1. Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma.
- Author
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Kinzler MN, Schulze F, Jeroch J, Schmitt C, Ebner S, Gretser S, Bein J, Finkelmeier F, Trojan J, Zeuzem S, Schnitzbauer AA, Demes MC, Reis H, Wild PJ, and Walter D
- Subjects
- Humans, Retrospective Studies, Mutation, Bile Ducts, Intrahepatic pathology, Mucoproteins genetics, Oncogene Proteins genetics, Cholangiocarcinoma genetics, Cholangiocarcinoma pathology, Bile Duct Neoplasms genetics, Bile Duct Neoplasms pathology
- Abstract
Aims: The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions., Methods and Results: All patients treated with surgically resected iCCA at Frankfurt University Hospital between December 2005 and March 2023 were retrospectively analysed. Histomorphological features of SD- and LD-iCCA were evaluated by an expert hepatobiliary pathologist. Tissue samples suspicious for subtype heterogeneity were further investigated. Immunohistochemistry for N-cadherin, S100P, MUC5AC, MUC6, TFF1 and AGR2 and mutational profiling with the Illumina TruSight Oncology 500 (TSO500) assay were performed separately for the SD- and LD-iCCA regions. Of 129 patients with surgically resected iCCA, features of either SD- or LD-iCCA were present in 67.4% (n = 87) and 24.8% of the patients (n = 32), respectively; 7.8% (n = 10) had histomorphological features of both SD- and LD-iCCA, seven patients (5.4%) of which had sufficient formalin-fixed, paraffin-embedded tissue for further analysis. Heterogeneity of both subtypes could be confirmed with immunohistochemistry. In five of seven (71.4%) patients, molecular profiling revealed intratumoural differences in genetic alterations between the SD- and LD-iCCA region. In one patient, a BRAF mutation (p.V600E) was found in the SD-iCCA but not in the LD-iCCA region of the tumour., Conclusions: A marked portion of patients with iCCA exhibits both SD- and LD-iCCA in different tumour regions. In case of the presence of histopathological heterogeneity, mutational profiling should be considered to avoid missing therapeutically relevant genetic alterations., (© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.)
- Published
- 2024
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