Anogenital mammary–like glands (AGMLGs) are nowadays considered a normal component of the anogenital area. Lesions involving AGMLGs are histopathologically very similar to their mammary counterparts, but the information on molecular biological mechanisms in these vulvar/perianal tumors is scarce. Mutations in the PI3K-AKT cascade have been found in hidradenoma papilliferum. The authors studied selected BRCA1, BRCA2, and PIK3CA mutations in series of benign and malignant neoplasms thought to be associated with AGMLGs, including 9 cases of primary extramammary Paget disease, 3 different cases of mammary-type carcinoma (adenoid cystic like, tubulolobular, and invasive ductal like), and 5 cases of hidradenoma papilliferum. No BRCA mutation was detected, whereas 3 neoplasms yielded PIK3CA mutation, including extramammary Paget disease, mammary-type invasive ductal carcinoma, and tubulolobular carcinoma. Our study expands the spectrum of lesions of AGMLGs harboring mutations in genes encoding the PI3K-AKT cascade. Further studies of the whole BRCA1 and BRCA2 genes using a larger cohort are needed to clarify their role in the pathogenesis of AGMLG lesions.

Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account.

Syringocystadenoma papilliferum (SCAP) is a benign tumor most commonly located on the head and neck area often associated with nevus sebaceus. In its usual location, the human papillomavirus (HPV) DNA and mutations in the RAS/mitogen-activated protein kinase signaling pathway have been detected in SCAP. We studied 16 cases of SCAP in the anogenital areas and buttock where this neoplasm is rare and attempted to find out whether SCAP in these sites have different histopathological and molecular biological features. It seems that there is no significant difference between the morphology of anogenital SCAP and SCAP in other locations. Several tumors in our cohort demonstrated features resembling those seen in warts, but HPV DNA was not found in these lesions. On the contrary, we identified DNA of HPV high-risk types in some tumors without HPV-related morphology. Our study confirms the role of HRAS and BRAF V600 mutations in the pathogenesis of SCAP, including SCAP in the anogenital areas and buttock.

The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface.