Perianal Paget Disease With an Enteric Phenotype and Associated In-Situ/Dysplastic Glandular Component: Report of a Potentially Novel Entity and Review of the Literature.

Extramammary Paget disease is an uncommon cutaneous malignancy that primarily affects areas rich in apocrine glands. Here, we aim to present an 84-year-old woman with a distinctive perianal neoplastic process comprised of conventional Paget disease with an intertwined in-situ glandular component. Rare foci of glands embedded in pools of mucin were also identified in the most recent excision, consistent with mucinous adenocarcinoma. Immunohistochemical staining demonstrated an enteric phenotype of the tumor cells, with expression of keratin 20, caudal type homeobox transcription factor 2 (CDX2), and special AT-rich sequence binding protein 2 (SATB2) (patchy, weak); keratin 7 and BerEP4 staining were also noted. Molecular analysis via next generation sequencing revealed pathogenic variants in ERBB2, TP53, and SF3B1. Given the unique histomorphology and immunohistochemical staining pattern, suspicion for a colorectal primary tumor was high, however; extensive workup including imaging, testing for tumor markers, and colonoscopic evaluation has not identified any other lesion thus far. Multiple biopsies and excisions in the area demonstrated recurrent disease over a 4-year span; with no evidence of deep invasion or metastasis. This tumor appears to be exceptional among reports in the literature given its extensive in-situ glandular component; and we are not aware of any documented SF3B1 mutation to date. Disease recurrence in this patient highlights the need for clinical vigilance. Defining the molecular profile in these lesions can also be useful, particularly when assessing potential treatment options for advanced disease.