Photo Challenge

The Diagnosis: Eruptive Syringoma 

A punch biopsy of a lesion on the penis was performed. Histopathologic examination revealed many tadpole-shaped cords of epithelial cells and small ducts in the dermis (Figure). Based on clinical and histopathological findings, a diagnosis of eruptive syringoma was made. The patient declined treatment.  

Syringomas are common benign eccrine neoplasms. They present clinically as small flesh-colored to brownish papules symmetrically distributed on the face, neck, trunk, pubic area, arms, and legs.^1-3 Classic syringoma occurs more frequently in young adult women.¹ Eruptive syringoma is a rare variant, and the age of onset ranges from 3 to 50 years.^1-13  Eruptive syringoma is the term for multiple lesions that occur synchronously in any part of the body.^1,4,13 The term eruptive is not the opposite of localized and refers to the time of onset of the lesion. There may be both a generalized eruptive syringoma or a localized eruptive syringoma depending on the distribution of the lesions.¹ The most common site for syringoma occurrence is the eyelid; penile syringoma is extremely rare. Several cases of penile syringoma have been reported, but eruptive penile syringoma is rare.^3,5-10,12,13  

Histopathology is essential for the diagnosis of syringoma. Hematoxylin and eosin stain shows multiple small cystic ducts and epithelial cell nests in the dermis. Ductal structures sometimes appear tadpolelike or comma shaped depending on the section.^1,2,7,12 

The clinical differential diagnosis of syringoma includes sebaceous hyperplasia, verruca plana, molluscum contagiosum, bowenoid papulosis, condyloma acuminatum, lichen planus, lichen nitidus, milia, angiofibroma, epidermal cyst, calcinosis cutis, granuloma annulare, and sarcoidosis.^3,8,12 

Because syringoma is benign, treatment is not necessary unless there is a cosmetic problem.^3,5,7,8,12 There is no satisfactory treatment of eruptive penile syringoma. Treatment options include topical tretinoin and adapalene, oral isotretinoin, cryotherapy, microelectrodesiccation with an epilating needle, dermabrasion, CO₂ laser, and surgical excision.^2,3,7,8,12  

Adult patients with penile syringoma may be concerned about sexually transmitted diseases due to the appearance of the papules. If cosmesis is not an issue, clinicians should reassure the patient after a biopsy that the lesions are benign and self-limiting without recommending treatment.  

The Diagnosis: Eruptive Syringoma 

A punch biopsy of a lesion on the penis was performed. Histopathologic examination revealed many tadpole-shaped cords of epithelial cells and small ducts in the dermis (Figure). Based on clinical and histopathological findings, a diagnosis of eruptive syringoma was made. The patient declined treatment.  

Syringomas are common benign eccrine neoplasms. They present clinically as small flesh-colored to brownish papules symmetrically distributed on the face, neck, trunk, pubic area, arms, and legs.^1-3 Classic syringoma occurs more frequently in young adult women.¹ Eruptive syringoma is a rare variant, and the age of onset ranges from 3 to 50 years.^1-13  Eruptive syringoma is the term for multiple lesions that occur synchronously in any part of the body.^1,4,13 The term eruptive is not the opposite of localized and refers to the time of onset of the lesion. There may be both a generalized eruptive syringoma or a localized eruptive syringoma depending on the distribution of the lesions.¹ The most common site for syringoma occurrence is the eyelid; penile syringoma is extremely rare. Several cases of penile syringoma have been reported, but eruptive penile syringoma is rare.^3,5-10,12,13  

Histopathology is essential for the diagnosis of syringoma. Hematoxylin and eosin stain shows multiple small cystic ducts and epithelial cell nests in the dermis. Ductal structures sometimes appear tadpolelike or comma shaped depending on the section.^1,2,7,12 

The clinical differential diagnosis of syringoma includes sebaceous hyperplasia, verruca plana, molluscum contagiosum, bowenoid papulosis, condyloma acuminatum, lichen planus, lichen nitidus, milia, angiofibroma, epidermal cyst, calcinosis cutis, granuloma annulare, and sarcoidosis.^3,8,12 

Because syringoma is benign, treatment is not necessary unless there is a cosmetic problem.^3,5,7,8,12 There is no satisfactory treatment of eruptive penile syringoma. Treatment options include topical tretinoin and adapalene, oral isotretinoin, cryotherapy, microelectrodesiccation with an epilating needle, dermabrasion, CO₂ laser, and surgical excision.^2,3,7,8,12  

Adult patients with penile syringoma may be concerned about sexually transmitted diseases due to the appearance of the papules. If cosmesis is not an issue, clinicians should reassure the patient after a biopsy that the lesions are benign and self-limiting without recommending treatment.  

The Diagnosis: Eruptive Syringoma 

A punch biopsy of a lesion on the penis was performed. Histopathologic examination revealed many tadpole-shaped cords of epithelial cells and small ducts in the dermis (Figure). Based on clinical and histopathological findings, a diagnosis of eruptive syringoma was made. The patient declined treatment.  

Syringomas are common benign eccrine neoplasms. They present clinically as small flesh-colored to brownish papules symmetrically distributed on the face, neck, trunk, pubic area, arms, and legs.^1-3 Classic syringoma occurs more frequently in young adult women.¹ Eruptive syringoma is a rare variant, and the age of onset ranges from 3 to 50 years.^1-13  Eruptive syringoma is the term for multiple lesions that occur synchronously in any part of the body.^1,4,13 The term eruptive is not the opposite of localized and refers to the time of onset of the lesion. There may be both a generalized eruptive syringoma or a localized eruptive syringoma depending on the distribution of the lesions.¹ The most common site for syringoma occurrence is the eyelid; penile syringoma is extremely rare. Several cases of penile syringoma have been reported, but eruptive penile syringoma is rare.^3,5-10,12,13  

Histopathology is essential for the diagnosis of syringoma. Hematoxylin and eosin stain shows multiple small cystic ducts and epithelial cell nests in the dermis. Ductal structures sometimes appear tadpolelike or comma shaped depending on the section.^1,2,7,12 

The clinical differential diagnosis of syringoma includes sebaceous hyperplasia, verruca plana, molluscum contagiosum, bowenoid papulosis, condyloma acuminatum, lichen planus, lichen nitidus, milia, angiofibroma, epidermal cyst, calcinosis cutis, granuloma annulare, and sarcoidosis.^3,8,12 

Because syringoma is benign, treatment is not necessary unless there is a cosmetic problem.^3,5,7,8,12 There is no satisfactory treatment of eruptive penile syringoma. Treatment options include topical tretinoin and adapalene, oral isotretinoin, cryotherapy, microelectrodesiccation with an epilating needle, dermabrasion, CO₂ laser, and surgical excision.^2,3,7,8,12  

Adult patients with penile syringoma may be concerned about sexually transmitted diseases due to the appearance of the papules. If cosmesis is not an issue, clinicians should reassure the patient after a biopsy that the lesions are benign and self-limiting without recommending treatment.  

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination demonstrated acanthosis and coarse hypergranulosis with enlarged keratinocytes exhibiting blue cytoplasmic discoloration (Figure), which was suggestive of acquired epidermodysplasia verruciformis (EV).  

Acquired EV is a rare dermatologic condition associated with specific human papillomavirus (HPV) types that presents with recalcitrant lesions most commonly in the setting of immunosuppression.¹ The most common HPV types associated with EV are HPV-5 and -8, but associations with HPV-3, -9, -10, -12, -14, -15, -17, -19 to -25, -36 to -38, -47, and -50 also have been reported.^1,2 Acquired EV has been identified in individuals with human immunodeficiency virus, as well as in immunosuppressed patients with organ transplantation, Hodgkin lymphoma, systemic lupus erythematosus, and IgM deficiency, and in patients taking immunosuppressive medications such as tumor necrosis factor α inhibitors.^1,3 The diagnosis is clinicopathological with potential polymerase chain reaction studies to identify underlying HPV types. 

Acquired EV presents as hypopigmented to red, tinea versicolor-like macules or as verrucous, flat-topped papules on the trunk, arms, and/or legs.⁴ Histopathology reveals viral epidermal cytopathic changes, blue cytoplasm, and coarse hypogranulosis.⁴ 

There is no standardized treatment regimen for acquired EV, and no single approach has proven to yield an efficacious clinical outcome. Topical treatment options include steroids, retinoids, immunomodulators, cryotherapy, and electrosurgery, whereas retinoids or interferon alfa have been used as oral systemic therapy. Photodynamic therapy also has been shown to improve symptoms.³ Combination therapy such as interferon alfa with zidovudine or imiquimod with oral isotretinoin has shown better results than any single treatment.⁴ Due to the underlying HPV infection and its role in promotion of skin cancer development, lesions can characteristically undergo malignant transformations into Bowen disease but most commonly invasive squamous cell carcinoma (SCC), with initial lesions preferentially affecting sun-exposed areas due to the synergistic effect of UV light with EV-HPV lesions. The EV-HPV strains ^{5, 8,} and 41 carry the highest oncogenic potential.5 Little is known of the true incidence of oncogenicity for acquired EV. Regardless, consistent sun protection and lifelong clinical examinations are critical for prognosis.⁵  

The differential diagnosis of EV presenting in a tattoo includes allergic contact dermatitis, cutaneous sarcoidosis, pityriasis versicolor, and SCC. The pathology is critical to differentiate between these entities. The most frequently reported skin reactions to tattoo ink include inflammatory diseases (eg, allergic contact dermatitis, granulomatous reaction) or infectious diseases (eg, bacterial, viral, fungal).⁶ Allergic contact dermatitis, typically red pigment, is a common tattoo reaction. The most common histologic feature, however, is spongiosis, which results from intercellular edema. It often is limited to the lower epidermis but may affect the upper layers if the reaction is severe.⁷ Cutaneous sarcoidosis is a great masquerader that can present in various ways; however, its salient features on pathology are noncaseating granuloma involving the basal cell layer and epithelioid granuloma consisting of Langerhans giant cells.⁸ Although pityriasis versicolor can present in young immunocompromised adults, histologically salient features are the presence of both spores and hyphae in the stratum corneum.⁹ Although immunosuppression is a known risk factor for SCC, it is characterized histologically by hyperkeratosis, parakeratosis, and acanthosis with thickened and elongated rete ridges. Scattered atypical cells and frequent mitoses are present.¹⁰ 

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination demonstrated acanthosis and coarse hypergranulosis with enlarged keratinocytes exhibiting blue cytoplasmic discoloration (Figure), which was suggestive of acquired epidermodysplasia verruciformis (EV).  

Acquired EV is a rare dermatologic condition associated with specific human papillomavirus (HPV) types that presents with recalcitrant lesions most commonly in the setting of immunosuppression.¹ The most common HPV types associated with EV are HPV-5 and -8, but associations with HPV-3, -9, -10, -12, -14, -15, -17, -19 to -25, -36 to -38, -47, and -50 also have been reported.^1,2 Acquired EV has been identified in individuals with human immunodeficiency virus, as well as in immunosuppressed patients with organ transplantation, Hodgkin lymphoma, systemic lupus erythematosus, and IgM deficiency, and in patients taking immunosuppressive medications such as tumor necrosis factor α inhibitors.^1,3 The diagnosis is clinicopathological with potential polymerase chain reaction studies to identify underlying HPV types. 

