Photo Challenge

The Diagnosis: Tripe Palms and Acanthosis Nigricans

A shave biopsy specimen from the left palm showed slight epidermal hyperplasia with substantial papillomatosis and compact orthokeratosis. The complete blood cell count, thy­rotropin level, uric acid level, liver function tests, mammogram, Papanicolaou test, and chest radio­graph were unremarkable. A basic metabolic panel showed mildly elevated blood glucose at 111 mg/dL (reference range, 70-99 mg/dL) and hemoglobin A_1c at 6.3% (reference range, <6.0%). Full-body com­puted tomography, endoscopy, and colonoscopy ini­tially were normal. One year later after presenting with tripe palms, the patient had a bowel obstruction secondary to omental carcinomatosis from a primary ovarian tumor.

The term tripe in tripe palms refers to the resem­blance to the edible lining of the bovine foregut. It originated in 1963 from a patient's own description of the rugose velvety texture of the palms.¹ In the lit­erature, tripe palms also is called acanthosis palmaris, acanthosis nigricans of the palms, palmar hyperkera­tosis, palmar keratoderma, and pachydermatoglyphy. It is a rare cutaneous finding. Tripe palms is associated with other cutaneous paraneoplastic syndromes such as malignant acanthosis nigricans (72% of cases) and Leser-Trélat sign (10% of cases). It affects more men than women (63% vs 37%) and is almost exclusively seen in adults (median age, 62 years).¹

The clinical appearance of tripe palms includes hypertrophy of the palms and often the soles with papillations producing a velvety or honeycomb appearance. In addition, the dermatoglyphics are pro­nounced. The histologic findings typically show hy­perkeratosis and acanthosis. Other features that can be seen include dermal mucinosis and increased mast cells in the dermis. To differentiate tripe palms from other keratodermas, substantial papillations can be seen with less diffuse hyperkeratosis.¹

Tripe palms has been associated with an underlying malignancy in more than 90% of published cases. In two-thirds of cases, tripe palms either appears before or concurrent with the diagnosis of cancer.² It is rarely reported as an idiopathic finding or associated with nonneoplastic disorders. Malignancies most common­ly associated are adenocarcinomas, especially of the stomach (27%) and lungs (22%). Other neoplasms, such as in our patient, include those of the genito­urinary tract and breast. In a patient with tripe palms in the absence of acanthosis nigricans, the most com­mon neoplasm is of the lung, especially when clubbing of the nails also is present.² Thus, after a diagnosis of tripe palms is established, a thorough investigation for an underlying malignancy is the next most important step to direct specific therapy.

The Diagnosis: Tripe Palms and Acanthosis Nigricans

A shave biopsy specimen from the left palm showed slight epidermal hyperplasia with substantial papillomatosis and compact orthokeratosis. The complete blood cell count, thy­rotropin level, uric acid level, liver function tests, mammogram, Papanicolaou test, and chest radio­graph were unremarkable. A basic metabolic panel showed mildly elevated blood glucose at 111 mg/dL (reference range, 70-99 mg/dL) and hemoglobin A_1c at 6.3% (reference range, <6.0%). Full-body com­puted tomography, endoscopy, and colonoscopy ini­tially were normal. One year later after presenting with tripe palms, the patient had a bowel obstruction secondary to omental carcinomatosis from a primary ovarian tumor.

The term tripe in tripe palms refers to the resem­blance to the edible lining of the bovine foregut. It originated in 1963 from a patient's own description of the rugose velvety texture of the palms.¹ In the lit­erature, tripe palms also is called acanthosis palmaris, acanthosis nigricans of the palms, palmar hyperkera­tosis, palmar keratoderma, and pachydermatoglyphy. It is a rare cutaneous finding. Tripe palms is associated with other cutaneous paraneoplastic syndromes such as malignant acanthosis nigricans (72% of cases) and Leser-Trélat sign (10% of cases). It affects more men than women (63% vs 37%) and is almost exclusively seen in adults (median age, 62 years).¹

The clinical appearance of tripe palms includes hypertrophy of the palms and often the soles with papillations producing a velvety or honeycomb appearance. In addition, the dermatoglyphics are pro­nounced. The histologic findings typically show hy­perkeratosis and acanthosis. Other features that can be seen include dermal mucinosis and increased mast cells in the dermis. To differentiate tripe palms from other keratodermas, substantial papillations can be seen with less diffuse hyperkeratosis.¹

Tripe palms has been associated with an underlying malignancy in more than 90% of published cases. In two-thirds of cases, tripe palms either appears before or concurrent with the diagnosis of cancer.² It is rarely reported as an idiopathic finding or associated with nonneoplastic disorders. Malignancies most common­ly associated are adenocarcinomas, especially of the stomach (27%) and lungs (22%). Other neoplasms, such as in our patient, include those of the genito­urinary tract and breast. In a patient with tripe palms in the absence of acanthosis nigricans, the most com­mon neoplasm is of the lung, especially when clubbing of the nails also is present.² Thus, after a diagnosis of tripe palms is established, a thorough investigation for an underlying malignancy is the next most important step to direct specific therapy.

