Dermatopathology

To the Editor:

Pseudoepitheliomatous hyperplasia (PEH) is an uncommon type of reactive epidermal proliferation that can occur from a variety of causes, including an underlying infection, inflammation, neoplastic condition, or trauma induced from tattooing.¹ Diagnosis can be challenging and requires clinicopathologic correlation, as PEH can mimic malignancy on histopathology.^2-4 Histologically, PEH shows irregular hyperplasia of the epidermis and adnexal epithelium, elongation of the rete ridges, and extension of the reactive proliferation into the dermis. Absence of cytologic atypia is key to the diagnosis of PEH, helping to distinguish it from squamous cell carcinoma and keratoacanthoma. Clinically, patients typically present with well-demarcated, erythematous, scaly plaques or nodules in reactive areas, which can be symptomatically pruritic.

A 48-year-old woman presented with scaly and crusted verrucous plaques of 2 months’ duration that were isolated to the areas of purple pigment within a tattoo on the right lower leg. The patient reported pruritus in the affected areas that occurred immediately after obtaining the tattoo, which was her first and only tattoo. She denied any pertinent medical history, including an absence of immunosuppression and autoimmune or chronic inflammatory diseases.

Physical examination revealed scaly and crusted plaques isolated to areas of purple tattoo pigment (Figure 1). Areas of red, green, black, and blue pigmentation within the tattoo were uninvolved. With the initial suspicion of allergic contact dermatitis, two 6-mm punch biopsies were taken from adjacent linear plaques on the right leg for histology and tissue culture. Histopathologic evaluation revealed dermal tattoo pigment with overlying PEH and was negative for signs of infection (Figure 2). Infectious stains such as periodic acid–Schiff, Grocott-Gomori methenamine-silver, and Gram stains were performed and found to be negative. In addition, culture for mycobacteria came back negative. Prurigo was on the differential; however, histopathologic changes were more compatible with a PEH reaction to the tattoo.

An increase in the popularity of tattooing has led to more reports of various tattoo skin reactions.^4-6 The differential diagnosis is broad for tattoo reactions and includes granulomatous inflammation, sarcoidosis, psoriasis (Köbner phenomenon), allergic contact dermatitis, lichen planus, morphealike reactions, squamous cell carcinoma, and keratoacanthoma,⁵ which makes clinicopathologic correlation essential for accurate diagnosis. Our case demonstrated the characteristic epithelial hyperplasia in the absence of cytologic atypia. In addition, the presence of mixed dermal inflammation histologically was noted in our patient.

We report an unusual case of PEH occurring secondary to purple tattoo pigment. Our report also demonstrates the clinical and symptomatic improvement of PEH that can be achieved through the use of intralesional corticosteroid therapy. Our patient represents a case of PEH reactive to tattooing with purple ink. Further research to elucidate the precise pathogenesis of PEH tattoo reactions would be helpful in identifying high-risk patients and determining the most efficacious treatments.

To the Editor:

Pseudoepitheliomatous hyperplasia (PEH) is an uncommon type of reactive epidermal proliferation that can occur from a variety of causes, including an underlying infection, inflammation, neoplastic condition, or trauma induced from tattooing.¹ Diagnosis can be challenging and requires clinicopathologic correlation, as PEH can mimic malignancy on histopathology.^2-4 Histologically, PEH shows irregular hyperplasia of the epidermis and adnexal epithelium, elongation of the rete ridges, and extension of the reactive proliferation into the dermis. Absence of cytologic atypia is key to the diagnosis of PEH, helping to distinguish it from squamous cell carcinoma and keratoacanthoma. Clinically, patients typically present with well-demarcated, erythematous, scaly plaques or nodules in reactive areas, which can be symptomatically pruritic.

A 48-year-old woman presented with scaly and crusted verrucous plaques of 2 months’ duration that were isolated to the areas of purple pigment within a tattoo on the right lower leg. The patient reported pruritus in the affected areas that occurred immediately after obtaining the tattoo, which was her first and only tattoo. She denied any pertinent medical history, including an absence of immunosuppression and autoimmune or chronic inflammatory diseases.

Physical examination revealed scaly and crusted plaques isolated to areas of purple tattoo pigment (Figure 1). Areas of red, green, black, and blue pigmentation within the tattoo were uninvolved. With the initial suspicion of allergic contact dermatitis, two 6-mm punch biopsies were taken from adjacent linear plaques on the right leg for histology and tissue culture. Histopathologic evaluation revealed dermal tattoo pigment with overlying PEH and was negative for signs of infection (Figure 2). Infectious stains such as periodic acid–Schiff, Grocott-Gomori methenamine-silver, and Gram stains were performed and found to be negative. In addition, culture for mycobacteria came back negative. Prurigo was on the differential; however, histopathologic changes were more compatible with a PEH reaction to the tattoo.

An increase in the popularity of tattooing has led to more reports of various tattoo skin reactions.^4-6 The differential diagnosis is broad for tattoo reactions and includes granulomatous inflammation, sarcoidosis, psoriasis (Köbner phenomenon), allergic contact dermatitis, lichen planus, morphealike reactions, squamous cell carcinoma, and keratoacanthoma,⁵ which makes clinicopathologic correlation essential for accurate diagnosis. Our case demonstrated the characteristic epithelial hyperplasia in the absence of cytologic atypia. In addition, the presence of mixed dermal inflammation histologically was noted in our patient.

We report an unusual case of PEH occurring secondary to purple tattoo pigment. Our report also demonstrates the clinical and symptomatic improvement of PEH that can be achieved through the use of intralesional corticosteroid therapy. Our patient represents a case of PEH reactive to tattooing with purple ink. Further research to elucidate the precise pathogenesis of PEH tattoo reactions would be helpful in identifying high-risk patients and determining the most efficacious treatments.

To the Editor:

Pseudoepitheliomatous hyperplasia (PEH) is an uncommon type of reactive epidermal proliferation that can occur from a variety of causes, including an underlying infection, inflammation, neoplastic condition, or trauma induced from tattooing.¹ Diagnosis can be challenging and requires clinicopathologic correlation, as PEH can mimic malignancy on histopathology.^2-4 Histologically, PEH shows irregular hyperplasia of the epidermis and adnexal epithelium, elongation of the rete ridges, and extension of the reactive proliferation into the dermis. Absence of cytologic atypia is key to the diagnosis of PEH, helping to distinguish it from squamous cell carcinoma and keratoacanthoma. Clinically, patients typically present with well-demarcated, erythematous, scaly plaques or nodules in reactive areas, which can be symptomatically pruritic.

A 48-year-old woman presented with scaly and crusted verrucous plaques of 2 months’ duration that were isolated to the areas of purple pigment within a tattoo on the right lower leg. The patient reported pruritus in the affected areas that occurred immediately after obtaining the tattoo, which was her first and only tattoo. She denied any pertinent medical history, including an absence of immunosuppression and autoimmune or chronic inflammatory diseases.

Physical examination revealed scaly and crusted plaques isolated to areas of purple tattoo pigment (Figure 1). Areas of red, green, black, and blue pigmentation within the tattoo were uninvolved. With the initial suspicion of allergic contact dermatitis, two 6-mm punch biopsies were taken from adjacent linear plaques on the right leg for histology and tissue culture. Histopathologic evaluation revealed dermal tattoo pigment with overlying PEH and was negative for signs of infection (Figure 2). Infectious stains such as periodic acid–Schiff, Grocott-Gomori methenamine-silver, and Gram stains were performed and found to be negative. In addition, culture for mycobacteria came back negative. Prurigo was on the differential; however, histopathologic changes were more compatible with a PEH reaction to the tattoo.

An increase in the popularity of tattooing has led to more reports of various tattoo skin reactions.^4-6 The differential diagnosis is broad for tattoo reactions and includes granulomatous inflammation, sarcoidosis, psoriasis (Köbner phenomenon), allergic contact dermatitis, lichen planus, morphealike reactions, squamous cell carcinoma, and keratoacanthoma,⁵ which makes clinicopathologic correlation essential for accurate diagnosis. Our case demonstrated the characteristic epithelial hyperplasia in the absence of cytologic atypia. In addition, the presence of mixed dermal inflammation histologically was noted in our patient.

We report an unusual case of PEH occurring secondary to purple tattoo pigment. Our report also demonstrates the clinical and symptomatic improvement of PEH that can be achieved through the use of intralesional corticosteroid therapy. Our patient represents a case of PEH reactive to tattooing with purple ink. Further research to elucidate the precise pathogenesis of PEH tattoo reactions would be helpful in identifying high-risk patients and determining the most efficacious treatments.

The Diagnosis: Papuloerythroderma of Ofuji 

The patient presented with a characteristic finding of skinfold sparing, known as the "deck-chair sign" (Figure 1).¹ A repeat biopsy at our institution revealed a dermal perivascular and bandlike infiltrate with lymphocytes and occasional eosinophils (Figure 2). The epidermis showed mild spongiosis, lymphocytic exocytosis, and rare necrotic keratinocytes. A T-cell gene rearrangement assay was negative for a monoclonal population of T lymphocytes. Based on the clinical and histologic features, the diagnosis was most consistent with papuloerythroderma of Ofuji (PEO); however, a lymphoproliferative disorder needed to be excluded. Further workup included a peripheral smear, complete blood cell count with differential, comprehensive metabolic panel, IgE level, and hepatitis panel; all were normal, except for an elevated serum IgE level. Human immunodeficiency virus and age-appropriate malignancy screening were negative. The patient was prescribed betamethasone dipropionate cream 0.05% twice daily, which resulted in near-complete resolution of the rash and marked improvement in pruritus.

In 1984, PEO was described as an entity of generalized pruritic erythroderma characterized by flat-topped, red to brown, coalescing papules with sparing of the skinfolds, later coined the deck-chair sign.^1,2 Papuloerythroderma of Ofuji commonly presents in elderly Asian males with a male to female ratio of 4:1.³ Papuloerythroderma of Ofuji is a T cell-mediated skin disease; however, the etiology of the signature rash remains unclear. One explanation includes circulating factors in the skin that elicit an inflammatory response, which does not occur in areas of external pressure.³ The deck-chair sign may occur more frequently in elderly individuals due to increased skin laxity, which creates crease lines that are spared from rubbing and excoriations.⁴  

Although Ofuji et al² initially reported 4 idiopathic cases, subsequent authors described PEO in association with other conditions, including cutaneous T-cell lymphoma (CTCL) and atopic diathesis, and infections, as well as secondary to medications. Some authors have suggested that PEO may be an early variant of mycosis fungoides; therefore, physicians should monitor patients closely.^5-7 Maher et al⁶ commented that multiple causative factors including CTCL underlie the development of papuloerythroderma.  

In a review of PEO, Torchia et al³ proposed diagnostic criteria and an etiologic classification to address whether PEO represents an independent entity or an unusual manifestation of other dermatoses. They established 4 categories of papuloerythroderma--primary, secondary, papuloerythrodermalike CTCL, and pseudopapuloerythroderma--and proposed that primary PEO is a diagnosis of exclusion. If no secondary association is found, they proposed 10 criteria for primary PEO: 5 major criteria include coalescing flat-topped papules, the deck-chair sign, pruritus, histopathologic exclusion of diseases such as CTCL, and a negative workup to exclude other causes.³ In 2018, Maher et al⁶ recommended workup to rule out cutaneous malignancy, including skin biopsy, flow cytometry, Sézary cell count, T-cell rearrangement, lactate dehydrogenase, and human T-cell lymphotropic virus 1. The 5 minor criteria proposed by Torchia et al³ include age older than 55 years, male sex, eosinophilia, elevated IgE level, and lymphopenia. Our patient fulfilled all 5 major criteria and 3 minor criteria; eosinophilia and lymphopenia were absent.  

Clinically, PEO has been associated with the deck-chair sign, a pattern of selective sparing of skinfolds, including axillary, inguinal, submammary, and other flexural areas. Although the deck-chair sign was originally considered pathognomonic for PEO, this clinical pattern also has been observed in other entities, such as angioimmunoblastic lymphoma, cutaneous Waldenström macroglobulinemia, and acanthosis nigricans.^5,8,9  

Specific characteristics of the rash and certain clinical symptoms may help to distinguish the deck-chair sign of PEO from its other causes. Although malignant acanthosis nigricans may spare the skinfolds, lesions have a classic velvety thickening and brownish hyperpigmentation, which is not characteristic of the reddish brown, flat-topped papules of PEO.⁹ Pai et al⁵ described a patient with parthenium dermatitis presenting with the deck-chair sign that developed years after repeated exposure to the allergen. Our patient did not have a history of repeated episodes of allergic contact dermatitis. In addition, areas of sparing may mimic the appearance of pityriasis rubra pilaris. As in our patient, those with PEO generally lack the follicular hyperkeratotic papules, palmoplantar keratoderma, widespread orange-red erythema, and characteristic histopathologic finding of hyperkeratosis with alternating orthokeratosis and parakeratosis, allowing these entities to be easily distinguished in most instances.¹⁰ 

Histopathologically, primary PEO shows a nonspecific spongiotic dermatitis-like pattern characterized by slight epidermal hyperplasia with spongiosis and a predominantly perivascular dermal infiltrate with lymphocytes, histiocytes, and eosinophils.³ These histologic findings may at times show some overlap with CTCL, and therefore T-cell gene rearrangement and flow cytometry may be performed in those instances.⁶  

Treatment includes the management of any underlying condition causing the papuloerythroderma.^3,6 There are no large clinical trials of treatment options for primary PEO due to its rarity. Topical or systemic corticosteroids remain the mainstay of treatment.³ Alternative treatments used with variable success include phototherapy, interferon, etretinate, cyclosporine, and azathioprine.¹¹ Allegue et al¹¹ successfully used methotrexate to treat a patient with primary PEO and postulated that methotrexate may act through an immunosuppressive mechanism on activated T cells due to the involvement of helper T cells T_H2 and T_H22 in its pathogenesis. 

