determining the etiology of hypogonadism by measuring gonadotropins, initiating a discussion of risks and benefits of TRT, and assessing clinical improvement and obtaining an updated hematocrit test within 3 to 6 months of initiation.
The VA Puget Sound Health Care System (VAPSHCS) developed a local prior authorization template to assist health care practitioners (HCPs) to address the OIG recommendations. This testosterone order template (TOT) aimed to improve the diagnosis, evaluation, and monitoring of TRT in males with hypogonadism, combined with existing VA pharmacy criteria for the use of testosterone based on Endocrine Society guidelines. A version of the VAPSHCS TOT was approved as the national VA Computerized Patient Record System (CPRS) template.
Preliminary evaluation of the TOT suggested improved short-term adherence to guideline recommendations following implementation.16 This quality improvement study sought to assess the long-term effectiveness of the TOT with respect to clinical practice guideline adherence. The OIG did not address prostate-specific antigen (PSA) monitoring because understanding of the relationship between TRT and the risks of elevated PSA levels remains incomplete.6,17 This project hypothesized that implementation of a pharmacy-managed TOT incorporated into CPRS would result in higher adherence rates to guideline-recommended clinical and laboratory evaluation, in addition to counseling of men with hypogonadism prior to initiation of TRT.
Methods
Eligible participants were cisgender males who received a new testosterone prescription, had ≥ 2 clinic visits at VAPSHCS, and no previous testosterone prescription in the previous 2 years. Individuals were excluded if they had testosterone administered at VAPSHCS; were prescribed testosterone at another facility (VA or community-based); pilot tested an initial version of the TOT prior to November 30, 2019; or had an International Classification of Diseases, Tenth Revision codes for hypopituitarism, gender identity disorder, history of sexual assignment, or Klinefelter syndrome for which testosterone therapy was already approved. Patients who met the inclusion criteria were identified by an algorithm developed by the VAPSHCS pharmacoeconomist.
This quality improvement project used a retrospective, pre-post experimental design. Electronic chart review and systematic manual review of all eligible patient charts were performed for the pretemplate period (December 1, 2018, to November 30, 2019) and after the template implementation, (December 1, 2021, to November 30, 2022).
An initial version of the TOT was implemented on July 1, 2019, but was not fully integrated into CPRS until early 2020; individuals in whom the TOT was used prior to November 30, 2019, were excluded. Data from the initial period of the COVID-19 pandemic were avoided because of alterations in clinic and prescribing practices. As a quality improvement project, the TOT evaluation was exempt from formal review by the VAPSHCS Institutional Review Board, as determined by the Director of the Office of Transformation/Quality/Safety/Value.
Interventions
Testosterone is a Schedule III controlled substance with potential risks and a propensity for varied prescribing practices. It was designated as a restricted drug requiring a prior authorization drug request (PADR) for which a specific TOT was developed, approved by the VAPSHCS Pharmacy and Therapeutics Committee, and incorporated into CPRS. A team of pharmacists, primary care physicians, geriatricians, endocrinologists, and health informatics experts created and developed the TOT. Pharmacists managed and monitored its completion.
The process for prescribing testosterone via the TOT is outlined in the eAppendix. When an HCP orders testosterone in CPRS, reminders prompt them to use the TOT and indicate required laboratory measurements (an order set is provided). Completion of TOT is not necessary to order testosterone for patients with an existing diagnosis of an organic cause of hypogonadism (eg, Klinefelter syndrome or hypopituitarism) or transgender women (assigned male at birth). In the TOT, the prescriber must also indicate signs and symptoms of testosterone deficiency; required laboratory tests; and counseling regarding potential risks and benefits of TRT. A pharmacist reviews the TOT and either approves or rejects the testosterone prescription and provides follow-up guidance to the prescriber. The completed TOT serves as documentation of guideline adherence in CPRS. The TOT also includes sections for first renewal testosterone prescriptions, addressing guideline recommendations for follow-up laboratory evaluation and clinical response to TRT. Due to limited completion of this section in the posttemplate period, evaluating adherence to follow-up recommendations was not feasible.
Measures
This project assessed the percentage of patients in the posttemplate period vs pretemplate period with an approved PADR. Documentation of specific guideline-recommended measures was assessed: signs and symptoms of testosterone deficiency; ≥ 2 serum testosterone measurements (≥ 2 total, free and total, or 2 free testosterone levels, and ≥ 1 testosterone level before 10
The project also assessed the proportion of patients in the posttemplate period vs pretemplate period who had all hormone tests (≥ 2 serum testosterone and LH and FSH concentrations), all laboratory tests (hormone tests and hematocrit), and all 5 guideline-recommended measures.
Analysis
Statistical comparisons between the proportions of patients in the pretemplate and posttemplate periods for each measure were performed using a χ2 test, without correction for multiple comparisons. All analyses were conducted using Stata version 10.0. A P value < .05 was considered significant for all comparisons.
Results
Chart review identified 189 patients in the pretemplate period and 113 patients in the posttemplate period with a new testosterone prescription (Figure). After exclusions, 91 and 49 patients, respectively, met eligibility criteria (Table 1). Fifty-six patients (62%) pretemplate and 40 patients (82%) posttemplate (P = .015) had approved PADRs and comprised the groups that were analyzed (Table 2).



The mean age and body mass index were similar in the pretemplate and posttemplate periods, but there was variation in the proportions of patients aged < 70 years and those with a body mass index < 30 between the groups. The most common diagnosis in both groups was testicular hypofunction, and the most common comorbidity was type 2 diabetes mellitus. Concomitant use of opioids or glucocorticoids that can lower testosterone levels was rare. Most testosterone prescriptions originated from primary care clinics in both periods: 68 (75%) in the pretemplate period and 35 (71%) in the posttemplate period. Most testosterone treatment was delivered by intramuscular injection.
In the posttemplate period vs pretemplate period, the proportion of patients with an approved PADR (82% vs 62%, P = .02), and documentation of signs and symptoms of hypogonadism (93% vs 71%, P = .002) prior to starting TRT were higher, while the percentage of patients having ≥ 2 testosterone measurements (85% vs 89%, P = .53), ≥ 1 testosterone level before 10 AM (78% vs 75%, P = .70), and hematocrit measured (95% vs 91%, P = .47) were similar. Rates of LH and FSH testing were higher in the posttemplate period (80%) vs the pretemplate period (63%) but did not achieve statistical significance (P = .07), and discussion of the risks and benefits of TRT was higher in the posttemplate period (58%) vs the pretemplate period (34%) (P = .02). The percentage of patients who had all hormone measurements (total and/or free testosterone, LH, and FSH) was higher in the posttemplate period (78%) vs the pretemplate period (59%) but did not achieve statistical significance (P = .06). The rates of all guideline-recommended laboratory test orders were higher in the posttemplate period (78%) vs the pretemplate period (55%) (P = .03), and all 5 guideline-recommended clinical and laboratory measures were higher in the posttemplate period (45%) vs the pretemplate period (18%) (P = .004).
Discussion
The implementation of a pharmacy-managed TOT in CPRS demonstrated higher adherence to evidence-based guidelines for diagnosing and evaluating hypogonadism before TRT. After TOT implementation, a higher proportion of patients had documented signs and symptoms of testosterone deficiency, underwent all recommended laboratory tests, and had discussions about the risks and benefits of TRT. Adherence to 5 clinical and laboratory measures recommended by Endocrine Society guidelines was higher after TOT implementation, indicating improved prescribing practices.4
The requirement for TOT completion before testosterone prescription and its management by trained pharmacists likely contributed to higher adherence to guideline recommendations than previously reported. Integration of the TOT into CPRS with pharmacy oversight may have enhanced adherence by summarizing and codifying evidence-based guideline recommendations for clinical and biochemical evaluation prior to TRT initiation, offering relevant education to clinicians and pharmacists, automatically importing pertinent clinical information and laboratory results, and generating CPRS documentation to reduce clinician burden during patient care.
The proportion of patients with documented signs and symptoms of testosterone deficiency before TRT increased from the pretemplate period (71%) to the posttemplate period (93%), indicating that most patients receiving TRT had clinical manifestations of hypogonadism. This aligns with Endocrine Society guidelines, which define hypogonadism as a clinical disorder characterized by clinical manifestations of testosterone deficiency and persistently low serum testosterone levels on ≥ 2 separate occasions.4,6 However, recent trends in direct-to-consumer advertising for testosterone and the rise of “low T” clinics may contribute to increased testing, varied practices, and inappropriate testosterone therapy initiation (eg, in men with low testosterone levels who lack symptoms of hypogonadism).18 Improved adherence in documenting clinical hypogonadism with implementation of the TOT reinforces the value of incorporating educational material, as previously reported.11
Adherence to guideline recommendations following implementation of the TOT in this project was higher than those previously reported. In a study of 111,631 outpatient veterans prescribed testosterone from 2009 to 2012, only 18.3% had ≥ 2 testosterone prescriptions, and 3.5% had ≥ 2 testosterone, LH, and FSH levels measured prior to the initiation of a TRT.9 In a report of 63,534 insured patients who received TRT from 2010 to 2012, 40.3% had ≥ 2 testosterone prescriptions, and 12% had LH and/or FSH measured prior to the initiation.8
Low rates of guideline-recommended laboratory tests prior to initiation of testosterone treatment were reported in prior non-VA studies.19,20 Poor guideline adherence reinforces the need for clinician education or other methods to improve TRT and ensure appropriate prescribing practices across health care systems. The TOT described in this project is a sustainable clinical tool with the potential to improve testosterone prescribing practices.
The high rates of adherence to guideline recommendations at VAPSHCS likely stem from local endocrine expertise and ongoing educational initiatives, as well as the requirement for template completion before testosterone prescription. However, most testosterone prescriptions were initiated by primary care and monitored by pharmacists with varying degrees of training and clinical experience in hypogonadism and TRT.
However, adherence to guideline recommendations was modest, suggesting there is still an opportunity for improvement. The decision to initiate therapy should be made only after appropriate counseling with patients regarding its potential benefits and risks. Reports on the CV risk of TRT have been mixed. The 2023 TRAVERSE study found no increase in major adverse CV events among older men with hypogonadism and pre-existing CV risks undergoing TRT, but noted higher instances of pulmonary embolism, atrial fibrillation, and acute kidney injury.21 This highlights the need for clinicians to continue to engage in informed decision-making with patients. Effective pretreatment counseling is important but time-consuming; future TOT monitoring and modifications could consider mandatory checkboxes to document counseling on TRT risks and benefits.
The TOT described in this study could be adapted and incorporated into the prescribing process and electronic health record of larger health care systems. Use of an electronic template allows for automatic real-time dashboard monitoring of organization performance. The TOT described could be modified or simplified for specialty or primary care clinics or individual practitioners to improve adherence to evidence-based guideline recommendations and quality of care.
Strengths
A strength of this study is the multidisciplinary team (composed of stakeholders with experience in VA health care system and subject matter experts in hypogonadism) that developed and incorporated a user-friendly template for testosterone prescriptions; the use of evidence-based guideline recommendations; and the use of a structured chart review permitted accurate assessment of adherence to recommendations to document signs and symptoms of testosterone deficiency and a discussion of potential risks and benefits prior to TRT. To our knowledge, these recommendations have not been assessed in previous reports.
Limitations
The retrospective pre-post design of this study precludes a conclusion that implementation of the TOT caused the increase in adherence to guideline recommendations. Improved adherence could have resulted from the ongoing development of the preauthorization process for testosterone prescriptions or other changes over time. However, the preauthorization process had already been established for many years prior to template implementation. Forty-nine patients had new prescriptions for testosterone in the posttemplate period compared to 91 in the pretemplate period, but TRT was initiated in accordance with guideline recommendations more appropriately in the posttemplate period. The study’s sample size was small, and many eligible patients were excluded; however, exclusions were necessary to evaluate men who had new testosterone prescriptions for which the template was designed. Most men excluded were already taking testosterone.
Conclusions
The implementation of a CPRS-based TOT improved adherence to evidence-based guidelines for the diagnosis, evaluation, and counseling of patients with hypogonadism before starting TRT. While there were improvements in adherence with the TOT, the relatively low proportion of patients with documentation of TRT risks and benefits and all guideline recommendations highlights the need for additional efforts to further strengthen adherence to guideline recommendations and ensure appropriate evaluation, counseling, and prescribing practices before initiating TRT.
- Layton JB, Li D, Meier CR, et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J Clin Endocrinol Metab. 2014;99:835-842. doi:10.1210/jc.2013-3570
- Baillargeon J, Kuo YF, Westra JR, et al. Testosterone prescribing in the United States, 2002-2016. JAMA. 2018;320:200-202. doi:10.1001/jama.2018.7999
- Jasuja GK, Bhasin S, Rose AJ. Patterns of testosterone prescription overuse. Curr Opin Endocrinol Diabetes Obes. 2017;24:240-245. doi:10.1097/MED.0000000000000336
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2006;91:1995-2010. doi:10.1210/jc.2005-2847
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536-2559. doi:10.1210/jc.2009-2354
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:1715-1744. doi:10.1210/jc.2018-00229
- Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200:423-432. doi:10.1016/j.juro.2018.03.115
- Muram D, Zhang X, Cui Z, et al. Use of hormone testing for the diagnosis and evaluation of male hypogonadism and monitoring of testosterone therapy: application of hormone testing guideline recommendations in clinical practice. J Sex Med. 2015;12:1886-1894. doi:10.1111/jsm.12968
- Jasuja GK, Bhasin S, Reisman JI, et al. Ascertainment of testosterone prescribing practices in the VA. Med Care. 2015;53:746-752. doi:10.1097/MLR.0000000000000398?
- Jasuja GK, Bhasin S, Reisman JI, et al. Who gets testosterone? Patient characteristics associated with testosterone prescribing in the Veteran Affairs system: a cross-sectional study. J Gen Intern Med. 2017;32:304-311. doi:10.1007/s11606-016-3940-7
- Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109-122. doi:10.1056/NEJMoa1000485
- Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829-1836. doi:10.1001/jama.2013.280386
- Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9:e85805. doi:10.1371/journal.pone.0085805
- US Food and Drug Administration. FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. FDA.gov. March 3, 2015. Updated February 28, 2025. Accessed July 8, 2025. http://www.fda.gov/Drugs/DrugSafety/ucm436259.htm
- US Dept of Veterans Affairs, Office of Inspector General. Healthcare inspection – testosterone replacement therapy initiation and follow-up evaluation in VA male patients. April 11, 2018. Accessed July 8, 2025. https://www.vaoig.gov/reports/national-healthcare-review/healthcare-inspection-testosterone-replacement-therapy
- Narla R, Mobley D, Nguyen EHK, et al. Preliminary evaluation of an order template to improve diagnosis and testosterone therapy of hypogonadism in veterans. Fed Pract. 2021;38:121-127. doi:10.12788/fp.0103
- Bhasin S, Travison TG, Pencina KM, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Netw Open. 2023;6:e2348692. doi:10.1001/jamanetworkopen.2023.48692
- Dubin JM, Jesse E, Fantus RJ, et al. Guideline-discordant care among direct-to-consumer testosterone therapy platforms. JAMA Intern Med. 2022;182:1321-1323. doi:10.1001/jamainternmed.2022.4928
- Baillargeon J, Urban RJ, Ottenbacher KJ, et al. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med. 2013;173:1465-1466. doi:10.1001/jamainternmed.2013.6895
- Locke JA, Flannigan R, Günther OP, et al. Testosterone therapy: prescribing and monitoring patterns of practice in British Columbia. Can Urol Assoc J. 2021;15:e110-e117. doi:10.5489/cuaj.6586
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389:107-117. doi:10.1056/NEJMoa2215025
- Layton JB, Li D, Meier CR, et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J Clin Endocrinol Metab. 2014;99:835-842. doi:10.1210/jc.2013-3570
- Baillargeon J, Kuo YF, Westra JR, et al. Testosterone prescribing in the United States, 2002-2016. JAMA. 2018;320:200-202. doi:10.1001/jama.2018.7999
- Jasuja GK, Bhasin S, Rose AJ. Patterns of testosterone prescription overuse. Curr Opin Endocrinol Diabetes Obes. 2017;24:240-245. doi:10.1097/MED.0000000000000336
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2006;91:1995-2010. doi:10.1210/jc.2005-2847
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536-2559. doi:10.1210/jc.2009-2354
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:1715-1744. doi:10.1210/jc.2018-00229
- Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200:423-432. doi:10.1016/j.juro.2018.03.115
- Muram D, Zhang X, Cui Z, et al. Use of hormone testing for the diagnosis and evaluation of male hypogonadism and monitoring of testosterone therapy: application of hormone testing guideline recommendations in clinical practice. J Sex Med. 2015;12:1886-1894. doi:10.1111/jsm.12968
- Jasuja GK, Bhasin S, Reisman JI, et al. Ascertainment of testosterone prescribing practices in the VA. Med Care. 2015;53:746-752. doi:10.1097/MLR.0000000000000398?
