Intraductal Tubulopapillary Neoplasm of the Pancreas

Abstract

Background Intraductal tubulopapillary neoplasm (ITPN) is a relatively recently described member of the pancreatic intraductal neoplasm family. Thus, the literature on its histologic and immunohistochemical features, clinical behavior, and its similarities and differences from other pancreatic neoplasms is limited. Design Thirty-three cases of ITPN, the largest series to date, were identified. Immunohistochemical labeling for cytokeratins, glycoproteins, pancreatic enzymes, markers for intestinal and neuroendocrine differentiation, and antibodies associated with genetic alterations previously described in pancreatic neoplasms were performed. Clinicopathologic features and survival was assessed. Results Seventeen patients were female, fourteen were male. Mean age was 55 years (range, 25–79). Median overall tumor size was 4.5 cm (range, 0.5–15). Forty-five percent of the tumors occurred in the head, 32% in the body/tail, and 23% showed diffuse involvement. Microscopically, the tumors were characterized by intraductal nodules composed of tightly packed small tubular glands lined by cuboidal cells lacking apparent mucin. Although it was often challenging to determine its extent, invasion was present in 71%. Almost all tumors labeled for CAM5.2, CK7 and CK19; most expressed CA19.9, MUC1 and MUC6. CDX2, MUC2, trypsin, chymotrypsin, chromogranin and synaptophysin were not expressed. SMAD4 expression was retained in 100%, p16 expression and p53 overexpression was seen in 33% and 27%. Follow-up information was available for twenty-two patients (median follow-up, 45 months; range, 11–173). Two patients with invasive carcinoma died of disease at 23 and 41 months. One patient died of unrelated causes at 49 months. Twelve patients were alive with disease. Seven patients were alive with no evidence of disease. The overall 1-, 3- and 5-year survival rates were 100% in patients without an invasive component and 100%, 91% and 71% in patients with an invasive component (p=0.7). Conclusions ITPN is a distinct clinicopathologic entity in the pancreas. Despite the difficulties of determining the extent of invasive carcinoma in many cases, the overall outcome appears relatively favorable and substantially better than that of conventional ductal adenocarcinoma, even when only the cases with invasive carcinoma are considered.

Precursor Lesions of Pancreatic Cancer

“…ITPNs are usually positive for MUC1 and MUC6, but negative for MUC2 and MUC5AC [65,68,71], differentiating them from IPMN, especially the pancreatobiliary type (MUC1+, MUC5AC+, and MUC6−/+some; table 1) [43,65,69]. p53 overexpression is observed in a third of ITPNs, but SMAD4 expression is retained [66]. Molecular pathological aspects of ITPNs differ from those of IPMNs and the associated PDACs.…”

“…ITPN is a grossly detectable (> 1 cm) epithelial neoplasm characterized by an intraductal solid nodular mass within a distended pancreatic duct with minimal cyst formation and consisting of tumor cells with a tubular architecture without accompanying overt mucin production [65,66]. ITPN is rare, comprising < 1% of exocrine tumors of the pancreas [67].…”

“…Molecular pathological aspects of ITPNs differ from those of IPMNs and the associated PDACs. ITPNs do not harbor KRAS or BRAF mutations, which are common in IPMNs and associated PDACs [66,72]. Several genes involved in chromatin remodeling ( MLL1 , MLL2 , MLL3 , BAP1 , and PBRM1 ) and genes involved in the phosphatidylinositol 3-kinase pathway ( PIK3CA , PIK3CB , and PTEN ) are commonly mutated in ITPNs [72].…”

“…More than half of ITPNs are associated with PDACs [66]. It is challenging to diagnose the invasive carcinoma component and its extent due to the absence of the peripheral rim of non-neoplastic ductal epithelial cells [66,68].…”

“…The mean age is 55 years with slight female predominance [66]. Half of all ITPNs occur in the head and a third occur in the body or tail of the pancreas [66]. …”