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The Diagnosis: Pachydermoperiostosis

Histopathology of the forehead punch biopsy demonstrated sebaceous hyperplasia with an occupation rate of greater than 40%, increased mucin, elastic fiber degeneration, and fibrosis. Pachydermia is graded from 0 to 3 depending on the degree of these changes; our patient met criteria for grade 3 pachydermia (Figure 1). Radiography revealed diffuse cortical thickening of the long bones that was most marked in the left femur (Figure 2); however, no other findings were demonstrative of Paget disease.

Pachydermoperiostosis (PDP)(also known as Touraine-Solente-Golé syndrome or primary hypertrophic osteoarthropathy) is a rare genetic condition that affects both the dermatologic and skeletal systems. Clinical features of the disease include progressive thickening and furrowing of the skin on the scalp and face (known as pachydermia), digital clubbing, and periostosis. Other potential cutaneous features include seborrhea, acne, hyperhidrosis of the palms and soles, cutis verticis gyrata, eczema, and a burning sensation of the hands and feet. Myelofibrosis and gastrointestinal abnormalities also have been reported.¹

The disease typically affects males (7:1 ratio); also, men typically display a more severe phenotype of the disease.² It most commonly begins during puberty and follows a generally progressive course of 5 to 20 years before eventually stabilizing. Both autosomal-dominant with incomplete penetrance and recessive inheritance versions of PDP can occur. Prostaglandin E₂ (PGE₂) has been implicated in the pathogenesis of PDP; PGE₂ is important in the inflammatory response and may evolve from disrupted protein degradation pathways.³ Sasaki et al⁴ additionally reported that the severity of pachydermia clinically and histologically appeared to correlate with the serum PGE₂ levels in affected patients. Prostaglandin E₂ causes a vasodilatory effect, perhaps explaining the clubbing observed in PDP, and also modifies the activity of osteoblasts and osteoclasts, causing the bone remodeling observed in the disease.⁴

In our patient, the initial differential diagnosis included PDP, as well as lepromatous leprosy, acromegaly, Paget disease of the bone, amyloidosis, scleromyxedema, and cutaneous T-cell lymphoma. However, the time course of the disease, lack of numerous symmetric thickened plaques and madarosis, and pathology argued against lepromatous leprosy. Acromegaly was ruled out due to lack of macroglossia as well as laboratory analysis within reference range including IGF-1 levels and thyroid function tests. Biopsy findings ultimately ruled out amyloidosis and cutaneous T-cell lymphoma. The bone scan revealed diffuse cortical thickening consistent with PDP, and there were no other radiologic findings suggestive of Paget disease. Pachydermoperiostosis is diagnosed using the Borochowitz criteria, which entails that 2 of the following 4 fulfillment criteria must be met: familial transmission, pachydermia, digital clubbing, and/or bony involvement with evidence of radiologic alterations or pain. Our patient met all 4 criteria. The clinical manifestations of PDP are variable with respect to skin and bone changes. The various clinical expressions include the complete form (ie, pachydermia, cutis verticis gyrata, periostosis), the incomplete form (ie, absence of cutis verticis gyrata), and forme fruste (ie, pachydermia with minimal or absent periostosis).⁵

Management for PDP involves surgical correction for cosmesis as well as for functional concerns if present. Symptoms secondary to periostosis should be managed with symptomatic treatment such as nonsteroidal antiinflammatory drugs. Patients managed with etoricoxib, a COX-2–selective nonsteroidal anti-inflammatory drug, have had normalized inflammatory markers that resulted in the lessening of forehead skin folds. Oral aescin has been shown to relieve joint pain due to its antiedematous effect.⁶ Our patient received treatment with nonsteroidal anti-inflammatory drugs for symptomatic management of the associated joint pain but unfortunately was lost to follow-up.

The Diagnosis: Pachydermoperiostosis

Histopathology of the forehead punch biopsy demonstrated sebaceous hyperplasia with an occupation rate of greater than 40%, increased mucin, elastic fiber degeneration, and fibrosis. Pachydermia is graded from 0 to 3 depending on the degree of these changes; our patient met criteria for grade 3 pachydermia (Figure 1). Radiography revealed diffuse cortical thickening of the long bones that was most marked in the left femur (Figure 2); however, no other findings were demonstrative of Paget disease.

Pachydermoperiostosis (PDP)(also known as Touraine-Solente-Golé syndrome or primary hypertrophic osteoarthropathy) is a rare genetic condition that affects both the dermatologic and skeletal systems. Clinical features of the disease include progressive thickening and furrowing of the skin on the scalp and face (known as pachydermia), digital clubbing, and periostosis. Other potential cutaneous features include seborrhea, acne, hyperhidrosis of the palms and soles, cutis verticis gyrata, eczema, and a burning sensation of the hands and feet. Myelofibrosis and gastrointestinal abnormalities also have been reported.¹

The disease typically affects males (7:1 ratio); also, men typically display a more severe phenotype of the disease.² It most commonly begins during puberty and follows a generally progressive course of 5 to 20 years before eventually stabilizing. Both autosomal-dominant with incomplete penetrance and recessive inheritance versions of PDP can occur. Prostaglandin E₂ (PGE₂) has been implicated in the pathogenesis of PDP; PGE₂ is important in the inflammatory response and may evolve from disrupted protein degradation pathways.³ Sasaki et al⁴ additionally reported that the severity of pachydermia clinically and histologically appeared to correlate with the serum PGE₂ levels in affected patients. Prostaglandin E₂ causes a vasodilatory effect, perhaps explaining the clubbing observed in PDP, and also modifies the activity of osteoblasts and osteoclasts, causing the bone remodeling observed in the disease.⁴

In our patient, the initial differential diagnosis included PDP, as well as lepromatous leprosy, acromegaly, Paget disease of the bone, amyloidosis, scleromyxedema, and cutaneous T-cell lymphoma. However, the time course of the disease, lack of numerous symmetric thickened plaques and madarosis, and pathology argued against lepromatous leprosy. Acromegaly was ruled out due to lack of macroglossia as well as laboratory analysis within reference range including IGF-1 levels and thyroid function tests. Biopsy findings ultimately ruled out amyloidosis and cutaneous T-cell lymphoma. The bone scan revealed diffuse cortical thickening consistent with PDP, and there were no other radiologic findings suggestive of Paget disease. Pachydermoperiostosis is diagnosed using the Borochowitz criteria, which entails that 2 of the following 4 fulfillment criteria must be met: familial transmission, pachydermia, digital clubbing, and/or bony involvement with evidence of radiologic alterations or pain. Our patient met all 4 criteria. The clinical manifestations of PDP are variable with respect to skin and bone changes. The various clinical expressions include the complete form (ie, pachydermia, cutis verticis gyrata, periostosis), the incomplete form (ie, absence of cutis verticis gyrata), and forme fruste (ie, pachydermia with minimal or absent periostosis).⁵

Management for PDP involves surgical correction for cosmesis as well as for functional concerns if present. Symptoms secondary to periostosis should be managed with symptomatic treatment such as nonsteroidal antiinflammatory drugs. Patients managed with etoricoxib, a COX-2–selective nonsteroidal anti-inflammatory drug, have had normalized inflammatory markers that resulted in the lessening of forehead skin folds. Oral aescin has been shown to relieve joint pain due to its antiedematous effect.⁶ Our patient received treatment with nonsteroidal anti-inflammatory drugs for symptomatic management of the associated joint pain but unfortunately was lost to follow-up.

The Diagnosis: Pachydermoperiostosis

Histopathology of the forehead punch biopsy demonstrated sebaceous hyperplasia with an occupation rate of greater than 40%, increased mucin, elastic fiber degeneration, and fibrosis. Pachydermia is graded from 0 to 3 depending on the degree of these changes; our patient met criteria for grade 3 pachydermia (Figure 1). Radiography revealed diffuse cortical thickening of the long bones that was most marked in the left femur (Figure 2); however, no other findings were demonstrative of Paget disease.

Pachydermoperiostosis (PDP)(also known as Touraine-Solente-Golé syndrome or primary hypertrophic osteoarthropathy) is a rare genetic condition that affects both the dermatologic and skeletal systems. Clinical features of the disease include progressive thickening and furrowing of the skin on the scalp and face (known as pachydermia), digital clubbing, and periostosis. Other potential cutaneous features include seborrhea, acne, hyperhidrosis of the palms and soles, cutis verticis gyrata, eczema, and a burning sensation of the hands and feet. Myelofibrosis and gastrointestinal abnormalities also have been reported.¹

The disease typically affects males (7:1 ratio); also, men typically display a more severe phenotype of the disease.² It most commonly begins during puberty and follows a generally progressive course of 5 to 20 years before eventually stabilizing. Both autosomal-dominant with incomplete penetrance and recessive inheritance versions of PDP can occur. Prostaglandin E₂ (PGE₂) has been implicated in the pathogenesis of PDP; PGE₂ is important in the inflammatory response and may evolve from disrupted protein degradation pathways.³ Sasaki et al⁴ additionally reported that the severity of pachydermia clinically and histologically appeared to correlate with the serum PGE₂ levels in affected patients. Prostaglandin E₂ causes a vasodilatory effect, perhaps explaining the clubbing observed in PDP, and also modifies the activity of osteoblasts and osteoclasts, causing the bone remodeling observed in the disease.⁴

In our patient, the initial differential diagnosis included PDP, as well as lepromatous leprosy, acromegaly, Paget disease of the bone, amyloidosis, scleromyxedema, and cutaneous T-cell lymphoma. However, the time course of the disease, lack of numerous symmetric thickened plaques and madarosis, and pathology argued against lepromatous leprosy. Acromegaly was ruled out due to lack of macroglossia as well as laboratory analysis within reference range including IGF-1 levels and thyroid function tests. Biopsy findings ultimately ruled out amyloidosis and cutaneous T-cell lymphoma. The bone scan revealed diffuse cortical thickening consistent with PDP, and there were no other radiologic findings suggestive of Paget disease. Pachydermoperiostosis is diagnosed using the Borochowitz criteria, which entails that 2 of the following 4 fulfillment criteria must be met: familial transmission, pachydermia, digital clubbing, and/or bony involvement with evidence of radiologic alterations or pain. Our patient met all 4 criteria. The clinical manifestations of PDP are variable with respect to skin and bone changes. The various clinical expressions include the complete form (ie, pachydermia, cutis verticis gyrata, periostosis), the incomplete form (ie, absence of cutis verticis gyrata), and forme fruste (ie, pachydermia with minimal or absent periostosis).⁵

Management for PDP involves surgical correction for cosmesis as well as for functional concerns if present. Symptoms secondary to periostosis should be managed with symptomatic treatment such as nonsteroidal antiinflammatory drugs. Patients managed with etoricoxib, a COX-2–selective nonsteroidal anti-inflammatory drug, have had normalized inflammatory markers that resulted in the lessening of forehead skin folds. Oral aescin has been shown to relieve joint pain due to its antiedematous effect.⁶ Our patient received treatment with nonsteroidal anti-inflammatory drugs for symptomatic management of the associated joint pain but unfortunately was lost to follow-up.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Plaque-type Syringoma

A biopsy demonstrated multiple basaloid islands of tumor cells in the reticular dermis with ductal differentiation, some with a commalike tail. The ducts were lined by 2 to 3 layers of small uniform cuboidal cells without atypia and contained inspissated secretions within the lumina of scattered ducts. There was an associated fibrotic collagenous stroma. There was no evidence of perineural invasion and no deep dermal or subcutaneous extension (Figure 1). Additional cytokeratin immunohistochemical staining highlighted the adnexal proliferation (Figure 2). A diagnosis of plaque-type syringoma (PTS) was made.

