Dermatopathology

Case Report

A 60-year-old man with a history of Hodgkin lymphoma that had been treated with chemotherapy 6 years prior presented to our dermatology clinic with a persistent pruritic rash on the back, abdomen, and bilateral arms and legs. The eruption initially began as localized discrete lesions on the lower back 1 year prior to the current presentation; at that time a diagnosis of psoriasis was made at an outside dermatology clinic, and treatment with mometasone furoate cream was initiated. Despite the patient’s compliance with this treatment, the lesions did not resolve and began spreading to the arms, legs, chest, and abdomen. His current medications included lisinopril, escitalopram, aspirin, and omeprazole.

On presentation to our clinic, physical examination revealed round, scaly, pink plaques and tumors of variable sizes (3–10 cm) distributed asymmetrically on the chest, back, abdomen, arms, and legs (Figure 1). The lesions were grouped in well-defined areas encompassing approximately 30% of the body surface area. No lymphadenopathy was appreciated. In vivo reflectance confocal microscopy (RCM) performed on one of the lesions revealed disarray of the epidermis with small, weakly refractile, round to oval cells scattered within the spinous layer and dermoepidermal junction (Figure 2). Additionally, these weakly refractile, round to oval cells also were seen in vesiclelike dark spaces, and hyporefractile basal cells were appreciated surrounding the dermal papillae. Mycosis fungoides (MF) was diagnosed following correlation of the RCM findings with the clinical picture.

A biopsy was performed, with pathologic examination confirming the diagnosis of tumor-stage MF. Parakeratosis with epidermotropism of lymphocytes was noted along the basal layer and into the spinous layer of the epidermis (Figure 3). Underlying the epidermis there was a dense mononuclear infiltrate and conspicuous eosinophils extending to the deeper reticular dermis. The infiltrating cells had cerebriform nuclei and large pale cytoplasm. On immunostaining, the lymphocytes were positive for CD3 and CD4, and negative for CD5, CD7, and CD8. The patient was referred to the oncology department for disease management. Staging workup including computed tomography, flow cytometry, and T-cell receptor gene rearrangement were consistent with tumor-stage MF (T3N0M0B0).

 

Comment

Clinical Presentation of MF
Mycosis fungoides, a non-Hodgkin lymphoma of T-cell origin, is the most commonly diagnosed cutaneous lymphoma worldwide.¹ It has an annual incidence of approximately 0.36 per 100,000 persons, and this number continues to rise.^2,3 The median age of diagnosis is 55 to 60 years, and MF occurs twice as often in men versus women.⁴

The clinical presentation of MF varies and is classified by stages including patches, plaques, tumors, and erythroderma.⁵ Classically, MF is slowly progressive and begins as pruritic erythematous patches that have a predilection for non–sun-exposed areas of the skin. Over time, these patches may evolve into plaques and tumors. Early or patch-stage MF often presents as well-demarcated lesions of various sizes and shapes that tend to enlarge.⁶ These lesions may resemble eczema or psoriasis if there is scaling, such as in our patient. At the tumor stage, flat or dome-shaped nodules that may vary in color and are deeper than plaques begin to appear. Ulcerations, which were absent in our case, may often be seen.

Because of the diverse clinical manifestations of MF, which can mimic other common dermatoses, diagnosis often is challenging for clinicians. Furthermore, histology can yield nonspecific diagnostic results and may even resemble chronic inflammatory dermatoses.⁷ As a result, patients frequently are subjected to multiple skin biopsies to establish the diagnosis,⁸ and diagnosis may be delayed, with the median time from onset of skin symptoms to diagnosis being approximately 6 years.⁹

Reflectance Confocal Microscopy
In vivo RCM is a noninvasive technique that allows visualization of the skin at a cellular level and recently has been evaluated as a diagnostic tool for many skin conditions.^10,11 Reflectance confocal microscopy findings have been well established for many cutaneous malignancies as well as inflammatory conditions such as psoriasis and atopic dermatitis.^12,13 Specifically, 2 preliminary descriptive studies utilized RCM to visualize the characteristic features of MF in vivo.^14,15 These studies reported the histopathologic correlation of RCM findings in biopsy-proven MF lesions. Consistent in all stages of MF is the presence of small, weakly refractile, round to oval cells within the spinous layer that correlate with atypical lymphocytes, in addition to hyporefractile basal cells surrounding the dermal papillae. Patch-stage MF lesions have more subtle epidermal findings compared to plaque-stage lesions, which tend to have more prominent vesiclelike dark spaces filled with collections of monomorphous, weakly refractile, round to oval cells corresponding with Pautrier microabscesses and evidence of spongiosis.^14,15 The first descriptive study of RCM in the diagnosis of MF failed to identify features of tumor-stage MF that would distinguish it from patch- or plaque-stage disease. The investigators also stated that deep nodular collections of atypical lymphocytes seen on histopathology in tumor-stage MF were missed on RCM evaluation.¹⁴ Furthermore, the second descriptive study of RCM and MF, which included 2 patients with tumor-stage disease, also failed to differentiate tumor-stage MF from the patch or plaque stages.¹⁵

Because of these 2 descriptive studies, a pilot study was conducted to determine the applicability and reproducibility of RCM findings for MF diagnosis.¹⁶ Two blinded confocalists were asked to diagnose RCM images as MF when compared to either normal skin or a variety of lymphoproliferative disorders. Of 15 patients, the confocalists correctly diagnosed MF in 84% and 90% of cases, respectively. Additionally, they reported the specificity and sensitivity of the following RCM features in the diagnosis of MF: spongiosis, 88.9% and 94.7%; loss of demarcation, 88.9% and 94.7%; disarray of the epidermis, 77.8% and 89.5%; hyporefractile rings, 88.9% and 78.9%; junctional atypical lymphocytes, 100% and 73.7%; and vesiclelike structures (Pautrier microabscesses), 100% and 73.7%. Importantly, this study did not evaluate the specificity and sensitivity of MF diagnosis compared to other eczematous or inflammatory conditions that may share similar RCM findings; therefore, these results are not generalizable, and many of the RCM findings characteristically seen in MF are not specific to its diagnosis.¹⁶

One study assessed the diagnostic accuracy of RCM in evaluating erythematosquamous diseases including MF, psoriasis, contact dermatitis, discoid lupus, and subacute cutaneous lupus.¹⁷ In this study, 3 blinded confocalists achieved a 95.41% and 92.89% specificity and 89.13% and 63.33% sensitivity for psoriasis and MF, respectively. Typical features of psoriasis on RCM included parakeratosis, reduction or absence of the granular layer, papillomatosis, acanthosis with normal honeycomb pattern of the epidermis, and dilated vessels in the upper dermis. Features that were more specific to MF included epidermotropic atypical lymphocytes, interface dermatitis, pleomorphic tumor cells, and dendritic cells.¹⁷ However, atypical lymphocytes and interface dermatitis also may be seen in cutaneous lupus; therefore, additional studies are still needed to validate RCM’s utility in differentiating between erythematosquamous skin diseases, including psoriasis, cutaneous lupus, and MF. Currently, RCM findings must be interpreted in conjunction with the clinical and histologic picture.

Importantly, RCM also is limited when evaluating MF due to its limited depth of visualization, as it allows imaging only to the superficial papillary dermis. Furthermore, any infiltrative process such as epidermal hyperplasia, spongiosis, or scaling, which can be seen in MF, may further impair the imaging quality of the deeper dermis.

Conclusion

Despite its limitations, RCM has the potential to be advantageous in evaluating skin lesions suspicious for MF in real time and is a promising technology for a quick noninvasive bedside adjunct tool. Its utility in selecting the optimal site for biopsy for better yield of histopathologic results in suspected MF cases has been demonstrated.¹⁶ However, large-scale studies still are needed to evaluate RCM in the diagnosis of the wide diversity of MF lesions as well as its efficacy in selecting optimal biopsy sites.

Case Report

A 60-year-old man with a history of Hodgkin lymphoma that had been treated with chemotherapy 6 years prior presented to our dermatology clinic with a persistent pruritic rash on the back, abdomen, and bilateral arms and legs. The eruption initially began as localized discrete lesions on the lower back 1 year prior to the current presentation; at that time a diagnosis of psoriasis was made at an outside dermatology clinic, and treatment with mometasone furoate cream was initiated. Despite the patient’s compliance with this treatment, the lesions did not resolve and began spreading to the arms, legs, chest, and abdomen. His current medications included lisinopril, escitalopram, aspirin, and omeprazole.

On presentation to our clinic, physical examination revealed round, scaly, pink plaques and tumors of variable sizes (3–10 cm) distributed asymmetrically on the chest, back, abdomen, arms, and legs (Figure 1). The lesions were grouped in well-defined areas encompassing approximately 30% of the body surface area. No lymphadenopathy was appreciated. In vivo reflectance confocal microscopy (RCM) performed on one of the lesions revealed disarray of the epidermis with small, weakly refractile, round to oval cells scattered within the spinous layer and dermoepidermal junction (Figure 2). Additionally, these weakly refractile, round to oval cells also were seen in vesiclelike dark spaces, and hyporefractile basal cells were appreciated surrounding the dermal papillae. Mycosis fungoides (MF) was diagnosed following correlation of the RCM findings with the clinical picture.

A biopsy was performed, with pathologic examination confirming the diagnosis of tumor-stage MF. Parakeratosis with epidermotropism of lymphocytes was noted along the basal layer and into the spinous layer of the epidermis (Figure 3). Underlying the epidermis there was a dense mononuclear infiltrate and conspicuous eosinophils extending to the deeper reticular dermis. The infiltrating cells had cerebriform nuclei and large pale cytoplasm. On immunostaining, the lymphocytes were positive for CD3 and CD4, and negative for CD5, CD7, and CD8. The patient was referred to the oncology department for disease management. Staging workup including computed tomography, flow cytometry, and T-cell receptor gene rearrangement were consistent with tumor-stage MF (T3N0M0B0).

 

Comment

Clinical Presentation of MF
Mycosis fungoides, a non-Hodgkin lymphoma of T-cell origin, is the most commonly diagnosed cutaneous lymphoma worldwide.¹ It has an annual incidence of approximately 0.36 per 100,000 persons, and this number continues to rise.^2,3 The median age of diagnosis is 55 to 60 years, and MF occurs twice as often in men versus women.⁴

The clinical presentation of MF varies and is classified by stages including patches, plaques, tumors, and erythroderma.⁵ Classically, MF is slowly progressive and begins as pruritic erythematous patches that have a predilection for non–sun-exposed areas of the skin. Over time, these patches may evolve into plaques and tumors. Early or patch-stage MF often presents as well-demarcated lesions of various sizes and shapes that tend to enlarge.⁶ These lesions may resemble eczema or psoriasis if there is scaling, such as in our patient. At the tumor stage, flat or dome-shaped nodules that may vary in color and are deeper than plaques begin to appear. Ulcerations, which were absent in our case, may often be seen.

