Extra-Appendiceal Goblet Cell Adenocarcinoma: Clinicopathological Features of a Series of Tumors in the Gastrointestinal Tract and Bile Duct

ObjectivesGoblet cell adenocarcinoma is an amphicrine tumor composed primarily of goblet-like mucinous cells with variable numbers of endocrine cells and Paneth-like cells, typically arranged in crypt-like tubules. It typically arises in the appendix; primary extra-appendiceal goblet cell adenocarcinoma is rare. This study aimed to analyze the clinicopathological characteristics of extra-appendiceal goblet cell adenocarcinoma.MethodsWe retrospectively examined the clinicopathological, immunophenotypic and molecular features of patients with gastrointestinal and biliary goblet cell adenocarcinoma.ResultsEight patients (four women) with tumors in the stomach (<i>n</i> = 4), colorectum (<i>n</i> = 3), and extrahepatic bile duct (<i>n</i> = 1) were evaluated. Tumors exhibited goblet or signet ring-like cells arranged in tubular, fused, infiltrative single-file, or anastomosing cord patterns. Some higher-grade tumors exhibited solid sheet-like growth with scattered goblet-like cells. Tumors were classified as low-grade (<i>n</i> = 2), intermediate-grade (<i>n</i> = 2), or high-grade (<i>n</i> = 4). All tumors expressed at least one neuroendocrine marker (synaptophysin, chromogranin A, insulinoma-associated protein 1). No mutations were detected in the <i>KRAS</i>, <i>NRAS</i>, <i>PIK3CA</i>, or <i>BRAF</i>. All seven tested tumors were microsatellite stable. Two of the patients had early-stage disease, while six had advanced disease, with two patients of death.ConclusionsExtra-appendiceal goblet cell adenocarcinoma is rare and distinct, exhibiting similar histological, immunophenotypic and molecular features to its appendiceal counterpart. Histological grade and tumor stage have some predictive value with regard to prognosis. The incidence of this tumor may be underestimated, as it can be misdiagnosed as other tumors; awareness of it remains insufficient. These preliminary findings, constrained by a limited sample size, warrant validation in larger cohorts.