Inguinal annular plaque with central maceration

A 77-year-old man with a history of chronic obstructive pulmonary disease was hospitalized for management of pneumothorax. Dermatology was consulted for a persistent groin eruption. On examination, he was ill-appearing and short of breath. A malodorous, erythematous, annular plaque with central maceration was noted along the left inguinal fold (Fig 1). Laboratory testing was notable for leukocytosis (white blood cell: 12.38 K/uL) and normocytic anemia (hemoglobin: 11.3 g/dL). A 4 mm punch biopsy was performed and sent for histopathology (Fig 2) and tissue culture.

Fig 1.

Fig 2.

Question 1: What is the most likely diagnosis?

• A.Tinea cruris
• B.Inverse psoriasis
• C.Squamous cell carcinoma in situ
• D.Intertrigo
• E.Extramammary Paget’s disease (EMPD)

Answers

• A.Tinea cruris – Incorrect. Caused by a superficial fungal infection, tinea cruris may present with a malodorous, scaly, annular plaque as seen with our patient, most commonly in an intertriginous distribution. However, it is often bilateral, with pathology confirming the presence of fungal organisms.
• B.Inverse psoriasis – Incorrect. Inverse psoriasis presents intertriginously, unlike classic plaque psoriasis which affects the flexural surfaces. Histopathology characteristically demonstrates hypogranulosis, parakeratosis, and thinning of the suprapapillary plate.¹
• C.Squamous cell carcinoma in situ – Incorrect. Also referred to as Bowen Disease, squamous cell carcinoma in situ presents histopathologically with keratinocyte atypia without basal layer invasion, parakeratosis, and keratin pearls.²
• D.Intertrigo – Incorrect. This is an inflammatory condition resulting from excessive moisture, friction, or trauma, most often occurring intertriginously, which may demonstrate evidence of inflammation on histopathology.
• E.Extramammary Paget’s disease (EMPD) – Correct. EMPD is an adenocarcinoma most commonly arising in apocrine gland-rich regions on the skin. Primary EMPD is thought to originate from pluripotent keratinocyte stem cells in the epidermis, whereas secondary EMPD arises from the spread of a visceral organ malignancy to the skin. Diagnosis is confirmed with a biopsy, and immunohistochemistry, together with clinical correlation, is often used to differentiate primary (+cytokeratin-7 [CK7], - cytokeratin-20 [CK20]) from secondary EMPD (+CK20, ± CK7).³ Staining for other visceral tumor markers are often used in conjunction to determine the etiology of malignancy.

Question 2: Which of the following topical therapies is most effective in treating this condition?

• A.Topical antifungal therapy
• B.Topical imiquimod
• C.Topical steroid therapy
• D.Topical antibiotic therapy
• E.Topical 5-fluorouracil

Answers:

• A.Topical antifungal therapy – Incorrect. This would be appropriate for the management of tinea cruris or intertrigo. It is important to note that EMPD can mimic fungal or inflammatory conditions, which often results in delays in diagnosis and management.
• B.Topical imiquimod – Correct. Topical imiquimod is often used as a first line agent and has been shown to provide a complete response in up to 73% of patients. Its efficacy is due to its ability to stimulate an immune response against tumor cells.⁴
• C.Topical steroid therapy – Incorrect. Topical steroid therapy does not have a role in the management of EMPD.
• D.Topical antibiotic therapy – Incorrect. Topical antibiotic therapy is not applicable in the management approach for EMPD, as it does not target the underlying malignant pathology.
• E.Topical 5-fluorouracil – Incorrect. While it has been shown to be effective in some case series, it is not effective as a monotherapy. Instead, it must be paired with other agents, such as imiquimod or calcipotriene, and is often reserved for refractory cases.⁴

Question 3: In addition to CK7 positivity, which of the following additional staining patterns would be expected if this were a primary localized cutaneous process?

• A.CK20 negative
• B.CK20 positive
• C.Periodic Acid Schiff negative
• D.Gross cystic disease fluid protein-15 negative
• E.Caudal-related homeobox transcription factor (CDX)-2 positive

Answers:

• A.CK20 negative – Correct. On histopathology, the immunophenotype for primary EMPD most commonly reveals CK7 positivity with negative CK20 staining, a phenotype seen in up to 100% of patients with primary EMPD.⁵ Our patient’s staining pattern revealed CK7 positivity in the absence of CK20 with diffuse membranous and cytoplasmic staining in tumor cells, as well as dermal invasion and full-thickness epidermal spread (Fig 3). This suggests primary EMPD as the underlying process.
• B.CK20 positive – Incorrect. For the reasons mentioned above, CK7 positivity in the absence of CK20 is most commonly seen in primary EMPD. Conversely, CK20 positivity can indicate secondary EMPD, and further stains to elucidate the underlying malignancy should be pursued.³
• C.Periodic Acid Schiff negative – Incorrect. In both primary and secondary EMPD, Paget cells produce mucin and will therefore stain positively for Periodic Acid Schiff.³
• D.Gross cystic disease fluid protein-15 negative – Incorrect. In addition to being CK7 positive and CK20 negative, primary EMPD is characteristically gross cystic disease fluid protein-15 positive.³ The absence of this stain suggests secondary EMPD.
• E.Caudal-related homeobox transcription factor (CDX)-2 positive – Incorrect. In the absence of indicators for primary EMPD, additional staining to evaluate underlying causes for a secondary process, such as CDX-2 for colorectal cancer, may be pursued.³ Primary EMPD should therefore be negative for CDX-2.

Fig 3.

Conflict of interest

None disclosed.