Primary gallbladder carcinomas showing pancreatic acinar features in the absence of a pancreatic primary

Aims Acinar cell carcinoma (ACC) is a lineage‐specific carcinoma that occurs nearly exclusively in the pancreas. We report, to our knowledge, the first series of gallbladder carcinoma demonstrating extensive acinar differentiation in the absence of a pancreatic primary. Methods Three gallbladder carcinomas with extensive acinar differentiation were identified from an international cohort. Clinical, radiologic, macroscopic, histologic, immunophenotypic and molecular features were reviewed. Results All tumours lacked an associated pancreatic primary on imaging and clinical evaluation. Two tumours formed well‐demarcated mural nodules lacking an exophytic mucosal component, while one tumour was associated with wall thickening. The neoplasms showed mural‐based infiltrative lesions composed of nests and acinar structures of cells with amphophilic cytoplasm and prominent nucleoli. One tumour arose in association with high‐grade dysplasia and BCL10‐positive pyloric‐type glands. Two tumours showed pure acinar morphology, while one demonstrated a mixed acinar cell carcinoma and small‐cell carcinoma. Immunohistochemically, all tumours showed diffuse expression of trypsin, and two tumours showed diffuse BCL10 positivity. Molecular profiling revealed heterogeneous alterations including TP53 mutations in two cases, RB1 inactivation in the mixed tumour. Conclusions Gallbladder carcinomas may rarely exhibit acinar differentiation that closely mirrors pancreatic ACC. Recognition of this phenotype expands the morphologic repertoire of gallbladder carcinomas.