A Genetic Twist: Cytologic Evaluation of Pancreatic Adenocarcinoma and Steatohepatitic Hepatocellular Carcinoma in a Patient With a Rare POLE Mutation

Abstract

Mutations in the DNA polymerase epsilon (POLE) gene are associated with an increased risk of various malignancies, including colorectal and other gastrointestinal, endometrial, ovarian, breast, and brain cancers. In extremely rare cases, POLE mutations have also been associated with pancreatic and hepatobiliary carcinomas. We present the case of an 87-year-old female with a complex medical history including multiple malignancies, who underwent endoscopic ultrasound-guided fine-needle aspirations of a pancreatic head mass and a liver lesion. Utilizing rapid on-site evaluation (ROSE) and full cytologic workup, she was ultimately diagnosed with synchronous pancreatic adenocarcinoma and the steatohepatitic variant of hepatocellular carcinoma. Given her history of multiple malignancies, she underwent genetic testing, and a rare germline POLE mutation was discovered. This case expands the phenotypic spectrum of potential POLE-associated syndromes and highlights the critical role of cytopathology in fine-needle aspiration procedures for diagnosis and management of complex oncologic cases.