J Gastric Cancer.  2018 Jun;18(2):200-207. 10.5230/jgc.2018.18.e16.

Multiregion Comprehensive Genomic Profiling of a Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm with Trilineage Differentiation

Affiliations
  • 1Department of Medicine, Stony Brook University Hospital, Stony Brook, NY, USA. Minsig.Choi@stonybrookmedicine.edu
  • 2Department of Pathology, Stony Brook University Hospital, Stony Brook, NY, USA.
  • 3Department of Surgery, Stony Brook University Hospital, Stony Brook, NY, USA.
  • 4Laboratory of Molecular Genetics, Department of Pathology, Stony Brook University Hospital, Stony Brook, NY, USA.
  • 5Division of Hematology/Oncology, Department of Medicine, Stony Brook University Hospital, Stony Brook, NY, USA.

Abstract

Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) are a group of rare tumors previously known as mixed adenoneuroendocrine carcinomas (MANECs). The neuroendocrine component is high-grade and may consist of small-cell carcinoma or large-cell neuroendocrine carcinoma. The nonneuroendocrine component may consist of adenocarcinoma or squamous cell carcinoma. We report a unique case of a MiNEN with trilineage differentiation: large-cell neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma. The reported patient presented with symptoms of an upper gastrointestinal bleed and was ultimately diagnosed with a MiNEN with trilineage differentiation. This is the first report of this exceedingly rare tumor type to include next-generation sequencing of the 3 separate tumor entities. In addition, we review the current literature and discuss the role of next-generation sequencing in classifying and treating MiNEN tumors.

Keyword

Neuroendocrine neoplasm; Gastric cancer; Precision medicine

MeSH Terms

Adenocarcinoma
Carcinoma, Neuroendocrine
Carcinoma, Squamous Cell
Humans
Precision Medicine
Stomach Neoplasms

Figure

  • Fig. 1 Case pathology. (A) MiNEN with large-cell NEC, SCC, and AC in a collision tumor pattern (H&E, 20× magnification). (B) Synaptophysin immunohistochemical stain showing positive staining of the neuroendocrine component (20× magnification). (C) P63 immunohisotochemical stain showing positive staining of the squamous component (20× magnification). (D) Ki-67 immunohisotochemical stain demonstrating an overall high proliferation index (20× magnification; 152×116 mm [144×144 DPI]).NEC = neuroendocrine carcinoma; SCC = squamous cell carcinoma; AC = adenocarcinoma; H&E = hematoxylin and eosin.

  • Fig. 2 A spatial relationship of the genomic alterations in each histologic component of the gastric MiNEN at our institution.PC = primary clone; NEC = neuroendocrine carcinoma; AC = adenocarcinoma; SCC = squamous cell carcinoma.*Mutations with identified treatment options.


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