Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment

Simple Summary Ampullary tumors are rare malignancies of the upper gastrointestinal tract. Histologic, immunohistochemical and, most recently, genomic biomarkers have been used to improve prognostication and identify patient subsets most likely to benefit from systemic therapies. Contemporary genomic evaluation has unveiled altered genes and cellular signaling pathways, with potential implications for precision oncology. This review provides a summary of the literature regarding ampullary adenocarcinoma, and outlines current and future directions to improve the oncologic treatment of this disease.Abstract Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved survival versus the pancreatobiliary subtype, although studies on the prognostic value of immunomorphologic classification have been inconsistent. Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. Multi-institutional collaboration will be necessary to better understand how molecular classification can guide type and sequencing of multimodality therapy.