The Diagnosis: Tripe Palms and Acanthosis Nigricans

A shave biopsy specimen from the left palm showed slight epidermal hyperplasia with substantial papillomatosis and compact orthokeratosis. The complete blood cell count, thy­rotropin level, uric acid level, liver function tests, mammogram, Papanicolaou test, and chest radio­graph were unremarkable. A basic metabolic panel showed mildly elevated blood glucose at 111 mg/dL (reference range, 70-99 mg/dL) and hemoglobin A_1c at 6.3% (reference range, <6.0%). Full-body com­puted tomography, endoscopy, and colonoscopy ini­tially were normal. One year later after presenting with tripe palms, the patient had a bowel obstruction secondary to omental carcinomatosis from a primary ovarian tumor.

The term tripe in tripe palms refers to the resem­blance to the edible lining of the bovine foregut. It originated in 1963 from a patient's own description of the rugose velvety texture of the palms.¹ In the lit­erature, tripe palms also is called acanthosis palmaris, acanthosis nigricans of the palms, palmar hyperkera­tosis, palmar keratoderma, and pachydermatoglyphy. It is a rare cutaneous finding. Tripe palms is associated with other cutaneous paraneoplastic syndromes such as malignant acanthosis nigricans (72% of cases) and Leser-Trélat sign (10% of cases). It affects more men than women (63% vs 37%) and is almost exclusively seen in adults (median age, 62 years).¹

The clinical appearance of tripe palms includes hypertrophy of the palms and often the soles with papillations producing a velvety or honeycomb appearance. In addition, the dermatoglyphics are pro­nounced. The histologic findings typically show hy­perkeratosis and acanthosis. Other features that can be seen include dermal mucinosis and increased mast cells in the dermis. To differentiate tripe palms from other keratodermas, substantial papillations can be seen with less diffuse hyperkeratosis.¹

Tripe palms has been associated with an underlying malignancy in more than 90% of published cases. In two-thirds of cases, tripe palms either appears before or concurrent with the diagnosis of cancer.² It is rarely reported as an idiopathic finding or associated with nonneoplastic disorders. Malignancies most common­ly associated are adenocarcinomas, especially of the stomach (27%) and lungs (22%). Other neoplasms, such as in our patient, include those of the genito­urinary tract and breast. In a patient with tripe palms in the absence of acanthosis nigricans, the most com­mon neoplasm is of the lung, especially when clubbing of the nails also is present.² Thus, after a diagnosis of tripe palms is established, a thorough investigation for an underlying malignancy is the next most important step to direct specific therapy.

The Diagnosis: Pilomatricoma

Pilomatricoma, first described by Malherbe and Chenantais¹ in 1880, is a benign appendageal tumor derived from hair follicle matrix cells. It classically manifests as a solitary, asymptomatic, firm dermal nodule with a normal overlying epidermis. Less common morphologic variants include perforating, lymphagiectatic, keratoacanthomalike, pigmented, and anetodermalike surface changes.² Inflammation and erosion through the skin surface are observed in the rare perforating variant, as seen in our patient. The average size is 1 cm, and it rarely exceeds 3 cm in diameter.³ The tumors predominantly occur on the head, neck, and upper extremities, with only 9.5% on the scalp.² It may occur at any age, though it has a bimodal distribution with peaks in childhood and in adults older than 60 years. A slight preponderance in females has been observed with a female to male ratio of 1.5 to 1.² Although our patient is black, most reported cases have occurred in individuals of European descent. Because cases of pilomatricoma are not systematically reported, it is uncertain if this finding represents a publication bias or if race is an actual risk factor. Multiple pilomatricomas and familial cases have been described in association with myotonic dystrophy, Turner syndrome, Gardner syndrome, Rubinstein-Taybi syndrome, polyfactorial coagulopathy, trisomy 9, xeroderma pigmentosum, and basal cell nevus syndrome.^2,4

It has been shown that the proliferating cells of pilomatricomas stain with antibodies directed against Lef1 (lymphoid enhancer binding factor 1), a marker from hair matrix cells, providing biochemical evidence for the morphologic appearance of these neoplasms.⁵ Pilomatricomas have been associated with B-cell/chronic lymphocytic leukemia lymphoma 2 gene, BCL2, expression, a proto-oncogene that suppresses apoptosis in benign and malignant neoplasms, which may contribute to the pathogenesis of these tumors.⁶ Pilomatricomas also have been associated with β-catenin mutation, expression of Bmp2 (bone morphogenetic protein 2), and human hair keratin basic 1.^7-9

Definitive diagnosis is obtained through biopsy, looking for characteristic histopathologic findings. The lesion usually is found in the lower dermis and subcutaneous fat. However, in the perforating variant, the lesion is more superficial, located in the papillary and mid dermis, as seen in our patient.¹⁰

Islands of pale eosinophilic shadow cells with an intense dermal infiltrate consisting of lymphocytes, histiocytes, plasma cells, and neutrophils (H&amp;E, original magnification ×400).

Pilomatricomas are sharply demarcated, often surrounded by a connective-tissue capsule. Histopathologic analysis reveals islands of epithelial cells comprised of 3 subtypes: basophilic cells with scant cytoplasm, shadow cells with a central pallor (Figure), and transitional cells between the former 2 cellular types.¹¹ The number of basophilic and transitional cells is inversely related to the number of shadow cells. In older lesions, the shadow cells predominate, while the basophilic cells are few in number or absent. Calcium deposits are seen in 80% of lesions with von Kossa staining.¹²

Transformation into malignancy, known as pilomatrical carcinoma, is rare. These malignant neoplasms are characterized by aggressive biologic behavior such as recurrence, diffuse spread, or metastasis, or by cytologic abnormalities such as poor cellular organization, squamous differentiation, and conspicuous mitotic activity.¹³ The recent growth of the long-standing lesion in our patient might be interpreted as a sign of malignant transformation. However, this observation may be related to the intense inflammatory reaction supported by the histopathology.