Syringomas are benign dermal sweat gland tumors that typically present as flesh-colored papules on the cheeks or periorbital area of young females. Plaque-type tumors as well as papulonodular, eruptive, disseminated, urticaria pigmentosa–like, lichen planus–like, or milialike syringomas also have been reported. Syringomas may be associated with certain medical conditions such as Down syndrome, Nicolau-Balus syndrome, and both scarring and nonscarring alopecias.¹ The clear cell variant of syringoma often is associated with diabetes mellitus.² Kikuchi et al³ first described PTS in 1979. Plaque-type syringomas rarely are reported in the literature, and sites of involvement include the head and neck region, upper lip, chest, upper extremities, vulva, penis, and scrotum.^4-6

Histologically, syringomatous lesions are composed of multiple small ducts lined by 2 to 3 layers of cuboidal epithelium. The ducts may be arranged in nests or strands of basaloid cells surrounded by a dense fibrotic stroma. Occasionally, the ducts will form a comma- or teardropshaped tail; however, this also may be observed in desmoplastic trichoepithelioma (DTE).⁷ Perineural invasion is absent in syringomas. Syringomas exhibit a lateral growth pattern that typically is limited to the upper half of the reticular dermis and spares the underlying subcutis, muscle, and bone. The growth pattern may be discontinuous with proliferations juxtaposed by normal-appearing skin.⁸ Syringomas usually express progesterone receptors and are known to proliferate at puberty, suggesting that these neoplasms are under hormonal control.⁹ Although syringomas are benign, various treatment options that may be pursued for cosmetic purposes include radiofrequency, staged excision, laser ablation, and oral isotretinoin.^8,10 If only a superficial biopsy is obtained, syringomas may display features of other adnexal neoplasms, including microcystic adnexal carcinoma (MAC), DTE, morpheaform basal cell carcinoma (BCC), and inflammatory linear verrucous epidermal nevus (ILVEN).

Microcystic adnexal carcinoma is a locally aggressive neoplasm first described by Goldstein et al¹¹ in 1982 an indurated, ill-defined plaque or nodule on the face with a predilection for the upper and lower lip. Prior radiation therapy and immunosuppression are risk factors for the development of MAC.¹² Histologically, the superficial portion displays small cornifying cysts interspersed with islands of basaloid cells and may mimic a syringoma. However, the deeper portions demonstrate ducts lined by a single layer of cells with a background of hyalinized and sclerotic stroma. The tumor cells may occupy the deep dermis and underlying subcutis, muscle, or bone and demonstrate an infiltrative growth pattern and perineural invasion. Treatment includes Mohs micrographic surgery.

Desmoplastic trichoepitheliomas most commonly present as solitary white to yellowish annular papules or plaques with a central dell located on sun-exposed areas of the face, cheeks, or chin. This benign neoplasm has a bimodal age distribution, primarily affecting females either in childhood or adulthood.¹³ Histologically, strands and nests of basaloid epithelial cells proliferate in a dense eosinophilic desmoplastic stroma. The basaloid islands are narrow and cordlike with growth parallel to the surface epidermis and do not dive deeply into the deep dermis or subcutis. Ductal differentiation with associated secretions typically is not seen in DTE.¹ Calcifications and foreign body granulomatous infiltrates may be present. Merkel cells also are present in this tumor and may be highlighted by immunohistochemistry with cytokeratin 20.¹⁴ Rarely, desmoplastic trichoepitheliomas may transform into trichoblastic carcinomas. Treatment may consist of surgical excision or Mohs micrographic surgery.

Morpheaform BCC also is included in the clinical and histopathologic differential diagnosis of infiltrative basaloid neoplasms. It is one of the more aggressive variants of BCC. The use of immunohistochemical staining may aid in differentiating between these sclerosing adnexal neoplasms.¹⁵ For example, pleckstrin homologylike domain family A member 1 (PHLDA1) is a stem cell marker that is heavily expressed in DTE as a specific follicular bulge marker but is not present in a morpheaform BCC. This highlights the follicular nature of DTEs at the molecular level. BerEP4 is a monoclonal antibody that serves as an epithelial marker for 2 glycopolypeptides: 34 and 39 kDa. This antibody may demonstrate positivity in morpheaform BCC but does not stain cells of interest in MAC.

Inflammatory linear verrucous epidermal nevus clinically presents with erythematous and warty papules in a linear distribution following the Blaschko lines. The papules often are reported to be intensely pruritic and usually are localized to one extremity.¹⁶ Although adultonset forms of ILVEN have been described,¹⁷ it most commonly is diagnosed in young children. Histologically, ILVEN consists of psoriasiform epidermal hyperplasia with alternating areas of parakeratosis and orthokeratosis with underlying agranulosis and hypergranulosis, respectively.¹⁸ The upper dermis contains a perivascular lymphocytic infiltrate. Treatment with laser therapy and surgical excision has led to both symptomatic and clinical improvement of ILVEN.¹⁶

Plaque-type syringomas are a rare variant of syringomas that clinically may mimic other common inflammatory and neoplastic conditions. An adequate biopsy is imperative to differentiate between adnexal neoplasms, as a small superficial biopsy of a syringoma may demonstrate features observed in other malignant or locally aggressive neoplasms. In our patient, the small ducts lined by cuboidal epithelium with no cellular atypia and no deep dermal growth or perineural invasion allowed for the diagnosis of PTS. Therapeutic options were reviewed with our patient, including oral isotretinoin, laser therapy, and staged excision. Ultimately, our patient elected not to pursue treatment, and she is being monitored clinically for any changes in appearance or symptoms.

The Diagnosis: Plaque-type Syringoma

A biopsy demonstrated multiple basaloid islands of tumor cells in the reticular dermis with ductal differentiation, some with a commalike tail. The ducts were lined by 2 to 3 layers of small uniform cuboidal cells without atypia and contained inspissated secretions within the lumina of scattered ducts. There was an associated fibrotic collagenous stroma. There was no evidence of perineural invasion and no deep dermal or subcutaneous extension (Figure 1). Additional cytokeratin immunohistochemical staining highlighted the adnexal proliferation (Figure 2). A diagnosis of plaque-type syringoma (PTS) was made.

Syringomas are benign dermal sweat gland tumors that typically present as flesh-colored papules on the cheeks or periorbital area of young females. Plaque-type tumors as well as papulonodular, eruptive, disseminated, urticaria pigmentosa–like, lichen planus–like, or milialike syringomas also have been reported. Syringomas may be associated with certain medical conditions such as Down syndrome, Nicolau-Balus syndrome, and both scarring and nonscarring alopecias.¹ The clear cell variant of syringoma often is associated with diabetes mellitus.² Kikuchi et al³ first described PTS in 1979. Plaque-type syringomas rarely are reported in the literature, and sites of involvement include the head and neck region, upper lip, chest, upper extremities, vulva, penis, and scrotum.^4-6

Histologically, syringomatous lesions are composed of multiple small ducts lined by 2 to 3 layers of cuboidal epithelium. The ducts may be arranged in nests or strands of basaloid cells surrounded by a dense fibrotic stroma. Occasionally, the ducts will form a comma- or teardropshaped tail; however, this also may be observed in desmoplastic trichoepithelioma (DTE).⁷ Perineural invasion is absent in syringomas. Syringomas exhibit a lateral growth pattern that typically is limited to the upper half of the reticular dermis and spares the underlying subcutis, muscle, and bone. The growth pattern may be discontinuous with proliferations juxtaposed by normal-appearing skin.⁸ Syringomas usually express progesterone receptors and are known to proliferate at puberty, suggesting that these neoplasms are under hormonal control.⁹ Although syringomas are benign, various treatment options that may be pursued for cosmetic purposes include radiofrequency, staged excision, laser ablation, and oral isotretinoin.^8,10 If only a superficial biopsy is obtained, syringomas may display features of other adnexal neoplasms, including microcystic adnexal carcinoma (MAC), DTE, morpheaform basal cell carcinoma (BCC), and inflammatory linear verrucous epidermal nevus (ILVEN).

Microcystic adnexal carcinoma is a locally aggressive neoplasm first described by Goldstein et al¹¹ in 1982 an indurated, ill-defined plaque or nodule on the face with a predilection for the upper and lower lip. Prior radiation therapy and immunosuppression are risk factors for the development of MAC.¹² Histologically, the superficial portion displays small cornifying cysts interspersed with islands of basaloid cells and may mimic a syringoma. However, the deeper portions demonstrate ducts lined by a single layer of cells with a background of hyalinized and sclerotic stroma. The tumor cells may occupy the deep dermis and underlying subcutis, muscle, or bone and demonstrate an infiltrative growth pattern and perineural invasion. Treatment includes Mohs micrographic surgery.

Desmoplastic trichoepitheliomas most commonly present as solitary white to yellowish annular papules or plaques with a central dell located on sun-exposed areas of the face, cheeks, or chin. This benign neoplasm has a bimodal age distribution, primarily affecting females either in childhood or adulthood.¹³ Histologically, strands and nests of basaloid epithelial cells proliferate in a dense eosinophilic desmoplastic stroma. The basaloid islands are narrow and cordlike with growth parallel to the surface epidermis and do not dive deeply into the deep dermis or subcutis. Ductal differentiation with associated secretions typically is not seen in DTE.¹ Calcifications and foreign body granulomatous infiltrates may be present. Merkel cells also are present in this tumor and may be highlighted by immunohistochemistry with cytokeratin 20.¹⁴ Rarely, desmoplastic trichoepitheliomas may transform into trichoblastic carcinomas. Treatment may consist of surgical excision or Mohs micrographic surgery.

Morpheaform BCC also is included in the clinical and histopathologic differential diagnosis of infiltrative basaloid neoplasms. It is one of the more aggressive variants of BCC. The use of immunohistochemical staining may aid in differentiating between these sclerosing adnexal neoplasms.¹⁵ For example, pleckstrin homologylike domain family A member 1 (PHLDA1) is a stem cell marker that is heavily expressed in DTE as a specific follicular bulge marker but is not present in a morpheaform BCC. This highlights the follicular nature of DTEs at the molecular level. BerEP4 is a monoclonal antibody that serves as an epithelial marker for 2 glycopolypeptides: 34 and 39 kDa. This antibody may demonstrate positivity in morpheaform BCC but does not stain cells of interest in MAC.

Inflammatory linear verrucous epidermal nevus clinically presents with erythematous and warty papules in a linear distribution following the Blaschko lines. The papules often are reported to be intensely pruritic and usually are localized to one extremity.¹⁶ Although adultonset forms of ILVEN have been described,¹⁷ it most commonly is diagnosed in young children. Histologically, ILVEN consists of psoriasiform epidermal hyperplasia with alternating areas of parakeratosis and orthokeratosis with underlying agranulosis and hypergranulosis, respectively.¹⁸ The upper dermis contains a perivascular lymphocytic infiltrate. Treatment with laser therapy and surgical excision has led to both symptomatic and clinical improvement of ILVEN.¹⁶

Plaque-type syringomas are a rare variant of syringomas that clinically may mimic other common inflammatory and neoplastic conditions. An adequate biopsy is imperative to differentiate between adnexal neoplasms, as a small superficial biopsy of a syringoma may demonstrate features observed in other malignant or locally aggressive neoplasms. In our patient, the small ducts lined by cuboidal epithelium with no cellular atypia and no deep dermal growth or perineural invasion allowed for the diagnosis of PTS. Therapeutic options were reviewed with our patient, including oral isotretinoin, laser therapy, and staged excision. Ultimately, our patient elected not to pursue treatment, and she is being monitored clinically for any changes in appearance or symptoms.

The Diagnosis: Plaque-type Syringoma

A biopsy demonstrated multiple basaloid islands of tumor cells in the reticular dermis with ductal differentiation, some with a commalike tail. The ducts were lined by 2 to 3 layers of small uniform cuboidal cells without atypia and contained inspissated secretions within the lumina of scattered ducts. There was an associated fibrotic collagenous stroma. There was no evidence of perineural invasion and no deep dermal or subcutaneous extension (Figure 1). Additional cytokeratin immunohistochemical staining highlighted the adnexal proliferation (Figure 2). A diagnosis of plaque-type syringoma (PTS) was made.

Syringomas are benign dermal sweat gland tumors that typically present as flesh-colored papules on the cheeks or periorbital area of young females. Plaque-type tumors as well as papulonodular, eruptive, disseminated, urticaria pigmentosa–like, lichen planus–like, or milialike syringomas also have been reported. Syringomas may be associated with certain medical conditions such as Down syndrome, Nicolau-Balus syndrome, and both scarring and nonscarring alopecias.¹ The clear cell variant of syringoma often is associated with diabetes mellitus.² Kikuchi et al³ first described PTS in 1979. Plaque-type syringomas rarely are reported in the literature, and sites of involvement include the head and neck region, upper lip, chest, upper extremities, vulva, penis, and scrotum.^4-6

Histologically, syringomatous lesions are composed of multiple small ducts lined by 2 to 3 layers of cuboidal epithelium. The ducts may be arranged in nests or strands of basaloid cells surrounded by a dense fibrotic stroma. Occasionally, the ducts will form a comma- or teardropshaped tail; however, this also may be observed in desmoplastic trichoepithelioma (DTE).⁷ Perineural invasion is absent in syringomas. Syringomas exhibit a lateral growth pattern that typically is limited to the upper half of the reticular dermis and spares the underlying subcutis, muscle, and bone. The growth pattern may be discontinuous with proliferations juxtaposed by normal-appearing skin.⁸ Syringomas usually express progesterone receptors and are known to proliferate at puberty, suggesting that these neoplasms are under hormonal control.⁹ Although syringomas are benign, various treatment options that may be pursued for cosmetic purposes include radiofrequency, staged excision, laser ablation, and oral isotretinoin.^8,10 If only a superficial biopsy is obtained, syringomas may display features of other adnexal neoplasms, including microcystic adnexal carcinoma (MAC), DTE, morpheaform basal cell carcinoma (BCC), and inflammatory linear verrucous epidermal nevus (ILVEN).