Although the cutaneous manifestations of PEO may respond well to topical steroids, it is important to consider the possible presence of an underlying malignancy and other associated systemic conditions.

The Diagnosis: Papuloerythroderma of Ofuji 

The patient presented with a characteristic finding of skinfold sparing, known as the "deck-chair sign" (Figure 1).¹ A repeat biopsy at our institution revealed a dermal perivascular and bandlike infiltrate with lymphocytes and occasional eosinophils (Figure 2). The epidermis showed mild spongiosis, lymphocytic exocytosis, and rare necrotic keratinocytes. A T-cell gene rearrangement assay was negative for a monoclonal population of T lymphocytes. Based on the clinical and histologic features, the diagnosis was most consistent with papuloerythroderma of Ofuji (PEO); however, a lymphoproliferative disorder needed to be excluded. Further workup included a peripheral smear, complete blood cell count with differential, comprehensive metabolic panel, IgE level, and hepatitis panel; all were normal, except for an elevated serum IgE level. Human immunodeficiency virus and age-appropriate malignancy screening were negative. The patient was prescribed betamethasone dipropionate cream 0.05% twice daily, which resulted in near-complete resolution of the rash and marked improvement in pruritus.

In 1984, PEO was described as an entity of generalized pruritic erythroderma characterized by flat-topped, red to brown, coalescing papules with sparing of the skinfolds, later coined the deck-chair sign.^1,2 Papuloerythroderma of Ofuji commonly presents in elderly Asian males with a male to female ratio of 4:1.³ Papuloerythroderma of Ofuji is a T cell-mediated skin disease; however, the etiology of the signature rash remains unclear. One explanation includes circulating factors in the skin that elicit an inflammatory response, which does not occur in areas of external pressure.³ The deck-chair sign may occur more frequently in elderly individuals due to increased skin laxity, which creates crease lines that are spared from rubbing and excoriations.⁴  

Although Ofuji et al² initially reported 4 idiopathic cases, subsequent authors described PEO in association with other conditions, including cutaneous T-cell lymphoma (CTCL) and atopic diathesis, and infections, as well as secondary to medications. Some authors have suggested that PEO may be an early variant of mycosis fungoides; therefore, physicians should monitor patients closely.^5-7 Maher et al⁶ commented that multiple causative factors including CTCL underlie the development of papuloerythroderma.  

In a review of PEO, Torchia et al³ proposed diagnostic criteria and an etiologic classification to address whether PEO represents an independent entity or an unusual manifestation of other dermatoses. They established 4 categories of papuloerythroderma--primary, secondary, papuloerythrodermalike CTCL, and pseudopapuloerythroderma--and proposed that primary PEO is a diagnosis of exclusion. If no secondary association is found, they proposed 10 criteria for primary PEO: 5 major criteria include coalescing flat-topped papules, the deck-chair sign, pruritus, histopathologic exclusion of diseases such as CTCL, and a negative workup to exclude other causes.³ In 2018, Maher et al⁶ recommended workup to rule out cutaneous malignancy, including skin biopsy, flow cytometry, Sézary cell count, T-cell rearrangement, lactate dehydrogenase, and human T-cell lymphotropic virus 1. The 5 minor criteria proposed by Torchia et al³ include age older than 55 years, male sex, eosinophilia, elevated IgE level, and lymphopenia. Our patient fulfilled all 5 major criteria and 3 minor criteria; eosinophilia and lymphopenia were absent.  

Clinically, PEO has been associated with the deck-chair sign, a pattern of selective sparing of skinfolds, including axillary, inguinal, submammary, and other flexural areas. Although the deck-chair sign was originally considered pathognomonic for PEO, this clinical pattern also has been observed in other entities, such as angioimmunoblastic lymphoma, cutaneous Waldenström macroglobulinemia, and acanthosis nigricans.^5,8,9  

Specific characteristics of the rash and certain clinical symptoms may help to distinguish the deck-chair sign of PEO from its other causes. Although malignant acanthosis nigricans may spare the skinfolds, lesions have a classic velvety thickening and brownish hyperpigmentation, which is not characteristic of the reddish brown, flat-topped papules of PEO.⁹ Pai et al⁵ described a patient with parthenium dermatitis presenting with the deck-chair sign that developed years after repeated exposure to the allergen. Our patient did not have a history of repeated episodes of allergic contact dermatitis. In addition, areas of sparing may mimic the appearance of pityriasis rubra pilaris. As in our patient, those with PEO generally lack the follicular hyperkeratotic papules, palmoplantar keratoderma, widespread orange-red erythema, and characteristic histopathologic finding of hyperkeratosis with alternating orthokeratosis and parakeratosis, allowing these entities to be easily distinguished in most instances.¹⁰ 

Histopathologically, primary PEO shows a nonspecific spongiotic dermatitis-like pattern characterized by slight epidermal hyperplasia with spongiosis and a predominantly perivascular dermal infiltrate with lymphocytes, histiocytes, and eosinophils.³ These histologic findings may at times show some overlap with CTCL, and therefore T-cell gene rearrangement and flow cytometry may be performed in those instances.⁶  

Treatment includes the management of any underlying condition causing the papuloerythroderma.^3,6 There are no large clinical trials of treatment options for primary PEO due to its rarity. Topical or systemic corticosteroids remain the mainstay of treatment.³ Alternative treatments used with variable success include phototherapy, interferon, etretinate, cyclosporine, and azathioprine.¹¹ Allegue et al¹¹ successfully used methotrexate to treat a patient with primary PEO and postulated that methotrexate may act through an immunosuppressive mechanism on activated T cells due to the involvement of helper T cells T_H2 and T_H22 in its pathogenesis. 

Although the cutaneous manifestations of PEO may respond well to topical steroids, it is important to consider the possible presence of an underlying malignancy and other associated systemic conditions.

The Diagnosis: Papuloerythroderma of Ofuji 

The patient presented with a characteristic finding of skinfold sparing, known as the "deck-chair sign" (Figure 1).¹ A repeat biopsy at our institution revealed a dermal perivascular and bandlike infiltrate with lymphocytes and occasional eosinophils (Figure 2). The epidermis showed mild spongiosis, lymphocytic exocytosis, and rare necrotic keratinocytes. A T-cell gene rearrangement assay was negative for a monoclonal population of T lymphocytes. Based on the clinical and histologic features, the diagnosis was most consistent with papuloerythroderma of Ofuji (PEO); however, a lymphoproliferative disorder needed to be excluded. Further workup included a peripheral smear, complete blood cell count with differential, comprehensive metabolic panel, IgE level, and hepatitis panel; all were normal, except for an elevated serum IgE level. Human immunodeficiency virus and age-appropriate malignancy screening were negative. The patient was prescribed betamethasone dipropionate cream 0.05% twice daily, which resulted in near-complete resolution of the rash and marked improvement in pruritus.

In 1984, PEO was described as an entity of generalized pruritic erythroderma characterized by flat-topped, red to brown, coalescing papules with sparing of the skinfolds, later coined the deck-chair sign.^1,2 Papuloerythroderma of Ofuji commonly presents in elderly Asian males with a male to female ratio of 4:1.³ Papuloerythroderma of Ofuji is a T cell-mediated skin disease; however, the etiology of the signature rash remains unclear. One explanation includes circulating factors in the skin that elicit an inflammatory response, which does not occur in areas of external pressure.³ The deck-chair sign may occur more frequently in elderly individuals due to increased skin laxity, which creates crease lines that are spared from rubbing and excoriations.⁴  

Although Ofuji et al² initially reported 4 idiopathic cases, subsequent authors described PEO in association with other conditions, including cutaneous T-cell lymphoma (CTCL) and atopic diathesis, and infections, as well as secondary to medications. Some authors have suggested that PEO may be an early variant of mycosis fungoides; therefore, physicians should monitor patients closely.^5-7 Maher et al⁶ commented that multiple causative factors including CTCL underlie the development of papuloerythroderma.  

In a review of PEO, Torchia et al³ proposed diagnostic criteria and an etiologic classification to address whether PEO represents an independent entity or an unusual manifestation of other dermatoses. They established 4 categories of papuloerythroderma--primary, secondary, papuloerythrodermalike CTCL, and pseudopapuloerythroderma--and proposed that primary PEO is a diagnosis of exclusion. If no secondary association is found, they proposed 10 criteria for primary PEO: 5 major criteria include coalescing flat-topped papules, the deck-chair sign, pruritus, histopathologic exclusion of diseases such as CTCL, and a negative workup to exclude other causes.³ In 2018, Maher et al⁶ recommended workup to rule out cutaneous malignancy, including skin biopsy, flow cytometry, Sézary cell count, T-cell rearrangement, lactate dehydrogenase, and human T-cell lymphotropic virus 1. The 5 minor criteria proposed by Torchia et al³ include age older than 55 years, male sex, eosinophilia, elevated IgE level, and lymphopenia. Our patient fulfilled all 5 major criteria and 3 minor criteria; eosinophilia and lymphopenia were absent.  

Clinically, PEO has been associated with the deck-chair sign, a pattern of selective sparing of skinfolds, including axillary, inguinal, submammary, and other flexural areas. Although the deck-chair sign was originally considered pathognomonic for PEO, this clinical pattern also has been observed in other entities, such as angioimmunoblastic lymphoma, cutaneous Waldenström macroglobulinemia, and acanthosis nigricans.^5,8,9  

Specific characteristics of the rash and certain clinical symptoms may help to distinguish the deck-chair sign of PEO from its other causes. Although malignant acanthosis nigricans may spare the skinfolds, lesions have a classic velvety thickening and brownish hyperpigmentation, which is not characteristic of the reddish brown, flat-topped papules of PEO.⁹ Pai et al⁵ described a patient with parthenium dermatitis presenting with the deck-chair sign that developed years after repeated exposure to the allergen. Our patient did not have a history of repeated episodes of allergic contact dermatitis. In addition, areas of sparing may mimic the appearance of pityriasis rubra pilaris. As in our patient, those with PEO generally lack the follicular hyperkeratotic papules, palmoplantar keratoderma, widespread orange-red erythema, and characteristic histopathologic finding of hyperkeratosis with alternating orthokeratosis and parakeratosis, allowing these entities to be easily distinguished in most instances.¹⁰ 

Histopathologically, primary PEO shows a nonspecific spongiotic dermatitis-like pattern characterized by slight epidermal hyperplasia with spongiosis and a predominantly perivascular dermal infiltrate with lymphocytes, histiocytes, and eosinophils.³ These histologic findings may at times show some overlap with CTCL, and therefore T-cell gene rearrangement and flow cytometry may be performed in those instances.⁶  

Treatment includes the management of any underlying condition causing the papuloerythroderma.^3,6 There are no large clinical trials of treatment options for primary PEO due to its rarity. Topical or systemic corticosteroids remain the mainstay of treatment.³ Alternative treatments used with variable success include phototherapy, interferon, etretinate, cyclosporine, and azathioprine.¹¹ Allegue et al¹¹ successfully used methotrexate to treat a patient with primary PEO and postulated that methotrexate may act through an immunosuppressive mechanism on activated T cells due to the involvement of helper T cells T_H2 and T_H22 in its pathogenesis. 

Although the cutaneous manifestations of PEO may respond well to topical steroids, it is important to consider the possible presence of an underlying malignancy and other associated systemic conditions.

The Diagnosis: Cutaneous Crohn Disease 

Crohn disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal (GI) tract from the mouth to the anus but most commonly presents in the terminal ileum, colon, or small bowel with transmural inflammation, fistula formation, and knife-cut fissures among the frequently described findings. Extraintestinal manifestations may be found in the liver, eyes, and joints, with cutaneous extraintestinal manifestations occurring in up to one-third of patients.¹ 

Crohn disease can be associated with multiple cutaneous findings, including erythema nodosum, pyoderma gangrenosum, aphthous ulcers, pyodermatitis-pyostomatitis vegetans, necrotizing vasculitis, and metastatic Crohn disease (MCD).² Typical histopathologic findings seen in MCD such as noncaseating granulomatous inflammation in the papillary and reticular dermis, possibly extending to the subcutaneous fat, are not specific to MCD. Associated genital edema is thought to be a consequence of granulomatous inflammation of lymphatics. In one study reviewing specimens from 10 cases of CD, a mean of 46% of all granulomas identified on the slides (264 granulomas in total) were located proximal to lymphatic vessels, suggesting a common pathway for development of intestinal disease and genital edema.³ The differential diagnosis for penile and scrotal swelling is broad, and the diagnosis may be missed if attention is not given to the clinical history of the patient in addition to histopathologic findings.² 

Skin changes in CD also can be separated into perianal disease and true metastatic disease--the former recognized when anal lesions appear associated with segmental involvement of the GI tract and the latter as ulceration of the skin separated from the GI tract by normal tissue.¹ The term sarcoidal reaction often is used to describe histopathologic findings in cutaneous CD, as it refers to the noncaseating granulomas found in approximately 60% of all cases.⁴ Ultimately, the location of noncaseating granulomas within the dermis of our patient's biopsy, taken in conjunction with the clinical history and the lack of defining features for other potential etiologies (eg, polarizable material, organisms on special stains), led to the diagnosis of cutaneous CD.  

