Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features

PLoS One. 2013 Jul 4;8(7):e68343. doi: 10.1371/journal.pone.0068343. Print 2013.

Abstract

Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent, clonal TCRβ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (n = 1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology*
  • Celiac Disease / diagnosis
  • Celiac Disease / immunology
  • Celiac Disease / metabolism
  • Celiac Disease / pathology
  • Diagnosis, Differential
  • Diarrhea / pathology
  • Female
  • Gene Expression / immunology
  • Gene Expression Profiling
  • Humans
  • Immunophenotyping
  • Intestine, Small / immunology
  • Intestine, Small / metabolism
  • Intestine, Small / pathology*
  • Lymphoma, T-Cell, Peripheral / diagnosis
  • Lymphoma, T-Cell, Peripheral / immunology
  • Lymphoma, T-Cell, Peripheral / metabolism
  • Lymphoma, T-Cell, Peripheral / pathology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Weight Loss

Substances

  • Antigens, CD
  • Receptors, Antigen, T-Cell

Grants and funding

The authors have no support or funding to report.