Microcystic adnexal carcinoma is a locally aggressive neoplasm first described by Goldstein et al¹¹ in 1982 an indurated, ill-defined plaque or nodule on the face with a predilection for the upper and lower lip. Prior radiation therapy and immunosuppression are risk factors for the development of MAC.¹² Histologically, the superficial portion displays small cornifying cysts interspersed with islands of basaloid cells and may mimic a syringoma. However, the deeper portions demonstrate ducts lined by a single layer of cells with a background of hyalinized and sclerotic stroma. The tumor cells may occupy the deep dermis and underlying subcutis, muscle, or bone and demonstrate an infiltrative growth pattern and perineural invasion. Treatment includes Mohs micrographic surgery.

Desmoplastic trichoepitheliomas most commonly present as solitary white to yellowish annular papules or plaques with a central dell located on sun-exposed areas of the face, cheeks, or chin. This benign neoplasm has a bimodal age distribution, primarily affecting females either in childhood or adulthood.¹³ Histologically, strands and nests of basaloid epithelial cells proliferate in a dense eosinophilic desmoplastic stroma. The basaloid islands are narrow and cordlike with growth parallel to the surface epidermis and do not dive deeply into the deep dermis or subcutis. Ductal differentiation with associated secretions typically is not seen in DTE.¹ Calcifications and foreign body granulomatous infiltrates may be present. Merkel cells also are present in this tumor and may be highlighted by immunohistochemistry with cytokeratin 20.¹⁴ Rarely, desmoplastic trichoepitheliomas may transform into trichoblastic carcinomas. Treatment may consist of surgical excision or Mohs micrographic surgery.

Morpheaform BCC also is included in the clinical and histopathologic differential diagnosis of infiltrative basaloid neoplasms. It is one of the more aggressive variants of BCC. The use of immunohistochemical staining may aid in differentiating between these sclerosing adnexal neoplasms.¹⁵ For example, pleckstrin homologylike domain family A member 1 (PHLDA1) is a stem cell marker that is heavily expressed in DTE as a specific follicular bulge marker but is not present in a morpheaform BCC. This highlights the follicular nature of DTEs at the molecular level. BerEP4 is a monoclonal antibody that serves as an epithelial marker for 2 glycopolypeptides: 34 and 39 kDa. This antibody may demonstrate positivity in morpheaform BCC but does not stain cells of interest in MAC.

Inflammatory linear verrucous epidermal nevus clinically presents with erythematous and warty papules in a linear distribution following the Blaschko lines. The papules often are reported to be intensely pruritic and usually are localized to one extremity.¹⁶ Although adultonset forms of ILVEN have been described,¹⁷ it most commonly is diagnosed in young children. Histologically, ILVEN consists of psoriasiform epidermal hyperplasia with alternating areas of parakeratosis and orthokeratosis with underlying agranulosis and hypergranulosis, respectively.¹⁸ The upper dermis contains a perivascular lymphocytic infiltrate. Treatment with laser therapy and surgical excision has led to both symptomatic and clinical improvement of ILVEN.¹⁶

Plaque-type syringomas are a rare variant of syringomas that clinically may mimic other common inflammatory and neoplastic conditions. An adequate biopsy is imperative to differentiate between adnexal neoplasms, as a small superficial biopsy of a syringoma may demonstrate features observed in other malignant or locally aggressive neoplasms. In our patient, the small ducts lined by cuboidal epithelium with no cellular atypia and no deep dermal growth or perineural invasion allowed for the diagnosis of PTS. Therapeutic options were reviewed with our patient, including oral isotretinoin, laser therapy, and staged excision. Ultimately, our patient elected not to pursue treatment, and she is being monitored clinically for any changes in appearance or symptoms.

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

The Diagnosis: Cutaneous Blastomycosis

A skin biopsy and fungal cultures confirmed the diagnosis of cutaneous blastomycosis. Grocott- Gomori methenamine-silver staining highlighted fungal organisms with refractile walls and broad-based budding consistent with cutaneous blastomycosis (Figure 1). The histopathologic specimen also demonstrated marked pseudoepitheliomatous hyperplasia (Figure 2A) with neutrophilic microabscesses (Figure 2B). Acid-fast bacillus and Fite staining were negative for bacterial organisms. A fungal culture was positive for Blastomyces dermatitidis. Urine and serum blastomycosis antigen were positive. Although Histoplasma serum antigen also was positive, this likely was from cross-reactivity. Chest radiography was negative for lung involvement, and the patient displayed no neurologic symptoms. He was started on oral itraconazole therapy for the treatment of cutaneous blastomycosis.

Blastomyces dermatitidis, the causative organism of blastomycosis, is endemic to the Ohio and Mississippi River valleys, Great Lakes region, and southeastern United States. It is a thermally dimorphic fungus found in soils that grows as a mold at 25 °C and yeast at 37 °C. Primary infection of the lungs—blastomycosis pneumonia—often is the only clinical manifestation¹; however, subsequent hematogenous dissemination to extrapulmonary sites such as the skin, bones, and genitourinary system can occur. Cutaneous blastomycosis, the most common extrapulmonary manifestation, typically follows pulmonary infection. In rare cases, it can occur from direct inoculation.^2,3 Skin lesions can occur anywhere but frequently are found on exposed surfaces of the head, neck, and extremities. Lesions classically present as verrucous crusting plaques with draining microabscesses. Violaceous nodules, ulcers, and pustules also may occur.¹

Diagnosis involves obtaining a thorough history of possible environmental exposures such as the patient’s geographic area of residence, occupation, and outdoor activities involving soil or decaying wood. Because blastomycosis can remain latent, remote exposures are relevant. Definitive diagnosis of cutaneous blastomycosis involves skin biopsy of the lesion with fungal culture, but the yeast’s distinctive thick wall and broad-based budding seen with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining provides a rapid presumptive diagnosis.³ Pseudoepitheliomatous hyperplasia and microabscesses also are characteristic features.² Urine antigen testing for a component of the polysaccharide cell wall has a sensitivity of 93% but a lower specificity of 79% due to cross-reactivity with histoplasmosis.⁴ Treatment consists of itraconazole for mild to moderate blastomycosis or amphotericin B for those with severe disease or central nervous system involvement or those who are immunosuppressed.¹

The differential diagnosis for our patient’s lesion included infectious vs neoplastic etiologies. Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, also is endemic to the Ohio and Mississippi River valleys. It is found in soil and droppings of some bats and birds such as chickens and pigeons. Similar to blastomycosis, the primary infection site most commonly is the lungs. It subsequently may disseminate to the skin or less commonly via direct inoculation of injured skin. It can present as papules, plaques, ulcers, purpura, or abscesses. Unlike blastomycosis, tissue biopsy of a cutaneous lesion reveals granuloma formation and distinctive oval, narrow-based budding yeast.⁵ Atypical mycobacteria are another source of infection to consider. For example, cutaneous Mycobacterium kansasii may present as papules and pustules forming verrucous or granulomatous plaques and ulceration. Histopathologic findings distinguishing mycobacterial infection from blastomycosis include granulomas and acid-fast bacilli in histiocytes.⁶

Noninfectious etiologies in the differential may include cutaneous squamous cell carcinoma or pemphigus vegetans. Squamous cell carcinoma may present with a broad range of clinical features—papules, plaques, or nodules with smooth, scaly, verrucous, or ulcerative secondary features all are possible presentations.⁷ Fairskinned individuals, such as our patient, would be at a higher risk in sun-damaged skin. Histologically, cutaneous squamous cell carcinoma is defined as an invasion of the dermis by neoplastic squamous epithelial cells in the form of cords, sheets, individual cells, nodules, or cystic structures.⁷ Pemphigus vegetans is the rarest variant of a group of autoimmune vesiculobullous diseases known as pemphigus. It can be differentiated from the most common variant—pemphigus vulgaris—by the presence of vegetative plaques in intertriginous areas. However, these verrucous vegetations can be misleading and make clinical diagnosis difficult. Histopathologic findings of hyperkeratosis, pseudoepitheliomatous hyperplasia, papillomatosis, and acantholysis with a suprabasal cleft would confirm the diagnosis.⁸

In summary, cutaneous blastomycosis classically presents as verrucous crusting plaques, as seen in our patient. It is important to conduct a thorough history for environmental exposures, but definitive diagnosis of cutaneous blastomycosis involves skin biopsy with fungal culture. Treatment depends on the severity of disease and organ involvement. Itraconazole would be appropriate for mild to moderate blastomycosis.

The Diagnosis: Cutaneous Blastomycosis

A skin biopsy and fungal cultures confirmed the diagnosis of cutaneous blastomycosis. Grocott- Gomori methenamine-silver staining highlighted fungal organisms with refractile walls and broad-based budding consistent with cutaneous blastomycosis (Figure 1). The histopathologic specimen also demonstrated marked pseudoepitheliomatous hyperplasia (Figure 2A) with neutrophilic microabscesses (Figure 2B). Acid-fast bacillus and Fite staining were negative for bacterial organisms. A fungal culture was positive for Blastomyces dermatitidis. Urine and serum blastomycosis antigen were positive. Although Histoplasma serum antigen also was positive, this likely was from cross-reactivity. Chest radiography was negative for lung involvement, and the patient displayed no neurologic symptoms. He was started on oral itraconazole therapy for the treatment of cutaneous blastomycosis.

Blastomyces dermatitidis, the causative organism of blastomycosis, is endemic to the Ohio and Mississippi River valleys, Great Lakes region, and southeastern United States. It is a thermally dimorphic fungus found in soils that grows as a mold at 25 °C and yeast at 37 °C. Primary infection of the lungs—blastomycosis pneumonia—often is the only clinical manifestation¹; however, subsequent hematogenous dissemination to extrapulmonary sites such as the skin, bones, and genitourinary system can occur. Cutaneous blastomycosis, the most common extrapulmonary manifestation, typically follows pulmonary infection. In rare cases, it can occur from direct inoculation.^2,3 Skin lesions can occur anywhere but frequently are found on exposed surfaces of the head, neck, and extremities. Lesions classically present as verrucous crusting plaques with draining microabscesses. Violaceous nodules, ulcers, and pustules also may occur.¹

Diagnosis involves obtaining a thorough history of possible environmental exposures such as the patient’s geographic area of residence, occupation, and outdoor activities involving soil or decaying wood. Because blastomycosis can remain latent, remote exposures are relevant. Definitive diagnosis of cutaneous blastomycosis involves skin biopsy of the lesion with fungal culture, but the yeast’s distinctive thick wall and broad-based budding seen with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining provides a rapid presumptive diagnosis.³ Pseudoepitheliomatous hyperplasia and microabscesses also are characteristic features.² Urine antigen testing for a component of the polysaccharide cell wall has a sensitivity of 93% but a lower specificity of 79% due to cross-reactivity with histoplasmosis.⁴ Treatment consists of itraconazole for mild to moderate blastomycosis or amphotericin B for those with severe disease or central nervous system involvement or those who are immunosuppressed.¹

The differential diagnosis for our patient’s lesion included infectious vs neoplastic etiologies. Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, also is endemic to the Ohio and Mississippi River valleys. It is found in soil and droppings of some bats and birds such as chickens and pigeons. Similar to blastomycosis, the primary infection site most commonly is the lungs. It subsequently may disseminate to the skin or less commonly via direct inoculation of injured skin. It can present as papules, plaques, ulcers, purpura, or abscesses. Unlike blastomycosis, tissue biopsy of a cutaneous lesion reveals granuloma formation and distinctive oval, narrow-based budding yeast.⁵ Atypical mycobacteria are another source of infection to consider. For example, cutaneous Mycobacterium kansasii may present as papules and pustules forming verrucous or granulomatous plaques and ulceration. Histopathologic findings distinguishing mycobacterial infection from blastomycosis include granulomas and acid-fast bacilli in histiocytes.⁶

Noninfectious etiologies in the differential may include cutaneous squamous cell carcinoma or pemphigus vegetans. Squamous cell carcinoma may present with a broad range of clinical features—papules, plaques, or nodules with smooth, scaly, verrucous, or ulcerative secondary features all are possible presentations.⁷ Fairskinned individuals, such as our patient, would be at a higher risk in sun-damaged skin. Histologically, cutaneous squamous cell carcinoma is defined as an invasion of the dermis by neoplastic squamous epithelial cells in the form of cords, sheets, individual cells, nodules, or cystic structures.⁷ Pemphigus vegetans is the rarest variant of a group of autoimmune vesiculobullous diseases known as pemphigus. It can be differentiated from the most common variant—pemphigus vulgaris—by the presence of vegetative plaques in intertriginous areas. However, these verrucous vegetations can be misleading and make clinical diagnosis difficult. Histopathologic findings of hyperkeratosis, pseudoepitheliomatous hyperplasia, papillomatosis, and acantholysis with a suprabasal cleft would confirm the diagnosis.⁸

In summary, cutaneous blastomycosis classically presents as verrucous crusting plaques, as seen in our patient. It is important to conduct a thorough history for environmental exposures, but definitive diagnosis of cutaneous blastomycosis involves skin biopsy with fungal culture. Treatment depends on the severity of disease and organ involvement. Itraconazole would be appropriate for mild to moderate blastomycosis.

