Bhavana Bhatnagar, Christen Jordan, Cara Randall, Andrew Gordon, Christinea Marino, Angela Burrie and Ashkan Emadi*
A diagnosis of synchronous cancers within the same individual poses a multitude of diagnostic and treatment-related challenges. Many of these challenges pertain to the vast heterogeneity in cancers and presentations, patient ineligibility for clinical trials, lack of standardized guidelines to direct management and an incomplete understanding of the molecular mechanisms that contribute to the development of these cancers. We present a case of concurrent diagnoses of Pancreatic Ductal Adenocarcinoma (PDAC) and Acute Myeloid Leukemia (AML) with a comprehensive mutational analysis of the pancreatic tumor, AML blasts, and germline DNA collected from cultured skin fibroblast samples. In addition to some commonly detected mutations (e.g. KRAS Gly12Asp in PDAC and TP53 Met237lle in AML), the genetic testing revealed the presence of DDX41 and MUTYH gene mutations in both germline DNA and tumor tissue specimens. This case underscores the importance of addressing the interplay of genetic, lifestyle and environmental factors in the development of synchronous cancers in an individual, and only by doing so, evidence-based guidelines for early detection and management may be developed.