- Jasuja GK, Bhasin S, Reisman JI, et al. Who gets testosterone? Patient characteristics associated with testosterone prescribing in the Veteran Affairs system: a cross-sectional study. J Gen Intern Med. 2017;32:304-311. doi:10.1007/s11606-016-3940-7
- Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109-122. doi:10.1056/NEJMoa1000485
- Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829-1836. doi:10.1001/jama.2013.280386
- Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9:e85805. doi:10.1371/journal.pone.0085805
- US Food and Drug Administration. FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. FDA.gov. March 3, 2015. Updated February 28, 2025. Accessed July 8, 2025. http://www.fda.gov/Drugs/DrugSafety/ucm436259.htm
- US Dept of Veterans Affairs, Office of Inspector General. Healthcare inspection – testosterone replacement therapy initiation and follow-up evaluation in VA male patients. April 11, 2018. Accessed July 8, 2025. https://www.vaoig.gov/reports/national-healthcare-review/healthcare-inspection-testosterone-replacement-therapy
- Narla R, Mobley D, Nguyen EHK, et al. Preliminary evaluation of an order template to improve diagnosis and testosterone therapy of hypogonadism in veterans. Fed Pract. 2021;38:121-127. doi:10.12788/fp.0103
- Bhasin S, Travison TG, Pencina KM, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Netw Open. 2023;6:e2348692. doi:10.1001/jamanetworkopen.2023.48692
- Dubin JM, Jesse E, Fantus RJ, et al. Guideline-discordant care among direct-to-consumer testosterone therapy platforms. JAMA Intern Med. 2022;182:1321-1323. doi:10.1001/jamainternmed.2022.4928
- Baillargeon J, Urban RJ, Ottenbacher KJ, et al. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med. 2013;173:1465-1466. doi:10.1001/jamainternmed.2013.6895
- Locke JA, Flannigan R, Günther OP, et al. Testosterone therapy: prescribing and monitoring patterns of practice in British Columbia. Can Urol Assoc J. 2021;15:e110-e117. doi:10.5489/cuaj.6586
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389:107-117. doi:10.1056/NEJMoa2215025
Streamlined Testosterone Order Template to Improve the Diagnosis and Evaluation of Hypogonadism in Veterans
Streamlined Testosterone Order Template to Improve the Diagnosis and Evaluation of Hypogonadism in Veterans
Steatocystomas: Update on Clinical Manifestations, Diagnosis, and Management
Steatocystomas: Update on Clinical Manifestations, Diagnosis, and Management
Steatocystomas are small sebum-filled cysts that typically manifest in the dermis and originate from sebaceous follicles. Although commonly asymptomatic, these lesions can manifest with pruritus or become infected, predisposing patients to further complications.1 Steatocystomas can manifest as single (steatocystoma simplex [SS]) or numerous (steatocystoma multiplex [SM]) lesions; the lesions also can spontaneously rupture with characteristics that resemble hidradenitis suppurativa (HS)(steatocystoma multiplex suppurativa [SMS]).1,2
Steatocystomas are relatively rare, and there is limited consensus in the published literature on the etiology and management of this condition. In this article, we present a comprehensive review of steatocystomas in the current literature. We highlight important features to consider when making the diagnosis and also offer recommendations for best-practice treatment.
Historical Background
Although not explicitly identified by name, the first documentation of steatocystomas is a case report published in 1873. In this account, the author described a patient who presented with approximately 250 flesh-colored dermal cysts across the body that varied in size.3 In 1899, the term steatocystoma multiple—derived from Greek roots meaning “fatty bag”—was first used.4
In 1982, almost a century later, Brownstein5 reported some of the earliest cases of SS. This solitary subtype is identical to SM on a microscopic level; however, unlike SM, this variant occurs as a single lesion that typically forms in adulthood and in the absence of family history. Other benign adnexal tumors (eg, pilomatricomas, pilar cysts, and sebaceous hyperplasias) also can manifest as either solitary or multiple lesions.
In 1976, McDonald and Reed6 reported the first known cases of patients with both SM and HS. At the time, the co-occurrence of these conditions was viewed as coincidental, but there were postulations of a shared inflammatory process and hereditary link6; it was not until 1982 that the term steatocystoma multiplex suppurativum was coined to describe this variant.7 Although rare, there have been multiple documented instances of SMS since. It has been suggested that the convergence of these conditions may indicate a shared follicular proliferation defect.8 Ongoing investigation is warranted to explain the underlying pathogenesis of this unique variant.
Epidemiology
The available epidemiologic data primarily relate to SM, the most common steatocystoma variant. Nevertheless, SM is a relatively rare condition, and the exact incidence and prevalence remain unknown.8,9 Steatocystomas typically manifest in the first and second decades of life and have been observed in patients of both sexes, with studies demonstrating no notable sex bias.4,9
Etiology and Pathophysiology
Steatocystomas can occur sporadically or may be inherited as an autosomal-dominant condition.4 Typically, SS tends to manifest as an isolated occurrence without any inherent genetic predisposition.5 Alternatively, SM may develop sporadically or be associated with a mutation in the keratin 17 gene (KRT17).4 Steatocystoma multiplex also has been associated with at least 4 different missense mutations, including N92H, R94H, and R94C, located on the long (q) arm of chromosome 17.4,10-12
The keratin 17 gene is responsible for encoding the keratin 17 protein, a type I intermediate filament predominantly synthesized in the basal cells of epithelial tissue. This fibrous structural protein can regulate many processes, including inflammation and cell proliferation, and is found in regions such as the sebaceous glands, hair follicles, and eccrine sweat glands. Overexpression of KRT17 has been suggested in other cutaneous conditions, most notably psoriasis.12 Despite KRT17’s many roles, it remains unclear why SM typically manifests with a myriad of sebum-containing cysts as the primary symptom.12 Continued investigation into the genetic underpinnings of SM and the keratin 17 protein is necessary to further elucidate a more comprehensive understanding of this condition.
Hormonal influences have been suggested as a potential trigger for steatocystoma growth.4,13 This condition is associated with dysfunction of the sebaceous glands, and, correspondingly, the incidence of disease is highest in pubertal patients, in whom androgen levels and sebum production are elevated.4,13,14 Two cases of transgender men taking testosterone therapy presenting with steatocystomas provide additional clinical support for this association.15
Additionally, the use of immunomodulatory agents, such as ustekinumab (anti–interleukin 12/interleukin 23), has been shown to trigger SM. It is predicted that the reduced expression of certain interferons and interleukins may lead to downstream consequences in the keratin 17 pathway and lead to SM lesion formation in genetically susceptible individuals.16 Targeting these potential causes in the future may prove efficacious in the secondary prevention of familial SM manifestation or exacerbations.
Mutations in the KRT17 gene also have been implicated in pachyonychia congenita type 2 (PC-2).4 Marked by extensive systemic hyperkeratosis, PC-2 has been observed to coincide with SM in certain patients.4,5 Interestingly, the location of the KRT17 mutations are identical in both PC-2 and SM.4 Although most individuals with hereditary SM do not exhibit the characteristic features of PC-2, mild nail and dental abnormalities have been observed in some SM cases.4,10 This relationship suggests that SM may be a less severe variant of PC-2 or part of a complex polygenetic spectrum of disease.10 Further research is imperative to determine the exact nature and extent of the relationship between these conditions.
Clinical Manifestations
Steatocystomas are flesh-colored subcutaneous cysts that range in size from less than 3 mm to larger than 3 cm in diameter (Figure). They form within a single pilosebaceous unit and typically display firm attachment due to their origination in the dermis.2,7,17 Steatocystomas generally contain lipid material, and less frequently, keratin and hair shafts, distinguishing them as the only “true” sebaceous cysts.18 Their color can range from flesh-toned to yellow, with reports of occasional dark-blue shades and calcifications.19,20 Steatocystomas can persist indefinitely, and they usually are asymptomatic.
Diagnosis of steatocystoma is confirmed by biopsy.4 Steatocystomas are characterized by a dermal cyst lined by stratified squamous cell epithelium (eFigures 1 and 2).21 Classically they feature flattened sebaceous lobules, multinucleated giant cells, and abortive hair follicles. The lining of these cysts is marked by lymphocytic infiltrate and a dense, wrinkled, eosinophilic keratin cuticle that replaces the granular layer.22 The cyst maintains an epidermal connection through a follicular infundibulum characterized by clumps of keratinocytes, sebocytes, corneocytes, and/or hair follicles.7 Aspirated contents reveal crystalline structures and anucleate squamous cells upon microscopic analysis. That being said, variable histologic findings of steatocystomas have been described.23
Steatocystoma simplex, as the name implies, classifies a single isolated steatocystoma. This subtype exhibits similar histopathologic and clinical features to the other subtypes of steatocystomas. Notably, SS is not associated with a genetic mutation and is not an inherited condition within families.5 Steatocystoma multiplex manifests with many steatocystomas, often distributed widely across the body.3,4 The chest, axillae, and groin are the most common locations; however, these cysts can manifest on the face, back, abdomen, and extremities.4,18-22 Rare occurrences of SM limited to the face, scalp, and distal extremities have been documented.18,21,24,25 Due to the possibility of an autosomal-dominant inheritance, it is advisable to take a comprehensive family history in patients for whom SM is in the differential.17
Steatocystoma multiplex—especially familial variants—has been shown to develop in conjunction with other dermatologic conditions, including eruptive vellus hair (EVH) cysts, persistent infantile milia, and epidermoid/dermoid cysts.26 While some investigators regard these as separate entities due to their varied genetic etiology, it has been suggested that these conditions may be related and that the diagnosis is determined by the location of cyst origin along the sebaceous ducts.26,27 Other dermatologic conditions and lesions that frequently manifest comorbidly with SM include hidrocystomas, syringomas, pilonidal cysts, lichen planus, nodulocystic acne, trichotillomania, trichoblastomas, trichoepithelioma, HS, keratoacanthomas, acrokeratosis verruciformis of Hopf, and embryonal hair formation. Steatocystoma multiplex, manifesting comorbidly with dental and orofacial malformations (eg, partial noneruption of secondary teeth, natal and defective teeth, and bilateral preauricular sinuses) has been classified as SM natal teeth syndrome.6
Steatocystoma multiplex suppurativa is a rare and serious variant of SM characterized by inflammation, cyst rupture, sinus tract formation, and scarring.24 Patients with SMS typically have multiple intact SM cysts, which can aid in differentiation from HS.2,24 Steatocystoma multiplex suppurativa is associated with more complications than SS and SM, including cyst perforation, development of purulent and/or foul-smelling discharge, infection, scarring, pain, and overall discomfort.2
Given its rarity and the potential manifestations that overlap with other conditions, steatocystomas easily can be misdiagnosed. In some clinical instances, EVHs may share similar characteristics with SM; however, certain distinguishing features exist, including a central tuft of protruding hairs and different expressed contents, such as the vellus hair shafts, from the cyst’s lumen.28 Furthermore, histologic examination of EVHs reveals epidermoid keratinization of the lining as well as a lack of sebaceous glands within the wall.28,29 Other similar conditions include epidermoid cysts, pilar cysts, lipomas, epidermal inclusion cysts, dermoid cysts, sebaceous hyperplasia, folliculitis, xanthomas, neurofibromatosis, and syringomas.30 Occasionally, SMS can be mistaken for HS or acne conglobata, and SM lesions with a facial distribution can mimic acne vulgaris.1,31 These conditions should be excluded before a diagnosis of SS, SM, or SMS is made.
Importantly, SM is visually indistinguishable from subcutaneous metastasis on physical examination, and there are reports of oncologic conditions (eg, pulmonary adenocarcinoma metastasized to the skin) being mistaken for SS or SM.32 Therefore, a thorough clinical examination, histopathologic analysis, and potential use of other imaging modalities such as ultrasonography (US) are needed to ensure an accurate diagnosis.
Ultrasonography has demonstrated utility in diagnosing steatocystomas.33-35 Steatocystomas have incidentally been found on routine mammograms and can demonstrate well-defined circular nodules with radiolucent characteristics and a thin radiodense outline.33,36 Homogeneous hypoechoic nodules within the dermis without posterior acoustic features generally are observed (eFigure 3).33,37 In patients declining biopsy, US may be useful in further characterization of an unknown lesion. Color Doppler US can be used to distinguish SMS from HS. Specifically, SM typically exhibits an absence of Doppler signaling due to a lack of vascularity, providing a helpful diagnostic clue for the SMS variant.33
Management and Treatment Options
There is no established standard treatment for steatocystomas; therefore, the approach to management is contingent on clinical presentation and patient preferences. Various medical, surgical, and laser management options are available, each with its own advantages and limitations. Treatment of SM is difficult due to the large number of lesions.38 In many cases, continued observation is a viable treatment option, as most SS and SM lesions are asymptomatic; however, cosmetic concerns can be debilitating for patients with SM and may warrant intervention.39 More extensive medical and surgical management often are necessary in SMS due to associated morbidity. Discussing options and goals as well as setting realistic expectations with the patient are essential in determining the optimal approach.
Medical Management—In medical literature, oral isotretinoin (13-cis-retinoic acid) has been the mainstay of therapy for steatocystoma, as its effect on the size and activity of sebaceous glands is hypothesized to decrease disease activity.38,40 Interventional studies and case reports have exhibited varying degrees of effectiveness.1,38-41 Some reports depict a reduction in the formation of new lesions and a decrease in the size of pre-existing lesions, some show mild delayed therapeutic efficacy, and others suggest exacerbation of the condition.1,38-41 This outcome variability is attributed to isotretinoin’s preferential efficacy in treating inflammatory lesions.40,42
Tetracycline derivatives and intralesional steroid injections also have been employed with some efficacy in patients with focal inflammatory SM and SMS.43 There is limited evidence on the long-term outcomes of these interventions, and intralesional injections often are not recommended in conditions such as SM, in which there are many lesions present.
Surgical Management—Minimally invasive surgical procedures including drainage and resections have been used with varying efficacy in SS and SM. Typically, a 2- to 3-mm incision or sharp-tipped cautery is employed to puncture the cyst. Alternatively, radiofrequency probes with a 2.4-MHz frequency setting have been used to minimize incision size.44 The contents then are expressed with manual pressure or forceps, and the cyst sac is extracted using forceps and/or a vein hook (eFigure 4).44,45 The specific surgical techniques and their respective advantages and limitations are summarized in the eTable. Reported advantages and limitations of surgical techniques are derived from information provided by the authors of steatocystoma case reports, which are based on observations of a very limited sample size.