Acquired EV presents as hypopigmented to red, tinea versicolor-like macules or as verrucous, flat-topped papules on the trunk, arms, and/or legs.⁴ Histopathology reveals viral epidermal cytopathic changes, blue cytoplasm, and coarse hypogranulosis.⁴ 

There is no standardized treatment regimen for acquired EV, and no single approach has proven to yield an efficacious clinical outcome. Topical treatment options include steroids, retinoids, immunomodulators, cryotherapy, and electrosurgery, whereas retinoids or interferon alfa have been used as oral systemic therapy. Photodynamic therapy also has been shown to improve symptoms.³ Combination therapy such as interferon alfa with zidovudine or imiquimod with oral isotretinoin has shown better results than any single treatment.⁴ Due to the underlying HPV infection and its role in promotion of skin cancer development, lesions can characteristically undergo malignant transformations into Bowen disease but most commonly invasive squamous cell carcinoma (SCC), with initial lesions preferentially affecting sun-exposed areas due to the synergistic effect of UV light with EV-HPV lesions. The EV-HPV strains ^{5, 8,} and 41 carry the highest oncogenic potential.5 Little is known of the true incidence of oncogenicity for acquired EV. Regardless, consistent sun protection and lifelong clinical examinations are critical for prognosis.⁵  

The differential diagnosis of EV presenting in a tattoo includes allergic contact dermatitis, cutaneous sarcoidosis, pityriasis versicolor, and SCC. The pathology is critical to differentiate between these entities. The most frequently reported skin reactions to tattoo ink include inflammatory diseases (eg, allergic contact dermatitis, granulomatous reaction) or infectious diseases (eg, bacterial, viral, fungal).⁶ Allergic contact dermatitis, typically red pigment, is a common tattoo reaction. The most common histologic feature, however, is spongiosis, which results from intercellular edema. It often is limited to the lower epidermis but may affect the upper layers if the reaction is severe.⁷ Cutaneous sarcoidosis is a great masquerader that can present in various ways; however, its salient features on pathology are noncaseating granuloma involving the basal cell layer and epithelioid granuloma consisting of Langerhans giant cells.⁸ Although pityriasis versicolor can present in young immunocompromised adults, histologically salient features are the presence of both spores and hyphae in the stratum corneum.⁹ Although immunosuppression is a known risk factor for SCC, it is characterized histologically by hyperkeratosis, parakeratosis, and acanthosis with thickened and elongated rete ridges. Scattered atypical cells and frequent mitoses are present.¹⁰ 

The Diagnosis: Epidermodysplasia Verruciformis 

Histopathologic examination demonstrated acanthosis and coarse hypergranulosis with enlarged keratinocytes exhibiting blue cytoplasmic discoloration (Figure), which was suggestive of acquired epidermodysplasia verruciformis (EV).  

Acquired EV is a rare dermatologic condition associated with specific human papillomavirus (HPV) types that presents with recalcitrant lesions most commonly in the setting of immunosuppression.¹ The most common HPV types associated with EV are HPV-5 and -8, but associations with HPV-3, -9, -10, -12, -14, -15, -17, -19 to -25, -36 to -38, -47, and -50 also have been reported.^1,2 Acquired EV has been identified in individuals with human immunodeficiency virus, as well as in immunosuppressed patients with organ transplantation, Hodgkin lymphoma, systemic lupus erythematosus, and IgM deficiency, and in patients taking immunosuppressive medications such as tumor necrosis factor α inhibitors.^1,3 The diagnosis is clinicopathological with potential polymerase chain reaction studies to identify underlying HPV types. 

Acquired EV presents as hypopigmented to red, tinea versicolor-like macules or as verrucous, flat-topped papules on the trunk, arms, and/or legs.⁴ Histopathology reveals viral epidermal cytopathic changes, blue cytoplasm, and coarse hypogranulosis.⁴ 

There is no standardized treatment regimen for acquired EV, and no single approach has proven to yield an efficacious clinical outcome. Topical treatment options include steroids, retinoids, immunomodulators, cryotherapy, and electrosurgery, whereas retinoids or interferon alfa have been used as oral systemic therapy. Photodynamic therapy also has been shown to improve symptoms.³ Combination therapy such as interferon alfa with zidovudine or imiquimod with oral isotretinoin has shown better results than any single treatment.⁴ Due to the underlying HPV infection and its role in promotion of skin cancer development, lesions can characteristically undergo malignant transformations into Bowen disease but most commonly invasive squamous cell carcinoma (SCC), with initial lesions preferentially affecting sun-exposed areas due to the synergistic effect of UV light with EV-HPV lesions. The EV-HPV strains ^{5, 8,} and 41 carry the highest oncogenic potential.5 Little is known of the true incidence of oncogenicity for acquired EV. Regardless, consistent sun protection and lifelong clinical examinations are critical for prognosis.⁵  

The differential diagnosis of EV presenting in a tattoo includes allergic contact dermatitis, cutaneous sarcoidosis, pityriasis versicolor, and SCC. The pathology is critical to differentiate between these entities. The most frequently reported skin reactions to tattoo ink include inflammatory diseases (eg, allergic contact dermatitis, granulomatous reaction) or infectious diseases (eg, bacterial, viral, fungal).⁶ Allergic contact dermatitis, typically red pigment, is a common tattoo reaction. The most common histologic feature, however, is spongiosis, which results from intercellular edema. It often is limited to the lower epidermis but may affect the upper layers if the reaction is severe.⁷ Cutaneous sarcoidosis is a great masquerader that can present in various ways; however, its salient features on pathology are noncaseating granuloma involving the basal cell layer and epithelioid granuloma consisting of Langerhans giant cells.⁸ Although pityriasis versicolor can present in young immunocompromised adults, histologically salient features are the presence of both spores and hyphae in the stratum corneum.⁹ Although immunosuppression is a known risk factor for SCC, it is characterized histologically by hyperkeratosis, parakeratosis, and acanthosis with thickened and elongated rete ridges. Scattered atypical cells and frequent mitoses are present.¹⁰ 

The Diagnosis: Plasma Cell Gingivitis 

Microscopic analysis demonstrated an acanthotic stratified squamous epithelium with an edematous fibrous stroma containing dense perivascular infiltrates of plasma cells and lymphocytes (Figure 1). Immunohistochemical analysis with kappa, lambda, and CD79a immunostains indicated a polyclonal proliferation of plasma cells that excluded monoclonal plasma cell neoplasia (Figure 2). Direct immunofluorescence (DIF) was negative. Serum enzyme-linked immunosorbent assay for bullous pemphigoid 180 and 230 antibodies  as well as desmoglein 1  and 3 antibodies was normal. The cumulative findings were consistent with plasma cell gingivitis (PCG). It was recommended that the patient avoid possible foods (eg, citrus) and oral hygiene products (eg, mint-flavored toothpaste) that could trigger PCG. With patient compliance to an elimination diet for 3 months, the condition resolved (Figure 3). 

Plasma cell gingivitis is a rare condition characterized by generalized edema and erythema of the attached gingiva. It was described in the 1960s and classified into 3 types based on etiology: (1) hypersensitivity (most common), (2) neoplastic, and (3) PCG of unknown origin.^1,2 Spices, herbs, and flavoring agents are implicated as potential triggers of hypersensitivity PCG, while neoplastic PCG is associated with monoclonal plasma cell neoplasms, such as multiple myeloma and extramedullary plasmacytoma.^2,3 Histologically, a diffuse subepithelial infiltrate of a polyclonal mixture of plasma cells typically is observed in hypersensitivity PCG.³ The plasma cell infiltration in hypersensitivity PCG is a benign reactive process without known risk for development of plasma cell malignancy, but the presence of a notable number of plasma cells may require special tissue staining to rule out the possibility of associated neoplasia.^2,3 There are no standardized protocols for management of PCG.⁴ Elimination of potential allergens, including flavored oral hygiene products, may result in resolution of hypersensitivity PCG lesions, as exemplified in our patient.¹ Neoplastic PCG responds to treatment of the underlying malignancy.⁵ Topical, intralesional, and/or systemic steroids may be considered in symptomatic cases of PCG.⁴ 

Clinical presentation of PCG can mimic immune-mediated mucocutaneous diseases such as mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), and oral lichen planus; microscopic analysis is needed to establish the diagnosis.⁶ Mucous membrane pemphigoid is a chronic autoimmune blistering disease involving the mucous membranes with possible cutaneous involvement. It is characterized by a complement-mediated autoantibody process against one or several antigens in the epithelial basement membrane. The oral mucosa is involved in 85% of MMP patients, and 65% of patients experience complications involving the ocular conjunctiva. Intraorally, MMP typically manifests as painful erosions, ulcerations, desquamative gingivitis, and/or occasionally intact blisters. Ocular complications include conjunctivitis and corneal erosions that often scar, resulting in blindness in approximately 15% of patients with ocular involvement. Microscopic features of MMP classically exhibit subepithelial separation with a mixed inflammatory cell infiltrate on routine analysis and linear deposition of IgG, IgA, or C3 within the basement membrane zone on DIF. Treatment of MMP involves topical or systemic immunosuppressants to control symptoms, minimize complications, and alter disease progression.⁶ 

Pemphigus vulgaris is an autoimmune vesiculobullous disease that affects the oral mucosa with or without cutaneous involvement.⁷ Desmogleins 1 and 3, transmembrane glycoproteins of desmosomes that convene cell-to-cell adhesion, are identified as antigens in PV. Antibodies against these desmoglein proteins result in intraepithelial separation, which leads to blister formation.⁷ Oral manifestations of PV include mucosal erosions and ulcerations as well as desquamative gingivitis. Bullae rarely are seen in the oral cavity, as they tend to rupture, leaving nonhealing ulcerations.⁸ Histologically, PV is characterized by acantholysis of the suprabasal cell layers with an intact basement membrane zone on routine examination. The distinctive microscopic feature of PV is the detection of cell surface-bound IgG within the epidermis on DIF.⁷ Treatment of PV may include topical and/or systemic corticosteroids and other immunosuppressants. Rituximab, a monoclonal antibody, has been successful in the management of PV.⁸ 

Oral lichen planus is a T-cell mediated autoimmune condition that leads to subepithelial lymphocytic infiltration and excessive keratinocyte apoptosis.⁹ Women typically are affected more often than men, and 75% of patients also have cutaneous manifestations of the condition. Desquamation and/or erythema of the gingiva may be the initial manifestation of oral lichen planus.⁹ Other commonly involved sites include the buccal mucosa, tongue, and palate. Biopsy of affected tissues typically demonstrates degeneration of the basal cell layer with subjacent bandlike lymphocytic infiltration on routine staining. Linear fibrinogen at the basement membrane zone usually is observed on DIF. Topical corticosteroids are considered first-line therapy, but systemic therapy including corticosteroids, steroid-sparing agents, or immunomodulators may be used in severe cases.⁹ 

There are 3 variants of plasma cell neoplasms including multiple myeloma, medullary plasmacytoma (also known as solitary bone plasmacytoma), and extramedullary plasmacytoma (EMP).¹⁰ Extramedullary plasmacytoma, sometimes referred to as extraosseous plasmacytoma, is described as a solitary or multiple plasma cell neoplasm contained in the soft tissue. Its occurrence is rare, accounting for only 3% of plasma cell neoplasms. Approximately 90% of EMPs affect the head and neck region, and males are affected 4 times more often than females. The oral cavity is one of the sites of clinical presentation; the gingival tissue infrequently is affected. When EMP affects the gingiva, it can mimic any form of gingivitis as well as other benign inflammatory conditions, such as pyogenic granuloma. Biopsy is the gold standard diagnostic method for differentiating EMP from other conditions, and specific immunohistochemical stains are essential for the diagnosis. Extramedullary plasmacytoma has the best prognosis among plasma cell neoplasms, despite the risk for progression to multiple myeloma. Extramedullary plasmacytoma lesions are very sensitive to radiotherapy, and the 10-year survival rate is approximately 70%.¹⁰ 

The Diagnosis: Plasma Cell Gingivitis 

Microscopic analysis demonstrated an acanthotic stratified squamous epithelium with an edematous fibrous stroma containing dense perivascular infiltrates of plasma cells and lymphocytes (Figure 1). Immunohistochemical analysis with kappa, lambda, and CD79a immunostains indicated a polyclonal proliferation of plasma cells that excluded monoclonal plasma cell neoplasia (Figure 2). Direct immunofluorescence (DIF) was negative. Serum enzyme-linked immunosorbent assay for bullous pemphigoid 180 and 230 antibodies  as well as desmoglein 1  and 3 antibodies was normal. The cumulative findings were consistent with plasma cell gingivitis (PCG). It was recommended that the patient avoid possible foods (eg, citrus) and oral hygiene products (eg, mint-flavored toothpaste) that could trigger PCG. With patient compliance to an elimination diet for 3 months, the condition resolved (Figure 3). 