The Diagnosis: Cutaneous Blastomycosis

A skin biopsy and fungal cultures confirmed the diagnosis of cutaneous blastomycosis. Grocott- Gomori methenamine-silver staining highlighted fungal organisms with refractile walls and broad-based budding consistent with cutaneous blastomycosis (Figure 1). The histopathologic specimen also demonstrated marked pseudoepitheliomatous hyperplasia (Figure 2A) with neutrophilic microabscesses (Figure 2B). Acid-fast bacillus and Fite staining were negative for bacterial organisms. A fungal culture was positive for Blastomyces dermatitidis. Urine and serum blastomycosis antigen were positive. Although Histoplasma serum antigen also was positive, this likely was from cross-reactivity. Chest radiography was negative for lung involvement, and the patient displayed no neurologic symptoms. He was started on oral itraconazole therapy for the treatment of cutaneous blastomycosis.

Blastomyces dermatitidis, the causative organism of blastomycosis, is endemic to the Ohio and Mississippi River valleys, Great Lakes region, and southeastern United States. It is a thermally dimorphic fungus found in soils that grows as a mold at 25 °C and yeast at 37 °C. Primary infection of the lungs—blastomycosis pneumonia—often is the only clinical manifestation¹; however, subsequent hematogenous dissemination to extrapulmonary sites such as the skin, bones, and genitourinary system can occur. Cutaneous blastomycosis, the most common extrapulmonary manifestation, typically follows pulmonary infection. In rare cases, it can occur from direct inoculation.^2,3 Skin lesions can occur anywhere but frequently are found on exposed surfaces of the head, neck, and extremities. Lesions classically present as verrucous crusting plaques with draining microabscesses. Violaceous nodules, ulcers, and pustules also may occur.¹

Diagnosis involves obtaining a thorough history of possible environmental exposures such as the patient’s geographic area of residence, occupation, and outdoor activities involving soil or decaying wood. Because blastomycosis can remain latent, remote exposures are relevant. Definitive diagnosis of cutaneous blastomycosis involves skin biopsy of the lesion with fungal culture, but the yeast’s distinctive thick wall and broad-based budding seen with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining provides a rapid presumptive diagnosis.³ Pseudoepitheliomatous hyperplasia and microabscesses also are characteristic features.² Urine antigen testing for a component of the polysaccharide cell wall has a sensitivity of 93% but a lower specificity of 79% due to cross-reactivity with histoplasmosis.⁴ Treatment consists of itraconazole for mild to moderate blastomycosis or amphotericin B for those with severe disease or central nervous system involvement or those who are immunosuppressed.¹

The differential diagnosis for our patient’s lesion included infectious vs neoplastic etiologies. Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, also is endemic to the Ohio and Mississippi River valleys. It is found in soil and droppings of some bats and birds such as chickens and pigeons. Similar to blastomycosis, the primary infection site most commonly is the lungs. It subsequently may disseminate to the skin or less commonly via direct inoculation of injured skin. It can present as papules, plaques, ulcers, purpura, or abscesses. Unlike blastomycosis, tissue biopsy of a cutaneous lesion reveals granuloma formation and distinctive oval, narrow-based budding yeast.⁵ Atypical mycobacteria are another source of infection to consider. For example, cutaneous Mycobacterium kansasii may present as papules and pustules forming verrucous or granulomatous plaques and ulceration. Histopathologic findings distinguishing mycobacterial infection from blastomycosis include granulomas and acid-fast bacilli in histiocytes.⁶

Noninfectious etiologies in the differential may include cutaneous squamous cell carcinoma or pemphigus vegetans. Squamous cell carcinoma may present with a broad range of clinical features—papules, plaques, or nodules with smooth, scaly, verrucous, or ulcerative secondary features all are possible presentations.⁷ Fairskinned individuals, such as our patient, would be at a higher risk in sun-damaged skin. Histologically, cutaneous squamous cell carcinoma is defined as an invasion of the dermis by neoplastic squamous epithelial cells in the form of cords, sheets, individual cells, nodules, or cystic structures.⁷ Pemphigus vegetans is the rarest variant of a group of autoimmune vesiculobullous diseases known as pemphigus. It can be differentiated from the most common variant—pemphigus vulgaris—by the presence of vegetative plaques in intertriginous areas. However, these verrucous vegetations can be misleading and make clinical diagnosis difficult. Histopathologic findings of hyperkeratosis, pseudoepitheliomatous hyperplasia, papillomatosis, and acantholysis with a suprabasal cleft would confirm the diagnosis.⁸

In summary, cutaneous blastomycosis classically presents as verrucous crusting plaques, as seen in our patient. It is important to conduct a thorough history for environmental exposures, but definitive diagnosis of cutaneous blastomycosis involves skin biopsy with fungal culture. Treatment depends on the severity of disease and organ involvement. Itraconazole would be appropriate for mild to moderate blastomycosis.

The Diagnosis: Tinea Corporis Bullosa

At the time of presentation, a potassium hydroxide (KOH) preparation, fungal culture, and punch biopsy of the right ventral wrist was performed. The KOH preparation was positive for fungal hyphae characteristic of dermatophyte infections. Histologically, the biopsy showed intraepidermal and subepidermal blisters with neutrophil- and lymphocyte-rich contents (Figure 1). Fungal hyphae and spores were present within the stratum corneum and superficial epidermis (Figure 2), and fungal cultures grew Microsporum canis. The extent of the rash (upper and lower extremities, chest, and back), positive fungal culture, and KOH preparation all supported the diagnosis of tinea corporis bullosa, which was confirmed with biopsy. Oral prednisone use was discouraged and triamcinolone ointment was discontinued given that inappropriate treatment with steroids in the setting of fungal infection suppresses an inflammatory response and alters clinical appearance, obviating the persistent underlying infection.

Tinea corporis bullosa is a rare superficial dermatophyte fungal infection that often is acquired by close personto- person contact or contact with domestic animals. The infection begins as a circular pruritic plaque, generally with raised borders, which may be erythematous or hyperpigmented. By definition, tinea corporis occurs in sites other than the face, feet, hands, or groin area. Bullae formation is thought to be secondary to a delayed hypersensitivity reaction provoked by the presence of a dermatophyte antigen.¹

Linear IgA bullous dermatosis is an immunemediated disease characterized by IgA deposition at the dermoepidermal junction. Linear IgA bullous dermatosis classically presents as widespread tense vesicles in an arciform or annular pattern. Mucosal involvement is common and typically presents with erosions, ulcerations, and scarring.² Given the absence of mucosal involvement in our patient and a positive KOH preparation, linear IgA bullous dermatosis was an unlikely diagnosis.

Benign inoculation lymphoreticulosis, more commonly known as cat scratch disease (CSD), is a Bartonella henselae infection that results from a cat scratch or bite. Cat scratch disease can present as localized cutaneous and nodal involvement (lymphadenopathy) near the site of inoculation, or it may present as disseminated disease. Cutaneous lesions generally progress through vesicular, erythematous, and papular phases. Regional lymphadenopathy proximal to the inoculation site is the hallmark of CSD.³ Given the absence of lymphadenopathy in our patient as well as the sporadic distribution of lesions, CSD was an unlikely diagnosis.

Dermatitis herpetiformis (DH) is an autoimmune disorder with cutaneous manifestations of gluten sensitivity. Dermatitis herpetiformis presents as extremely pruritic papules and vesicles arranged in groups on areas such as the elbows, dorsal aspects of the forearms, knees, scalp, back, and buttocks. Most patients with DH have celiac disease or small bowel disease related to gluten sensitivity.4 Given our patient’s acute presentation in adulthood and lack of gluten sensitivity, DH was an unlikely diagnosis.

Bullous fixed drug reaction is a cutaneous eruption that typically presents in the setting of exposure to an offending drug/agent. Drug reactions can have various cutaneous presentations, with the most common being pigmented macules that progress into plaques.⁵ Given the isolated nature of our patient’s episode and apparent lack of association with medication, bullous fixed drug reaction was an unlikely diagnosis.

Tinea corporis bullosa is a rare clinical variant of tinea corporis that has only been reported in patients with a history of contact with different animals. There are many causative organisms related to tinea corporis; Trichophyton rubrum is the most common etiology of tinea corporis, while tinea corporis due to close contact with domesticated animals often is caused by M canis.⁶ The immunoinhibitory properties of the mannans in the fungal cell wall allow the organisms to adhere to the skin prior to invasion. Cutaneous invasion into dead cornified layers of the skin is credited to the proteases, subtilisinlike proteases (subtilases), and keratinases produced by the fungus.¹ There are many different clinical presentations of tinea corporis due to the variability of causative organisms. An annular (ring-shaped) lesion with a central plaque and advancing border is the most typical presentation. Tinea corporis bullosa is characterized by the presence of bullae or vesicles in the borders of the scaly plaque. Rupture of the bullae subsequently leads to erosions and crusts over the plaque.

The diagnosis of tinea corporis bullosa often is clinical if the lesion is typical and can be confirmed using KOH preparation and fungal culture. Once the diagnosis is confirmed, topical antifungals are the standard treatment approach for localized superficial tinea corporis. Systemic antifungal treatment can be initiated if the lesion is extensive, recurrent, chronic, or unresponsive to topical treatment.¹ Given our patient’s characteristic presentation, she was managed with an over-the-counter topical antifungal (terbinafine). The patient’s lesions dramatically improved, rendering oral therapy unnecessary. At 1-month follow-up, the rash had nearly resolved.

The Diagnosis: Tinea Corporis Bullosa

At the time of presentation, a potassium hydroxide (KOH) preparation, fungal culture, and punch biopsy of the right ventral wrist was performed. The KOH preparation was positive for fungal hyphae characteristic of dermatophyte infections. Histologically, the biopsy showed intraepidermal and subepidermal blisters with neutrophil- and lymphocyte-rich contents (Figure 1). Fungal hyphae and spores were present within the stratum corneum and superficial epidermis (Figure 2), and fungal cultures grew Microsporum canis. The extent of the rash (upper and lower extremities, chest, and back), positive fungal culture, and KOH preparation all supported the diagnosis of tinea corporis bullosa, which was confirmed with biopsy. Oral prednisone use was discouraged and triamcinolone ointment was discontinued given that inappropriate treatment with steroids in the setting of fungal infection suppresses an inflammatory response and alters clinical appearance, obviating the persistent underlying infection.

Tinea corporis bullosa is a rare superficial dermatophyte fungal infection that often is acquired by close personto- person contact or contact with domestic animals. The infection begins as a circular pruritic plaque, generally with raised borders, which may be erythematous or hyperpigmented. By definition, tinea corporis occurs in sites other than the face, feet, hands, or groin area. Bullae formation is thought to be secondary to a delayed hypersensitivity reaction provoked by the presence of a dermatophyte antigen.¹

Linear IgA bullous dermatosis is an immunemediated disease characterized by IgA deposition at the dermoepidermal junction. Linear IgA bullous dermatosis classically presents as widespread tense vesicles in an arciform or annular pattern. Mucosal involvement is common and typically presents with erosions, ulcerations, and scarring.² Given the absence of mucosal involvement in our patient and a positive KOH preparation, linear IgA bullous dermatosis was an unlikely diagnosis.

