Case 14

A 60-year-old male with a 2.5 cm liver nodule.

1. What is the diagnosis by morphology?

   A: Hepatocellular adenoma

   B: Focal nodular hyperplasia

   C: Cirrhosis

   D: Dysplasic nodule

   E: Hepatocellular carcinoma

Answer

The correct answer is E. HCC typically showed thickened hepatic plates (>3 cells thick); pseudoacini/pseudogland formation; Polygonal cells with nuclear atypia, including high N:C ratio, irregular nuclear membrane, multinucleation and prominent nucleoli. In this case, the first picture is the normal background liver and in picture 3, the left lower quadrant there is seemingly non-tumor hepatocytes with small nuclei size, no nucleoli. The hallmark of dysplastic nodule are increased cellularity (2x) and unpaired arteries. Three-marker panel of GS, HSP70, and GPC3 can be used.

The characteristic IHC panels showed:

Reticulin→ Widening of hepatic plates

CD34→ Diffuse sinusoidal (“capillarization”)

Glypican-3→ +/- (but negative in benign liver, Positive staining supports malignancy)

Arginase1: useful in confirming hepatocellular differentiation; highly sensitive and specific, thus more useful than HepPar1 for poorly differentiated hepatocellular carcinoma.

HepPar1: overall highly sensitive but 50% of poorly differentiated hepatocellular carcinoma lose expression

AFP: cytoplasmic; highly specific but low sensitivity; frequently negative in well differentiated hepatocellular carcinoma

Polyclonal CEA, villin and CD10 reveal a canalicular pattern; limited sensitivity in poorly differentiated hepatocellular carcinoma

Albumin ISH: high sensitivity for primary liver carcinoma, although this can also be positive in other adenocarcinomas of biliary origin

References:

https://www.pathologyoutlines.com/topic/livertumorhcc.htm

https://schaberg.faculty.ucdavis.edu/wp-content/uploads/sites/604/2020/05/Liver-_Tumors2.pdf

Case credit: UCSD Pathology

Author: Wangpan Jackson Shi, MD