Distinctive histopathological features that support a diagnosis of cholesterol ester storage disease in liver biopsy specimens

Hůlková H & Elleder M (2012) Histopathology 60, 1107–1113 Distinctive histopathological features that support a diagnosis of cholesterol ester storage disease in liver biopsy specimens Aims: To identify reliable criteria with which to improve the diagnosis of lysosomal acid lipase (LAL) deficiency of the cholesterol ester storage disease (CESD) type in liver biopsies. Methods and results: We analysed a series of 16 liver biopsies of LAL deficiency of the CESD type confirmed by enzyme testing and DNA sequencing. The biopsy appearances were compared with those of biopsies of other causes of fatty liver. A predominantly microvesicular steatosis in CESD patients could not be reliably distinguished from other causes of fatty liver with cytosolic lipid accumulation in fixed paraffin‐embedded tissues routinely stained with haematoxylin and eosin. The presence of luminal (cathepsin D) and membrane lysosomal markers [lysosomal‐associated membrane protein (LAMP)1, LAMP2, and lysosomal integral membrane protein 2] around the lipid vacuoles facilitated the diagnosis of CESD in fixed paraffin‐embedded material. Additional diagnostic clues included autofluorescent detection of ceroid induction in storage macrophages and the absence of lipopigment in hepatocytes. Stored liquid crystals of cholesteryl esters, which are associated with Maltese cross‐type birefringence, were best appreciated in unfixed biopsy samples. Conclusions: The pathological diagnosis of CESD requires a high index of suspicion, and can be rapidly and effectively appreciated at the light microscopy level, even in routine fixed paraffin‐embedded liver samples with immuohistochemical staining for lysosomal markers.