Pilomatricomas are not associated with mortality. Pilomatrical carcinomas are uncommon but are locally invasive and can cause visceral metastases and death. Spontaneous regression has never been observed and medical treatment is ineffective. The treatment of choice is incision and curettage or surgical excision.¹⁴ Although recurrence has only been reported in 2.6% of cases from a large case series (N=228), patients should be monitored after surgical excision.¹²

The Diagnosis: Pilomatricoma

Pilomatricoma, first described by Malherbe and Chenantais¹ in 1880, is a benign appendageal tumor derived from hair follicle matrix cells. It classically manifests as a solitary, asymptomatic, firm dermal nodule with a normal overlying epidermis. Less common morphologic variants include perforating, lymphagiectatic, keratoacanthomalike, pigmented, and anetodermalike surface changes.² Inflammation and erosion through the skin surface are observed in the rare perforating variant, as seen in our patient. The average size is 1 cm, and it rarely exceeds 3 cm in diameter.³ The tumors predominantly occur on the head, neck, and upper extremities, with only 9.5% on the scalp.² It may occur at any age, though it has a bimodal distribution with peaks in childhood and in adults older than 60 years. A slight preponderance in females has been observed with a female to male ratio of 1.5 to 1.² Although our patient is black, most reported cases have occurred in individuals of European descent. Because cases of pilomatricoma are not systematically reported, it is uncertain if this finding represents a publication bias or if race is an actual risk factor. Multiple pilomatricomas and familial cases have been described in association with myotonic dystrophy, Turner syndrome, Gardner syndrome, Rubinstein-Taybi syndrome, polyfactorial coagulopathy, trisomy 9, xeroderma pigmentosum, and basal cell nevus syndrome.^2,4

It has been shown that the proliferating cells of pilomatricomas stain with antibodies directed against Lef1 (lymphoid enhancer binding factor 1), a marker from hair matrix cells, providing biochemical evidence for the morphologic appearance of these neoplasms.⁵ Pilomatricomas have been associated with B-cell/chronic lymphocytic leukemia lymphoma 2 gene, BCL2, expression, a proto-oncogene that suppresses apoptosis in benign and malignant neoplasms, which may contribute to the pathogenesis of these tumors.⁶ Pilomatricomas also have been associated with β-catenin mutation, expression of Bmp2 (bone morphogenetic protein 2), and human hair keratin basic 1.^7-9

Definitive diagnosis is obtained through biopsy, looking for characteristic histopathologic findings. The lesion usually is found in the lower dermis and subcutaneous fat. However, in the perforating variant, the lesion is more superficial, located in the papillary and mid dermis, as seen in our patient.¹⁰

Islands of pale eosinophilic shadow cells with an intense dermal infiltrate consisting of lymphocytes, histiocytes, plasma cells, and neutrophils (H&amp;E, original magnification ×400).

Pilomatricomas are sharply demarcated, often surrounded by a connective-tissue capsule. Histopathologic analysis reveals islands of epithelial cells comprised of 3 subtypes: basophilic cells with scant cytoplasm, shadow cells with a central pallor (Figure), and transitional cells between the former 2 cellular types.¹¹ The number of basophilic and transitional cells is inversely related to the number of shadow cells. In older lesions, the shadow cells predominate, while the basophilic cells are few in number or absent. Calcium deposits are seen in 80% of lesions with von Kossa staining.¹²

Transformation into malignancy, known as pilomatrical carcinoma, is rare. These malignant neoplasms are characterized by aggressive biologic behavior such as recurrence, diffuse spread, or metastasis, or by cytologic abnormalities such as poor cellular organization, squamous differentiation, and conspicuous mitotic activity.¹³ The recent growth of the long-standing lesion in our patient might be interpreted as a sign of malignant transformation. However, this observation may be related to the intense inflammatory reaction supported by the histopathology.

Pilomatricomas are not associated with mortality. Pilomatrical carcinomas are uncommon but are locally invasive and can cause visceral metastases and death. Spontaneous regression has never been observed and medical treatment is ineffective. The treatment of choice is incision and curettage or surgical excision.¹⁴ Although recurrence has only been reported in 2.6% of cases from a large case series (N=228), patients should be monitored after surgical excision.¹²

The Diagnosis: Pilomatricoma

Pilomatricoma, first described by Malherbe and Chenantais¹ in 1880, is a benign appendageal tumor derived from hair follicle matrix cells. It classically manifests as a solitary, asymptomatic, firm dermal nodule with a normal overlying epidermis. Less common morphologic variants include perforating, lymphagiectatic, keratoacanthomalike, pigmented, and anetodermalike surface changes.² Inflammation and erosion through the skin surface are observed in the rare perforating variant, as seen in our patient. The average size is 1 cm, and it rarely exceeds 3 cm in diameter.³ The tumors predominantly occur on the head, neck, and upper extremities, with only 9.5% on the scalp.² It may occur at any age, though it has a bimodal distribution with peaks in childhood and in adults older than 60 years. A slight preponderance in females has been observed with a female to male ratio of 1.5 to 1.² Although our patient is black, most reported cases have occurred in individuals of European descent. Because cases of pilomatricoma are not systematically reported, it is uncertain if this finding represents a publication bias or if race is an actual risk factor. Multiple pilomatricomas and familial cases have been described in association with myotonic dystrophy, Turner syndrome, Gardner syndrome, Rubinstein-Taybi syndrome, polyfactorial coagulopathy, trisomy 9, xeroderma pigmentosum, and basal cell nevus syndrome.^2,4

