title: Refractory sprue syndrome with clonal intraepithelial lymphocytes evolving into overt enteropathy-type intestinal T-cell lymphoma.
abstract: BACKGROUND
  Recently, patients with refractory sprue have been shown to contain a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes in their intestine. Whether this signifies early enteropathy-type intestinal T-cell lymphoma (EITCL) or a reactive condition is not clear. We report on a patient presenting with the findings of refractory sprue who subsequently developed overt EITCL.
  
  
  METHODS
  Duodenal biopsies from 1997 (refractory sprue) and duodenal and jejunal biopsies from 1998 (intestinal T-cell lymphoma) were compared by immunohistochemistry and PCR for the detection of T-cell receptor (TCR)-gamma gene rearrangements. Clonal PCR products were sequenced.
  
  
  RESULTS
  The duodenal biopsies from both 1997 and 1998 and the jejunal tumor biopsy showed villus atrophy and an increase of intraepithelial lymphocytes with an abnormal immunophenotype (CD3+, CD4-, CD8- and TCR-beta-). In all duodenal specimens including the one from 1997, and the jenunal tumor biopsy, an identical clonal amplificate was detected by enzymatic amplification of the TCR-gamma gene.
  
  
  CONCLUSIONS
  These data suggest that refractory sprue containing a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes may represent an early manifestation of EITCL. The detection of immunohistochemical negativity for several antigens normally found on intraepithelial lymphocytes such as CD8 or the TCR-beta chain in combination with clonal T-cell populations by PCR may be helpful in identifying refractory sprue with a malignant transformation.
authors.affiliation: Department of Gastroenterology and Infectious Diseases, Klinikum Benjamin Franklin, Free University of Berlin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Daum
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: D
authors.initials: D
authors.lastname: Weiss
authors.forename: M
authors.initials: M
authors.lastname: Peters
authors.forename: B
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: F
authors.initials: F
authors.lastname: Schäper
authors.forename: H
authors.initials: H
authors.lastname: Stein
authors.forename: E O
authors.initials: EO
authors.lastname: Riecken
authors.forename: H
authors.initials: H
authors.lastname: Foss
mesh_terms: D017252:CD3 Complex / Q000032:analysis; D002446:Celiac Disease / Q000150:complications* / Q000276:immunology; D004386:Duodenum / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000276:immunology; D007583:Jejunum / Q000473:pathology; D016131:Lymphocyte Subsets; D016399:Lymphoma, T-Cell / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000145:classification
chemical_list: D017252:CD3 Complex