Double Rarities, Double Challenges: Extra-Mammary Paget’s Disease and Anal Adenocarcinoma

A 77-year-old woman was initially evaluated with complaints of a perianal pruritic rash of unknown duration. Physical examination revealed two erythematous plaques immediately adjacent to the right and left of the anal opening, 2 and 3 cm in diameter, respectively. Biopsies confirmed extra-mammary Paget’s disease; an immunohistochemical profile was suggestive of a colorectal primary (CK20, CK7, CEA, CDX2 positive; S100, melan-A negative). The patient was referred to a colorectal surgeon for management who found no abnormalities when the patient was examined digitally or with anoscopy. Colonoscopy demonstrated a tubular adenoma in the cecum, diverticulosis, and small internal hemorrhoids. The patient underwent wide local excision of the perianal lesions; a laparoscopic loop ileostomy was created for diversion of the fecal stream away from the open wound in anticipation of the need for skin grafting. Final pathology confirmed extra-mammary Paget’s disease, although positive margins were present. On postoperative day 4, she was taken back to the operating room for re-excision of the positive perianal margins, with the incision extended by an additional 0.5 cm (taken circumferentially), up to the posterior vulva. Pathology demonstrated a posterior hemorrhoid involved by Paget’s and invasive adenocarcinoma with a positive surgical margin (Fig. 1). Metastatic evaluation included computed tomography (CT) scan and positron emission tomography (PET) of the chest, abdomen, and pelvis; both studies were negative for metastatic disease. The serum concentration of carcinoembryonic antigen (CEA) was 5 ng/mL. After discussion of her case at a multidisciplinary gastrointestinal tumor board, she underwent short-course radiation therapy of 25 Gy, in five fractions to the anus, internal iliac lymph nodes, rectum, and mesorectum. One week later, she underwent laparoscopic abdominoperineal resection (APR) with ileostomy closure and end colostomy with gluteal fasciocutaneous advancement flaps for reconstruction (Fig. 2). Her final pathology demonstrated negative margins with seven of nine lymph nodes involved by metastatic adenocarcinoma, intact expression of mismatch repair proteins (MSS), and a pathologic stage of anal adenocarcinoma of ypT1 ypN1. After she recovered, she underwent adjuvant chemoradiation therapy of 45 Gy in 28 fractions to the external iliac and inguinal regions with concurrent capecitabine (Xeloda, 825 mg/m). Surveillance imaging 6 weeks after the commencement of adjuvant therapy demonstrated significant gastrohepatic, periportal, and retroperitoneal lymphadenopathy. As she had experienced significant adverse effects attributed to capecitabine therapy, she underwent systemic chemotherapy with a lower dose of capecitabine (700 mg/m) and oxaliplatin (75 mg/m), a regimen that appeared to stabilize her disease after four cycles. One year after initial evaluation and 4 months after completing her chemotherapy regimen, she was evaluated in the emergency department with complaints of severe postprandial abdominal pain, increasing distension, and minimal oral intake. A CT scan disclosed increased lymphadenopathy with compression of the porta hepatis, pancreatic duct, and right ureter due to mass effect, representing significant disease progression. The patient was admitted for an endoscopic retrograde cholangiopancreatography & Sepideh Gholami gholami.sepideh@gmail.com