It has been shown that the proliferating cells of pilomatricomas stain with antibodies directed against Lef1 (lymphoid enhancer binding factor 1), a marker from hair matrix cells, providing biochemical evidence for the morphologic appearance of these neoplasms.⁵ Pilomatricomas have been associated with B-cell/chronic lymphocytic leukemia lymphoma 2 gene, BCL2, expression, a proto-oncogene that suppresses apoptosis in benign and malignant neoplasms, which may contribute to the pathogenesis of these tumors.⁶ Pilomatricomas also have been associated with β-catenin mutation, expression of Bmp2 (bone morphogenetic protein 2), and human hair keratin basic 1.^7-9

Definitive diagnosis is obtained through biopsy, looking for characteristic histopathologic findings. The lesion usually is found in the lower dermis and subcutaneous fat. However, in the perforating variant, the lesion is more superficial, located in the papillary and mid dermis, as seen in our patient.¹⁰

Islands of pale eosinophilic shadow cells with an intense dermal infiltrate consisting of lymphocytes, histiocytes, plasma cells, and neutrophils (H&amp;E, original magnification ×400).

Pilomatricomas are sharply demarcated, often surrounded by a connective-tissue capsule. Histopathologic analysis reveals islands of epithelial cells comprised of 3 subtypes: basophilic cells with scant cytoplasm, shadow cells with a central pallor (Figure), and transitional cells between the former 2 cellular types.¹¹ The number of basophilic and transitional cells is inversely related to the number of shadow cells. In older lesions, the shadow cells predominate, while the basophilic cells are few in number or absent. Calcium deposits are seen in 80% of lesions with von Kossa staining.¹²

Transformation into malignancy, known as pilomatrical carcinoma, is rare. These malignant neoplasms are characterized by aggressive biologic behavior such as recurrence, diffuse spread, or metastasis, or by cytologic abnormalities such as poor cellular organization, squamous differentiation, and conspicuous mitotic activity.¹³ The recent growth of the long-standing lesion in our patient might be interpreted as a sign of malignant transformation. However, this observation may be related to the intense inflammatory reaction supported by the histopathology.

Pilomatricomas are not associated with mortality. Pilomatrical carcinomas are uncommon but are locally invasive and can cause visceral metastases and death. Spontaneous regression has never been observed and medical treatment is ineffective. The treatment of choice is incision and curettage or surgical excision.¹⁴ Although recurrence has only been reported in 2.6% of cases from a large case series (N=228), patients should be monitored after surgical excision.¹²

The Diagnosis: Disseminated Coccidioidomycosis

Fungi of the genus Coccidioides cause coccidioidomycosis and live in the soil of endemic areas including the southwestern United States (eg, Arizona, New Mexico, California) and Mexico. Coccidioides is a dimorphic fungus with parasitic and infectious saprophytic phases. Each year there are approximately 150,000 new infections of coccidioidomycosis in the United States, almost exclusively in the southwest.¹ Coccidioidomycosis typically is an asymptomatic or mild infection in an immunocompetent patient. Although the lungs are nearly always the primary sites of infection, common sites of dissemination include the skin, meninges, bones, and joints. The skin is the most common site of disseminated, or secondary, coccidioidomycosis.² Less commonly and usually caused by traumatic implantation, the skin is the site of primary infection.

Disseminated coccidioidomycosis occurs in approximately 1 in 200 infected individuals.^2,3 Certain populations of patients are more likely to be affected by disseminated coccidioidomycosis, including specific ethnic groups such as black individuals, Filipinos, and Mexicans^4,5; pregnant women⁶; and immunosuppressed patients such as those with human immunodeficiency virus, hematogenous malignancy, or organ transplantation.^7-9 When skin lesions are present, they usually develop after the initial lung manifestation. The location of the lesion in cutaneous disseminated disease can be highly variable, but the face and head are the most common locations (30%).¹⁰

Cutaneous manifestations of coccidioidomycosis may be classified as being caused by the presence of the organism in the skin (organism specific) or a reactive process. Organism-specific cutaneous lesions are commonly due to systemic disease with secondary skin involvement, but they also may be due to a primary infection. These organism-specific lesions can present as papules, nodules, macules, verrucous plaques, abscesses, or pustules. Reactive cutaneous manifestations are only associated with disseminated disease; do not contain any organisms; and include manifestations such as erythema nodosum, acute exanthem, erythema multiforme, and possibly Sweet syndrome.¹¹

The clinical differential diagnosis of cutaneous coccidioidomycosis includes other

Coccidioidal spherules in the dermis (Periodic acid–Schiff, original magnification ×600).

mycoses such as histoplasmosis and blastomycosis, as well as tuberculosis, sarcoidosis, basal cell and squamous cell carcinoma, and verruca vulgaris. The diagnosis of cutaneous coccidioidomycosis can be made with skin biopsy, culture, and serologic tests. The characteristic spherules can be visualized on routine hematoxylin and eosin stain or more readily with fungal stains (Figure). Spherules are thick walled and distinguishable from other fungi because of the characteristic endospores inside as well as their larger size. Organisms also may be detected via culture within 2 to 5 days.