Cutaneous manifestations of sarcoidosis most commonly occur as papules, plaques, and subcutaneous nodules predominantly on the face, upper back, arms, and legs. Although the histologic features of sarcoidosis are characterized by lymphocyte-poor noncaseating granulomas (Figure 1), these findings also can be seen as a consequence of multiple granulomatous causes.^5,6 In a review of 48 cutaneous specimens from patients with sarcoidosis, the granulomas were found most frequently in the deep dermis (34/48 [70.8%]), with superficial dermis (21/48) and subcutaneous fat granulomas (20/48) each present in less than 50% of biopsies.⁵ Although less typical, cutaneous sarcoidosis also has been noted in the literature to present in the perianal and gluteal region, demonstrating dermal noncaseating granulomas on biopsy.⁷ One distinction in particular to be noted between sarcoid and CD is that sarcoid lesions in the skin rarely ulcerate, while the lesions of cutaneous CD often are ulcerated.^4,6 

Lesions including abscesses in the groin may raise concern for hidradenitis suppurativa (HS), a disease of the apocrine gland-bearing skin. Typical lesions are tender subcutaneous erythematous nodules, cysts, and comedones that develop rapidly and may rupture to drain suppurative bloody discharge, subsequently healing with an atrophic scar.⁸ More persistent inflammation and rupture of nodules into the dermis may lead to formation of dermal tunnels with palpable cords and sinus tracts.⁸ Typical areas of disease involvement are in the axillae, inframammary folds, groin, or perigenital or perineal regions, with the diagnosis made on a combination of lesion morphology, location, and progression/recurrence frequency.⁹ Histologic examination of HS specimens can demonstrate a perifollicular lymphocytic infiltrate, with more advanced disease characterized by increased inflammatory cells, predominantly neutrophils, monocytes, and mast cells (Figure 2). The presence of granulomas in HS most often is of the foreign body type.⁹ Epithelioid granulomas noted in an area separate from inflammation in a patient with HS serve as a clue to be alert for systemic granulomatous disease.¹⁰  

Mycosis fungoides is the most common primary cutaneous lymphoma to show a granulomatous infiltrate; the granuloma generally is sarcoidal, though other forms are described (Figure 3).¹¹ Beyond these granulomatous foci, the key histopathologic feature of granulomatous mycosis fungoides (GMF) is diffuse dermal infiltration by atypical lymphoid cells. Epidermotropism and sparing of dermal nerves is the most critical finding in the diagnosis of GMF, especially in geographic regions where leprosy is endemic and high on the differential, as the conditions have histopathologic similarities.^11,12 At the same time, lack of epidermotropism does not exclude the diagnosis of GMF.¹³ Clinically, GMF presentation is variable, but common findings include erythematous and hyperpigmented patches and plaques. Given the lack of clear clinical criteria, the diagnosis relies primarily on histopathologic features.¹¹ 

Mycobacterial skin and soft tissue infections may be attributed to both tuberculous and nontuberculous strains (atypical species).¹⁴ Clinical features range from small papules to large deformative plaques and ulcers.¹⁵ Histologic features also distinguish cutaneous tuberculosis (TB) from nontuberculous mycobacterial causes. Cutaneous TB shows caseous granulomas in the upper and mid dermis, while nontuberculous mycobacterial infections have more prominent neutrophil infiltration and interstitial granulomas (Figure 4).¹⁶ 

In cutaneous TB specifically, extrapulmonary manifestations may involve the skin in 1% to 1.5% of all TB cases, and although rare, ulcerative skin TB has been noted in one report as a nonhealing perianal ulcer that showed necrotizing granulomas on biopsy.¹⁷ Ultimately, diagnosis of cutaneous mycobacterial infection is confirmed with detection of acid-fast bacilli in the biopsy specimen.¹⁶ 

Diagnosis of cutaneous CD requires clinicopathologic correlation, as the clinical and histopathologic differential diagnoses of genital edema and noncaseating granulomas, respectively, are broad. Even though the clinical context was appropriate for cutaneous CD in this case, correct diagnosis required confirmatory histologic findings. Furthermore, taking multiple biopsies is prudent. In our patient, diagnostic findings only were present in the biopsy from the scrotum.  

The Diagnosis: Cutaneous Crohn Disease 

Crohn disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal (GI) tract from the mouth to the anus but most commonly presents in the terminal ileum, colon, or small bowel with transmural inflammation, fistula formation, and knife-cut fissures among the frequently described findings. Extraintestinal manifestations may be found in the liver, eyes, and joints, with cutaneous extraintestinal manifestations occurring in up to one-third of patients.¹ 

Crohn disease can be associated with multiple cutaneous findings, including erythema nodosum, pyoderma gangrenosum, aphthous ulcers, pyodermatitis-pyostomatitis vegetans, necrotizing vasculitis, and metastatic Crohn disease (MCD).² Typical histopathologic findings seen in MCD such as noncaseating granulomatous inflammation in the papillary and reticular dermis, possibly extending to the subcutaneous fat, are not specific to MCD. Associated genital edema is thought to be a consequence of granulomatous inflammation of lymphatics. In one study reviewing specimens from 10 cases of CD, a mean of 46% of all granulomas identified on the slides (264 granulomas in total) were located proximal to lymphatic vessels, suggesting a common pathway for development of intestinal disease and genital edema.³ The differential diagnosis for penile and scrotal swelling is broad, and the diagnosis may be missed if attention is not given to the clinical history of the patient in addition to histopathologic findings.² 

Skin changes in CD also can be separated into perianal disease and true metastatic disease--the former recognized when anal lesions appear associated with segmental involvement of the GI tract and the latter as ulceration of the skin separated from the GI tract by normal tissue.¹ The term sarcoidal reaction often is used to describe histopathologic findings in cutaneous CD, as it refers to the noncaseating granulomas found in approximately 60% of all cases.⁴ Ultimately, the location of noncaseating granulomas within the dermis of our patient's biopsy, taken in conjunction with the clinical history and the lack of defining features for other potential etiologies (eg, polarizable material, organisms on special stains), led to the diagnosis of cutaneous CD.  

Cutaneous manifestations of sarcoidosis most commonly occur as papules, plaques, and subcutaneous nodules predominantly on the face, upper back, arms, and legs. Although the histologic features of sarcoidosis are characterized by lymphocyte-poor noncaseating granulomas (Figure 1), these findings also can be seen as a consequence of multiple granulomatous causes.^5,6 In a review of 48 cutaneous specimens from patients with sarcoidosis, the granulomas were found most frequently in the deep dermis (34/48 [70.8%]), with superficial dermis (21/48) and subcutaneous fat granulomas (20/48) each present in less than 50% of biopsies.⁵ Although less typical, cutaneous sarcoidosis also has been noted in the literature to present in the perianal and gluteal region, demonstrating dermal noncaseating granulomas on biopsy.⁷ One distinction in particular to be noted between sarcoid and CD is that sarcoid lesions in the skin rarely ulcerate, while the lesions of cutaneous CD often are ulcerated.^4,6 

Lesions including abscesses in the groin may raise concern for hidradenitis suppurativa (HS), a disease of the apocrine gland-bearing skin. Typical lesions are tender subcutaneous erythematous nodules, cysts, and comedones that develop rapidly and may rupture to drain suppurative bloody discharge, subsequently healing with an atrophic scar.⁸ More persistent inflammation and rupture of nodules into the dermis may lead to formation of dermal tunnels with palpable cords and sinus tracts.⁸ Typical areas of disease involvement are in the axillae, inframammary folds, groin, or perigenital or perineal regions, with the diagnosis made on a combination of lesion morphology, location, and progression/recurrence frequency.⁹ Histologic examination of HS specimens can demonstrate a perifollicular lymphocytic infiltrate, with more advanced disease characterized by increased inflammatory cells, predominantly neutrophils, monocytes, and mast cells (Figure 2). The presence of granulomas in HS most often is of the foreign body type.⁹ Epithelioid granulomas noted in an area separate from inflammation in a patient with HS serve as a clue to be alert for systemic granulomatous disease.¹⁰  

Mycosis fungoides is the most common primary cutaneous lymphoma to show a granulomatous infiltrate; the granuloma generally is sarcoidal, though other forms are described (Figure 3).¹¹ Beyond these granulomatous foci, the key histopathologic feature of granulomatous mycosis fungoides (GMF) is diffuse dermal infiltration by atypical lymphoid cells. Epidermotropism and sparing of dermal nerves is the most critical finding in the diagnosis of GMF, especially in geographic regions where leprosy is endemic and high on the differential, as the conditions have histopathologic similarities.^11,12 At the same time, lack of epidermotropism does not exclude the diagnosis of GMF.¹³ Clinically, GMF presentation is variable, but common findings include erythematous and hyperpigmented patches and plaques. Given the lack of clear clinical criteria, the diagnosis relies primarily on histopathologic features.¹¹ 

Mycobacterial skin and soft tissue infections may be attributed to both tuberculous and nontuberculous strains (atypical species).¹⁴ Clinical features range from small papules to large deformative plaques and ulcers.¹⁵ Histologic features also distinguish cutaneous tuberculosis (TB) from nontuberculous mycobacterial causes. Cutaneous TB shows caseous granulomas in the upper and mid dermis, while nontuberculous mycobacterial infections have more prominent neutrophil infiltration and interstitial granulomas (Figure 4).¹⁶ 

In cutaneous TB specifically, extrapulmonary manifestations may involve the skin in 1% to 1.5% of all TB cases, and although rare, ulcerative skin TB has been noted in one report as a nonhealing perianal ulcer that showed necrotizing granulomas on biopsy.¹⁷ Ultimately, diagnosis of cutaneous mycobacterial infection is confirmed with detection of acid-fast bacilli in the biopsy specimen.¹⁶ 

Diagnosis of cutaneous CD requires clinicopathologic correlation, as the clinical and histopathologic differential diagnoses of genital edema and noncaseating granulomas, respectively, are broad. Even though the clinical context was appropriate for cutaneous CD in this case, correct diagnosis required confirmatory histologic findings. Furthermore, taking multiple biopsies is prudent. In our patient, diagnostic findings only were present in the biopsy from the scrotum.  

The Diagnosis: Cutaneous Crohn Disease 

Crohn disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal (GI) tract from the mouth to the anus but most commonly presents in the terminal ileum, colon, or small bowel with transmural inflammation, fistula formation, and knife-cut fissures among the frequently described findings. Extraintestinal manifestations may be found in the liver, eyes, and joints, with cutaneous extraintestinal manifestations occurring in up to one-third of patients.¹ 

Crohn disease can be associated with multiple cutaneous findings, including erythema nodosum, pyoderma gangrenosum, aphthous ulcers, pyodermatitis-pyostomatitis vegetans, necrotizing vasculitis, and metastatic Crohn disease (MCD).² Typical histopathologic findings seen in MCD such as noncaseating granulomatous inflammation in the papillary and reticular dermis, possibly extending to the subcutaneous fat, are not specific to MCD. Associated genital edema is thought to be a consequence of granulomatous inflammation of lymphatics. In one study reviewing specimens from 10 cases of CD, a mean of 46% of all granulomas identified on the slides (264 granulomas in total) were located proximal to lymphatic vessels, suggesting a common pathway for development of intestinal disease and genital edema.³ The differential diagnosis for penile and scrotal swelling is broad, and the diagnosis may be missed if attention is not given to the clinical history of the patient in addition to histopathologic findings.² 

Skin changes in CD also can be separated into perianal disease and true metastatic disease--the former recognized when anal lesions appear associated with segmental involvement of the GI tract and the latter as ulceration of the skin separated from the GI tract by normal tissue.¹ The term sarcoidal reaction often is used to describe histopathologic findings in cutaneous CD, as it refers to the noncaseating granulomas found in approximately 60% of all cases.⁴ Ultimately, the location of noncaseating granulomas within the dermis of our patient's biopsy, taken in conjunction with the clinical history and the lack of defining features for other potential etiologies (eg, polarizable material, organisms on special stains), led to the diagnosis of cutaneous CD.  

