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PA24.9 | Liver Disease & Tumour Morphology — Practical — SDL Guide (Part 3)

The 4-Panel Comparison: Reading Composite Specimens

A 2×2 histology comparison diagram of macrovesicular steatosis, cirrhosis, alcoholic hepatitis, and hepatocellular carcinoma with key diagnostic features labelled. — **Panel A:** Macrovesicular steatosis: preserved hepatic plates, large clear fat vacuoles, peripheral hepatocyte nuclei.. **Panel B:** Cirrhosis: regenerative nodules, blue fibrous septa on Masson trichrome stain, absent central vein.. **Panel C:** Alcoholic hepatitis: ballooned hepatocytes, Mallory-Denk bodies, neutrophilic satellitosis.. **Panel D:** Hepatocellular carcinoma: thick neoplastic trabeculae, bile plugs, nuclear pleomorphism..

The following composite image shows four liver conditions side-by-side in a 2×2 grid. Use it to practise rapid pattern recognition before attempting the final quiz.

A labeled 2×2 histology comparison grid showing macrovesicular steatosis, cirrhosis, alcoholic hepatitis, and hepatocellular carcinoma. — **Panel A:** Macrovesicular steatosis: clear fat vacuoles, peripherally displaced nuclei, compressed hepatocyte cytoplasm, hepatocyte plates.. **Panel B:** Cirrhosis on Masson trichrome: regenerative nodules, blue fibrous septa, distorted architecture, absent central veins.. **Panel C:** Alcoholic hepatitis: Mallory-Denk bodies, neutrophilic satellitosis, ballooned hepatocytes, inflammatory infiltrate.. **Panel D:** Hepatocellular carcinoma: thick trabeculae, bile plugs, pleomorphic nuclei, malignant hepatocytes and sinusoid-like spaces..

For each panel, apply the reading framework: architecture → hepatocyte changes → inflammation/fibrosis → diagnosis. Note how architecture is the first discriminator:
- Panels A and C preserve lobular architecture (disease is ongoing but not yet restructured).
- Panel B has lost it entirely — no central vein, only nodules.
- Panel D shows an entirely different architecture: neoplastic trabeculae replacing normal plates.

Hepatocellular Carcinoma (HCC)

Four-panel medical diagram of hepatocellular carcinoma showing gross liver morphology, trabecular histology, microscopic diagnostic hallmarks, and distinction from metastatic adenocarcinoma. — **Panel A:** Gross cirrhotic liver with solitary tan-green HCC mass, multifocal satellite nodules, haemorrhage, necrosis, and portal vein tumour thrombus.. **Panel B:** H&E-style 20x histology showing trabecular growth pattern with tumour trabeculae 3-4 cells thick, polygonal hepatocyte-like cells, and endothelial-lined sinusoids.. **Panel C:** Microscopic hallmarks including canalicular bile plug, nuclear pleomorphism, hyperchromasia, prominent nucleolus, multinucleate giant cell, and vascular invasion.. **Panel D:** Comparison of HCC with metastatic adenocarcinoma: canalicular bile and polygonal hepatocyte-like cells versus gland formation, mucin, and absence of canalicular bile..

HCC is the most common primary liver malignancy; ~85% arise in cirrhotic livers (HBV, HCV, alcohol, NAFLD, haemochromatosis).

Gross:
- Solitary large mass, or multifocal nodules on a cirrhotic background.
- Cut surface: tan-green (bile-producing), haemorrhagic, necrotic.
- Portal vein tumour thrombus — a naked-eye clue to vascular invasion.

Microscopic hallmarks:
1. Trabecular pattern — Tumour cells arranged in trabeculae (plates) 2-20 cells thick, lined by endothelial-like sinusoids. The most common HCC pattern (>80%).
2. Bile production — Bile plugs (green canalicular deposits) within tumour trabeculae. Present in ~50%; pathognomonic of hepatocellular (not cholangiocarcinoma or metastasis) origin.
3. Cellular atypia — Nuclear pleomorphism, hyperchromasia, prominent nucleoli, multinucleate giant cells; loss of nuclear:cytoplasmic ratio regularity.
4. Vascular (sinusoidal) invasion — Tumour cells within vascular channels; associated with satellite nodules and portal vein thrombus.

