Question

Difficulty: Very hardPathology and Biopsy Interpretation

A hepatobiliary tumor board is reviewing the pathologic and immunohistochemical findings of five distinct hepatic lesions to finalize their diagnoses. Which definitive pathologic diagnosis best matches each histopathologic description and biomarker profile?

  • A biopsy of an unencapsulated hepatic mass in a young woman reveals bland hepatocytes in plates 1-2 cells thick, completely lacking portal tracts; immunohistochemistry demonstrates loss of liver fatty acid-binding protein (LFABP) expression.HNF1A-inactivated Hepatocellular Adenoma
  • A biopsy of a circumscribed hepatic mass reveals benign-appearing hepatocytes compartmentalized by fibrous septa containing malformed arteries and ductular reactions; immunohistochemistry shows a classic 'map-like' pattern of glutamine synthetase positivity.Focal Nodular Hyperplasia
  • A biopsy of a large mass in a cirrhotic liver shows thickened hepatocyte trabeculae (>3>3 cells thick) with nuclear atypia; immunohistochemistry is strongly positive for arginase-1, and CD34 staining highlights diffuse capillarization of the sinusoids.Hepatocellular Carcinoma
  • A biopsy of a firm, white hepatic mass reveals infiltrating malignant glandular structures inciting a dense desmoplastic stroma; the tumor cells are positive for cytokeratin 7 and mucicarmine, but negative for arginase-1 and HepPar-1.Intrahepatic Cholangiocarcinoma
  • A biopsy of a hemorrhagic liver lesion in an older man reveals an infiltrative proliferation of highly pleomorphic, mitotically active spindle cells forming irregular vascular channels; tumor cells are strongly positive for CD31 and ERG.Hepatic Angiosarcoma

Answer

The correct matches pair precise histomorphological patterns and unique immunohistochemical signatures (LFABP, Glutamine Synthetase, Arginase-1, CK7, CD31/ERG) with their corresponding benign, malignant, or vascular primary hepatic neoplasms.
Accurate diagnosis of primary hepatic tumors relies on integrating cellular morphology, architectural patterns (e.g., trabecular vs. glandular), and specific immunohistochemistry. HNF1A-inactivated adenomas uniquely lose LFABP expression. Focal Nodular Hyperplasia displays characteristic map-like glutamine synthetase positivity. Hepatocellular Carcinoma is confirmed by arginase-1 and diffuse CD34 sinusoidal capillarization. Intrahepatic Cholangiocarcinoma shows a biliary phenotype (CK7+, mucin+) with intense desmoplasia. Hepatic Angiosarcoma is identified by malignant endothelial channels expressing CD31 and ERG.

Step-by-Step Solution

1
Evaluate the biopsy showing loss of LFABP and absent portal tracts.
Identify as HNF1A-inactivated Hepatocellular Adenoma.
LFABP loss is the pathognomonic molecular phenotype for this specific, low-risk adenoma variant.
2
Analyze the circumscribed mass with a central scar, ductular reactions, and map-like glutamine synthetase.
Identify as Focal Nodular Hyperplasia.
The map-like GS staining and ductular reactions distinguish FNH from hepatocellular adenomas.
3
Assess the thickened trabeculae (>3>3 cells) with arginase-1 positivity and CD34 capillarization.
Identify as Hepatocellular Carcinoma.
Arginase-1 confirms hepatocellular origin, while CD34 capillarization differentiates it from benign regenerative nodules.
4
Analyze the mucin-producing glands with desmoplastic stroma and CK7 positivity.
Identify as Intrahepatic Cholangiocarcinoma.
The biliary immunophenotype (CK7+) and lack of hepatocyte markers rule out HCC and confirm a biliary origin.
5
Evaluate the pleomorphic spindle cells forming vascular channels positive for CD31 and ERG.
Identify as Hepatic Angiosarcoma.
CD31 and ERG are definitive endothelial markers confirming a malignant vascular neoplasm.

Key Concept

Integration of morphologic patterns with specific immunohistochemical markers is required to accurately subtype hepatic neoplasms and distinguish benign mimics from aggressive malignancies.
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