Plasma cell gingivitis is a rare condition characterized by generalized edema and erythema of the attached gingiva. It was described in the 1960s and classified into 3 types based on etiology: (1) hypersensitivity (most common), (2) neoplastic, and (3) PCG of unknown origin.^1,2 Spices, herbs, and flavoring agents are implicated as potential triggers of hypersensitivity PCG, while neoplastic PCG is associated with monoclonal plasma cell neoplasms, such as multiple myeloma and extramedullary plasmacytoma.^2,3 Histologically, a diffuse subepithelial infiltrate of a polyclonal mixture of plasma cells typically is observed in hypersensitivity PCG.³ The plasma cell infiltration in hypersensitivity PCG is a benign reactive process without known risk for development of plasma cell malignancy, but the presence of a notable number of plasma cells may require special tissue staining to rule out the possibility of associated neoplasia.^2,3 There are no standardized protocols for management of PCG.⁴ Elimination of potential allergens, including flavored oral hygiene products, may result in resolution of hypersensitivity PCG lesions, as exemplified in our patient.¹ Neoplastic PCG responds to treatment of the underlying malignancy.⁵ Topical, intralesional, and/or systemic steroids may be considered in symptomatic cases of PCG.⁴ 

Clinical presentation of PCG can mimic immune-mediated mucocutaneous diseases such as mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), and oral lichen planus; microscopic analysis is needed to establish the diagnosis.⁶ Mucous membrane pemphigoid is a chronic autoimmune blistering disease involving the mucous membranes with possible cutaneous involvement. It is characterized by a complement-mediated autoantibody process against one or several antigens in the epithelial basement membrane. The oral mucosa is involved in 85% of MMP patients, and 65% of patients experience complications involving the ocular conjunctiva. Intraorally, MMP typically manifests as painful erosions, ulcerations, desquamative gingivitis, and/or occasionally intact blisters. Ocular complications include conjunctivitis and corneal erosions that often scar, resulting in blindness in approximately 15% of patients with ocular involvement. Microscopic features of MMP classically exhibit subepithelial separation with a mixed inflammatory cell infiltrate on routine analysis and linear deposition of IgG, IgA, or C3 within the basement membrane zone on DIF. Treatment of MMP involves topical or systemic immunosuppressants to control symptoms, minimize complications, and alter disease progression.⁶ 

Pemphigus vulgaris is an autoimmune vesiculobullous disease that affects the oral mucosa with or without cutaneous involvement.⁷ Desmogleins 1 and 3, transmembrane glycoproteins of desmosomes that convene cell-to-cell adhesion, are identified as antigens in PV. Antibodies against these desmoglein proteins result in intraepithelial separation, which leads to blister formation.⁷ Oral manifestations of PV include mucosal erosions and ulcerations as well as desquamative gingivitis. Bullae rarely are seen in the oral cavity, as they tend to rupture, leaving nonhealing ulcerations.⁸ Histologically, PV is characterized by acantholysis of the suprabasal cell layers with an intact basement membrane zone on routine examination. The distinctive microscopic feature of PV is the detection of cell surface-bound IgG within the epidermis on DIF.⁷ Treatment of PV may include topical and/or systemic corticosteroids and other immunosuppressants. Rituximab, a monoclonal antibody, has been successful in the management of PV.⁸ 

Oral lichen planus is a T-cell mediated autoimmune condition that leads to subepithelial lymphocytic infiltration and excessive keratinocyte apoptosis.⁹ Women typically are affected more often than men, and 75% of patients also have cutaneous manifestations of the condition. Desquamation and/or erythema of the gingiva may be the initial manifestation of oral lichen planus.⁹ Other commonly involved sites include the buccal mucosa, tongue, and palate. Biopsy of affected tissues typically demonstrates degeneration of the basal cell layer with subjacent bandlike lymphocytic infiltration on routine staining. Linear fibrinogen at the basement membrane zone usually is observed on DIF. Topical corticosteroids are considered first-line therapy, but systemic therapy including corticosteroids, steroid-sparing agents, or immunomodulators may be used in severe cases.⁹ 

There are 3 variants of plasma cell neoplasms including multiple myeloma, medullary plasmacytoma (also known as solitary bone plasmacytoma), and extramedullary plasmacytoma (EMP).¹⁰ Extramedullary plasmacytoma, sometimes referred to as extraosseous plasmacytoma, is described as a solitary or multiple plasma cell neoplasm contained in the soft tissue. Its occurrence is rare, accounting for only 3% of plasma cell neoplasms. Approximately 90% of EMPs affect the head and neck region, and males are affected 4 times more often than females. The oral cavity is one of the sites of clinical presentation; the gingival tissue infrequently is affected. When EMP affects the gingiva, it can mimic any form of gingivitis as well as other benign inflammatory conditions, such as pyogenic granuloma. Biopsy is the gold standard diagnostic method for differentiating EMP from other conditions, and specific immunohistochemical stains are essential for the diagnosis. Extramedullary plasmacytoma has the best prognosis among plasma cell neoplasms, despite the risk for progression to multiple myeloma. Extramedullary plasmacytoma lesions are very sensitive to radiotherapy, and the 10-year survival rate is approximately 70%.¹⁰ 

The Diagnosis: Plasma Cell Gingivitis 

Microscopic analysis demonstrated an acanthotic stratified squamous epithelium with an edematous fibrous stroma containing dense perivascular infiltrates of plasma cells and lymphocytes (Figure 1). Immunohistochemical analysis with kappa, lambda, and CD79a immunostains indicated a polyclonal proliferation of plasma cells that excluded monoclonal plasma cell neoplasia (Figure 2). Direct immunofluorescence (DIF) was negative. Serum enzyme-linked immunosorbent assay for bullous pemphigoid 180 and 230 antibodies  as well as desmoglein 1  and 3 antibodies was normal. The cumulative findings were consistent with plasma cell gingivitis (PCG). It was recommended that the patient avoid possible foods (eg, citrus) and oral hygiene products (eg, mint-flavored toothpaste) that could trigger PCG. With patient compliance to an elimination diet for 3 months, the condition resolved (Figure 3). 

Plasma cell gingivitis is a rare condition characterized by generalized edema and erythema of the attached gingiva. It was described in the 1960s and classified into 3 types based on etiology: (1) hypersensitivity (most common), (2) neoplastic, and (3) PCG of unknown origin.^1,2 Spices, herbs, and flavoring agents are implicated as potential triggers of hypersensitivity PCG, while neoplastic PCG is associated with monoclonal plasma cell neoplasms, such as multiple myeloma and extramedullary plasmacytoma.^2,3 Histologically, a diffuse subepithelial infiltrate of a polyclonal mixture of plasma cells typically is observed in hypersensitivity PCG.³ The plasma cell infiltration in hypersensitivity PCG is a benign reactive process without known risk for development of plasma cell malignancy, but the presence of a notable number of plasma cells may require special tissue staining to rule out the possibility of associated neoplasia.^2,3 There are no standardized protocols for management of PCG.⁴ Elimination of potential allergens, including flavored oral hygiene products, may result in resolution of hypersensitivity PCG lesions, as exemplified in our patient.¹ Neoplastic PCG responds to treatment of the underlying malignancy.⁵ Topical, intralesional, and/or systemic steroids may be considered in symptomatic cases of PCG.⁴ 

Clinical presentation of PCG can mimic immune-mediated mucocutaneous diseases such as mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), and oral lichen planus; microscopic analysis is needed to establish the diagnosis.⁶ Mucous membrane pemphigoid is a chronic autoimmune blistering disease involving the mucous membranes with possible cutaneous involvement. It is characterized by a complement-mediated autoantibody process against one or several antigens in the epithelial basement membrane. The oral mucosa is involved in 85% of MMP patients, and 65% of patients experience complications involving the ocular conjunctiva. Intraorally, MMP typically manifests as painful erosions, ulcerations, desquamative gingivitis, and/or occasionally intact blisters. Ocular complications include conjunctivitis and corneal erosions that often scar, resulting in blindness in approximately 15% of patients with ocular involvement. Microscopic features of MMP classically exhibit subepithelial separation with a mixed inflammatory cell infiltrate on routine analysis and linear deposition of IgG, IgA, or C3 within the basement membrane zone on DIF. Treatment of MMP involves topical or systemic immunosuppressants to control symptoms, minimize complications, and alter disease progression.⁶ 

Pemphigus vulgaris is an autoimmune vesiculobullous disease that affects the oral mucosa with or without cutaneous involvement.⁷ Desmogleins 1 and 3, transmembrane glycoproteins of desmosomes that convene cell-to-cell adhesion, are identified as antigens in PV. Antibodies against these desmoglein proteins result in intraepithelial separation, which leads to blister formation.⁷ Oral manifestations of PV include mucosal erosions and ulcerations as well as desquamative gingivitis. Bullae rarely are seen in the oral cavity, as they tend to rupture, leaving nonhealing ulcerations.⁸ Histologically, PV is characterized by acantholysis of the suprabasal cell layers with an intact basement membrane zone on routine examination. The distinctive microscopic feature of PV is the detection of cell surface-bound IgG within the epidermis on DIF.⁷ Treatment of PV may include topical and/or systemic corticosteroids and other immunosuppressants. Rituximab, a monoclonal antibody, has been successful in the management of PV.⁸ 

Oral lichen planus is a T-cell mediated autoimmune condition that leads to subepithelial lymphocytic infiltration and excessive keratinocyte apoptosis.⁹ Women typically are affected more often than men, and 75% of patients also have cutaneous manifestations of the condition. Desquamation and/or erythema of the gingiva may be the initial manifestation of oral lichen planus.⁹ Other commonly involved sites include the buccal mucosa, tongue, and palate. Biopsy of affected tissues typically demonstrates degeneration of the basal cell layer with subjacent bandlike lymphocytic infiltration on routine staining. Linear fibrinogen at the basement membrane zone usually is observed on DIF. Topical corticosteroids are considered first-line therapy, but systemic therapy including corticosteroids, steroid-sparing agents, or immunomodulators may be used in severe cases.⁹ 

There are 3 variants of plasma cell neoplasms including multiple myeloma, medullary plasmacytoma (also known as solitary bone plasmacytoma), and extramedullary plasmacytoma (EMP).¹⁰ Extramedullary plasmacytoma, sometimes referred to as extraosseous plasmacytoma, is described as a solitary or multiple plasma cell neoplasm contained in the soft tissue. Its occurrence is rare, accounting for only 3% of plasma cell neoplasms. Approximately 90% of EMPs affect the head and neck region, and males are affected 4 times more often than females. The oral cavity is one of the sites of clinical presentation; the gingival tissue infrequently is affected. When EMP affects the gingiva, it can mimic any form of gingivitis as well as other benign inflammatory conditions, such as pyogenic granuloma. Biopsy is the gold standard diagnostic method for differentiating EMP from other conditions, and specific immunohistochemical stains are essential for the diagnosis. Extramedullary plasmacytoma has the best prognosis among plasma cell neoplasms, despite the risk for progression to multiple myeloma. Extramedullary plasmacytoma lesions are very sensitive to radiotherapy, and the 10-year survival rate is approximately 70%.¹⁰ 

The Diagnosis: Disseminated Strongyloidiasis  

Strongyloidiasis is a parasitic infection caused by Strongyloides stercoralis. In the United States it is most prevalent in the Appalachian region. During the filariform larval stage of the parasite's life cycle, larvae from contaminated soil infect the human skin and spread to the intestinal epithelium,¹ then the larvae mature into adult female worms that can produce eggs asexually. Rhabditiform larvae hatch from the eggs and are either excreted in the stool or develop into infectious filariform larvae. The latter can cause autoinfection of the intestinal mucosa or nearby skin; in addition, if the larvae enter the bloodstream, they can spread throughout the body and lead to disseminated strongyloidiasis and hyperinfection syndrome.² This often fatal progression most commonly occurs in immunosuppressed individuals.³ The mortality rate has been reported to be up to 87%.^2,4  

Fever, abdominal pain, nausea, and diarrhea are clinically common in disseminated strongyloidiasis and hyperinfection syndrome.⁵ Patients also may exhibit dyspnea, cough, wheezing, and hemoptysis.² Cutaneous manifestations are rare and typically include pruritus and petechiae.⁶ Eosinophilia may be present but is not a reliable indicator.¹  

Our patient displayed several risk factors and an early clinical presentation for disseminated strongyloidiasis and hyperinfection syndrome, which evolved over the course of hospitalization. Clues to the diagnosis included an immunosuppressed state; erythematous pruritic macules at presentation that later developed into reticulated petechial patches; and fever, general abdominal symptoms, and dyspnea. However, the patient's overall physical examination findings were subtle and nonspecific. Additionally, the patient did not display the classic larva currens for strongyloidiasis or the pathognomonic periumbilical thumbprint purpura of disseminated infection,^6,7 which may indicate that the latter is a later-stage finding. Although graft-vs-host disease initially was suspected, a third skin biopsy revealed basophilic Strongyloides larvae, extravasated erythrocytes, and mild perivascular inflammation (Figure).

