82 A Rare Case of Goblet Cell Adenocarcinoma of the Colon in a Patient With Ulcerative Colitis and Primary Sclerosing Cholangitis

Introduction: Patients with ulcerative colitis (UC) have an increased risk of developing colorectal adenocarcinoma, particularly when associated with primary sclerosing cholangitis (PSC). Goblet cell adenocarcinoma (GCA) is a rare malignancy, accounting for less than 1% of colorectal neoplasms. It combines epithelial (adenocarcinoma) and neuroendocrine (carcinoid) features, occurring predominantly in the appendix, while primary extra-appendiceal cases are exceedingly uncommon. We report a case of UC associated with PSC, with an incidental finding of colonic GCA, concomitant with conventional intramucosal adenocarcinoma. Case Description/Methods: A 39-year-old male, mixed race, was diagnosed with ulcerative colitis (UC) in 2014, presenting as pancolitis. The disease evolved with recurrent flares requiring multiple courses of corticosteroids. He was treated with mesalamine, azathioprine 2 mg/kg/day, and infliximab 5 mg/kg every 8 weeks until 2020. In 2020, he was diagnosed with primary sclerosing cholangitis (PSC) through MR cholangiography, with evidence of chronic liver disease and portal hypertension. Due to the high oncologic risk associated with UC + PSC, vedolizumab was initiated every 8 weeks in 2022, along with annual surveillance colonoscopy. In 2022, colonoscopy revealed a poorly defined area of erythema and erosions in the cecum. Biopsy showed high-grade dysplasia. A repeat colonoscopy was not performed until 2024, as the patient underwent treatment for a pathological vertebral fracture related to long-term corticosteroid use. In the 2024 colonoscopy, the same poorly defined inflammatory area in the cecum persisted, with high-grade dysplasia confirmed. A total colectomy with ileorectal anastomosis was performed. Examination of the surgical specimen revealed an incidental invasive goblet cell adenocarcinoma associated with an extensive area of high-grade dysplasia and a focus of conventional intramucosal adenocarcinoma. Immunohistochemistry was positive for CDX2, CK7, CK20 and synaptophysin, negative for chromogranin A. The cecal appendix was also resected and found to be free of neoplasia. No lymph node involvement or metastases were identified. Conclusions: Goblet cell adenocarcinoma (GCA) typically presents in the fifth to sixth decades of life, with no gender predominance. It may be associated with conditions such as UC, neurofibromatosis type 1, and mucinous ovarian cystadenocarcinoma, and can occasionally coexist with conventional colorectal adenocarcinoma. Thought to arise from pluripotent stem cells in intestinal crypts, GCA displays a distinct histological pattern of mucin-filled goblet cells, neuroendocrine cells, and sometimes Paneth cells, arranged in infiltrative and organoid formations. Unlike classic neuroendocrine tumors, it shows only focal chromogranin A and synaptophysin expression. Because of its severity, it is categorised as adenocarcinoma. Diagnosis is often delayed due to nonspecific symptoms and typically advanced-stage presentation. Exclusion of the appendix as the primary site is essential, as demonstrated in our case. Key differentials include mixed adenoneuroendocrine carcinoma, mucinous adenocarcinoma, and signet-ring cell carcinoma. Given its rarity and lack of standardized guidelines, treatment is challenging. Surgical resection is preferred for localized disease, while chemotherapy may be used in advanced stages. Metastases commonly involve the peritoneum, omentum, abdominal wall, and ovaries. Prognosis is stage- and grade-dependent, with follow-up similar to colorectal adenocarcinoma.