A 63-year-old man presents with abdominal pain and jaundice. His labs are significant for elevated AST, ALT, alkaline phosphatase, and CA 19-9. An MRCP shows marked dilatation of intrahepatic biliary ducts, and an MRI is suspicious for a biliary mass of the right hepatic lobe. He undergoes right hepatectomy; gross exam and microscopy reveal the lesion pictured below. It is situated within the bile ducts and there is focal invasion noted.
The correct answer is ...
The diagnosis in this case is: MUC1 (+), MUC2 (-).
The gross photograph shows a well-circumscribed mass contained within a dilated bile duct. Microscopy shows papillary projections of biliary epithelium seated within a bile duct with focal invasion. This leads to a diagnosis of invasive carcinoma arising within an intraductal papillary neoplasm of the bile duct (IPNB).
IPNB is essentially the biliary counterpart to intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Similar to IPMN, IPNB has four morphologic subtypes. The distinction of these subtypes can be aided by their staining patterns for antibodies against two mucin core (MUC) proteins, MUC1 and MUC2.
The pancreaticobiliary subtype displays tall, columnar cells that approximate normal biliary epithelial cells. This is the most common subtype of IPNB, as well as the one most associated with invasive components, and is also the one seen in this case. It is typically positive for MUC1 and negative for MUC2.
The intestinal subtype consists of villous architecture with columnar epithelial cells resembling small intestine tissue. It is generally MUC1 negative and MUC2 positive.
The gastric subtype approximates the foveolar epithelium of the stomach and grows in a tubular pattern. It is typically negative for both MUC1 and MUC2.
The oncocytic subtype shows plump cells with eccentrically-placed nuclei and prominently pink cytoplasm. It can show focal positivity for both MUC1 and MUC2.
Ryan Kendziora, M.D.
Resident, Anatomic and Clinical Pathology
Lizhi Zhang, M.D.
Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science