Case Letter

Acantholytic Anaplastic Extramammary Paget Disease

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Practice Points

  • The acantholytic anaplastic variant of extramammary Paget disease (EMPD) can be mimicked by many other entities including Bowen disease, acantholytic dyskeratosis of the genitocrural area, and pemphigus vulgaris.
  • A good immunohistochemical panel to evaluate for EMPD includes cytokeratin (CK) 7, pancytokeratin (CKAE1/AE3), CK20, and carcinoembryonic antigen.



To the Editor:

Extramammary Paget disease (EMPD) is a rare intraepidermal neoplasm with glandular differentiation that is classically known as a mimicker of Bowen disease (squamous cell carcinoma in situ of the skin) due to their histologic similarities.1,2 However, acantholytic anaplastic EMPD (AAEMPD) is a rare variant that can pose a particularly difficult diagnostic challenge because of its histologic similarity to benign acantholytic disorders and other malignant neoplasms. Major histologic features suggestive of AAEMPD include full-thickness atypia of the epidermis, loss of nuclear polarity, marked cytologic anaplasia, intraepidermal acantholysis, and Paget cells.3 The differential diagnosis of EMPD typically includes Bowen disease and pagetoid Bowen disease, but the acantholytic anaplastic variant more often is confused with intraepidermal acantholytic lesions such as acantholytic dyskeratosis of the genitocrural area, familial benign pemphigus (Hailey-Hailey disease), pemphigus vulgaris, and acantholytic Bowen disease. Immunohistochemistry (IHC) studies to assist in the definitive diagnosis of AAEMPD are strongly advised because of these difficulties in diagnosis.4 Cases of EMPD with an acantholytic appearance have rarely been reported in the literature.5-7

A 78-year-old man with a history of arthritis, heart disease, hypertension, and gastrointestinal disease presented for evaluation of a tender lesion of the right genitocrural crease of 5 years’ duration. He had no history of cutaneous or internal malignancy. Previously the lesion had been treated by dermatology with a variety of topical products including antifungal and antibiotic creams with no improvement. Physical examination revealed a well-defined, 7×5-cm, tender, erythematous, macerated plaque on the right upper inner thigh adjacent to the scrotum with an odor possibly due to secondary infection (Figure 1).

Figure 1. A well-defined, 7×5-cm, tender, erythematous, macerated
plaque on the right upper inner thigh adjacent to the scrotum.

A biopsy of the lesion was performed, and the specimen was submitted for pathologic examination. Bacterial cultures taken at the time of biopsy revealed polybacterial colonization with Acinetobacter, Morganella, and mixed skin flora. The patient was treated with a 10-day course of oral sulfamethoxazole 800 mg and trimethoprim 160 mg twice daily once culture results returned. The biopsy results were communicated to the patient; however, he subsequently relocated, assumed care at another facility, and has since been lost to follow-up.

The biopsy specimen was examined grossly, serially sectioned, and submitted for routine processing with hematoxylin and eosin, periodic acid–Schiff, and Hale colloidal iron staining. Routine IHC was performed with antibodies to cytokeratin (CK) 7, CK20, carcinoembryonic antigen (CEA), pancytokeratin (CKAE1/AE3), and low- molecular-weight cytokeratin (LMWCK).

Pathologic examination of the biopsy showed prominent acanthosis of the epidermis composed of a proliferation of epithelial cells with associated full-thickness suprabasal acantholysis (Figure 2A). On inspection at higher magnification, the neoplastic cells demonstrated anaplasia as cytologic atypia with prominent and frequently multiple nucleoli, scant cytoplasm, and a high nuclear to cytoplasmic ratio (Figure 2B). There was a marked increase in mitotic activity with as many as 5 mitotic figures per high-power field. A fairly dense mixed inflammatory infiltrate comprised of lymphocytes, plasma cells, neutrophils, and eosinophils was present in the dermis. No fungal elements were observed on periodic acid–Schiff staining. The vast majority of tumor cells demonstrated moderate to abundant cytoplasmic mucin on Hale colloidal iron staining (Figure 3).

Figure 2. A, Prominent thickening of the epidermis with marked acantholysis and inflammation (H&E, original magnification ×100). B, Pleomorphic cells with features of anaplasia such as prominent and multiple nucleoli, scant cytoplasm, a high nuclear to cytoplasmic ratio, and frequent mitoses can be appreciated on higher magnification
(H&E, original magnification ×400).

Figure 3. Hale colloidal iron staining showed moderate to abundant cytoplasmic mucin (original magnification ×525).


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