Familial pancreatic cancer--status quo

Familial pancreatic cancer (FPC) is defined by families with at least two first-degree relatives with confirmed pancreatic ductal adenocarcinoma (PDAC) that do not fulfill the criteria of other inherited tumor syndromes with an increased risk for the development of PDAC, such as hereditary pancreatitis or hereditary breast and ovarian cancer. FPC is mostly autosomal dominant inherited and presents with a heterogeneous phenotype. Although the major gene defect has not yet been identified, some important germline mutations in the BRCA2-, PALB2-, and ATM-genes are causative in some FPC families.

It is suggested by experts to include high-risk individuals in a screening program with a multidisciplinary approach under research protocol conditions. However, neither biomarkers nor reliable imaging modalities for the detection of high-grade precursor lesions are yet available. Most screening programs are currently based on endoscopic ultrasound and magnetic resonance imaging, and first data demonstrated that precursor lesions (pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm) of PDAC can be identified. Timing and extent of surgery are still a matter of debate.

The present review focuses on the clinical phenotype of FPC, its histopathological characteristics, known underlying genetic changes, genetic counseling, and screening.