Because of the diverse clinical manifestations of MF, which can mimic other common dermatoses, diagnosis often is challenging for clinicians. Furthermore, histology can yield nonspecific diagnostic results and may even resemble chronic inflammatory dermatoses.⁷ As a result, patients frequently are subjected to multiple skin biopsies to establish the diagnosis,⁸ and diagnosis may be delayed, with the median time from onset of skin symptoms to diagnosis being approximately 6 years.⁹

Reflectance Confocal Microscopy
In vivo RCM is a noninvasive technique that allows visualization of the skin at a cellular level and recently has been evaluated as a diagnostic tool for many skin conditions.^10,11 Reflectance confocal microscopy findings have been well established for many cutaneous malignancies as well as inflammatory conditions such as psoriasis and atopic dermatitis.^12,13 Specifically, 2 preliminary descriptive studies utilized RCM to visualize the characteristic features of MF in vivo.^14,15 These studies reported the histopathologic correlation of RCM findings in biopsy-proven MF lesions. Consistent in all stages of MF is the presence of small, weakly refractile, round to oval cells within the spinous layer that correlate with atypical lymphocytes, in addition to hyporefractile basal cells surrounding the dermal papillae. Patch-stage MF lesions have more subtle epidermal findings compared to plaque-stage lesions, which tend to have more prominent vesiclelike dark spaces filled with collections of monomorphous, weakly refractile, round to oval cells corresponding with Pautrier microabscesses and evidence of spongiosis.^14,15 The first descriptive study of RCM in the diagnosis of MF failed to identify features of tumor-stage MF that would distinguish it from patch- or plaque-stage disease. The investigators also stated that deep nodular collections of atypical lymphocytes seen on histopathology in tumor-stage MF were missed on RCM evaluation.¹⁴ Furthermore, the second descriptive study of RCM and MF, which included 2 patients with tumor-stage disease, also failed to differentiate tumor-stage MF from the patch or plaque stages.¹⁵

Because of these 2 descriptive studies, a pilot study was conducted to determine the applicability and reproducibility of RCM findings for MF diagnosis.¹⁶ Two blinded confocalists were asked to diagnose RCM images as MF when compared to either normal skin or a variety of lymphoproliferative disorders. Of 15 patients, the confocalists correctly diagnosed MF in 84% and 90% of cases, respectively. Additionally, they reported the specificity and sensitivity of the following RCM features in the diagnosis of MF: spongiosis, 88.9% and 94.7%; loss of demarcation, 88.9% and 94.7%; disarray of the epidermis, 77.8% and 89.5%; hyporefractile rings, 88.9% and 78.9%; junctional atypical lymphocytes, 100% and 73.7%; and vesiclelike structures (Pautrier microabscesses), 100% and 73.7%. Importantly, this study did not evaluate the specificity and sensitivity of MF diagnosis compared to other eczematous or inflammatory conditions that may share similar RCM findings; therefore, these results are not generalizable, and many of the RCM findings characteristically seen in MF are not specific to its diagnosis.¹⁶

One study assessed the diagnostic accuracy of RCM in evaluating erythematosquamous diseases including MF, psoriasis, contact dermatitis, discoid lupus, and subacute cutaneous lupus.¹⁷ In this study, 3 blinded confocalists achieved a 95.41% and 92.89% specificity and 89.13% and 63.33% sensitivity for psoriasis and MF, respectively. Typical features of psoriasis on RCM included parakeratosis, reduction or absence of the granular layer, papillomatosis, acanthosis with normal honeycomb pattern of the epidermis, and dilated vessels in the upper dermis. Features that were more specific to MF included epidermotropic atypical lymphocytes, interface dermatitis, pleomorphic tumor cells, and dendritic cells.¹⁷ However, atypical lymphocytes and interface dermatitis also may be seen in cutaneous lupus; therefore, additional studies are still needed to validate RCM’s utility in differentiating between erythematosquamous skin diseases, including psoriasis, cutaneous lupus, and MF. Currently, RCM findings must be interpreted in conjunction with the clinical and histologic picture.

Importantly, RCM also is limited when evaluating MF due to its limited depth of visualization, as it allows imaging only to the superficial papillary dermis. Furthermore, any infiltrative process such as epidermal hyperplasia, spongiosis, or scaling, which can be seen in MF, may further impair the imaging quality of the deeper dermis.

Conclusion

Despite its limitations, RCM has the potential to be advantageous in evaluating skin lesions suspicious for MF in real time and is a promising technology for a quick noninvasive bedside adjunct tool. Its utility in selecting the optimal site for biopsy for better yield of histopathologic results in suspected MF cases has been demonstrated.¹⁶ However, large-scale studies still are needed to evaluate RCM in the diagnosis of the wide diversity of MF lesions as well as its efficacy in selecting optimal biopsy sites.

Case Report

A 60-year-old man with a history of Hodgkin lymphoma that had been treated with chemotherapy 6 years prior presented to our dermatology clinic with a persistent pruritic rash on the back, abdomen, and bilateral arms and legs. The eruption initially began as localized discrete lesions on the lower back 1 year prior to the current presentation; at that time a diagnosis of psoriasis was made at an outside dermatology clinic, and treatment with mometasone furoate cream was initiated. Despite the patient’s compliance with this treatment, the lesions did not resolve and began spreading to the arms, legs, chest, and abdomen. His current medications included lisinopril, escitalopram, aspirin, and omeprazole.

On presentation to our clinic, physical examination revealed round, scaly, pink plaques and tumors of variable sizes (3–10 cm) distributed asymmetrically on the chest, back, abdomen, arms, and legs (Figure 1). The lesions were grouped in well-defined areas encompassing approximately 30% of the body surface area. No lymphadenopathy was appreciated. In vivo reflectance confocal microscopy (RCM) performed on one of the lesions revealed disarray of the epidermis with small, weakly refractile, round to oval cells scattered within the spinous layer and dermoepidermal junction (Figure 2). Additionally, these weakly refractile, round to oval cells also were seen in vesiclelike dark spaces, and hyporefractile basal cells were appreciated surrounding the dermal papillae. Mycosis fungoides (MF) was diagnosed following correlation of the RCM findings with the clinical picture.

A biopsy was performed, with pathologic examination confirming the diagnosis of tumor-stage MF. Parakeratosis with epidermotropism of lymphocytes was noted along the basal layer and into the spinous layer of the epidermis (Figure 3). Underlying the epidermis there was a dense mononuclear infiltrate and conspicuous eosinophils extending to the deeper reticular dermis. The infiltrating cells had cerebriform nuclei and large pale cytoplasm. On immunostaining, the lymphocytes were positive for CD3 and CD4, and negative for CD5, CD7, and CD8. The patient was referred to the oncology department for disease management. Staging workup including computed tomography, flow cytometry, and T-cell receptor gene rearrangement were consistent with tumor-stage MF (T3N0M0B0).

 

Comment

Clinical Presentation of MF
Mycosis fungoides, a non-Hodgkin lymphoma of T-cell origin, is the most commonly diagnosed cutaneous lymphoma worldwide.¹ It has an annual incidence of approximately 0.36 per 100,000 persons, and this number continues to rise.^2,3 The median age of diagnosis is 55 to 60 years, and MF occurs twice as often in men versus women.⁴

The clinical presentation of MF varies and is classified by stages including patches, plaques, tumors, and erythroderma.⁵ Classically, MF is slowly progressive and begins as pruritic erythematous patches that have a predilection for non–sun-exposed areas of the skin. Over time, these patches may evolve into plaques and tumors. Early or patch-stage MF often presents as well-demarcated lesions of various sizes and shapes that tend to enlarge.⁶ These lesions may resemble eczema or psoriasis if there is scaling, such as in our patient. At the tumor stage, flat or dome-shaped nodules that may vary in color and are deeper than plaques begin to appear. Ulcerations, which were absent in our case, may often be seen.

Because of the diverse clinical manifestations of MF, which can mimic other common dermatoses, diagnosis often is challenging for clinicians. Furthermore, histology can yield nonspecific diagnostic results and may even resemble chronic inflammatory dermatoses.⁷ As a result, patients frequently are subjected to multiple skin biopsies to establish the diagnosis,⁸ and diagnosis may be delayed, with the median time from onset of skin symptoms to diagnosis being approximately 6 years.⁹

Reflectance Confocal Microscopy
In vivo RCM is a noninvasive technique that allows visualization of the skin at a cellular level and recently has been evaluated as a diagnostic tool for many skin conditions.^10,11 Reflectance confocal microscopy findings have been well established for many cutaneous malignancies as well as inflammatory conditions such as psoriasis and atopic dermatitis.^12,13 Specifically, 2 preliminary descriptive studies utilized RCM to visualize the characteristic features of MF in vivo.^14,15 These studies reported the histopathologic correlation of RCM findings in biopsy-proven MF lesions. Consistent in all stages of MF is the presence of small, weakly refractile, round to oval cells within the spinous layer that correlate with atypical lymphocytes, in addition to hyporefractile basal cells surrounding the dermal papillae. Patch-stage MF lesions have more subtle epidermal findings compared to plaque-stage lesions, which tend to have more prominent vesiclelike dark spaces filled with collections of monomorphous, weakly refractile, round to oval cells corresponding with Pautrier microabscesses and evidence of spongiosis.^14,15 The first descriptive study of RCM in the diagnosis of MF failed to identify features of tumor-stage MF that would distinguish it from patch- or plaque-stage disease. The investigators also stated that deep nodular collections of atypical lymphocytes seen on histopathology in tumor-stage MF were missed on RCM evaluation.¹⁴ Furthermore, the second descriptive study of RCM and MF, which included 2 patients with tumor-stage disease, also failed to differentiate tumor-stage MF from the patch or plaque stages.¹⁵

Because of these 2 descriptive studies, a pilot study was conducted to determine the applicability and reproducibility of RCM findings for MF diagnosis.¹⁶ Two blinded confocalists were asked to diagnose RCM images as MF when compared to either normal skin or a variety of lymphoproliferative disorders. Of 15 patients, the confocalists correctly diagnosed MF in 84% and 90% of cases, respectively. Additionally, they reported the specificity and sensitivity of the following RCM features in the diagnosis of MF: spongiosis, 88.9% and 94.7%; loss of demarcation, 88.9% and 94.7%; disarray of the epidermis, 77.8% and 89.5%; hyporefractile rings, 88.9% and 78.9%; junctional atypical lymphocytes, 100% and 73.7%; and vesiclelike structures (Pautrier microabscesses), 100% and 73.7%. Importantly, this study did not evaluate the specificity and sensitivity of MF diagnosis compared to other eczematous or inflammatory conditions that may share similar RCM findings; therefore, these results are not generalizable, and many of the RCM findings characteristically seen in MF are not specific to its diagnosis.¹⁶

One study assessed the diagnostic accuracy of RCM in evaluating erythematosquamous diseases including MF, psoriasis, contact dermatitis, discoid lupus, and subacute cutaneous lupus.¹⁷ In this study, 3 blinded confocalists achieved a 95.41% and 92.89% specificity and 89.13% and 63.33% sensitivity for psoriasis and MF, respectively. Typical features of psoriasis on RCM included parakeratosis, reduction or absence of the granular layer, papillomatosis, acanthosis with normal honeycomb pattern of the epidermis, and dilated vessels in the upper dermis. Features that were more specific to MF included epidermotropic atypical lymphocytes, interface dermatitis, pleomorphic tumor cells, and dendritic cells.¹⁷ However, atypical lymphocytes and interface dermatitis also may be seen in cutaneous lupus; therefore, additional studies are still needed to validate RCM’s utility in differentiating between erythematosquamous skin diseases, including psoriasis, cutaneous lupus, and MF. Currently, RCM findings must be interpreted in conjunction with the clinical and histologic picture.

Importantly, RCM also is limited when evaluating MF due to its limited depth of visualization, as it allows imaging only to the superficial papillary dermis. Furthermore, any infiltrative process such as epidermal hyperplasia, spongiosis, or scaling, which can be seen in MF, may further impair the imaging quality of the deeper dermis.

Conclusion

Despite its limitations, RCM has the potential to be advantageous in evaluating skin lesions suspicious for MF in real time and is a promising technology for a quick noninvasive bedside adjunct tool. Its utility in selecting the optimal site for biopsy for better yield of histopathologic results in suspected MF cases has been demonstrated.¹⁶ However, large-scale studies still are needed to evaluate RCM in the diagnosis of the wide diversity of MF lesions as well as its efficacy in selecting optimal biopsy sites.

The Diagnosis: Nodular Fasciitis

The diagnosis of spindle cell tumors can be challenging; however, by using a variety of immunoperoxidase stains and fluorescent in situ hybridization (FISH) testing in conjunction with histology, it often is possible to arrive at a definitive diagnosis. For this case, the histologic features in conjunction with the immunoperoxidase stains and FISH were consistent with a diagnosis of nodular fasciitis.

Nodular fasciitis is a benign, self-limiting, myofibroblastic, soft-tissue proliferation typically found in the subcutaneous tissue.¹ It can be found anywhere on the body but most commonly on the upper arms and trunk. It most often is seen in young adults, and many cases have been reported in association with a history of trauma to the area.^1,2 It typically measures less than 2 cm in diameter.³ The diagnosis of nodular fasciitis is particularly challenging because it mimics sarcoma, both in presentation and in histologic findings with rapid growth, high mitotic activity, and increased cellularity.^1,4-7 In contrast to malignancy, nodular fasciitis has no atypical mitoses and little cytologic atypia.^8,9 Rather, it contains plump myofibroblasts loosely arranged in a myxoid or fibrous stroma that also may contain lymphocytes, extravasated erythrocytes, and osteoclastlike giant cells distributed throughout.^5,10,11 In this case, lymphocytes, extravasated red blood cells, and myxoid change are present, suggesting the diagnosis of nodular fasciitis. In other cases, however, these features may be much more limited, making the diagnosis more challenging. The spindle cells are arranged in poorly defined short fascicles. The tumor cells do not infiltrate between individual adipocytes. There is no notable cytologic atypia.

