A 64-year-old man with chronic hepatitis B cirrhosis presents with right upper quadrant fullness, anorexia, and 7 kg weight loss. Triphasic CT shows a 6 cm hypervascular mass in segment VII with arterial-phase wash-in and portal/delayed-phase wash-out (LI-RADS 5). Resection histology is shown. The structure marked **A** displays thick trabecular cords (>3 cells thick) with abundant granular eosinophilic cytoplasm, prominent nucleoli, and intracytoplasmic round eosinophilic inclusions consistent with Mallory-Denk bodies. Immunohistochemistry shows HEPPAR-1 and Glypican-3 positivity. Which of the following best describes the composition of the Mallory-Denk bodies seen in this tumor?
A. Aggregates of damaged intermediate filaments (keratins 8/18) cross-linked by p62 and ubiquitin
B. Deposits of hemosiderin and lipofuscin from hepatocellular necrosis
C. Hyaline globules composed of polymerized alpha-1 antitrypsin
D. Crystalline inclusions of bilirubin and conjugated bile salts
Explanation
Why "Aggregates of damaged intermediate filaments (keratins 8/18) cross-linked by p62 and ubiquitin" is right
Mallory-Denk bodies (also called Mallory bodies) are pathognomonic round intracytoplasmic eosinophilic inclusions found in hepatocellular carcinoma and other liver diseases. They are composed of aggregates of damaged intermediate filaments—specifically keratins 8 and 18—that are cross-linked and stabilized by the ubiquitin-binding protein p62 and ubiquitin itself. This is a hallmark histologic feature of HCC and is directly cited in AASLD/BCLC pathology standards for HCC diagnosis.
Why each distractor is wrong
Deposits of hemosiderin and lipofuscin from hepatocellular necrosis: While hemosiderin and lipofuscin can be seen in cirrhotic livers, they are not the composition of Mallory-Denk bodies. Hemosiderin appears as golden-brown granules on H&E and stains with Prussian blue; lipofuscin is a brown pigment of cellular aging. Neither forms the characteristic round eosinophilic inclusions of Mallory bodies.
Crystalline inclusions of bilirubin and conjugated bile salts: Bile plugs (intracanalicular bile) and bilirubin deposits may be present in HCC, but these are not Mallory-Denk bodies. Bile appears as golden-brown material within canaliculi or cytoplasm, not as discrete round eosinophilic inclusions.
Hyaline globules composed of polymerized alpha-1 antitrypsin: Hyaline globules (PAS-D positive) can be seen in HCC and are indeed composed of alpha-1 antitrypsin or other proteins, but they are distinct from Mallory-Denk bodies. Hyaline globules are larger, more irregular, and stain with PAS-D; Mallory bodies are smaller, round, and composed of keratins.
High-YieldNEET PG
Mallory-Denk bodies = keratins 8/18 + p62 + ubiquitin aggregates; pathognomonic for HCC and other liver injury; round eosinophilic inclusions on H&E.
