Dual pancreatic carcinomas: clonally related or independent primaries?

Dual pancreatic cancers, either synchronous or metachronous in presentation, are a rare occurrence. It remains unclear if these lesions are clonally related or independently occurring primary malignancies. Herein we present a cohort (N = 22) with dual pancreatic ductal adenocarcinoma (PDAC) tumors to resolve previously conflicting reports and interrogate the underlying biological and clinical characteristics of this patient population. Next-generation sequencing of paired lesions (N = 10) revealed that while most dual PDAC are clonally related, independently occurring lesions do occur, irrespective of the interval between lesions. Integrated clinical, genomic, and histopathological analyses revealed a high frequency of lymph node-negative, intraductal papillary mucinous neoplasm (IPMN)-associated cancers, KRAS and/or SMAD4 wild-type tumors, and classical subtype by immunohistochemistry, all collectively associated with more favorable outcomes. Acknowledging the highly selected nature of this cohort, isolated intrapancreatic metastases demonstrate a more indolent biology and these patients may benefit from personalized management approaches beyond traditional paradigms.