Laser Treatment—Various laser modalities have been used in the management of steatocystomas, including carbon dioxide lasers, erbium-doped yttrium aluminum garnet lasers, 1450-nm diode plus 1550-nm fractionated erbium-doped fiber lasers, and 1927-nm diode lasers.54,55-57 These lasers are used to perforate the cyst before extirpation and have displayed advantages in minimizing scar length.58 The super-pulse mode of carbon dioxide lasers demonstrates efficacy with minimal scarring and recurrence, and this mode is preferred to minimize thermal damage.54,59 Furthermore, this modality can be especially useful in patients whose condition is refractory to other noninvasive options.59 Similarly, the erbium-doped yttrium aluminum garnet laser was well tolerated with no complications noted.55 The 1927-nm diode laser also displayed good outcomes as well as no recurrence.57 With laser use, it is important to note that multiple treatments are needed to see optimal outcomes.54 Moreover, laser settings must be carefully considered, especially in patients with Fitzpatrick skin type III or higher, and topical anti-inflammatory agents should be considered posttreatment to minimize complications.54,59,60
Recommendations
For management of SS, we recommend conservative therapy of watchful observation, as scarring or postinflammatory pigment change may be brought on by medical or surgical therapy; however, if SS is cosmetically bothersome, laser or surgical excision can be done (eFigure 4).4,43-53 It is important to counsel the patient on risks/benefits. For SM, watchful observation also is indicated; however, systemic therapies aimed at prevention may be the most efficacious by limiting disease progression, and oral tetracycline or isotretinoin may be tried.4 Tetracyclines have the risk for photosensitivity and are teratogenic, while isotretinoin is extremely teratogenic, requires laboratory monitoring and regular pregnancy tests in women, and often causes substantial mucosal dryness. If lesions are bothersome or refractory to these therapies, intralesional steroids or surgical/laser procedures can be tried throughout multiple visits.43-53 For SMS, systemic therapies frequently are recommended. The risks of systemic tetracycline and isotretinoin therapies must be discussed. Patients with treatment-refractory SMS may require surgical excision or deroofing of sinus tracts.43-53 This management is similar to that of HS and must be tailored to the patient.
Conclusion
Overall, steatocystomas are a relatively rare pathology, with a limited consensus on their etiology and management. This review summarizes the current knowledge on the condition to support clinicians in diagnosis and management, ranging from watchful waiting to surgical removal. By individualizing treatment plans, clinicians ultimately can optimize outcomes in patients with steatocystomas.
- Santana CN, Pereira DD, Lisboa AP, et al. Steatocystoma multiplex suppurativa: case report of a rare condition. An Bras Dermatol. 2016;91(5 suppl 1):51-53.
- Atzori L, Zanniello R, Pilloni L, et al. Steatocystoma multiplex suppurativa associated with hidradenitis suppurativa successfully treated with adalimumab. J Eur Acad Dermatol Venereol. 2019;33(Suppl 6):42-44.
- Jamieson WA. Case of numerous cutaneous cysts scattered over the body. Edinb Med J. 1873;19:223-225.
- Kamra HT, Gadgil PA, Ovhal AG, et al. Steatocystoma multiplex-a rare genetic disorder: a case report and review of the literature. J Clin Diagn Res. 2013;7:166-168.
- Brownstein MH. Steatocystoma simplex. A solitary steatocystoma. Arch Dermatol. 1982;118:409-411.
- McDonald RM, Reed WB. Natal teeth and steatocystoma multiplex complicated by hidradenitis suppurativa. A new syndrome. Arch Dermatol. 1976;112:1132-1134.
- Plewig G, Wolff HH, Braun-Falco O. Steatocystoma multiplex: anatomic reevaluation, electron microscopy, and autoradiography. Arch Dermatol. 1982;272:363-380.
- Fletcher J, Posso-De Los Rios C, Jambrosic J, A, et al. Coexistence of hidradenitis suppurativa and steatocystoma multiplex: is it a new variant of hidradenitis suppurativa? J Cutan Med Surg. 2021;25:586-590.
- Cho S, Chang SE, Choi JH, et al. Clinical and histologic features of 64 cases of steatocystoma multiplex. J Dermatol. 2002;29:152-156.
- Covello SP, Smith FJ, Sillevis Smitt JH, et al. Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2. Br J Dermatol. 1998;139:475-480.
- Liu Q, Wu W, Lu J, et al. Steatocystoma multiplex is associated with the R94C mutation in the KRTl7 gene. Mol Med Rep. 2015;12:5072-5076.
- Yang L, Zhang S, Wang G. Keratin 17 in disease pathogenesis: from cancer to dermatoses. J Pathol. 2019;247:158-165.
- Shamloul G, Khachemoune A. An updated review of the sebaceous gland and its role in health and diseases Part 1: embryology, evolution, structure, and function of sebaceous glands. Dermatol Ther. 2021;34:e14695.
- Del Rosso JQ, Kircik LH, Stein Gold L, et al. Androgens, androgen receptors, and the skin: from the laboratory to the clinic with emphasis on clinical and therapeutic implications. J Drugs Dermatol. 2020;19:30-35.
- Porras Fimbres DC, Wolfe SA, Kelley CE. Proliferation of steatocystomas in 2 transgender men. JAAD Case Rep. 2022;26:70-72.
- Marasca C, Megna M, Donnarumma M, et al. A case of steatocystoma multiplex in a psoriatic patient during treatment with anti-IL-12/23. Skin Appendage Disord. 2020;6:309-311.
- Gordon Spratt EA, Kaplan J, Patel RR, et al. Steatocystoma. Dermatol Online J. 2013;19:20721.
- Sharma A, Agrawal S, Dhurat R, et al. An unusual case of facial steatocystoma multiplex: a clinicopathologic and dermoscopic report. Dermatopathology (Basel). 2018;5:58-63.
- Rahman MH, Islam MS, Ansari NP. Atypical steatocystoma multiplex with calcification. ISRN Dermatol. 2011;2011:381901.
- Beyer AV, Vossmann D. Steatocystoma multiplex. Article in German. Hautarzt. 1996;47:469-471.
- Yanagi T, Matsumura T. Steatocystoma multiplex presenting as acral subcutaneous nodules. Acta Derm Venereol. 2006;86:374-375.
- Marzano AV, Tavecchio S, Balice Y, et al. Acral subcutaneous steatocystoma multiplex: a distinct subtype of the disease? Australas J Dermatol. 2012;53:198-201.
- Ferrandiz C, Peyri J. Steatocystoma multiplex. Article in Spanish. Med Cutan Ibero Lat Am. 1984;12:173-176.
- Alotaibi L, Alsaif M, Alhumidi A, et al. Steatocystoma multiplex suppurativa: a case with unusual giant cysts over the scalp and neck. Case Rep Dermatol. 2019;11:71-76.
- Kim SJ, Park HJ, Oh ST, et al. A case of steatocystoma multiplex limited to scalp. Ann Dermatol. 2009;21:106-109.
- Patrizi A, Neri I, Guerrini V, et al. Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts: variable expression of multiple pilosebaceous cysts within an affected family. Dermatology. 1998;196:392-396.
- Tomková H, Fujimoto W, Arata J. Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts. Am J Dermatopathol. 1997;19:250-253.
- Patokar AS, Holani AR, Khandait GH, et al. Eruptive vellus hair cysts: an underdiagnosed entity. Int J Trichology. 2022;14:31-33.
- Ohtake N, Kubota Y, Takayama O, et al. Relationship between steatocystoma multiplex and eruptive vellus hair cysts. J Am Acad Dermatol. 1992;26(5 Pt 2):876-878.
- Yoon H, Kang Y, Park H, et al. Sonographic appearance of steatocystoma: an analysis of 14 pathologically confirmed lesions. Taehan Yongsang Uihakhoe Chi. 2021;82:382-392.
- Varshney M, Aziz M, Maheshwari V, et al. Steatocystoma multiplex. BMJ Case Rep. 2011;2011:bcr0420114165.
- Tsai MH, Hsiao YP, Lin WL, et al. Steatocystoma multiplex as initial impression of non-small cell lung cancer with complete response to gefitinib. Chin J Cancer Res. 2014;26:E5-E9.
- Zussino M, Nazzaro G, Moltrasio C, et al. Coexistence of steatocystoma multiplex and hidradenitis suppurativa: assessment of this unique association by means of ultrasonography and color Doppler. Skin Res Technol. 2019;25:877-880.
- Whittle C, Silva-Hirschberg C, Loyola K, et al. Ultrasonographic spectrum of cutaneous cysts with stratified squamous epithelium in pediatric dermatology: pictorial essay. J Ultrasound Med. 2023;42:923-930.
- Arceu M, Martinez G, Alfaro D, et al. Ultrasound morphologic features of steatocystoma multiplex with clinical correlation. J Ultrasound Med. 2020;39:2255-2260.
- Reick-Mitrisin V, Reddy A, Shah BA. A breast imaging case of steatocystoma multiplex: a rare condition involving multiple anatomic regions. Cureus. 2022;14:E27756.
- Yoon H, Kang Y, Park H, et al. Sonographic appearance of steatocystoma: an analysis of 14 pathologically confirmed lesions. Taehan Yongsang Uihakhoe Chi. 2021;82:382-392.
- Apaydin R, Bilen N, Bayramgurler D, et al. Steatocystoma multiplex suppurativum: oral isotretinoin treatment combined with cryotherapy. Australas J Dermatol. 2000;41:98-100.
- Sharma A, Agrawal S, Dhurat R, et al. An unusual case of facial steatocystoma multiplex: a clinicopathologic and dermoscopic report. Dermatopathology (Basel). 2018;5:58-63.
- Moritz DL, Silverman RA. Steatocystoma multiplex treated with isotretinoin: a delayed response. Cutis. 1988;42:437-439.
- Schwartz JL, Goldsmith LA. Steatocystoma multiplex suppurativum: treatment with isotretinoin. Cutis. 1984;34:149-153.
- Kim SJ, Park HJ, Oh ST, et al. A case of steatocystoma multiplex limited to the scalp. Ann Dermatol. 2009;21:106-109.
- Fekete GL, Fekete JE. Steatocystoma multiplex generalisata partially suppurativa--case report. Acta Dermatovenerol Croat. 2010;18:114-119.
- Choudhary S, Koley S, Salodkar A. A modified surgical technique for steatocystoma multiplex. J Cutan Aesthet Surg. 2010;3:25-28.
- Kaya TI, Ikizoglu G, Kokturk A, et al. A simple surgical technique for the treatment of steatocystoma multiplex. Int J Dermatol. 2001;40:785-788.
- Oertel YC, Scott DM. Cytologic-pathologic correlations: fine needle aspiration of three cases of steatocystoma multiplex. Ann Diagn Pathol. 1998;2:318-320.
- Egbert BM, Price NM, Segal RJ. Steatocystoma multiplex. Report of a florid case and a review. Arch Dermatol. 1979;115:334-335.
- Adams BB, Mutasim DF, Nordlund JJ. Steatocystoma multiplex: a quick removal technique. Cutis. 1999;64:127-130.
- Lee SJ, Choe YS, Park BC, et al. The vein hook successfully used for eradication of steatocystoma multiplex. Dermatol Surg. 2007;33:82-84.
- Bettes PSL, Lopes SL, Prestes MA, et al. Treatment of a facial variant of the multiple steatocystoma with skin graft: case report. Rev Bras Cir Plást. 1998;13:31-36
- Düzova AN, Sentürk GB. Suggestion for the treatment of steatocystoma multiplex located exclusively on the face. Int J Dermatol. 2004;43:60-62. doi:10.1111/j.1365-4632.2004.02068.x
- Choudhary S, Koley S, Salodkar A. A modified surgical technique for steatocystoma multiplex. J Cutan Aesthet Surg. 2010;3:25-28.
- Kaya TI, Ikizoglu G, Kokturk A, et al. A simple surgical technique for the treatment of steatocystoma multiplex. Int J Dermatol. 2001;40:785-788.
- Bakkour W, Madan V. Carbon dioxide laser perforation and extirpation of steatocystoma multiplex. Dermatol Surg. 2014;40:658-662.
- Mumcuog?lu CT, Gurel MS, Kiremitci U, et al. Er: yag laser therapy for steatocystoma multiplex. Indian J Dermatol. 2010;55:300-301.
- Moody MN, Landau JM, Goldberg LH, et al. 1,450-nm diode laser in combination with the 1550-nm fractionated erbium-doped fiber laser for the treatment of steatocystoma multiplex: a case report. Dermatol Surg. 2012;38(7 Pt 1):1104-1106.
- Cheon DU, Ko JY. 1927-nm fiber-optic diode laser: a novel therapeutic option for facial steatocystoma multiplex. J Cosmet Dermatol. 2019;18:1326-1329.
- Kim KT, Sun H, Chung EH. Comparison of complete surgical excision and minimally invasive excision using CO2 laser for removal of epidermal cysts on the face. Arch Craniofac Surg. 2019;20:84-88.
- Kassira S, Korta DZ, de Feraudy S, et al. Fractionated ablative carbon dioxide laser treatment of steatocystoma multiplex. J Cosmet Laser Ther. 2016;18:364-366.
- Dixit N, Sardana K, Paliwal P. The rationale of ideal pulse duration and pulse interval in the treatment of steatocystoma multiplex using the carbon dioxide laser in a super-pulse mode as opposedto the ultra-pulse mode. Indian J Dermatol Venereol Leprol. 2020;86:454-456.
Steatocystomas are small sebum-filled cysts that typically manifest in the dermis and originate from sebaceous follicles. Although commonly asymptomatic, these lesions can manifest with pruritus or become infected, predisposing patients to further complications.1 Steatocystomas can manifest as single (steatocystoma simplex [SS]) or numerous (steatocystoma multiplex [SM]) lesions; the lesions also can spontaneously rupture with characteristics that resemble hidradenitis suppurativa (HS)(steatocystoma multiplex suppurativa [SMS]).1,2
Steatocystomas are relatively rare, and there is limited consensus in the published literature on the etiology and management of this condition. In this article, we present a comprehensive review of steatocystomas in the current literature. We highlight important features to consider when making the diagnosis and also offer recommendations for best-practice treatment.
Historical Background
Although not explicitly identified by name, the first documentation of steatocystomas is a case report published in 1873. In this account, the author described a patient who presented with approximately 250 flesh-colored dermal cysts across the body that varied in size.3 In 1899, the term steatocystoma multiple—derived from Greek roots meaning “fatty bag”—was first used.4
In 1982, almost a century later, Brownstein5 reported some of the earliest cases of SS. This solitary subtype is identical to SM on a microscopic level; however, unlike SM, this variant occurs as a single lesion that typically forms in adulthood and in the absence of family history. Other benign adnexal tumors (eg, pilomatricomas, pilar cysts, and sebaceous hyperplasias) also can manifest as either solitary or multiple lesions.
In 1976, McDonald and Reed6 reported the first known cases of patients with both SM and HS. At the time, the co-occurrence of these conditions was viewed as coincidental, but there were postulations of a shared inflammatory process and hereditary link6; it was not until 1982 that the term steatocystoma multiplex suppurativum was coined to describe this variant.7 Although rare, there have been multiple documented instances of SMS since. It has been suggested that the convergence of these conditions may indicate a shared follicular proliferation defect.8 Ongoing investigation is warranted to explain the underlying pathogenesis of this unique variant.
Epidemiology
The available epidemiologic data primarily relate to SM, the most common steatocystoma variant. Nevertheless, SM is a relatively rare condition, and the exact incidence and prevalence remain unknown.8,9 Steatocystomas typically manifest in the first and second decades of life and have been observed in patients of both sexes, with studies demonstrating no notable sex bias.4,9
Etiology and Pathophysiology
Steatocystomas can occur sporadically or may be inherited as an autosomal-dominant condition.4 Typically, SS tends to manifest as an isolated occurrence without any inherent genetic predisposition.5 Alternatively, SM may develop sporadically or be associated with a mutation in the keratin 17 gene (KRT17).4 Steatocystoma multiplex also has been associated with at least 4 different missense mutations, including N92H, R94H, and R94C, located on the long (q) arm of chromosome 17.4,10-12
The keratin 17 gene is responsible for encoding the keratin 17 protein, a type I intermediate filament predominantly synthesized in the basal cells of epithelial tissue. This fibrous structural protein can regulate many processes, including inflammation and cell proliferation, and is found in regions such as the sebaceous glands, hair follicles, and eccrine sweat glands. Overexpression of KRT17 has been suggested in other cutaneous conditions, most notably psoriasis.12 Despite KRT17’s many roles, it remains unclear why SM typically manifests with a myriad of sebum-containing cysts as the primary symptom.12 Continued investigation into the genetic underpinnings of SM and the keratin 17 protein is necessary to further elucidate a more comprehensive understanding of this condition.