Cutaneous manifestations of sarcoidosis most commonly occur as papules, plaques, and subcutaneous nodules predominantly on the face, upper back, arms, and legs. Although the histologic features of sarcoidosis are characterized by lymphocyte-poor noncaseating granulomas (Figure 1), these findings also can be seen as a consequence of multiple granulomatous causes.^5,6 In a review of 48 cutaneous specimens from patients with sarcoidosis, the granulomas were found most frequently in the deep dermis (34/48 [70.8%]), with superficial dermis (21/48) and subcutaneous fat granulomas (20/48) each present in less than 50% of biopsies.⁵ Although less typical, cutaneous sarcoidosis also has been noted in the literature to present in the perianal and gluteal region, demonstrating dermal noncaseating granulomas on biopsy.⁷ One distinction in particular to be noted between sarcoid and CD is that sarcoid lesions in the skin rarely ulcerate, while the lesions of cutaneous CD often are ulcerated.^4,6 

Lesions including abscesses in the groin may raise concern for hidradenitis suppurativa (HS), a disease of the apocrine gland-bearing skin. Typical lesions are tender subcutaneous erythematous nodules, cysts, and comedones that develop rapidly and may rupture to drain suppurative bloody discharge, subsequently healing with an atrophic scar.⁸ More persistent inflammation and rupture of nodules into the dermis may lead to formation of dermal tunnels with palpable cords and sinus tracts.⁸ Typical areas of disease involvement are in the axillae, inframammary folds, groin, or perigenital or perineal regions, with the diagnosis made on a combination of lesion morphology, location, and progression/recurrence frequency.⁹ Histologic examination of HS specimens can demonstrate a perifollicular lymphocytic infiltrate, with more advanced disease characterized by increased inflammatory cells, predominantly neutrophils, monocytes, and mast cells (Figure 2). The presence of granulomas in HS most often is of the foreign body type.⁹ Epithelioid granulomas noted in an area separate from inflammation in a patient with HS serve as a clue to be alert for systemic granulomatous disease.¹⁰  

Mycosis fungoides is the most common primary cutaneous lymphoma to show a granulomatous infiltrate; the granuloma generally is sarcoidal, though other forms are described (Figure 3).¹¹ Beyond these granulomatous foci, the key histopathologic feature of granulomatous mycosis fungoides (GMF) is diffuse dermal infiltration by atypical lymphoid cells. Epidermotropism and sparing of dermal nerves is the most critical finding in the diagnosis of GMF, especially in geographic regions where leprosy is endemic and high on the differential, as the conditions have histopathologic similarities.^11,12 At the same time, lack of epidermotropism does not exclude the diagnosis of GMF.¹³ Clinically, GMF presentation is variable, but common findings include erythematous and hyperpigmented patches and plaques. Given the lack of clear clinical criteria, the diagnosis relies primarily on histopathologic features.¹¹ 

Mycobacterial skin and soft tissue infections may be attributed to both tuberculous and nontuberculous strains (atypical species).¹⁴ Clinical features range from small papules to large deformative plaques and ulcers.¹⁵ Histologic features also distinguish cutaneous tuberculosis (TB) from nontuberculous mycobacterial causes. Cutaneous TB shows caseous granulomas in the upper and mid dermis, while nontuberculous mycobacterial infections have more prominent neutrophil infiltration and interstitial granulomas (Figure 4).¹⁶ 

In cutaneous TB specifically, extrapulmonary manifestations may involve the skin in 1% to 1.5% of all TB cases, and although rare, ulcerative skin TB has been noted in one report as a nonhealing perianal ulcer that showed necrotizing granulomas on biopsy.¹⁷ Ultimately, diagnosis of cutaneous mycobacterial infection is confirmed with detection of acid-fast bacilli in the biopsy specimen.¹⁶ 

Diagnosis of cutaneous CD requires clinicopathologic correlation, as the clinical and histopathologic differential diagnoses of genital edema and noncaseating granulomas, respectively, are broad. Even though the clinical context was appropriate for cutaneous CD in this case, correct diagnosis required confirmatory histologic findings. Furthermore, taking multiple biopsies is prudent. In our patient, diagnostic findings only were present in the biopsy from the scrotum.  

The Diagnosis: Tophaceous Gout  

Biopsy revealed amorphous pink material within the center of palisading granulomas lined by histiocytes and giant cells. Scattered crystal remnants also were identified within the center of the granulomas; however, the majority of the crystals were dissolved during the formalin processing of the tissue to become the amorphous material. A perivascular mixed inflammatory infiltrate composed of lymphocytes, histiocytes, and plasma cells surrounded the tophi nodules. A biopsy confirmed the diagnosis of tophaceous gout (Figure). 

Gout is a systemic metabolic disease characterized by the supersaturation of monosodium urate (MSU) crystals in joints and bursae. Peripheral joints most commonly are affected due to the poor solubility of MSU crystals at low temperatures.¹ It is one of the most common forms of inflammatory arthritis, with an estimated prevalence of 4% of adults in the United States.² An estimated $1 billion is spent each year on ambulatory care for gout.³ Gout occurs most commonly in men and usually manifests in the fifth or sixth decades of life.⁴ Risk factors for the development of gout include obesity, hypertension, poor dietary habits and kidney function, excessive alcohol intake, and diuretic use.³ 

Disease manifestations range from asymptomatic hyperuricemia to acute gouty arthritis and chronic tophaceous gout. Patients may present with chronic tophaceous gout without a prior clinically apparent acute gout episode.^5,6 Uncontrolled gout may result in large accumulations of MSU crystals, leading to well-circumscribed masses (known as tophi), as demonstrated in our patient.¹ Tophi are pathognomonic features of gout and are the sine qua non of advanced gout (also known as chronic tophaceous gout).² Clinically, these tophi appear as subcutaneous, yellowish white, firm and smooth nodules that are highlighted on the skin.⁴ Tophi most commonly are found on the helix, articular and periarticular tissue, and the tissue of the hands and feet. They usually are visible on physical examination but also may be detected on imaging studies.^2,4 

Gouty tophi have been reported in extraordinary locations, such as in sclerae; vocal cords; heart valves; abdominal striae; nerves; axial skeleton^4,7; and the penis, as in our patient and one other case.² These gouty deposits can appear similarly to lipomas, rheumatoid and osteoarthritic nodules, and infectious and malignant processes.^1,5 When tophi present in unusual locations, tissue biopsy often is necessary to confirm the diagnosis. Tissue preservation in alcohol is required to preserve the urate crystals. Microscopically, urate crystals appear as tightly packed, brown, needle-shaped crystals surrounded by granulomatous inflammation with foreign body giant cells, macrophages, and possibly some fibrosis. When examined under polarized light, the MSU crystals are negatively birefringent. However, when clinical suspicion for gout is low and the tissue is instead formalin fixed, as was performed in our case, the crystals dissolve into fibrillary amorphous deposits within the center of the granulomatous inflammation, which is another characteristic histologic finding in tophaceous gout.⁸ 

Management of gout focuses on urate-lowering therapy including lifestyle changes. Lower serum urate levels are associated with a decreased incidence of acute gout attacks and chronic tophaceous gout.² Urate-lowering drugs often are combined with anti-inflammatory drugs during acute attacks. Lifestyle changes, such as weight loss, exercise, reduced alcohol consumption, high fluid intake, and a low-purine diet also are beneficial.^3,4 Although gout cannot be cured, it can be effectively managed, and appropriate treatment can improve quality of life and reduce the risk for permanent joint damage and structural deformities. If medical treatment and lifestyle changes fail to adequately control tophaceous gout or if tophi become symptomatic, surgical removal of tophi is appropriate.⁴ 

At follow-up, our patient opted for surgical removal of the penile tophi. Using local anesthesia, surgical debulking via curettage was performed. Open defects were closed with fine absorbable sutures, and prophylactic antibiotics were given. Allopurinol also was started. Six weeks following extraction, the patient reported no complications and the area was continuing to heal.

Tophaceous gout would be distinguished from conditions in the differential diagnosis based on histologic findings from hematoxylin and eosin (H&E)-stained sections. Actinomycotic mycetoma is rare in the United States and is characterized by a seropurulent or stringy exudate with grains, ulcerations, melicerous scabs, and retractable scarring.⁹ On H&E-stained sections, actinomyces appear filamentous with deeply basophilic staining and radially oriented acidophilic projections.¹⁰ Calcinosis cutis of the penis has been reported to appear as asymptomatic papules; however, microscopic sections reveal deeply basophilic calcium deposits within the tissue.¹¹ Multinodular syphilis shows characteristic histology with lichenoid or vacuolar interface dermatitis, slender acanthosis, plasma cells, and endothelial swelling of the small vessels. A Treponema pallidum immunoperoxidase stain shows numerous organisms. Planar xanthoma shows xanthomatous or foamy histiocytes throughout the dermis on H&E-stained sections.¹²  

The Diagnosis: Tophaceous Gout  

Biopsy revealed amorphous pink material within the center of palisading granulomas lined by histiocytes and giant cells. Scattered crystal remnants also were identified within the center of the granulomas; however, the majority of the crystals were dissolved during the formalin processing of the tissue to become the amorphous material. A perivascular mixed inflammatory infiltrate composed of lymphocytes, histiocytes, and plasma cells surrounded the tophi nodules. A biopsy confirmed the diagnosis of tophaceous gout (Figure). 

Gout is a systemic metabolic disease characterized by the supersaturation of monosodium urate (MSU) crystals in joints and bursae. Peripheral joints most commonly are affected due to the poor solubility of MSU crystals at low temperatures.¹ It is one of the most common forms of inflammatory arthritis, with an estimated prevalence of 4% of adults in the United States.² An estimated $1 billion is spent each year on ambulatory care for gout.³ Gout occurs most commonly in men and usually manifests in the fifth or sixth decades of life.⁴ Risk factors for the development of gout include obesity, hypertension, poor dietary habits and kidney function, excessive alcohol intake, and diuretic use.³ 

Disease manifestations range from asymptomatic hyperuricemia to acute gouty arthritis and chronic tophaceous gout. Patients may present with chronic tophaceous gout without a prior clinically apparent acute gout episode.^5,6 Uncontrolled gout may result in large accumulations of MSU crystals, leading to well-circumscribed masses (known as tophi), as demonstrated in our patient.¹ Tophi are pathognomonic features of gout and are the sine qua non of advanced gout (also known as chronic tophaceous gout).² Clinically, these tophi appear as subcutaneous, yellowish white, firm and smooth nodules that are highlighted on the skin.⁴ Tophi most commonly are found on the helix, articular and periarticular tissue, and the tissue of the hands and feet. They usually are visible on physical examination but also may be detected on imaging studies.^2,4 

Gouty tophi have been reported in extraordinary locations, such as in sclerae; vocal cords; heart valves; abdominal striae; nerves; axial skeleton^4,7; and the penis, as in our patient and one other case.² These gouty deposits can appear similarly to lipomas, rheumatoid and osteoarthritic nodules, and infectious and malignant processes.^1,5 When tophi present in unusual locations, tissue biopsy often is necessary to confirm the diagnosis. Tissue preservation in alcohol is required to preserve the urate crystals. Microscopically, urate crystals appear as tightly packed, brown, needle-shaped crystals surrounded by granulomatous inflammation with foreign body giant cells, macrophages, and possibly some fibrosis. When examined under polarized light, the MSU crystals are negatively birefringent. However, when clinical suspicion for gout is low and the tissue is instead formalin fixed, as was performed in our case, the crystals dissolve into fibrillary amorphous deposits within the center of the granulomatous inflammation, which is another characteristic histologic finding in tophaceous gout.⁸ 

Management of gout focuses on urate-lowering therapy including lifestyle changes. Lower serum urate levels are associated with a decreased incidence of acute gout attacks and chronic tophaceous gout.² Urate-lowering drugs often are combined with anti-inflammatory drugs during acute attacks. Lifestyle changes, such as weight loss, exercise, reduced alcohol consumption, high fluid intake, and a low-purine diet also are beneficial.^3,4 Although gout cannot be cured, it can be effectively managed, and appropriate treatment can improve quality of life and reduce the risk for permanent joint damage and structural deformities. If medical treatment and lifestyle changes fail to adequately control tophaceous gout or if tophi become symptomatic, surgical removal of tophi is appropriate.⁴ 

At follow-up, our patient opted for surgical removal of the penile tophi. Using local anesthesia, surgical debulking via curettage was performed. Open defects were closed with fine absorbable sutures, and prophylactic antibiotics were given. Allopurinol also was started. Six weeks following extraction, the patient reported no complications and the area was continuing to heal.

Tophaceous gout would be distinguished from conditions in the differential diagnosis based on histologic findings from hematoxylin and eosin (H&E)-stained sections. Actinomycotic mycetoma is rare in the United States and is characterized by a seropurulent or stringy exudate with grains, ulcerations, melicerous scabs, and retractable scarring.⁹ On H&E-stained sections, actinomyces appear filamentous with deeply basophilic staining and radially oriented acidophilic projections.¹⁰ Calcinosis cutis of the penis has been reported to appear as asymptomatic papules; however, microscopic sections reveal deeply basophilic calcium deposits within the tissue.¹¹ Multinodular syphilis shows characteristic histology with lichenoid or vacuolar interface dermatitis, slender acanthosis, plasma cells, and endothelial swelling of the small vessels. A Treponema pallidum immunoperoxidase stain shows numerous organisms. Planar xanthoma shows xanthomatous or foamy histiocytes throughout the dermis on H&E-stained sections.¹²  

The Diagnosis: Tophaceous Gout  

Biopsy revealed amorphous pink material within the center of palisading granulomas lined by histiocytes and giant cells. Scattered crystal remnants also were identified within the center of the granulomas; however, the majority of the crystals were dissolved during the formalin processing of the tissue to become the amorphous material. A perivascular mixed inflammatory infiltrate composed of lymphocytes, histiocytes, and plasma cells surrounded the tophi nodules. A biopsy confirmed the diagnosis of tophaceous gout (Figure). 

