title: Intraductal Tubulopapillary Neoplasm of the Pancreas: A Clinicopathologic and Immunohistochemical Analysis of 33 Cases.
abstract: 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. 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 was performed. Clinicopathologic features and survival was assessed. Seventeen patients were female and 14 were male. Mean age was 55 years (range, 25 to 79 y). Median overall tumor size was 4.5 cm (range, 0.5 to 15 cm). 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%, respectively. Follow-up information was available for 22 patients (median follow-up, 45 mo; range, 11 to 173 mo). Two patients with invasive carcinoma died of disease at 23 and 41 months, respectively. 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%, respectively, in patients with an invasive component (P=0.7). 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 seems to be relatively favorable and substantially better than that of conventional pancreatic ductal adenocarcinoma, even when only the cases with invasive carcinoma are considered.
authors.affiliation: Departments of *Pathology #Surgery, Memorial Sloan Kettering Cancer Center, New York, NY †Departments of Pathology, Emory University School of Medicine, Atlanta, GA ‡Departments of Pathology, University of Verona and Negrar Hospital, Verona, Italy §Departments of Pathology, Hakujikai Memorial Hospital, Tokyo, Japan ∥Departments of Pathology, Centro Hospitalar São João/University of Porto and Institute for Research and Innovation in Health/Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal. ¶Departments of Pathology, Heinrich-Heine-University of Düsseldorf, Düsseldorf **Departments of Pathology, Technical University, Munich, Germany.
authors.forename: Olca
authors.initials: O
authors.lastname: Basturk
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
authors.forename: Gokce
authors.initials: G
authors.lastname: Askan
authors.forename: Deepti
authors.initials: D
authors.lastname: Dhall
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.forename: Michio
authors.initials: M
authors.lastname: Shimizu
authors.forename: Karina
authors.initials: K
authors.lastname: Cymes
authors.forename: Fatima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Serdar
authors.initials: S
authors.lastname: Balci
authors.forename: Carlie
authors.initials: C
authors.lastname: Sigel
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Reid
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Helena
authors.initials: H
authors.lastname: Baldaia
authors.forename: Peter
authors.initials: P
authors.lastname: Allen
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor