Answer: Metastatic adenocarcinoma of the pancreas

Histology: Sections show portion of omentum with fat necrosis and desmoplastic reaction surrounding glandular structures that are lined by cuboidal columnar cells that have intracytoplasmic mucin vacuoles. The nuclei are basally located and show low mild pleomorphism. Focally, poorly formed glands and small clusters of more atypical tumor cells are seen infiltrating the stroma. Immunostains demonstrate that the tumor cells are focally and weakly CDX-2 positive and show uniform loss of DPC4. Additional stains (not shown) demonstrated that the tumor cells are CA19.9, CK7, CEA and EMA positive, while AFP, Heppar1, CK20, PSA, thyroglobulin and TTF-1 negative.

Discussion: Based on the morphologic appearance the differential diagnosis includes a pancreato-biliary, upper GI and less likely lung primary. The immunostains support this differential diagnosis and with addition of DPC4 favor a pancreatobiliary origin. DPC4B8 (SMAD4) expression is lost in approximately 50% of pancreatic adenocarcinomas, whereas it is usually retained in upper GI and lung adenocarcinomas. DPC4 loss has also been described in a small subset of colon carcinomas. CDX-2 expression is present in the large majority of lower GI tract adenocarcinomas and in a subset of upper GI tumors. In the pancreas focal weak staining can also be seen in rare cases.