Mucosal intraepithelial T-lymphocytes in refractory celiac disease: a neoplastic population with a variable CD8 phenotype

Am J Surg Pathol. 2008 May;32(5):744-51. doi: 10.1097/PAS.0b013e318159b478.


Celiac disease (CD) is characterized by villous atrophy and an increase in intraepithelial lymphocytes (IEL). The IEL usually exhibit a suppressor/cytotoxic phenotype (CD3 and CD8) and display a polyclonal profile for T-cell receptor (TCR) rearrangement as opposed to the monoclonality of refractory CD (RCD) with CD8 IEL. A complication of CD is the loss of response to a gluten-free diet called RCD that may progress to an enteropathy-associated T-cell lymphoma. We reviewed 20 uncomplicated CD and 23 complicated CD (19 RCD and 4 diagnosed at the same time as enteropathy-associated T-cell lymphoma). In complicated CD, the IEL phenotype was CD8 in 9 cases and CD8 in 14 cases. In 100% of cases, IEL showed a monoclonal TCR rearrangement. All the 9 CD8 complicated CD exhibited a monoclonal TCR rearrangement and 3 of them were associated with a T-cell lymphoma (2 at the same time as CD and 1 after 43-mo follow-up) and bore the same monoclonal rearrangement in IEL and in lymphoma. Interestingly, the 13 cases (100%) of CD with a CD8 phenotype were also found monoclonal and 2 of them were associated with a T-cell lymphoma diagnosed at the same time as CD and exhibiting the same rearrangement in IEL and in lymphoma. An aberrant CD3 CD8 IEL phenotype is a good criterion for RCD diagnosis. However, cases with a normal CD3 CD8 IEL phenotype may correspond to RCD. In such cases, we suggest that molecular analysis of TCR-gamma genes is a useful method for identifying cases with RCD.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • Celiac Disease / genetics
  • Celiac Disease / immunology
  • Celiac Disease / pathology*
  • Clone Cells
  • DNA / analysis
  • Female
  • Genes, T-Cell Receptor beta / genetics
  • Genes, T-Cell Receptor beta / immunology
  • Humans
  • Immunoenzyme Techniques
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology*
  • Intestinal Neoplasms / genetics
  • Intestinal Neoplasms / immunology
  • Intestinal Neoplasms / pathology*
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*


  • Biomarkers, Tumor
  • CD3 Complex
  • CD8 Antigens
  • DNA