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Development of intraductal papillary neoplasm of the bile duct in patients with occupational cholangiocarcinoma

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Abstract

This study aimed to investigate the clinicopathological findings of intraductal papillary neoplasm of the bile duct (IPNB) in patients with occupational cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane to elucidate the development of IPNB to cholangiocarcinoma. The clinicopathological findings of 17 IPNB lesions according to the size (1.5–20 mm in diameter) and their comparison between type 1 (n = 9) and type 2 IPNBs (n = 8) were investigated. An IPNB of <5 mm in size was classified as micro IPNB (n = 7), while those ≥5 mm in size were classified as ordinary IPNB (n = 10). Both types 1 and 2 IPNBs were observed in micro IPNB, and their proportions were not different between micro and ordinary IPNBs. The clinicopathological characteristics of types 1 and 2 IPNBs were fundamentally similar to those previously reported. IPNB with invasive carcinoma was only found in ordinary IPNB although the proportions of low-grade and high-grade epithelium were not different between micro IPNB and ordinary IPNB. All IPNB exhibited γH2AX and S100P, indicating the occurrence of DNA injury and malignant transformation in micro and ordinary IPNBs. These results indicate that the carcinogens may induce micro IPNB with types 1 or 2 at the initiation and then develop ordinary IPNB with types 1 or 2, subsequently, progressing to IPNB with invasive carcinoma in patients with occupational cholangiocarcinoma.

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References

  1. Nakanuma Y, Basturk O, Esposito I, Kimstra DS, Komuta M, Zen Y (2019) Intraductal papillary neoplasm of the bile ducts. In: Board E (ed) WHO classification of tumours of the digestive system, 5th edn. IARC, Lyon, pp 279–282

    Google Scholar 

  2. Zen Y, Sasaki M, Fujii T, Chen TC, Chen MF, Yeh TS et al (2006) Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct-an immunohistochemical study of 110 cases of hepatolithiasis. J Hepatol. 44:350–358

    Article  CAS  PubMed  Google Scholar 

  3. Itatsu K, Zen Y, Ohira S, Ishikawa A, Sato Y, Harada K et al (2007) Immunohistochemical analysis of the progression of flat and papillary preneoplastic lesions in intrahepatic cholangiocarcinogenesis in hepatolithiasis. Liver Int. 27:1174–1184

    Article  PubMed  Google Scholar 

  4. Kubo S, Nakanuma Y, Takemura S, Sakata C, Urata Y, Nozawa A et al (2014) Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan. J Hepatobiliary Pancreat Sci. 21:479–488

    Article  PubMed  Google Scholar 

  5. Kubo S, Kinoshita M, Takemura S, Tanaka S, Shinkawa H, Nishioka T et al (2014) Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 21:809–817

    Article  PubMed  Google Scholar 

  6. Nakamura Y, Jang KT, Fukushima N, Furukawa T, Hong SM, Kim H et al (2018) A statement by the Japan-Korea expert pathologists for future clinicopathological and molecular analyses toward consensus building of intraductal papillary neoplasm of the bile duct through several opinions at the present stage. J Hepatobiliary Pancreat Sci. 25:181–187

    Article  Google Scholar 

  7. Kubota K, Jang JY, Nakanuma Y, Jang KT, Haruyama Y, Fukushima N et al (2020) Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan-Korea collaborative study. J Hepatobiliary Pancreat Sci. 27:581–597

    Article  PubMed  Google Scholar 

  8. Aoki Y, Mizuma M, Hata T, Aoki T, Omori Y, Ono Y et al (2020) Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes. J Pathol. 251:38–48

    Article  CAS  PubMed  Google Scholar 

  9. Luvira V (2021) Progression of intraductal papillary neoplasm of the bile duct (IPNB): a proposed model through the observation of patients with non-resected tumors. Ann Hepatol 23:100299

    Article  PubMed  Google Scholar 

  10. Kubo S, Takemura S, Tanaka S, Shinkawa H, Kinoshita M, Hamano G et al (2016) Outcomes after resection of occupational cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 23:556–564

    Article  PubMed  Google Scholar 

  11. Kinoshita M, Kubo S, Nakanuma Y, Sato Y, Takemura S, Tanaka S et al (2016) Pathological spectrum of bile duct lesions from chronic bile duct injury to invasive cholangiocarcinoma corresponding to bile duct imaging findings of occupational cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 23:92–101