Hormonal influences have been suggested as a potential trigger for steatocystoma growth.4,13 This condition is associated with dysfunction of the sebaceous glands, and, correspondingly, the incidence of disease is highest in pubertal patients, in whom androgen levels and sebum production are elevated.4,13,14 Two cases of transgender men taking testosterone therapy presenting with steatocystomas provide additional clinical support for this association.15
Additionally, the use of immunomodulatory agents, such as ustekinumab (anti–interleukin 12/interleukin 23), has been shown to trigger SM. It is predicted that the reduced expression of certain interferons and interleukins may lead to downstream consequences in the keratin 17 pathway and lead to SM lesion formation in genetically susceptible individuals.16 Targeting these potential causes in the future may prove efficacious in the secondary prevention of familial SM manifestation or exacerbations.
Mutations in the KRT17 gene also have been implicated in pachyonychia congenita type 2 (PC-2).4 Marked by extensive systemic hyperkeratosis, PC-2 has been observed to coincide with SM in certain patients.4,5 Interestingly, the location of the KRT17 mutations are identical in both PC-2 and SM.4 Although most individuals with hereditary SM do not exhibit the characteristic features of PC-2, mild nail and dental abnormalities have been observed in some SM cases.4,10 This relationship suggests that SM may be a less severe variant of PC-2 or part of a complex polygenetic spectrum of disease.10 Further research is imperative to determine the exact nature and extent of the relationship between these conditions.
Clinical Manifestations
Steatocystomas are flesh-colored subcutaneous cysts that range in size from less than 3 mm to larger than 3 cm in diameter (Figure). They form within a single pilosebaceous unit and typically display firm attachment due to their origination in the dermis.2,7,17 Steatocystomas generally contain lipid material, and less frequently, keratin and hair shafts, distinguishing them as the only “true” sebaceous cysts.18 Their color can range from flesh-toned to yellow, with reports of occasional dark-blue shades and calcifications.19,20 Steatocystomas can persist indefinitely, and they usually are asymptomatic.
Diagnosis of steatocystoma is confirmed by biopsy.4 Steatocystomas are characterized by a dermal cyst lined by stratified squamous cell epithelium (eFigures 1 and 2).21 Classically they feature flattened sebaceous lobules, multinucleated giant cells, and abortive hair follicles. The lining of these cysts is marked by lymphocytic infiltrate and a dense, wrinkled, eosinophilic keratin cuticle that replaces the granular layer.22 The cyst maintains an epidermal connection through a follicular infundibulum characterized by clumps of keratinocytes, sebocytes, corneocytes, and/or hair follicles.7 Aspirated contents reveal crystalline structures and anucleate squamous cells upon microscopic analysis. That being said, variable histologic findings of steatocystomas have been described.23
Steatocystoma simplex, as the name implies, classifies a single isolated steatocystoma. This subtype exhibits similar histopathologic and clinical features to the other subtypes of steatocystomas. Notably, SS is not associated with a genetic mutation and is not an inherited condition within families.5 Steatocystoma multiplex manifests with many steatocystomas, often distributed widely across the body.3,4 The chest, axillae, and groin are the most common locations; however, these cysts can manifest on the face, back, abdomen, and extremities.4,18-22 Rare occurrences of SM limited to the face, scalp, and distal extremities have been documented.18,21,24,25 Due to the possibility of an autosomal-dominant inheritance, it is advisable to take a comprehensive family history in patients for whom SM is in the differential.17
Steatocystoma multiplex—especially familial variants—has been shown to develop in conjunction with other dermatologic conditions, including eruptive vellus hair (EVH) cysts, persistent infantile milia, and epidermoid/dermoid cysts.26 While some investigators regard these as separate entities due to their varied genetic etiology, it has been suggested that these conditions may be related and that the diagnosis is determined by the location of cyst origin along the sebaceous ducts.26,27 Other dermatologic conditions and lesions that frequently manifest comorbidly with SM include hidrocystomas, syringomas, pilonidal cysts, lichen planus, nodulocystic acne, trichotillomania, trichoblastomas, trichoepithelioma, HS, keratoacanthomas, acrokeratosis verruciformis of Hopf, and embryonal hair formation. Steatocystoma multiplex, manifesting comorbidly with dental and orofacial malformations (eg, partial noneruption of secondary teeth, natal and defective teeth, and bilateral preauricular sinuses) has been classified as SM natal teeth syndrome.6
Steatocystoma multiplex suppurativa is a rare and serious variant of SM characterized by inflammation, cyst rupture, sinus tract formation, and scarring.24 Patients with SMS typically have multiple intact SM cysts, which can aid in differentiation from HS.2,24 Steatocystoma multiplex suppurativa is associated with more complications than SS and SM, including cyst perforation, development of purulent and/or foul-smelling discharge, infection, scarring, pain, and overall discomfort.2
Given its rarity and the potential manifestations that overlap with other conditions, steatocystomas easily can be misdiagnosed. In some clinical instances, EVHs may share similar characteristics with SM; however, certain distinguishing features exist, including a central tuft of protruding hairs and different expressed contents, such as the vellus hair shafts, from the cyst’s lumen.28 Furthermore, histologic examination of EVHs reveals epidermoid keratinization of the lining as well as a lack of sebaceous glands within the wall.28,29 Other similar conditions include epidermoid cysts, pilar cysts, lipomas, epidermal inclusion cysts, dermoid cysts, sebaceous hyperplasia, folliculitis, xanthomas, neurofibromatosis, and syringomas.30 Occasionally, SMS can be mistaken for HS or acne conglobata, and SM lesions with a facial distribution can mimic acne vulgaris.1,31 These conditions should be excluded before a diagnosis of SS, SM, or SMS is made.
Importantly, SM is visually indistinguishable from subcutaneous metastasis on physical examination, and there are reports of oncologic conditions (eg, pulmonary adenocarcinoma metastasized to the skin) being mistaken for SS or SM.32 Therefore, a thorough clinical examination, histopathologic analysis, and potential use of other imaging modalities such as ultrasonography (US) are needed to ensure an accurate diagnosis.
Ultrasonography has demonstrated utility in diagnosing steatocystomas.33-35 Steatocystomas have incidentally been found on routine mammograms and can demonstrate well-defined circular nodules with radiolucent characteristics and a thin radiodense outline.33,36 Homogeneous hypoechoic nodules within the dermis without posterior acoustic features generally are observed (eFigure 3).33,37 In patients declining biopsy, US may be useful in further characterization of an unknown lesion. Color Doppler US can be used to distinguish SMS from HS. Specifically, SM typically exhibits an absence of Doppler signaling due to a lack of vascularity, providing a helpful diagnostic clue for the SMS variant.33
Management and Treatment Options
There is no established standard treatment for steatocystomas; therefore, the approach to management is contingent on clinical presentation and patient preferences. Various medical, surgical, and laser management options are available, each with its own advantages and limitations. Treatment of SM is difficult due to the large number of lesions.38 In many cases, continued observation is a viable treatment option, as most SS and SM lesions are asymptomatic; however, cosmetic concerns can be debilitating for patients with SM and may warrant intervention.39 More extensive medical and surgical management often are necessary in SMS due to associated morbidity. Discussing options and goals as well as setting realistic expectations with the patient are essential in determining the optimal approach.
Medical Management—In medical literature, oral isotretinoin (13-cis-retinoic acid) has been the mainstay of therapy for steatocystoma, as its effect on the size and activity of sebaceous glands is hypothesized to decrease disease activity.38,40 Interventional studies and case reports have exhibited varying degrees of effectiveness.1,38-41 Some reports depict a reduction in the formation of new lesions and a decrease in the size of pre-existing lesions, some show mild delayed therapeutic efficacy, and others suggest exacerbation of the condition.1,38-41 This outcome variability is attributed to isotretinoin’s preferential efficacy in treating inflammatory lesions.40,42
Tetracycline derivatives and intralesional steroid injections also have been employed with some efficacy in patients with focal inflammatory SM and SMS.43 There is limited evidence on the long-term outcomes of these interventions, and intralesional injections often are not recommended in conditions such as SM, in which there are many lesions present.
Surgical Management—Minimally invasive surgical procedures including drainage and resections have been used with varying efficacy in SS and SM. Typically, a 2- to 3-mm incision or sharp-tipped cautery is employed to puncture the cyst. Alternatively, radiofrequency probes with a 2.4-MHz frequency setting have been used to minimize incision size.44 The contents then are expressed with manual pressure or forceps, and the cyst sac is extracted using forceps and/or a vein hook (eFigure 4).44,45 The specific surgical techniques and their respective advantages and limitations are summarized in the eTable. Reported advantages and limitations of surgical techniques are derived from information provided by the authors of steatocystoma case reports, which are based on observations of a very limited sample size.

Laser Treatment—Various laser modalities have been used in the management of steatocystomas, including carbon dioxide lasers, erbium-doped yttrium aluminum garnet lasers, 1450-nm diode plus 1550-nm fractionated erbium-doped fiber lasers, and 1927-nm diode lasers.54,55-57 These lasers are used to perforate the cyst before extirpation and have displayed advantages in minimizing scar length.58 The super-pulse mode of carbon dioxide lasers demonstrates efficacy with minimal scarring and recurrence, and this mode is preferred to minimize thermal damage.54,59 Furthermore, this modality can be especially useful in patients whose condition is refractory to other noninvasive options.59 Similarly, the erbium-doped yttrium aluminum garnet laser was well tolerated with no complications noted.55 The 1927-nm diode laser also displayed good outcomes as well as no recurrence.57 With laser use, it is important to note that multiple treatments are needed to see optimal outcomes.54 Moreover, laser settings must be carefully considered, especially in patients with Fitzpatrick skin type III or higher, and topical anti-inflammatory agents should be considered posttreatment to minimize complications.54,59,60
Recommendations
For management of SS, we recommend conservative therapy of watchful observation, as scarring or postinflammatory pigment change may be brought on by medical or surgical therapy; however, if SS is cosmetically bothersome, laser or surgical excision can be done (eFigure 4).4,43-53 It is important to counsel the patient on risks/benefits. For SM, watchful observation also is indicated; however, systemic therapies aimed at prevention may be the most efficacious by limiting disease progression, and oral tetracycline or isotretinoin may be tried.4 Tetracyclines have the risk for photosensitivity and are teratogenic, while isotretinoin is extremely teratogenic, requires laboratory monitoring and regular pregnancy tests in women, and often causes substantial mucosal dryness. If lesions are bothersome or refractory to these therapies, intralesional steroids or surgical/laser procedures can be tried throughout multiple visits.43-53 For SMS, systemic therapies frequently are recommended. The risks of systemic tetracycline and isotretinoin therapies must be discussed. Patients with treatment-refractory SMS may require surgical excision or deroofing of sinus tracts.43-53 This management is similar to that of HS and must be tailored to the patient.
Conclusion
Overall, steatocystomas are a relatively rare pathology, with a limited consensus on their etiology and management. This review summarizes the current knowledge on the condition to support clinicians in diagnosis and management, ranging from watchful waiting to surgical removal. By individualizing treatment plans, clinicians ultimately can optimize outcomes in patients with steatocystomas.
Steatocystomas are small sebum-filled cysts that typically manifest in the dermis and originate from sebaceous follicles. Although commonly asymptomatic, these lesions can manifest with pruritus or become infected, predisposing patients to further complications.1 Steatocystomas can manifest as single (steatocystoma simplex [SS]) or numerous (steatocystoma multiplex [SM]) lesions; the lesions also can spontaneously rupture with characteristics that resemble hidradenitis suppurativa (HS)(steatocystoma multiplex suppurativa [SMS]).1,2
Steatocystomas are relatively rare, and there is limited consensus in the published literature on the etiology and management of this condition. In this article, we present a comprehensive review of steatocystomas in the current literature. We highlight important features to consider when making the diagnosis and also offer recommendations for best-practice treatment.
Historical Background
Although not explicitly identified by name, the first documentation of steatocystomas is a case report published in 1873. In this account, the author described a patient who presented with approximately 250 flesh-colored dermal cysts across the body that varied in size.3 In 1899, the term steatocystoma multiple—derived from Greek roots meaning “fatty bag”—was first used.4
In 1982, almost a century later, Brownstein5 reported some of the earliest cases of SS. This solitary subtype is identical to SM on a microscopic level; however, unlike SM, this variant occurs as a single lesion that typically forms in adulthood and in the absence of family history. Other benign adnexal tumors (eg, pilomatricomas, pilar cysts, and sebaceous hyperplasias) also can manifest as either solitary or multiple lesions.
In 1976, McDonald and Reed6 reported the first known cases of patients with both SM and HS. At the time, the co-occurrence of these conditions was viewed as coincidental, but there were postulations of a shared inflammatory process and hereditary link6; it was not until 1982 that the term steatocystoma multiplex suppurativum was coined to describe this variant.7 Although rare, there have been multiple documented instances of SMS since. It has been suggested that the convergence of these conditions may indicate a shared follicular proliferation defect.8 Ongoing investigation is warranted to explain the underlying pathogenesis of this unique variant.
Epidemiology
The available epidemiologic data primarily relate to SM, the most common steatocystoma variant. Nevertheless, SM is a relatively rare condition, and the exact incidence and prevalence remain unknown.8,9 Steatocystomas typically manifest in the first and second decades of life and have been observed in patients of both sexes, with studies demonstrating no notable sex bias.4,9
Etiology and Pathophysiology
Steatocystomas can occur sporadically or may be inherited as an autosomal-dominant condition.4 Typically, SS tends to manifest as an isolated occurrence without any inherent genetic predisposition.5 Alternatively, SM may develop sporadically or be associated with a mutation in the keratin 17 gene (KRT17).4 Steatocystoma multiplex also has been associated with at least 4 different missense mutations, including N92H, R94H, and R94C, located on the long (q) arm of chromosome 17.4,10-12
The keratin 17 gene is responsible for encoding the keratin 17 protein, a type I intermediate filament predominantly synthesized in the basal cells of epithelial tissue. This fibrous structural protein can regulate many processes, including inflammation and cell proliferation, and is found in regions such as the sebaceous glands, hair follicles, and eccrine sweat glands. Overexpression of KRT17 has been suggested in other cutaneous conditions, most notably psoriasis.12 Despite KRT17’s many roles, it remains unclear why SM typically manifests with a myriad of sebum-containing cysts as the primary symptom.12 Continued investigation into the genetic underpinnings of SM and the keratin 17 protein is necessary to further elucidate a more comprehensive understanding of this condition.
Hormonal influences have been suggested as a potential trigger for steatocystoma growth.4,13 This condition is associated with dysfunction of the sebaceous glands, and, correspondingly, the incidence of disease is highest in pubertal patients, in whom androgen levels and sebum production are elevated.4,13,14 Two cases of transgender men taking testosterone therapy presenting with steatocystomas provide additional clinical support for this association.15
Additionally, the use of immunomodulatory agents, such as ustekinumab (anti–interleukin 12/interleukin 23), has been shown to trigger SM. It is predicted that the reduced expression of certain interferons and interleukins may lead to downstream consequences in the keratin 17 pathway and lead to SM lesion formation in genetically susceptible individuals.16 Targeting these potential causes in the future may prove efficacious in the secondary prevention of familial SM manifestation or exacerbations.
Mutations in the KRT17 gene also have been implicated in pachyonychia congenita type 2 (PC-2).4 Marked by extensive systemic hyperkeratosis, PC-2 has been observed to coincide with SM in certain patients.4,5 Interestingly, the location of the KRT17 mutations are identical in both PC-2 and SM.4 Although most individuals with hereditary SM do not exhibit the characteristic features of PC-2, mild nail and dental abnormalities have been observed in some SM cases.4,10 This relationship suggests that SM may be a less severe variant of PC-2 or part of a complex polygenetic spectrum of disease.10 Further research is imperative to determine the exact nature and extent of the relationship between these conditions.
Clinical Manifestations
Steatocystomas are flesh-colored subcutaneous cysts that range in size from less than 3 mm to larger than 3 cm in diameter (Figure). They form within a single pilosebaceous unit and typically display firm attachment due to their origination in the dermis.2,7,17 Steatocystomas generally contain lipid material, and less frequently, keratin and hair shafts, distinguishing them as the only “true” sebaceous cysts.18 Their color can range from flesh-toned to yellow, with reports of occasional dark-blue shades and calcifications.19,20 Steatocystomas can persist indefinitely, and they usually are asymptomatic.
