Diagnostic Errors in Patients With Rashes, Moles, and Other Skin Findings

Graeme M. Lipper, MD


September 06, 2017

A Stubborn, Itchy Rash

An older Asian man presents with a "stubborn rash" with redness, burning, and chronic pruritus in the inguinal folds extending onto his scrotum, which began 2 years previously. His primary-care provider originally diagnosed candidiasis and treated him with topical ketoconazole 2% cream, adding oral itraconazole when he failed to improve. He subsequently saw a dermatologist, who diagnosed inverse psoriasis and prescribed topical corticosteroids followed by calcipotriene ointment. When these treatments didn't work, the dermatologist suspected erythrasma and switched therapy to oral erythromycin and a topical calcineurin inhibitor, which also failed to improve the condition. The patient's history is significant for childhood "eczema" and stage I prostate adenocarcinoma, which was treated 10 years ago with external radiation therapy.

Examination reveals well-demarcated bright red plaques in the inguinal folds extending onto the scrotal base, ventral penile shaft, and glans with focal maceration, lichenification, and scattered erosions. He has no inguinal lymphadenopathy (Figure 6).

Figure 6. Rash in the inguinal folds. Image courtesy of Ann McGowan-Tuskes, MD (regionalderm.com).

What medical diagnostic error occurred?

Why a Biopsy Is Indicated

In a case like this—when a patient who presents with chronic inguinal dermatitis that fails to respond to treatments appropriate for candidal intertrigo, tinea cruris, inverse psoriasis, or erythrasma—a skin biopsy should always be performed. This is especially important given this patient's history of prostate cancer, which raises the suspicion of extramammary Paget's disease (EMPD)—a rare malignancy of apocrine gland-bearing skin that may be primary or metastatic.

EMPD presents with chronic, sharply demarcated bright red erythematous or leukoplakic plaques, usually in skin rich in apocrine glands (eg, vulvar, perineal, perianal, scrotal, and penile). The disease may be primary (originating from intraepidermal cells or apocrine glands) or secondary (associated with an underlying adenocarcinoma such as prostate or anorectal).

In the case described above, a punch biopsy revealed an intraepidermal infiltrate of large round cells with pale cytoplasm and prominent vesicular nuclei, arranged in strands with focal nests. Immunohistochemical markers (cytokeratin 7 and 20) were both negative, consistent with secondary EMPD, which in this case, was likely associated with metastatic prostate adenocarcinoma[5] (Figure 7).

Figure 7. Micrograph, H&E stain of extramammary Paget's disease. Image from Wikimedia.

EMPD may be multifocal, with skip areas or confluent plaques that sometimes bleed or become erosive. Ominous features suggestive of invasive or metastatic disease include associated lymphadenopathy and palpable masses. As in this case, these patients complain of chronic and refractory pruritus and burning, although EMPD may be asymptomatic in up to 10% of affected persons.[5] EMPD is often misdiagnosed as a fungal or yeast infection, inverse psoriasis, seborrheic dermatitis, contact dermatitis, or erythrasma, delaying correct diagnosis by an average of 35 months.[6] In addition to testing for associated malignancy, the disease can be treated with local radiation therapy, topical imiquimod or 5-fluorouracil, topical photodynamic therapy, or surgical excision.[6]


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