Gout is a systemic metabolic disease characterized by the supersaturation of monosodium urate (MSU) crystals in joints and bursae. Peripheral joints most commonly are affected due to the poor solubility of MSU crystals at low temperatures.¹ It is one of the most common forms of inflammatory arthritis, with an estimated prevalence of 4% of adults in the United States.² An estimated $1 billion is spent each year on ambulatory care for gout.³ Gout occurs most commonly in men and usually manifests in the fifth or sixth decades of life.⁴ Risk factors for the development of gout include obesity, hypertension, poor dietary habits and kidney function, excessive alcohol intake, and diuretic use.³ 

Disease manifestations range from asymptomatic hyperuricemia to acute gouty arthritis and chronic tophaceous gout. Patients may present with chronic tophaceous gout without a prior clinically apparent acute gout episode.^5,6 Uncontrolled gout may result in large accumulations of MSU crystals, leading to well-circumscribed masses (known as tophi), as demonstrated in our patient.¹ Tophi are pathognomonic features of gout and are the sine qua non of advanced gout (also known as chronic tophaceous gout).² Clinically, these tophi appear as subcutaneous, yellowish white, firm and smooth nodules that are highlighted on the skin.⁴ Tophi most commonly are found on the helix, articular and periarticular tissue, and the tissue of the hands and feet. They usually are visible on physical examination but also may be detected on imaging studies.^2,4 

Gouty tophi have been reported in extraordinary locations, such as in sclerae; vocal cords; heart valves; abdominal striae; nerves; axial skeleton^4,7; and the penis, as in our patient and one other case.² These gouty deposits can appear similarly to lipomas, rheumatoid and osteoarthritic nodules, and infectious and malignant processes.^1,5 When tophi present in unusual locations, tissue biopsy often is necessary to confirm the diagnosis. Tissue preservation in alcohol is required to preserve the urate crystals. Microscopically, urate crystals appear as tightly packed, brown, needle-shaped crystals surrounded by granulomatous inflammation with foreign body giant cells, macrophages, and possibly some fibrosis. When examined under polarized light, the MSU crystals are negatively birefringent. However, when clinical suspicion for gout is low and the tissue is instead formalin fixed, as was performed in our case, the crystals dissolve into fibrillary amorphous deposits within the center of the granulomatous inflammation, which is another characteristic histologic finding in tophaceous gout.⁸ 

Management of gout focuses on urate-lowering therapy including lifestyle changes. Lower serum urate levels are associated with a decreased incidence of acute gout attacks and chronic tophaceous gout.² Urate-lowering drugs often are combined with anti-inflammatory drugs during acute attacks. Lifestyle changes, such as weight loss, exercise, reduced alcohol consumption, high fluid intake, and a low-purine diet also are beneficial.^3,4 Although gout cannot be cured, it can be effectively managed, and appropriate treatment can improve quality of life and reduce the risk for permanent joint damage and structural deformities. If medical treatment and lifestyle changes fail to adequately control tophaceous gout or if tophi become symptomatic, surgical removal of tophi is appropriate.⁴ 

At follow-up, our patient opted for surgical removal of the penile tophi. Using local anesthesia, surgical debulking via curettage was performed. Open defects were closed with fine absorbable sutures, and prophylactic antibiotics were given. Allopurinol also was started. Six weeks following extraction, the patient reported no complications and the area was continuing to heal.

Tophaceous gout would be distinguished from conditions in the differential diagnosis based on histologic findings from hematoxylin and eosin (H&E)-stained sections. Actinomycotic mycetoma is rare in the United States and is characterized by a seropurulent or stringy exudate with grains, ulcerations, melicerous scabs, and retractable scarring.⁹ On H&E-stained sections, actinomyces appear filamentous with deeply basophilic staining and radially oriented acidophilic projections.¹⁰ Calcinosis cutis of the penis has been reported to appear as asymptomatic papules; however, microscopic sections reveal deeply basophilic calcium deposits within the tissue.¹¹ Multinodular syphilis shows characteristic histology with lichenoid or vacuolar interface dermatitis, slender acanthosis, plasma cells, and endothelial swelling of the small vessels. A Treponema pallidum immunoperoxidase stain shows numerous organisms. Planar xanthoma shows xanthomatous or foamy histiocytes throughout the dermis on H&E-stained sections.¹²  

The Diagnosis: Epidermolysis Bullosa Acquisita 

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disorder characterized by tense bullae, skin fragility, atrophic scarring, and milia formation.¹ Blisters occur on a noninflammatory base in the classic variant and are trauma induced, hence the predilection for the extensor surfaces.² Mucosal involvement also has been described.¹ The characteristic findings in EBA are IgG autoantibodies directed at the N-terminal collagenous domain of type VII collagen, which composes the anchoring fibrils in the basement membrane zone.¹ Differentiating EBA from other subepidermal bullous diseases, especially bullous pemphigoid (BP), can be difficult, necessitating specialized tests.  

Biopsy of the perilesional skin can help identify the location of the blister formation. Our patient's biopsy showed a subepidermal blister with granulocytes. The differential diagnosis of a subepidermal blister includes BP, herpes gestationis, cicatricial pemphigoid, EBA, bullous systemic lupus erythematosus, dermatitis herpetiformis, linear IgA disease, and porphyria cutanea tarda. 

Direct immunofluorescence (DIF) was performed on the biopsy from our patient, which showed linear/particulate IgG, C3, and IgA deposits in the basement membrane zone, narrowing the differential diagnosis to BP or EBA. To differentiate EBA from BP, DIF of perilesional skin using a salt-split preparation was performed. This test distinguishes the location of the immunoreactants at the basement membrane zone. The antibody complexes in BP are found on the epidermal side of the split, while the antibody complexes in EBA are found on the dermal side of the split. Indirect immunofluorescence on salt-split skin also has been used to distinguish EBA from BP but is only conclusive if there are circulating autoantibodies to the basement membrane zone in the serum, which occurs in approximately 50% of patients with EBA and 15% of patients with BP.³ The immune complexes in our patient were found to be on the dermal side of the split after DIF on salt-split skin, confirming the diagnosis of EBA (Figure).  

Differentiating EBA from BP has great value, as the diagnosis affects treatment options. Bullous pemphigoid is fairly easy to treat, with most patients responding to prednisone.³ Epidermolysis bullosa acquisita usually is resistant to therapy. The disease course is chronic with  exacerbations and remissions. Dapsone often is used to control the disease, though this therapy for EBA is not currently approved by the US Food and Drug Administration. The recommended initial dose of dapsone is 50 mg daily and should be increased by 50 mg each week until remission, usually 100 to 250 mg.⁴ We prescribed dapsone for our patient upon clinical suspicion of EBA before the DIF on salt-split skin was completed. A trial of prednisone may be warranted for EBA if there is no response to dapsone or colchicine, but the response is unpredictable. Cyclosporine usually results in a quick response and may be considered if there is clinically severe disease and other treatment alternatives have failed.⁴ 

The Diagnosis: Epidermolysis Bullosa Acquisita 

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disorder characterized by tense bullae, skin fragility, atrophic scarring, and milia formation.¹ Blisters occur on a noninflammatory base in the classic variant and are trauma induced, hence the predilection for the extensor surfaces.² Mucosal involvement also has been described.¹ The characteristic findings in EBA are IgG autoantibodies directed at the N-terminal collagenous domain of type VII collagen, which composes the anchoring fibrils in the basement membrane zone.¹ Differentiating EBA from other subepidermal bullous diseases, especially bullous pemphigoid (BP), can be difficult, necessitating specialized tests.  

Biopsy of the perilesional skin can help identify the location of the blister formation. Our patient's biopsy showed a subepidermal blister with granulocytes. The differential diagnosis of a subepidermal blister includes BP, herpes gestationis, cicatricial pemphigoid, EBA, bullous systemic lupus erythematosus, dermatitis herpetiformis, linear IgA disease, and porphyria cutanea tarda. 

Direct immunofluorescence (DIF) was performed on the biopsy from our patient, which showed linear/particulate IgG, C3, and IgA deposits in the basement membrane zone, narrowing the differential diagnosis to BP or EBA. To differentiate EBA from BP, DIF of perilesional skin using a salt-split preparation was performed. This test distinguishes the location of the immunoreactants at the basement membrane zone. The antibody complexes in BP are found on the epidermal side of the split, while the antibody complexes in EBA are found on the dermal side of the split. Indirect immunofluorescence on salt-split skin also has been used to distinguish EBA from BP but is only conclusive if there are circulating autoantibodies to the basement membrane zone in the serum, which occurs in approximately 50% of patients with EBA and 15% of patients with BP.³ The immune complexes in our patient were found to be on the dermal side of the split after DIF on salt-split skin, confirming the diagnosis of EBA (Figure).  

Differentiating EBA from BP has great value, as the diagnosis affects treatment options. Bullous pemphigoid is fairly easy to treat, with most patients responding to prednisone.³ Epidermolysis bullosa acquisita usually is resistant to therapy. The disease course is chronic with  exacerbations and remissions. Dapsone often is used to control the disease, though this therapy for EBA is not currently approved by the US Food and Drug Administration. The recommended initial dose of dapsone is 50 mg daily and should be increased by 50 mg each week until remission, usually 100 to 250 mg.⁴ We prescribed dapsone for our patient upon clinical suspicion of EBA before the DIF on salt-split skin was completed. A trial of prednisone may be warranted for EBA if there is no response to dapsone or colchicine, but the response is unpredictable. Cyclosporine usually results in a quick response and may be considered if there is clinically severe disease and other treatment alternatives have failed.⁴ 

The Diagnosis: Epidermolysis Bullosa Acquisita 

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disorder characterized by tense bullae, skin fragility, atrophic scarring, and milia formation.¹ Blisters occur on a noninflammatory base in the classic variant and are trauma induced, hence the predilection for the extensor surfaces.² Mucosal involvement also has been described.¹ The characteristic findings in EBA are IgG autoantibodies directed at the N-terminal collagenous domain of type VII collagen, which composes the anchoring fibrils in the basement membrane zone.¹ Differentiating EBA from other subepidermal bullous diseases, especially bullous pemphigoid (BP), can be difficult, necessitating specialized tests.  

Biopsy of the perilesional skin can help identify the location of the blister formation. Our patient's biopsy showed a subepidermal blister with granulocytes. The differential diagnosis of a subepidermal blister includes BP, herpes gestationis, cicatricial pemphigoid, EBA, bullous systemic lupus erythematosus, dermatitis herpetiformis, linear IgA disease, and porphyria cutanea tarda. 

Direct immunofluorescence (DIF) was performed on the biopsy from our patient, which showed linear/particulate IgG, C3, and IgA deposits in the basement membrane zone, narrowing the differential diagnosis to BP or EBA. To differentiate EBA from BP, DIF of perilesional skin using a salt-split preparation was performed. This test distinguishes the location of the immunoreactants at the basement membrane zone. The antibody complexes in BP are found on the epidermal side of the split, while the antibody complexes in EBA are found on the dermal side of the split. Indirect immunofluorescence on salt-split skin also has been used to distinguish EBA from BP but is only conclusive if there are circulating autoantibodies to the basement membrane zone in the serum, which occurs in approximately 50% of patients with EBA and 15% of patients with BP.³ The immune complexes in our patient were found to be on the dermal side of the split after DIF on salt-split skin, confirming the diagnosis of EBA (Figure).  

Differentiating EBA from BP has great value, as the diagnosis affects treatment options. Bullous pemphigoid is fairly easy to treat, with most patients responding to prednisone.³ Epidermolysis bullosa acquisita usually is resistant to therapy. The disease course is chronic with  exacerbations and remissions. Dapsone often is used to control the disease, though this therapy for EBA is not currently approved by the US Food and Drug Administration. The recommended initial dose of dapsone is 50 mg daily and should be increased by 50 mg each week until remission, usually 100 to 250 mg.⁴ We prescribed dapsone for our patient upon clinical suspicion of EBA before the DIF on salt-split skin was completed. A trial of prednisone may be warranted for EBA if there is no response to dapsone or colchicine, but the response is unpredictable. Cyclosporine usually results in a quick response and may be considered if there is clinically severe disease and other treatment alternatives have failed.⁴ 

Central centrifugal cicatricial alopecia (CCCA) appears to be distinguished from other scarring forms of alopecia by the predominance of CD4+ cells in the lymphocytic inflammatory infiltrate, according to a histopathological study of biopsy specimens.

“Evaluation of the T-cell infiltrate may be a useful way to distinguish CCCA from lichen planopilaris or frontal fibrosing alopecia in some cases when histopathological features alone cannot be used to definitely distinguish between them,” reported Alexandra Flamm, MD, Ata Moshiri, MD, and coauthors from the departments of dermatology and pathology, University of Pennsylvania, Philadelphia.

The histopathological features of CCCA have been characterized previously, but the goal of this study was to go further in piecing together the pathophysiology, they noted.