Because of the difficulty in making the diagnosis, overtreatment of this benign condition can be a problem, causing increased morbidity.¹ Erickson-Johnson et al¹² identified the role of an ubiquitin-specific peptidase 6, USP6, gene rearrangement on chromosome 17p13 in 92% (44/48) of cases of nodular fasciitis. The USP6 gene most often is rearranged with the myosin heavy chain 9 gene, MYH9, on chromosome 22q12.3. With this rearrangement, the MYH9 promoter leads to the overexpression of USP6, causing tumor formation.^2,13 The use of multiple immunoperoxidase stains can be important in the identification of nodular fasciitis. Nodular fasciitis stains negative for S-100, epithelial membrane antigen, CD34, β-catenin, and cytokeratin, but typically stains positive for smooth muscle actin.⁹

Although dermatofibrosarcoma protuberans (DFSP) was in the differential diagnosis, these tumors tend to have greater cellularity than nodular fasciitis. In addition, the spindle cells of DFSP typically are arranged in a storiform pattern. Another characteristic feature of DFSP is that the tumor cells will infiltrate between adipose cells creating a lacelike or honeycomblike appearance within the subcutaneous tissue (Figure 1). Immunohistochemistry staining and FISH testing may be useful in making a diagnosis of DFSP. These tumors typically are positive for CD34 by immunoperoxidase staining and demonstrate a translocation t(17;22)(q21;q13) between platelet-derived growth factor subunit B gene, PDGFB, and collagen type I alpha 1 chain gene, COL1A1, by FISH.

The distinction between the fibrous phase of nodular fasciitis and fibromatosis can be challenging. The size of the lesion may be helpful, with most lesions of nodular fasciitis being less than 3 cm, while lesions of fibromatosis have a mean diameter of 7 cm.^5,14 Microscopically, both tumors demonstrate a fascicular growth pattern; however, the fascicles in nodular fasciitis tend to be short and irregular compared to the longer fascicles seen in fibromatosis (Figure 2). Immunohistochemistry staining has limited utility with only 56% (14/25) of superficial fibromatoses having positive nuclear staining for β-catenin.¹⁵

Low-grade fibromyxoid sarcoma (LGFMS) would be unusual in this clinical scenario. Only 13% to 19% of cases present in patients younger than 18 years (mean age, 33 years).¹⁶ In LGFMS there are cytologically bland spindle cells that are typically arranged in a patternless or whorled pattern (Figure 3), though fascicular architecture may be seen. There are alternating areas of fibrous and myxoid stroma. A curvilinear vasculature network and lack of lymphocytes and extravasated red blood cells are histologic features favoring LGFMS over nodular fasciitis. Immunohistochemistry staining and FISH testing can be useful in making the diagnosis of LGFMS. These tumors are characterized by a translocation t(7;16)(q34;p11) involving the fusion in sarcoma, FUS, and cAMP responsive element binding protein 3 like 2, CREB3L2, genes.¹⁶ Positive immunohistochemistry staining for MUC4 can be seen in up to 100% of LGFMS and is absent in many other spindle cell tumors.¹⁶

Plexiform fibrohistiocytic tumor (PFT) is least likely to be confused with nodular fasciitis. Histologically these tumors are characterized by multiple small nodules arranged in a plexiform pattern (Figure 4). Within the nodules, 3 cell types may be noted: spindle fibroblast-like cells, mononuclear histiocyte-like cells, and osteoclastlike cells.¹⁷ Either the spindle cells or the mononuclear cells may predominate in cases of PFT. Immunohistochemistry staining of PFT is nonspecific and there are no molecular/FISH studies that can be used to help confirm the diagnosis.

The Diagnosis: Nodular Fasciitis

The diagnosis of spindle cell tumors can be challenging; however, by using a variety of immunoperoxidase stains and fluorescent in situ hybridization (FISH) testing in conjunction with histology, it often is possible to arrive at a definitive diagnosis. For this case, the histologic features in conjunction with the immunoperoxidase stains and FISH were consistent with a diagnosis of nodular fasciitis.

Nodular fasciitis is a benign, self-limiting, myofibroblastic, soft-tissue proliferation typically found in the subcutaneous tissue.¹ It can be found anywhere on the body but most commonly on the upper arms and trunk. It most often is seen in young adults, and many cases have been reported in association with a history of trauma to the area.^1,2 It typically measures less than 2 cm in diameter.³ The diagnosis of nodular fasciitis is particularly challenging because it mimics sarcoma, both in presentation and in histologic findings with rapid growth, high mitotic activity, and increased cellularity.^1,4-7 In contrast to malignancy, nodular fasciitis has no atypical mitoses and little cytologic atypia.^8,9 Rather, it contains plump myofibroblasts loosely arranged in a myxoid or fibrous stroma that also may contain lymphocytes, extravasated erythrocytes, and osteoclastlike giant cells distributed throughout.^5,10,11 In this case, lymphocytes, extravasated red blood cells, and myxoid change are present, suggesting the diagnosis of nodular fasciitis. In other cases, however, these features may be much more limited, making the diagnosis more challenging. The spindle cells are arranged in poorly defined short fascicles. The tumor cells do not infiltrate between individual adipocytes. There is no notable cytologic atypia.

Because of the difficulty in making the diagnosis, overtreatment of this benign condition can be a problem, causing increased morbidity.¹ Erickson-Johnson et al¹² identified the role of an ubiquitin-specific peptidase 6, USP6, gene rearrangement on chromosome 17p13 in 92% (44/48) of cases of nodular fasciitis. The USP6 gene most often is rearranged with the myosin heavy chain 9 gene, MYH9, on chromosome 22q12.3. With this rearrangement, the MYH9 promoter leads to the overexpression of USP6, causing tumor formation.^2,13 The use of multiple immunoperoxidase stains can be important in the identification of nodular fasciitis. Nodular fasciitis stains negative for S-100, epithelial membrane antigen, CD34, β-catenin, and cytokeratin, but typically stains positive for smooth muscle actin.⁹

Although dermatofibrosarcoma protuberans (DFSP) was in the differential diagnosis, these tumors tend to have greater cellularity than nodular fasciitis. In addition, the spindle cells of DFSP typically are arranged in a storiform pattern. Another characteristic feature of DFSP is that the tumor cells will infiltrate between adipose cells creating a lacelike or honeycomblike appearance within the subcutaneous tissue (Figure 1). Immunohistochemistry staining and FISH testing may be useful in making a diagnosis of DFSP. These tumors typically are positive for CD34 by immunoperoxidase staining and demonstrate a translocation t(17;22)(q21;q13) between platelet-derived growth factor subunit B gene, PDGFB, and collagen type I alpha 1 chain gene, COL1A1, by FISH.

The distinction between the fibrous phase of nodular fasciitis and fibromatosis can be challenging. The size of the lesion may be helpful, with most lesions of nodular fasciitis being less than 3 cm, while lesions of fibromatosis have a mean diameter of 7 cm.^5,14 Microscopically, both tumors demonstrate a fascicular growth pattern; however, the fascicles in nodular fasciitis tend to be short and irregular compared to the longer fascicles seen in fibromatosis (Figure 2). Immunohistochemistry staining has limited utility with only 56% (14/25) of superficial fibromatoses having positive nuclear staining for β-catenin.¹⁵

Low-grade fibromyxoid sarcoma (LGFMS) would be unusual in this clinical scenario. Only 13% to 19% of cases present in patients younger than 18 years (mean age, 33 years).¹⁶ In LGFMS there are cytologically bland spindle cells that are typically arranged in a patternless or whorled pattern (Figure 3), though fascicular architecture may be seen. There are alternating areas of fibrous and myxoid stroma. A curvilinear vasculature network and lack of lymphocytes and extravasated red blood cells are histologic features favoring LGFMS over nodular fasciitis. Immunohistochemistry staining and FISH testing can be useful in making the diagnosis of LGFMS. These tumors are characterized by a translocation t(7;16)(q34;p11) involving the fusion in sarcoma, FUS, and cAMP responsive element binding protein 3 like 2, CREB3L2, genes.¹⁶ Positive immunohistochemistry staining for MUC4 can be seen in up to 100% of LGFMS and is absent in many other spindle cell tumors.¹⁶

Plexiform fibrohistiocytic tumor (PFT) is least likely to be confused with nodular fasciitis. Histologically these tumors are characterized by multiple small nodules arranged in a plexiform pattern (Figure 4). Within the nodules, 3 cell types may be noted: spindle fibroblast-like cells, mononuclear histiocyte-like cells, and osteoclastlike cells.¹⁷ Either the spindle cells or the mononuclear cells may predominate in cases of PFT. Immunohistochemistry staining of PFT is nonspecific and there are no molecular/FISH studies that can be used to help confirm the diagnosis.

The Diagnosis: Nodular Fasciitis

The diagnosis of spindle cell tumors can be challenging; however, by using a variety of immunoperoxidase stains and fluorescent in situ hybridization (FISH) testing in conjunction with histology, it often is possible to arrive at a definitive diagnosis. For this case, the histologic features in conjunction with the immunoperoxidase stains and FISH were consistent with a diagnosis of nodular fasciitis.

Nodular fasciitis is a benign, self-limiting, myofibroblastic, soft-tissue proliferation typically found in the subcutaneous tissue.¹ It can be found anywhere on the body but most commonly on the upper arms and trunk. It most often is seen in young adults, and many cases have been reported in association with a history of trauma to the area.^1,2 It typically measures less than 2 cm in diameter.³ The diagnosis of nodular fasciitis is particularly challenging because it mimics sarcoma, both in presentation and in histologic findings with rapid growth, high mitotic activity, and increased cellularity.^1,4-7 In contrast to malignancy, nodular fasciitis has no atypical mitoses and little cytologic atypia.^8,9 Rather, it contains plump myofibroblasts loosely arranged in a myxoid or fibrous stroma that also may contain lymphocytes, extravasated erythrocytes, and osteoclastlike giant cells distributed throughout.^5,10,11 In this case, lymphocytes, extravasated red blood cells, and myxoid change are present, suggesting the diagnosis of nodular fasciitis. In other cases, however, these features may be much more limited, making the diagnosis more challenging. The spindle cells are arranged in poorly defined short fascicles. The tumor cells do not infiltrate between individual adipocytes. There is no notable cytologic atypia.

Because of the difficulty in making the diagnosis, overtreatment of this benign condition can be a problem, causing increased morbidity.¹ Erickson-Johnson et al¹² identified the role of an ubiquitin-specific peptidase 6, USP6, gene rearrangement on chromosome 17p13 in 92% (44/48) of cases of nodular fasciitis. The USP6 gene most often is rearranged with the myosin heavy chain 9 gene, MYH9, on chromosome 22q12.3. With this rearrangement, the MYH9 promoter leads to the overexpression of USP6, causing tumor formation.^2,13 The use of multiple immunoperoxidase stains can be important in the identification of nodular fasciitis. Nodular fasciitis stains negative for S-100, epithelial membrane antigen, CD34, β-catenin, and cytokeratin, but typically stains positive for smooth muscle actin.⁹

Although dermatofibrosarcoma protuberans (DFSP) was in the differential diagnosis, these tumors tend to have greater cellularity than nodular fasciitis. In addition, the spindle cells of DFSP typically are arranged in a storiform pattern. Another characteristic feature of DFSP is that the tumor cells will infiltrate between adipose cells creating a lacelike or honeycomblike appearance within the subcutaneous tissue (Figure 1). Immunohistochemistry staining and FISH testing may be useful in making a diagnosis of DFSP. These tumors typically are positive for CD34 by immunoperoxidase staining and demonstrate a translocation t(17;22)(q21;q13) between platelet-derived growth factor subunit B gene, PDGFB, and collagen type I alpha 1 chain gene, COL1A1, by FISH.

The distinction between the fibrous phase of nodular fasciitis and fibromatosis can be challenging. The size of the lesion may be helpful, with most lesions of nodular fasciitis being less than 3 cm, while lesions of fibromatosis have a mean diameter of 7 cm.^5,14 Microscopically, both tumors demonstrate a fascicular growth pattern; however, the fascicles in nodular fasciitis tend to be short and irregular compared to the longer fascicles seen in fibromatosis (Figure 2). Immunohistochemistry staining has limited utility with only 56% (14/25) of superficial fibromatoses having positive nuclear staining for β-catenin.¹⁵

Low-grade fibromyxoid sarcoma (LGFMS) would be unusual in this clinical scenario. Only 13% to 19% of cases present in patients younger than 18 years (mean age, 33 years).¹⁶ In LGFMS there are cytologically bland spindle cells that are typically arranged in a patternless or whorled pattern (Figure 3), though fascicular architecture may be seen. There are alternating areas of fibrous and myxoid stroma. A curvilinear vasculature network and lack of lymphocytes and extravasated red blood cells are histologic features favoring LGFMS over nodular fasciitis. Immunohistochemistry staining and FISH testing can be useful in making the diagnosis of LGFMS. These tumors are characterized by a translocation t(7;16)(q34;p11) involving the fusion in sarcoma, FUS, and cAMP responsive element binding protein 3 like 2, CREB3L2, genes.¹⁶ Positive immunohistochemistry staining for MUC4 can be seen in up to 100% of LGFMS and is absent in many other spindle cell tumors.¹⁶

Plexiform fibrohistiocytic tumor (PFT) is least likely to be confused with nodular fasciitis. Histologically these tumors are characterized by multiple small nodules arranged in a plexiform pattern (Figure 4). Within the nodules, 3 cell types may be noted: spindle fibroblast-like cells, mononuclear histiocyte-like cells, and osteoclastlike cells.¹⁷ Either the spindle cells or the mononuclear cells may predominate in cases of PFT. Immunohistochemistry staining of PFT is nonspecific and there are no molecular/FISH studies that can be used to help confirm the diagnosis.

