Recurrent gastric amphicrine tumor with neuroendocrine and pancreatic acinar cell differentiation and somatic MEN1 inactivation arisen during immunotherapy

Virchows Arch. 2023 Sep;483(3):415-419. doi: 10.1007/s00428-023-03624-4. Epub 2023 Aug 15.

Abstract

Amphicrine neoplasms (ANs) are poorly understood epithelial malignancies composed of cells with co-existing exocrine-neuroendocrine features. Here, we report a recurrent mucin-producing gastric amphicrine tumor co-expressing neuroendocrine (chromogranin-A, synaptophysin, and CD56) and pancreatic acinar cell (BCL10 and trypsin) markers, arisen in a 64-year-old woman during adjuvant immunotherapy for melanoma. Ki-67 was < 2%. The gastric background context was atrophic gastritis. Next-generation sequencing showed MEN1 mutation (p.P71fs*42) coupled with loss of heterozygosity. The key lessons were as follows: (1) gastric ANs can show the co-existence of exocrine mucin-producing elements with neuroendocrine and pancreatic acinar differentiation; (2) they may represent a new entity arising in the context of atrophic gastritis and during immunotherapy; (3) they should be considered in the diagnostic workup of gastric neuroendocrine tumors; and (4) their molecular profile can show striking similarities with well-differentiated neuroendocrine tumors. These findings may be of help to improve the knowledge and the biological taxonomy of ANs.

Keywords: Amphicrine; Immunotherapy; MEN1; MiNEN; Mixed; Neuroendocrine.

Publication types

  • Case Reports

MeSH terms

  • Acinar Cells / pathology
  • Biomarkers, Tumor / genetics
  • Cell Differentiation
  • Female
  • Gastritis, Atrophic*
  • Humans
  • Middle Aged
  • Mucins
  • Neoplasm Recurrence, Local
  • Neuroendocrine Tumors* / diagnosis
  • Neuroendocrine Tumors* / therapy
  • Pancreatic Neoplasms* / diagnosis
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / therapy
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / therapy

Substances

  • Mucins
  • Biomarkers, Tumor