Mallory body
Summary
Mallory bodies (Mallory-Denk bodies) are intracytoplasmic eosinophilic inclusions found in hepatocytes, composed of damaged keratin intermediate filaments aggregated with ubiquitin. They are classically associated with alcoholic liver disease but are also seen in other hepatic conditions.
Detail
Mallory-Denk bodies are eosinophilic, ropey-appearing cytoplasmic inclusions seen on H&E staining of hepatocytes. Ultrastructurally, they consist of aggregated, hyperphosphorylated cytokeratin intermediate filaments (mainly keratin 8 and 18) that are ubiquitinated and cross-linked, reflecting a failure of the proteasome-ubiquitin degradation pathway to clear damaged cytoskeletal proteins. They are most classically associated with alcoholic hepatitis/alcoholic steatohepatitis, where they are found alongside hepatocyte ballooning degeneration, neutrophilic infiltration, and steatosis. However, they are not pathognomonic for alcohol use and can also be seen in non-alcoholic steatohepatitis (NASH), Wilson disease, primary biliary cholangitis, chronic cholestatic disorders, and hepatocellular carcinoma. Clinically, their presence supports a diagnosis of steatohepatitis (alcoholic or non-alcoholic) when correlated with clinical history and other histologic findings. They are a marker of hepatocyte injury but do not have direct pathogenic significance on their own—rather, they indicate a shared pathway of cytoskeletal damage response across multiple liver diseases. On Step 1/Step 2, Mallory bodies are a classic buzzword for alcoholic liver disease and appear frequently in vignette-based questions about chronic alcohol use presenting with hepatomegaly, elevated AST:ALT ratio (>2:1), and steatohepatitis on biopsy.
Sources
- Robbins and Cotran Pathologic Basis of Disease, 10th ed.
- Goljan Rapid Review Pathology
- First Aid for the USMLE Step 1
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