Anatomic Pathology: Liver Pathology

234) The liver biopsy specimen shown in the image is MOST likely to come from which of the following patients?

• Microvesicular (small droplet) steatosis is defined as the accumulation of many small lipid vacuoles within the cytoplasm of hepatocytes surrounding a centrally located nucleus.

• The histologic differential diagnosis of microvesicular steatosis includes inherited and acquired conditions and exposures to hepatotoxic agents that cause serious impairment of mitochondrial beta oxidation of fatty acids. Examples of drugs that may result in microvesicular steatosis include valproic acid, nucleoside reverse transcriptase inhibitors, and tetracycline and its derivatives.

• Microvesicular steatosis may be associated with liver failure, hypoglycemia, and encephalopathy.

• The classic trio of conditions associated with microvesicular steatosis includes Reye syndrome, acute fatty liver of pregnancy (third trimester), and tetracycline toxicity. Oil red O staining of frozen liver biopsy material is occasionally necessary for exclusion of acute fatty liver of pregnancy to confirm this diagnosis.

• The use of terms such as macrosteatosis and microsteatosis should be avoided because they represent a bowdlerization of the appropriate terms macrovesicular steatosis and microvesicular steatosis.

Differential Diagnosis of Steatosis
Macrovesicular Steatosis Microvesicular Steatosis
Ethanol Antiretroviral agents
Obesity Acute fatty liver of pregnancy
Diabetes Reye syndrome
Hyperlipidemia Tetracycline toxicity
Metabolic syndrome/insulin resistance Alcoholic foamy degeneration
Corticosteroid therapy Valproic acid toxicity
Burt AD, Mutton A, Day CP: Diagnosis and interpretation of steatosis and steatohepatitis. Semin Diagn Pathol 1998;15(4):246-258.

Labbe G, Pessayre D, Fromenty B: Drug-induced liver injury through mitochondrial dysfunction: mechanisms and detection during preclinical safety studies. Fundam Clin Pharmacol 2008;22(4):335-353.

Núñez M: Clinical syndromes and consequences of antiretroviral-related hepatotoxicity. Hepatology 2010;52(3):1143-1155.

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