Distinguishing primary cutaneous from disseminated skin lesions can be challenging but can have notable treatment implications. Although histology typically cannot distinguish primary from disseminated cutaneous infections, clinical history and serologic studies have been found to be useful. In disseminated disease, IgG antibodies are elevated, while in primary cutaneous disease, IgM antibodies are elevated but typically not IgG.¹² Therefore, tube precipitin and latex particle agglutination tests that detect IgM antibodies should be positive in primary infections.¹³ Primary lesions can spontaneously resolve within months to years and may not require treatment if symptomatic, while secondary lesions must be therapeutically addressed.¹² Despite the lack of treatment needed, primary cutaneous infections often are treated with azoles.¹⁴ In contrast, disseminated cutaneous infection requires systemic therapy. Treatment of disseminated infection with cutaneous coccidioidomycosis typically includes amphotericin B until a clinical response is achieved and antibody titers decline. Amphotericin B can then be replaced with an oral azole such as itraconozole or fluconazole.¹⁵

The patient discussed in this case demonstrates the typical clinical presentation of disseminated coccidioidomycosis with classical and diagnostic pathology. This case also highlights the importance of a detailed travel history; in the era of globalization, patients often present with diseases in nonendemic areas. Clinicians must consider the diagnosis of coccidioidomycosis, even in immunocompetent patients in nonendemic areas when their history and presentation are appropriate. The diagnosis should be confirmed with biopsy, culture, and/or serology.

The Diagnosis: Disseminated Coccidioidomycosis

Fungi of the genus Coccidioides cause coccidioidomycosis and live in the soil of endemic areas including the southwestern United States (eg, Arizona, New Mexico, California) and Mexico. Coccidioides is a dimorphic fungus with parasitic and infectious saprophytic phases. Each year there are approximately 150,000 new infections of coccidioidomycosis in the United States, almost exclusively in the southwest.¹ Coccidioidomycosis typically is an asymptomatic or mild infection in an immunocompetent patient. Although the lungs are nearly always the primary sites of infection, common sites of dissemination include the skin, meninges, bones, and joints. The skin is the most common site of disseminated, or secondary, coccidioidomycosis.² Less commonly and usually caused by traumatic implantation, the skin is the site of primary infection.

Disseminated coccidioidomycosis occurs in approximately 1 in 200 infected individuals.^2,3 Certain populations of patients are more likely to be affected by disseminated coccidioidomycosis, including specific ethnic groups such as black individuals, Filipinos, and Mexicans^4,5; pregnant women⁶; and immunosuppressed patients such as those with human immunodeficiency virus, hematogenous malignancy, or organ transplantation.^7-9 When skin lesions are present, they usually develop after the initial lung manifestation. The location of the lesion in cutaneous disseminated disease can be highly variable, but the face and head are the most common locations (30%).¹⁰

Cutaneous manifestations of coccidioidomycosis may be classified as being caused by the presence of the organism in the skin (organism specific) or a reactive process. Organism-specific cutaneous lesions are commonly due to systemic disease with secondary skin involvement, but they also may be due to a primary infection. These organism-specific lesions can present as papules, nodules, macules, verrucous plaques, abscesses, or pustules. Reactive cutaneous manifestations are only associated with disseminated disease; do not contain any organisms; and include manifestations such as erythema nodosum, acute exanthem, erythema multiforme, and possibly Sweet syndrome.¹¹

The clinical differential diagnosis of cutaneous coccidioidomycosis includes other

Coccidioidal spherules in the dermis (Periodic acid–Schiff, original magnification ×600).

mycoses such as histoplasmosis and blastomycosis, as well as tuberculosis, sarcoidosis, basal cell and squamous cell carcinoma, and verruca vulgaris. The diagnosis of cutaneous coccidioidomycosis can be made with skin biopsy, culture, and serologic tests. The characteristic spherules can be visualized on routine hematoxylin and eosin stain or more readily with fungal stains (Figure). Spherules are thick walled and distinguishable from other fungi because of the characteristic endospores inside as well as their larger size. Organisms also may be detected via culture within 2 to 5 days.

Distinguishing primary cutaneous from disseminated skin lesions can be challenging but can have notable treatment implications. Although histology typically cannot distinguish primary from disseminated cutaneous infections, clinical history and serologic studies have been found to be useful. In disseminated disease, IgG antibodies are elevated, while in primary cutaneous disease, IgM antibodies are elevated but typically not IgG.¹² Therefore, tube precipitin and latex particle agglutination tests that detect IgM antibodies should be positive in primary infections.¹³ Primary lesions can spontaneously resolve within months to years and may not require treatment if symptomatic, while secondary lesions must be therapeutically addressed.¹² Despite the lack of treatment needed, primary cutaneous infections often are treated with azoles.¹⁴ In contrast, disseminated cutaneous infection requires systemic therapy. Treatment of disseminated infection with cutaneous coccidioidomycosis typically includes amphotericin B until a clinical response is achieved and antibody titers decline. Amphotericin B can then be replaced with an oral azole such as itraconozole or fluconazole.¹⁵

The patient discussed in this case demonstrates the typical clinical presentation of disseminated coccidioidomycosis with classical and diagnostic pathology. This case also highlights the importance of a detailed travel history; in the era of globalization, patients often present with diseases in nonendemic areas. Clinicians must consider the diagnosis of coccidioidomycosis, even in immunocompetent patients in nonendemic areas when their history and presentation are appropriate. The diagnosis should be confirmed with biopsy, culture, and/or serology.