Diagnosis of steatocystoma is confirmed by biopsy.4 Steatocystomas are characterized by a dermal cyst lined by stratified squamous cell epithelium (eFigures 1 and 2).21 Classically they feature flattened sebaceous lobules, multinucleated giant cells, and abortive hair follicles. The lining of these cysts is marked by lymphocytic infiltrate and a dense, wrinkled, eosinophilic keratin cuticle that replaces the granular layer.22 The cyst maintains an epidermal connection through a follicular infundibulum characterized by clumps of keratinocytes, sebocytes, corneocytes, and/or hair follicles.7 Aspirated contents reveal crystalline structures and anucleate squamous cells upon microscopic analysis. That being said, variable histologic findings of steatocystomas have been described.23
Steatocystoma simplex, as the name implies, classifies a single isolated steatocystoma. This subtype exhibits similar histopathologic and clinical features to the other subtypes of steatocystomas. Notably, SS is not associated with a genetic mutation and is not an inherited condition within families.5 Steatocystoma multiplex manifests with many steatocystomas, often distributed widely across the body.3,4 The chest, axillae, and groin are the most common locations; however, these cysts can manifest on the face, back, abdomen, and extremities.4,18-22 Rare occurrences of SM limited to the face, scalp, and distal extremities have been documented.18,21,24,25 Due to the possibility of an autosomal-dominant inheritance, it is advisable to take a comprehensive family history in patients for whom SM is in the differential.17
Steatocystoma multiplex—especially familial variants—has been shown to develop in conjunction with other dermatologic conditions, including eruptive vellus hair (EVH) cysts, persistent infantile milia, and epidermoid/dermoid cysts.26 While some investigators regard these as separate entities due to their varied genetic etiology, it has been suggested that these conditions may be related and that the diagnosis is determined by the location of cyst origin along the sebaceous ducts.26,27 Other dermatologic conditions and lesions that frequently manifest comorbidly with SM include hidrocystomas, syringomas, pilonidal cysts, lichen planus, nodulocystic acne, trichotillomania, trichoblastomas, trichoepithelioma, HS, keratoacanthomas, acrokeratosis verruciformis of Hopf, and embryonal hair formation. Steatocystoma multiplex, manifesting comorbidly with dental and orofacial malformations (eg, partial noneruption of secondary teeth, natal and defective teeth, and bilateral preauricular sinuses) has been classified as SM natal teeth syndrome.6
Steatocystoma multiplex suppurativa is a rare and serious variant of SM characterized by inflammation, cyst rupture, sinus tract formation, and scarring.24 Patients with SMS typically have multiple intact SM cysts, which can aid in differentiation from HS.2,24 Steatocystoma multiplex suppurativa is associated with more complications than SS and SM, including cyst perforation, development of purulent and/or foul-smelling discharge, infection, scarring, pain, and overall discomfort.2
Given its rarity and the potential manifestations that overlap with other conditions, steatocystomas easily can be misdiagnosed. In some clinical instances, EVHs may share similar characteristics with SM; however, certain distinguishing features exist, including a central tuft of protruding hairs and different expressed contents, such as the vellus hair shafts, from the cyst’s lumen.28 Furthermore, histologic examination of EVHs reveals epidermoid keratinization of the lining as well as a lack of sebaceous glands within the wall.28,29 Other similar conditions include epidermoid cysts, pilar cysts, lipomas, epidermal inclusion cysts, dermoid cysts, sebaceous hyperplasia, folliculitis, xanthomas, neurofibromatosis, and syringomas.30 Occasionally, SMS can be mistaken for HS or acne conglobata, and SM lesions with a facial distribution can mimic acne vulgaris.1,31 These conditions should be excluded before a diagnosis of SS, SM, or SMS is made.
Importantly, SM is visually indistinguishable from subcutaneous metastasis on physical examination, and there are reports of oncologic conditions (eg, pulmonary adenocarcinoma metastasized to the skin) being mistaken for SS or SM.32 Therefore, a thorough clinical examination, histopathologic analysis, and potential use of other imaging modalities such as ultrasonography (US) are needed to ensure an accurate diagnosis.
Ultrasonography has demonstrated utility in diagnosing steatocystomas.33-35 Steatocystomas have incidentally been found on routine mammograms and can demonstrate well-defined circular nodules with radiolucent characteristics and a thin radiodense outline.33,36 Homogeneous hypoechoic nodules within the dermis without posterior acoustic features generally are observed (eFigure 3).33,37 In patients declining biopsy, US may be useful in further characterization of an unknown lesion. Color Doppler US can be used to distinguish SMS from HS. Specifically, SM typically exhibits an absence of Doppler signaling due to a lack of vascularity, providing a helpful diagnostic clue for the SMS variant.33
Management and Treatment Options
There is no established standard treatment for steatocystomas; therefore, the approach to management is contingent on clinical presentation and patient preferences. Various medical, surgical, and laser management options are available, each with its own advantages and limitations. Treatment of SM is difficult due to the large number of lesions.38 In many cases, continued observation is a viable treatment option, as most SS and SM lesions are asymptomatic; however, cosmetic concerns can be debilitating for patients with SM and may warrant intervention.39 More extensive medical and surgical management often are necessary in SMS due to associated morbidity. Discussing options and goals as well as setting realistic expectations with the patient are essential in determining the optimal approach.
Medical Management—In medical literature, oral isotretinoin (13-cis-retinoic acid) has been the mainstay of therapy for steatocystoma, as its effect on the size and activity of sebaceous glands is hypothesized to decrease disease activity.38,40 Interventional studies and case reports have exhibited varying degrees of effectiveness.1,38-41 Some reports depict a reduction in the formation of new lesions and a decrease in the size of pre-existing lesions, some show mild delayed therapeutic efficacy, and others suggest exacerbation of the condition.1,38-41 This outcome variability is attributed to isotretinoin’s preferential efficacy in treating inflammatory lesions.40,42
Tetracycline derivatives and intralesional steroid injections also have been employed with some efficacy in patients with focal inflammatory SM and SMS.43 There is limited evidence on the long-term outcomes of these interventions, and intralesional injections often are not recommended in conditions such as SM, in which there are many lesions present.
Surgical Management—Minimally invasive surgical procedures including drainage and resections have been used with varying efficacy in SS and SM. Typically, a 2- to 3-mm incision or sharp-tipped cautery is employed to puncture the cyst. Alternatively, radiofrequency probes with a 2.4-MHz frequency setting have been used to minimize incision size.44 The contents then are expressed with manual pressure or forceps, and the cyst sac is extracted using forceps and/or a vein hook (eFigure 4).44,45 The specific surgical techniques and their respective advantages and limitations are summarized in the eTable. Reported advantages and limitations of surgical techniques are derived from information provided by the authors of steatocystoma case reports, which are based on observations of a very limited sample size.

Laser Treatment—Various laser modalities have been used in the management of steatocystomas, including carbon dioxide lasers, erbium-doped yttrium aluminum garnet lasers, 1450-nm diode plus 1550-nm fractionated erbium-doped fiber lasers, and 1927-nm diode lasers.54,55-57 These lasers are used to perforate the cyst before extirpation and have displayed advantages in minimizing scar length.58 The super-pulse mode of carbon dioxide lasers demonstrates efficacy with minimal scarring and recurrence, and this mode is preferred to minimize thermal damage.54,59 Furthermore, this modality can be especially useful in patients whose condition is refractory to other noninvasive options.59 Similarly, the erbium-doped yttrium aluminum garnet laser was well tolerated with no complications noted.55 The 1927-nm diode laser also displayed good outcomes as well as no recurrence.57 With laser use, it is important to note that multiple treatments are needed to see optimal outcomes.54 Moreover, laser settings must be carefully considered, especially in patients with Fitzpatrick skin type III or higher, and topical anti-inflammatory agents should be considered posttreatment to minimize complications.54,59,60
Recommendations
For management of SS, we recommend conservative therapy of watchful observation, as scarring or postinflammatory pigment change may be brought on by medical or surgical therapy; however, if SS is cosmetically bothersome, laser or surgical excision can be done (eFigure 4).4,43-53 It is important to counsel the patient on risks/benefits. For SM, watchful observation also is indicated; however, systemic therapies aimed at prevention may be the most efficacious by limiting disease progression, and oral tetracycline or isotretinoin may be tried.4 Tetracyclines have the risk for photosensitivity and are teratogenic, while isotretinoin is extremely teratogenic, requires laboratory monitoring and regular pregnancy tests in women, and often causes substantial mucosal dryness. If lesions are bothersome or refractory to these therapies, intralesional steroids or surgical/laser procedures can be tried throughout multiple visits.43-53 For SMS, systemic therapies frequently are recommended. The risks of systemic tetracycline and isotretinoin therapies must be discussed. Patients with treatment-refractory SMS may require surgical excision or deroofing of sinus tracts.43-53 This management is similar to that of HS and must be tailored to the patient.
Conclusion
Overall, steatocystomas are a relatively rare pathology, with a limited consensus on their etiology and management. This review summarizes the current knowledge on the condition to support clinicians in diagnosis and management, ranging from watchful waiting to surgical removal. By individualizing treatment plans, clinicians ultimately can optimize outcomes in patients with steatocystomas.
- Santana CN, Pereira DD, Lisboa AP, et al. Steatocystoma multiplex suppurativa: case report of a rare condition. An Bras Dermatol. 2016;91(5 suppl 1):51-53.
- Atzori L, Zanniello R, Pilloni L, et al. Steatocystoma multiplex suppurativa associated with hidradenitis suppurativa successfully treated with adalimumab. J Eur Acad Dermatol Venereol. 2019;33(Suppl 6):42-44.
- Jamieson WA. Case of numerous cutaneous cysts scattered over the body. Edinb Med J. 1873;19:223-225.
- Kamra HT, Gadgil PA, Ovhal AG, et al. Steatocystoma multiplex-a rare genetic disorder: a case report and review of the literature. J Clin Diagn Res. 2013;7:166-168.
- Brownstein MH. Steatocystoma simplex. A solitary steatocystoma. Arch Dermatol. 1982;118:409-411.
- McDonald RM, Reed WB. Natal teeth and steatocystoma multiplex complicated by hidradenitis suppurativa. A new syndrome. Arch Dermatol. 1976;112:1132-1134.
- Plewig G, Wolff HH, Braun-Falco O. Steatocystoma multiplex: anatomic reevaluation, electron microscopy, and autoradiography. Arch Dermatol. 1982;272:363-380.
- Fletcher J, Posso-De Los Rios C, Jambrosic J, A, et al. Coexistence of hidradenitis suppurativa and steatocystoma multiplex: is it a new variant of hidradenitis suppurativa? J Cutan Med Surg. 2021;25:586-590.
- Cho S, Chang SE, Choi JH, et al. Clinical and histologic features of 64 cases of steatocystoma multiplex. J Dermatol. 2002;29:152-156.
- Covello SP, Smith FJ, Sillevis Smitt JH, et al. Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2. Br J Dermatol. 1998;139:475-480.
- Liu Q, Wu W, Lu J, et al. Steatocystoma multiplex is associated with the R94C mutation in the KRTl7 gene. Mol Med Rep. 2015;12:5072-5076.
- Yang L, Zhang S, Wang G. Keratin 17 in disease pathogenesis: from cancer to dermatoses. J Pathol. 2019;247:158-165.
- Shamloul G, Khachemoune A. An updated review of the sebaceous gland and its role in health and diseases Part 1: embryology, evolution, structure, and function of sebaceous glands. Dermatol Ther. 2021;34:e14695.
- Del Rosso JQ, Kircik LH, Stein Gold L, et al. Androgens, androgen receptors, and the skin: from the laboratory to the clinic with emphasis on clinical and therapeutic implications. J Drugs Dermatol. 2020;19:30-35.
- Porras Fimbres DC, Wolfe SA, Kelley CE. Proliferation of steatocystomas in 2 transgender men. JAAD Case Rep. 2022;26:70-72.
- Marasca C, Megna M, Donnarumma M, et al. A case of steatocystoma multiplex in a psoriatic patient during treatment with anti-IL-12/23. Skin Appendage Disord. 2020;6:309-311.
- Gordon Spratt EA, Kaplan J, Patel RR, et al. Steatocystoma. Dermatol Online J. 2013;19:20721.
- Sharma A, Agrawal S, Dhurat R, et al. An unusual case of facial steatocystoma multiplex: a clinicopathologic and dermoscopic report. Dermatopathology (Basel). 2018;5:58-63.
- Rahman MH, Islam MS, Ansari NP. Atypical steatocystoma multiplex with calcification. ISRN Dermatol. 2011;2011:381901.
- Beyer AV, Vossmann D. Steatocystoma multiplex. Article in German. Hautarzt. 1996;47:469-471.
- Yanagi T, Matsumura T. Steatocystoma multiplex presenting as acral subcutaneous nodules. Acta Derm Venereol. 2006;86:374-375.
- Marzano AV, Tavecchio S, Balice Y, et al. Acral subcutaneous steatocystoma multiplex: a distinct subtype of the disease? Australas J Dermatol. 2012;53:198-201.
- Ferrandiz C, Peyri J. Steatocystoma multiplex. Article in Spanish. Med Cutan Ibero Lat Am. 1984;12:173-176.
- Alotaibi L, Alsaif M, Alhumidi A, et al. Steatocystoma multiplex suppurativa: a case with unusual giant cysts over the scalp and neck. Case Rep Dermatol. 2019;11:71-76.
- Kim SJ, Park HJ, Oh ST, et al. A case of steatocystoma multiplex limited to scalp. Ann Dermatol. 2009;21:106-109.
- Patrizi A, Neri I, Guerrini V, et al. Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts: variable expression of multiple pilosebaceous cysts within an affected family. Dermatology. 1998;196:392-396.
- Tomková H, Fujimoto W, Arata J. Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts. Am J Dermatopathol. 1997;19:250-253.
- Patokar AS, Holani AR, Khandait GH, et al. Eruptive vellus hair cysts: an underdiagnosed entity. Int J Trichology. 2022;14:31-33.
- Ohtake N, Kubota Y, Takayama O, et al. Relationship between steatocystoma multiplex and eruptive vellus hair cysts. J Am Acad Dermatol. 1992;26(5 Pt 2):876-878.
- Yoon H, Kang Y, Park H, et al. Sonographic appearance of steatocystoma: an analysis of 14 pathologically confirmed lesions. Taehan Yongsang Uihakhoe Chi. 2021;82:382-392.
- Varshney M, Aziz M, Maheshwari V, et al. Steatocystoma multiplex. BMJ Case Rep. 2011;2011:bcr0420114165.
- Tsai MH, Hsiao YP, Lin WL, et al. Steatocystoma multiplex as initial impression of non-small cell lung cancer with complete response to gefitinib. Chin J Cancer Res. 2014;26:E5-E9.
- Zussino M, Nazzaro G, Moltrasio C, et al. Coexistence of steatocystoma multiplex and hidradenitis suppurativa: assessment of this unique association by means of ultrasonography and color Doppler. Skin Res Technol. 2019;25:877-880.
- Whittle C, Silva-Hirschberg C, Loyola K, et al. Ultrasonographic spectrum of cutaneous cysts with stratified squamous epithelium in pediatric dermatology: pictorial essay. J Ultrasound Med. 2023;42:923-930.
- Arceu M, Martinez G, Alfaro D, et al. Ultrasound morphologic features of steatocystoma multiplex with clinical correlation. J Ultrasound Med. 2020;39:2255-2260.
- Reick-Mitrisin V, Reddy A, Shah BA. A breast imaging case of steatocystoma multiplex: a rare condition involving multiple anatomic regions. Cureus. 2022;14:E27756.
- Yoon H, Kang Y, Park H, et al. Sonographic appearance of steatocystoma: an analysis of 14 pathologically confirmed lesions. Taehan Yongsang Uihakhoe Chi. 2021;82:382-392.
- Apaydin R, Bilen N, Bayramgurler D, et al. Steatocystoma multiplex suppurativum: oral isotretinoin treatment combined with cryotherapy. Australas J Dermatol. 2000;41:98-100.
- Sharma A, Agrawal S, Dhurat R, et al. An unusual case of facial steatocystoma multiplex: a clinicopathologic and dermoscopic report. Dermatopathology (Basel). 2018;5:58-63.
