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
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.