Cellular aspects of granulomas.

We investigated granulomas of sarcoidosis and de Quervain's thyroiditis of man as well as experimental granulomas of the rat-peritoneum. Though differing in their cellular composition, they show common features in their organisation. A central zone consisting predominantly of epithelioid cells, epithelioid cell equivalents and macrophages without phagosomes in contact with lymphocytes. An outer zone mainly consisting of large macrophages, rich in phagosomes, dark epithelioid cells, necrotic elements and newly immigrated cells. The outer zone is considered to be a functional transitional area. Many of the newly immigrated monocytes are often binucleate, which we consider to be due to disturbances in the spindle cleavage of mitosis following injury. Ordered multinucleate giant cells (Langhans type) are centrally organised under the influence of centrioles and cytoskeleton. They have one phagocytic pole, one large pluricorpuscular cytocentre and a nuclear pole. The ordered internal structure of these lightly stained giant cells indicates their functional activity. In contrast we consider the darkly stained giant cells to be exhausted elements possibly progressing to coagulative necrosis. Intercellular contacts in granulomas e.g. between macrophages are seen as interdigitations of microvilli with the formation of desmosome-similar junctions. We suppose them to be in part for exchange of information and fixation. Epithelioid cells are characterised by their prominent secretory apparatus as well as by a large centrosphere with radially diverging numerous Golgi dictyosomes. Microtubules, together with microfilaments, are significantly involved in transporting secretory granules towards the periphery of the cell. Degranulation also occurs in co-operation with the various components of the cytoskeleton. Disintegration of the membranes of epithelioid cells leading to necrosis may result from massive degranulation. We suppose the various subtypes of epithelioid cells described by other authors to be various stages of the same but not different types of epithelioid cells.