Subsequent gastric aspirates and stool cultures revealed S stercoralis. A bronchoalveolar lavage specimen and serum enzyme-linked immunosorbent assay for Strongyloides antibody were negative. The patient was treated with an extended 16-day course of ivermectin 12 mg daily until gastric aspirates and stool cultures were negative for the parasite. The rash receded by the end of the patient's 32-day hospital stay.  

Because of the high mortality rate of untreated disseminated strongyloidiasis and hyperinfection syndrome, early diagnosis and initiation of anthelmintic treatment is vital in improving patient outcomes. As such, the diagnosis of disseminated strongyloidiasis should be considered in any immunosuppressed patient with multisystemic symptoms and/or petechiae. The differential diagnosis includes graft-vs-host disease, drug-induced urticaria, disseminated intravascular coagulation, and other opportunistic parasites.^6,8,9

The Diagnosis: Disseminated Strongyloidiasis  

Strongyloidiasis is a parasitic infection caused by Strongyloides stercoralis. In the United States it is most prevalent in the Appalachian region. During the filariform larval stage of the parasite's life cycle, larvae from contaminated soil infect the human skin and spread to the intestinal epithelium,¹ then the larvae mature into adult female worms that can produce eggs asexually. Rhabditiform larvae hatch from the eggs and are either excreted in the stool or develop into infectious filariform larvae. The latter can cause autoinfection of the intestinal mucosa or nearby skin; in addition, if the larvae enter the bloodstream, they can spread throughout the body and lead to disseminated strongyloidiasis and hyperinfection syndrome.² This often fatal progression most commonly occurs in immunosuppressed individuals.³ The mortality rate has been reported to be up to 87%.^2,4  

Fever, abdominal pain, nausea, and diarrhea are clinically common in disseminated strongyloidiasis and hyperinfection syndrome.⁵ Patients also may exhibit dyspnea, cough, wheezing, and hemoptysis.² Cutaneous manifestations are rare and typically include pruritus and petechiae.⁶ Eosinophilia may be present but is not a reliable indicator.¹  

Our patient displayed several risk factors and an early clinical presentation for disseminated strongyloidiasis and hyperinfection syndrome, which evolved over the course of hospitalization. Clues to the diagnosis included an immunosuppressed state; erythematous pruritic macules at presentation that later developed into reticulated petechial patches; and fever, general abdominal symptoms, and dyspnea. However, the patient's overall physical examination findings were subtle and nonspecific. Additionally, the patient did not display the classic larva currens for strongyloidiasis or the pathognomonic periumbilical thumbprint purpura of disseminated infection,^6,7 which may indicate that the latter is a later-stage finding. Although graft-vs-host disease initially was suspected, a third skin biopsy revealed basophilic Strongyloides larvae, extravasated erythrocytes, and mild perivascular inflammation (Figure).

Subsequent gastric aspirates and stool cultures revealed S stercoralis. A bronchoalveolar lavage specimen and serum enzyme-linked immunosorbent assay for Strongyloides antibody were negative. The patient was treated with an extended 16-day course of ivermectin 12 mg daily until gastric aspirates and stool cultures were negative for the parasite. The rash receded by the end of the patient's 32-day hospital stay.  

Because of the high mortality rate of untreated disseminated strongyloidiasis and hyperinfection syndrome, early diagnosis and initiation of anthelmintic treatment is vital in improving patient outcomes. As such, the diagnosis of disseminated strongyloidiasis should be considered in any immunosuppressed patient with multisystemic symptoms and/or petechiae. The differential diagnosis includes graft-vs-host disease, drug-induced urticaria, disseminated intravascular coagulation, and other opportunistic parasites.^6,8,9

The Diagnosis: Disseminated Strongyloidiasis  

Strongyloidiasis is a parasitic infection caused by Strongyloides stercoralis. In the United States it is most prevalent in the Appalachian region. During the filariform larval stage of the parasite's life cycle, larvae from contaminated soil infect the human skin and spread to the intestinal epithelium,¹ then the larvae mature into adult female worms that can produce eggs asexually. Rhabditiform larvae hatch from the eggs and are either excreted in the stool or develop into infectious filariform larvae. The latter can cause autoinfection of the intestinal mucosa or nearby skin; in addition, if the larvae enter the bloodstream, they can spread throughout the body and lead to disseminated strongyloidiasis and hyperinfection syndrome.² This often fatal progression most commonly occurs in immunosuppressed individuals.³ The mortality rate has been reported to be up to 87%.^2,4  

Fever, abdominal pain, nausea, and diarrhea are clinically common in disseminated strongyloidiasis and hyperinfection syndrome.⁵ Patients also may exhibit dyspnea, cough, wheezing, and hemoptysis.² Cutaneous manifestations are rare and typically include pruritus and petechiae.⁶ Eosinophilia may be present but is not a reliable indicator.¹  

Our patient displayed several risk factors and an early clinical presentation for disseminated strongyloidiasis and hyperinfection syndrome, which evolved over the course of hospitalization. Clues to the diagnosis included an immunosuppressed state; erythematous pruritic macules at presentation that later developed into reticulated petechial patches; and fever, general abdominal symptoms, and dyspnea. However, the patient's overall physical examination findings were subtle and nonspecific. Additionally, the patient did not display the classic larva currens for strongyloidiasis or the pathognomonic periumbilical thumbprint purpura of disseminated infection,^6,7 which may indicate that the latter is a later-stage finding. Although graft-vs-host disease initially was suspected, a third skin biopsy revealed basophilic Strongyloides larvae, extravasated erythrocytes, and mild perivascular inflammation (Figure).

Subsequent gastric aspirates and stool cultures revealed S stercoralis. A bronchoalveolar lavage specimen and serum enzyme-linked immunosorbent assay for Strongyloides antibody were negative. The patient was treated with an extended 16-day course of ivermectin 12 mg daily until gastric aspirates and stool cultures were negative for the parasite. The rash receded by the end of the patient's 32-day hospital stay.  

Because of the high mortality rate of untreated disseminated strongyloidiasis and hyperinfection syndrome, early diagnosis and initiation of anthelmintic treatment is vital in improving patient outcomes. As such, the diagnosis of disseminated strongyloidiasis should be considered in any immunosuppressed patient with multisystemic symptoms and/or petechiae. The differential diagnosis includes graft-vs-host disease, drug-induced urticaria, disseminated intravascular coagulation, and other opportunistic parasites.^6,8,9

The Diagnosis: Pseudo-Black Hairy Tongue

Pseudo-black hairy tongue is a benign and painless disorder characterized by transient hyperpigmentation of the tongue with a substance that can be easily scraped off. In this case, the patient's lingual discoloration was secondary to the ingestion of bismuth salicylate. The phenomenon is thought to occur due to a reaction between bismuth and sulfur-containing compounds in the saliva, resulting in the characteristic black substance on the surface of the tongue that nestles between the lingual papillae.¹ An associated feature may include black stools. Other etiologic factors involved in pseudo-black hairy tongue include food coloring, tobacco, and other drugs such antibiotics and antidepressants.²  

The differential diagnosis of lingual hyperpigmentation includes lingua villosa nigra (also known as black hairy tongue), pigmented fungiform papillae of the tongue, acanthosis nigricans, and oral hairy leukoplakia. Lingua villosa nigra is a similar condition in which individuals present with a black tongue; however, the tongue also appears hairy. The tongue may appear as other colors such as brown, yellow, or green. Patients additionally may have symptoms of burning, dysgeusia, halitosis, or gagging. Poor oral hygiene, xerostomia, use of tobacco or alcohol, and different medications including antibiotics and antipsychotic medications increase the risk for developing lingua villosa nigra.^2,3 This condition is distinguished from pseudo-black hairy tongue by proliferation and elongation of the filiform papillae.³ Pigmented fungiform papillae of the tongue is a normal variant of tongue morphology, is more common in individuals with darker skin types, and primarily affects the lateral aspect and apex of the tongue.⁴ Acanthosis nigricans can appear in the oral cavity as multiple pigmented papillary lesions on the dorsal and lateral regions of the tongue and frequently involves the lips; this condition may be associated with metabolic disorders or underlying malignancy.^2,3 Oral hairy leukoplakia is caused by Epstein-Barr virus infection and typically presents as white plaques on the dorsal and ventral surfaces of the tongue; this condition largely is found in immunocompromised patients.⁵

In our patient there was an acute onset of tongue discoloration associated with ingestion of bismuth salicylate, no hypertrophy or lengthening of the lingual papillae, and no involvement of the patient's lips, which was consistent with the diagnosis of pseudo-black hairy tongue. Pseudo-black hairy tongue is transient and treated by discontinuation of offending agents and proper hygiene practices.

The Diagnosis: Pseudo-Black Hairy Tongue

Pseudo-black hairy tongue is a benign and painless disorder characterized by transient hyperpigmentation of the tongue with a substance that can be easily scraped off. In this case, the patient's lingual discoloration was secondary to the ingestion of bismuth salicylate. The phenomenon is thought to occur due to a reaction between bismuth and sulfur-containing compounds in the saliva, resulting in the characteristic black substance on the surface of the tongue that nestles between the lingual papillae.¹ An associated feature may include black stools. Other etiologic factors involved in pseudo-black hairy tongue include food coloring, tobacco, and other drugs such antibiotics and antidepressants.²  

The differential diagnosis of lingual hyperpigmentation includes lingua villosa nigra (also known as black hairy tongue), pigmented fungiform papillae of the tongue, acanthosis nigricans, and oral hairy leukoplakia. Lingua villosa nigra is a similar condition in which individuals present with a black tongue; however, the tongue also appears hairy. The tongue may appear as other colors such as brown, yellow, or green. Patients additionally may have symptoms of burning, dysgeusia, halitosis, or gagging. Poor oral hygiene, xerostomia, use of tobacco or alcohol, and different medications including antibiotics and antipsychotic medications increase the risk for developing lingua villosa nigra.^2,3 This condition is distinguished from pseudo-black hairy tongue by proliferation and elongation of the filiform papillae.³ Pigmented fungiform papillae of the tongue is a normal variant of tongue morphology, is more common in individuals with darker skin types, and primarily affects the lateral aspect and apex of the tongue.⁴ Acanthosis nigricans can appear in the oral cavity as multiple pigmented papillary lesions on the dorsal and lateral regions of the tongue and frequently involves the lips; this condition may be associated with metabolic disorders or underlying malignancy.^2,3 Oral hairy leukoplakia is caused by Epstein-Barr virus infection and typically presents as white plaques on the dorsal and ventral surfaces of the tongue; this condition largely is found in immunocompromised patients.⁵

In our patient there was an acute onset of tongue discoloration associated with ingestion of bismuth salicylate, no hypertrophy or lengthening of the lingual papillae, and no involvement of the patient's lips, which was consistent with the diagnosis of pseudo-black hairy tongue. Pseudo-black hairy tongue is transient and treated by discontinuation of offending agents and proper hygiene practices.

The Diagnosis: Pseudo-Black Hairy Tongue

Pseudo-black hairy tongue is a benign and painless disorder characterized by transient hyperpigmentation of the tongue with a substance that can be easily scraped off. In this case, the patient's lingual discoloration was secondary to the ingestion of bismuth salicylate. The phenomenon is thought to occur due to a reaction between bismuth and sulfur-containing compounds in the saliva, resulting in the characteristic black substance on the surface of the tongue that nestles between the lingual papillae.¹ An associated feature may include black stools. Other etiologic factors involved in pseudo-black hairy tongue include food coloring, tobacco, and other drugs such antibiotics and antidepressants.²  

The differential diagnosis of lingual hyperpigmentation includes lingua villosa nigra (also known as black hairy tongue), pigmented fungiform papillae of the tongue, acanthosis nigricans, and oral hairy leukoplakia. Lingua villosa nigra is a similar condition in which individuals present with a black tongue; however, the tongue also appears hairy. The tongue may appear as other colors such as brown, yellow, or green. Patients additionally may have symptoms of burning, dysgeusia, halitosis, or gagging. Poor oral hygiene, xerostomia, use of tobacco or alcohol, and different medications including antibiotics and antipsychotic medications increase the risk for developing lingua villosa nigra.^2,3 This condition is distinguished from pseudo-black hairy tongue by proliferation and elongation of the filiform papillae.³ Pigmented fungiform papillae of the tongue is a normal variant of tongue morphology, is more common in individuals with darker skin types, and primarily affects the lateral aspect and apex of the tongue.⁴ Acanthosis nigricans can appear in the oral cavity as multiple pigmented papillary lesions on the dorsal and lateral regions of the tongue and frequently involves the lips; this condition may be associated with metabolic disorders or underlying malignancy.^2,3 Oral hairy leukoplakia is caused by Epstein-Barr virus infection and typically presents as white plaques on the dorsal and ventral surfaces of the tongue; this condition largely is found in immunocompromised patients.⁵

In our patient there was an acute onset of tongue discoloration associated with ingestion of bismuth salicylate, no hypertrophy or lengthening of the lingual papillae, and no involvement of the patient's lips, which was consistent with the diagnosis of pseudo-black hairy tongue. Pseudo-black hairy tongue is transient and treated by discontinuation of offending agents and proper hygiene practices.