Benign inoculation lymphoreticulosis, more commonly known as cat scratch disease (CSD), is a Bartonella henselae infection that results from a cat scratch or bite. Cat scratch disease can present as localized cutaneous and nodal involvement (lymphadenopathy) near the site of inoculation, or it may present as disseminated disease. Cutaneous lesions generally progress through vesicular, erythematous, and papular phases. Regional lymphadenopathy proximal to the inoculation site is the hallmark of CSD.³ Given the absence of lymphadenopathy in our patient as well as the sporadic distribution of lesions, CSD was an unlikely diagnosis.

Dermatitis herpetiformis (DH) is an autoimmune disorder with cutaneous manifestations of gluten sensitivity. Dermatitis herpetiformis presents as extremely pruritic papules and vesicles arranged in groups on areas such as the elbows, dorsal aspects of the forearms, knees, scalp, back, and buttocks. Most patients with DH have celiac disease or small bowel disease related to gluten sensitivity.4 Given our patient’s acute presentation in adulthood and lack of gluten sensitivity, DH was an unlikely diagnosis.

Bullous fixed drug reaction is a cutaneous eruption that typically presents in the setting of exposure to an offending drug/agent. Drug reactions can have various cutaneous presentations, with the most common being pigmented macules that progress into plaques.⁵ Given the isolated nature of our patient’s episode and apparent lack of association with medication, bullous fixed drug reaction was an unlikely diagnosis.

Tinea corporis bullosa is a rare clinical variant of tinea corporis that has only been reported in patients with a history of contact with different animals. There are many causative organisms related to tinea corporis; Trichophyton rubrum is the most common etiology of tinea corporis, while tinea corporis due to close contact with domesticated animals often is caused by M canis.⁶ The immunoinhibitory properties of the mannans in the fungal cell wall allow the organisms to adhere to the skin prior to invasion. Cutaneous invasion into dead cornified layers of the skin is credited to the proteases, subtilisinlike proteases (subtilases), and keratinases produced by the fungus.¹ There are many different clinical presentations of tinea corporis due to the variability of causative organisms. An annular (ring-shaped) lesion with a central plaque and advancing border is the most typical presentation. Tinea corporis bullosa is characterized by the presence of bullae or vesicles in the borders of the scaly plaque. Rupture of the bullae subsequently leads to erosions and crusts over the plaque.

The diagnosis of tinea corporis bullosa often is clinical if the lesion is typical and can be confirmed using KOH preparation and fungal culture. Once the diagnosis is confirmed, topical antifungals are the standard treatment approach for localized superficial tinea corporis. Systemic antifungal treatment can be initiated if the lesion is extensive, recurrent, chronic, or unresponsive to topical treatment.¹ Given our patient’s characteristic presentation, she was managed with an over-the-counter topical antifungal (terbinafine). The patient’s lesions dramatically improved, rendering oral therapy unnecessary. At 1-month follow-up, the rash had nearly resolved.

The Diagnosis: Tinea Corporis Bullosa

At the time of presentation, a potassium hydroxide (KOH) preparation, fungal culture, and punch biopsy of the right ventral wrist was performed. The KOH preparation was positive for fungal hyphae characteristic of dermatophyte infections. Histologically, the biopsy showed intraepidermal and subepidermal blisters with neutrophil- and lymphocyte-rich contents (Figure 1). Fungal hyphae and spores were present within the stratum corneum and superficial epidermis (Figure 2), and fungal cultures grew Microsporum canis. The extent of the rash (upper and lower extremities, chest, and back), positive fungal culture, and KOH preparation all supported the diagnosis of tinea corporis bullosa, which was confirmed with biopsy. Oral prednisone use was discouraged and triamcinolone ointment was discontinued given that inappropriate treatment with steroids in the setting of fungal infection suppresses an inflammatory response and alters clinical appearance, obviating the persistent underlying infection.

Tinea corporis bullosa is a rare superficial dermatophyte fungal infection that often is acquired by close personto- person contact or contact with domestic animals. The infection begins as a circular pruritic plaque, generally with raised borders, which may be erythematous or hyperpigmented. By definition, tinea corporis occurs in sites other than the face, feet, hands, or groin area. Bullae formation is thought to be secondary to a delayed hypersensitivity reaction provoked by the presence of a dermatophyte antigen.¹

Linear IgA bullous dermatosis is an immunemediated disease characterized by IgA deposition at the dermoepidermal junction. Linear IgA bullous dermatosis classically presents as widespread tense vesicles in an arciform or annular pattern. Mucosal involvement is common and typically presents with erosions, ulcerations, and scarring.² Given the absence of mucosal involvement in our patient and a positive KOH preparation, linear IgA bullous dermatosis was an unlikely diagnosis.

Benign inoculation lymphoreticulosis, more commonly known as cat scratch disease (CSD), is a Bartonella henselae infection that results from a cat scratch or bite. Cat scratch disease can present as localized cutaneous and nodal involvement (lymphadenopathy) near the site of inoculation, or it may present as disseminated disease. Cutaneous lesions generally progress through vesicular, erythematous, and papular phases. Regional lymphadenopathy proximal to the inoculation site is the hallmark of CSD.³ Given the absence of lymphadenopathy in our patient as well as the sporadic distribution of lesions, CSD was an unlikely diagnosis.

Dermatitis herpetiformis (DH) is an autoimmune disorder with cutaneous manifestations of gluten sensitivity. Dermatitis herpetiformis presents as extremely pruritic papules and vesicles arranged in groups on areas such as the elbows, dorsal aspects of the forearms, knees, scalp, back, and buttocks. Most patients with DH have celiac disease or small bowel disease related to gluten sensitivity.4 Given our patient’s acute presentation in adulthood and lack of gluten sensitivity, DH was an unlikely diagnosis.

Bullous fixed drug reaction is a cutaneous eruption that typically presents in the setting of exposure to an offending drug/agent. Drug reactions can have various cutaneous presentations, with the most common being pigmented macules that progress into plaques.⁵ Given the isolated nature of our patient’s episode and apparent lack of association with medication, bullous fixed drug reaction was an unlikely diagnosis.

Tinea corporis bullosa is a rare clinical variant of tinea corporis that has only been reported in patients with a history of contact with different animals. There are many causative organisms related to tinea corporis; Trichophyton rubrum is the most common etiology of tinea corporis, while tinea corporis due to close contact with domesticated animals often is caused by M canis.⁶ The immunoinhibitory properties of the mannans in the fungal cell wall allow the organisms to adhere to the skin prior to invasion. Cutaneous invasion into dead cornified layers of the skin is credited to the proteases, subtilisinlike proteases (subtilases), and keratinases produced by the fungus.¹ There are many different clinical presentations of tinea corporis due to the variability of causative organisms. An annular (ring-shaped) lesion with a central plaque and advancing border is the most typical presentation. Tinea corporis bullosa is characterized by the presence of bullae or vesicles in the borders of the scaly plaque. Rupture of the bullae subsequently leads to erosions and crusts over the plaque.

The diagnosis of tinea corporis bullosa often is clinical if the lesion is typical and can be confirmed using KOH preparation and fungal culture. Once the diagnosis is confirmed, topical antifungals are the standard treatment approach for localized superficial tinea corporis. Systemic antifungal treatment can be initiated if the lesion is extensive, recurrent, chronic, or unresponsive to topical treatment.¹ Given our patient’s characteristic presentation, she was managed with an over-the-counter topical antifungal (terbinafine). The patient’s lesions dramatically improved, rendering oral therapy unnecessary. At 1-month follow-up, the rash had nearly resolved.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

The Diagnosis: Lymphomatoid Papulosis

At the time of the initial visit, a punch biopsy was performed on the posterior shoulder girdle. Histopathology revealed mild epidermal spongiosis and acanthosis with associated parakeratosis and a dermal lymphocytic infiltrate with extravasated erythrocytes consistent with pityriasis rosea (Figure 1). Two weeks after the biopsy, the patient returned for suture removal and to discuss the biopsy results. The patient reported more evolving lesions despite completing the prescribed course of dicloxacillin. At this time, physical examination revealed the persistence of several reddishbrown papules along with new nodular lesions on the arms and thighs, some with central ulceration and crusting (Figure 2). A second biopsy of a nodular lesion on the right distal forearm was performed at this visit along with a superficial tissue culture, which was negative for bacterial or fungal elements. The biopsy revealed an atypical CD30⁺ lymphoid proliferation (Figure 3). These cells were strongly PD-L1 positive and also positive for CD3, CD4, and granzyme-B. Ki67 showed a high proliferation rate, and T-cell gene rearrangement studies were positive. Given these histologic findings and the clinical context of rapidly evolving skin lesions from small papules to nodular skin tumors, a diagnosis of lymphomatoid papulosis (LyP) was established.

Because of the notable pathologic discordance between the 2 biopsy specimens, re-evaluation of the initial specimen was requested. The initial biopsy was subsequently found to be CD30⁺ with an identical peak on gene rearrangement studies as the second biopsy, further validating the diagnosis of LyP (Figure 4). Our patient was offered low-dose methotrexate therapy but declined the treatment plan, as the skin lesions had begun to resolve.

Lymphomatoid papulosis is a chronic CD30⁺ lymphoproliferative disorder with a characteristic recurrent and self-remitting disease course.^1,2 Although it typically has a benign clinical course, it is histologically malignant and considered a low-grade variant of cutaneous T-cell lymphoma. ^2,3 The classic clinical presentation of LyP involves the presence of reddish-brown papules and nodules typically measuring less than 2.0 cm, which may show evidence of central ulceration, hemorrhage, necrosis, and/or crust formation.^1-5 It is characteristic that a patient may present with these skin lesions in different stages of evolution and that biopsies of these lesions may reflect different histologic features depending on the age of the lesion, making a definitive diagnosis more difficult to obtain if not clinically correlated.^1,2 Any part of the body may be involved; however, there appears to be a predilection for the trunk and extremities in most cases.^1-3,5 The skin eruptions usually are asymptomatic, but pruritus is a commonly associated concern.^1,2,4,5

Lymphomatoid papulosis can have a localized, clustered, or generalized distribution pattern and typically will spontaneously regress without treatment within 3 to 12 weeks of symptom onset.^2,3 Lymphomatoid papulosis has a slight male predominance with a male to female ratio of 1.5:1. It occurs most commonly between 35 and 45 years of age, though it can present at any age. The overall duration of the disease can range from months to decades.^2,3 Lymphomatoid papulosis makes up approximately 15% of all cutaneous T-cell lymphomas.^2,3 Although the overall prognosis is excellent, patients with LyP are at an increased risk of developing cutaneous or systemic lymphoma, most commonly mycosis fungoides, anaplastic large cell lymphoma, or Hodgkin lymphoma.^1-3 This increased lifelong risk is the reason that patients with LyP must be followed long-term every 6 to 12 months for surveillance of emerging malignancy.^1,2,6

The pathogenesis of LyP remains unknown. Some have hypothesized a possible viral trigger; however, there is insufficient data to support this theory.^2,6 A diagnostic hallmark of LyP is its CD30 positivity, which is a known marker for T-cell activation.6 The spontaneous regression of skin lesions that is characteristic of LyP is believed to involve the interactions between CD30 and its ligand (CD30L), which may contribute to apoptosis of neoplastic T cells.^2,3,6 With regards to the possible mechanisms contributing to tumor progression in LyP, a mutation in the transforming growth factor β receptor gene on CD30+ tumor cells within LyP lesions may allow for these cells to evade growth regulation and progress to lymphoma.^2,6 A large percentage of LyP biopsy specimens show evidence of T-cell receptor gene monoclonal rearrangement, which can aid in establishing a diagnosis.^1,2

The histologic features of LyP can vary greatly depending on the age of the lesion sampled.^1,2 Histologic subtypes of LyP have been established, with type A being the most common (approximately 75% of cases), displaying a wedge-shaped infiltrate of scattered or clustered, large, atypical CD30+ T cells.^1,2 Types B through E vary in histologic features, with the exception that all subtypes contain a CD30+ lymphocytic infiltrate.^2,3