    Article  PubMed  Google Scholar 

  12. Kubo S, Takemura S, Tanaka S, Shinkawa H, Kinoshita M, Hamano G et al (2017) Occupational cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane. Ann Gastroenterol Surg. 2:99–105

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sato Y, Kubo S, Takemura S, Sugawara Y, Tanaka S, Fujikawa M et al (2014) Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan. Int J Clin Exp Pathol. 7:4745–4754

    PubMed  PubMed Central  Google Scholar 

  14. Mimaki S, Totsuka Y, Suzuki Y, Nakai C, Goto M, Kojima M et al (2016) Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes. Carcinogenesis. 37:817–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mimaki S, Watanabe M, Kinoshita M, Yamashita R, Haeno H, Takemura S et al (2020) Multifocal origin of occupational cholangiocarcinoma revealed by comparison of multilesion mutational profiles. Carcinogenesis. 41:368–376

    Article  CAS  PubMed  Google Scholar 

  16. Sasaki M, Matsubara T, Nitta T, Sato Y, Nakanuma Y (2013) GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile duct. PLOS One. 8:e81706

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sato Y, Harada K, Sasaki M, Nakanuma Y (2014) Histological characterization of biliary intraepithelial neoplasia with respect to pancreatic intraepithelial neoplasia. Int J Hepatology. 2014:678260

    Article  Google Scholar 

  18. Kinoshita M, Sato Y, Nebiki H, Tamamori Y, Ishii N, Inoue T et al (2019) Occupational cholangiocarcinoma diagnosed 18 years after the end of exposure to 1,2-dichloropropane and dichloromethane at a printing company: a case report. Surg Case Rep. 5:65

    Article  PubMed  PubMed Central  Google Scholar 

  19. Singhi AD, Wood LD, Parks E, Torbenson MS, Felsenstein M, Hruban RH et al (2020) Recurrent rearrangements in PRKACA and PRKACB in intraductal oncocytic papillary neoplasms of the pancreas and bile duct. Gastroenterology. 158:573–582

    Article  CAS  PubMed  Google Scholar 

  20. Nakanuma Y, Kakuda Y, Sugino T, Sato Y, Fukumura Y (2022) Pathologies of precursor lesions of biliary tract carcinoma. Cancers. 14:5358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Enago (WWW.enago.jp) for the English language review.

Funding

This work was supported in part by the Japan Society for the Promotion of Science KAKENHI Grant Number 17K10674 (Elucidation of carcinogenesis and establishment of the treatment strategy for intrahepatic cholangiocarcinoma by genetic and immunological analyses).

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Authors

Contributions

Study design: SK, MK, and YS designed the study. Acquisition of data: S. Tanaka, MK, HS, and TI. Pathological aspect of the study: MK and YS. Data analysis: SK, MK, and YS. Manuscript drafted by SK and YS. All authors reviewed the manuscript.

Corresponding author

Correspondence to Shoji Kubo.

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Ethics approval

The study was approved by the ethics committee of Osaka City University (current Osaka Metropolitan University.

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The authors declare no competing interests.

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Supplementary information

ESM 1

Supplemental Figure 1 Multiple lesions of micro IPNB in patient no. 5. A: lesion 5-1, 16 mm, ordinary IPNB, type 2, x40, scale bar 1 mm; B: The lesion 5-1 was mainly composed of oncocytic type (left side), and pancreatobiliary type (right side) was admixed. x 200; C: lesion 5-1, invasive area of ordinary IPNB, x200; D: lesion 5-2, ordinary IPNB, type 1, gastric type, x100, scale bar 0.5 mm; E: lesion 5-3, micro IPNB, type 1, pancreatobiliary type, x20, scale bar 2 mm; F: lesion 5-4, micro IPNB, type 2, pancreatobiliary type, x100, scale bar 0.5 mm; G: lesion 5-5, micro IPNB, type 1, gastric type, x40, scale bar 1 mm; H: lesion 5-6, micro IPNB, type 2, pancreatobiliary type, x40, scale bar 1 mm; I: lesion 5-7, micro IPNB, type 2, pancreatobiliary type, x100, scale bar 0.5 mm.

ESM 2

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Kubo, S., Tanaka, S., Kinoshita, M. et al. Development of intraductal papillary neoplasm of the bile duct in patients with occupational cholangiocarcinoma. Virchows Arch 482, 745–753 (2023). https://doi.org/10.1007/s00428-023-03499-5

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  • DOI: https://doi.org/10.1007/s00428-023-03499-5

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