Gastric carcinoma with lymphoid stroma

Editorial Board Member: Aaron R. Huber, D.O.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Carolina Martinez Ciarpaglini, M.D., Ph.D.

Last author update: 12 July 2021
Last staff update: 13 October 2023

Copyright: 2003-2024,, Inc.

PubMed Search: gastric carcinoma with lymphoid stroma [TI]

Carolina Martinez Ciarpaglini, M.D., Ph.D.
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Cite this page: Martinez-Ciarpaglini C. Gastric carcinoma with lymphoid stroma. website. Accessed February 22nd, 2024.
Definition / general
  • Gastric carcinoma composed of small nests of cancer cells broadly distributed in a background of dense and prominent lymphoid stroma, histologicically similar to nasopharyngeal carcinoma (Arch Pathol Lab Med 2008;132:706)
Essential features
  • Infrequent subtype of gastric cancer composed of small trabeculae and nests of epithelial cells embedded in a dense lymphoid infiltrate reminiscent of lymphoid tissue
  • Strongly associated with Epstein-Barr virus (EBV) infection and microsatellite instability (mutually exclusive)
  • PDL1 is usually overexpressed, making these tumors prone to immune checkpoint blockade therapy
  • Lymphoepithelioma-like carcinoma
  • Medullary carcinoma
  • Undifferentiated carcinoma with lymphoid stroma
ICD coding
  • ICD-O: 8140/3 - adenocarcinoma, NOS
Radiology description
  • CT scan: well circumscribed mass with a large thickness to length ratio with the low density stripe of the normal gastric wall abruptly terminated at the edge of the lesion (Medicine (Baltimore) 2019;98:e14839)
Prognostic factors
Case reports
  • Localized cases are prone to curative submucosal dissection (World J Gastroenterol 2014;20:1365)
  • High sensitivity to immune checkpoint blockade therapy with pembrolizumab (anti-PD1 antibody) has been observed in advanced EBV and microsatellite instability gastric cancer (overall response rate of 85.7% in microsatellite instability and overall response rate of 100% in EBV positive cases) (Nat Med 2018;24:1449)
Gross description
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Carolina Martinez-Ciarpaglini, M.D., Ph.D.

Dense lymphoid infiltrate

Trabecular pattern

Tumor cells (high power)

Primitive tubular pattern

EBER expression

Cytokeratin expresion

T cell infiltrate (CD3)

Positive stains
Negative stains
Molecular / cytogenetics description
  • For microsatellite instability evaluation in gastric cancer, the immunohistochemical study of MMR proteins and PCR show an excellent concordance (ESMO Open 2019;4:e000470)
  • EBV positive tumors show the higher prevalence of DNA hypermethylation among all gastric tumors (Nature 2014;513:202)
  • The main molecular alterations in EBV associated cases include hypermethylation of the promoter region of the gene CDKN2A (p16INK4A) and mutation in phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) in about 5 - 10% (Oncotarget 2016;7:32925, Nature 2014;513:202, ESMO Open 2019;4:e000470)
  • MLH1 hypermethylation is characteristic of microsatellite instability associated cases (Nature 2014;513:202)
  • Microsatellite instability cases show high tumor mutation burden and KRAS alterations (56%) (Am J Surg Pathol 2018;42:453)
Sample pathology report
  • Gastric mass, upper body, endoscopic biopsy:
    • Gastric carcinoma with lymphoid stroma
    • In situ hybridization study for EBER is diffusely positive in all tumor cells
Differential diagnosis
Board review style question #1

    The image shows a gastric endoscopic biopsy of a well circumscribed tumor located in the antrum. Epstein-Barr in situ hybridization study was completely negative. Which molecular alteration is probably present in this lesion?

  1. BRAF mutation
  2. HER2 overexpression
  3. Microsatellite instability
  4. MYC translocation
Board review style question #2
    Which of the following proteins is frequently overexpressed in gastric carcinoma with lymphoid stroma?

  1. HER2
  2. p16
  3. p53
  4. PDL1
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