The Diagnosis: Disseminated Coccidioidomycosis

Fungi of the genus Coccidioides cause coccidioidomycosis and live in the soil of endemic areas including the southwestern United States (eg, Arizona, New Mexico, California) and Mexico. Coccidioides is a dimorphic fungus with parasitic and infectious saprophytic phases. Each year there are approximately 150,000 new infections of coccidioidomycosis in the United States, almost exclusively in the southwest.¹ Coccidioidomycosis typically is an asymptomatic or mild infection in an immunocompetent patient. Although the lungs are nearly always the primary sites of infection, common sites of dissemination include the skin, meninges, bones, and joints. The skin is the most common site of disseminated, or secondary, coccidioidomycosis.² Less commonly and usually caused by traumatic implantation, the skin is the site of primary infection.

Disseminated coccidioidomycosis occurs in approximately 1 in 200 infected individuals.^2,3 Certain populations of patients are more likely to be affected by disseminated coccidioidomycosis, including specific ethnic groups such as black individuals, Filipinos, and Mexicans^4,5; pregnant women⁶; and immunosuppressed patients such as those with human immunodeficiency virus, hematogenous malignancy, or organ transplantation.^7-9 When skin lesions are present, they usually develop after the initial lung manifestation. The location of the lesion in cutaneous disseminated disease can be highly variable, but the face and head are the most common locations (30%).¹⁰

Cutaneous manifestations of coccidioidomycosis may be classified as being caused by the presence of the organism in the skin (organism specific) or a reactive process. Organism-specific cutaneous lesions are commonly due to systemic disease with secondary skin involvement, but they also may be due to a primary infection. These organism-specific lesions can present as papules, nodules, macules, verrucous plaques, abscesses, or pustules. Reactive cutaneous manifestations are only associated with disseminated disease; do not contain any organisms; and include manifestations such as erythema nodosum, acute exanthem, erythema multiforme, and possibly Sweet syndrome.¹¹

The clinical differential diagnosis of cutaneous coccidioidomycosis includes other

Coccidioidal spherules in the dermis (Periodic acid–Schiff, original magnification ×600).

mycoses such as histoplasmosis and blastomycosis, as well as tuberculosis, sarcoidosis, basal cell and squamous cell carcinoma, and verruca vulgaris. The diagnosis of cutaneous coccidioidomycosis can be made with skin biopsy, culture, and serologic tests. The characteristic spherules can be visualized on routine hematoxylin and eosin stain or more readily with fungal stains (Figure). Spherules are thick walled and distinguishable from other fungi because of the characteristic endospores inside as well as their larger size. Organisms also may be detected via culture within 2 to 5 days.

Distinguishing primary cutaneous from disseminated skin lesions can be challenging but can have notable treatment implications. Although histology typically cannot distinguish primary from disseminated cutaneous infections, clinical history and serologic studies have been found to be useful. In disseminated disease, IgG antibodies are elevated, while in primary cutaneous disease, IgM antibodies are elevated but typically not IgG.¹² Therefore, tube precipitin and latex particle agglutination tests that detect IgM antibodies should be positive in primary infections.¹³ Primary lesions can spontaneously resolve within months to years and may not require treatment if symptomatic, while secondary lesions must be therapeutically addressed.¹² Despite the lack of treatment needed, primary cutaneous infections often are treated with azoles.¹⁴ In contrast, disseminated cutaneous infection requires systemic therapy. Treatment of disseminated infection with cutaneous coccidioidomycosis typically includes amphotericin B until a clinical response is achieved and antibody titers decline. Amphotericin B can then be replaced with an oral azole such as itraconozole or fluconazole.¹⁵

The patient discussed in this case demonstrates the typical clinical presentation of disseminated coccidioidomycosis with classical and diagnostic pathology. This case also highlights the importance of a detailed travel history; in the era of globalization, patients often present with diseases in nonendemic areas. Clinicians must consider the diagnosis of coccidioidomycosis, even in immunocompetent patients in nonendemic areas when their history and presentation are appropriate. The diagnosis should be confirmed with biopsy, culture, and/or serology.

The Diagnosis: Prayer Callus

After our patient demonstrated his routine position for prayer (Figure), the

The position of the patient’s left foot while praying.

diagnosis of prayer callus was confirmed. We suggested he use a foam pad under his foot during prayer. The patient did not return for follow-up.

Prayer calluses have been documented in the literature as prayer nodules^1-3 or marks.⁴ Callus is a preferred term, as it implies the act of repeated pressure or friction to an area of the skin. It is more descriptive than marks and avoids the inclusion of nodules caused by different prayer or religious activities such as ritual scarring.⁵

Abanmi et al⁴ studied a large group (N=349) of Muslim patients with regular praying habits and found a high prevalence of what they referred to as prayer marks, defined by lichenification and/or hyperpigmentation, on the knees, forehead, ankles, and dorsal aspects of the feet. They studied the histopathology of 33 marks. No statistical analysis was performed. They reported common histologic findings of compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. In contrast to lichen simplex chronicus, the authors found that the dermal fibrosis did not exhibit collagen bundles perpendicular to the epidermis.⁴

This study found that a higher prevalence of lichenification was observed on the left foot (males, 57%; females, 39%) than the right foot (males, 14%; females, 19%), which was attributed to a more typical prayer position that placed pressure on the left foot.⁴ Our patient only had calluses on his left foot, which was consistent with the prayer position.

