Diagnosis of intestinal microsporidiosis in patients with AIDS.

Large granular lymphocyte (LGL) leukaemia is an uncommon disorder characterised by clonal expansion of large granular lymphocyte subsets in bone marrow, spleen, and peripheral blood. ' We describe an analysis of the spleen from a 56 year old woman with LGL leukaemia which shows a pattern of LGL accumulation that seems to be characteristic of this disorder and therefore of potential diagnostic value. The presenting clinical features described previously2 included anaemiahaemoglobin 9 4 g/dl and a white cell count 15-1 x 109/l with a differential of neutrophils 14%, monocytes 4%, lymphocytes 82% (95% large granular type). The lymphocytes showed a CD2 + CD3 + CD8 + Leu7 + CD llb CD16 surface antigen phenotype. Within 12 months the haemoglobin concentration fell to 6-6 g/dl and the patient had to be transfused regularly. Her spleen was removed which resulted in an initial improvement of the anaemia followed by relapse (haemoglobin 7 0 g/dl, white cell count 70 x 109/1). Subsequent treatment with cyclophosphamide (100 mg/day) improved and stabilised the haematological indices (haemoglobin 11 5 g/dl, white cell count 8-0 x 109/1). The spleen weighed 520 g, the cut surface showed even distribution of multiple, pale nodules about 1 mm in diameter. Microscopically the splenic architecture was preserved, the white pulp was increased, and as well as apparently normal peri-arteriolar lymphocyte cuffs, there were many germinal follicles. The red pulp showed a homogeneous infiltration of sinusoids and cords by small, apparently mature lymphocytes. The few previous reports of the morphological detail ofthe spleen in LGL leukaemia also noted red pulp infiltration by lymphocytes, together with white pulp preservation, including prominent germinal follicles,"5 suggesting that this histological pattern is highly characteristic. Comparison with the splenic histology in other lymphoproliferative disorders indicates clear differences that may be of value in the differential diagnosis: in B cell chronic lymphocytic leukaemia and well differentiated B cell lymphomas the white pulp is usually infiltrated, whereas in conditions with red pulp infiltration-for example, hairy cell leukaemia-usually atrophy or obliteration of the white pulp occurs. The immunohistochemical staining reactions of the various splenic zones are shown in the table. The normal white pulp populations of small lymphocytes were preserved, there was no white pulp infiltration by LGL phenotype cells. The phenotype of lymphocytes infiltrating the red pulp was characteristic of LGLs, although it differed from the circulating cells by the possession of the CD16 marker corresponding to the IgFc gamma receptor. A similar difference in IgFc gamma receptor expression between splenic and blood LGLs has also been noted in a previous case.5 The reason for this discrepancy is unclear but is unlikely to be due to selective accumulation of CD16+ cells in the spleen as we were not able to show any increase in circulating CD16 + cells after removal of the spleen. Although most cases of LGL leukaemia are now diagnosed by circulating cell surface antigens, some may still be diagnosed only when the spleen is removed, as at presentation 50% have splenomegaly and 30% do not have a lymphocytosis. ' Recognition of the characteristic histological pattern of splenic disease described here should expedite confirmation of the diagnosis by the appropriate lymphocyte marker studies.