Tumoral Intraductal Neoplasms of the Bile Ducts Comprise Morphologically and Genetically Distinct Entities

Tao Wang; Gokce Askan; Kerem Ozcan; Satshil Rana; Ahmet Zehir; Umeshkumar K Bhanot; Rhonda K Yantiss; Deepthi S Rao; Samuel J Wahl; Pelin Bagci; Serdar Balci; Vinod Balachandran; William R Jarnagin; N Volkan Adsay; David S Klimstra; Olca Basturk

doi:10.5858/arpa.2022-0343-OA

Tumoral Intraductal Neoplasms of the Bile Ducts Comprise Morphologically and Genetically Distinct Entities

Arch Pathol Lab Med. 2023 Dec 1;147(12):1390-1401. doi: 10.5858/arpa.2022-0343-OA.

Authors

Affiliations

¹ From the Department of Pathology and Laboratory Medicine (Wang, Askan, Ozcan, Rana, Zehir, Bhanot, Rao, Klimstra, Basturk), Memorial Sloan Kettering Cancer Center, New York, New York.
² Department of Pathology, Weill Cornell Medicine, New York, New York (Yantiss).
³ Department of Pathology, Lenox Hill Hospital, New York, New York (Wahl).
⁴ Department of Pathology, Marmara University Hospital, Istanbul, Turkey (Bagci).
⁵ Department of Pathology, Memorial Healthcare Group, Istanbul, Turkey (Balci).
⁶ The Department of Surgery (Balachandran, Jarnagin), Memorial Sloan Kettering Cancer Center, New York, New York.
⁷ The Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey (Adsay).

PMID: 36821179
DOI: 10.5858/arpa.2022-0343-OA

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.

MeSH terms

Aged
Bile Duct Neoplasms* / genetics
Bile Duct Neoplasms* / pathology
Bile Ducts / pathology
Carcinoma, Pancreatic Ductal* / pathology
Carcinoma, Papillary* / pathology
Female
Humans
Male
Pancreatic Neoplasms* / pathology