Heterogeneity of intraepithelial lymphocytes in refractory sprue: potential implications of CD30 expression

Abstract

Background: Refractory sprue is defined as primary or secondary failure to respond to a gluten free diet in patients with coeliac disease-like enteropathy and may signify cryptic or overt enteropathy associated T cell lymphoma.

Aims: To study in detail jejunal morphology and immunophenotypes in patients with refractory sprue in the search for features that might be useful to predict prognosis.

Patients: Seven patients are described, representing all such cases identified in our hospital over a 13 year period.

Methods: Biopsy and/or surgical resection specimens were examined by morphology, immunohistochemistry, including enzymatic and immunofluorescent detection, and molecular biology.

Results: All patients had phenotypically abnormal intraepithelial lymphocytes (IELs) that lacked CD8, T cell receptor alpha beta (or gamma delta), and/or expressed CD30 in addition to variable expression of the natural killer cell receptor CD94. A monoclonal T cell population was present in six cases, data from the seventh being inconclusive. Three patients had overt lymphoma with CD30+ tumour tissue intervening between intact mucosa that contained neoplastic IELs. Intriguingly, CD30+ IELs were observed both a long way away from, and in direct continuity with, the tumours in these patients. Such CD30+ cells were hardly detected in patients without tumours, two of which are in good health several years after the initial diagnosis.

Conclusions: Our data suggest that abnormal IELs in patients with refractory sprue are phenotypically heterogeneous. CD30 expression by these cells may indicate a worse prognosis, including the occurrence of overt lymphoma.

Figure 1

Immunomorphological and genotypic observations in overt enteropathy associated T cell lymphoma (EATL) (A–C, patient No 5; D–F, patient No 6). (A) Detail of ulcerated tumour with CD30+ tumour cells in a surgical resection specimen (original magnification ×200). (B) Detail of epithelium adjacent to CD30+ tumour in (A) (original magnification ×400). Numerous intraepithelial lymphocytes express CD30 (arrows). (C) Occasional intraepithelial lymphocytes express CD30 (arrows) in a jejunal biopsy specimen (original magnification ×400). (D) Detail of ulcerated tumour with CD30+ tumour cells in a surgical resection specimen (original magnification ×100). (E) Villus a long way away from the tumour showing numerous intraepithelial and lamina propria cells (arrows) expressing CD30 (original magnification ×400). (F) Polymerase chain reaction analysis of DNA extracted from tumour and intact mucosa (villi). Samples were undiluted (u), or diluted 1/5 or 1/25; visible bands (arrows) were present in the same position of all samples, indicating that the same T cell clone was present in villi and in the tumour.