The Diagnosis: Cutaneous Metastasis 

Histopathology demonstrated ulceration of the epidermis with necrosis of the papillary dermis. There was a diffuse infiltration of pleomorphic and atypical epithelioid cells in the reticular dermis (Figure). Focally there was ductal and glandular differentiation. The stroma was sclerotic. At the deep aspect of the biopsy specimen, tumor cells intercalated between collagen bundles in linear strands. Atypical mitoses were common, and necrosis en masse was seen. An immunohistochemical panel also was performed. Tissue from the biopsy was strongly positive for CDX-2 and cytokeratin 20 and diffusely negative for cytokeratin 7, gross cystic disease fluid protein 15, and prostate-specific antigen. The other biopsy was sent for cultures and grew no organisms, which confirmed the diagnosis of cutaneous metastasis from the patient's primary colonic adenocarcinoma. Due to the poor prognosis and his overall poor health, our patient opted for palliative care. 

Based on large retrospective studies, the frequency of cutaneous metastasis for patients diagnosed with any malignancy is 0.7% to 9.0%.^1-4 The third most common malignancy in both sexes is colorectal cancer, affecting approximately 5% of the US population.³ The frequency of cutaneous metastases from colorectal cancer is 0.81% to 3.9%.^1,2,4,5 Generally, cutaneous metastases present within 2 to 3 years from diagnosis of primary malignancy.^6,7 The most common sites for cutaneous metastases in a patient with colorectal cancer are the abdomen and pelvic region, often at surgical sites.^1-4,6-9  

The clinical presentation of cutaneous metastases varies greatly, and as a result, they commonly are misdiagnosed.^6,7 Although treatment with many antibiotics and antifungals had failed in our patient, the examination still was concerning for a possible granulomatous infection vs malignancy. With the history of colon cancer, radiation treatment, and chemotherapy, the possible malignancy diagnoses included primary skin cancers, viral tumors, and cutaneous metastasis. The initial evaluations had focused on infectious causes and resulted in 6 weeks of misdiagnosis and inappropriate therapy. Despite cutaneous metastases being uncommon, there should be a high index of suspicion for lesions in patients who have a history of cancer, especially if the lesion does not respond to treatment.^2,6,7  

Physical examination in our patient showed a high tumor burden as well as evidence of carcinoma erysipeloides on the lower abdomen and thighs, in addition to carcinoma en cuirasse throughout the pubic region. Carcinoma erysipeloides was first described in 1893 in a patient with breast cancer: "The erythematous infiltration of the skin was very superficial, and was attended simply by redness with a slight degree of induration. Until touched by the finger the condition might easily have been taken for a slightly-marked form of erysipelas."¹⁰ The clinical findings are a result of lymphatic and vascular obstruction.^3,9 The breast is the most common location to find carcinoma erysipeloides.³ It is an unusual occurrence to find it on the abdomen from colonic adenocarcinoma. The term cancer en cuirasse was coined in 1838 to describe the cutaneous manifestation of breast cancer that caused the skin to resemble the metal breastplate of a cuirasser.⁴ Similar to carcinoma erysipeloides, carcinoma en cuirasse most commonly is found as cutaneous metastasis from breast cancer, not from colonic adenocarcinoma.³  

The histologic characteristics of cutaneous metastases in general are similar to the primary malignancy but can be more poorly differentiated.⁷ Generally, neoplastic cells are seen in the lymphatic and blood vessels, and a large portion of the tumor is confined to the deep dermis and in the subcutaneous fat.^3,6 Histologic features of colonic adenocarcinoma metastases can demonstrate a well-differentiated, glandular architecture with mucin-secreting cells.^3,8,9 There also is a histologic pattern of neoplastic cells arranging themselves between collagen bundles in linear strands; this finding more commonly is seen in adenocarcinoma of the breast but also was seen in our patient.^3,9 With immunohistochemical staining, a truncated panel of cytokeratin 7, cytokeratin 20, and S-100 had a diagnostic accuracy of 100% for cutaneous metastases from colonic adenocarcinoma in one study. The pattern of all colonic adenocarcinomas was cytokeratin 20 positive and cytokeratin 7 and S-100 negative.⁶ 

Cutaneous metastases typically demonstrate widespread and rapidly progressive disease.^3,9 Survival studies of cutaneous metastases showed that 48% to 66% of patients died within the first 6 months.^3,6 Specifically, cutaneous metastases from colorectal cancers showed a median survival of 3 to 5 months.^6,7 Currently there are no treatment guidelines for cutaneous metastases.   

The Diagnosis: Cutaneous Metastasis 

Histopathology demonstrated ulceration of the epidermis with necrosis of the papillary dermis. There was a diffuse infiltration of pleomorphic and atypical epithelioid cells in the reticular dermis (Figure). Focally there was ductal and glandular differentiation. The stroma was sclerotic. At the deep aspect of the biopsy specimen, tumor cells intercalated between collagen bundles in linear strands. Atypical mitoses were common, and necrosis en masse was seen. An immunohistochemical panel also was performed. Tissue from the biopsy was strongly positive for CDX-2 and cytokeratin 20 and diffusely negative for cytokeratin 7, gross cystic disease fluid protein 15, and prostate-specific antigen. The other biopsy was sent for cultures and grew no organisms, which confirmed the diagnosis of cutaneous metastasis from the patient's primary colonic adenocarcinoma. Due to the poor prognosis and his overall poor health, our patient opted for palliative care. 

Based on large retrospective studies, the frequency of cutaneous metastasis for patients diagnosed with any malignancy is 0.7% to 9.0%.^1-4 The third most common malignancy in both sexes is colorectal cancer, affecting approximately 5% of the US population.³ The frequency of cutaneous metastases from colorectal cancer is 0.81% to 3.9%.^1,2,4,5 Generally, cutaneous metastases present within 2 to 3 years from diagnosis of primary malignancy.^6,7 The most common sites for cutaneous metastases in a patient with colorectal cancer are the abdomen and pelvic region, often at surgical sites.^1-4,6-9  

The clinical presentation of cutaneous metastases varies greatly, and as a result, they commonly are misdiagnosed.^6,7 Although treatment with many antibiotics and antifungals had failed in our patient, the examination still was concerning for a possible granulomatous infection vs malignancy. With the history of colon cancer, radiation treatment, and chemotherapy, the possible malignancy diagnoses included primary skin cancers, viral tumors, and cutaneous metastasis. The initial evaluations had focused on infectious causes and resulted in 6 weeks of misdiagnosis and inappropriate therapy. Despite cutaneous metastases being uncommon, there should be a high index of suspicion for lesions in patients who have a history of cancer, especially if the lesion does not respond to treatment.^2,6,7  

Physical examination in our patient showed a high tumor burden as well as evidence of carcinoma erysipeloides on the lower abdomen and thighs, in addition to carcinoma en cuirasse throughout the pubic region. Carcinoma erysipeloides was first described in 1893 in a patient with breast cancer: "The erythematous infiltration of the skin was very superficial, and was attended simply by redness with a slight degree of induration. Until touched by the finger the condition might easily have been taken for a slightly-marked form of erysipelas."¹⁰ The clinical findings are a result of lymphatic and vascular obstruction.^3,9 The breast is the most common location to find carcinoma erysipeloides.³ It is an unusual occurrence to find it on the abdomen from colonic adenocarcinoma. The term cancer en cuirasse was coined in 1838 to describe the cutaneous manifestation of breast cancer that caused the skin to resemble the metal breastplate of a cuirasser.⁴ Similar to carcinoma erysipeloides, carcinoma en cuirasse most commonly is found as cutaneous metastasis from breast cancer, not from colonic adenocarcinoma.³  

The histologic characteristics of cutaneous metastases in general are similar to the primary malignancy but can be more poorly differentiated.⁷ Generally, neoplastic cells are seen in the lymphatic and blood vessels, and a large portion of the tumor is confined to the deep dermis and in the subcutaneous fat.^3,6 Histologic features of colonic adenocarcinoma metastases can demonstrate a well-differentiated, glandular architecture with mucin-secreting cells.^3,8,9 There also is a histologic pattern of neoplastic cells arranging themselves between collagen bundles in linear strands; this finding more commonly is seen in adenocarcinoma of the breast but also was seen in our patient.^3,9 With immunohistochemical staining, a truncated panel of cytokeratin 7, cytokeratin 20, and S-100 had a diagnostic accuracy of 100% for cutaneous metastases from colonic adenocarcinoma in one study. The pattern of all colonic adenocarcinomas was cytokeratin 20 positive and cytokeratin 7 and S-100 negative.⁶ 

Cutaneous metastases typically demonstrate widespread and rapidly progressive disease.^3,9 Survival studies of cutaneous metastases showed that 48% to 66% of patients died within the first 6 months.^3,6 Specifically, cutaneous metastases from colorectal cancers showed a median survival of 3 to 5 months.^6,7 Currently there are no treatment guidelines for cutaneous metastases.   

The Diagnosis: Cutaneous Metastasis 

Histopathology demonstrated ulceration of the epidermis with necrosis of the papillary dermis. There was a diffuse infiltration of pleomorphic and atypical epithelioid cells in the reticular dermis (Figure). Focally there was ductal and glandular differentiation. The stroma was sclerotic. At the deep aspect of the biopsy specimen, tumor cells intercalated between collagen bundles in linear strands. Atypical mitoses were common, and necrosis en masse was seen. An immunohistochemical panel also was performed. Tissue from the biopsy was strongly positive for CDX-2 and cytokeratin 20 and diffusely negative for cytokeratin 7, gross cystic disease fluid protein 15, and prostate-specific antigen. The other biopsy was sent for cultures and grew no organisms, which confirmed the diagnosis of cutaneous metastasis from the patient's primary colonic adenocarcinoma. Due to the poor prognosis and his overall poor health, our patient opted for palliative care. 

Based on large retrospective studies, the frequency of cutaneous metastasis for patients diagnosed with any malignancy is 0.7% to 9.0%.^1-4 The third most common malignancy in both sexes is colorectal cancer, affecting approximately 5% of the US population.³ The frequency of cutaneous metastases from colorectal cancer is 0.81% to 3.9%.^1,2,4,5 Generally, cutaneous metastases present within 2 to 3 years from diagnosis of primary malignancy.^6,7 The most common sites for cutaneous metastases in a patient with colorectal cancer are the abdomen and pelvic region, often at surgical sites.^1-4,6-9  

The clinical presentation of cutaneous metastases varies greatly, and as a result, they commonly are misdiagnosed.^6,7 Although treatment with many antibiotics and antifungals had failed in our patient, the examination still was concerning for a possible granulomatous infection vs malignancy. With the history of colon cancer, radiation treatment, and chemotherapy, the possible malignancy diagnoses included primary skin cancers, viral tumors, and cutaneous metastasis. The initial evaluations had focused on infectious causes and resulted in 6 weeks of misdiagnosis and inappropriate therapy. Despite cutaneous metastases being uncommon, there should be a high index of suspicion for lesions in patients who have a history of cancer, especially if the lesion does not respond to treatment.^2,6,7  

Physical examination in our patient showed a high tumor burden as well as evidence of carcinoma erysipeloides on the lower abdomen and thighs, in addition to carcinoma en cuirasse throughout the pubic region. Carcinoma erysipeloides was first described in 1893 in a patient with breast cancer: "The erythematous infiltration of the skin was very superficial, and was attended simply by redness with a slight degree of induration. Until touched by the finger the condition might easily have been taken for a slightly-marked form of erysipelas."¹⁰ The clinical findings are a result of lymphatic and vascular obstruction.^3,9 The breast is the most common location to find carcinoma erysipeloides.³ It is an unusual occurrence to find it on the abdomen from colonic adenocarcinoma. The term cancer en cuirasse was coined in 1838 to describe the cutaneous manifestation of breast cancer that caused the skin to resemble the metal breastplate of a cuirasser.⁴ Similar to carcinoma erysipeloides, carcinoma en cuirasse most commonly is found as cutaneous metastasis from breast cancer, not from colonic adenocarcinoma.³  

The histologic characteristics of cutaneous metastases in general are similar to the primary malignancy but can be more poorly differentiated.⁷ Generally, neoplastic cells are seen in the lymphatic and blood vessels, and a large portion of the tumor is confined to the deep dermis and in the subcutaneous fat.^3,6 Histologic features of colonic adenocarcinoma metastases can demonstrate a well-differentiated, glandular architecture with mucin-secreting cells.^3,8,9 There also is a histologic pattern of neoplastic cells arranging themselves between collagen bundles in linear strands; this finding more commonly is seen in adenocarcinoma of the breast but also was seen in our patient.^3,9 With immunohistochemical staining, a truncated panel of cytokeratin 7, cytokeratin 20, and S-100 had a diagnostic accuracy of 100% for cutaneous metastases from colonic adenocarcinoma in one study. The pattern of all colonic adenocarcinomas was cytokeratin 20 positive and cytokeratin 7 and S-100 negative.⁶ 

Cutaneous metastases typically demonstrate widespread and rapidly progressive disease.^3,9 Survival studies of cutaneous metastases showed that 48% to 66% of patients died within the first 6 months.^3,6 Specifically, cutaneous metastases from colorectal cancers showed a median survival of 3 to 5 months.^6,7 Currently there are no treatment guidelines for cutaneous metastases.   