To the Editor:

A 46-year-old man presented with multiple tense bullae and denuded patches on the palms (Figure 1A) and soles (Figure 1B). The blisters first appeared 2 months prior to presentation, shortly after he was diagnosed with stage IVB mantle cell lymphoma, and waxed and waned in intensity since then. He denied antecedent trauma or friction and reported that all sites were painful. He had no family or personal history of blistering disorders.

The mantle cell lymphoma initially was treated with 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy more than 2.5 years prior to the current presentation, which resulted in partial remission, followed by R-ICE (rituximab, ifosfamide, carboplatin, etoposide) therapy as well as autologous stem cell transplantation; complete remission was achieved. His recovery was complicated by a necrotic small bowel leading to resection. Eighteen months following the second course of chemotherapy, a mass was noted on the neck; biopsy performed by an outside dermatologist revealed mantle cell lymphoma.

Punch biopsy revealed a subepidermal bulla. Six weeks later, biopsy of a newly developed hand lesion performed at our office revealed a subepidermal cleft with minimal dermal infiltrate (Figure 2). Direct immunofluorescence was negative for immunoglobulin and complement deposition. Porphyrin elevation was not detected with a 24-hour urine assay. New lesions were drained and injected with triamcinolone, which appeared to hasten healing.

Mantle cell lymphoma is a distinct lymphoproliferative disorder of B cells that represents less than 7% of non-Hodgkin lymphoma cases.¹ The tumor cells originate in the mantle zone of the lymph nodes. Most patients present with advanced disease involving lymph nodes and other organs. The disease is characterized by male predominance and an aggressive course with a median overall survival of less than 5 years.¹

Epidermolysis bullosa acquisita is a rare blistering disease that usually develops in adulthood. It is a subepidermal disorder characterized by the appearance of fragile tense bullae. Epidermolysis bullosa acquisita can be divided into 2 subtypes: inflammatory and mechanobullous (classic EBA).² Inflammatory EBA presents similarly to bullous pemphigoid and other subepithelial autoimmune blistering diseases. Vesiculobullous lesions predominate on the trunk and extremities and often are accompanied by intense pruritus. The less common mechanobullous noninflammatory subtype, illustrated in our case, presents in trauma-prone areas with skin fragility and tense noninflamed vesicles and bullae that rupture leaving erosions. Associated findings may include milia and scarring. Lesions appear in areas exposed to friction and trauma such as the hands, feet, elbows, knees, and lower back. The differential diagnosis includes dystrophic epidermolysis bullosa, porphyria cutanea tarda, and pseudoporphyria. Dystrophic epidermolysis bullosa is ruled out by family history and disease onset at birth. The lesions of porphyria cutanea tarda and pseudoporphyria occur on sun-exposed areas; porphyrin levels are elevated in the former. Direct immunofluorescence of a perilesional EBA site usually reveals IgG deposition.³ Negative direct immunofluorescence in our case could have resulted from technical error, sample location, or response to systemic immunosuppressive treatment.⁴

Epidermolysis bullosa acquisita is caused by autoantibodies against type VII collagen.^2,3 After the autoantibodies bind, a complement cascade reaction is activated, leading to deposition of C3a and C5a, which recruit leukocytes and mast cells. The anchoring fibrils in the basement membrane zones of the skin and mucosa are disrupted.^5,6 Injection of anti–type VII collagen antibodies into mice induces a blistering disease resembling EBA.⁷ In a study of 14 patients with EBA, disease severity was correlated to levels of anticollagen autoantibodies measured by enzyme-linked immunosorbent assay.⁸

Epidermolysis bullosa acquisita has been linked to Crohn disease and approximately 30% of EBA cases occur in patients with this disease.^9,10 Two case reports document an association with multiple myeloma.^11,12 Treatment often proves challenging and unsatisfactory; valid controlled clinical trials are impossible given the paucity of cases. Successful therapeutic outcomes have been reported with oral prednisone,¹³ colchicine,¹⁴ cyclosporine,¹⁵ dapsone,¹⁶ and rituximab.¹⁷ Our patient received 2 separate courses of rituximab as part of chemotherapy for mantle cell lymphoma without measurable improvement. He was lost to follow-up after recurrence of the lymphoma and we learned from his wife that he had died.

To the Editor:

A 46-year-old man presented with multiple tense bullae and denuded patches on the palms (Figure 1A) and soles (Figure 1B). The blisters first appeared 2 months prior to presentation, shortly after he was diagnosed with stage IVB mantle cell lymphoma, and waxed and waned in intensity since then. He denied antecedent trauma or friction and reported that all sites were painful. He had no family or personal history of blistering disorders.

The mantle cell lymphoma initially was treated with 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy more than 2.5 years prior to the current presentation, which resulted in partial remission, followed by R-ICE (rituximab, ifosfamide, carboplatin, etoposide) therapy as well as autologous stem cell transplantation; complete remission was achieved. His recovery was complicated by a necrotic small bowel leading to resection. Eighteen months following the second course of chemotherapy, a mass was noted on the neck; biopsy performed by an outside dermatologist revealed mantle cell lymphoma.

Punch biopsy revealed a subepidermal bulla. Six weeks later, biopsy of a newly developed hand lesion performed at our office revealed a subepidermal cleft with minimal dermal infiltrate (Figure 2). Direct immunofluorescence was negative for immunoglobulin and complement deposition. Porphyrin elevation was not detected with a 24-hour urine assay. New lesions were drained and injected with triamcinolone, which appeared to hasten healing.

Mantle cell lymphoma is a distinct lymphoproliferative disorder of B cells that represents less than 7% of non-Hodgkin lymphoma cases.¹ The tumor cells originate in the mantle zone of the lymph nodes. Most patients present with advanced disease involving lymph nodes and other organs. The disease is characterized by male predominance and an aggressive course with a median overall survival of less than 5 years.¹

Epidermolysis bullosa acquisita is a rare blistering disease that usually develops in adulthood. It is a subepidermal disorder characterized by the appearance of fragile tense bullae. Epidermolysis bullosa acquisita can be divided into 2 subtypes: inflammatory and mechanobullous (classic EBA).² Inflammatory EBA presents similarly to bullous pemphigoid and other subepithelial autoimmune blistering diseases. Vesiculobullous lesions predominate on the trunk and extremities and often are accompanied by intense pruritus. The less common mechanobullous noninflammatory subtype, illustrated in our case, presents in trauma-prone areas with skin fragility and tense noninflamed vesicles and bullae that rupture leaving erosions. Associated findings may include milia and scarring. Lesions appear in areas exposed to friction and trauma such as the hands, feet, elbows, knees, and lower back. The differential diagnosis includes dystrophic epidermolysis bullosa, porphyria cutanea tarda, and pseudoporphyria. Dystrophic epidermolysis bullosa is ruled out by family history and disease onset at birth. The lesions of porphyria cutanea tarda and pseudoporphyria occur on sun-exposed areas; porphyrin levels are elevated in the former. Direct immunofluorescence of a perilesional EBA site usually reveals IgG deposition.³ Negative direct immunofluorescence in our case could have resulted from technical error, sample location, or response to systemic immunosuppressive treatment.⁴

Epidermolysis bullosa acquisita is caused by autoantibodies against type VII collagen.^2,3 After the autoantibodies bind, a complement cascade reaction is activated, leading to deposition of C3a and C5a, which recruit leukocytes and mast cells. The anchoring fibrils in the basement membrane zones of the skin and mucosa are disrupted.^5,6 Injection of anti–type VII collagen antibodies into mice induces a blistering disease resembling EBA.⁷ In a study of 14 patients with EBA, disease severity was correlated to levels of anticollagen autoantibodies measured by enzyme-linked immunosorbent assay.⁸

Epidermolysis bullosa acquisita has been linked to Crohn disease and approximately 30% of EBA cases occur in patients with this disease.^9,10 Two case reports document an association with multiple myeloma.^11,12 Treatment often proves challenging and unsatisfactory; valid controlled clinical trials are impossible given the paucity of cases. Successful therapeutic outcomes have been reported with oral prednisone,¹³ colchicine,¹⁴ cyclosporine,¹⁵ dapsone,¹⁶ and rituximab.¹⁷ Our patient received 2 separate courses of rituximab as part of chemotherapy for mantle cell lymphoma without measurable improvement. He was lost to follow-up after recurrence of the lymphoma and we learned from his wife that he had died.

To the Editor:

A 46-year-old man presented with multiple tense bullae and denuded patches on the palms (Figure 1A) and soles (Figure 1B). The blisters first appeared 2 months prior to presentation, shortly after he was diagnosed with stage IVB mantle cell lymphoma, and waxed and waned in intensity since then. He denied antecedent trauma or friction and reported that all sites were painful. He had no family or personal history of blistering disorders.

The mantle cell lymphoma initially was treated with 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy more than 2.5 years prior to the current presentation, which resulted in partial remission, followed by R-ICE (rituximab, ifosfamide, carboplatin, etoposide) therapy as well as autologous stem cell transplantation; complete remission was achieved. His recovery was complicated by a necrotic small bowel leading to resection. Eighteen months following the second course of chemotherapy, a mass was noted on the neck; biopsy performed by an outside dermatologist revealed mantle cell lymphoma.

Punch biopsy revealed a subepidermal bulla. Six weeks later, biopsy of a newly developed hand lesion performed at our office revealed a subepidermal cleft with minimal dermal infiltrate (Figure 2). Direct immunofluorescence was negative for immunoglobulin and complement deposition. Porphyrin elevation was not detected with a 24-hour urine assay. New lesions were drained and injected with triamcinolone, which appeared to hasten healing.

Mantle cell lymphoma is a distinct lymphoproliferative disorder of B cells that represents less than 7% of non-Hodgkin lymphoma cases.¹ The tumor cells originate in the mantle zone of the lymph nodes. Most patients present with advanced disease involving lymph nodes and other organs. The disease is characterized by male predominance and an aggressive course with a median overall survival of less than 5 years.¹

Epidermolysis bullosa acquisita is a rare blistering disease that usually develops in adulthood. It is a subepidermal disorder characterized by the appearance of fragile tense bullae. Epidermolysis bullosa acquisita can be divided into 2 subtypes: inflammatory and mechanobullous (classic EBA).² Inflammatory EBA presents similarly to bullous pemphigoid and other subepithelial autoimmune blistering diseases. Vesiculobullous lesions predominate on the trunk and extremities and often are accompanied by intense pruritus. The less common mechanobullous noninflammatory subtype, illustrated in our case, presents in trauma-prone areas with skin fragility and tense noninflamed vesicles and bullae that rupture leaving erosions. Associated findings may include milia and scarring. Lesions appear in areas exposed to friction and trauma such as the hands, feet, elbows, knees, and lower back. The differential diagnosis includes dystrophic epidermolysis bullosa, porphyria cutanea tarda, and pseudoporphyria. Dystrophic epidermolysis bullosa is ruled out by family history and disease onset at birth. The lesions of porphyria cutanea tarda and pseudoporphyria occur on sun-exposed areas; porphyrin levels are elevated in the former. Direct immunofluorescence of a perilesional EBA site usually reveals IgG deposition.³ Negative direct immunofluorescence in our case could have resulted from technical error, sample location, or response to systemic immunosuppressive treatment.⁴

Epidermolysis bullosa acquisita is caused by autoantibodies against type VII collagen.^2,3 After the autoantibodies bind, a complement cascade reaction is activated, leading to deposition of C3a and C5a, which recruit leukocytes and mast cells. The anchoring fibrils in the basement membrane zones of the skin and mucosa are disrupted.^5,6 Injection of anti–type VII collagen antibodies into mice induces a blistering disease resembling EBA.⁷ In a study of 14 patients with EBA, disease severity was correlated to levels of anticollagen autoantibodies measured by enzyme-linked immunosorbent assay.⁸

Epidermolysis bullosa acquisita has been linked to Crohn disease and approximately 30% of EBA cases occur in patients with this disease.^9,10 Two case reports document an association with multiple myeloma.^11,12 Treatment often proves challenging and unsatisfactory; valid controlled clinical trials are impossible given the paucity of cases. Successful therapeutic outcomes have been reported with oral prednisone,¹³ colchicine,¹⁴ cyclosporine,¹⁵ dapsone,¹⁶ and rituximab.¹⁷ Our patient received 2 separate courses of rituximab as part of chemotherapy for mantle cell lymphoma without measurable improvement. He was lost to follow-up after recurrence of the lymphoma and we learned from his wife that he had died.