Treatment of LyP depends on the symptom/disease burden that the patient is experiencing. For patients with a limited number of nonscarring skin lesions in areas that are not cosmetically sensitive, observation is recommended. ^1-3 For symptomatic patients with an extensive number of lesions, particularly those that may be scarring and/or in cosmetically sensitive areas, low-dose oral methotrexate therapy is considered first-line treatment.^1-4 A methotrexate dose of 5 to 20 mg weekly can be effective in reducing the number and severity of lesions, with duration of treatment depending on clinical response.^1,2 For patients who have contraindications to or who cannot tolerate oral methotrexate, phototherapy using psoralen plus UVA twice weekly for 6 to 8 weeks is another treatment option.^1,2 Topical corticosteroids also can be used in children or for patients experiencing substantial pruritus.^1,2,4 Oral or topical retinoids, topical carmustine or mechlorethamine, and brentuximab (an anti-CD30 monoclonal antibody) are all alternative therapies that have shown some beneficial effects.^1,2 In the event that any of the skin lesions do not spontaneously regress within a 3- to 12-week time frame, surgical excision or radiotherapy can be performed on those lesions.²

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is another CD30+ lymphoproliferative disorder with overlapping clinical and histopathological features of LyP. Recurrent crops of multiple lesions favor a diagnosis of LyP, whereas solitary lesions favor C-ALCL; however, multifocal C-ALCL cases may occur.² Mycosis fungoides is the most common type of cutaneous T-cell lymphoma that characteristically presents in a patch, plaque, tumor progression. Although mycosis fungoides eventually may transform into a CD30⁺ lymphoma, our patient did not display the characteristic clinical progression to suggest this diagnosis. Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica also fall into the spectrum of clonal T-cell cutaneous disorders that more commonly affect the pediatric population. Pityriasis lichenoides et varioliformis acuta has a marked CD8⁺ lymphocyte infiltrate, whereas pityriasis lichenoides chronica has more CD4⁺ lymphocytes. These disorders typically do not stain positive for CD30.²

All patients with a diagnosis of LyP should maintain lifelong, regular, 6- to 12-month follow-up visits to monitor disease status and screen for any evidence of developing malignancy.^1,2,6 A thorough review of clinical history, complete skin examination, and physical examination with a particular focus on detection of lymphadenopathy and hepatosplenomegaly should be included at every followup visit.1 Systemic symptoms such as fever, night sweats, or weight loss are not typical features of LyP; therefore, patients who begin to develop these symptoms should be promptly evaluated for systemic lymphoma.¹

The Diagnosis: Lymphomatoid Papulosis

At the time of the initial visit, a punch biopsy was performed on the posterior shoulder girdle. Histopathology revealed mild epidermal spongiosis and acanthosis with associated parakeratosis and a dermal lymphocytic infiltrate with extravasated erythrocytes consistent with pityriasis rosea (Figure 1). Two weeks after the biopsy, the patient returned for suture removal and to discuss the biopsy results. The patient reported more evolving lesions despite completing the prescribed course of dicloxacillin. At this time, physical examination revealed the persistence of several reddishbrown papules along with new nodular lesions on the arms and thighs, some with central ulceration and crusting (Figure 2). A second biopsy of a nodular lesion on the right distal forearm was performed at this visit along with a superficial tissue culture, which was negative for bacterial or fungal elements. The biopsy revealed an atypical CD30⁺ lymphoid proliferation (Figure 3). These cells were strongly PD-L1 positive and also positive for CD3, CD4, and granzyme-B. Ki67 showed a high proliferation rate, and T-cell gene rearrangement studies were positive. Given these histologic findings and the clinical context of rapidly evolving skin lesions from small papules to nodular skin tumors, a diagnosis of lymphomatoid papulosis (LyP) was established.

Because of the notable pathologic discordance between the 2 biopsy specimens, re-evaluation of the initial specimen was requested. The initial biopsy was subsequently found to be CD30⁺ with an identical peak on gene rearrangement studies as the second biopsy, further validating the diagnosis of LyP (Figure 4). Our patient was offered low-dose methotrexate therapy but declined the treatment plan, as the skin lesions had begun to resolve.

Lymphomatoid papulosis is a chronic CD30⁺ lymphoproliferative disorder with a characteristic recurrent and self-remitting disease course.^1,2 Although it typically has a benign clinical course, it is histologically malignant and considered a low-grade variant of cutaneous T-cell lymphoma. ^2,3 The classic clinical presentation of LyP involves the presence of reddish-brown papules and nodules typically measuring less than 2.0 cm, which may show evidence of central ulceration, hemorrhage, necrosis, and/or crust formation.^1-5 It is characteristic that a patient may present with these skin lesions in different stages of evolution and that biopsies of these lesions may reflect different histologic features depending on the age of the lesion, making a definitive diagnosis more difficult to obtain if not clinically correlated.^1,2 Any part of the body may be involved; however, there appears to be a predilection for the trunk and extremities in most cases.^1-3,5 The skin eruptions usually are asymptomatic, but pruritus is a commonly associated concern.^1,2,4,5

Lymphomatoid papulosis can have a localized, clustered, or generalized distribution pattern and typically will spontaneously regress without treatment within 3 to 12 weeks of symptom onset.^2,3 Lymphomatoid papulosis has a slight male predominance with a male to female ratio of 1.5:1. It occurs most commonly between 35 and 45 years of age, though it can present at any age. The overall duration of the disease can range from months to decades.^2,3 Lymphomatoid papulosis makes up approximately 15% of all cutaneous T-cell lymphomas.^2,3 Although the overall prognosis is excellent, patients with LyP are at an increased risk of developing cutaneous or systemic lymphoma, most commonly mycosis fungoides, anaplastic large cell lymphoma, or Hodgkin lymphoma.^1-3 This increased lifelong risk is the reason that patients with LyP must be followed long-term every 6 to 12 months for surveillance of emerging malignancy.^1,2,6

The pathogenesis of LyP remains unknown. Some have hypothesized a possible viral trigger; however, there is insufficient data to support this theory.^2,6 A diagnostic hallmark of LyP is its CD30 positivity, which is a known marker for T-cell activation.6 The spontaneous regression of skin lesions that is characteristic of LyP is believed to involve the interactions between CD30 and its ligand (CD30L), which may contribute to apoptosis of neoplastic T cells.^2,3,6 With regards to the possible mechanisms contributing to tumor progression in LyP, a mutation in the transforming growth factor β receptor gene on CD30+ tumor cells within LyP lesions may allow for these cells to evade growth regulation and progress to lymphoma.^2,6 A large percentage of LyP biopsy specimens show evidence of T-cell receptor gene monoclonal rearrangement, which can aid in establishing a diagnosis.^1,2

The histologic features of LyP can vary greatly depending on the age of the lesion sampled.^1,2 Histologic subtypes of LyP have been established, with type A being the most common (approximately 75% of cases), displaying a wedge-shaped infiltrate of scattered or clustered, large, atypical CD30+ T cells.^1,2 Types B through E vary in histologic features, with the exception that all subtypes contain a CD30+ lymphocytic infiltrate.^2,3

Treatment of LyP depends on the symptom/disease burden that the patient is experiencing. For patients with a limited number of nonscarring skin lesions in areas that are not cosmetically sensitive, observation is recommended. ^1-3 For symptomatic patients with an extensive number of lesions, particularly those that may be scarring and/or in cosmetically sensitive areas, low-dose oral methotrexate therapy is considered first-line treatment.^1-4 A methotrexate dose of 5 to 20 mg weekly can be effective in reducing the number and severity of lesions, with duration of treatment depending on clinical response.^1,2 For patients who have contraindications to or who cannot tolerate oral methotrexate, phototherapy using psoralen plus UVA twice weekly for 6 to 8 weeks is another treatment option.^1,2 Topical corticosteroids also can be used in children or for patients experiencing substantial pruritus.^1,2,4 Oral or topical retinoids, topical carmustine or mechlorethamine, and brentuximab (an anti-CD30 monoclonal antibody) are all alternative therapies that have shown some beneficial effects.^1,2 In the event that any of the skin lesions do not spontaneously regress within a 3- to 12-week time frame, surgical excision or radiotherapy can be performed on those lesions.²

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is another CD30+ lymphoproliferative disorder with overlapping clinical and histopathological features of LyP. Recurrent crops of multiple lesions favor a diagnosis of LyP, whereas solitary lesions favor C-ALCL; however, multifocal C-ALCL cases may occur.² Mycosis fungoides is the most common type of cutaneous T-cell lymphoma that characteristically presents in a patch, plaque, tumor progression. Although mycosis fungoides eventually may transform into a CD30⁺ lymphoma, our patient did not display the characteristic clinical progression to suggest this diagnosis. Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica also fall into the spectrum of clonal T-cell cutaneous disorders that more commonly affect the pediatric population. Pityriasis lichenoides et varioliformis acuta has a marked CD8⁺ lymphocyte infiltrate, whereas pityriasis lichenoides chronica has more CD4⁺ lymphocytes. These disorders typically do not stain positive for CD30.²

All patients with a diagnosis of LyP should maintain lifelong, regular, 6- to 12-month follow-up visits to monitor disease status and screen for any evidence of developing malignancy.^1,2,6 A thorough review of clinical history, complete skin examination, and physical examination with a particular focus on detection of lymphadenopathy and hepatosplenomegaly should be included at every followup visit.1 Systemic symptoms such as fever, night sweats, or weight loss are not typical features of LyP; therefore, patients who begin to develop these symptoms should be promptly evaluated for systemic lymphoma.¹

The Diagnosis: Lymphomatoid Papulosis

At the time of the initial visit, a punch biopsy was performed on the posterior shoulder girdle. Histopathology revealed mild epidermal spongiosis and acanthosis with associated parakeratosis and a dermal lymphocytic infiltrate with extravasated erythrocytes consistent with pityriasis rosea (Figure 1). Two weeks after the biopsy, the patient returned for suture removal and to discuss the biopsy results. The patient reported more evolving lesions despite completing the prescribed course of dicloxacillin. At this time, physical examination revealed the persistence of several reddishbrown papules along with new nodular lesions on the arms and thighs, some with central ulceration and crusting (Figure 2). A second biopsy of a nodular lesion on the right distal forearm was performed at this visit along with a superficial tissue culture, which was negative for bacterial or fungal elements. The biopsy revealed an atypical CD30⁺ lymphoid proliferation (Figure 3). These cells were strongly PD-L1 positive and also positive for CD3, CD4, and granzyme-B. Ki67 showed a high proliferation rate, and T-cell gene rearrangement studies were positive. Given these histologic findings and the clinical context of rapidly evolving skin lesions from small papules to nodular skin tumors, a diagnosis of lymphomatoid papulosis (LyP) was established.

Because of the notable pathologic discordance between the 2 biopsy specimens, re-evaluation of the initial specimen was requested. The initial biopsy was subsequently found to be CD30⁺ with an identical peak on gene rearrangement studies as the second biopsy, further validating the diagnosis of LyP (Figure 4). Our patient was offered low-dose methotrexate therapy but declined the treatment plan, as the skin lesions had begun to resolve.