The Diagnosis: Dermatofibroma With Sebaceous Induction 

The biopsy of the lesion revealed a fibrohistiocytic dermal pattern with overlying benign epidermal and sebaceous hyperplasia with a proliferation of fibroblasts in the dermis. Other sections revealed hyperplastic sebaceous glands of the superficial and mid dermis. These findings were suggestive of a dermatofibroma (DF) that had induced epidermal and sebaceous hyperplasia.  

Dermatofibromas are common benign fibrous soft tissue growths that account for approximately 3% of dermatopathology specimens.¹ The etiology of DFs is unknown; however, they are thought to arise from sites of prior trauma or arthropod bites. Multiple or eruptive DFs have been reported in patients with lupus and atopic dermatitis.² They commonly appear as round firm nodules measuring less than 1 cm in diameter on the extremities of young adults. Eruptive dermatofibromas also have been reported in human immunodeficiency virus-positive and immunosuppressed patients.^3,4 On physical examination, gently pinching the lesion causes a downward movement known as the "dimple sign." If left undisturbed, DFs persist but may undergo partial regression, especially in the center; they also may be excised if symptomatic.  

The clinical differential for this papule included a scar and sebaceous hyperplasia. The lack of history of skin cancer or prior procedure made a scar less likely. Sebaceous glands are less prominent on the shoulders, making sebaceous hyperplasia less likely, though dermoscopy showed pale yellow lobules. Sebaceous adenomas most commonly are seen on the head or neck and present as a flesh-colored papule. Sebaceous induction by DFs is rare but has been reported in the literature.^5,6 

The histology of DFs is described as a nodular proliferation of spindle-shaped fibroblasts and myofibroblasts with short intersecting fascicles. A predilection for sebaceous induction from an underlying DF on the shoulder has been reported.⁵ Sebaceous differentiation has been reported in 16% to 31.6% of DFs.^5,6 Seborrheic keratosis-like epidermal hyperplasia frequently has been seen in DFs with sebaceous induction in comparison to DFs without sebaceous induction.⁵ Immunohistochemical stains are important to help differentiate DF from dermatofibrosarcoma protuberans, especially when approaching the subcutis. Dermatofibromas stain positive for factor XIIIa and negative for CD34, whereas dermatofibrosarcoma protuberans stain negative for factor XIIIa and positive for CD34.⁷ Dermatofibromas also demonstrate positive immunostaining for vimentin, stromelysin 3,⁸ muscle-specific actin, and CD68.  

The Diagnosis: Dermatofibroma With Sebaceous Induction 

The biopsy of the lesion revealed a fibrohistiocytic dermal pattern with overlying benign epidermal and sebaceous hyperplasia with a proliferation of fibroblasts in the dermis. Other sections revealed hyperplastic sebaceous glands of the superficial and mid dermis. These findings were suggestive of a dermatofibroma (DF) that had induced epidermal and sebaceous hyperplasia.  

Dermatofibromas are common benign fibrous soft tissue growths that account for approximately 3% of dermatopathology specimens.¹ The etiology of DFs is unknown; however, they are thought to arise from sites of prior trauma or arthropod bites. Multiple or eruptive DFs have been reported in patients with lupus and atopic dermatitis.² They commonly appear as round firm nodules measuring less than 1 cm in diameter on the extremities of young adults. Eruptive dermatofibromas also have been reported in human immunodeficiency virus-positive and immunosuppressed patients.^3,4 On physical examination, gently pinching the lesion causes a downward movement known as the "dimple sign." If left undisturbed, DFs persist but may undergo partial regression, especially in the center; they also may be excised if symptomatic.  

The clinical differential for this papule included a scar and sebaceous hyperplasia. The lack of history of skin cancer or prior procedure made a scar less likely. Sebaceous glands are less prominent on the shoulders, making sebaceous hyperplasia less likely, though dermoscopy showed pale yellow lobules. Sebaceous adenomas most commonly are seen on the head or neck and present as a flesh-colored papule. Sebaceous induction by DFs is rare but has been reported in the literature.^5,6 

The histology of DFs is described as a nodular proliferation of spindle-shaped fibroblasts and myofibroblasts with short intersecting fascicles. A predilection for sebaceous induction from an underlying DF on the shoulder has been reported.⁵ Sebaceous differentiation has been reported in 16% to 31.6% of DFs.^5,6 Seborrheic keratosis-like epidermal hyperplasia frequently has been seen in DFs with sebaceous induction in comparison to DFs without sebaceous induction.⁵ Immunohistochemical stains are important to help differentiate DF from dermatofibrosarcoma protuberans, especially when approaching the subcutis. Dermatofibromas stain positive for factor XIIIa and negative for CD34, whereas dermatofibrosarcoma protuberans stain negative for factor XIIIa and positive for CD34.⁷ Dermatofibromas also demonstrate positive immunostaining for vimentin, stromelysin 3,⁸ muscle-specific actin, and CD68.  

The Diagnosis: Dermatofibroma With Sebaceous Induction 

The biopsy of the lesion revealed a fibrohistiocytic dermal pattern with overlying benign epidermal and sebaceous hyperplasia with a proliferation of fibroblasts in the dermis. Other sections revealed hyperplastic sebaceous glands of the superficial and mid dermis. These findings were suggestive of a dermatofibroma (DF) that had induced epidermal and sebaceous hyperplasia.  

Dermatofibromas are common benign fibrous soft tissue growths that account for approximately 3% of dermatopathology specimens.¹ The etiology of DFs is unknown; however, they are thought to arise from sites of prior trauma or arthropod bites. Multiple or eruptive DFs have been reported in patients with lupus and atopic dermatitis.² They commonly appear as round firm nodules measuring less than 1 cm in diameter on the extremities of young adults. Eruptive dermatofibromas also have been reported in human immunodeficiency virus-positive and immunosuppressed patients.^3,4 On physical examination, gently pinching the lesion causes a downward movement known as the "dimple sign." If left undisturbed, DFs persist but may undergo partial regression, especially in the center; they also may be excised if symptomatic.  

The clinical differential for this papule included a scar and sebaceous hyperplasia. The lack of history of skin cancer or prior procedure made a scar less likely. Sebaceous glands are less prominent on the shoulders, making sebaceous hyperplasia less likely, though dermoscopy showed pale yellow lobules. Sebaceous adenomas most commonly are seen on the head or neck and present as a flesh-colored papule. Sebaceous induction by DFs is rare but has been reported in the literature.^5,6 

The histology of DFs is described as a nodular proliferation of spindle-shaped fibroblasts and myofibroblasts with short intersecting fascicles. A predilection for sebaceous induction from an underlying DF on the shoulder has been reported.⁵ Sebaceous differentiation has been reported in 16% to 31.6% of DFs.^5,6 Seborrheic keratosis-like epidermal hyperplasia frequently has been seen in DFs with sebaceous induction in comparison to DFs without sebaceous induction.⁵ Immunohistochemical stains are important to help differentiate DF from dermatofibrosarcoma protuberans, especially when approaching the subcutis. Dermatofibromas stain positive for factor XIIIa and negative for CD34, whereas dermatofibrosarcoma protuberans stain negative for factor XIIIa and positive for CD34.⁷ Dermatofibromas also demonstrate positive immunostaining for vimentin, stromelysin 3,⁸ muscle-specific actin, and CD68.  

The Diagnosis: Rumpel-Leede Phenomenon 

Rumpel-Leede (R-L) phenomenon describes the rare benign occurrence of dermal capillaries acutely rupturing following the administration of a tourniquetlike force on an extremity,¹ which manifests as asymptomatic petechiae and ecchymoses on a distal extremity, usually following noninvasive measurement of blood pressure.² Rumpel-Leede phenomenon represents an underrecognized entity that either is excluded or minimally referenced in most dermatology textbooks. The R-L sign initially was described in the early 1900s after it was observed that tourniquets applied to the arms of patients with scarlet fever would lead to the development of petechiae in that extremity.³ It later was elucidated that underlying vascular disease predisposes to dermal capillary fragility, a risk factor for R-L phenomenon to occur upon application of a tourniquet. Rumpel-Leede phenomenon has been noted in patients with diabetes mellitus, acute or chronic hypertension, and thrombocytopenia.⁴ In addition to being hypertensive and diabetic, our patient had been taking amlodipine and diltiazem. Calcium channel blockers have been linked to R-L phenomenon in case reports as well as in a study of calcium channel blockers inducing capillary fragility in vivo.⁵ Rumpel-Leede phenomenon also has been noted in patients with tightly fitting garments and infants carried in baby carriers.¹ 

The differential diagnosis for R-L phenomenon includes actinic purpura, small vessel vasculitis, disseminated intravascular coagulation (DIC), and deep vein thrombosis (DVT). Actinic purpura, also called solar purpura or senile purpura, represents the petechiae and ecchymoses that are associated with aging skin. It is thought to occur when DNA damage, UV-induced solar elastosis, and decreased lipids in the stratum corneum cause a weakened ability to contain red blood cell extravasation from capillaries.⁶ Due to the lack of history of trauma and clear association with the blood pressure cuff placement in our patient, a diagnosis of actinic purpura was unlikely. In small vessel vasculitis, patients classically present with nonblanching palpable purpura frequently distributed over the lower extremities. The isolation of the lesions to only the left arm lowered the suspicion for vasculitis. Cutaneous manifestations of DIC and other hypercoagulable states may include purpura, livedo reticularis, atrophie blanche, and in extreme cases purpura fulminans. Routine laboratory examination reveals thrombocytopenia, prolonged prothrombin time/partial thromboplastin time, and hemolytic anemia.⁷ Although our patient had the risk factors of recent infection and surgery, a hemoglobin level of 10.9 g/dL (reference range, 14.0-17.5 g/dL) and platelet count of 279,000/µL (reference range, 150,000-350,000/µL) excluded DIC as the probable diagnosis. Our patient was at an overall increased risk for DVT due to his prolonged hospital stay, increased age, and other factors. Despite these risk factors, the lack of pain or swelling made this diagnosis unlikely. Furthermore, our patient was heparinized throughout his hospital stay, and upper extremity DVT accounts for only 4% to 10% of the total DVT incidence.⁵ 

Although R-L phenomenon is a benign, self-limited condition, it may be necessary in some cases to rule out more serious underlying etiologies with investigative workup comprised of a complete blood cell count, coagulation profile, and basic metabolic panel. However, recognition of the R-L phenomenon in the right clinical context of localized petechiae or ecchymoses with a history of a tourniquetlike force may prevent an unnecessary and costly workup. Patients should be encouraged that R-L phenomenon will resolve over time with identification and correction of the tourniquetlike force. In this case, we recommended loosening of the sphygmomanometer cuff and alternating extremities to which the cuff was to be placed, which resulted in complete clearance of the petechiae and ecchymoses within 5 days.  