Horizontal sections of 4-mm punch biopsy specimens were examined from 18 black women with a known diagnosis of CCCA. Both affected and unaffected follicles were evaluated with attention to the number and percentage of CD1a+ Langerhans cells, CD3+, CD4+, and CD8+ lymphocytes.

In this series, the lymphocytic infiltrate in both the affected and unaffected follicles was predominantly composed of CD4+ cells. The perifollicular ratio for CD4+ to CD8+ cells in affected follicles was 5.3:1. It was only modestly lower in unaffected follicles (4.3:1) and in the intrafollicular space of affected follicles (2.5:1).

Affected follicles had a higher number of CD1a+ Langerhans cells than unaffected follicles. This finding suggests, as others have hypothesized, that the antigen-presenting Langerhans cells draw lymphocytes to the follicle, according to the investigators. Elevated numbers of Langerhans cells have also been reported in other forms of scarring alopecia, such as lichen planopilaris (LPP).

In the case of CCCA, CD1a+ Langerhans cells appear to localize to the hair follicle in response to stimulus such as an injury. The CD4+ cells that follow the Langerhans cells participate in an inflammatory reaction that drives follicle destruction. In addition to this damage and scarring, the inflammatory response is also likely to be disrupting the blood supply.

“Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium,” the authors explained. Ultimately, “the mucinous fibroplasia and perifollicular fibrosis may disrupt and fragment blood vessels in the fibrous sheath, leaving only small clusters of vessels more distant to the keratinocytes in the outer root sheath.”

Prior studies of scarring alopecia diseases, including LLP, frontal fibrosing alopecia (FFA), and keratosis follicularis spinulosa decalvans (KFSD), have typically described a predominantly CD8+ lymphocytic infiltrate. The evidence from this study that the infiltrate is CD4+ predominant in CCCA supports the conclusion that the pathophysiologic features of this type of alopecia are unique, according to the authors.

Work by others has associated CCCA with mutations in the PAD13 gene, which suggests a defect in the formation of hair shaft structure, but this may speak to susceptibility but not the mechanism of hair follicle damage. Rather, this study suggests that it is the concentration of a CD4+ predominant lymphocytic infiltrate in the perifollicular space that induces the pathological events.

For determining the fundamental cause of CCCA, “it will be important to determine what recruits the Langerhans cells to affected follicles,” the investigators suggested. Meanwhile, they expressed hope that the progress being made into decoding the pathogenesis of CCCA will lead to novel therapeutic strategies.

The authors did not list any disclosures. The funding source was listed as the Center for Scientific Review (Grant/Award).

SOURCE: Flamm A et al. J Cutan Pathol. 2020 Feb 18.doi: 10.1111/cup.13666.

Central centrifugal cicatricial alopecia (CCCA) appears to be distinguished from other scarring forms of alopecia by the predominance of CD4+ cells in the lymphocytic inflammatory infiltrate, according to a histopathological study of biopsy specimens.

“Evaluation of the T-cell infiltrate may be a useful way to distinguish CCCA from lichen planopilaris or frontal fibrosing alopecia in some cases when histopathological features alone cannot be used to definitely distinguish between them,” reported Alexandra Flamm, MD, Ata Moshiri, MD, and coauthors from the departments of dermatology and pathology, University of Pennsylvania, Philadelphia.

The histopathological features of CCCA have been characterized previously, but the goal of this study was to go further in piecing together the pathophysiology, they noted.

Horizontal sections of 4-mm punch biopsy specimens were examined from 18 black women with a known diagnosis of CCCA. Both affected and unaffected follicles were evaluated with attention to the number and percentage of CD1a+ Langerhans cells, CD3+, CD4+, and CD8+ lymphocytes.

In this series, the lymphocytic infiltrate in both the affected and unaffected follicles was predominantly composed of CD4+ cells. The perifollicular ratio for CD4+ to CD8+ cells in affected follicles was 5.3:1. It was only modestly lower in unaffected follicles (4.3:1) and in the intrafollicular space of affected follicles (2.5:1).

Affected follicles had a higher number of CD1a+ Langerhans cells than unaffected follicles. This finding suggests, as others have hypothesized, that the antigen-presenting Langerhans cells draw lymphocytes to the follicle, according to the investigators. Elevated numbers of Langerhans cells have also been reported in other forms of scarring alopecia, such as lichen planopilaris (LPP).

In the case of CCCA, CD1a+ Langerhans cells appear to localize to the hair follicle in response to stimulus such as an injury. The CD4+ cells that follow the Langerhans cells participate in an inflammatory reaction that drives follicle destruction. In addition to this damage and scarring, the inflammatory response is also likely to be disrupting the blood supply.

“Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium,” the authors explained. Ultimately, “the mucinous fibroplasia and perifollicular fibrosis may disrupt and fragment blood vessels in the fibrous sheath, leaving only small clusters of vessels more distant to the keratinocytes in the outer root sheath.”

Prior studies of scarring alopecia diseases, including LLP, frontal fibrosing alopecia (FFA), and keratosis follicularis spinulosa decalvans (KFSD), have typically described a predominantly CD8+ lymphocytic infiltrate. The evidence from this study that the infiltrate is CD4+ predominant in CCCA supports the conclusion that the pathophysiologic features of this type of alopecia are unique, according to the authors.

Work by others has associated CCCA with mutations in the PAD13 gene, which suggests a defect in the formation of hair shaft structure, but this may speak to susceptibility but not the mechanism of hair follicle damage. Rather, this study suggests that it is the concentration of a CD4+ predominant lymphocytic infiltrate in the perifollicular space that induces the pathological events.

For determining the fundamental cause of CCCA, “it will be important to determine what recruits the Langerhans cells to affected follicles,” the investigators suggested. Meanwhile, they expressed hope that the progress being made into decoding the pathogenesis of CCCA will lead to novel therapeutic strategies.

The authors did not list any disclosures. The funding source was listed as the Center for Scientific Review (Grant/Award).

SOURCE: Flamm A et al. J Cutan Pathol. 2020 Feb 18.doi: 10.1111/cup.13666.

Central centrifugal cicatricial alopecia (CCCA) appears to be distinguished from other scarring forms of alopecia by the predominance of CD4+ cells in the lymphocytic inflammatory infiltrate, according to a histopathological study of biopsy specimens.

“Evaluation of the T-cell infiltrate may be a useful way to distinguish CCCA from lichen planopilaris or frontal fibrosing alopecia in some cases when histopathological features alone cannot be used to definitely distinguish between them,” reported Alexandra Flamm, MD, Ata Moshiri, MD, and coauthors from the departments of dermatology and pathology, University of Pennsylvania, Philadelphia.

The histopathological features of CCCA have been characterized previously, but the goal of this study was to go further in piecing together the pathophysiology, they noted.

Horizontal sections of 4-mm punch biopsy specimens were examined from 18 black women with a known diagnosis of CCCA. Both affected and unaffected follicles were evaluated with attention to the number and percentage of CD1a+ Langerhans cells, CD3+, CD4+, and CD8+ lymphocytes.

In this series, the lymphocytic infiltrate in both the affected and unaffected follicles was predominantly composed of CD4+ cells. The perifollicular ratio for CD4+ to CD8+ cells in affected follicles was 5.3:1. It was only modestly lower in unaffected follicles (4.3:1) and in the intrafollicular space of affected follicles (2.5:1).

Affected follicles had a higher number of CD1a+ Langerhans cells than unaffected follicles. This finding suggests, as others have hypothesized, that the antigen-presenting Langerhans cells draw lymphocytes to the follicle, according to the investigators. Elevated numbers of Langerhans cells have also been reported in other forms of scarring alopecia, such as lichen planopilaris (LPP).

In the case of CCCA, CD1a+ Langerhans cells appear to localize to the hair follicle in response to stimulus such as an injury. The CD4+ cells that follow the Langerhans cells participate in an inflammatory reaction that drives follicle destruction. In addition to this damage and scarring, the inflammatory response is also likely to be disrupting the blood supply.

“Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium,” the authors explained. Ultimately, “the mucinous fibroplasia and perifollicular fibrosis may disrupt and fragment blood vessels in the fibrous sheath, leaving only small clusters of vessels more distant to the keratinocytes in the outer root sheath.”

Prior studies of scarring alopecia diseases, including LLP, frontal fibrosing alopecia (FFA), and keratosis follicularis spinulosa decalvans (KFSD), have typically described a predominantly CD8+ lymphocytic infiltrate. The evidence from this study that the infiltrate is CD4+ predominant in CCCA supports the conclusion that the pathophysiologic features of this type of alopecia are unique, according to the authors.

Work by others has associated CCCA with mutations in the PAD13 gene, which suggests a defect in the formation of hair shaft structure, but this may speak to susceptibility but not the mechanism of hair follicle damage. Rather, this study suggests that it is the concentration of a CD4+ predominant lymphocytic infiltrate in the perifollicular space that induces the pathological events.

For determining the fundamental cause of CCCA, “it will be important to determine what recruits the Langerhans cells to affected follicles,” the investigators suggested. Meanwhile, they expressed hope that the progress being made into decoding the pathogenesis of CCCA will lead to novel therapeutic strategies.

The authors did not list any disclosures. The funding source was listed as the Center for Scientific Review (Grant/Award).

SOURCE: Flamm A et al. J Cutan Pathol. 2020 Feb 18.doi: 10.1111/cup.13666.

The Diagnosis: Cutaneous Metastatic Gastric Carcinoma  

Cutaneous metastasis of primary gastric carcinoma is a rare occurrence, with the more common metastatic sites being the lymph nodes, liver, and peritoneal cavity. The incidence of visceral neoplasm metastasis to the skin ranges from 0.7% to 9% and is less than 1% for upper digestive tract carcinomas.¹ Cutaneous metastases make up 2% of all tumors of the skin and commonly are located near the site of the primary tumor.² The most common cutaneous metastasis sites for gastric carcinoma include the neck, chest, and head.³ One of the more typical sites of cutaneous metastasis from gastric cancer is the umbilicus (ie, Sister Mary Joseph nodule). Cutaneous metastases from gastric carcinoma commonly present as asymptomatic hyperpigmented nodules.^1,3  

In our patient, histopathologic sections showed diffuse infiltration of the dermis by atypical polygonal/round cells arranged in cords and small aggregates. Some of the neoplastic cells had signet ring morphology (Figure). Tumor cells demonstrated positive immunostaining for CDX2, villin, CAM 5.2, and epithelial membrane antigen; they were negative for S-100, MART-1 (melanoma-associated antigen recognized by T cells 1), leukocyte common antigen, gross cystic disease fluid protein 15, estrogen and progesterone receptor, and HER2/neu (human epidermal growth factor receptor 2).  

Our patient's presentation was rare in that she developed an asymptomatic erythematous papule on the skin of the abdomen. However, her history of stage IIIB gastric adenocarcinoma in conjunction with the clinical picture and microscopic findings were most consistent with metastatic carcinoma of gastrointestinal origin. The histologic hallmarks of cutaneous metastatic gastric carcinoma include aggregates of neoplastic cells arranged in cords, sometimes forming glands, embedded in a fibrous stroma. Tumor cells may demonstrate signet ring morphology. These unique histologic findings, as well as positive immunostaining for CDX2, villin, CAM 5.2, and epithelial membrane antigen, rule out other potential diagnoses for an asymptomatic solitary papule.  

Dermatofibrosarcoma protuberans presents as an asymptomatic, slow-growing, indurated papule or plaque that develops into a red or brownish nodule. Histologically, dermatofibrosarcoma protuberans is characterized by spindled cells, few mitotic figures, infiltration of the subcutaneous tissue in a honeycomblike pattern, and obliteration of the adnexal structures.⁴  

Cutaneous B-cell lymphoma (CBCL) can present as single or multiple red papules or nodules located on the trunk, face, or extremities. Histologically, CBCL would show a nodular or diffuse infiltrate throughout the dermis, frequently with accentuation in the deep reticular dermis, sparing of the epidermis, and the presence of a grenz zone. The infiltrate in CBCL consists of CD20⁺, CD19⁺, and CD79a⁺ B cells. Identification of a monoclonal B-cell population either by immunohistochemistry or polymerase chain reaction would further support a diagnosis of CBCL.⁴ These specific histologic findings and the immunohistochemical staining pattern helped rule out CBCL as the diagnosis in our patient. 

Amelanotic melanomas present as flesh-colored to light pink papules, making them especially challenging to diagnose clinically. Asymmetrical, poorly circumscribed nests of atypical melanocytes as well as single melanocytes within the epidermis and dermis are seen histologically; mitotic figures are common. Immunohistochemical staining for melanoma includes S-100, human melanoma black 45, MART-1/Melan-A, tyrosinase, and microphthalmia-associated transcription factor 1.⁴  

Neurothekeomas can present as asymptomatic, solitary, flesh-colored papules located on the head, neck, and upper trunk. Histologically, neurothekeomas have a distinct appearance consisting of a well-defined mass composed of variable-sized lobules of spindled and epithelioid cells dispersed in a myxoid stroma within the reticular dermis.⁴ These specific histologic findings helped rule out neurothekeoma in our patient. 

