Immunohistochemistry staining of tumor cells was positive for CK7, CEA, pancytokeratin (CKAE1/AE3), and LMWCK. The tumor cells were negative for CK20. On the basis of the histopathologic and IHC findings, the patient was diagnosed with AAEMPD.
Extramammary Paget disease is a rare intraepidermal neoplasm with glandular differentiation. The most commonly involved sites are the anogenital areas including the vulvar, perianal, perineal, scrotal, and penile regions, as well as other areas rich in apocrine glands such as the axillae.8 Extramammary Paget disease most commonly originates as a primary intraepidermal neoplasm (type 1 EMPD), but an underlying malignant neoplasm that spreads intraepithelially is seen in a minority of cases (types 2 and 3 EMPD). In the vulva, type 1a refers to cutaneous noninvasive Paget disease, type 1b refers to dermal invasion of Paget disease, type 1c refers to vulvar adenocarcinoma–associated Paget disease, type 2 refers to rectal/anal adenocarcinoma–associated Paget disease, and type 3 refers to urogenital neoplasia–associated Paget disease.9
The acantholytic anaplastic variant of EMPD can be challenging to diagnose because of its similarities to many other lesions, including acantholytic dyskeratosis of the genitocrural area, familial benign pemphigus (Hailey-Hailey disease), pemphigus vulgaris, Bowen disease, pagetoid Bowen disease, and acantholytic Bowen disease. Major histologic features of AAEMPD include full-thickness atypia of the epidermis, loss of nuclear polarity, marked cytologic anaplasia, intraepidermal acantholysis, and Paget cells.3 The acantholytic anaplastic variant of EMPD can be differentiated from other diagnoses using IHC studies, with findings indicative of AAEMPD outlined below.
The proliferative neoplastic cell in EMPD is the Paget cell, which can be identified as a large round cell located in the epidermis with pale-staining cytoplasm, a large nucleus, and sometimes a prominent nucleolus. Paget cells can be distributed singly or in clusters, nests, or glandular structures within the epidermis and adjacent to adnexal structures.10 Extramammary Paget disease can have many patterns, including glandular, acantholysis-like, upper nest, tall nest, budding, and sheetlike.11
Immunohistochemically, Paget cells in EMPD typically express pancytokeratins (CKAE1/AE3), low-molecular-weight/simple epithelial type keratins (CK7, CAM 5.2), sweat gland antigens (epithelial membrane antigen, CEA, gross cystic disease fluid protein 15 [GCDFP15]), mucin 5AC (MUC5AC), and often androgen receptor.12-18 Paget cells contain cytoplasmic mucin and demonstrate prominent cytoplasmic staining with Hale colloidal iron.17 Paget cells typically do not express high-molecular-weight cytokeratin (eg, CK5/6), melanocytic antigens, estrogen receptor, or progesterone receptor.15,18
Immunohistochemical staining has been shown to differ between primary cutaneous (type 1) and secondary (types 2 and 3) EMPD. Primary cutaneous EMPD typically expresses sweat gland markers (CK7+, CK20−, GCDFP15+). Secondary EMPD typically expresses an endodermal phenotype (CK7+, CK20+, GCDFP15−).12