Lymphomatoid papulosis is a chronic CD30⁺ lymphoproliferative disorder with a characteristic recurrent and self-remitting disease course.^1,2 Although it typically has a benign clinical course, it is histologically malignant and considered a low-grade variant of cutaneous T-cell lymphoma. ^2,3 The classic clinical presentation of LyP involves the presence of reddish-brown papules and nodules typically measuring less than 2.0 cm, which may show evidence of central ulceration, hemorrhage, necrosis, and/or crust formation.^1-5 It is characteristic that a patient may present with these skin lesions in different stages of evolution and that biopsies of these lesions may reflect different histologic features depending on the age of the lesion, making a definitive diagnosis more difficult to obtain if not clinically correlated.^1,2 Any part of the body may be involved; however, there appears to be a predilection for the trunk and extremities in most cases.^1-3,5 The skin eruptions usually are asymptomatic, but pruritus is a commonly associated concern.^1,2,4,5

Lymphomatoid papulosis can have a localized, clustered, or generalized distribution pattern and typically will spontaneously regress without treatment within 3 to 12 weeks of symptom onset.^2,3 Lymphomatoid papulosis has a slight male predominance with a male to female ratio of 1.5:1. It occurs most commonly between 35 and 45 years of age, though it can present at any age. The overall duration of the disease can range from months to decades.^2,3 Lymphomatoid papulosis makes up approximately 15% of all cutaneous T-cell lymphomas.^2,3 Although the overall prognosis is excellent, patients with LyP are at an increased risk of developing cutaneous or systemic lymphoma, most commonly mycosis fungoides, anaplastic large cell lymphoma, or Hodgkin lymphoma.^1-3 This increased lifelong risk is the reason that patients with LyP must be followed long-term every 6 to 12 months for surveillance of emerging malignancy.^1,2,6

The pathogenesis of LyP remains unknown. Some have hypothesized a possible viral trigger; however, there is insufficient data to support this theory.^2,6 A diagnostic hallmark of LyP is its CD30 positivity, which is a known marker for T-cell activation.6 The spontaneous regression of skin lesions that is characteristic of LyP is believed to involve the interactions between CD30 and its ligand (CD30L), which may contribute to apoptosis of neoplastic T cells.^2,3,6 With regards to the possible mechanisms contributing to tumor progression in LyP, a mutation in the transforming growth factor β receptor gene on CD30+ tumor cells within LyP lesions may allow for these cells to evade growth regulation and progress to lymphoma.^2,6 A large percentage of LyP biopsy specimens show evidence of T-cell receptor gene monoclonal rearrangement, which can aid in establishing a diagnosis.^1,2

The histologic features of LyP can vary greatly depending on the age of the lesion sampled.^1,2 Histologic subtypes of LyP have been established, with type A being the most common (approximately 75% of cases), displaying a wedge-shaped infiltrate of scattered or clustered, large, atypical CD30+ T cells.^1,2 Types B through E vary in histologic features, with the exception that all subtypes contain a CD30+ lymphocytic infiltrate.^2,3

Treatment of LyP depends on the symptom/disease burden that the patient is experiencing. For patients with a limited number of nonscarring skin lesions in areas that are not cosmetically sensitive, observation is recommended. ^1-3 For symptomatic patients with an extensive number of lesions, particularly those that may be scarring and/or in cosmetically sensitive areas, low-dose oral methotrexate therapy is considered first-line treatment.^1-4 A methotrexate dose of 5 to 20 mg weekly can be effective in reducing the number and severity of lesions, with duration of treatment depending on clinical response.^1,2 For patients who have contraindications to or who cannot tolerate oral methotrexate, phototherapy using psoralen plus UVA twice weekly for 6 to 8 weeks is another treatment option.^1,2 Topical corticosteroids also can be used in children or for patients experiencing substantial pruritus.^1,2,4 Oral or topical retinoids, topical carmustine or mechlorethamine, and brentuximab (an anti-CD30 monoclonal antibody) are all alternative therapies that have shown some beneficial effects.^1,2 In the event that any of the skin lesions do not spontaneously regress within a 3- to 12-week time frame, surgical excision or radiotherapy can be performed on those lesions.²

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is another CD30+ lymphoproliferative disorder with overlapping clinical and histopathological features of LyP. Recurrent crops of multiple lesions favor a diagnosis of LyP, whereas solitary lesions favor C-ALCL; however, multifocal C-ALCL cases may occur.² Mycosis fungoides is the most common type of cutaneous T-cell lymphoma that characteristically presents in a patch, plaque, tumor progression. Although mycosis fungoides eventually may transform into a CD30⁺ lymphoma, our patient did not display the characteristic clinical progression to suggest this diagnosis. Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica also fall into the spectrum of clonal T-cell cutaneous disorders that more commonly affect the pediatric population. Pityriasis lichenoides et varioliformis acuta has a marked CD8⁺ lymphocyte infiltrate, whereas pityriasis lichenoides chronica has more CD4⁺ lymphocytes. These disorders typically do not stain positive for CD30.²

All patients with a diagnosis of LyP should maintain lifelong, regular, 6- to 12-month follow-up visits to monitor disease status and screen for any evidence of developing malignancy.^1,2,6 A thorough review of clinical history, complete skin examination, and physical examination with a particular focus on detection of lymphadenopathy and hepatosplenomegaly should be included at every followup visit.1 Systemic symptoms such as fever, night sweats, or weight loss are not typical features of LyP; therefore, patients who begin to develop these symptoms should be promptly evaluated for systemic lymphoma.¹

The Diagnosis: Granuloma Annulare

A biopsy of a lesion on the right flank demonstrated granulomatous inflammation and interstitial mucin (Figure), characteristic of granuloma annulare (GA).^1,2 Granuloma annulare is a relatively common skin disorder with an unknown etiology. It typically presents as smooth, annular, erythematous plaques.¹ The most common variants of GA are localized, generalized, and subcutaneous. Our case demonstrated Wolf isotopic response, an unrelated skin disease that forms at the same location as a previously healed skin lesion.² It is important to be aware of this phenomenon so that it is not confused with a recurrence of herpes zoster virus (HZV).

Although relatively infrequent, GA is the most common isotopic response following HZV infections.^3-5 Other postherpetic isotopic eruptions include cutaneous malignancies, lichen planus, sarcoidosis, morphea, reactive perforating collagenosis, psoriasis, and infections, among others.^3,5,6 The time between HZV infection and GA can be variable, ranging from a few weeks to many years apart.³

Oftentimes GA will spontaneously resolve within 2 years; however, recurrence is common.^7-9 There currently are no standard treatment guidelines. The most promising treatment options include intralesional or topical glucocorticoids for localized GA as well as phototherapy or hydroxychloroquine for widespread disease.^8,10  

Annular elastolytic giant cell granuloma (also called actinic granuloma) is a rare idiopathic inflammatory skin disease. It is characterized by erythematous annular papules or plaques mainly found on sun-exposed skin, such as the backs of the hands, forearms, or face.^11,12 Therefore, based on the distribution of our patient’s lesions, annular elastolytic giant cell granuloma was an unlikely diagnosis. Furthermore, it is not a known postherpetic isotopic reaction. Annular elastolytic giant cell granuloma can appear histologically similar to GA. Differentiating histologic features include a nonpalisading granuloma as well as the absence of mucin and necrobiosis.¹²

Annular lichen planus is a long-recognized but uncommon clinical variant of lichen planus that typically presents as pruritic, purple, annular plaques on the penis, scrotum, or intertriginous areas.¹³ The violaceous coloring is more characteristic of lichen planus. Histology is helpful in differentiating from GA.

Nummular eczema presents as scattered, welldefined, pruritic, erythematous, coin-shaped, coin-sized plaques in patients with diffusely dry skin.¹⁴ The scaling and serous crusting as well as more prominent pruritus help distinguish it from GA. The appearance of nummular eczema is quite characteristic; therefore, a biopsy typically is unnecessary for diagnosis. However, a potassium hydroxide wet mount examination of a skin scraping should be performed if tinea corporis also is suspected.

Superficial erythema annulare centrifugum classically presents as an annular or arciform pruritic lesion with an advancing outer erythematous edge with an inner rim of scale that most commonly occurs on the lower extremities. ¹⁵ The presence of pruritus and trailing scale helps distinguish this lesion from GA. Histologically, there are epidermal changes of hyperplasia, spongiosis, and parakeratosis, as well as lymphohistiocytic infiltrate surrounding the superficial dermal vessels^.16

We report this case to highlight GA as the most common postherpetic isotopic response. It should be on the differential diagnosis when a patient presents with erythematous, smooth, annular plaques occurring in the distribution of a resolved case of HZV.

The Diagnosis: Granuloma Annulare

A biopsy of a lesion on the right flank demonstrated granulomatous inflammation and interstitial mucin (Figure), characteristic of granuloma annulare (GA).^1,2 Granuloma annulare is a relatively common skin disorder with an unknown etiology. It typically presents as smooth, annular, erythematous plaques.¹ The most common variants of GA are localized, generalized, and subcutaneous. Our case demonstrated Wolf isotopic response, an unrelated skin disease that forms at the same location as a previously healed skin lesion.² It is important to be aware of this phenomenon so that it is not confused with a recurrence of herpes zoster virus (HZV).

Although relatively infrequent, GA is the most common isotopic response following HZV infections.^3-5 Other postherpetic isotopic eruptions include cutaneous malignancies, lichen planus, sarcoidosis, morphea, reactive perforating collagenosis, psoriasis, and infections, among others.^3,5,6 The time between HZV infection and GA can be variable, ranging from a few weeks to many years apart.³

Oftentimes GA will spontaneously resolve within 2 years; however, recurrence is common.^7-9 There currently are no standard treatment guidelines. The most promising treatment options include intralesional or topical glucocorticoids for localized GA as well as phototherapy or hydroxychloroquine for widespread disease.^8,10  

Annular elastolytic giant cell granuloma (also called actinic granuloma) is a rare idiopathic inflammatory skin disease. It is characterized by erythematous annular papules or plaques mainly found on sun-exposed skin, such as the backs of the hands, forearms, or face.^11,12 Therefore, based on the distribution of our patient’s lesions, annular elastolytic giant cell granuloma was an unlikely diagnosis. Furthermore, it is not a known postherpetic isotopic reaction. Annular elastolytic giant cell granuloma can appear histologically similar to GA. Differentiating histologic features include a nonpalisading granuloma as well as the absence of mucin and necrobiosis.¹²

Annular lichen planus is a long-recognized but uncommon clinical variant of lichen planus that typically presents as pruritic, purple, annular plaques on the penis, scrotum, or intertriginous areas.¹³ The violaceous coloring is more characteristic of lichen planus. Histology is helpful in differentiating from GA.

Nummular eczema presents as scattered, welldefined, pruritic, erythematous, coin-shaped, coin-sized plaques in patients with diffusely dry skin.¹⁴ The scaling and serous crusting as well as more prominent pruritus help distinguish it from GA. The appearance of nummular eczema is quite characteristic; therefore, a biopsy typically is unnecessary for diagnosis. However, a potassium hydroxide wet mount examination of a skin scraping should be performed if tinea corporis also is suspected.

Superficial erythema annulare centrifugum classically presents as an annular or arciform pruritic lesion with an advancing outer erythematous edge with an inner rim of scale that most commonly occurs on the lower extremities. ¹⁵ The presence of pruritus and trailing scale helps distinguish this lesion from GA. Histologically, there are epidermal changes of hyperplasia, spongiosis, and parakeratosis, as well as lymphohistiocytic infiltrate surrounding the superficial dermal vessels^.16

We report this case to highlight GA as the most common postherpetic isotopic response. It should be on the differential diagnosis when a patient presents with erythematous, smooth, annular plaques occurring in the distribution of a resolved case of HZV.

The Diagnosis: Granuloma Annulare

A biopsy of a lesion on the right flank demonstrated granulomatous inflammation and interstitial mucin (Figure), characteristic of granuloma annulare (GA).^1,2 Granuloma annulare is a relatively common skin disorder with an unknown etiology. It typically presents as smooth, annular, erythematous plaques.¹ The most common variants of GA are localized, generalized, and subcutaneous. Our case demonstrated Wolf isotopic response, an unrelated skin disease that forms at the same location as a previously healed skin lesion.² It is important to be aware of this phenomenon so that it is not confused with a recurrence of herpes zoster virus (HZV).

Although relatively infrequent, GA is the most common isotopic response following HZV infections.^3-5 Other postherpetic isotopic eruptions include cutaneous malignancies, lichen planus, sarcoidosis, morphea, reactive perforating collagenosis, psoriasis, and infections, among others.^3,5,6 The time between HZV infection and GA can be variable, ranging from a few weeks to many years apart.³

Oftentimes GA will spontaneously resolve within 2 years; however, recurrence is common.^7-9 There currently are no standard treatment guidelines. The most promising treatment options include intralesional or topical glucocorticoids for localized GA as well as phototherapy or hydroxychloroquine for widespread disease.^8,10  

Annular elastolytic giant cell granuloma (also called actinic granuloma) is a rare idiopathic inflammatory skin disease. It is characterized by erythematous annular papules or plaques mainly found on sun-exposed skin, such as the backs of the hands, forearms, or face.^11,12 Therefore, based on the distribution of our patient’s lesions, annular elastolytic giant cell granuloma was an unlikely diagnosis. Furthermore, it is not a known postherpetic isotopic reaction. Annular elastolytic giant cell granuloma can appear histologically similar to GA. Differentiating histologic features include a nonpalisading granuloma as well as the absence of mucin and necrobiosis.¹²

Annular lichen planus is a long-recognized but uncommon clinical variant of lichen planus that typically presents as pruritic, purple, annular plaques on the penis, scrotum, or intertriginous areas.¹³ The violaceous coloring is more characteristic of lichen planus. Histology is helpful in differentiating from GA.

