Heterogeneous histopathologic findings in ECD lesional tissue. Brain biopsy in ECD yielded mostly lamellar fibrotic tissue (A) with only small regions (B) with lipid-laden histiocytes (yellow arrows) and Touton giant cells (blue arrow). (C) Another sample of a CNS lesion demonstrated a florid lymphohistiocytic infiltrate with regions of pale, nonfoamy histiocytes (inset). (D) Reactive astrocytes and Rosenthal fibers were seen in a separate CNS biopsy from the same case. (E) Biopsy of perinephric infiltrate on low power view demonstrates perirenal fat with septa widened by fibrous tissue and scant inflammatory infiltrate. The stranding apparent at low power correlates with the known radiographic appearance. (F) Higher power in this case shows a Touton giant cell but few histiocytes. (G) Pericardial biopsy shows pale and granular histiocytes without foamy appearance. Occasional lymphocytes, plasma cells, and eosinophils are present. (H) Lung biopsy from the same patient taken concurrently demonstrates septal fibrosis with scant cellular infiltrate including histiocytes. Higher power (inset) shows pale (nonfoamy) histiocytes.