Treatment options for prayer calluses include debridement, either mechanical or with topical keratolytic preparations. There is a high likelihood of recurrence if prayer practices are not changed. Optimally, more definitive treatment, which can be combined with initial debridement, would be position adjustment to lessen pressure or friction to the area or protection over the area with a cushion, as we attempted with our patient in the form of a foam pad.

The Diagnosis: Prayer Callus

After our patient demonstrated his routine position for prayer (Figure), the

The position of the patient’s left foot while praying.

diagnosis of prayer callus was confirmed. We suggested he use a foam pad under his foot during prayer. The patient did not return for follow-up.

Prayer calluses have been documented in the literature as prayer nodules^1-3 or marks.⁴ Callus is a preferred term, as it implies the act of repeated pressure or friction to an area of the skin. It is more descriptive than marks and avoids the inclusion of nodules caused by different prayer or religious activities such as ritual scarring.⁵

Abanmi et al⁴ studied a large group (N=349) of Muslim patients with regular praying habits and found a high prevalence of what they referred to as prayer marks, defined by lichenification and/or hyperpigmentation, on the knees, forehead, ankles, and dorsal aspects of the feet. They studied the histopathology of 33 marks. No statistical analysis was performed. They reported common histologic findings of compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. In contrast to lichen simplex chronicus, the authors found that the dermal fibrosis did not exhibit collagen bundles perpendicular to the epidermis.⁴

This study found that a higher prevalence of lichenification was observed on the left foot (males, 57%; females, 39%) than the right foot (males, 14%; females, 19%), which was attributed to a more typical prayer position that placed pressure on the left foot.⁴ Our patient only had calluses on his left foot, which was consistent with the prayer position.

Treatment options for prayer calluses include debridement, either mechanical or with topical keratolytic preparations. There is a high likelihood of recurrence if prayer practices are not changed. Optimally, more definitive treatment, which can be combined with initial debridement, would be position adjustment to lessen pressure or friction to the area or protection over the area with a cushion, as we attempted with our patient in the form of a foam pad.

The Diagnosis: Prayer Callus

After our patient demonstrated his routine position for prayer (Figure), the

The position of the patient’s left foot while praying.

diagnosis of prayer callus was confirmed. We suggested he use a foam pad under his foot during prayer. The patient did not return for follow-up.

Prayer calluses have been documented in the literature as prayer nodules^1-3 or marks.⁴ Callus is a preferred term, as it implies the act of repeated pressure or friction to an area of the skin. It is more descriptive than marks and avoids the inclusion of nodules caused by different prayer or religious activities such as ritual scarring.⁵

Abanmi et al⁴ studied a large group (N=349) of Muslim patients with regular praying habits and found a high prevalence of what they referred to as prayer marks, defined by lichenification and/or hyperpigmentation, on the knees, forehead, ankles, and dorsal aspects of the feet. They studied the histopathology of 33 marks. No statistical analysis was performed. They reported common histologic findings of compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. In contrast to lichen simplex chronicus, the authors found that the dermal fibrosis did not exhibit collagen bundles perpendicular to the epidermis.⁴

This study found that a higher prevalence of lichenification was observed on the left foot (males, 57%; females, 39%) than the right foot (males, 14%; females, 19%), which was attributed to a more typical prayer position that placed pressure on the left foot.⁴ Our patient only had calluses on his left foot, which was consistent with the prayer position.

Treatment options for prayer calluses include debridement, either mechanical or with topical keratolytic preparations. There is a high likelihood of recurrence if prayer practices are not changed. Optimally, more definitive treatment, which can be combined with initial debridement, would be position adjustment to lessen pressure or friction to the area or protection over the area with a cushion, as we attempted with our patient in the form of a foam pad.

The Diagnosis: Atrophic Lupus Erythematosus

Cutaneous lupus erythematosus is divided into acute, subacute, and chronic cutaneous lupus erythematosus (CCLE). There are more than 20 subtypes of CCLE mentioned in the literature including atrophic lupus erythematosus (ALE).¹ The most typical presentation is CCLE with discoid lesions. Most commonly, discoid CCLE is an entirely cutaneous process without systemic involvement.Discoid lesions appear as scaly red macules or papules primarily on the face and scalp.² They may evolve into hyperkeratotic plaques with irregular hyperpigmented borders and develop a central hypopigmented depression with atrophy and scarring.^2,3 Discoid CCLE has a female predominance and commonly occurs between 20 and 30 years of age. Triggers of discoid lesions include UV exposure, trauma, and infection.² 

Our case of multiple atrophic plaques of the face, scalp, trunk, and upper extremities demonstrated a diagnostic challenge. Our patient presented with atrophic facial plaques, which are not typical of discoid lesions of CCLE. Our patient’s findings appeared clinically similar to acne scarring or atrophoderma. Histology showed common features of CCLE, including basal liquefactive degeneration, thickening of the basement membrane zone, increased melanin, and a lymphocytic inflammatory infiltrate (Figure).^2,3 There was no evidence of hyperkeratosis, which often is seen in discoid lesions of CCLE.