Following the diagnosis of cutaneous metastatic gastric carcinoma in our patient, positron emission tomography and computed tomography of the chest, abdomen, and pelvis were unremarkable for distant disease. Subsequently, the patient underwent surgical excision of the papule with clear margins, followed by a short course of radiation therapy. She currently is under close monitoring but remains in remission with no new cutaneous manifestations of the gastric carcinoma. 

The Diagnosis: Cutaneous Metastatic Gastric Carcinoma  

Cutaneous metastasis of primary gastric carcinoma is a rare occurrence, with the more common metastatic sites being the lymph nodes, liver, and peritoneal cavity. The incidence of visceral neoplasm metastasis to the skin ranges from 0.7% to 9% and is less than 1% for upper digestive tract carcinomas.¹ Cutaneous metastases make up 2% of all tumors of the skin and commonly are located near the site of the primary tumor.² The most common cutaneous metastasis sites for gastric carcinoma include the neck, chest, and head.³ One of the more typical sites of cutaneous metastasis from gastric cancer is the umbilicus (ie, Sister Mary Joseph nodule). Cutaneous metastases from gastric carcinoma commonly present as asymptomatic hyperpigmented nodules.^1,3  

In our patient, histopathologic sections showed diffuse infiltration of the dermis by atypical polygonal/round cells arranged in cords and small aggregates. Some of the neoplastic cells had signet ring morphology (Figure). Tumor cells demonstrated positive immunostaining for CDX2, villin, CAM 5.2, and epithelial membrane antigen; they were negative for S-100, MART-1 (melanoma-associated antigen recognized by T cells 1), leukocyte common antigen, gross cystic disease fluid protein 15, estrogen and progesterone receptor, and HER2/neu (human epidermal growth factor receptor 2).  

Our patient's presentation was rare in that she developed an asymptomatic erythematous papule on the skin of the abdomen. However, her history of stage IIIB gastric adenocarcinoma in conjunction with the clinical picture and microscopic findings were most consistent with metastatic carcinoma of gastrointestinal origin. The histologic hallmarks of cutaneous metastatic gastric carcinoma include aggregates of neoplastic cells arranged in cords, sometimes forming glands, embedded in a fibrous stroma. Tumor cells may demonstrate signet ring morphology. These unique histologic findings, as well as positive immunostaining for CDX2, villin, CAM 5.2, and epithelial membrane antigen, rule out other potential diagnoses for an asymptomatic solitary papule.  

Dermatofibrosarcoma protuberans presents as an asymptomatic, slow-growing, indurated papule or plaque that develops into a red or brownish nodule. Histologically, dermatofibrosarcoma protuberans is characterized by spindled cells, few mitotic figures, infiltration of the subcutaneous tissue in a honeycomblike pattern, and obliteration of the adnexal structures.⁴  

Cutaneous B-cell lymphoma (CBCL) can present as single or multiple red papules or nodules located on the trunk, face, or extremities. Histologically, CBCL would show a nodular or diffuse infiltrate throughout the dermis, frequently with accentuation in the deep reticular dermis, sparing of the epidermis, and the presence of a grenz zone. The infiltrate in CBCL consists of CD20⁺, CD19⁺, and CD79a⁺ B cells. Identification of a monoclonal B-cell population either by immunohistochemistry or polymerase chain reaction would further support a diagnosis of CBCL.⁴ These specific histologic findings and the immunohistochemical staining pattern helped rule out CBCL as the diagnosis in our patient. 

Amelanotic melanomas present as flesh-colored to light pink papules, making them especially challenging to diagnose clinically. Asymmetrical, poorly circumscribed nests of atypical melanocytes as well as single melanocytes within the epidermis and dermis are seen histologically; mitotic figures are common. Immunohistochemical staining for melanoma includes S-100, human melanoma black 45, MART-1/Melan-A, tyrosinase, and microphthalmia-associated transcription factor 1.⁴  

Neurothekeomas can present as asymptomatic, solitary, flesh-colored papules located on the head, neck, and upper trunk. Histologically, neurothekeomas have a distinct appearance consisting of a well-defined mass composed of variable-sized lobules of spindled and epithelioid cells dispersed in a myxoid stroma within the reticular dermis.⁴ These specific histologic findings helped rule out neurothekeoma in our patient. 

Following the diagnosis of cutaneous metastatic gastric carcinoma in our patient, positron emission tomography and computed tomography of the chest, abdomen, and pelvis were unremarkable for distant disease. Subsequently, the patient underwent surgical excision of the papule with clear margins, followed by a short course of radiation therapy. She currently is under close monitoring but remains in remission with no new cutaneous manifestations of the gastric carcinoma. 

The Diagnosis: Cutaneous Metastatic Gastric Carcinoma  

Cutaneous metastasis of primary gastric carcinoma is a rare occurrence, with the more common metastatic sites being the lymph nodes, liver, and peritoneal cavity. The incidence of visceral neoplasm metastasis to the skin ranges from 0.7% to 9% and is less than 1% for upper digestive tract carcinomas.¹ Cutaneous metastases make up 2% of all tumors of the skin and commonly are located near the site of the primary tumor.² The most common cutaneous metastasis sites for gastric carcinoma include the neck, chest, and head.³ One of the more typical sites of cutaneous metastasis from gastric cancer is the umbilicus (ie, Sister Mary Joseph nodule). Cutaneous metastases from gastric carcinoma commonly present as asymptomatic hyperpigmented nodules.^1,3  

In our patient, histopathologic sections showed diffuse infiltration of the dermis by atypical polygonal/round cells arranged in cords and small aggregates. Some of the neoplastic cells had signet ring morphology (Figure). Tumor cells demonstrated positive immunostaining for CDX2, villin, CAM 5.2, and epithelial membrane antigen; they were negative for S-100, MART-1 (melanoma-associated antigen recognized by T cells 1), leukocyte common antigen, gross cystic disease fluid protein 15, estrogen and progesterone receptor, and HER2/neu (human epidermal growth factor receptor 2).  

Our patient's presentation was rare in that she developed an asymptomatic erythematous papule on the skin of the abdomen. However, her history of stage IIIB gastric adenocarcinoma in conjunction with the clinical picture and microscopic findings were most consistent with metastatic carcinoma of gastrointestinal origin. The histologic hallmarks of cutaneous metastatic gastric carcinoma include aggregates of neoplastic cells arranged in cords, sometimes forming glands, embedded in a fibrous stroma. Tumor cells may demonstrate signet ring morphology. These unique histologic findings, as well as positive immunostaining for CDX2, villin, CAM 5.2, and epithelial membrane antigen, rule out other potential diagnoses for an asymptomatic solitary papule.  

Dermatofibrosarcoma protuberans presents as an asymptomatic, slow-growing, indurated papule or plaque that develops into a red or brownish nodule. Histologically, dermatofibrosarcoma protuberans is characterized by spindled cells, few mitotic figures, infiltration of the subcutaneous tissue in a honeycomblike pattern, and obliteration of the adnexal structures.⁴  

Cutaneous B-cell lymphoma (CBCL) can present as single or multiple red papules or nodules located on the trunk, face, or extremities. Histologically, CBCL would show a nodular or diffuse infiltrate throughout the dermis, frequently with accentuation in the deep reticular dermis, sparing of the epidermis, and the presence of a grenz zone. The infiltrate in CBCL consists of CD20⁺, CD19⁺, and CD79a⁺ B cells. Identification of a monoclonal B-cell population either by immunohistochemistry or polymerase chain reaction would further support a diagnosis of CBCL.⁴ These specific histologic findings and the immunohistochemical staining pattern helped rule out CBCL as the diagnosis in our patient. 

Amelanotic melanomas present as flesh-colored to light pink papules, making them especially challenging to diagnose clinically. Asymmetrical, poorly circumscribed nests of atypical melanocytes as well as single melanocytes within the epidermis and dermis are seen histologically; mitotic figures are common. Immunohistochemical staining for melanoma includes S-100, human melanoma black 45, MART-1/Melan-A, tyrosinase, and microphthalmia-associated transcription factor 1.⁴  

Neurothekeomas can present as asymptomatic, solitary, flesh-colored papules located on the head, neck, and upper trunk. Histologically, neurothekeomas have a distinct appearance consisting of a well-defined mass composed of variable-sized lobules of spindled and epithelioid cells dispersed in a myxoid stroma within the reticular dermis.⁴ These specific histologic findings helped rule out neurothekeoma in our patient. 

Following the diagnosis of cutaneous metastatic gastric carcinoma in our patient, positron emission tomography and computed tomography of the chest, abdomen, and pelvis were unremarkable for distant disease. Subsequently, the patient underwent surgical excision of the papule with clear margins, followed by a short course of radiation therapy. She currently is under close monitoring but remains in remission with no new cutaneous manifestations of the gastric carcinoma. 

The Diagnosis: Hyperkeratosis Lenticularis Perstans (Flegel Disease) 

Hyperkeratosis lenticularis perstans, also known as Flegel disease, is a rare dermatosis first described by Flegel¹ in 1958. This benign disorder is characterized by multiple asymptomatic 1- to 5-mm keratotic papules in a symmetric distribution favoring the dorsal aspects of the feet and distal extremities in adults. An autosomal-dominant inheritance pattern has been postulated, though many cases sporadically occur.² The characteristic spiky papules typically appear during mid to late adulthood and tend to persist. Treatment options are lacking, with reports of partial or no response to topical calcipotriol, topical 5-fluorouracil, cryotherapy, and topical and oral retinoids.^3,4  

The histopathology of hyperkeratosis lenticularis perstans is distinct, showing a central discrete area of orthohyperkeratosis with patchy parakeratosis flanked by a normal stratum corneum. The underlying epidermis typically shows effacement of the rete ridge pattern with subtle basal zone vacuolization and rare necrotic keratinocytes with an underlying lichenoid infiltrate within the papillary dermis comprised of lymphomononuclear cells.  

In contrast, punctate porokeratosis clinically tends to involve the palms and soles, though the arms and legs also may be involved. This entity tends to occur during adolescence. A raised hyperkeratotic papule clinically is present. Histopathologically, the epidermis has a cup-shaped depression filled with hyperkeratosis and a column of parakeratosis (coronoid lamellae)(Figure 1).  

Acrokeratosis verruciformis of Hopf clinically appears on the dorsal aspects of the hands and feet as small warty papules in association with Darier disease. It typically presents during early childhood. Histopathology shows tiered hyperkeratosis, papillomatosis, and acanthosis (Figure 2).  

Perforating granuloma annulare presents on the dorsal aspects of the hands and fingers as scaly papules with either central umbilication or keratotic plugs. Histopathology shows transepidermal elimination of degenerated collagen (Figure 3).  

Stucco keratoses present on the dorsal aspects of the feet and ankles but are waxy smooth papules as opposed to hyperkeratotic spiky papules. Histologically, they are characterized by retention hyperkeratosis with lack of parakeratosis and regular acanthosis with a "string sign" indicating that the lesion extends to a uniform depth. (Figure 4).  

The Diagnosis: Hyperkeratosis Lenticularis Perstans (Flegel Disease) 

Hyperkeratosis lenticularis perstans, also known as Flegel disease, is a rare dermatosis first described by Flegel¹ in 1958. This benign disorder is characterized by multiple asymptomatic 1- to 5-mm keratotic papules in a symmetric distribution favoring the dorsal aspects of the feet and distal extremities in adults. An autosomal-dominant inheritance pattern has been postulated, though many cases sporadically occur.² The characteristic spiky papules typically appear during mid to late adulthood and tend to persist. Treatment options are lacking, with reports of partial or no response to topical calcipotriol, topical 5-fluorouracil, cryotherapy, and topical and oral retinoids.^3,4  

The histopathology of hyperkeratosis lenticularis perstans is distinct, showing a central discrete area of orthohyperkeratosis with patchy parakeratosis flanked by a normal stratum corneum. The underlying epidermis typically shows effacement of the rete ridge pattern with subtle basal zone vacuolization and rare necrotic keratinocytes with an underlying lichenoid infiltrate within the papillary dermis comprised of lymphomononuclear cells.  

In contrast, punctate porokeratosis clinically tends to involve the palms and soles, though the arms and legs also may be involved. This entity tends to occur during adolescence. A raised hyperkeratotic papule clinically is present. Histopathologically, the epidermis has a cup-shaped depression filled with hyperkeratosis and a column of parakeratosis (coronoid lamellae)(Figure 1).  

Acrokeratosis verruciformis of Hopf clinically appears on the dorsal aspects of the hands and feet as small warty papules in association with Darier disease. It typically presents during early childhood. Histopathology shows tiered hyperkeratosis, papillomatosis, and acanthosis (Figure 2).  

Perforating granuloma annulare presents on the dorsal aspects of the hands and fingers as scaly papules with either central umbilication or keratotic plugs. Histopathology shows transepidermal elimination of degenerated collagen (Figure 3).  

Stucco keratoses present on the dorsal aspects of the feet and ankles but are waxy smooth papules as opposed to hyperkeratotic spiky papules. Histologically, they are characterized by retention hyperkeratosis with lack of parakeratosis and regular acanthosis with a "string sign" indicating that the lesion extends to a uniform depth. (Figure 4).  

