Humpath.com - Human pathology

Home > E. Pathology by systems > Digestive system > Liver and pancreatobiliary system > Liver > fibrolamellar hepatocellular carcinoma

fibrolamellar hepatocellular carcinoma

Thursday 19 January 2006

fibrolamellar variant of hepatocellular carcinoma, FHCC, Fibrolamellar HCC

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression.

Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA.

FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity.

Images

- Fibrolamellar (hepatocellular) carcinoma, DNAJB1-PRKACA fusion positive

- Touchprep of Fibrolamellar HCC

Synopsis

- Predominantly young patients without cirrhosis
- Account for almost 50% of liver cell carcinomas in the US in patients @<@35 years

Macroscopy

Fibrolamellar carcinoma is large, well circumscribed, multinodular, and yellow.

Microscopy

Fibrolamellar carcinoma shows tumor lobules separated by wide fibrous bands.

- oncocytic appearance of the tumor cells.
- polygonal tumoral cells with fibrous stroma
- fibrosis arranged in a lamellar fashion around the neoplastic hepatocytes.
- Tumor cells are polygonal and deeply eosinophilic
- tumor lobules separated by wide fibrous bands
- oncocytic appearance of the tumor cells.

Immunochemistry

- express cytokeratins 8 (CK8) and 18 (CK18) (like those of conventional liver cell carcinoma), but also CK7 and (to a lesser extent) CK19

Ultrastructure

- numerous mitochondria, in keeping with their oncocytic appearance at the light microscopic level
-  bile canaliculi-like lumina
- sometimes neurosecretory-type dense-core granules
- Collagen deposited around the tumor cells is predominantly composed of types I, III, and V

Pathogenesis

- It may be pathogenetically related to focal nodular hyperplasia (FNH) because of architectural similarities and occasional coexistence of the two entities.

Associations

- hepatocellular adenoma (14736278)
- Fanconi anemia

Molecular biology

- DNAJB1-PRKACA fusion gene in 100% of tumors (24578576)

  • Detection of a Recurrent DNAJB1-PRKACA Chimeric Transcript in Fibrolamellar Hepatocellular Carcinoma

- overexpression of genes in the RAS, MAPK, PIK3, and xenobiotic degradation pathways (17367606)
- EGFR overexpression (16564914)

CGH (11338475, 12768875)

- gains

- losses

Cytogenetics

- 1q anomaly (8986150)
- near triploid karyotype (8986150)
- complex karyotype (8640730, 11338475, 12768875)

See also

- hepatic tumors

Open references

- Molecular testing for the clinical diagnosis of fibrolamellar carcinoma. Graham RP, Yeh MM, Lam-Himlin D el al. Mod Pathol. 2018 Jan;31(1):141-149. doi : 10.1038/modpathol.2017.103 PMID: 28862261

- Hepatocellular Carcinoma, Fibrolamellar Variant: Diagnostic Pathologic Criteria and Molecular Pathology Update. A Primer. 2016. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808818/

- Detection of a Recurrent DNAJB1-PRKACA Chimeric Transcript in Fibrolamellar Hepatocellular Carcinoma. 2015. (24578576) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286414/

References

- Kannangai R, Vivekanandan P, Martinez-Murillo F, Choti M, Torbenson M. Fibrolamellar carcinomas show overexpression of genes in the RAS, MAPK, PIK3, and xenobiotic degradation pathways. Hum Pathol. 2007 Apr;38(4):639-44. PMID: 17367606

- Buckley AF, Burgart LJ, Kakar S. Epidermal growth factor receptor expression and gene copy number in fibrolamellar hepatocellular carcinoma. Hum Pathol. 2006 Apr;37(4):410-4. PMID: 16564914