- Moritz DL, Silverman RA. Steatocystoma multiplex treated with isotretinoin: a delayed response. Cutis. 1988;42:437-439.
- Schwartz JL, Goldsmith LA. Steatocystoma multiplex suppurativum: treatment with isotretinoin. Cutis. 1984;34:149-153.
- Kim SJ, Park HJ, Oh ST, et al. A case of steatocystoma multiplex limited to the scalp. Ann Dermatol. 2009;21:106-109.
- Fekete GL, Fekete JE. Steatocystoma multiplex generalisata partially suppurativa--case report. Acta Dermatovenerol Croat. 2010;18:114-119.
- Choudhary S, Koley S, Salodkar A. A modified surgical technique for steatocystoma multiplex. J Cutan Aesthet Surg. 2010;3:25-28.
- Kaya TI, Ikizoglu G, Kokturk A, et al. A simple surgical technique for the treatment of steatocystoma multiplex. Int J Dermatol. 2001;40:785-788.
- Oertel YC, Scott DM. Cytologic-pathologic correlations: fine needle aspiration of three cases of steatocystoma multiplex. Ann Diagn Pathol. 1998;2:318-320.
- Egbert BM, Price NM, Segal RJ. Steatocystoma multiplex. Report of a florid case and a review. Arch Dermatol. 1979;115:334-335.
- Adams BB, Mutasim DF, Nordlund JJ. Steatocystoma multiplex: a quick removal technique. Cutis. 1999;64:127-130.
- Lee SJ, Choe YS, Park BC, et al. The vein hook successfully used for eradication of steatocystoma multiplex. Dermatol Surg. 2007;33:82-84.
- Bettes PSL, Lopes SL, Prestes MA, et al. Treatment of a facial variant of the multiple steatocystoma with skin graft: case report. Rev Bras Cir Plást. 1998;13:31-36
- Düzova AN, Sentürk GB. Suggestion for the treatment of steatocystoma multiplex located exclusively on the face. Int J Dermatol. 2004;43:60-62. doi:10.1111/j.1365-4632.2004.02068.x
- Choudhary S, Koley S, Salodkar A. A modified surgical technique for steatocystoma multiplex. J Cutan Aesthet Surg. 2010;3:25-28.
- Kaya TI, Ikizoglu G, Kokturk A, et al. A simple surgical technique for the treatment of steatocystoma multiplex. Int J Dermatol. 2001;40:785-788.
- Bakkour W, Madan V. Carbon dioxide laser perforation and extirpation of steatocystoma multiplex. Dermatol Surg. 2014;40:658-662.
- Mumcuog?lu CT, Gurel MS, Kiremitci U, et al. Er: yag laser therapy for steatocystoma multiplex. Indian J Dermatol. 2010;55:300-301.
- Moody MN, Landau JM, Goldberg LH, et al. 1,450-nm diode laser in combination with the 1550-nm fractionated erbium-doped fiber laser for the treatment of steatocystoma multiplex: a case report. Dermatol Surg. 2012;38(7 Pt 1):1104-1106.
- Cheon DU, Ko JY. 1927-nm fiber-optic diode laser: a novel therapeutic option for facial steatocystoma multiplex. J Cosmet Dermatol. 2019;18:1326-1329.
- Kim KT, Sun H, Chung EH. Comparison of complete surgical excision and minimally invasive excision using CO2 laser for removal of epidermal cysts on the face. Arch Craniofac Surg. 2019;20:84-88.
- Kassira S, Korta DZ, de Feraudy S, et al. Fractionated ablative carbon dioxide laser treatment of steatocystoma multiplex. J Cosmet Laser Ther. 2016;18:364-366.
- Dixit N, Sardana K, Paliwal P. The rationale of ideal pulse duration and pulse interval in the treatment of steatocystoma multiplex using the carbon dioxide laser in a super-pulse mode as opposedto the ultra-pulse mode. Indian J Dermatol Venereol Leprol. 2020;86:454-456.
- Santana CN, Pereira DD, Lisboa AP, et al. Steatocystoma multiplex suppurativa: case report of a rare condition. An Bras Dermatol. 2016;91(5 suppl 1):51-53.
- Atzori L, Zanniello R, Pilloni L, et al. Steatocystoma multiplex suppurativa associated with hidradenitis suppurativa successfully treated with adalimumab. J Eur Acad Dermatol Venereol. 2019;33(Suppl 6):42-44.
- Jamieson WA. Case of numerous cutaneous cysts scattered over the body. Edinb Med J. 1873;19:223-225.
- Kamra HT, Gadgil PA, Ovhal AG, et al. Steatocystoma multiplex-a rare genetic disorder: a case report and review of the literature. J Clin Diagn Res. 2013;7:166-168.
- Brownstein MH. Steatocystoma simplex. A solitary steatocystoma. Arch Dermatol. 1982;118:409-411.
- McDonald RM, Reed WB. Natal teeth and steatocystoma multiplex complicated by hidradenitis suppurativa. A new syndrome. Arch Dermatol. 1976;112:1132-1134.
- Plewig G, Wolff HH, Braun-Falco O. Steatocystoma multiplex: anatomic reevaluation, electron microscopy, and autoradiography. Arch Dermatol. 1982;272:363-380.
- Fletcher J, Posso-De Los Rios C, Jambrosic J, A, et al. Coexistence of hidradenitis suppurativa and steatocystoma multiplex: is it a new variant of hidradenitis suppurativa? J Cutan Med Surg. 2021;25:586-590.
- Cho S, Chang SE, Choi JH, et al. Clinical and histologic features of 64 cases of steatocystoma multiplex. J Dermatol. 2002;29:152-156.
- Covello SP, Smith FJ, Sillevis Smitt JH, et al. Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2. Br J Dermatol. 1998;139:475-480.
- Liu Q, Wu W, Lu J, et al. Steatocystoma multiplex is associated with the R94C mutation in the KRTl7 gene. Mol Med Rep. 2015;12:5072-5076.
- Yang L, Zhang S, Wang G. Keratin 17 in disease pathogenesis: from cancer to dermatoses. J Pathol. 2019;247:158-165.
- Shamloul G, Khachemoune A. An updated review of the sebaceous gland and its role in health and diseases Part 1: embryology, evolution, structure, and function of sebaceous glands. Dermatol Ther. 2021;34:e14695.
- Del Rosso JQ, Kircik LH, Stein Gold L, et al. Androgens, androgen receptors, and the skin: from the laboratory to the clinic with emphasis on clinical and therapeutic implications. J Drugs Dermatol. 2020;19:30-35.
- Porras Fimbres DC, Wolfe SA, Kelley CE. Proliferation of steatocystomas in 2 transgender men. JAAD Case Rep. 2022;26:70-72.
- Marasca C, Megna M, Donnarumma M, et al. A case of steatocystoma multiplex in a psoriatic patient during treatment with anti-IL-12/23. Skin Appendage Disord. 2020;6:309-311.
- Gordon Spratt EA, Kaplan J, Patel RR, et al. Steatocystoma. Dermatol Online J. 2013;19:20721.
- Sharma A, Agrawal S, Dhurat R, et al. An unusual case of facial steatocystoma multiplex: a clinicopathologic and dermoscopic report. Dermatopathology (Basel). 2018;5:58-63.
- Rahman MH, Islam MS, Ansari NP. Atypical steatocystoma multiplex with calcification. ISRN Dermatol. 2011;2011:381901.
- Beyer AV, Vossmann D. Steatocystoma multiplex. Article in German. Hautarzt. 1996;47:469-471.
- Yanagi T, Matsumura T. Steatocystoma multiplex presenting as acral subcutaneous nodules. Acta Derm Venereol. 2006;86:374-375.
- Marzano AV, Tavecchio S, Balice Y, et al. Acral subcutaneous steatocystoma multiplex: a distinct subtype of the disease? Australas J Dermatol. 2012;53:198-201.
- Ferrandiz C, Peyri J. Steatocystoma multiplex. Article in Spanish. Med Cutan Ibero Lat Am. 1984;12:173-176.
- Alotaibi L, Alsaif M, Alhumidi A, et al. Steatocystoma multiplex suppurativa: a case with unusual giant cysts over the scalp and neck. Case Rep Dermatol. 2019;11:71-76.
- Kim SJ, Park HJ, Oh ST, et al. A case of steatocystoma multiplex limited to scalp. Ann Dermatol. 2009;21:106-109.
- Patrizi A, Neri I, Guerrini V, et al. Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts: variable expression of multiple pilosebaceous cysts within an affected family. Dermatology. 1998;196:392-396.
- Tomková H, Fujimoto W, Arata J. Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts. Am J Dermatopathol. 1997;19:250-253.
- Patokar AS, Holani AR, Khandait GH, et al. Eruptive vellus hair cysts: an underdiagnosed entity. Int J Trichology. 2022;14:31-33.
- Ohtake N, Kubota Y, Takayama O, et al. Relationship between steatocystoma multiplex and eruptive vellus hair cysts. J Am Acad Dermatol. 1992;26(5 Pt 2):876-878.
- Yoon H, Kang Y, Park H, et al. Sonographic appearance of steatocystoma: an analysis of 14 pathologically confirmed lesions. Taehan Yongsang Uihakhoe Chi. 2021;82:382-392.
- Varshney M, Aziz M, Maheshwari V, et al. Steatocystoma multiplex. BMJ Case Rep. 2011;2011:bcr0420114165.
- Tsai MH, Hsiao YP, Lin WL, et al. Steatocystoma multiplex as initial impression of non-small cell lung cancer with complete response to gefitinib. Chin J Cancer Res. 2014;26:E5-E9.
- Zussino M, Nazzaro G, Moltrasio C, et al. Coexistence of steatocystoma multiplex and hidradenitis suppurativa: assessment of this unique association by means of ultrasonography and color Doppler. Skin Res Technol. 2019;25:877-880.
- Whittle C, Silva-Hirschberg C, Loyola K, et al. Ultrasonographic spectrum of cutaneous cysts with stratified squamous epithelium in pediatric dermatology: pictorial essay. J Ultrasound Med. 2023;42:923-930.
- Arceu M, Martinez G, Alfaro D, et al. Ultrasound morphologic features of steatocystoma multiplex with clinical correlation. J Ultrasound Med. 2020;39:2255-2260.
- Reick-Mitrisin V, Reddy A, Shah BA. A breast imaging case of steatocystoma multiplex: a rare condition involving multiple anatomic regions. Cureus. 2022;14:E27756.
- Yoon H, Kang Y, Park H, et al. Sonographic appearance of steatocystoma: an analysis of 14 pathologically confirmed lesions. Taehan Yongsang Uihakhoe Chi. 2021;82:382-392.
- Apaydin R, Bilen N, Bayramgurler D, et al. Steatocystoma multiplex suppurativum: oral isotretinoin treatment combined with cryotherapy. Australas J Dermatol. 2000;41:98-100.
- Sharma A, Agrawal S, Dhurat R, et al. An unusual case of facial steatocystoma multiplex: a clinicopathologic and dermoscopic report. Dermatopathology (Basel). 2018;5:58-63.
- Moritz DL, Silverman RA. Steatocystoma multiplex treated with isotretinoin: a delayed response. Cutis. 1988;42:437-439.
- Schwartz JL, Goldsmith LA. Steatocystoma multiplex suppurativum: treatment with isotretinoin. Cutis. 1984;34:149-153.
- Kim SJ, Park HJ, Oh ST, et al. A case of steatocystoma multiplex limited to the scalp. Ann Dermatol. 2009;21:106-109.
- Fekete GL, Fekete JE. Steatocystoma multiplex generalisata partially suppurativa--case report. Acta Dermatovenerol Croat. 2010;18:114-119.
- Choudhary S, Koley S, Salodkar A. A modified surgical technique for steatocystoma multiplex. J Cutan Aesthet Surg. 2010;3:25-28.
- Kaya TI, Ikizoglu G, Kokturk A, et al. A simple surgical technique for the treatment of steatocystoma multiplex. Int J Dermatol. 2001;40:785-788.
- Oertel YC, Scott DM. Cytologic-pathologic correlations: fine needle aspiration of three cases of steatocystoma multiplex. Ann Diagn Pathol. 1998;2:318-320.
- Egbert BM, Price NM, Segal RJ. Steatocystoma multiplex. Report of a florid case and a review. Arch Dermatol. 1979;115:334-335.
- Adams BB, Mutasim DF, Nordlund JJ. Steatocystoma multiplex: a quick removal technique. Cutis. 1999;64:127-130.
- Lee SJ, Choe YS, Park BC, et al. The vein hook successfully used for eradication of steatocystoma multiplex. Dermatol Surg. 2007;33:82-84.
- Bettes PSL, Lopes SL, Prestes MA, et al. Treatment of a facial variant of the multiple steatocystoma with skin graft: case report. Rev Bras Cir Plást. 1998;13:31-36
- Düzova AN, Sentürk GB. Suggestion for the treatment of steatocystoma multiplex located exclusively on the face. Int J Dermatol. 2004;43:60-62. doi:10.1111/j.1365-4632.2004.02068.x
- Choudhary S, Koley S, Salodkar A. A modified surgical technique for steatocystoma multiplex. J Cutan Aesthet Surg. 2010;3:25-28.
- Kaya TI, Ikizoglu G, Kokturk A, et al. A simple surgical technique for the treatment of steatocystoma multiplex. Int J Dermatol. 2001;40:785-788.
- Bakkour W, Madan V. Carbon dioxide laser perforation and extirpation of steatocystoma multiplex. Dermatol Surg. 2014;40:658-662.
- Mumcuog?lu CT, Gurel MS, Kiremitci U, et al. Er: yag laser therapy for steatocystoma multiplex. Indian J Dermatol. 2010;55:300-301.
- Moody MN, Landau JM, Goldberg LH, et al. 1,450-nm diode laser in combination with the 1550-nm fractionated erbium-doped fiber laser for the treatment of steatocystoma multiplex: a case report. Dermatol Surg. 2012;38(7 Pt 1):1104-1106.
- Cheon DU, Ko JY. 1927-nm fiber-optic diode laser: a novel therapeutic option for facial steatocystoma multiplex. J Cosmet Dermatol. 2019;18:1326-1329.
- Kim KT, Sun H, Chung EH. Comparison of complete surgical excision and minimally invasive excision using CO2 laser for removal of epidermal cysts on the face. Arch Craniofac Surg. 2019;20:84-88.
- Kassira S, Korta DZ, de Feraudy S, et al. Fractionated ablative carbon dioxide laser treatment of steatocystoma multiplex. J Cosmet Laser Ther. 2016;18:364-366.
- Dixit N, Sardana K, Paliwal P. The rationale of ideal pulse duration and pulse interval in the treatment of steatocystoma multiplex using the carbon dioxide laser in a super-pulse mode as opposedto the ultra-pulse mode. Indian J Dermatol Venereol Leprol. 2020;86:454-456.
Steatocystomas: Update on Clinical Manifestations, Diagnosis, and Management
Steatocystomas: Update on Clinical Manifestations, Diagnosis, and Management
Practice Points
- Steatocystomas, which manifest as single or multiple flesh-colored subcutaneous cysts ranging from less than 3 mm to more than 3 cm, typically are asymptomatic and can persist indefinitely.
- Treatment options for steatocystomas include oral isotretinoin, tetracycline derivatives, and intralesional steroid injections. Minimally invasive procedures such as drainage and resection also are available, employing techniques such as blade incision, radiofrequency probes, and laser treatments to minimize scarring and recurrence.
- Conservative therapies such as watchful waiting are recommended for the simplex and multiplex variants, while more aggressive management such as surgical removal is recommended for the multiplex suppurativa variant due to its elevated risk for complications.
Operational Risk Management in Dermatologic Procedures
Operational Risk Management in Dermatologic Procedures
Operational risk management (ORM) refers to the systematic identification and assessment of daily operational risks within an organization designed to mitigate negative financial, reputational, and safety outcomes while maximizing efficiency and achievement of objectives.1 Operational risk management is indispensable to modern military operations, optimizing mission readiness while minimizing complications and personnel morbidity. Application of ORM in medicine holds considerable promise due to the emphasis on precise and efficient decision-making in high-stakes environments, where the margin for error is minimal. In this article, we propose integrating ORM principles into dermatologic surgery to enhance patient-centered care through improved counseling, risk assessment, and procedural outcomes.