Clinicopathologically, our case was consistent with ALE. A review of the literature revealed similar cases documented by Christianson and Mitchell⁴ in 1969; they described annular atrophic plaques of the skin of unknown diagnostic classification. Chorzelski et al⁵ reiterated the difficulty of defining diagnostically similar atrophic plaques of the face showing histopathologic features consistent with lupus and suggested these cases may represent an uncharacteristic presentation of discoid lupus erythematosus. Our patient demonstrated this rare subtype of discoid lupus erythematosus, known as ALE. There are few reports in the literature of ALE; thus we have managed our patient similar to other CCLE patients. Management of CCLE patients includes strict sun protection. Treatment options include corticosteroids, calcineurin inhibitors, antimalarial agents, and thalidomide.² Our patient started using tacrolimus ointment 0.1% daily and hydroxychloroquine 200 mg twice daily. She also was practicing strict photoprotection. The patient was lost to follow-up. Topical steroids are not an option in ALE. It is important for dermatologists to recognize this rare variant of CCLE to prevent disfigurement.

The Diagnosis: Atrophic Lupus Erythematosus

Cutaneous lupus erythematosus is divided into acute, subacute, and chronic cutaneous lupus erythematosus (CCLE). There are more than 20 subtypes of CCLE mentioned in the literature including atrophic lupus erythematosus (ALE).¹ The most typical presentation is CCLE with discoid lesions. Most commonly, discoid CCLE is an entirely cutaneous process without systemic involvement.Discoid lesions appear as scaly red macules or papules primarily on the face and scalp.² They may evolve into hyperkeratotic plaques with irregular hyperpigmented borders and develop a central hypopigmented depression with atrophy and scarring.^2,3 Discoid CCLE has a female predominance and commonly occurs between 20 and 30 years of age. Triggers of discoid lesions include UV exposure, trauma, and infection.² 

Our case of multiple atrophic plaques of the face, scalp, trunk, and upper extremities demonstrated a diagnostic challenge. Our patient presented with atrophic facial plaques, which are not typical of discoid lesions of CCLE. Our patient’s findings appeared clinically similar to acne scarring or atrophoderma. Histology showed common features of CCLE, including basal liquefactive degeneration, thickening of the basement membrane zone, increased melanin, and a lymphocytic inflammatory infiltrate (Figure).^2,3 There was no evidence of hyperkeratosis, which often is seen in discoid lesions of CCLE.

Clinicopathologically, our case was consistent with ALE. A review of the literature revealed similar cases documented by Christianson and Mitchell⁴ in 1969; they described annular atrophic plaques of the skin of unknown diagnostic classification. Chorzelski et al⁵ reiterated the difficulty of defining diagnostically similar atrophic plaques of the face showing histopathologic features consistent with lupus and suggested these cases may represent an uncharacteristic presentation of discoid lupus erythematosus. Our patient demonstrated this rare subtype of discoid lupus erythematosus, known as ALE. There are few reports in the literature of ALE; thus we have managed our patient similar to other CCLE patients. Management of CCLE patients includes strict sun protection. Treatment options include corticosteroids, calcineurin inhibitors, antimalarial agents, and thalidomide.² Our patient started using tacrolimus ointment 0.1% daily and hydroxychloroquine 200 mg twice daily. She also was practicing strict photoprotection. The patient was lost to follow-up. Topical steroids are not an option in ALE. It is important for dermatologists to recognize this rare variant of CCLE to prevent disfigurement.

The Diagnosis: Atrophic Lupus Erythematosus

Cutaneous lupus erythematosus is divided into acute, subacute, and chronic cutaneous lupus erythematosus (CCLE). There are more than 20 subtypes of CCLE mentioned in the literature including atrophic lupus erythematosus (ALE).¹ The most typical presentation is CCLE with discoid lesions. Most commonly, discoid CCLE is an entirely cutaneous process without systemic involvement.Discoid lesions appear as scaly red macules or papules primarily on the face and scalp.² They may evolve into hyperkeratotic plaques with irregular hyperpigmented borders and develop a central hypopigmented depression with atrophy and scarring.^2,3 Discoid CCLE has a female predominance and commonly occurs between 20 and 30 years of age. Triggers of discoid lesions include UV exposure, trauma, and infection.² 

Our case of multiple atrophic plaques of the face, scalp, trunk, and upper extremities demonstrated a diagnostic challenge. Our patient presented with atrophic facial plaques, which are not typical of discoid lesions of CCLE. Our patient’s findings appeared clinically similar to acne scarring or atrophoderma. Histology showed common features of CCLE, including basal liquefactive degeneration, thickening of the basement membrane zone, increased melanin, and a lymphocytic inflammatory infiltrate (Figure).^2,3 There was no evidence of hyperkeratosis, which often is seen in discoid lesions of CCLE.

Clinicopathologically, our case was consistent with ALE. A review of the literature revealed similar cases documented by Christianson and Mitchell⁴ in 1969; they described annular atrophic plaques of the skin of unknown diagnostic classification. Chorzelski et al⁵ reiterated the difficulty of defining diagnostically similar atrophic plaques of the face showing histopathologic features consistent with lupus and suggested these cases may represent an uncharacteristic presentation of discoid lupus erythematosus. Our patient demonstrated this rare subtype of discoid lupus erythematosus, known as ALE. There are few reports in the literature of ALE; thus we have managed our patient similar to other CCLE patients. Management of CCLE patients includes strict sun protection. Treatment options include corticosteroids, calcineurin inhibitors, antimalarial agents, and thalidomide.² Our patient started using tacrolimus ointment 0.1% daily and hydroxychloroquine 200 mg twice daily. She also was practicing strict photoprotection. The patient was lost to follow-up. Topical steroids are not an option in ALE. It is important for dermatologists to recognize this rare variant of CCLE to prevent disfigurement.