The Diagnosis: Circumscribed Palmar Hypokeratosis

Circumscribed palmar hypokeratosis is a rare, benign, acquired dermatosis that was first described by Pérez et al¹ in 2002 and is characterized by annular plaques with an atrophic center and hyperkeratotic edges. Classically, the lesions present on the thenar and hypothenar eminences of the palms.² The condition predominantly affects women (4:1 ratio), with a mean age of onset of 65 years.³

Although the pathogenesis of circumscribed palmar hypokeratosis is unknown, local trauma generally is considered to be the causative factor. Other hypotheses include human papillomaviruses 4 and 6 infection and primary abnormal keratinization in the epidermis.³ Immunohistochemical studies have demonstrated increased expression of keratin 16 and Ki-67 in cutaneous lesions, which is postulated to be responsible for keratinocyte fragility associated with epidermal hyperproliferation. Other reported cases have shown diminished keratin 9, keratin 2e, and connexin 26 expression, which normally are abundant in the acral epidermis. Abnormal expression of antigens associated with epidermal proliferation and differentiation also have been reported,³ suggesting that there is an altered regulation of the cutaneous desquamation process.

Histologically, circumscribed palmar hypokeratosis is characterized by an abrupt reduction in the stratum corneum (Figure), forming a step between the lesion and the perilesional normal skin.^2,3 The clinical appearance of erythema is due to visualization of dermal blood circulation in the area of corneal thinning and is not a result of vasodilation. The dermis is uninvolved, and inflammation is absent. The differential diagnosis includes psoriasis, Bowen disease, porokeratosis, and dermatophytosis.³

Circumscribed palmar hypokeratosis is a chronic condition, and there are no known reports of development of malignancy. Treatment is not required but may include cryotherapy; topical therapy with corticosteroids, retinoids, urea, and calcipotriene; and photodynamic therapy. Circumscribed hypokeratosis should be included in the differential diagnosis of palmar lesions.

The Diagnosis: Circumscribed Palmar Hypokeratosis

Circumscribed palmar hypokeratosis is a rare, benign, acquired dermatosis that was first described by Pérez et al¹ in 2002 and is characterized by annular plaques with an atrophic center and hyperkeratotic edges. Classically, the lesions present on the thenar and hypothenar eminences of the palms.² The condition predominantly affects women (4:1 ratio), with a mean age of onset of 65 years.³

Although the pathogenesis of circumscribed palmar hypokeratosis is unknown, local trauma generally is considered to be the causative factor. Other hypotheses include human papillomaviruses 4 and 6 infection and primary abnormal keratinization in the epidermis.³ Immunohistochemical studies have demonstrated increased expression of keratin 16 and Ki-67 in cutaneous lesions, which is postulated to be responsible for keratinocyte fragility associated with epidermal hyperproliferation. Other reported cases have shown diminished keratin 9, keratin 2e, and connexin 26 expression, which normally are abundant in the acral epidermis. Abnormal expression of antigens associated with epidermal proliferation and differentiation also have been reported,³ suggesting that there is an altered regulation of the cutaneous desquamation process.

Histologically, circumscribed palmar hypokeratosis is characterized by an abrupt reduction in the stratum corneum (Figure), forming a step between the lesion and the perilesional normal skin.^2,3 The clinical appearance of erythema is due to visualization of dermal blood circulation in the area of corneal thinning and is not a result of vasodilation. The dermis is uninvolved, and inflammation is absent. The differential diagnosis includes psoriasis, Bowen disease, porokeratosis, and dermatophytosis.³

Circumscribed palmar hypokeratosis is a chronic condition, and there are no known reports of development of malignancy. Treatment is not required but may include cryotherapy; topical therapy with corticosteroids, retinoids, urea, and calcipotriene; and photodynamic therapy. Circumscribed hypokeratosis should be included in the differential diagnosis of palmar lesions.

The Diagnosis: Circumscribed Palmar Hypokeratosis

Circumscribed palmar hypokeratosis is a rare, benign, acquired dermatosis that was first described by Pérez et al¹ in 2002 and is characterized by annular plaques with an atrophic center and hyperkeratotic edges. Classically, the lesions present on the thenar and hypothenar eminences of the palms.² The condition predominantly affects women (4:1 ratio), with a mean age of onset of 65 years.³

Although the pathogenesis of circumscribed palmar hypokeratosis is unknown, local trauma generally is considered to be the causative factor. Other hypotheses include human papillomaviruses 4 and 6 infection and primary abnormal keratinization in the epidermis.³ Immunohistochemical studies have demonstrated increased expression of keratin 16 and Ki-67 in cutaneous lesions, which is postulated to be responsible for keratinocyte fragility associated with epidermal hyperproliferation. Other reported cases have shown diminished keratin 9, keratin 2e, and connexin 26 expression, which normally are abundant in the acral epidermis. Abnormal expression of antigens associated with epidermal proliferation and differentiation also have been reported,³ suggesting that there is an altered regulation of the cutaneous desquamation process.

Histologically, circumscribed palmar hypokeratosis is characterized by an abrupt reduction in the stratum corneum (Figure), forming a step between the lesion and the perilesional normal skin.^2,3 The clinical appearance of erythema is due to visualization of dermal blood circulation in the area of corneal thinning and is not a result of vasodilation. The dermis is uninvolved, and inflammation is absent. The differential diagnosis includes psoriasis, Bowen disease, porokeratosis, and dermatophytosis.³

Circumscribed palmar hypokeratosis is a chronic condition, and there are no known reports of development of malignancy. Treatment is not required but may include cryotherapy; topical therapy with corticosteroids, retinoids, urea, and calcipotriene; and photodynamic therapy. Circumscribed hypokeratosis should be included in the differential diagnosis of palmar lesions.

The Diagnosis: Cutaneous Crohn Disease

A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.

Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.

Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.¹ This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.² The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.³

Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.¹ The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.^4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.⁶

Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.⁵

Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.³ Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.⁷ For disseminated disease, systemic corticosteroids have shown efficacy.³ Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.³

Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.

The Diagnosis: Cutaneous Crohn Disease

A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.

Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.

Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.¹ This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.² The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.³

Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.¹ The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.^4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.⁶

Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.⁵

Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.³ Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.⁷ For disseminated disease, systemic corticosteroids have shown efficacy.³ Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.³

Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.

The Diagnosis: Cutaneous Crohn Disease

A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.

Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.

Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.¹ This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.² The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.³

Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.¹ The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.^4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.⁶

Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.⁵

Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.³ Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.⁷ For disseminated disease, systemic corticosteroids have shown efficacy.³ Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.³

Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

An 84-year-old man was admitted to the hospital with 5 erythematous cutaneous nodules of several days’ duration on the legs ranging in size from 1.0 to 1.5 cm. Upon admission, the patient also had a chest radiograph suspicious for pneumonia. The patient had received sulfamethoxazole/trimethoprim for a urinary tract infection as an outpatient 5 days prior to presentation, but he stopped the medication due to the appearance of the cutaneous nodules. Of note, the patient also reported unintentional weight loss of 15 pounds over the last few months.

New nodules had developed at a rate of 1 to 2 lesions daily in the 3 days prior to presentation and continued to develop after admission to the hospital. The nodules appeared as tender, erythematous lesions that evolved to form pustules and developed overlying crusts in later stages (Figure 1). They were limited to the arms and legs, primarily involving the lower legs. There was no evidence of oral or ocular involvement. A hemoglobin count of 10.9 g/dL (reference range, 14.0–17.5 g/dL), white blood cell count of 8.8×10⁹/L (reference range, 4.5–11.0×10⁹/L), and erythrocyte sedimentation rate of 69 mm/h (reference range, 0–20 mm/h) were noted on admission.

The patient was started on ceftriaxone and azithromycin for suspected pneumonia. The differential diagnosis for the cutaneous nodules included lymphoma, acid-fast bacilli (AFB) infection, deep fungal infection, pyoderma gangrenosum, Sweet syndrome (SS), panniculitis, erythema elevatum diutinum, and polyarteritis nodosa. A punch biopsy of a nodule on the left foot was performed. Histopathology demonstrated a neutrophilic panniculitis (Figure 2) with an epidermal abscess. No vasculitis was identified, and periodic acid–Schiff and AFB staining of the skin biopsy were negative. These findings were consistent with SS. Computed tomography scans of the chest, abdomen, and pelvis, which were completed early in the course of hospitalization due to concern for underlying malignancy, revealed pericardial and pleural effusions as well as cystic lesions in the lungs, spleen, kidneys, and prostate, with the largest lesion on the spleen measuring 5.6×4.8 cm (Figure 3). Computed tomography scanning was negative for areas of consolidation in the lungs. A splenic biopsy was performed by an interventional radiologist during the patient's hospitalization that identified an aseptic, neutrophilic process. Fungal, bacterial, and AFB cultures of the splenic tissue and cystic contents were negative. Bilateral pleural effusions also were identified, and a thoracentesis was performed. The pleural fluid indicated rare mesothelial cells in the background of acute inflammation with no growth of the bacterial, fungal, or AFB cultures.

Due to the association of hematologic malignances with SS, a bone marrow biopsy was performed, which revealed multiple myeloma. Serum protein electrophoresis demonstrated monoclonal gammopathy of κ light chains. During the course of his hospitalization, new skin lesions continued to develop on the hands, face, and trunk. The patient was discharged from the hospital shortly after diagnosis to receive outpatient treatment for multiple myeloma with lenalidomide and dexamethasone. Upon follow-up with the patient’s family via telephone 3 weeks into treatment, his son confirmed that the nodules were resolving.

Our case could be consistent with either drug-induced or malignancy-associated SS. Sweet syndrome initially was described in 1964 in 8 female patients with leukocytosis and cutaneous plaques infiltrated by neutrophils.¹ The skin lesions typically are red and painful, ranging in size from 0.5 cm to 12.0 cm, and can last weeks to years if not treated.² Variations of skin lesions include bullous and pustular morphologies.³

Diagnostic criteria for SS have been established.⁴ Both of the major criteria must be met as well as 2 of 4 minor criteria. Major criteria include abrupt onset of tender erythematous plaques and nodules; secondly, a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis must be seen on histopathology. Minor criteria include pyrexia, association with underlying condition (malignancy, pregnancy, drug exposure, inflammatory disorder), responsiveness to systemic steroids, and abnormal laboratory values (erythrocyte sedimentation rate, white blood cell count, C-reactive protein, neutrophilia).⁴

Sweet syndrome can be divided into 3 classifications: classical or idiopathic, drug-induced, or malignancy-associated.⁴ Classical SS most commonly is seen in middle-aged women after an upper respiratory or gastrointestinal infection. Drug-induced SS most often is associated with granulocyte-stimulating factor colony therapy⁴; however, it has been associated with use of trimethoprim/sulfamethoxazole.⁵ Malignancy-associated SS most commonly is seen in individuals with hematologic malignancy, specifically acute myeloid leukemia. Although its association with multiple myeloma is not as frequent, cases of malignancy-associated SS identifying this association have been reported.^6,7 Mucosal involvement in the form of aphthouslike lesions more frequently is seen in malignancy-associated SS.⁸ Differing from classical SS, which has a female predilection of around 4:1, the malignancy-associated disorder has a 1:1 female-to-male ratio.⁴

In the majority of cases of SS, the neutrophilic infiltrate is in the papillary and upper reticular dermis; however, if the neutrophilic infiltrate is predominately in the subcutaneous tissue (known as subcutaneous SS), there is a strong association with malignancy.⁹ The histopathology in our case demonstrated a neutrophilic infiltrate in the subcutaneous tissue.

Fever is the most common systemic manifestation of SS and is present in 54% to 65% of patients.^8,10 Besides the skin, the most common site affected is the eye, with 13% to 75% of patients reporting ocular involvement, usually conjunctivitis.^4,10 Although infrequent, extracutaneous SS has been identified in the bones, central nervous system, kidneys, heart, liver, spleen, lungs, ears, eyes, and intestines.⁴ A case of SS with splenic involvement in the form of sterile abscesses also was reported.¹¹ This case was related to parvovirus B19.

Sweet syndrome is a condition characterized by tender, erythematous cutaneous lesions with histopathology demonstrating neutrophilic infiltrate in the absence of vasculitis. We report a case of suspected extracutaneous SS in the form of splenic cysts in a patient whose SS was associated with malignancy and/or drug ingestion.