The Diagnosis: Rumpel-Leede Phenomenon 

Rumpel-Leede (R-L) phenomenon describes the rare benign occurrence of dermal capillaries acutely rupturing following the administration of a tourniquetlike force on an extremity,¹ which manifests as asymptomatic petechiae and ecchymoses on a distal extremity, usually following noninvasive measurement of blood pressure.² Rumpel-Leede phenomenon represents an underrecognized entity that either is excluded or minimally referenced in most dermatology textbooks. The R-L sign initially was described in the early 1900s after it was observed that tourniquets applied to the arms of patients with scarlet fever would lead to the development of petechiae in that extremity.³ It later was elucidated that underlying vascular disease predisposes to dermal capillary fragility, a risk factor for R-L phenomenon to occur upon application of a tourniquet. Rumpel-Leede phenomenon has been noted in patients with diabetes mellitus, acute or chronic hypertension, and thrombocytopenia.⁴ In addition to being hypertensive and diabetic, our patient had been taking amlodipine and diltiazem. Calcium channel blockers have been linked to R-L phenomenon in case reports as well as in a study of calcium channel blockers inducing capillary fragility in vivo.⁵ Rumpel-Leede phenomenon also has been noted in patients with tightly fitting garments and infants carried in baby carriers.¹ 

The differential diagnosis for R-L phenomenon includes actinic purpura, small vessel vasculitis, disseminated intravascular coagulation (DIC), and deep vein thrombosis (DVT). Actinic purpura, also called solar purpura or senile purpura, represents the petechiae and ecchymoses that are associated with aging skin. It is thought to occur when DNA damage, UV-induced solar elastosis, and decreased lipids in the stratum corneum cause a weakened ability to contain red blood cell extravasation from capillaries.⁶ Due to the lack of history of trauma and clear association with the blood pressure cuff placement in our patient, a diagnosis of actinic purpura was unlikely. In small vessel vasculitis, patients classically present with nonblanching palpable purpura frequently distributed over the lower extremities. The isolation of the lesions to only the left arm lowered the suspicion for vasculitis. Cutaneous manifestations of DIC and other hypercoagulable states may include purpura, livedo reticularis, atrophie blanche, and in extreme cases purpura fulminans. Routine laboratory examination reveals thrombocytopenia, prolonged prothrombin time/partial thromboplastin time, and hemolytic anemia.⁷ Although our patient had the risk factors of recent infection and surgery, a hemoglobin level of 10.9 g/dL (reference range, 14.0-17.5 g/dL) and platelet count of 279,000/µL (reference range, 150,000-350,000/µL) excluded DIC as the probable diagnosis. Our patient was at an overall increased risk for DVT due to his prolonged hospital stay, increased age, and other factors. Despite these risk factors, the lack of pain or swelling made this diagnosis unlikely. Furthermore, our patient was heparinized throughout his hospital stay, and upper extremity DVT accounts for only 4% to 10% of the total DVT incidence.⁵ 

Although R-L phenomenon is a benign, self-limited condition, it may be necessary in some cases to rule out more serious underlying etiologies with investigative workup comprised of a complete blood cell count, coagulation profile, and basic metabolic panel. However, recognition of the R-L phenomenon in the right clinical context of localized petechiae or ecchymoses with a history of a tourniquetlike force may prevent an unnecessary and costly workup. Patients should be encouraged that R-L phenomenon will resolve over time with identification and correction of the tourniquetlike force. In this case, we recommended loosening of the sphygmomanometer cuff and alternating extremities to which the cuff was to be placed, which resulted in complete clearance of the petechiae and ecchymoses within 5 days.  

The Diagnosis: Rumpel-Leede Phenomenon 

Rumpel-Leede (R-L) phenomenon describes the rare benign occurrence of dermal capillaries acutely rupturing following the administration of a tourniquetlike force on an extremity,¹ which manifests as asymptomatic petechiae and ecchymoses on a distal extremity, usually following noninvasive measurement of blood pressure.² Rumpel-Leede phenomenon represents an underrecognized entity that either is excluded or minimally referenced in most dermatology textbooks. The R-L sign initially was described in the early 1900s after it was observed that tourniquets applied to the arms of patients with scarlet fever would lead to the development of petechiae in that extremity.³ It later was elucidated that underlying vascular disease predisposes to dermal capillary fragility, a risk factor for R-L phenomenon to occur upon application of a tourniquet. Rumpel-Leede phenomenon has been noted in patients with diabetes mellitus, acute or chronic hypertension, and thrombocytopenia.⁴ In addition to being hypertensive and diabetic, our patient had been taking amlodipine and diltiazem. Calcium channel blockers have been linked to R-L phenomenon in case reports as well as in a study of calcium channel blockers inducing capillary fragility in vivo.⁵ Rumpel-Leede phenomenon also has been noted in patients with tightly fitting garments and infants carried in baby carriers.¹ 

The differential diagnosis for R-L phenomenon includes actinic purpura, small vessel vasculitis, disseminated intravascular coagulation (DIC), and deep vein thrombosis (DVT). Actinic purpura, also called solar purpura or senile purpura, represents the petechiae and ecchymoses that are associated with aging skin. It is thought to occur when DNA damage, UV-induced solar elastosis, and decreased lipids in the stratum corneum cause a weakened ability to contain red blood cell extravasation from capillaries.⁶ Due to the lack of history of trauma and clear association with the blood pressure cuff placement in our patient, a diagnosis of actinic purpura was unlikely. In small vessel vasculitis, patients classically present with nonblanching palpable purpura frequently distributed over the lower extremities. The isolation of the lesions to only the left arm lowered the suspicion for vasculitis. Cutaneous manifestations of DIC and other hypercoagulable states may include purpura, livedo reticularis, atrophie blanche, and in extreme cases purpura fulminans. Routine laboratory examination reveals thrombocytopenia, prolonged prothrombin time/partial thromboplastin time, and hemolytic anemia.⁷ Although our patient had the risk factors of recent infection and surgery, a hemoglobin level of 10.9 g/dL (reference range, 14.0-17.5 g/dL) and platelet count of 279,000/µL (reference range, 150,000-350,000/µL) excluded DIC as the probable diagnosis. Our patient was at an overall increased risk for DVT due to his prolonged hospital stay, increased age, and other factors. Despite these risk factors, the lack of pain or swelling made this diagnosis unlikely. Furthermore, our patient was heparinized throughout his hospital stay, and upper extremity DVT accounts for only 4% to 10% of the total DVT incidence.⁵ 

Although R-L phenomenon is a benign, self-limited condition, it may be necessary in some cases to rule out more serious underlying etiologies with investigative workup comprised of a complete blood cell count, coagulation profile, and basic metabolic panel. However, recognition of the R-L phenomenon in the right clinical context of localized petechiae or ecchymoses with a history of a tourniquetlike force may prevent an unnecessary and costly workup. Patients should be encouraged that R-L phenomenon will resolve over time with identification and correction of the tourniquetlike force. In this case, we recommended loosening of the sphygmomanometer cuff and alternating extremities to which the cuff was to be placed, which resulted in complete clearance of the petechiae and ecchymoses within 5 days.  

The Diagnosis: Fiddler's Neck 

A thorough patient history revealed that the patient was retired and played violin regularly in the local orchestra. Fiddler's neck, or violin hickey, is an uncommon physical examination finding and often is considered a badge of honor by musicians who develop it. Fiddler's neck is a hobby-related callus seen in highly dedicated violin and viola players, and in some circles, it is known as a mark of greatness. In one instance, members of the public were asked to display a violin hickey before they were allowed to play a $3.5 million violin on public display in London, England.¹ Fiddler's neck is a benign submandibular lesion caused by pressure and friction on the skin from extensive time spent playing the instrument. The primary cause is thought to be mechanical, but it is not fully understood why the lesion occurs in some musicians and not others, regardless of playing time.¹ This submandibular fiddler's neck is distinct from a similarly named supraclavicular lesion, which represents an allergic contact dermatitis to the nickel bracket of the instrument's chin rest and presents with eczematous scale and/or vesicles.^2,3 Submandibular fiddler's neck presents with some combination of erythema, edema, lichenification, and scarring just below the angle of the jaw. Occasionally, papules, pustules, and even cyst formation may be noted. Lesions are sometimes mistaken for malignancy or lymphedema. Therefore, a thorough history and clinical expertise are important, as surgical excision should be avoided.²  

Depending on presentation, the differential diagnosis also may include malignant melanoma due to irregular pigmentation, branchial cleft cyst or sialolithiasis due to location and texture, or a tumor of the salivary gland. 

Management of fiddler's neck may include topical steroids, neck or instrument padding, or decreased playing time. However, the lesion often is worn with pride, seen as a testament to the musician's dedication, and reassurance generally is most appropriate.¹  

The Diagnosis: Fiddler's Neck 

A thorough patient history revealed that the patient was retired and played violin regularly in the local orchestra. Fiddler's neck, or violin hickey, is an uncommon physical examination finding and often is considered a badge of honor by musicians who develop it. Fiddler's neck is a hobby-related callus seen in highly dedicated violin and viola players, and in some circles, it is known as a mark of greatness. In one instance, members of the public were asked to display a violin hickey before they were allowed to play a $3.5 million violin on public display in London, England.¹ Fiddler's neck is a benign submandibular lesion caused by pressure and friction on the skin from extensive time spent playing the instrument. The primary cause is thought to be mechanical, but it is not fully understood why the lesion occurs in some musicians and not others, regardless of playing time.¹ This submandibular fiddler's neck is distinct from a similarly named supraclavicular lesion, which represents an allergic contact dermatitis to the nickel bracket of the instrument's chin rest and presents with eczematous scale and/or vesicles.^2,3 Submandibular fiddler's neck presents with some combination of erythema, edema, lichenification, and scarring just below the angle of the jaw. Occasionally, papules, pustules, and even cyst formation may be noted. Lesions are sometimes mistaken for malignancy or lymphedema. Therefore, a thorough history and clinical expertise are important, as surgical excision should be avoided.²  

Depending on presentation, the differential diagnosis also may include malignant melanoma due to irregular pigmentation, branchial cleft cyst or sialolithiasis due to location and texture, or a tumor of the salivary gland. 

Management of fiddler's neck may include topical steroids, neck or instrument padding, or decreased playing time. However, the lesion often is worn with pride, seen as a testament to the musician's dedication, and reassurance generally is most appropriate.¹  

The Diagnosis: Fiddler's Neck 

A thorough patient history revealed that the patient was retired and played violin regularly in the local orchestra. Fiddler's neck, or violin hickey, is an uncommon physical examination finding and often is considered a badge of honor by musicians who develop it. Fiddler's neck is a hobby-related callus seen in highly dedicated violin and viola players, and in some circles, it is known as a mark of greatness. In one instance, members of the public were asked to display a violin hickey before they were allowed to play a $3.5 million violin on public display in London, England.¹ Fiddler's neck is a benign submandibular lesion caused by pressure and friction on the skin from extensive time spent playing the instrument. The primary cause is thought to be mechanical, but it is not fully understood why the lesion occurs in some musicians and not others, regardless of playing time.¹ This submandibular fiddler's neck is distinct from a similarly named supraclavicular lesion, which represents an allergic contact dermatitis to the nickel bracket of the instrument's chin rest and presents with eczematous scale and/or vesicles.^2,3 Submandibular fiddler's neck presents with some combination of erythema, edema, lichenification, and scarring just below the angle of the jaw. Occasionally, papules, pustules, and even cyst formation may be noted. Lesions are sometimes mistaken for malignancy or lymphedema. Therefore, a thorough history and clinical expertise are important, as surgical excision should be avoided.²  

Depending on presentation, the differential diagnosis also may include malignant melanoma due to irregular pigmentation, branchial cleft cyst or sialolithiasis due to location and texture, or a tumor of the salivary gland. 

Management of fiddler's neck may include topical steroids, neck or instrument padding, or decreased playing time. However, the lesion often is worn with pride, seen as a testament to the musician's dedication, and reassurance generally is most appropriate.¹  

The Diagnosis: Candidal Intertrigo  

The biopsy confirmed a diagnosis of severe hyperkeratotic candidal intertrigo with no evidence of Hailey-Hailey disease. Hematoxylin and eosin- stained sections demonstrated irregular acanthosis and variable spongiosis. The stratum corneum was predominantly orthokeratotic with overlying psuedohyphae and yeast fungal elements (Figure 1). 

