Cystic precursors to invasive pancreatic cancer

Abstract

Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not.

Integration of KRAS testing in the diagnosis of pancreatic cystic lesions: a clinical experience of 618 pancreatic cysts

“…In contrast, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) have the potential to progress to invasive pancreatic adenocarcinoma. [4][5][6][7] Consequently, international consensus guidelines for the management of IPMNs and MCNs were established and recently updated. 8,9 Therefore, an accurate diagnosis is critical for proper patient management.…”

Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways

“…However, once a cyst is identified, it poses a challenging life-long management problem (1,2,(9)(10)(11)(12)(13). Some cyst types are virtually always benign, some are low-grade malignant, and others are precursors to invasive pancreatic ductal adenocarcinomas (PDAs); PDAs are associated with a dismal prognosis (14)(15)(16)(17). The distinction among cyst types is therefore critical for the effective management of patients with pancreatic cysts.…”

The genetic classification of pancreatic neoplasia

“…As is true for other epithelial neoplasms, invasive PDA appears to arise from histologically well-characterized noninvasive precursor lesions. These include microscopic precursor lesions called pancreatic intraepithelial neoplasia (PanIN) lesions, and larger cystic precursor lesions called intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) [21,22]. These precursor lesions are important because they represent an opportunity to detect and treat pancreatic neoplasia before it progresses to an incurable invasive carcinoma [23].…”

“…Although it is clear that there is a strong familial component to pancreatic cancer, a causative germline mutation in a known pancreatic cancer susceptibility gene can be identified in only approximately 20 % of familial cases [50,51]. The genes that are known to predispose to pancreatic cancer (Table 1) include genes causing hereditary breast-ovarian cancer (caused by germline mutations in BRCA1, BRAC2, or PALB2; with a relative risk of 3.5-10 for BRCA2), familial atypical multiple mole melanoma syndrome (caused by germline mutations in p16/CDKN2A; with a relative risk of [13][14][15][16][17][18][19][20][21][22], Peutz-Jeghers syndrome (caused by germline mutations in STK11; with a relative risk of 132), hereditary pancreatitis (caused by germline mutations in PRSS1 or SPINK1; with a relative risk of 50-80), Lynch syndrome (caused by germline mutations in MLH1, MSH2, etc. ; with a relative risk of 8.6) [47,51,52], and ataxia-telangiectasia (caused by germline mutations in ATM) [7,53,54].…”

“…In contrast to IPMNs, the cysts of MCNs do not communicate with the pancreatic duct system. MCNs, like IPMNs and PanIN lesions, can be a precursor to invasive adenocarcinoma [21,72,97]. Microscopically, MCNs are characterized by a neoplastic mucin-rich columnar epithelium with varying degrees of dysplasia sitting on an ovarian-type stroma composed of spindle-shaped cells [72,98].…”