Tumoral intraductal neoplasms of the bile ducts comprise morphologically and genetically distinct entities Journal Article
| Authors: | Wang, T.; Askan, G.; Ozcan, K.; Rana, S.; Zehir, A.; Bhanot, U. K.; Yantiss, R. K.; Rao, D. S.; Wahl, S. J.; Bagci, P.; Balci, S.; Balachandran, V.; Jarnagin, W. R.; Volkan Adsay, N.; Klimstra, D. S.; Basturk, O. |
| Article Title: | Tumoral intraductal neoplasms of the bile ducts comprise morphologically and genetically distinct entities |
| Abstract: | Context.--Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized. Objective.--To investigate their morphologic, immunohistochemical, and molecular features. Design.--Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing. Results.--The mean age at diagnosis was 69 years (42- 81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n=5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P=.04, P = .01 and P=.002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%). Conclusions.--Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous. |
| Keywords: | immunohistochemistry; signal transduction; adult; aged; aged, 80 and over; sequence analysis; mutation; gene expression; descriptive statistics; funding source; middle age; human; male; female; bile duct neoplasms -- familial and genetic; bile ducts -- anatomy and histology |
| Journal Title: | Archives of Pathology & Laboratory Medicine |
| Volume: | 147 |
| Issue: | 12 |
| ISSN: | 0003-9985 |
| Publisher: | College of American Pathologists |
| Date Published: | 2023-12-01 |
| Start Page: | 1390 |
| End Page: | 1401 |
| Language: | English |
| DOI: | 10.5858/arpa.2022-0343-OA |
| PROVIDER: | EBSCOhost |
| PROVIDER: | cinahl |
| PUBMED: | 36821179 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Olca Basturk -- Source: Cinahl |
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