Stage IV Epstein-Barr Virus-Associated Early Gastric Cancer and Comparative Analysis of Genetic Alterations in Primary and Metastatic Tumors

J Nippon Med Sch. 2020;87(6):350-354. doi: 10.1272/jnms.JNMS.2020_87-608.

Abstract

Early gastric cancer (EGC) with synchronous distant metastasis is extremely rare. Here, we report a case of stage IV Epstein-Barr virus (EBV) -associated EGC. A 51-year-old man presented with vague abdominal pain of 3 weeks' duration. Imaging studies revealed enlargement of the left supraclavicular, perigastric, and para-aortic lymph nodes, a huge gastric polypoid mass, and multiple liver masses. Histopathological examination of a biopsy specimen of the supraclavicular lymph node showed poorly differentiated carcinoma expressing EBV in tumor cell nuclei. The gastric mass exhibited tubular adenocarcinoma, which also expressed EBV in tumor cell nuclei. After 3 weeks of palliative chemotherapy with fluoropyrimidine and platinum, the patient died of liver failure. Next-generation sequencing analysis revealed mutation of the CDKN1B gene in the metastatic carcinoma and mutations of the CTNNB1 and PIK3R1 genes in the gastric carcinoma. In addition to the rare presentation of EBV-associated EGC, this case showed marked morphological and molecular differences between primary and metastatic tumors, which suggests clonal evolution of EBV-associated GC.

Keywords: EBV; early gastric cancer; next-generation sequencing; stage IV.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / virology*
  • Class Ia Phosphatidylinositol 3-Kinase / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Fatal Outcome
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Neoplasms, Multiple Primary*
  • Palliative Care
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / virology*
  • beta Catenin / genetics

Substances

  • CDKN1B protein, human
  • CTNNB1 protein, human
  • beta Catenin
  • Cyclin-Dependent Kinase Inhibitor p27
  • PIK3R1 protein, human
  • Class Ia Phosphatidylinositol 3-Kinase