title: Small intestinal CD4+ T-cell lymphoma is a heterogenous entity with common pathology features.
abstract: OBJECTIVE
  Little is known about intestinal CD4+ T-cell lymphoma; this rare malignancy is misdiagnosed frequently. We evaluated diagnostic criteria and factors that might affect its development and outcome.
  
  
  METHODS
  In a retrospective analysis, we analyzed medical records and intestinal specimens from 10 patients diagnosed with intestinal CD4+ T-cell lymphoma among 115 consecutive patients examined for severe enteropathy with villous atrophy. Samples were analyzed by histology, flow cytometry, and comparative genomic hybridization.
  
  
  RESULTS
  Small-intestine epithelial and lamina propria tissues from patients who presented with chronic diarrhea and malnutrition had variable levels of infiltration of CD3+ CD4+ T cells. Flow cytometry showed a high frequency of CD4+ intraepithelial cells, which frequently expressed a specific Vβ chain. T-cell receptor β clonality was confirmed by DNA sequencing. Two patients had HLA and serology results compatible with celiac disease and autoimmune enteropathy, respectively. Two patients were found to have antibodies against human T-cell leukemia virus and 2 patients had signs of a recent infection with the herpes viruses. Comparative genomic hybridization analyses showed heterogeneous chromosomal abnormalities. Symptoms were reduced in patients treated with steroids (n = 5), but not in patients given purine analogues or chemotherapy. Antibodies against CD52 produced clinical and histologic responses in 2 of 2 patients, whereas severe adverse effects developed in 1 patient. At the latest follow-up evaluation, all patients were alive.
  
  
  CONCLUSIONS
  There is much heterogeneity in the onset and genetic features of intestinal CD4+ T-cell lymphomas, despite their common presentation as indolent lymphoproliferations of the intestinal mucosa. Patients should be treated with steroids, and possibly antibodies against CD52 (for the most aggressive forms of this disorder).
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Gastroenterology Department, Hôpital Européen Georges Pompidou Assistance Publique des Hôpitaux de Paris, Paris, France; Inserm U989, Paris, France; Institute Imagine, Paris, France. Electronic address: georgia.malamut@egp.aphp.fr.
authors: Georgia
authors: G
authors: Malamut
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Inserm U989, Paris, France; Institute Imagine, Paris, France.
authors: Bertrand
authors: B
authors: Meresse
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Cytogenetic Department, Hôpital Necker Enfants Malades Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Sophie
authors: S
authors: Kaltenbach
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Biological Hematology Department, Hôpital Necker Enfants Malades Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Coralie
authors: C
authors: Derrieux
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Pathology Department, Hôpital Necker Enfants Malades Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Virginie
authors: V
authors: Verkarre
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Biological Hematology Department, Hôpital Necker Enfants Malades Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Elizabeth
authors: E
authors: Macintyre
authors: Gastroenterology Department, Hôpital Saint-Antoine Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Agnès
authors: A
authors: Ruskone-Fourmestraux
authors: Pathology Department, Hôpital Saint-Antoine Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Bettina
authors: B
authors: Fabiani
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Cytogenetic Department, Hôpital Necker Enfants Malades Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Isabelle
authors: I
authors: Radford-Weiss
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Pathology Department, Hôpital Necker Enfants Malades Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Nicole
authors: N
authors: Brousse
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Institute Imagine, Paris, France; Hematology Department, Hôpital Necker Enfants Malades Assistance Publique des Hôpitaux de Paris, Paris, France.
authors: Olivier
authors: O
authors: Hermine
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Inserm U989, Paris, France; Institute Imagine, Paris, France.
authors: Nadine
authors: N
authors: Cerf-Bensussan
authors: Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Gastroenterology Department, Hôpital Européen Georges Pompidou Assistance Publique des Hôpitaux de Paris, Paris, France; Inserm U989, Paris, France; Institute Imagine, Paris, France.
authors: Christophe
authors: C
authors: Cellier
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D005434:Flow Cytometry; D006651:Histocytochemistry; D006801:Humans; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000209:etiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D012189:Retrospective Studies; D055815:Young Adult
keywords: Blood; HSV; HTLV; Lymphocyte; Treatment