The Diagnosis: Hyperkeratosis Lenticularis Perstans (Flegel Disease) 

Hyperkeratosis lenticularis perstans, also known as Flegel disease, is a rare dermatosis first described by Flegel¹ in 1958. This benign disorder is characterized by multiple asymptomatic 1- to 5-mm keratotic papules in a symmetric distribution favoring the dorsal aspects of the feet and distal extremities in adults. An autosomal-dominant inheritance pattern has been postulated, though many cases sporadically occur.² The characteristic spiky papules typically appear during mid to late adulthood and tend to persist. Treatment options are lacking, with reports of partial or no response to topical calcipotriol, topical 5-fluorouracil, cryotherapy, and topical and oral retinoids.^3,4  

The histopathology of hyperkeratosis lenticularis perstans is distinct, showing a central discrete area of orthohyperkeratosis with patchy parakeratosis flanked by a normal stratum corneum. The underlying epidermis typically shows effacement of the rete ridge pattern with subtle basal zone vacuolization and rare necrotic keratinocytes with an underlying lichenoid infiltrate within the papillary dermis comprised of lymphomononuclear cells.  

In contrast, punctate porokeratosis clinically tends to involve the palms and soles, though the arms and legs also may be involved. This entity tends to occur during adolescence. A raised hyperkeratotic papule clinically is present. Histopathologically, the epidermis has a cup-shaped depression filled with hyperkeratosis and a column of parakeratosis (coronoid lamellae)(Figure 1).  

Acrokeratosis verruciformis of Hopf clinically appears on the dorsal aspects of the hands and feet as small warty papules in association with Darier disease. It typically presents during early childhood. Histopathology shows tiered hyperkeratosis, papillomatosis, and acanthosis (Figure 2).  

Perforating granuloma annulare presents on the dorsal aspects of the hands and fingers as scaly papules with either central umbilication or keratotic plugs. Histopathology shows transepidermal elimination of degenerated collagen (Figure 3).  

Stucco keratoses present on the dorsal aspects of the feet and ankles but are waxy smooth papules as opposed to hyperkeratotic spiky papules. Histologically, they are characterized by retention hyperkeratosis with lack of parakeratosis and regular acanthosis with a "string sign" indicating that the lesion extends to a uniform depth. (Figure 4).  

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy characterized by diffuse blanchable telangiectases that usually develop in late adulthood. It appears morphologically identical to generalized essential telangiectasia (GET), but skin biopsy characteristically shows dilated superficial blood vessels in the papillary dermis that are surrounded by a thickened layer of type IV collagen.¹ We report a case of CCV occurring in an elderly white man.

A 72-year-old man presented with an asymptomatic rash on the arms, legs, and abdomen of 3 years’ duration. His medical history was remarkable for hypothyroidism, hypertension, reflex sympathetic dystrophy syndrome, coronary artery disease, and nonmelanoma skin cancer. He denied any changes in medications or illnesses prior to onset of the rash. Physical examination revealed diffuse, erythematous, blanchable telangiectases on the arms, legs, and trunk (Figure 1). No petechiae, atrophy, or epidermal changes were appreciated. Darier sign was negative.

Skin biopsy is essential to differentiate CCV from GET, which appears morphologically identical. Cutaneous collagenous vasculopathy may be underreported as a result of clinician choice not to biopsy due to a presumptive diagnosis of GET.³ Successful treatment with a pulsed dye laser has been reported,⁷ though the extent of disease may make complete destruction of the lesions difficult to accomplish. Although it is theorized that CCV may be a marker for underlying systemic disease or even a genetic defect causing abnormal collagen deposition, its cause has yet to be ascertained.⁵ Previously reported patients have had a variety of comorbidities, including several cases of type 2 diabetes mellitus.⁶ Another patient was reported to have recently started treatment with an angiotensin receptor blocker prior to onset of CCV.⁵

Our case contributes to the small series of reported patients with this rare diagnosis and further suggests that it may be underreported at this time. Similar to previously reported cases, our patient was an elderly white individual. Although our patient had long-standing iatrogenic hypothyroidism, no recent medication changes or underlying comorbidities could be tied to the development of CCV. Further studies are needed to determine if this disease process is associated with any underlying systemic illnesses, medications, or family history.

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy characterized by diffuse blanchable telangiectases that usually develop in late adulthood. It appears morphologically identical to generalized essential telangiectasia (GET), but skin biopsy characteristically shows dilated superficial blood vessels in the papillary dermis that are surrounded by a thickened layer of type IV collagen.¹ We report a case of CCV occurring in an elderly white man.

A 72-year-old man presented with an asymptomatic rash on the arms, legs, and abdomen of 3 years’ duration. His medical history was remarkable for hypothyroidism, hypertension, reflex sympathetic dystrophy syndrome, coronary artery disease, and nonmelanoma skin cancer. He denied any changes in medications or illnesses prior to onset of the rash. Physical examination revealed diffuse, erythematous, blanchable telangiectases on the arms, legs, and trunk (Figure 1). No petechiae, atrophy, or epidermal changes were appreciated. Darier sign was negative.

Skin biopsy is essential to differentiate CCV from GET, which appears morphologically identical. Cutaneous collagenous vasculopathy may be underreported as a result of clinician choice not to biopsy due to a presumptive diagnosis of GET.³ Successful treatment with a pulsed dye laser has been reported,⁷ though the extent of disease may make complete destruction of the lesions difficult to accomplish. Although it is theorized that CCV may be a marker for underlying systemic disease or even a genetic defect causing abnormal collagen deposition, its cause has yet to be ascertained.⁵ Previously reported patients have had a variety of comorbidities, including several cases of type 2 diabetes mellitus.⁶ Another patient was reported to have recently started treatment with an angiotensin receptor blocker prior to onset of CCV.⁵

Our case contributes to the small series of reported patients with this rare diagnosis and further suggests that it may be underreported at this time. Similar to previously reported cases, our patient was an elderly white individual. Although our patient had long-standing iatrogenic hypothyroidism, no recent medication changes or underlying comorbidities could be tied to the development of CCV. Further studies are needed to determine if this disease process is associated with any underlying systemic illnesses, medications, or family history.

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy characterized by diffuse blanchable telangiectases that usually develop in late adulthood. It appears morphologically identical to generalized essential telangiectasia (GET), but skin biopsy characteristically shows dilated superficial blood vessels in the papillary dermis that are surrounded by a thickened layer of type IV collagen.¹ We report a case of CCV occurring in an elderly white man.

A 72-year-old man presented with an asymptomatic rash on the arms, legs, and abdomen of 3 years’ duration. His medical history was remarkable for hypothyroidism, hypertension, reflex sympathetic dystrophy syndrome, coronary artery disease, and nonmelanoma skin cancer. He denied any changes in medications or illnesses prior to onset of the rash. Physical examination revealed diffuse, erythematous, blanchable telangiectases on the arms, legs, and trunk (Figure 1). No petechiae, atrophy, or epidermal changes were appreciated. Darier sign was negative.

Skin biopsy is essential to differentiate CCV from GET, which appears morphologically identical. Cutaneous collagenous vasculopathy may be underreported as a result of clinician choice not to biopsy due to a presumptive diagnosis of GET.³ Successful treatment with a pulsed dye laser has been reported,⁷ though the extent of disease may make complete destruction of the lesions difficult to accomplish. Although it is theorized that CCV may be a marker for underlying systemic disease or even a genetic defect causing abnormal collagen deposition, its cause has yet to be ascertained.⁵ Previously reported patients have had a variety of comorbidities, including several cases of type 2 diabetes mellitus.⁶ Another patient was reported to have recently started treatment with an angiotensin receptor blocker prior to onset of CCV.⁵

Our case contributes to the small series of reported patients with this rare diagnosis and further suggests that it may be underreported at this time. Similar to previously reported cases, our patient was an elderly white individual. Although our patient had long-standing iatrogenic hypothyroidism, no recent medication changes or underlying comorbidities could be tied to the development of CCV. Further studies are needed to determine if this disease process is associated with any underlying systemic illnesses, medications, or family history.

The Diagnosis: Adult Colloid Milium 

A 4-mm punch biopsy was performed and histopathologic evaluation revealed collections of amorphic eosinophilic material and fissures in the papillary dermis with sparing of the dermoepidermal junction, indicating adult colloid milium (Figure 1).  

Adult colloid milium is an uncommon condition with grouped translucent to whitish papules that present on sun-exposed skin on the hands, face, neck, or ears in middle-aged adults.¹ It has been associated with petrochemical exposure, tanning bed use, and excessive sun exposure. Our patient had a history of sun exposure, specifically to the left hand while driving. This condition is widely thought to be a result of photoinduced damage to elastic fibers and may potentially be a popular variant of severe solar elastosis.² Due to vascular fragility, trauma to these locations often will result in hemorrhage into individual lesions, as observed in our patient (Figure 2).  

Adult colloid milium is diagnosed clinically and may mimic lichen or systemic amyloidosis, syringomas, lipoid proteinosis, molluscum contagiosum, steatocystoma multiplex, and sarcoidosis.²  

Biopsy often is helpful in determining the diagnosis. Histopathology reveals amorphous eosinophilic deposits with fissures in the papillary dermis. These deposits are thought to be remnants of degenerated elastic fibers. Stains often are helpful, as the deposits are weakly apple-green birefringent on Congo red stain and are periodic acid-Schiff and thioflavin T positive. Laminin and type IV collagen stains are negative with adult colloid milium but are positive with amyloidosis and lipoid proteinosis.³ Electron microscopy also may help distinguish between amyloidosis and adult colloid milium, as these conditions may have a similar histologic appearance.

Treatment has not proven to be consistently helpful, as cryotherapy and dermabrasion have been the mainstay of treatment, often with disappointing results.⁴ Laser treatment has been shown to be of some benefit in treating these lesions.² 

The Diagnosis: Adult Colloid Milium 

A 4-mm punch biopsy was performed and histopathologic evaluation revealed collections of amorphic eosinophilic material and fissures in the papillary dermis with sparing of the dermoepidermal junction, indicating adult colloid milium (Figure 1).  

Adult colloid milium is an uncommon condition with grouped translucent to whitish papules that present on sun-exposed skin on the hands, face, neck, or ears in middle-aged adults.¹ It has been associated with petrochemical exposure, tanning bed use, and excessive sun exposure. Our patient had a history of sun exposure, specifically to the left hand while driving. This condition is widely thought to be a result of photoinduced damage to elastic fibers and may potentially be a popular variant of severe solar elastosis.² Due to vascular fragility, trauma to these locations often will result in hemorrhage into individual lesions, as observed in our patient (Figure 2).  

Adult colloid milium is diagnosed clinically and may mimic lichen or systemic amyloidosis, syringomas, lipoid proteinosis, molluscum contagiosum, steatocystoma multiplex, and sarcoidosis.²  

Biopsy often is helpful in determining the diagnosis. Histopathology reveals amorphous eosinophilic deposits with fissures in the papillary dermis. These deposits are thought to be remnants of degenerated elastic fibers. Stains often are helpful, as the deposits are weakly apple-green birefringent on Congo red stain and are periodic acid-Schiff and thioflavin T positive. Laminin and type IV collagen stains are negative with adult colloid milium but are positive with amyloidosis and lipoid proteinosis.³ Electron microscopy also may help distinguish between amyloidosis and adult colloid milium, as these conditions may have a similar histologic appearance.

Treatment has not proven to be consistently helpful, as cryotherapy and dermabrasion have been the mainstay of treatment, often with disappointing results.⁴ Laser treatment has been shown to be of some benefit in treating these lesions.² 

The Diagnosis: Adult Colloid Milium 

A 4-mm punch biopsy was performed and histopathologic evaluation revealed collections of amorphic eosinophilic material and fissures in the papillary dermis with sparing of the dermoepidermal junction, indicating adult colloid milium (Figure 1).  

Adult colloid milium is an uncommon condition with grouped translucent to whitish papules that present on sun-exposed skin on the hands, face, neck, or ears in middle-aged adults.¹ It has been associated with petrochemical exposure, tanning bed use, and excessive sun exposure. Our patient had a history of sun exposure, specifically to the left hand while driving. This condition is widely thought to be a result of photoinduced damage to elastic fibers and may potentially be a popular variant of severe solar elastosis.² Due to vascular fragility, trauma to these locations often will result in hemorrhage into individual lesions, as observed in our patient (Figure 2).  

Adult colloid milium is diagnosed clinically and may mimic lichen or systemic amyloidosis, syringomas, lipoid proteinosis, molluscum contagiosum, steatocystoma multiplex, and sarcoidosis.²  

Biopsy often is helpful in determining the diagnosis. Histopathology reveals amorphous eosinophilic deposits with fissures in the papillary dermis. These deposits are thought to be remnants of degenerated elastic fibers. Stains often are helpful, as the deposits are weakly apple-green birefringent on Congo red stain and are periodic acid-Schiff and thioflavin T positive. Laminin and type IV collagen stains are negative with adult colloid milium but are positive with amyloidosis and lipoid proteinosis.³ Electron microscopy also may help distinguish between amyloidosis and adult colloid milium, as these conditions may have a similar histologic appearance.

Treatment has not proven to be consistently helpful, as cryotherapy and dermabrasion have been the mainstay of treatment, often with disappointing results.⁴ Laser treatment has been shown to be of some benefit in treating these lesions.²