Prognostic Significance of Stromal and Intraepithelial Tumor-Infiltrating Lymphocytes in Small Intestinal Adenocarcinoma

Am J Clin Pathol. 2020 Jan 1;153(1):105-118. doi: 10.1093/ajcp/aqz136.


Objectives: Assessment of tumor-infiltrating lymphocytes (TILs) may predict the prognosis and therapeutic benefit of immunotherapy in small intestinal adenocarcinoma (SIAC) patients.

Methods: TILs were evaluated in 231 surgically resected SIACs and compared with microsatellite instability (MSI) and clinicopathologic variables. The average number of intraepithelial TILs (iTILs) and the average density of stromal TILs (sTILs) were calculated separately.

Results: High iTIL count (≥2 per high-power field) was associated with MSI-high, whereas high sTIL density (≥20% on ×200 magnification) was not. High iTIL count and high sTIL density were related to distal tumor location, medullary carcinoma, high Crohn-like lymphoid reaction counts, and fewer pancreatic invasions. SIAC patients with high iTIL count or high sTIL density had better survival than those with low values. On multivariate analysis, MSI, high sTIL density, proximal locations, lower N category, and absence of lymphovascular invasions and retroperitoneal seeding were the best independent prognostic predictors.

Conclusions: High sTIL density can be used as a prognostic indicator and high iTIL count may provide a basis for the clinical use of targeted immunotherapy in SIAC patients.

Keywords: Adenocarcinoma; Biomarkers; Lymphocyte; Medullary; Microsatellite instability; Prognosis; Small intestine; Tumor-infiltrating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Female
  • Humans
  • Immunity, Cellular*
  • Intestinal Neoplasms / diagnosis
  • Intestinal Neoplasms / pathology*
  • Intestinal Neoplasms / surgery
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Prognosis
  • Survival Analysis
  • Young Adult


  • Biomarkers, Tumor