Adenocarcinoma with pyloric gland phenotype of the extrahepatic bile ducts: a previously unrecognized and distinctive morphologic variant of extrahepatic bile duct carcinoma.

Carcinomas of the extrahepatic bile ducts are uncommon and morphologically heterogeneous. We report 3 unique examples of adenocarcinomas that show predominantly pyloric gland differentiation (80%-100%) and compare their immunohistochemical profile with that of pyloric gland adenomas of the gallbladder, foveolar, and intestinal-type adenocarcinomas of the extrahepatic bile duct. The 3 patients with pyloric gland adenocarcinomas were younger than those with conventional adenocarcinomas. The 3 tumors were very well differentiated but showed extensive perineural invasion. They consisted of a variable proportion of small, medium-sized, and cystically dilated glands separated by abundant desmoplastic stroma. The glands were lined by columnar cells with abundant mucin-containing cytoplasm and small hyperchromatic basally placed nuclei with inconspicuous nucleoli. A characteristic feature of these pyloric gland adenocarcinomas was that the glands had a stellar pattern that was not seen in foveolar-, intestinal-, or biliary-type adenocarcinomas. Two pyloric gland adenocarcinomas coexpressed MUC6 and MUC5AC. The diffuse pattern of reactivity of MUC5AC and MUC6 was similar to that of 10 pyloric gland adenomas of the gallbladder and 2 foveolar adenocarcinomas of the extrahepatic bile duct. In contrast, 5 intestinal adenocarcinomas of the extrahepatic bile duct labeled with the intestinal marker CDX2 and 3 with the colonic MUC2 but were negative for MUC6 and MUC5AC. We believe that these pyloric gland adenocarcinomas represent a previously unrecognized distinct clinicopathologic entity. Despite their deceptively benign microscopic appearance, 1 patient died with local recurrence and liver metastasis, another patient is living with tumor, and the third patient is asymptomatic but only 5 months after surgery.