Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T cell lymphoma, coeliac disease, and refractory sprue

Background-Clonal T cell receptor (TCR) gene rearrangements and loss of T c ell antigens such as CD8 and TCR-beta in intraepithelial lymphocytes (IELs) may indicate the development of an enteropathy-type intestinal T cell lymp homa (EITCL) in patients with refractory sprue. Aims-To define the diagnostic value of these markers in duodenal biopsies f rom patients with villous atrophy as a result of various underlying disorde rs. Patients and methods-Duodenal biopsies from eight patients with coeliac dis ease and five patients with villous atrophy caused by defined disorders wer e compared with three patients with refractory sprue evolving into overt EI TCL, two patients with ulcerative jejunitis, and with eight patients with o vert EITCL, for expression of CD3, CD4, CD8, and TCR-beta in IELs using imm unohistochemistry and for clonal TCR-gamma gene rearrangements using polyme rase chain reaction. In addition, biopsies from six consecutive patients wi th refractory sprue of uncertain cause were examined. Results-Clonal TCR-gamma gene rearrangements were found in all resected tum ours of patients with EITCL, in 3/8 duodenal biopsies of patients with EITC L, in 2/2 patients with ulcerative jejunitis, in 2/3 patients with refracto ry sprue evolving into overt EITCL, and in 1/6 patients with refractory spr ue. No rearrangements were found in biopsies from patients with refractory sprue caused by defined disorders or those with coeliac disease. Clonality in duodenal biopsies was associated with an abnormal phenotype of IELs in a ll cases and in all but one case in patients with evidence of underlying co eliac disease. Specificity for detection of an EITCL using immunohistology was 77% for CD8 and for TCR-beta staining, and 100% for detection of a clon al TCR-gamma gene rearrangement. Sensitivity was 62% for staining with CD8 and clonality investigation, while sensitivity reached 100% for TCR-P stain ing in all investigated patients with EITCL. Conclusions-Clonal proliferations of phenotypically abnormal IELs in refrac tory sprue represent an early manifestation of EITCL, for which the term "s prue-like intestinal T cell lymphoma" is proposed. This constellation is al so found in duodenal biopsies from patients with an overt EITCL and is not related to other sprue syndromes, resulting in a high specificity for detec tion of an EITCL or refractory sprue evolving into EITCL. Overt EITCL may d evelop directly from coeliac disease without a precursor lesion (refractory sprue with clonal IELs) being demonstrable in duodenal biopsies or via a " sprue-like intestinal T cell lymphoma". This latter entity is a complicatio n of coeliac disease.