Precursors to Pancreatic Cancer

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Infiltrating ductal adenocarcinoma of the pancreas is believed to arise from morphologically distinct noninvasive precursor lesions. These precursors include the intraductal papillary mucinous neoplasm, the mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. Intraductal papillary mucinous neoplasms are grossly visible mucin-producing epithelial neoplasms that arise in the main pancreatic duct or one of its branches. The cysts of mucinous cystic neoplasms do not communicate with the major pancreatic ducts, and these neoplasms are characterized by a distinct ovarian-type stroma. Pancreatic intraepithelial neoplasia is a microscopic lesion. This article focuses on the clinical significance of these three important precursor lesions, with emphasis on their clinical manifestations, detection, and treatment.

Section snippets

Definition of Precursor

  • Intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and pancreatic intraepithelial neoplasia (PanIN) all meet rigorous criteria for precursor lesions. A working definition of a cancer precursor (although employing the less desirable and more deterministic term precancer) recently was developed by a National Cancer Institute-sponsored consensus conference [7]. Five criteria were established to define a precursor to invasive cancer, and all three lesions in the

Clinical Features

Mucinous cystic neoplasms are defined as mucin-producing, cyst-forming epithelial neoplasms of the pancreas with a distinctive ovarian-type stroma (Fig. 1, Fig. 2) [2]. MCNs are far more common in women than men (female to male ratio of 20 to 1), and the mean age at diagnosis is between 40 and 50 years, with a range of 14 to 95 years [2], [18], [19], [20], [21]. Patients typically present with epigastric discomfort, a sense of abdominal fullness, or an abdominal mass [20], [21]. Some MCNs are

Clinical Features

IPMNs are grossly visible, noninvasive, mucin-producing epithelial neoplasms that usually form long finger-like papillae (Fig. 3, Fig. 4) [2], [31]. Most are at least 1 cm in size [31]. In contrast to MCNs, IPMNs, by definition, involve the main pancreatic duct or one of its branches (see Fig. 3) [2], [32]. IPMNs arise in the head of the pancreas more frequently than the tail, and IPMNs lack an ovarian-type stroma [2], [31], [35]. IPMNs affect men slightly more often than women (male to female

Clinicopathologic Features

Pancreatic intraepithelial neoplasia (PanIN) originally was recognized by Holst [3] over a century ago. It was not until this decade, however, that the PanIN nomenclature was developed, and careful molecular studies were performed to establish that PanINs are a precursor to invasive adenocarcinoma of the pancreas [4], [64].

PanINs are noninvasive microscopic epithelial neoplasms, located in the smaller pancreatic ducts, characterized by cytologic and architectural atypia (Fig. 6) [2], [31], [65]

Who Should be Screened?

Even if technological challenges of screening for small microscopic lesions in an inaccessible organ, such as the pancreas, can be overcome, one still would be faced with the very real challenge of identifying the appropriate population to screen. Pancreatic cancer, although extremely deadly, is simply too uncommon to make a nonselective screening effort practical. The incidence of pancreatic cancer in the United States is 9 per 100,000 per year [79]. Enormous sensitivity and specificity would

Screening for Asymptomatic Precursors

The discussion on screening up to this point has been largely theoretical. Nonetheless, a recent prospective controlled study by Canto and colleagues established that high-risk populations may be screened using existing technologies [92], [93]. Canto and colleagues screened 78 asymptomatic individuals with either a strong family history of pancreatic cancer or with the Peutz-Jeghers syndrome, and 149 controls, using CT and EUS [93], [94]. Eight patients who had neoplastic lesions of the

Summary

Three well-defined precursor lesions of adenocarcinoma of the pancreas have been identified. There is general agreement that, when possible, mucinous cystic neoplasms should be resected completely and, when resected, they should be examined completely by histology to identify or rule out small foci of infiltrating carcinoma. There is also general agreement that large (greater than 3 cm) intraductal papillary mucinous neoplasms should be resected, particularly when they contain a mural nodule or

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