Nummular eczema presents as scattered, welldefined, pruritic, erythematous, coin-shaped, coin-sized plaques in patients with diffusely dry skin.¹⁴ The scaling and serous crusting as well as more prominent pruritus help distinguish it from GA. The appearance of nummular eczema is quite characteristic; therefore, a biopsy typically is unnecessary for diagnosis. However, a potassium hydroxide wet mount examination of a skin scraping should be performed if tinea corporis also is suspected.

Superficial erythema annulare centrifugum classically presents as an annular or arciform pruritic lesion with an advancing outer erythematous edge with an inner rim of scale that most commonly occurs on the lower extremities. ¹⁵ The presence of pruritus and trailing scale helps distinguish this lesion from GA. Histologically, there are epidermal changes of hyperplasia, spongiosis, and parakeratosis, as well as lymphohistiocytic infiltrate surrounding the superficial dermal vessels^.16

We report this case to highlight GA as the most common postherpetic isotopic response. It should be on the differential diagnosis when a patient presents with erythematous, smooth, annular plaques occurring in the distribution of a resolved case of HZV.

The Diagnosis: Chromoblastomycosis

This case highlights the importance of routine skin biopsy and tissue culture when clinical suspicion for mycotic infection is high. Despite nonspecific biopsy results (Figure), a diagnosis of chromoblastomycosis (CBM) was reached based on tissue culture. Surgical excision was not possible in our patient due to the size and location of the lesion. The patient was referred to infectious disease, with the plan to start long-term itraconazole for at least 6 to 12 months.

Cases of CBM were first documented in 1914 and distinguished by the appearance of spherical, brown, muriform cells on skin biopsy—features that now serve as the hallmark of CBM diagnoses.^1,2 The implantation mycosis commonly is caused by agents such as Fonsecaea pedrosoi and Fonsecaea monophora of the bantiana-clade, as classified according to molecular phylogeny²; these agents have been isolated from soil, plants, and wood sources in tropical and subtropical regions and are strongly associated with agricultural activities.³

Chromoblastomycosis lesions tend to be asymptomatic with a variable amount of time between inoculation and lesion presentation, delaying medical care by months to years.³ The fungus causes a granulomatous reaction after skin damage, with noticeable pseudoepitheliomatous hyperplasia of the epidermis and granulomas formed by epithelioid and Langerhans cells in the dermis.⁴ Typically, CBM initially presents as an erythematous macular skin lesion, which then progresses to become more pink, papular, and sometimes pruritic.² Muriform (sclerotic) bodies, which reflect fungal components, extrude transepidermally and appear as black dots on the lesion’s surface.⁴ Chromoblastomycosis is limited to the subcutaneous tissue and has been classified into 5 types of lesions: nodular, tumoral, verrucous, scarring, and plaque.² Diagnosis is established using fungal tests such as potassium hydroxide direct microscopy, which exposes muriform bodies often in combination with dematiaceous hyphae, while fungal culture of F pedrosoi in Sabouraud agar produces velvety dark colonies.³ Although an immune response to CBM infection remains unclear, it has been demonstrated that the response differs based on the severity of the infection. The severe form of CBM produces high levels of IL-10, low levels of IFN-γ, and inefficient T-cell proliferation, while milder forms of CBM display low levels of IL-10, high levels of IFN-γ, and efficient T-cell proliferation.⁵ Complications of CBM include chronic lymphedema, ankylosis, and secondary bacterial infections, which largely are observed in advanced cases; malignant transformation to squamous cell carcinoma, though rare, also has been observed.⁶

Several therapeutic methods have been implemented in the treatment of CBM, but lesions often remain refractory, especially in advanced cases.⁶ Approaches to treatment can be divided into antifungal and physical methods. Commonly employed antifungal agents include itraconazole and terbinafine, which must be taken daily for a period ranging from 6 months to 1 year or longer; flucytosine with or without amphotericin also has been employed.⁴ Among the physical methods, surgical excision is not suggested due to possible dissemination of disease; other options include cryotherapy, thermotherapy, and laser vaporization.⁶ The prognosis has improved since the use of extended-spectrum triazoles, but high rates of refractory disease remain unchanged.²

The differential diagnosis includes other infections. Nocardiosis is a bacterial infection in which cutaneous disease can result in actinomycetoma, which presents with grains that are small, round, and stain blue on hematoxylin and eosin with eosinophilic rays at the periphery.⁷ Although the clinical features and pseudoepitheliomatous hyperplasia seen in CBM can mimic squamous cell carcinoma, the latter would show variable degrees of differentiation, keratinization, nuclear atypia, and architectural atypia with a negative tissue culture.⁸ Eumycetoma is a fungal infection that typically is not caused by F pedrosoi but rather most commonly Madurella mycetomatis.⁹ Leishmaniasis is a parasitic infection in which a biopsy of cutaneous lesions often displays parasite-filled histiocytes.¹⁰

The Diagnosis: Chromoblastomycosis

This case highlights the importance of routine skin biopsy and tissue culture when clinical suspicion for mycotic infection is high. Despite nonspecific biopsy results (Figure), a diagnosis of chromoblastomycosis (CBM) was reached based on tissue culture. Surgical excision was not possible in our patient due to the size and location of the lesion. The patient was referred to infectious disease, with the plan to start long-term itraconazole for at least 6 to 12 months.

Cases of CBM were first documented in 1914 and distinguished by the appearance of spherical, brown, muriform cells on skin biopsy—features that now serve as the hallmark of CBM diagnoses.^1,2 The implantation mycosis commonly is caused by agents such as Fonsecaea pedrosoi and Fonsecaea monophora of the bantiana-clade, as classified according to molecular phylogeny²; these agents have been isolated from soil, plants, and wood sources in tropical and subtropical regions and are strongly associated with agricultural activities.³

Chromoblastomycosis lesions tend to be asymptomatic with a variable amount of time between inoculation and lesion presentation, delaying medical care by months to years.³ The fungus causes a granulomatous reaction after skin damage, with noticeable pseudoepitheliomatous hyperplasia of the epidermis and granulomas formed by epithelioid and Langerhans cells in the dermis.⁴ Typically, CBM initially presents as an erythematous macular skin lesion, which then progresses to become more pink, papular, and sometimes pruritic.² Muriform (sclerotic) bodies, which reflect fungal components, extrude transepidermally and appear as black dots on the lesion’s surface.⁴ Chromoblastomycosis is limited to the subcutaneous tissue and has been classified into 5 types of lesions: nodular, tumoral, verrucous, scarring, and plaque.² Diagnosis is established using fungal tests such as potassium hydroxide direct microscopy, which exposes muriform bodies often in combination with dematiaceous hyphae, while fungal culture of F pedrosoi in Sabouraud agar produces velvety dark colonies.³ Although an immune response to CBM infection remains unclear, it has been demonstrated that the response differs based on the severity of the infection. The severe form of CBM produces high levels of IL-10, low levels of IFN-γ, and inefficient T-cell proliferation, while milder forms of CBM display low levels of IL-10, high levels of IFN-γ, and efficient T-cell proliferation.⁵ Complications of CBM include chronic lymphedema, ankylosis, and secondary bacterial infections, which largely are observed in advanced cases; malignant transformation to squamous cell carcinoma, though rare, also has been observed.⁶

Several therapeutic methods have been implemented in the treatment of CBM, but lesions often remain refractory, especially in advanced cases.⁶ Approaches to treatment can be divided into antifungal and physical methods. Commonly employed antifungal agents include itraconazole and terbinafine, which must be taken daily for a period ranging from 6 months to 1 year or longer; flucytosine with or without amphotericin also has been employed.⁴ Among the physical methods, surgical excision is not suggested due to possible dissemination of disease; other options include cryotherapy, thermotherapy, and laser vaporization.⁶ The prognosis has improved since the use of extended-spectrum triazoles, but high rates of refractory disease remain unchanged.²

The differential diagnosis includes other infections. Nocardiosis is a bacterial infection in which cutaneous disease can result in actinomycetoma, which presents with grains that are small, round, and stain blue on hematoxylin and eosin with eosinophilic rays at the periphery.⁷ Although the clinical features and pseudoepitheliomatous hyperplasia seen in CBM can mimic squamous cell carcinoma, the latter would show variable degrees of differentiation, keratinization, nuclear atypia, and architectural atypia with a negative tissue culture.⁸ Eumycetoma is a fungal infection that typically is not caused by F pedrosoi but rather most commonly Madurella mycetomatis.⁹ Leishmaniasis is a parasitic infection in which a biopsy of cutaneous lesions often displays parasite-filled histiocytes.¹⁰

The Diagnosis: Chromoblastomycosis

This case highlights the importance of routine skin biopsy and tissue culture when clinical suspicion for mycotic infection is high. Despite nonspecific biopsy results (Figure), a diagnosis of chromoblastomycosis (CBM) was reached based on tissue culture. Surgical excision was not possible in our patient due to the size and location of the lesion. The patient was referred to infectious disease, with the plan to start long-term itraconazole for at least 6 to 12 months.

Cases of CBM were first documented in 1914 and distinguished by the appearance of spherical, brown, muriform cells on skin biopsy—features that now serve as the hallmark of CBM diagnoses.^1,2 The implantation mycosis commonly is caused by agents such as Fonsecaea pedrosoi and Fonsecaea monophora of the bantiana-clade, as classified according to molecular phylogeny²; these agents have been isolated from soil, plants, and wood sources in tropical and subtropical regions and are strongly associated with agricultural activities.³

Chromoblastomycosis lesions tend to be asymptomatic with a variable amount of time between inoculation and lesion presentation, delaying medical care by months to years.³ The fungus causes a granulomatous reaction after skin damage, with noticeable pseudoepitheliomatous hyperplasia of the epidermis and granulomas formed by epithelioid and Langerhans cells in the dermis.⁴ Typically, CBM initially presents as an erythematous macular skin lesion, which then progresses to become more pink, papular, and sometimes pruritic.² Muriform (sclerotic) bodies, which reflect fungal components, extrude transepidermally and appear as black dots on the lesion’s surface.⁴ Chromoblastomycosis is limited to the subcutaneous tissue and has been classified into 5 types of lesions: nodular, tumoral, verrucous, scarring, and plaque.² Diagnosis is established using fungal tests such as potassium hydroxide direct microscopy, which exposes muriform bodies often in combination with dematiaceous hyphae, while fungal culture of F pedrosoi in Sabouraud agar produces velvety dark colonies.³ Although an immune response to CBM infection remains unclear, it has been demonstrated that the response differs based on the severity of the infection. The severe form of CBM produces high levels of IL-10, low levels of IFN-γ, and inefficient T-cell proliferation, while milder forms of CBM display low levels of IL-10, high levels of IFN-γ, and efficient T-cell proliferation.⁵ Complications of CBM include chronic lymphedema, ankylosis, and secondary bacterial infections, which largely are observed in advanced cases; malignant transformation to squamous cell carcinoma, though rare, also has been observed.⁶

Several therapeutic methods have been implemented in the treatment of CBM, but lesions often remain refractory, especially in advanced cases.⁶ Approaches to treatment can be divided into antifungal and physical methods. Commonly employed antifungal agents include itraconazole and terbinafine, which must be taken daily for a period ranging from 6 months to 1 year or longer; flucytosine with or without amphotericin also has been employed.⁴ Among the physical methods, surgical excision is not suggested due to possible dissemination of disease; other options include cryotherapy, thermotherapy, and laser vaporization.⁶ The prognosis has improved since the use of extended-spectrum triazoles, but high rates of refractory disease remain unchanged.²

The differential diagnosis includes other infections. Nocardiosis is a bacterial infection in which cutaneous disease can result in actinomycetoma, which presents with grains that are small, round, and stain blue on hematoxylin and eosin with eosinophilic rays at the periphery.⁷ Although the clinical features and pseudoepitheliomatous hyperplasia seen in CBM can mimic squamous cell carcinoma, the latter would show variable degrees of differentiation, keratinization, nuclear atypia, and architectural atypia with a negative tissue culture.⁸ Eumycetoma is a fungal infection that typically is not caused by F pedrosoi but rather most commonly Madurella mycetomatis.⁹ Leishmaniasis is a parasitic infection in which a biopsy of cutaneous lesions often displays parasite-filled histiocytes.¹⁰