Giant mitochondria in the alcoholic liver diseases – their identification, frequency and pathologic significance

Abstract

Three types of giant mitochondria were described in hepatocytes, and their ultrastructural features and occurrence in alcoholic liver disease [ALD] were studied. Type 1 mitochondria were spherical, with a paucity of cristae. Type 2 were elongated and had long crystalline insertions. Type 3 were relatively smaller and often bizarre in shape, containing multiple crystalline insertions. Megamitochondria was defined as spheroidal giant mitochondria with a diameter roughly > 1/3 of the hepatocyte nucleus and visible under light microscopy. Type 1 was the most common form of megamitochondria in livers with ALD. Megamitochondria were present in livers of 58 (27.8%) of 209 consecutive patients with ALD, compared with 1 (0.7%) of a series of 145 patients with nonalcoholic liver disease. The frequency and occurrence of megamitochondria varied in different types and/or stages of ALD. Livers with alcoholic foamy degeneration had significantly increased frequency and numbers of megamitochondria compared to other patterns of ALD. The ultrastructural studies showed that hepatocytes containing type 1 mitochondria frequently had other damaged organelles and extensive focal cytoplasmic degradation. Enzyme histochemistry showed the foamy hepatocytes containing type 1 had markedly decreased staining for glucose-6-phosphatase and slightly decreased staining for succinic dehydrogenase activities, while the hepatocytes with type 2 or 3 had normal staining. In general, type 1 giant mitochondria seemed more characteristic of ALD, or conditions that produced similar hepatic morphology. It was particularly seen in alcoholic foamy degeneration and may have been part of decompensation of the hepatocytes, while types 2 and 3 occurred in hepatocytes of alcoholic and nonalcoholic patients and had preserved function.