To the Editor:

An 84-year-old man was admitted to the hospital with 5 erythematous cutaneous nodules of several days’ duration on the legs ranging in size from 1.0 to 1.5 cm. Upon admission, the patient also had a chest radiograph suspicious for pneumonia. The patient had received sulfamethoxazole/trimethoprim for a urinary tract infection as an outpatient 5 days prior to presentation, but he stopped the medication due to the appearance of the cutaneous nodules. Of note, the patient also reported unintentional weight loss of 15 pounds over the last few months.

New nodules had developed at a rate of 1 to 2 lesions daily in the 3 days prior to presentation and continued to develop after admission to the hospital. The nodules appeared as tender, erythematous lesions that evolved to form pustules and developed overlying crusts in later stages (Figure 1). They were limited to the arms and legs, primarily involving the lower legs. There was no evidence of oral or ocular involvement. A hemoglobin count of 10.9 g/dL (reference range, 14.0–17.5 g/dL), white blood cell count of 8.8×10⁹/L (reference range, 4.5–11.0×10⁹/L), and erythrocyte sedimentation rate of 69 mm/h (reference range, 0–20 mm/h) were noted on admission.

The patient was started on ceftriaxone and azithromycin for suspected pneumonia. The differential diagnosis for the cutaneous nodules included lymphoma, acid-fast bacilli (AFB) infection, deep fungal infection, pyoderma gangrenosum, Sweet syndrome (SS), panniculitis, erythema elevatum diutinum, and polyarteritis nodosa. A punch biopsy of a nodule on the left foot was performed. Histopathology demonstrated a neutrophilic panniculitis (Figure 2) with an epidermal abscess. No vasculitis was identified, and periodic acid–Schiff and AFB staining of the skin biopsy were negative. These findings were consistent with SS. Computed tomography scans of the chest, abdomen, and pelvis, which were completed early in the course of hospitalization due to concern for underlying malignancy, revealed pericardial and pleural effusions as well as cystic lesions in the lungs, spleen, kidneys, and prostate, with the largest lesion on the spleen measuring 5.6×4.8 cm (Figure 3). Computed tomography scanning was negative for areas of consolidation in the lungs. A splenic biopsy was performed by an interventional radiologist during the patient's hospitalization that identified an aseptic, neutrophilic process. Fungal, bacterial, and AFB cultures of the splenic tissue and cystic contents were negative. Bilateral pleural effusions also were identified, and a thoracentesis was performed. The pleural fluid indicated rare mesothelial cells in the background of acute inflammation with no growth of the bacterial, fungal, or AFB cultures.

Due to the association of hematologic malignances with SS, a bone marrow biopsy was performed, which revealed multiple myeloma. Serum protein electrophoresis demonstrated monoclonal gammopathy of κ light chains. During the course of his hospitalization, new skin lesions continued to develop on the hands, face, and trunk. The patient was discharged from the hospital shortly after diagnosis to receive outpatient treatment for multiple myeloma with lenalidomide and dexamethasone. Upon follow-up with the patient’s family via telephone 3 weeks into treatment, his son confirmed that the nodules were resolving.

Our case could be consistent with either drug-induced or malignancy-associated SS. Sweet syndrome initially was described in 1964 in 8 female patients with leukocytosis and cutaneous plaques infiltrated by neutrophils.¹ The skin lesions typically are red and painful, ranging in size from 0.5 cm to 12.0 cm, and can last weeks to years if not treated.² Variations of skin lesions include bullous and pustular morphologies.³

Diagnostic criteria for SS have been established.⁴ Both of the major criteria must be met as well as 2 of 4 minor criteria. Major criteria include abrupt onset of tender erythematous plaques and nodules; secondly, a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis must be seen on histopathology. Minor criteria include pyrexia, association with underlying condition (malignancy, pregnancy, drug exposure, inflammatory disorder), responsiveness to systemic steroids, and abnormal laboratory values (erythrocyte sedimentation rate, white blood cell count, C-reactive protein, neutrophilia).⁴

Sweet syndrome can be divided into 3 classifications: classical or idiopathic, drug-induced, or malignancy-associated.⁴ Classical SS most commonly is seen in middle-aged women after an upper respiratory or gastrointestinal infection. Drug-induced SS most often is associated with granulocyte-stimulating factor colony therapy⁴; however, it has been associated with use of trimethoprim/sulfamethoxazole.⁵ Malignancy-associated SS most commonly is seen in individuals with hematologic malignancy, specifically acute myeloid leukemia. Although its association with multiple myeloma is not as frequent, cases of malignancy-associated SS identifying this association have been reported.^6,7 Mucosal involvement in the form of aphthouslike lesions more frequently is seen in malignancy-associated SS.⁸ Differing from classical SS, which has a female predilection of around 4:1, the malignancy-associated disorder has a 1:1 female-to-male ratio.⁴

In the majority of cases of SS, the neutrophilic infiltrate is in the papillary and upper reticular dermis; however, if the neutrophilic infiltrate is predominately in the subcutaneous tissue (known as subcutaneous SS), there is a strong association with malignancy.⁹ The histopathology in our case demonstrated a neutrophilic infiltrate in the subcutaneous tissue.

Fever is the most common systemic manifestation of SS and is present in 54% to 65% of patients.^8,10 Besides the skin, the most common site affected is the eye, with 13% to 75% of patients reporting ocular involvement, usually conjunctivitis.^4,10 Although infrequent, extracutaneous SS has been identified in the bones, central nervous system, kidneys, heart, liver, spleen, lungs, ears, eyes, and intestines.⁴ A case of SS with splenic involvement in the form of sterile abscesses also was reported.¹¹ This case was related to parvovirus B19.

Sweet syndrome is a condition characterized by tender, erythematous cutaneous lesions with histopathology demonstrating neutrophilic infiltrate in the absence of vasculitis. We report a case of suspected extracutaneous SS in the form of splenic cysts in a patient whose SS was associated with malignancy and/or drug ingestion.

To the Editor:

An 84-year-old man was admitted to the hospital with 5 erythematous cutaneous nodules of several days’ duration on the legs ranging in size from 1.0 to 1.5 cm. Upon admission, the patient also had a chest radiograph suspicious for pneumonia. The patient had received sulfamethoxazole/trimethoprim for a urinary tract infection as an outpatient 5 days prior to presentation, but he stopped the medication due to the appearance of the cutaneous nodules. Of note, the patient also reported unintentional weight loss of 15 pounds over the last few months.

New nodules had developed at a rate of 1 to 2 lesions daily in the 3 days prior to presentation and continued to develop after admission to the hospital. The nodules appeared as tender, erythematous lesions that evolved to form pustules and developed overlying crusts in later stages (Figure 1). They were limited to the arms and legs, primarily involving the lower legs. There was no evidence of oral or ocular involvement. A hemoglobin count of 10.9 g/dL (reference range, 14.0–17.5 g/dL), white blood cell count of 8.8×10⁹/L (reference range, 4.5–11.0×10⁹/L), and erythrocyte sedimentation rate of 69 mm/h (reference range, 0–20 mm/h) were noted on admission.

The patient was started on ceftriaxone and azithromycin for suspected pneumonia. The differential diagnosis for the cutaneous nodules included lymphoma, acid-fast bacilli (AFB) infection, deep fungal infection, pyoderma gangrenosum, Sweet syndrome (SS), panniculitis, erythema elevatum diutinum, and polyarteritis nodosa. A punch biopsy of a nodule on the left foot was performed. Histopathology demonstrated a neutrophilic panniculitis (Figure 2) with an epidermal abscess. No vasculitis was identified, and periodic acid–Schiff and AFB staining of the skin biopsy were negative. These findings were consistent with SS. Computed tomography scans of the chest, abdomen, and pelvis, which were completed early in the course of hospitalization due to concern for underlying malignancy, revealed pericardial and pleural effusions as well as cystic lesions in the lungs, spleen, kidneys, and prostate, with the largest lesion on the spleen measuring 5.6×4.8 cm (Figure 3). Computed tomography scanning was negative for areas of consolidation in the lungs. A splenic biopsy was performed by an interventional radiologist during the patient's hospitalization that identified an aseptic, neutrophilic process. Fungal, bacterial, and AFB cultures of the splenic tissue and cystic contents were negative. Bilateral pleural effusions also were identified, and a thoracentesis was performed. The pleural fluid indicated rare mesothelial cells in the background of acute inflammation with no growth of the bacterial, fungal, or AFB cultures.

Due to the association of hematologic malignances with SS, a bone marrow biopsy was performed, which revealed multiple myeloma. Serum protein electrophoresis demonstrated monoclonal gammopathy of κ light chains. During the course of his hospitalization, new skin lesions continued to develop on the hands, face, and trunk. The patient was discharged from the hospital shortly after diagnosis to receive outpatient treatment for multiple myeloma with lenalidomide and dexamethasone. Upon follow-up with the patient’s family via telephone 3 weeks into treatment, his son confirmed that the nodules were resolving.

Our case could be consistent with either drug-induced or malignancy-associated SS. Sweet syndrome initially was described in 1964 in 8 female patients with leukocytosis and cutaneous plaques infiltrated by neutrophils.¹ The skin lesions typically are red and painful, ranging in size from 0.5 cm to 12.0 cm, and can last weeks to years if not treated.² Variations of skin lesions include bullous and pustular morphologies.³

Diagnostic criteria for SS have been established.⁴ Both of the major criteria must be met as well as 2 of 4 minor criteria. Major criteria include abrupt onset of tender erythematous plaques and nodules; secondly, a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis must be seen on histopathology. Minor criteria include pyrexia, association with underlying condition (malignancy, pregnancy, drug exposure, inflammatory disorder), responsiveness to systemic steroids, and abnormal laboratory values (erythrocyte sedimentation rate, white blood cell count, C-reactive protein, neutrophilia).⁴

Sweet syndrome can be divided into 3 classifications: classical or idiopathic, drug-induced, or malignancy-associated.⁴ Classical SS most commonly is seen in middle-aged women after an upper respiratory or gastrointestinal infection. Drug-induced SS most often is associated with granulocyte-stimulating factor colony therapy⁴; however, it has been associated with use of trimethoprim/sulfamethoxazole.⁵ Malignancy-associated SS most commonly is seen in individuals with hematologic malignancy, specifically acute myeloid leukemia. Although its association with multiple myeloma is not as frequent, cases of malignancy-associated SS identifying this association have been reported.^6,7 Mucosal involvement in the form of aphthouslike lesions more frequently is seen in malignancy-associated SS.⁸ Differing from classical SS, which has a female predilection of around 4:1, the malignancy-associated disorder has a 1:1 female-to-male ratio.⁴

In the majority of cases of SS, the neutrophilic infiltrate is in the papillary and upper reticular dermis; however, if the neutrophilic infiltrate is predominately in the subcutaneous tissue (known as subcutaneous SS), there is a strong association with malignancy.⁹ The histopathology in our case demonstrated a neutrophilic infiltrate in the subcutaneous tissue.

Fever is the most common systemic manifestation of SS and is present in 54% to 65% of patients.^8,10 Besides the skin, the most common site affected is the eye, with 13% to 75% of patients reporting ocular involvement, usually conjunctivitis.^4,10 Although infrequent, extracutaneous SS has been identified in the bones, central nervous system, kidneys, heart, liver, spleen, lungs, ears, eyes, and intestines.⁴ A case of SS with splenic involvement in the form of sterile abscesses also was reported.¹¹ This case was related to parvovirus B19.

Sweet syndrome is a condition characterized by tender, erythematous cutaneous lesions with histopathology demonstrating neutrophilic infiltrate in the absence of vasculitis. We report a case of suspected extracutaneous SS in the form of splenic cysts in a patient whose SS was associated with malignancy and/or drug ingestion.