Principles and Processes of ORM
The ORM framework is built on 4 fundamental principles: accept risk when benefits outweigh the cost, accept no unnecessary risk, anticipate and manage risk by planning, and make risk decisions at the right level.2 These principles form the foundation of the ORM’s systematic 5-step approach to identify hazards, assess hazards, make risk decisions, implement controls, and supervise. Key to the ORM process is the use of risk assessment codes and the risk assessment matrix to quantify and prioritize risks. Risk assessment codes are numerical values assigned to hazards based on their assessed severity and probability. The risk assessment matrix is a tool that plots the severity of a hazard against its probability. By locating a hazard on the matrix, users can visualize its risk level in terms of severity and probability. Building and using the risk assessment matrix begins with determining severity by assessing the potential impact of a hazard and categorizing it into levels (catastrophic, critical, moderate, or negligible). Next, probability is determined by evaluating the likelihood of occurrence (frequent, likely, occasional, seldom, or unlikely). Finally, the severity and probability are combined to assign a risk assessment code, which indicates the risk level and helps visualize criticality. Systematically applying these principles and processes enables users to make informed decisions that balance mission objectives with safety.
Proposed Framework for ORM in Dermatology Surgery
Current risk mitigation in dermatologic surgery includes strict medication oversight, sterilization protocols, and photography to prevent wrong-site surgeries. Preoperative risk assessment through conducting a thorough patient history is vital, considering factors such as pregnancy, allergies, bleeding history, cardiac devices, and keloid propensity, all of which impact surgical outcomes.3-5 After gathering the patient’s history, dermatologists determine appropriateness for surgery and its inherent risks, typically via an informed consent process outlining the diagnosis and procedure purpose as well as a list of risks, benefits, and alternatives, including forgoing treatment.
Importantly, the standard process for dermatologic risk evaluation often lacks a comprehensive systematic approach seen in other higher-risk surgical fields. For example, general surgeons frequently utilize risk assessment calculators such as the one developed by the American College of Surgeons’ National Surgical Quality Improvement Program to estimate surgical complications.6 While specific guidelines exist for evaluating factors such as hypertension or anticoagulant use, no single tool synthesizes all patient risk factors for a unified assessment. Therefore, we propose integrating ORM as a structured decision-making process that offers a more consistent means for dermatologists to evaluate, synthesize, categorize, and present risks to patients. Our proposed process includes translating military mishap severity into a framework that helps patients better understand decisions about their health care when using ORM (eTable 1). The proposed process also provides dermatologists with a systematic, proactive, and iterative approach to assessing risks that allows them to consistently qualify medical decisions (eTable 2).


Patients often struggle to understand surgical risk severity, including overestimating the risks of routine minor procedures or underestimating the risks of more intensive procedures.7,8 Incorporating ORM into patient communication mirrors the provider’s process but uses patient-friendly terminology—it is discussion based and integrates patient preferences and tolerances (eTable 2). These steps often occur informally in dermatologic counseling; however, an organized structured approach, especially using a visual aid such as a risk assessment matrix, enhances patient comprehension, recall, and satisfaction.9
Practical Scenarios
Integrating ORM into dermatologic surgery is a proactive iterative process for both provider decision-making and patient communication. Leveraging a risk assessment matrix as a visual aid allows for clear identification, evaluation, and mitigation of hazards, fostering collaborative choices with regard to the treatment approach. Here we provide 2 case scenarios highlighting how ORM and the risk assessment matrix can be used in the management of a complex patient with a lesion in a high-risk location as well as to address patient anxiety and comorbidities. It is important to note that the way the matrices are completed in the examples provided may differ compared to other providers. The purpose of ORM is not to dictate risk categories but to serve as a tool for providers to take their own experiences and knowledge of the patient to guide their decision-making and counseling processes.
Case Scenario 1—An elderly man with a history of diabetes, cardiovascular accident, coronary artery bypass grafting, and multiple squamous cell carcinoma excisions presents for evaluation of a 1-cm squamous cell carcinoma in situ on the left leg. His current medications include an anticoagulant and antihypertensives.
In this scenario, the provider would apply ORM by identifying and assessing hazards, making risk decisions, implementing controls, and supervising care.
General hazards for excision on the leg include bleeding, infection, scarring, pain, delayed healing, activity limitations, and possible further procedures. Before the visit, the provider should prepare baseline risk matrices for 2 potential treatment options: wide local excision and electrodessication and curettage. For example, surgical bleeding may be assessed as negligible severity and almost certain probability for a general excision.
Next, the provider would incorporate the patient’s unique history in the risk matrices (eFigures 1 and 2). The patient’s use of an anticoagulant indicates a bleeding risk; therefore, the provider may shift the severity to minimal clinical concern, understanding the need for enhanced perioperative management. The history of diabetes also has a considerable impact on wound healing, so the provider might elevate the probability of delayed wound healing from rare to unlikely and the severity from moderate to severe. The prior cardiovascular accident also raises concerns about mobility and activity limitations during recovery, which could be escalated from minimal to moderate clinical concern if postoperative limitations on ambulation increase the risk for new clots. Based on this internal assessment, the provider identifies which risks are elevated and require further attention and discussion with the patient, helping tailor the counseling approach and potential treatment plan. The provider should begin to consider initial control measures such as coordinating anticoagulant management, ensuring diabetes is well controlled, and planning for postoperative ambulation support.
Once the provider has conducted the internal assessment, the ORM matrices become powerful tools for shared decision-making with the patient. The provider can walk the patient through the procedures and their common risks and then explain how their individual situation modifies the risks. The visual and explicit upgrade on the matrices allows the patient to clearly see how unique factors influence their personal risk profile, moving beyond a generic list of complications. The provider then should engage the patient in a discussion about their risk tolerance, which is crucial for mutual agreement on whether to proceed with treatment and, if so, which procedure is most appropriate given the patient’s comfort level with their individualized risk profile. Then the provider should reinforce the proactive steps planned to mitigate the identified risks to provide assurance and reinforce the collaborative approach to safety.
Finally, throughout the preoperative and postoperative phases, the provider should continuously monitor the patient’s condition and the effectiveness of the control measures, adjusting the plan as needed.
In this scenario, both the provider and the patient participated in the risk assessment, with the provider completing the assessment before the visit and presenting it to the patient or performing the assessment in real time with the patient present to explain the reasoning behind assignment of risk based on each procedure and the patient’s unique risk factors.
Case Scenario 2—A 38-year-old woman with a history of hypertension and procedural anxiety presents for evaluation of a biopsy-proven basal cell carcinoma on the nasal ala. The patient is taking diltiazem for hypertension and is compliant with her medication. Her blood pressure at the current visit is 148/96 mm Hg, which she attributes to white coat syndrome. Mohs micrographic surgery generally is the gold standard treatment for this case.
The provider’s ORM process, conducted either before or in real time during the visit, would begin with identification and assessment of the hazards. For Mohs surgery on the nasal ala, common hazards would include scarring, pain, infection, bleeding, and potential cosmetic distortion. Unique to this patient are the procedural anxiety and hypertension.
To populate the risk assessment matrix (eFigure 3), the provider would first map the baseline risks of Mohs surgery, which include considerable scarring as a moderate clinical concern but a seldom probability. Because the patient’s procedural anxiety directly increases the probability of intraoperative distress or elevated blood pressure during the procedure, the provider might assess patient distress/anxiety as a moderate clinical concern with a likely probability. While the patient’s blood pressure is controlled, the white coat syndrome raises the probability of hypertensive urgency/emergency during surgery; this might be elevated from unlikely to occasional or likely probability, and severity might increase from minimal to moderate due to its potential impact on procedural safety. The provider should consider strategies to address these elevated risks during the consultation. Then, as part of preprocedure planning, the provider should consider discussing anxiolytics, emphasizing medication compliance, and ensuring a calm environment for the patient’s surgery.
For this patient, the risk assessment matrix becomes a powerful tool to address fears and proactively manage her unique risk factors. To start the counseling process, the provider should explain the procedure, its benefits, and potential adverse effects. Then, the patient’s individualized risks can be visualized using the matrix, which also is an opportunity for reassurance, as it can alleviate patient fears by contextualizing rare but impactful outcomes.9
Now the provider can assess the patient’s risk tolerance. This discussion ensures that the patient’s comfort level and preferences are central to the treatment decision, even for a gold-standard procedure such as Mohs surgery. By listening and responding to the patient’s input, the provider can build trust and discuss strategies that can help control for some risk factors.
Finally, the provider would re-evaluate throughout the procedure by continuously monitoring the patient’s anxiety and vital signs. The provider should also be ready to adjust pain management or employ anxiety-reduction techniques.
Final Thoughts
Reviewing the risk assessment matrix can be an effective way to nonjudgmentally discuss a patient’s unique risk factors and provide a complete understanding of the planned treatment or procedure. It conveys to the patient that, as the provider, you are taking their health seriously when considering treatment options and can be a means to build patient rapport and trust. This approach mirrors risk communication strategies long employed in military operational planning, where transparency and structured risk evaluation are essential to maintaining mission readiness and unit cohesion.
- The OR Society. The history of OR. The OR Society. Published 2023.
- Naval Postgraduate School. ORM: operational risk management. Accessed September 12, 2025. https://nps.edu/web/safety/orm
- Smith C, Srivastava D, Nijhawan RI. Optimizing patient safety in dermatologic surgery. Dermatol Clin. 2019;37:319-328.
- Minkis K, Whittington A, Alam M. Dermatologic surgery emergencies: complications caused by systemic reactions, high-energy systems, and trauma. J Am Acad Dermatol. 2016;75:265-284.
- Pomerantz RG, Lee DA, Siegel DM. Risk assessment in surgical patients: balancing iatrogenic risks and benefits. Clin Dermatol. 2011;29:669-677.
- Bilimoria KY, Liu Y, Paruch JL, et al. Development and evaluation of the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and surgeons. J Am Coll Surgeons. 2013;217:833-842.
- Lloyd AJ. The extent of patients’ understanding of the risk of treatments. BMJ Qual Saf. 2001;10:i14-i18.
- Falagas ME, Korbila IP, Giannopoulou KP, et al. Informed consent: how much and what do patients understand? Am J Surg. 2009;198:420-435.
- Cohen SM, Baimas-George M, Ponce C, et al. Is a picture worth a thousand words? a scoping review of the impact of visual aids on patients undergoing surgery. J Surg Educ. 2024;81:1276-1292.
Operational risk management (ORM) refers to the systematic identification and assessment of daily operational risks within an organization designed to mitigate negative financial, reputational, and safety outcomes while maximizing efficiency and achievement of objectives.1 Operational risk management is indispensable to modern military operations, optimizing mission readiness while minimizing complications and personnel morbidity. Application of ORM in medicine holds considerable promise due to the emphasis on precise and efficient decision-making in high-stakes environments, where the margin for error is minimal. In this article, we propose integrating ORM principles into dermatologic surgery to enhance patient-centered care through improved counseling, risk assessment, and procedural outcomes.
Principles and Processes of ORM
The ORM framework is built on 4 fundamental principles: accept risk when benefits outweigh the cost, accept no unnecessary risk, anticipate and manage risk by planning, and make risk decisions at the right level.2 These principles form the foundation of the ORM’s systematic 5-step approach to identify hazards, assess hazards, make risk decisions, implement controls, and supervise. Key to the ORM process is the use of risk assessment codes and the risk assessment matrix to quantify and prioritize risks. Risk assessment codes are numerical values assigned to hazards based on their assessed severity and probability. The risk assessment matrix is a tool that plots the severity of a hazard against its probability. By locating a hazard on the matrix, users can visualize its risk level in terms of severity and probability. Building and using the risk assessment matrix begins with determining severity by assessing the potential impact of a hazard and categorizing it into levels (catastrophic, critical, moderate, or negligible). Next, probability is determined by evaluating the likelihood of occurrence (frequent, likely, occasional, seldom, or unlikely). Finally, the severity and probability are combined to assign a risk assessment code, which indicates the risk level and helps visualize criticality. Systematically applying these principles and processes enables users to make informed decisions that balance mission objectives with safety.
Proposed Framework for ORM in Dermatology Surgery
Current risk mitigation in dermatologic surgery includes strict medication oversight, sterilization protocols, and photography to prevent wrong-site surgeries. Preoperative risk assessment through conducting a thorough patient history is vital, considering factors such as pregnancy, allergies, bleeding history, cardiac devices, and keloid propensity, all of which impact surgical outcomes.3-5 After gathering the patient’s history, dermatologists determine appropriateness for surgery and its inherent risks, typically via an informed consent process outlining the diagnosis and procedure purpose as well as a list of risks, benefits, and alternatives, including forgoing treatment.
Importantly, the standard process for dermatologic risk evaluation often lacks a comprehensive systematic approach seen in other higher-risk surgical fields. For example, general surgeons frequently utilize risk assessment calculators such as the one developed by the American College of Surgeons’ National Surgical Quality Improvement Program to estimate surgical complications.6 While specific guidelines exist for evaluating factors such as hypertension or anticoagulant use, no single tool synthesizes all patient risk factors for a unified assessment. Therefore, we propose integrating ORM as a structured decision-making process that offers a more consistent means for dermatologists to evaluate, synthesize, categorize, and present risks to patients. Our proposed process includes translating military mishap severity into a framework that helps patients better understand decisions about their health care when using ORM (eTable 1). The proposed process also provides dermatologists with a systematic, proactive, and iterative approach to assessing risks that allows them to consistently qualify medical decisions (eTable 2).


Patients often struggle to understand surgical risk severity, including overestimating the risks of routine minor procedures or underestimating the risks of more intensive procedures.7,8 Incorporating ORM into patient communication mirrors the provider’s process but uses patient-friendly terminology—it is discussion based and integrates patient preferences and tolerances (eTable 2). These steps often occur informally in dermatologic counseling; however, an organized structured approach, especially using a visual aid such as a risk assessment matrix, enhances patient comprehension, recall, and satisfaction.9
Practical Scenarios
Integrating ORM into dermatologic surgery is a proactive iterative process for both provider decision-making and patient communication. Leveraging a risk assessment matrix as a visual aid allows for clear identification, evaluation, and mitigation of hazards, fostering collaborative choices with regard to the treatment approach. Here we provide 2 case scenarios highlighting how ORM and the risk assessment matrix can be used in the management of a complex patient with a lesion in a high-risk location as well as to address patient anxiety and comorbidities. It is important to note that the way the matrices are completed in the examples provided may differ compared to other providers. The purpose of ORM is not to dictate risk categories but to serve as a tool for providers to take their own experiences and knowledge of the patient to guide their decision-making and counseling processes.
Case Scenario 1—An elderly man with a history of diabetes, cardiovascular accident, coronary artery bypass grafting, and multiple squamous cell carcinoma excisions presents for evaluation of a 1-cm squamous cell carcinoma in situ on the left leg. His current medications include an anticoagulant and antihypertensives.
In this scenario, the provider would apply ORM by identifying and assessing hazards, making risk decisions, implementing controls, and supervising care.
General hazards for excision on the leg include bleeding, infection, scarring, pain, delayed healing, activity limitations, and possible further procedures. Before the visit, the provider should prepare baseline risk matrices for 2 potential treatment options: wide local excision and electrodessication and curettage. For example, surgical bleeding may be assessed as negligible severity and almost certain probability for a general excision.
Next, the provider would incorporate the patient’s unique history in the risk matrices (eFigures 1 and 2). The patient’s use of an anticoagulant indicates a bleeding risk; therefore, the provider may shift the severity to minimal clinical concern, understanding the need for enhanced perioperative management. The history of diabetes also has a considerable impact on wound healing, so the provider might elevate the probability of delayed wound healing from rare to unlikely and the severity from moderate to severe. The prior cardiovascular accident also raises concerns about mobility and activity limitations during recovery, which could be escalated from minimal to moderate clinical concern if postoperative limitations on ambulation increase the risk for new clots. Based on this internal assessment, the provider identifies which risks are elevated and require further attention and discussion with the patient, helping tailor the counseling approach and potential treatment plan. The provider should begin to consider initial control measures such as coordinating anticoagulant management, ensuring diabetes is well controlled, and planning for postoperative ambulation support.
