Molecular Analysis of Biliary Tract Neoplasms Associated with Familial Adenomatous Polyposis.

OBJECTIVES

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by multiple colorectal polyposis and is frequently associated with a variety of extracolonic lesions. However, neoplastic lesions of the biliary tract system, excluding those of the ampulla of Vater, are extremely rare in FAP, and the impact of APC alterations on their tumorigenesis remains unclear. We aimed to clarify the relationship between germline variants and somatic variants in the APC gene in biliary tract neoplasms (BTNs) of FAP patients.

METHODS

A total of 115 genetically confirmed FAP cases treated at our department between 1997 and 2024 were investigated regarding development of BTNs. APC gene analysis was performed in the BTNs.

RESULTS

Of 115 FAP cases, three developed BTNs. Case 1 was a 69-year-old female who underwent subtotal stomach-preserving pancreaticoduodenectomy for duodenal and middle bile duct carcinoma. Case 2 was a 67-year-old female who underwent pancreaticoduodenectomy for gastric, duodenal, and upper bile duct carcinoma. Case 3 was a 47-year-old male who underwent pancreas-sparing total duodenectomy with cholecystectomy for Spigelman Stage IV duodenal polyposis and gallbladder polyposis. In addition to germline pathogenic variants, somatic pathogenic variants of APC were identified in all the BTNs.

CONCLUSIONS

These findings suggest that the APC two-hit theory may underlie the tumorigenesis of these rare BTNs, consistent with the pathogenic process observed in colonic and other extracolonic lesions in patients with FAP.