Growth patterns beyond trabecular: acinar (pseudoglandular, mimics adenocarcinoma), solid/compact, and scirrhous (fibrous stroma).

Distinguishing HCC from metastatic adenocarcinoma: HCC has canalicular bile (not mucin), polygonal cells resembling hepatocytes, and lacks gland formation. IHC: HepPar-1, Arginase-1, GPC3 positive in HCC.

Three-panel educational H&E histology diagram of hepatocellular carcinoma showing thick tumour trabeculae, sinusoidal spaces, bile plug, nuclear pleomorphism, and prominent nucleoli. — **Panel A:** H&E 20x overview of hepatocellular carcinoma showing trabecular growth pattern, tumour trabeculae 3-4 cells thick, sinusoidal spaces, bile plug, nuclear pleomorphism, and prominent nucleoli.. **Panel B:** Magnified trabecular architecture showing thick tumour trabecula, sinusoidal space, and endothelial-lined channel.. **Panel C:** Magnified cytological detail showing nuclear pleomorphism, prominent nucleolus, mitotic figure, eosinophilic cytoplasm, and bile plug..

SELF-CHECK

A liver biopsy from a 60-year-old man with known HCV cirrhosis shows a mass composed of polygonal cells with prominent nucleoli arranged in trabeculae 4-5 cells thick, with green canalicular deposits between tumour cells. Which feature is MOST specific for hepatocellular (rather than cholangiocarcinoma or metastatic) origin?

A. Nuclear pleomorphism and prominent nucleoli

B. Polygonal cell shape

C. Canalicular bile (bile plugs) within tumour trabeculae

D. Vascular invasion

Reveal Answer

Answer: C. Canalicular bile (bile plugs) within tumour trabeculae

Bile production is the most specific marker of hepatocellular differentiation. Bile plugs (green canalicular deposits) represent actual bile secretion by tumour cells — only hepatocytes and HCC can produce bile, not biliary epithelial cells (cholangiocarcinoma) or metastatic adenocarcinoma. Nuclear pleomorphism (A) and vascular invasion (D) are features of malignancy in general. Polygonal shape (B) is a helpful clue but not specific, since some metastases mimic hepatocyte morphology.

Differential Diagnosis at a Glance

A six-panel schematic comparison of liver histology in steatosis, acute hepatitis, chronic hepatitis, alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma. — **Panel A:** Steatosis: preserved architecture, macrovesicular fat vacuoles, peripheral hepatocyte nucleus, minimal inflammation. **Panel B:** Acute hepatitis: preserved architecture, ballooned hepatocytes, Councilman bodies, lobular inflammation, spotty necrosis. **Panel C:** Chronic hepatitis: portal inflammation, interface hepatitis, variable fibrosis, ground-glass hepatocytes, ballooning. **Panel D:** Alcoholic hepatitis: Mallory-Denk bodies, ballooned hepatocytes, neutrophilic satellitosis, steatosis, pericellular fibrosis. **Panel E:** Cirrhosis: regenerative nodules, bridging fibrosis, lost normal architecture, distorted sinusoids, chronic inflammation. **Panel F:** Hepatocellular carcinoma: thick trabeculae, atypical hepatocytes, enlarged hyperchromatic nuclei, unpaired arteries, bile plugs.

A quick-reference comparison across all six conditions:

Feature	Steatosis	Acute Hepatitis	Chronic Hepatitis	Alcoholic Hepatitis	Cirrhosis	HCC
Architecture	Preserved	Preserved	Preserved → disrupted	Preserved	Lost (nodular)	Neoplastic
Key hepatocyte change	Fat vacuoles, peripheral nucleus	Ballooning, Councilman bodies	Ground-glass (HBV), ballooning	Mallory-Denk bodies, ballooning	Regenerative plates	Thick trabeculae, atypia
Inflammation	Absent/minimal	Lobular lymphocytes	Portal lymphocytes, interface	Neutrophils (satellitosis)	Variable	Absent/mild
Fibrosis	Absent	Absent	Portal → bridging	Perivenular (zone 3)	Diffuse septal	Absent/desmoplastic
Specific marker	Lipid on Oil Red O	Councilman body	Ground-glass on orcein	Mallory-Denk bodies	Trichrome septa, reticulin collapse	Bile plugs, HepPar-1

Use this table during revision. In practicals, the diagnosis is usually reached after columns 1-4 of the reading framework.