S1803 Extramammary Paget’s Disease of the Anal Canal: A Rare Diagnosis

Abstract

INTRODUCTION: Extramammary Paget's disease (EMPD) is an uncommon intraepithelial malignancy that often involves areas of skin with high apocrine gland density. Cases of EMPD involving the anal canal are extremely rare. We present a case of anal EMPD where subsequent work up was unsuccessful in locating the primary site of the associated gastrointestinal (GI) cancer. CASE DESCRIPTION/METHODS: 76 year old male with history of diabetes, hypertension, immune thrombocytopenic purpura treated with rituximab, and chronic lymphocytic leukemia in remission after treatment with chemotherapy, presented with chronic constipation. He denied hematochezia, weight loss, or family history of GI malignancy. He underwent colonoscopy where one polyp was removed from the cecum with pathology revealing a tubular adenoma as well as a one centimeter whitish area of abnormal-appearing mucosa in the anal canal extending proximally into the anal transition zone and initial biopsy demonstrated invasive EMPD (BerEP4, CK7, CK20 & mucicarmine positive) (Image 1). A second biopsy of the lesion showed anal intraepithelial neoplasia (AIN 2–3) with EMPD (CK7, CK20, CDX2 & mucicarmine positive) (Image 2). Later, PET/CT scan showed linear FDG uptake in the anorectal region and several FDG-avid lymph nodes in the right external iliac chain and inguinal region. Subsequent excisional biopsy of the right inguinal lymph nodes showed metastatic tumor, with an immunohistochemistry profile similar to prior EMPD biopsies (Image 3). Patient underwent a repeat colonoscopy which did not reveal any new findings. An EGD and capsule endoscopy were also done which did not show any suspicious masses or lesions. Wide local excision with lymph node dissection was recommended, but the patient declined further management. Two months later, the patient got a CT abdomen and pelvis due to increasing abdominal pain which showed worsening metastatic disease in the liver and abdominal lymph nodes. Patient opted for hospice care and died a few weeks afterwards. DISCUSSION: To our knowledge, EMPD involving the anal canal is a rare finding with only a handful of cases reported in the literature. It was an incidental diagnosis and most likely associated with an unidentified colorectal adenocarcinoma. Surgery is the treatment of choice for localized disease, provided there is no evidence of dermal invasion or distant metastasis. Radiation and chemotherapy may be trialed in advanced cases, but efficacy remains poor.Figure 1.: Colonoscopy (A &B) showing mucosal lesion in anal canal (arrows), extending proximally into the anal transition zone. Anus biopsy on H & E stain (C ) showing invasive extramammary Paget’s disease with nests of malignant epithelial cells showing a high nuclear-to-cytoplasmic ratio with arrows indicating invasive carcinoma which is confirmed with BerEP4 immunohistochemistry stain (D) confirming in situ (red arrows) and invasive extramammary Paget's disease (blue arrows).Figure 2.: Anus biopsy (20X) with H & E stain (B) showing foci of extramammary Paget’s disease (black arrows) in tissue composed of high grade anal intraepithelial neoplasia (AIN 2-3). CDX2 immunohistochemistry stain (C) and Mucicarmine stain (D) highlighting extramammary Paget's disease.Figure 3.: PET/CT (A) shows FDG-avid lymph nodes in the right external iliac chain and inguinal region (white arrow). Right inguinal lymph node biopsy shows metastatic extramammary Paget's disease (40X) with H & E stain (B), confirmed with CK 7 immunohistochemistry stain expression (10X) in (C) and CDX2 immunohistochemistry expression (40X) in (D).