Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP) were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the common hepatic duct. A bile duct excision was performed. Gross examination revealed a 3.6？cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive) surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC). Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bile duct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient’s poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas. 1. Case Report A 65-year-old man with a remote history of cholecystectomy for benign disease presented with a two-week history of painless jaundice, nausea, vomiting, and an unintentional 40-pound weight loss. His physical exam was within normal limits; specifically he was afebrile and did not have abdominal tenderness. Initial labs included a markedly elevated CA19-9 (2396？U/mL, normal range 0–35？U/mL), mildly elevated alpha fetoprotein (10.1？ng/mL, normal range 0.5–8.0？ng/mL), and normal CEA (1.3？ng/mL, normal range 0–3.0？ng/mL for non-smokers). Initial abdominal ultrasound demonstrated diffuse dilatation of the intrahepatic and common hepatic bile ducts. The largest intrahepatic duct had a diameter of 1.8？cm. At the level of the hepatic hilum, the common duct had a maximum diameter of 2.7？cm and a portion of the duct was filled with complex echogenic material. A triple phase liver CT showed a 3.8 × 2.5 × 2.1？cm enhancing mass in the expected region of the intra- and extrahepatic bile duct. Endoscopic retrograde cholangiopancreatography showed a severe filling defect measuring 1.7？cm in the middle portion of the common bile duct with proximal and distal dilation. Cholangioscopy demonstrated a soft, friable tumor,
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