Tuberous xanthoma in homozygous type II hyperlipoproteinemia. A histologic, histochemical, and electron microscopical study

Histologic, histochemical, and ultrastructural studies of a tuberous xanthoma from a patient with homozygous type II hyperlipoproteinemia showed that all of the lipid was within histocytic foam cells; no lipid was identified in interstitial regions or in blood vessels. Primitive mesenchymal cells, elongated perivascular and fibroblast like cells, and lysosome filled macrophages were also present with the xanthoma, indicating possible stages in the evolution of dermal mesenchymal cells into mature, cholesterol rich foam cells. Morphologically, the lipid was in 4 different forms: large droplets, which were the dominant form, and membrane bound crystals, concentric lamellar bodies, and ceroid. The paucity of membrane bound lipid forms, relative to the abundant free lipid droplets, indicated that lysosomal digestion was a minor metabolic pathway for the intracellular metabolism of lipid in the xanthoma. Thus, nonlysosomal lipid storage in foam cells is a characteristic tissue response to the underlying metabolic defect in type II hyperlipoproteinemia.