Hyperimmunoglobulinemia E syndrome (HIES), also known as hyper-IgE syndrome or Job syndrome, is a rare immunodeficiency disorder characterized by an eczematous dermatitis-like rash, recurrent skin and lung abscesses, eosinophilia, and elevated serum IgE. Facial asymmetry, prominent forehead, deep-set eyes, broad nose, and roughened facial skin with large pores are characteristic of the sporadic and autosomal-recessive forms. Other common findings include retained primary teeth, hyperextensible joints, and recurrent mucocutaneous candidiasis.¹ 

Although autosomal-dominant and autosomal-recessive inheritance patterns exist, sporadic mutations are the most common cause of HIES.² Several genes have been implicated depending on the inheritance pattern. The majority of autosomal-dominant cases are associated with inactivating STAT3 (signal transducer and activator of transcription 3) mutations, whereas the majority of autosomal-recessive cases are associated with inactivating DOCK8 (dedicator of cytokinesis 8) mutations.¹ Ultimately, all of these mutations lead to an impaired helper T cell (T_H17) response, which is crucial for clearing fungal and extracellular bacterial infections.³  

Skin eruptions typically are the first manifestation of HIES; they appear within the first week to month of life as papulopustular eruptions on the face and scalp and rapidly generalize to the rest of the body, favoring the shoulders, arms, chest, and buttocks. The pustules then coalesce into crusted plaques that resemble atopic dermatitis, frequently with superimposed Staphylococcus aureus infection. On microscopy, the pustules are folliculocentric and often contain eosinophils, whereas the plaques may contain intraepidermal collections of eosinophils.¹ 

Mucocutaneous candidiasis is seen in approximately 60% of HIES cases and is closely linked to STAT3 inactivating mutations.³ Histologically, there is marked acanthosis with neutrophil exocytosis and abundant yeast and pseudohyphal forms within the stratum corneum (Figure 2).⁴ Cutaneous candidal infections typically require both oral and topical antifungal agents to clear the infection.³ Most cases of mucocutaneous candidiasis are caused by Candida albicans; however, other known culprits include Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei.^5,6 Of note, species identification and antifungal susceptibility studies may be useful in refractory cases, especially with C glabrata, which is known to acquire resistance to azoles, such as fluconazole, with emerging resistance to echinocandins.⁶  

The differential diagnosis of this groin eruption included Hailey-Hailey disease; pemphigus vegetans, Hallopeau type; tinea cruris; and inverse psoriasis. Hailey-Hailey disease can be complicated by a superimposed candidal infection with similar clinical features, and biopsy may be required for definitive diagnosis. Hailey-Hailey disease typically presents with macerated fissured plaques that resemble macerated tissue paper with red fissures (Figure 3). Biopsy confirms full-thickness acantholysis resembling a dilapidated brick wall with minimal dyskeratosis.¹ Pemphigus vegetans is a localized variant of pemphigus vulgaris with a predilection for flexural surfaces. The lesions progress to vegetating erosive plaques.⁴ The Hallopeau type often is studded with pustules and typically remains more localized than the Neumann type. Direct immunofluorescence demonstrates intercellular deposition of IgG and C3, and routine sections characteristically show pseudoepitheliomatous hyperplasia with intraepidermal eosinophilic microabscesses.^1,4 Tinea cruris is characterized by erythematous annular lesions with raised scaly borders spreading down the inner thighs.⁷ The epidermis is variably spongiotic with parakeratosis, and neutrophils often present in a layered stratum corneum with basketweave keratin above a layer of more compact and eosinophilic keratin. Fungal stains, such as periodic acid-Schiff, will highlight the fungal hyphae within the stratum corneum. The inguinal folds are a typical location for inverse psoriasis, which generally appears as thin, sharply demarcated, shiny red plaques with less scale than plaque psoriasis.¹ Psoriasiform hyperplasia with a diminished granular layer and tortuous papillary dermal vessels would be expected histologically.¹ 

The Diagnosis: Candidal Intertrigo  

The biopsy confirmed a diagnosis of severe hyperkeratotic candidal intertrigo with no evidence of Hailey-Hailey disease. Hematoxylin and eosin- stained sections demonstrated irregular acanthosis and variable spongiosis. The stratum corneum was predominantly orthokeratotic with overlying psuedohyphae and yeast fungal elements (Figure 1). 

Hyperimmunoglobulinemia E syndrome (HIES), also known as hyper-IgE syndrome or Job syndrome, is a rare immunodeficiency disorder characterized by an eczematous dermatitis-like rash, recurrent skin and lung abscesses, eosinophilia, and elevated serum IgE. Facial asymmetry, prominent forehead, deep-set eyes, broad nose, and roughened facial skin with large pores are characteristic of the sporadic and autosomal-recessive forms. Other common findings include retained primary teeth, hyperextensible joints, and recurrent mucocutaneous candidiasis.¹ 

Although autosomal-dominant and autosomal-recessive inheritance patterns exist, sporadic mutations are the most common cause of HIES.² Several genes have been implicated depending on the inheritance pattern. The majority of autosomal-dominant cases are associated with inactivating STAT3 (signal transducer and activator of transcription 3) mutations, whereas the majority of autosomal-recessive cases are associated with inactivating DOCK8 (dedicator of cytokinesis 8) mutations.¹ Ultimately, all of these mutations lead to an impaired helper T cell (T_H17) response, which is crucial for clearing fungal and extracellular bacterial infections.³  

Skin eruptions typically are the first manifestation of HIES; they appear within the first week to month of life as papulopustular eruptions on the face and scalp and rapidly generalize to the rest of the body, favoring the shoulders, arms, chest, and buttocks. The pustules then coalesce into crusted plaques that resemble atopic dermatitis, frequently with superimposed Staphylococcus aureus infection. On microscopy, the pustules are folliculocentric and often contain eosinophils, whereas the plaques may contain intraepidermal collections of eosinophils.¹ 

Mucocutaneous candidiasis is seen in approximately 60% of HIES cases and is closely linked to STAT3 inactivating mutations.³ Histologically, there is marked acanthosis with neutrophil exocytosis and abundant yeast and pseudohyphal forms within the stratum corneum (Figure 2).⁴ Cutaneous candidal infections typically require both oral and topical antifungal agents to clear the infection.³ Most cases of mucocutaneous candidiasis are caused by Candida albicans; however, other known culprits include Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei.^5,6 Of note, species identification and antifungal susceptibility studies may be useful in refractory cases, especially with C glabrata, which is known to acquire resistance to azoles, such as fluconazole, with emerging resistance to echinocandins.⁶  

The differential diagnosis of this groin eruption included Hailey-Hailey disease; pemphigus vegetans, Hallopeau type; tinea cruris; and inverse psoriasis. Hailey-Hailey disease can be complicated by a superimposed candidal infection with similar clinical features, and biopsy may be required for definitive diagnosis. Hailey-Hailey disease typically presents with macerated fissured plaques that resemble macerated tissue paper with red fissures (Figure 3). Biopsy confirms full-thickness acantholysis resembling a dilapidated brick wall with minimal dyskeratosis.¹ Pemphigus vegetans is a localized variant of pemphigus vulgaris with a predilection for flexural surfaces. The lesions progress to vegetating erosive plaques.⁴ The Hallopeau type often is studded with pustules and typically remains more localized than the Neumann type. Direct immunofluorescence demonstrates intercellular deposition of IgG and C3, and routine sections characteristically show pseudoepitheliomatous hyperplasia with intraepidermal eosinophilic microabscesses.^1,4 Tinea cruris is characterized by erythematous annular lesions with raised scaly borders spreading down the inner thighs.⁷ The epidermis is variably spongiotic with parakeratosis, and neutrophils often present in a layered stratum corneum with basketweave keratin above a layer of more compact and eosinophilic keratin. Fungal stains, such as periodic acid-Schiff, will highlight the fungal hyphae within the stratum corneum. The inguinal folds are a typical location for inverse psoriasis, which generally appears as thin, sharply demarcated, shiny red plaques with less scale than plaque psoriasis.¹ Psoriasiform hyperplasia with a diminished granular layer and tortuous papillary dermal vessels would be expected histologically.¹ 

The Diagnosis: Candidal Intertrigo  

The biopsy confirmed a diagnosis of severe hyperkeratotic candidal intertrigo with no evidence of Hailey-Hailey disease. Hematoxylin and eosin- stained sections demonstrated irregular acanthosis and variable spongiosis. The stratum corneum was predominantly orthokeratotic with overlying psuedohyphae and yeast fungal elements (Figure 1). 

Hyperimmunoglobulinemia E syndrome (HIES), also known as hyper-IgE syndrome or Job syndrome, is a rare immunodeficiency disorder characterized by an eczematous dermatitis-like rash, recurrent skin and lung abscesses, eosinophilia, and elevated serum IgE. Facial asymmetry, prominent forehead, deep-set eyes, broad nose, and roughened facial skin with large pores are characteristic of the sporadic and autosomal-recessive forms. Other common findings include retained primary teeth, hyperextensible joints, and recurrent mucocutaneous candidiasis.¹ 

Although autosomal-dominant and autosomal-recessive inheritance patterns exist, sporadic mutations are the most common cause of HIES.² Several genes have been implicated depending on the inheritance pattern. The majority of autosomal-dominant cases are associated with inactivating STAT3 (signal transducer and activator of transcription 3) mutations, whereas the majority of autosomal-recessive cases are associated with inactivating DOCK8 (dedicator of cytokinesis 8) mutations.¹ Ultimately, all of these mutations lead to an impaired helper T cell (T_H17) response, which is crucial for clearing fungal and extracellular bacterial infections.³  

Skin eruptions typically are the first manifestation of HIES; they appear within the first week to month of life as papulopustular eruptions on the face and scalp and rapidly generalize to the rest of the body, favoring the shoulders, arms, chest, and buttocks. The pustules then coalesce into crusted plaques that resemble atopic dermatitis, frequently with superimposed Staphylococcus aureus infection. On microscopy, the pustules are folliculocentric and often contain eosinophils, whereas the plaques may contain intraepidermal collections of eosinophils.¹ 

Mucocutaneous candidiasis is seen in approximately 60% of HIES cases and is closely linked to STAT3 inactivating mutations.³ Histologically, there is marked acanthosis with neutrophil exocytosis and abundant yeast and pseudohyphal forms within the stratum corneum (Figure 2).⁴ Cutaneous candidal infections typically require both oral and topical antifungal agents to clear the infection.³ Most cases of mucocutaneous candidiasis are caused by Candida albicans; however, other known culprits include Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei.^5,6 Of note, species identification and antifungal susceptibility studies may be useful in refractory cases, especially with C glabrata, which is known to acquire resistance to azoles, such as fluconazole, with emerging resistance to echinocandins.⁶  

The differential diagnosis of this groin eruption included Hailey-Hailey disease; pemphigus vegetans, Hallopeau type; tinea cruris; and inverse psoriasis. Hailey-Hailey disease can be complicated by a superimposed candidal infection with similar clinical features, and biopsy may be required for definitive diagnosis. Hailey-Hailey disease typically presents with macerated fissured plaques that resemble macerated tissue paper with red fissures (Figure 3). Biopsy confirms full-thickness acantholysis resembling a dilapidated brick wall with minimal dyskeratosis.¹ Pemphigus vegetans is a localized variant of pemphigus vulgaris with a predilection for flexural surfaces. The lesions progress to vegetating erosive plaques.⁴ The Hallopeau type often is studded with pustules and typically remains more localized than the Neumann type. Direct immunofluorescence demonstrates intercellular deposition of IgG and C3, and routine sections characteristically show pseudoepitheliomatous hyperplasia with intraepidermal eosinophilic microabscesses.^1,4 Tinea cruris is characterized by erythematous annular lesions with raised scaly borders spreading down the inner thighs.⁷ The epidermis is variably spongiotic with parakeratosis, and neutrophils often present in a layered stratum corneum with basketweave keratin above a layer of more compact and eosinophilic keratin. Fungal stains, such as periodic acid-Schiff, will highlight the fungal hyphae within the stratum corneum. The inguinal folds are a typical location for inverse psoriasis, which generally appears as thin, sharply demarcated, shiny red plaques with less scale than plaque psoriasis.¹ Psoriasiform hyperplasia with a diminished granular layer and tortuous papillary dermal vessels would be expected histologically.¹