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Genomic analysis of an aggressive case with metastatic intrahepatic mucinous cholangiocarcinoma

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Abstract

Intrahepatic mucinous cholangiocarcinoma (IHMC) is rare and behaves notoriously; however, the details of the clinicopathological characteristics of IHMC remain unknown. A 70-year-old man was admitted for examination of the hepatic mass in the S1 segment. He underwent extended left hepatic lobectomy. Histopathological evaluation demonstrated mixed papillary carcinoma that comprised well to moderately differentiated tubular adenocarcinoma and signet-ring cell carcinoma with large amounts of mucus lakes. Tumor was relapsed 9 months after surgery. Although he received chemotherapy with the combination of gemcitabine and cisplatin, he had renal failure and discontinued the chemotherapy. He received palliative radiotherapy for metastasis in the cervical spine. Then, the patient treated with S-1, however, he died 16 months after the initial diagnosis. The autopsy findings showed multiple nodules in the lungs, pleura, kidneys, adrenal glands, stomach, pancreas, and lymph nodes. Histological examination revealed that all nodules were IHMC. Next-generation sequencing revealed that somatic mutations in ADGRB3, TAF1L and EPHA3 may affect carcinogenesis, and those in TAF1, EPHA3, PIK3C2B, FN1, ERBB3, BRIP1, SYNE1 and TGFBR2 may affect metastasis. Molecular carcinogenesis of IHMC may be distinct from that of ordinary cholangiocarcinoma. Further studies are needed to elucidate the genetic mutations and their functions in IHMC.

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Abbreviations

IHMC:

Intrahepatic mucinous cholangiocarcinoma

MC:

Mucinous carcinoma

CECT:

Contrast-enhanced computed tomography

MRI:

Magnetic resonance imaging

T2WI:

T2-weighted image

DWI:

Diffusion-weighted image

ADC:

Apparent diffusion coefficient

UICC:

The Union for International Cancer Control

GEM:

Gemcitabine

CDDP:

Cisplatin

NGS:

Next-generation sequencing

FFPE:

Formalin-fixed, paraffin-embedded

CNVs:

Copy number variations

WHO:

World Health Organization

HCC:

Hepatocellular carcinoma

IHCC:

Intrahepatic cholangiocarcinoma

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Funding

This study was supported in part by JSPS KAKENHI Grant Number 16H06279 (PAGS).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuoku, Sapporo, Hokkaido, 060-8543, Japan

    Yoshiharu Masaki, Noriyuki Akutsu, Keisuike Ishigami & Hiroshi Nakase

  2. Division of Gastroenterology, Department of Internal Medicine, Sapporo Shirakaba-Dai Hospital, Sapporo, Japan

    Yasushi Adachi, Norikazu Iwata & Takao Endo

  3. Department of Pathology, Sapporo Shirakaba-Dai Hospital, Sapporo, Japan

    Yoshifumi Ishii

  4. Department of Biology, Sapporo Medical University, Sapporo, Japan

    Yasushi Sasaki

  5. Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan

    Minoru Nagayama & Yasutoshi Kimura

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  1. Yoshiharu Masaki
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  2. Noriyuki Akutsu
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  11. Hiroshi Nakase
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Correspondence to Yoshiharu Masaki.

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All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Masaki, Y., Akutsu, N., Adachi, Y. et al. Genomic analysis of an aggressive case with metastatic intrahepatic mucinous cholangiocarcinoma. Clin J Gastroenterol 15, 809–817 (2022). https://doi.org/10.1007/s12328-022-01649-x

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  • DOI: https://doi.org/10.1007/s12328-022-01649-x

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