The ultrastructural features of developing epithelioid cell granulomas in man

The Kveim test provides a useful model for the ultrastructural study of developing epithelioid cell granulomas in man. This study was a controlled prospective investigation in which 78 patients with possible sarcoidosis had two simultaneous Kveim tests, one being biopsied at a varying interval and the other at 28 days; 40 patients showed a positive test. Controls were provided by the 38 negative tests, Kveim biopsies from 12 healthy subjects, and biopsies of normal spleen injection sites in a further 12 sarcoid patients. Kveim biopsies were also taken at a varying interval in a similar fashion for immunocytochemistry from a further 21 patients; 18 of these showed a positive test. In all three groups the initial response (3-5 days) was macrophage influx. Delayed hypersensitivity appeared not to be a feature of developing positive Kveim tests. From 8 to 10 days, in developing positive tests only, mononuclear cells with abundant rough endoplasmic reticulum appeared. A proportion of these cells were precursors of epithelioid cells; others showed no further differentiation. Evidence of phagocytosis declined with time. Mature epithelioid cells were seen at 12 to 14 days, when lymphocyte numbers and lymphocyte-histiocyte interactions were at a maximum. Epithelioid cells showed marked secretory activity; the ultrastructural features of the developing epithelioid cell vacuoles were identical to those seen in exocrine cells. Epithelioid cells increased in size with time; epithelioid cells from sarcoid granulomas were larger than those from Kveim test granulomas. There were two morphological populations of multinucleated giant cell in granulomas; one contained large numbers of epithelioid cell vacuoles, the other contained macrophage-type lysosomal vacuoles. Mast cells appeared not to be involved in the development of granulomas. Monoclonal antibodies were used to study the distribution of cell types and vascular structure of granulomas. Immunocytochemistry at an electron microscopic level was also performed.