Once the provider has conducted the internal assessment, the ORM matrices become powerful tools for shared decision-making with the patient. The provider can walk the patient through the procedures and their common risks and then explain how their individual situation modifies the risks. The visual and explicit upgrade on the matrices allows the patient to clearly see how unique factors influence their personal risk profile, moving beyond a generic list of complications. The provider then should engage the patient in a discussion about their risk tolerance, which is crucial for mutual agreement on whether to proceed with treatment and, if so, which procedure is most appropriate given the patient’s comfort level with their individualized risk profile. Then the provider should reinforce the proactive steps planned to mitigate the identified risks to provide assurance and reinforce the collaborative approach to safety.
Finally, throughout the preoperative and postoperative phases, the provider should continuously monitor the patient’s condition and the effectiveness of the control measures, adjusting the plan as needed.
In this scenario, both the provider and the patient participated in the risk assessment, with the provider completing the assessment before the visit and presenting it to the patient or performing the assessment in real time with the patient present to explain the reasoning behind assignment of risk based on each procedure and the patient’s unique risk factors.
Case Scenario 2—A 38-year-old woman with a history of hypertension and procedural anxiety presents for evaluation of a biopsy-proven basal cell carcinoma on the nasal ala. The patient is taking diltiazem for hypertension and is compliant with her medication. Her blood pressure at the current visit is 148/96 mm Hg, which she attributes to white coat syndrome. Mohs micrographic surgery generally is the gold standard treatment for this case.
The provider’s ORM process, conducted either before or in real time during the visit, would begin with identification and assessment of the hazards. For Mohs surgery on the nasal ala, common hazards would include scarring, pain, infection, bleeding, and potential cosmetic distortion. Unique to this patient are the procedural anxiety and hypertension.
To populate the risk assessment matrix (eFigure 3), the provider would first map the baseline risks of Mohs surgery, which include considerable scarring as a moderate clinical concern but a seldom probability. Because the patient’s procedural anxiety directly increases the probability of intraoperative distress or elevated blood pressure during the procedure, the provider might assess patient distress/anxiety as a moderate clinical concern with a likely probability. While the patient’s blood pressure is controlled, the white coat syndrome raises the probability of hypertensive urgency/emergency during surgery; this might be elevated from unlikely to occasional or likely probability, and severity might increase from minimal to moderate due to its potential impact on procedural safety. The provider should consider strategies to address these elevated risks during the consultation. Then, as part of preprocedure planning, the provider should consider discussing anxiolytics, emphasizing medication compliance, and ensuring a calm environment for the patient’s surgery.
For this patient, the risk assessment matrix becomes a powerful tool to address fears and proactively manage her unique risk factors. To start the counseling process, the provider should explain the procedure, its benefits, and potential adverse effects. Then, the patient’s individualized risks can be visualized using the matrix, which also is an opportunity for reassurance, as it can alleviate patient fears by contextualizing rare but impactful outcomes.9
Now the provider can assess the patient’s risk tolerance. This discussion ensures that the patient’s comfort level and preferences are central to the treatment decision, even for a gold-standard procedure such as Mohs surgery. By listening and responding to the patient’s input, the provider can build trust and discuss strategies that can help control for some risk factors.
Finally, the provider would re-evaluate throughout the procedure by continuously monitoring the patient’s anxiety and vital signs. The provider should also be ready to adjust pain management or employ anxiety-reduction techniques.
Final Thoughts
Reviewing the risk assessment matrix can be an effective way to nonjudgmentally discuss a patient’s unique risk factors and provide a complete understanding of the planned treatment or procedure. It conveys to the patient that, as the provider, you are taking their health seriously when considering treatment options and can be a means to build patient rapport and trust. This approach mirrors risk communication strategies long employed in military operational planning, where transparency and structured risk evaluation are essential to maintaining mission readiness and unit cohesion.
Operational risk management (ORM) refers to the systematic identification and assessment of daily operational risks within an organization designed to mitigate negative financial, reputational, and safety outcomes while maximizing efficiency and achievement of objectives.1 Operational risk management is indispensable to modern military operations, optimizing mission readiness while minimizing complications and personnel morbidity. Application of ORM in medicine holds considerable promise due to the emphasis on precise and efficient decision-making in high-stakes environments, where the margin for error is minimal. In this article, we propose integrating ORM principles into dermatologic surgery to enhance patient-centered care through improved counseling, risk assessment, and procedural outcomes.
Principles and Processes of ORM
The ORM framework is built on 4 fundamental principles: accept risk when benefits outweigh the cost, accept no unnecessary risk, anticipate and manage risk by planning, and make risk decisions at the right level.2 These principles form the foundation of the ORM’s systematic 5-step approach to identify hazards, assess hazards, make risk decisions, implement controls, and supervise. Key to the ORM process is the use of risk assessment codes and the risk assessment matrix to quantify and prioritize risks. Risk assessment codes are numerical values assigned to hazards based on their assessed severity and probability. The risk assessment matrix is a tool that plots the severity of a hazard against its probability. By locating a hazard on the matrix, users can visualize its risk level in terms of severity and probability. Building and using the risk assessment matrix begins with determining severity by assessing the potential impact of a hazard and categorizing it into levels (catastrophic, critical, moderate, or negligible). Next, probability is determined by evaluating the likelihood of occurrence (frequent, likely, occasional, seldom, or unlikely). Finally, the severity and probability are combined to assign a risk assessment code, which indicates the risk level and helps visualize criticality. Systematically applying these principles and processes enables users to make informed decisions that balance mission objectives with safety.
Proposed Framework for ORM in Dermatology Surgery
Current risk mitigation in dermatologic surgery includes strict medication oversight, sterilization protocols, and photography to prevent wrong-site surgeries. Preoperative risk assessment through conducting a thorough patient history is vital, considering factors such as pregnancy, allergies, bleeding history, cardiac devices, and keloid propensity, all of which impact surgical outcomes.3-5 After gathering the patient’s history, dermatologists determine appropriateness for surgery and its inherent risks, typically via an informed consent process outlining the diagnosis and procedure purpose as well as a list of risks, benefits, and alternatives, including forgoing treatment.
Importantly, the standard process for dermatologic risk evaluation often lacks a comprehensive systematic approach seen in other higher-risk surgical fields. For example, general surgeons frequently utilize risk assessment calculators such as the one developed by the American College of Surgeons’ National Surgical Quality Improvement Program to estimate surgical complications.6 While specific guidelines exist for evaluating factors such as hypertension or anticoagulant use, no single tool synthesizes all patient risk factors for a unified assessment. Therefore, we propose integrating ORM as a structured decision-making process that offers a more consistent means for dermatologists to evaluate, synthesize, categorize, and present risks to patients. Our proposed process includes translating military mishap severity into a framework that helps patients better understand decisions about their health care when using ORM (eTable 1). The proposed process also provides dermatologists with a systematic, proactive, and iterative approach to assessing risks that allows them to consistently qualify medical decisions (eTable 2).


Patients often struggle to understand surgical risk severity, including overestimating the risks of routine minor procedures or underestimating the risks of more intensive procedures.7,8 Incorporating ORM into patient communication mirrors the provider’s process but uses patient-friendly terminology—it is discussion based and integrates patient preferences and tolerances (eTable 2). These steps often occur informally in dermatologic counseling; however, an organized structured approach, especially using a visual aid such as a risk assessment matrix, enhances patient comprehension, recall, and satisfaction.9
Practical Scenarios
Integrating ORM into dermatologic surgery is a proactive iterative process for both provider decision-making and patient communication. Leveraging a risk assessment matrix as a visual aid allows for clear identification, evaluation, and mitigation of hazards, fostering collaborative choices with regard to the treatment approach. Here we provide 2 case scenarios highlighting how ORM and the risk assessment matrix can be used in the management of a complex patient with a lesion in a high-risk location as well as to address patient anxiety and comorbidities. It is important to note that the way the matrices are completed in the examples provided may differ compared to other providers. The purpose of ORM is not to dictate risk categories but to serve as a tool for providers to take their own experiences and knowledge of the patient to guide their decision-making and counseling processes.
Case Scenario 1—An elderly man with a history of diabetes, cardiovascular accident, coronary artery bypass grafting, and multiple squamous cell carcinoma excisions presents for evaluation of a 1-cm squamous cell carcinoma in situ on the left leg. His current medications include an anticoagulant and antihypertensives.
In this scenario, the provider would apply ORM by identifying and assessing hazards, making risk decisions, implementing controls, and supervising care.
General hazards for excision on the leg include bleeding, infection, scarring, pain, delayed healing, activity limitations, and possible further procedures. Before the visit, the provider should prepare baseline risk matrices for 2 potential treatment options: wide local excision and electrodessication and curettage. For example, surgical bleeding may be assessed as negligible severity and almost certain probability for a general excision.
Next, the provider would incorporate the patient’s unique history in the risk matrices (eFigures 1 and 2). The patient’s use of an anticoagulant indicates a bleeding risk; therefore, the provider may shift the severity to minimal clinical concern, understanding the need for enhanced perioperative management. The history of diabetes also has a considerable impact on wound healing, so the provider might elevate the probability of delayed wound healing from rare to unlikely and the severity from moderate to severe. The prior cardiovascular accident also raises concerns about mobility and activity limitations during recovery, which could be escalated from minimal to moderate clinical concern if postoperative limitations on ambulation increase the risk for new clots. Based on this internal assessment, the provider identifies which risks are elevated and require further attention and discussion with the patient, helping tailor the counseling approach and potential treatment plan. The provider should begin to consider initial control measures such as coordinating anticoagulant management, ensuring diabetes is well controlled, and planning for postoperative ambulation support.
Once the provider has conducted the internal assessment, the ORM matrices become powerful tools for shared decision-making with the patient. The provider can walk the patient through the procedures and their common risks and then explain how their individual situation modifies the risks. The visual and explicit upgrade on the matrices allows the patient to clearly see how unique factors influence their personal risk profile, moving beyond a generic list of complications. The provider then should engage the patient in a discussion about their risk tolerance, which is crucial for mutual agreement on whether to proceed with treatment and, if so, which procedure is most appropriate given the patient’s comfort level with their individualized risk profile. Then the provider should reinforce the proactive steps planned to mitigate the identified risks to provide assurance and reinforce the collaborative approach to safety.
Finally, throughout the preoperative and postoperative phases, the provider should continuously monitor the patient’s condition and the effectiveness of the control measures, adjusting the plan as needed.
In this scenario, both the provider and the patient participated in the risk assessment, with the provider completing the assessment before the visit and presenting it to the patient or performing the assessment in real time with the patient present to explain the reasoning behind assignment of risk based on each procedure and the patient’s unique risk factors.
Case Scenario 2—A 38-year-old woman with a history of hypertension and procedural anxiety presents for evaluation of a biopsy-proven basal cell carcinoma on the nasal ala. The patient is taking diltiazem for hypertension and is compliant with her medication. Her blood pressure at the current visit is 148/96 mm Hg, which she attributes to white coat syndrome. Mohs micrographic surgery generally is the gold standard treatment for this case.
The provider’s ORM process, conducted either before or in real time during the visit, would begin with identification and assessment of the hazards. For Mohs surgery on the nasal ala, common hazards would include scarring, pain, infection, bleeding, and potential cosmetic distortion. Unique to this patient are the procedural anxiety and hypertension.
To populate the risk assessment matrix (eFigure 3), the provider would first map the baseline risks of Mohs surgery, which include considerable scarring as a moderate clinical concern but a seldom probability. Because the patient’s procedural anxiety directly increases the probability of intraoperative distress or elevated blood pressure during the procedure, the provider might assess patient distress/anxiety as a moderate clinical concern with a likely probability. While the patient’s blood pressure is controlled, the white coat syndrome raises the probability of hypertensive urgency/emergency during surgery; this might be elevated from unlikely to occasional or likely probability, and severity might increase from minimal to moderate due to its potential impact on procedural safety. The provider should consider strategies to address these elevated risks during the consultation. Then, as part of preprocedure planning, the provider should consider discussing anxiolytics, emphasizing medication compliance, and ensuring a calm environment for the patient’s surgery.
For this patient, the risk assessment matrix becomes a powerful tool to address fears and proactively manage her unique risk factors. To start the counseling process, the provider should explain the procedure, its benefits, and potential adverse effects. Then, the patient’s individualized risks can be visualized using the matrix, which also is an opportunity for reassurance, as it can alleviate patient fears by contextualizing rare but impactful outcomes.9
Now the provider can assess the patient’s risk tolerance. This discussion ensures that the patient’s comfort level and preferences are central to the treatment decision, even for a gold-standard procedure such as Mohs surgery. By listening and responding to the patient’s input, the provider can build trust and discuss strategies that can help control for some risk factors.
Finally, the provider would re-evaluate throughout the procedure by continuously monitoring the patient’s anxiety and vital signs. The provider should also be ready to adjust pain management or employ anxiety-reduction techniques.
Final Thoughts
Reviewing the risk assessment matrix can be an effective way to nonjudgmentally discuss a patient’s unique risk factors and provide a complete understanding of the planned treatment or procedure. It conveys to the patient that, as the provider, you are taking their health seriously when considering treatment options and can be a means to build patient rapport and trust. This approach mirrors risk communication strategies long employed in military operational planning, where transparency and structured risk evaluation are essential to maintaining mission readiness and unit cohesion.
- The OR Society. The history of OR. The OR Society. Published 2023.
- Naval Postgraduate School. ORM: operational risk management. Accessed September 12, 2025. https://nps.edu/web/safety/orm
- Smith C, Srivastava D, Nijhawan RI. Optimizing patient safety in dermatologic surgery. Dermatol Clin. 2019;37:319-328.
- Minkis K, Whittington A, Alam M. Dermatologic surgery emergencies: complications caused by systemic reactions, high-energy systems, and trauma. J Am Acad Dermatol. 2016;75:265-284.
- Pomerantz RG, Lee DA, Siegel DM. Risk assessment in surgical patients: balancing iatrogenic risks and benefits. Clin Dermatol. 2011;29:669-677.
- Bilimoria KY, Liu Y, Paruch JL, et al. Development and evaluation of the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and surgeons. J Am Coll Surgeons. 2013;217:833-842.
- Lloyd AJ. The extent of patients’ understanding of the risk of treatments. BMJ Qual Saf. 2001;10:i14-i18.
- Falagas ME, Korbila IP, Giannopoulou KP, et al. Informed consent: how much and what do patients understand? Am J Surg. 2009;198:420-435.
- Cohen SM, Baimas-George M, Ponce C, et al. Is a picture worth a thousand words? a scoping review of the impact of visual aids on patients undergoing surgery. J Surg Educ. 2024;81:1276-1292.
- The OR Society. The history of OR. The OR Society. Published 2023.
- Naval Postgraduate School. ORM: operational risk management. Accessed September 12, 2025. https://nps.edu/web/safety/orm
- Smith C, Srivastava D, Nijhawan RI. Optimizing patient safety in dermatologic surgery. Dermatol Clin. 2019;37:319-328.
- Minkis K, Whittington A, Alam M. Dermatologic surgery emergencies: complications caused by systemic reactions, high-energy systems, and trauma. J Am Acad Dermatol. 2016;75:265-284.
- Pomerantz RG, Lee DA, Siegel DM. Risk assessment in surgical patients: balancing iatrogenic risks and benefits. Clin Dermatol. 2011;29:669-677.
- Bilimoria KY, Liu Y, Paruch JL, et al. Development and evaluation of the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and surgeons. J Am Coll Surgeons. 2013;217:833-842.
- Lloyd AJ. The extent of patients’ understanding of the risk of treatments. BMJ Qual Saf. 2001;10:i14-i18.
- Falagas ME, Korbila IP, Giannopoulou KP, et al. Informed consent: how much and what do patients understand? Am J Surg. 2009;198:420-435.
- Cohen SM, Baimas-George M, Ponce C, et al. Is a picture worth a thousand words? a scoping review of the impact of visual aids on patients undergoing surgery. J Surg Educ. 2024;81:1276-1292.
Operational Risk Management in Dermatologic Procedures
Operational Risk Management in Dermatologic Procedures