Abstract
Pancreatic cancer is an aggressive malignancy with increasing incidence. Pancreatic ductal adenocarcinoma (PDAC) accounts for > 90% of pancreatic cancer diagnoses, while other exocrine tumors are much rarer. In this review, we have focused on two rare cancers of the exocrine pancreas: adenosquamous carcinoma of the pancreas (ASCP) and pancreatic acinar cell carcinoma (PACC). The latest findings regarding their cellular and molecular pathology, clinical characteristics, prognosis, and clinical management are discussed. New genetic and transcriptomic data suggest that ASCP is related to or overlaps with the basal transcriptomic subtype of PDAC. These tumors are highly aggressive and driven by activated KRAS and MYC expression. Clinical outcomes remain poor and effective treatments are limited. PACC has no morphologic or genetic resemblance to PDAC and more favorable outcomes. Early stage PACC patients have improved survival with surgical resection and patients with advanced disease benefit most from platinum- or fluoropyrimidine-containing chemotherapy. Frequency of actionable genetic mutations is high in this disease and case reports suggest good outcomes when matched therapy is given. Dedicated clinical studies examining ASCP and PACC are limited and difficult to accrue. Further research is needed to define optimal clinical management for these rare diseases.