The ultrastructural features of developing Kveim test granulomas

The Kveim test provides a useful model for the ultrastructural study of developing epithelioid cell granulomas in man. We present a controlled prospective study in which 140 patients with possible sarcoidosis had two simultaneous Kveim tests, one being biopsed at a varying interval and the other at the usual 28 days: 52 patients showed a positive test. Controls were provided by the 88 negative tests, Kveim biopsis from 12 healthy subjects, and biopsies of normal spleen injection sites in a further 12 sarcoid patients. In all three groups the initial response (3 to 5 days) was macrophage influx. From 8 to 10 days, in developing positive tests only, mononuclear cells with abundant rough endoplasmic reticulum appeared. 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 are identical to those seen in exocrine cells. Mast cells are not involved in the development of granulomas.