Familial Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC), although a rare disease, has a poor prognosis. With 5-year overall survival of 8%, there is a critical need to detect PDAC early or at a premalignant stage. Current screening methods are largely imaging based, but a more focused screening approach based on modifiable and nonmodifiable risk factors may improve the efficacy and likely outcomes of screening. In addition, the pathologic mechanisms that lead to the development of PDAC are discussed in an effort to further understand the targets of pancreatic cancer screening. The focus of this article will be inherited pancreatic cancer syndromes and familial pancreatic cancer, which together compose up to 10% of PDAC. Understanding the methods and targets of PDAC screening in high-risk individuals may translate to improved morbidity and mortality.

Figure 1

Screening for pancreatic ductal adenocarcinoma in high-risk individuals. A–D: Screening for pancreatic ductal adenocarcinoma may include endoscopic ultrasound (EUS; A and D) or magnetic resonance imaging (MRI; B) with magnetic resonance cholangiopancreatography (MRCP; C). A: During an EUS, an endoscope with an ultrasound probe at its tip is placed in the oropharynx and passed through the esophagus into the stomach and small intestine (image from Ni-ka Ford, printed with permission from Mount Sinai Health System). From various stations in the stomach and small bowel, pancreatic lesions may be visualized and sampled, as appropriate. B: Arrow indicates 3 cm pancreatic cyst. B and C: Representative MRI and MRCP images, respectively, from a familial pancreatic cancer patient are shown. D: A representative EUS image from the same patient, noting a 3 cm cystic lesion in the pancreas with two small nodules (printed with permission from Christopher DiMaio). E: The patient ultimately underwent surgical resection, which demonstrated an intraductal papillary mucinous neoplasm lined by gastric foveolar-type epithelium with up to severe dysplasia (hematoxylin and eosin staining; printed with permission from Hongfa Zhu). Original magnification, ×100 (E).