The Diagnosis: Erythrasma

Erythrasma usually involves intertriginous areas (eg, axillae, groin, inframammary area). Patients present with well-demarcated, minimally scaly, red-brown patches. The interdigital web space of the toes also can be involved with macerated white plaques, often with coexistent dermatophyte infection. Corynebacterium minutissimum, the bacteria responsible for erythrasma, produces coproporphyrin type III, which emits coral red fluorescence under Wood lamp examination.¹ Bathing may result in removal of the porphyrin and result in a false-negative finding. Potassium hydroxide preparation of skin scrapings can show chains of bacilli. Biopsy appears relatively normal at low power but reveals compact orthokeratosis with coccobacilli and filamentous organisms in the superficial stratum corneum (quiz image). When not obvious on hematoxylin and eosin-stained sections, the organisms are Gram-positive and also are seen with periodic acid-Schiff (PAS) and methenamine silver stains. Unlike fungal hyphae, these organisms are thinner and nonrefractile. Inflammation typically is minimal. Due to the subtle histologic findings at low power, erythrasma is considered one of the invisible dermatoses.² The differential diagnosis of these inconspicuous dermatoses that appear normal at first glance can be approached in a stepwise fashion starting in the stratum corneum, followed by the granular layer, basal layer, dermal papillae, dermal inflammatory cells, dermal connective tissue, and eccrine glands, and should consider each of the following diagnoses: candidiasis, dermatophytosis, ichthyosis vulgaris, vitiligo, macular amyloid, urticaria, telangiectasia macularis eruptiva perstans, connective tissue nevus, and argyria.² 

Candidiasis, most commonly caused by Candida albicans, usually involves the oral cavity (eg, thrush, median rhomboid glossitis, angular cheilitis), intertriginous zones, nail fold (paronychia), genital areas (eg, vulvovaginitis, balanitis), and diaper area.³ The web space between the third and fourth fingers (erosio interdigitalis blastomycetica) can be involved in patients whose hands are frequently in water. Intertriginous candidiasis presents with bright red, sometimes erosive patches with satellite lesions. Spores and mycelia (filamentous forms) are noted on potassium hydroxide preparation of skin scrapings. Histologically, the epidermis often is acanthotic, mildly spongiotic, and contains groups of neutrophils in the superficial layers. The mnemonic device for diseases with clusters of neutrophils in the stratum corneum is PTICSS (psoriasis, tinea, impetigo, candida, seborrheic dermatitis, syphilis).² Yeast, pseudohyphae, and even true hyphae can be seen in the stratum corneum with hematoxylin and eosin-stained sections and PAS. The filamentous forms tend to be vertically oriented in relation to the skin surface (Figure 1) compared to dermatophyte hyphae that tend to be parallel to the surface.²

Pitted keratolysis is a superficial bacterial infection involving the soles of the feet. The classic clinical findings are shallow 1- to 2-mm pits in clusters that can coalesce on pressure-bearing areas. Hyperhidrosis, malodor, and maceration commonly are associated. Microscopic examination reveals clusters of small cocci and filamentous bacteria located in the dell or pit of a thick compact orthokeratotic stratum corneum of acral skin with no notable inflammatory infiltrate (Figure 2).² Special stains such as Gram, methenamine silver, or PAS can assist in visualization of the organisms. Pitted keratolysis is caused by Dermatophilus congolensis and Kytococcus sedentarius (formerly Micrococcus sedentarius), which produce keratinolytic enzymes causing the defect in the stratum corneum.³

Tinea cruris, also known as jock itch and ringworm of the groin, presents with advancing pruritic, circinate, erythematous, scaling patches with central clearing on the inner thighs and crural folds. Similar to tinea pedis, Trichophyton rubrum is the most common dermatophyte to cause tinea cruris.⁴ Potassium hydroxide preparation of skin scrapings from the advancing border show fungal hyphae that cross the keratin cell borders. The histopathology of dermatophyte infections can be subtle and resemble normal skin before close inspection of the stratum corneum, which can show compact orthokeratosis, neutrophils, or "sandwich sign" where hyphae are sandwiched between an upper basket weave layer and a lower compact cornified layer (orthokeratotic or parakeratotic)(Figure 3).¹ The presence of these patterns in the stratum corneum should result in performance of PAS to highlight obscure hyphae.

Tinea versicolor, also called pityriasis versicolor, usually presents with hypopigmented or less commonly hyperpigmented circular patches that coalesce on the upper trunk and shoulders. There is a fine fluffy scale that is most notable after scraping the skin for a potassium hydroxide preparation, which shows "spaghetti and meatballs" (hyphae and spores). Tinea versicolor typically is caused by the mycelial phase of the lipophilic yeast Malassezia globosae.³ Histologically, there are yeast and short septate hyphae scattered in a loose basket weave hyperkeratotic stratum corneum with minimal or no inflammation (Figure 4). On occasion, PAS is required for identification.

The Diagnosis: Erythrasma

Erythrasma usually involves intertriginous areas (eg, axillae, groin, inframammary area). Patients present with well-demarcated, minimally scaly, red-brown patches. The interdigital web space of the toes also can be involved with macerated white plaques, often with coexistent dermatophyte infection. Corynebacterium minutissimum, the bacteria responsible for erythrasma, produces coproporphyrin type III, which emits coral red fluorescence under Wood lamp examination.¹ Bathing may result in removal of the porphyrin and result in a false-negative finding. Potassium hydroxide preparation of skin scrapings can show chains of bacilli. Biopsy appears relatively normal at low power but reveals compact orthokeratosis with coccobacilli and filamentous organisms in the superficial stratum corneum (quiz image). When not obvious on hematoxylin and eosin-stained sections, the organisms are Gram-positive and also are seen with periodic acid-Schiff (PAS) and methenamine silver stains. Unlike fungal hyphae, these organisms are thinner and nonrefractile. Inflammation typically is minimal. Due to the subtle histologic findings at low power, erythrasma is considered one of the invisible dermatoses.² The differential diagnosis of these inconspicuous dermatoses that appear normal at first glance can be approached in a stepwise fashion starting in the stratum corneum, followed by the granular layer, basal layer, dermal papillae, dermal inflammatory cells, dermal connective tissue, and eccrine glands, and should consider each of the following diagnoses: candidiasis, dermatophytosis, ichthyosis vulgaris, vitiligo, macular amyloid, urticaria, telangiectasia macularis eruptiva perstans, connective tissue nevus, and argyria.² 

Candidiasis, most commonly caused by Candida albicans, usually involves the oral cavity (eg, thrush, median rhomboid glossitis, angular cheilitis), intertriginous zones, nail fold (paronychia), genital areas (eg, vulvovaginitis, balanitis), and diaper area.³ The web space between the third and fourth fingers (erosio interdigitalis blastomycetica) can be involved in patients whose hands are frequently in water. Intertriginous candidiasis presents with bright red, sometimes erosive patches with satellite lesions. Spores and mycelia (filamentous forms) are noted on potassium hydroxide preparation of skin scrapings. Histologically, the epidermis often is acanthotic, mildly spongiotic, and contains groups of neutrophils in the superficial layers. The mnemonic device for diseases with clusters of neutrophils in the stratum corneum is PTICSS (psoriasis, tinea, impetigo, candida, seborrheic dermatitis, syphilis).² Yeast, pseudohyphae, and even true hyphae can be seen in the stratum corneum with hematoxylin and eosin-stained sections and PAS. The filamentous forms tend to be vertically oriented in relation to the skin surface (Figure 1) compared to dermatophyte hyphae that tend to be parallel to the surface.²

Pitted keratolysis is a superficial bacterial infection involving the soles of the feet. The classic clinical findings are shallow 1- to 2-mm pits in clusters that can coalesce on pressure-bearing areas. Hyperhidrosis, malodor, and maceration commonly are associated. Microscopic examination reveals clusters of small cocci and filamentous bacteria located in the dell or pit of a thick compact orthokeratotic stratum corneum of acral skin with no notable inflammatory infiltrate (Figure 2).² Special stains such as Gram, methenamine silver, or PAS can assist in visualization of the organisms. Pitted keratolysis is caused by Dermatophilus congolensis and Kytococcus sedentarius (formerly Micrococcus sedentarius), which produce keratinolytic enzymes causing the defect in the stratum corneum.³

Tinea cruris, also known as jock itch and ringworm of the groin, presents with advancing pruritic, circinate, erythematous, scaling patches with central clearing on the inner thighs and crural folds. Similar to tinea pedis, Trichophyton rubrum is the most common dermatophyte to cause tinea cruris.⁴ Potassium hydroxide preparation of skin scrapings from the advancing border show fungal hyphae that cross the keratin cell borders. The histopathology of dermatophyte infections can be subtle and resemble normal skin before close inspection of the stratum corneum, which can show compact orthokeratosis, neutrophils, or "sandwich sign" where hyphae are sandwiched between an upper basket weave layer and a lower compact cornified layer (orthokeratotic or parakeratotic)(Figure 3).¹ The presence of these patterns in the stratum corneum should result in performance of PAS to highlight obscure hyphae.

Tinea versicolor, also called pityriasis versicolor, usually presents with hypopigmented or less commonly hyperpigmented circular patches that coalesce on the upper trunk and shoulders. There is a fine fluffy scale that is most notable after scraping the skin for a potassium hydroxide preparation, which shows "spaghetti and meatballs" (hyphae and spores). Tinea versicolor typically is caused by the mycelial phase of the lipophilic yeast Malassezia globosae.³ Histologically, there are yeast and short septate hyphae scattered in a loose basket weave hyperkeratotic stratum corneum with minimal or no inflammation (Figure 4). On occasion, PAS is required for identification.

The Diagnosis: Erythrasma

Erythrasma usually involves intertriginous areas (eg, axillae, groin, inframammary area). Patients present with well-demarcated, minimally scaly, red-brown patches. The interdigital web space of the toes also can be involved with macerated white plaques, often with coexistent dermatophyte infection. Corynebacterium minutissimum, the bacteria responsible for erythrasma, produces coproporphyrin type III, which emits coral red fluorescence under Wood lamp examination.¹ Bathing may result in removal of the porphyrin and result in a false-negative finding. Potassium hydroxide preparation of skin scrapings can show chains of bacilli. Biopsy appears relatively normal at low power but reveals compact orthokeratosis with coccobacilli and filamentous organisms in the superficial stratum corneum (quiz image). When not obvious on hematoxylin and eosin-stained sections, the organisms are Gram-positive and also are seen with periodic acid-Schiff (PAS) and methenamine silver stains. Unlike fungal hyphae, these organisms are thinner and nonrefractile. Inflammation typically is minimal. Due to the subtle histologic findings at low power, erythrasma is considered one of the invisible dermatoses.² The differential diagnosis of these inconspicuous dermatoses that appear normal at first glance can be approached in a stepwise fashion starting in the stratum corneum, followed by the granular layer, basal layer, dermal papillae, dermal inflammatory cells, dermal connective tissue, and eccrine glands, and should consider each of the following diagnoses: candidiasis, dermatophytosis, ichthyosis vulgaris, vitiligo, macular amyloid, urticaria, telangiectasia macularis eruptiva perstans, connective tissue nevus, and argyria.² 

Candidiasis, most commonly caused by Candida albicans, usually involves the oral cavity (eg, thrush, median rhomboid glossitis, angular cheilitis), intertriginous zones, nail fold (paronychia), genital areas (eg, vulvovaginitis, balanitis), and diaper area.³ The web space between the third and fourth fingers (erosio interdigitalis blastomycetica) can be involved in patients whose hands are frequently in water. Intertriginous candidiasis presents with bright red, sometimes erosive patches with satellite lesions. Spores and mycelia (filamentous forms) are noted on potassium hydroxide preparation of skin scrapings. Histologically, the epidermis often is acanthotic, mildly spongiotic, and contains groups of neutrophils in the superficial layers. The mnemonic device for diseases with clusters of neutrophils in the stratum corneum is PTICSS (psoriasis, tinea, impetigo, candida, seborrheic dermatitis, syphilis).² Yeast, pseudohyphae, and even true hyphae can be seen in the stratum corneum with hematoxylin and eosin-stained sections and PAS. The filamentous forms tend to be vertically oriented in relation to the skin surface (Figure 1) compared to dermatophyte hyphae that tend to be parallel to the surface.²

Pitted keratolysis is a superficial bacterial infection involving the soles of the feet. The classic clinical findings are shallow 1- to 2-mm pits in clusters that can coalesce on pressure-bearing areas. Hyperhidrosis, malodor, and maceration commonly are associated. Microscopic examination reveals clusters of small cocci and filamentous bacteria located in the dell or pit of a thick compact orthokeratotic stratum corneum of acral skin with no notable inflammatory infiltrate (Figure 2).² Special stains such as Gram, methenamine silver, or PAS can assist in visualization of the organisms. Pitted keratolysis is caused by Dermatophilus congolensis and Kytococcus sedentarius (formerly Micrococcus sedentarius), which produce keratinolytic enzymes causing the defect in the stratum corneum.³

Tinea cruris, also known as jock itch and ringworm of the groin, presents with advancing pruritic, circinate, erythematous, scaling patches with central clearing on the inner thighs and crural folds. Similar to tinea pedis, Trichophyton rubrum is the most common dermatophyte to cause tinea cruris.⁴ Potassium hydroxide preparation of skin scrapings from the advancing border show fungal hyphae that cross the keratin cell borders. The histopathology of dermatophyte infections can be subtle and resemble normal skin before close inspection of the stratum corneum, which can show compact orthokeratosis, neutrophils, or "sandwich sign" where hyphae are sandwiched between an upper basket weave layer and a lower compact cornified layer (orthokeratotic or parakeratotic)(Figure 3).¹ The presence of these patterns in the stratum corneum should result in performance of PAS to highlight obscure hyphae.

