The clinicopathological features of extensive small intestinal CD4 T cell infiltration

Abstract

Methods: Four patients with clinicopathological features suggesting a new distinct entity defining extensive small intestinal CD4 T cell infiltration were observed.

Results: All four patients presented with chronic diarrhoea, malabsorption, and weight loss. Biopsy specimens of the small intestine disclosed extensive and diffuse infiltration of the lamina propria by pleomorphic small T lymphocytes, which were positive for CD3, CD4, CD5, and the beta chain of T cell receptor in all three cases studied and negative for CD103 in all three cases studied. It is notable that, in all invaded areas, the infiltrating cells showed no histological change throughout the whole evolution. In three patients, lymphocyte proliferation was monoclonal and there was extraintestinal involvement. In one patient, lymphoproliferation was oligoclonal and confined to the small intestine. In all four patients, there was no evidence of coeliac disease. Although none of the four patients responded to single or multiple drug chemotherapy, median survival was five years.

Conclusion: Extensive small intestinal CD4 T cell infiltration is a rare entity, distinct from coeliac disease and associated with prolonged survival.

Figure 1

Surgical jejunal resection showing dense lymphoid infiltrate of mucosa and superficial part of submucosa and some degree of villous atrophy. There is no evidence of coeliac disease (patient 1). Haematoxylin-eosin G stain; original magnification × 75.

Figure 2

Surgical jejunal resection at a higher magnification, in which tumour cells appear as small pleomorphic cells with irregularly shaped indented nuclei (patient 2). Haematoxylin-eosin stain; original magnification × 3000.

Figure 3

Surgical jejunal resection from patient 2. Mucosal pleomorphic small T cell infiltrate, associated with a non-caseating granuloma, and extending into the muscularis mucosa. Haematoxylin-eosin stain; original magnification × 750.

Figure 4

Surgical jejunal resection from patient 3. Mucosal pleomorphic small T cell infiltrate is not associated with intraepithelial lymphocytosis. Enterocytes appear normal. Haematoxylin-eosin stain; original magnification × 750.

Figure 5

Immunohistochemical examination of a frozen jejunal biopsy specimen from patient 4 showing a dense intramucosal CD4+ T cell infiltrate. Anti-CD4 antibody-diaminobenzidine-peroxidase stain; original magnification × 300.

Figure 6

In situ hybridization on duodenojejunal biopsy specimen from patient 4 showing total villous atrophy and positivity of some cells within the lamina propria. EBER probe; original magnification × 300.