Increased Prevalence of Precursor Lesions in Familial Pancreatic Cancer Patients

Abstract

PURPOSE: Histologic findings in 51 pancreata resected from patients with a strong family history of pancreatic cancer were compared with the findings in 40 pancreata resected from patients with sporadic pancreatic cancer. None of the patients in the familial group had a known inherited syndrome other than familial pancreatic cancer. EXPERIMENTAL DESIGN: Precursor lesions, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and incipient IPMN, were quantified. Invasive cancers were classified using established histologic criteria. RESULTS: The individual precursor lesions identified in both groups were histologically similar. Precursor lesions were more common in the familial cases than in the sporadic cases. The relative rate of PanINs per square centimeter was 2.75-fold higher (95% confidence interval, 2.05-3.70; adjusted for age) in familial compared with sporadic cases. PanIN-3 lesions were more common in familial versus sporadic pancreatic cancer patients (relative rate, 4.20; 95% confidence interval, 2.22-7.93; adjusted for age). High-grade incipient IPMNs were only observed in the familial cases. Nine of the 51 (18%) familial pancreatic cancers and 4 of the 40 (10%) sporadic cancers arose in association with an IPMN. No significant differences were found in the types of invasive cancers. CONCLUSIONS: Noninvasive precursor lesions are more common in patients with a strong family history of pancreatic cancer than in patients with sporadic disease, and precursor lesions are of a higher grade in patients with a strong family history of pancreatic cancer. These findings can form a basis for the design of screening tests for the early detection of pancreatic neoplasia. (Clin Cancer Res 2009;15(24):7737-43).

Figure 1

Representative hematoxylin-eosin stained PanIN lesions from case 51 of the familial group. A: A PanIN-1 lesion showing mucinous columnar epithelial proliferation with little nuclear atypia (200X); B: A PanIN-2 lesion showing proliferated ductal epithelium with some nuclear atypia and pseudostratification (100X). C: A PanIN-3 lesion showing marked architectural and nuclear atypia (100X).

Figure 2

Representative hematoxylin-eosin section (40X) containing an IPMN lesion from case 21 of the familial group. The lesion had a prominent papillary structure associated with moderate to marked nuclear atypia.

Figure 3

PanIN lesions associated parenchymal abnormalities (hematoxylin-eosin, 40X) . A: A PanIN-1B lesion with associated lobular parenchyma showing partial acinar atrophy, acinar to ductal metaplasia. Note: residual normal acinar cells. B: A PanIN-3 lesion with associated parenchymal showing lobulocentric atrophy with loss of acinar parenchyma in a lobular pattern, fibrosis, and acinar-ductal metaplasia, and clusters of islet of Langerhans.