Tinea versicolor, also called pityriasis versicolor, usually presents with hypopigmented or less commonly hyperpigmented circular patches that coalesce on the upper trunk and shoulders. There is a fine fluffy scale that is most notable after scraping the skin for a potassium hydroxide preparation, which shows "spaghetti and meatballs" (hyphae and spores). Tinea versicolor typically is caused by the mycelial phase of the lipophilic yeast Malassezia globosae.³ Histologically, there are yeast and short septate hyphae scattered in a loose basket weave hyperkeratotic stratum corneum with minimal or no inflammation (Figure 4). On occasion, PAS is required for identification.

To the Editor:

A 68-year-old man presented with slightly itchy macules on the waist and abdomen of approximately 2 years’ duration. He reported that the initial lesions were dark red and subsequently coalesced to form a beltlike pigmentation on the abdomen. He denied any prior treatment, and the lesions did not spontaneously resolve. The patient was taking escitalopram oxalate, telmisartan, and aspirin for depression and cardiovascular disease that was diagnosed 3 years prior. He reported no exposure to UV radiation or a heat source. He denied use of any cosmetics on the body as well as a family history of similar symptoms.

Physical examination showed reticulate brown-purple macules with slight scale on the surface that had become confluent, forming a beltlike pigmentation on the waist and abdomen (Figure 1). Wickham striae were not seen. The oral mucosa and nails were not affected. Microscopic examination for fungal infections was negative.

Systematic physical and laboratory examinations revealed no abnormalities. A skin biopsy from a macule on the abdomen showed hyperkeratosis, thinned out stratum spinosum with flattening of rete ridges, hypergranulosis with vacuolar alteration of the basal cell layer, and bandlike infiltration of lymphocytes and melanophages with incontinence of pigment (Figure 2). Focalized purplish homogeneous deposits were observed in the upper dermis (Figure 3), of which positive crystal violet staining indicated amyloidosis (Figure 4). Congo red stain revealed amyloid deposition (Figure 5). Thus, the diagnosis of lichen planus pigmentosus (LPP) complicated with focal amyloidosis was made. The patient was treated with topical corticosteroids and tretinoin, and no notable therapeutic effects were observed at 3-month follow-up.

Lichen planus pigmentosus, a variant of lichen planus, is a condition of unknown etiology exhibiting dark brown macules and/or papules and a long clinical course. The face, neck, trunk, arms, and legs are the most common areas of presentation, whereas involvement of the scalp, nails, or oral mucosa is relatively rare.

The first clinicohistopathological study with a large sample size was documented by Bhutani et al¹ in 1974 who termed the currently recognized entity lichen planus pigmentosus. Lichen planus pigmentosus is a frequently encountered hyperpigmentation disorder in Indians, whereas sporadic cases also are reported in other regions and ethnicities.² In cases of LPP, the pigmentation is symmetrical, and its pattern most often is diffuse, then reticular, blotchy, and perifollicular.³ Two unique patterns of LPP have been documented, including linear/blaschkoid LPP and zosteriform LPP.^4,5 Our patient showed a unique beltlike distribution pattern.

The pathogenesis of LPP still is unclear, and several inciting factors such as mustard oil, gold therapy,⁶ and hepatitis C virus infection have been cited.⁷ Mancuso and Berdondini⁸ reported a case of LPP flaring immediately after relapse of nephrotic syndrome. It also has been considered as a paraneoplastic phenomen.⁹ No exact cause was found in our patient after a series of relative examinations.

The histopathologic changes associated with LPP consist of atrophic epidermis; bandlike lymphocytic infiltrate with vacuolar degeneration of the basal layer in the epidermis; and prominent melanin incontinence in the upper dermis, which can be diverse depending on different sites of skin biopsy and the phase of LPP. Histopathologic findings in our patient were consistent with LPP. The differential diagnosis for the reticulate pattern of pigmentation seen in our patient included confluent and reticulated papillomatosis and poikilodermalike cutaneous amyloidosis, both easily excluded with histopathologic confirmation.

Local amyloidosis also was confirmed by crystal violet staining in our case and its etiology was uncertain. Generalized and local amyloidosis has been reported in association with lichen planus. The diagnosis of lichen planus was followed by the diagnosis of amyloidosis, and the typical skin lesions of these 2 conditions were able to be differentiated in these reported cases.^10,11 However, beltlike pigmentation was the only manifestation for our patient and we could not separate the 2 conditions with the naked eye.

Chronic irritation to the skin resulting in excessive production of degenerate keratins and their subsequent conversion into amyloid deposits has been proposed to be an etiologic factor of amyloidosis.¹¹ Because of the distribution pattern in our case, we believe focal amyloidosis could be attributed to chronic friction and scratching.

To the Editor:

A 68-year-old man presented with slightly itchy macules on the waist and abdomen of approximately 2 years’ duration. He reported that the initial lesions were dark red and subsequently coalesced to form a beltlike pigmentation on the abdomen. He denied any prior treatment, and the lesions did not spontaneously resolve. The patient was taking escitalopram oxalate, telmisartan, and aspirin for depression and cardiovascular disease that was diagnosed 3 years prior. He reported no exposure to UV radiation or a heat source. He denied use of any cosmetics on the body as well as a family history of similar symptoms.

Physical examination showed reticulate brown-purple macules with slight scale on the surface that had become confluent, forming a beltlike pigmentation on the waist and abdomen (Figure 1). Wickham striae were not seen. The oral mucosa and nails were not affected. Microscopic examination for fungal infections was negative.

Systematic physical and laboratory examinations revealed no abnormalities. A skin biopsy from a macule on the abdomen showed hyperkeratosis, thinned out stratum spinosum with flattening of rete ridges, hypergranulosis with vacuolar alteration of the basal cell layer, and bandlike infiltration of lymphocytes and melanophages with incontinence of pigment (Figure 2). Focalized purplish homogeneous deposits were observed in the upper dermis (Figure 3), of which positive crystal violet staining indicated amyloidosis (Figure 4). Congo red stain revealed amyloid deposition (Figure 5). Thus, the diagnosis of lichen planus pigmentosus (LPP) complicated with focal amyloidosis was made. The patient was treated with topical corticosteroids and tretinoin, and no notable therapeutic effects were observed at 3-month follow-up.

Lichen planus pigmentosus, a variant of lichen planus, is a condition of unknown etiology exhibiting dark brown macules and/or papules and a long clinical course. The face, neck, trunk, arms, and legs are the most common areas of presentation, whereas involvement of the scalp, nails, or oral mucosa is relatively rare.

The first clinicohistopathological study with a large sample size was documented by Bhutani et al¹ in 1974 who termed the currently recognized entity lichen planus pigmentosus. Lichen planus pigmentosus is a frequently encountered hyperpigmentation disorder in Indians, whereas sporadic cases also are reported in other regions and ethnicities.² In cases of LPP, the pigmentation is symmetrical, and its pattern most often is diffuse, then reticular, blotchy, and perifollicular.³ Two unique patterns of LPP have been documented, including linear/blaschkoid LPP and zosteriform LPP.^4,5 Our patient showed a unique beltlike distribution pattern.

The pathogenesis of LPP still is unclear, and several inciting factors such as mustard oil, gold therapy,⁶ and hepatitis C virus infection have been cited.⁷ Mancuso and Berdondini⁸ reported a case of LPP flaring immediately after relapse of nephrotic syndrome. It also has been considered as a paraneoplastic phenomen.⁹ No exact cause was found in our patient after a series of relative examinations.

The histopathologic changes associated with LPP consist of atrophic epidermis; bandlike lymphocytic infiltrate with vacuolar degeneration of the basal layer in the epidermis; and prominent melanin incontinence in the upper dermis, which can be diverse depending on different sites of skin biopsy and the phase of LPP. Histopathologic findings in our patient were consistent with LPP. The differential diagnosis for the reticulate pattern of pigmentation seen in our patient included confluent and reticulated papillomatosis and poikilodermalike cutaneous amyloidosis, both easily excluded with histopathologic confirmation.

Local amyloidosis also was confirmed by crystal violet staining in our case and its etiology was uncertain. Generalized and local amyloidosis has been reported in association with lichen planus. The diagnosis of lichen planus was followed by the diagnosis of amyloidosis, and the typical skin lesions of these 2 conditions were able to be differentiated in these reported cases.^10,11 However, beltlike pigmentation was the only manifestation for our patient and we could not separate the 2 conditions with the naked eye.

Chronic irritation to the skin resulting in excessive production of degenerate keratins and their subsequent conversion into amyloid deposits has been proposed to be an etiologic factor of amyloidosis.¹¹ Because of the distribution pattern in our case, we believe focal amyloidosis could be attributed to chronic friction and scratching.

To the Editor:

A 68-year-old man presented with slightly itchy macules on the waist and abdomen of approximately 2 years’ duration. He reported that the initial lesions were dark red and subsequently coalesced to form a beltlike pigmentation on the abdomen. He denied any prior treatment, and the lesions did not spontaneously resolve. The patient was taking escitalopram oxalate, telmisartan, and aspirin for depression and cardiovascular disease that was diagnosed 3 years prior. He reported no exposure to UV radiation or a heat source. He denied use of any cosmetics on the body as well as a family history of similar symptoms.

Physical examination showed reticulate brown-purple macules with slight scale on the surface that had become confluent, forming a beltlike pigmentation on the waist and abdomen (Figure 1). Wickham striae were not seen. The oral mucosa and nails were not affected. Microscopic examination for fungal infections was negative.

Systematic physical and laboratory examinations revealed no abnormalities. A skin biopsy from a macule on the abdomen showed hyperkeratosis, thinned out stratum spinosum with flattening of rete ridges, hypergranulosis with vacuolar alteration of the basal cell layer, and bandlike infiltration of lymphocytes and melanophages with incontinence of pigment (Figure 2). Focalized purplish homogeneous deposits were observed in the upper dermis (Figure 3), of which positive crystal violet staining indicated amyloidosis (Figure 4). Congo red stain revealed amyloid deposition (Figure 5). Thus, the diagnosis of lichen planus pigmentosus (LPP) complicated with focal amyloidosis was made. The patient was treated with topical corticosteroids and tretinoin, and no notable therapeutic effects were observed at 3-month follow-up.

Lichen planus pigmentosus, a variant of lichen planus, is a condition of unknown etiology exhibiting dark brown macules and/or papules and a long clinical course. The face, neck, trunk, arms, and legs are the most common areas of presentation, whereas involvement of the scalp, nails, or oral mucosa is relatively rare.

The first clinicohistopathological study with a large sample size was documented by Bhutani et al¹ in 1974 who termed the currently recognized entity lichen planus pigmentosus. Lichen planus pigmentosus is a frequently encountered hyperpigmentation disorder in Indians, whereas sporadic cases also are reported in other regions and ethnicities.² In cases of LPP, the pigmentation is symmetrical, and its pattern most often is diffuse, then reticular, blotchy, and perifollicular.³ Two unique patterns of LPP have been documented, including linear/blaschkoid LPP and zosteriform LPP.^4,5 Our patient showed a unique beltlike distribution pattern.

The pathogenesis of LPP still is unclear, and several inciting factors such as mustard oil, gold therapy,⁶ and hepatitis C virus infection have been cited.⁷ Mancuso and Berdondini⁸ reported a case of LPP flaring immediately after relapse of nephrotic syndrome. It also has been considered as a paraneoplastic phenomen.⁹ No exact cause was found in our patient after a series of relative examinations.

The histopathologic changes associated with LPP consist of atrophic epidermis; bandlike lymphocytic infiltrate with vacuolar degeneration of the basal layer in the epidermis; and prominent melanin incontinence in the upper dermis, which can be diverse depending on different sites of skin biopsy and the phase of LPP. Histopathologic findings in our patient were consistent with LPP. The differential diagnosis for the reticulate pattern of pigmentation seen in our patient included confluent and reticulated papillomatosis and poikilodermalike cutaneous amyloidosis, both easily excluded with histopathologic confirmation.

Local amyloidosis also was confirmed by crystal violet staining in our case and its etiology was uncertain. Generalized and local amyloidosis has been reported in association with lichen planus. The diagnosis of lichen planus was followed by the diagnosis of amyloidosis, and the typical skin lesions of these 2 conditions were able to be differentiated in these reported cases.^10,11 However, beltlike pigmentation was the only manifestation for our patient and we could not separate the 2 conditions with the naked eye.

Chronic irritation to the skin resulting in excessive production of degenerate keratins and their subsequent conversion into amyloid deposits has been proposed to be an etiologic factor of amyloidosis.¹¹ Because of the distribution pattern in our case, we believe focal amyloidosis could be attributed to chronic friction and scratching.