Liver & intrahepatic bile ducts
Hepatocellular carcinoma
Fibrolamellar variant

Deputy Editor-in-Chief: Debra L. Zynger, M.D.
Raul S. Gonzalez, M.D.
Rondell P. Graham, M.B.B.S.

Topic Completed: 19 February 2021

Minor changes: 25 February 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Fibrolamellar hepatocellular carcinoma[TI] "loattrfree full text"[sb]


Raul S. Gonzalez, M.D.
Rondell P. Graham, M.B.B.S.
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Cite this page: Gonzalez RS, Graham RP. Fibrolamellar variant. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorfibrolamellar.html. Accessed March 4th, 2021.
Definition / general
  • Uncommon yet distinctive primary hepatocellular malignancy
  • Typically affects young individuals from teens to 40 years
  • Large oncocytic neoplastic cells forming tumor tongues separated by collagen bundles
  • Characteristically no underlying chronic liver disease
  • > 95% of cases harbor the oncogenic DNAJB1-PRKACA fusion gene formed by intrachromosomal deletion on chromosome 19 (Mod Pathol 2018;31:141)
  • Rare cases related to biallelic PRKAR1A loss (Hepatology 2018;68:1441)
  • Likely a distinct entity due to unique distinctive clinical, histologic and molecular biologic features
Essential features
  • Primary hepatocellular neoplasm
  • Eosinophilic tumor cells characterized by ample granular cytoplasm
  • Intratumoral fibrosis
  • Recurrent protein kinase A oncogenic driver abnormalities
Terminology
  • Fibrolamellar carcinoma
ICD coding
  • ICD-10: C22.0 - liver cell carcinoma
Epidemiology
  • Predilection for teenage to 40 years old
  • ~99% of cases diagnosed under the age of 50 years at presentation (Mod Pathol 2018;31:141)
  • Propensity for late recurrence
Sites
  • Liver
Etiology
Clinical features
  • Rare over 50 years old
  • No gender preference
  • Symptoms related to hepatic mass (Semin Diagn Pathol 2017;34:146)
  • Rarely associated with gynecomastia or other paraneoplastic phenomena (Lancet 1984;1:538)
  • Not associated with viral hepatitis, inborn errors of metabolism or cirrhosis
  • Metastasizes to abdominal lymph nodes and peritoneum with greater propensity than conventional hepatocellular carcinoma (Eur J Pediatr Surg 2014;24:461)
Diagnosis
  • Combination of
    • Compatible histomorphology
    • Appropriate immunophenotype (CK7, CD68 positive) or detection of key genomic events (DNAJB1-PRKACA, PRKACA rearrangement, PRKACA amplification, PRKAR1A loss)
Laboratory
  • Serum alpha fetoprotein is classically not elevated
  • No other routinely used serum or plasma markers
  • Circulating tumor DNA assay has yet to be made commercially available
Radiology description
  • CT scan and MRI: nonspecific findings; central scar (similar to focal nodular hyperplasia) may be identified; often calcified
Prognostic factors
Case reports
Treatment
Gross description
  • Single (75%), large (frequently > 10 cm), hard, well circumscribed, bulging, tan tumor with fibrous bands
  • Central stellate scar is noted in approximately 70%
  • Variable bile staining, hemorrhage and necrosis
Gross images

Images hosted on other servers:

Various images

Microscopic (histologic) description
  • Trabecula, sheets or cords of neoplastic cells with abundant oncocytic cytoplasm cells in background of dense collagen bundles frequently arranged in parallel lamellae
  • Cells are large and polygonal with well defined cell borders
  • Abundant granular and eosinophilic cytoplasm due to abundant mitochondria
  • Pale or pink bodies are frequently noted but not necessary for diagnosis
  • Typical nuclear features include open chromatin and prominent macronucleoli (Adv Anat Pathol 2007;14:217)
  • Vascular invasion may be seen
  • Histologically, fibrous bands coalesce into central scar
  • Nonneoplastic liver is within normal histologic limits
  • Radiologic calcification corresponds to stromal calcification
  • Calcified individual cells may be identified as well
  • Variable: focal nuclear anisonucleosis, sheet-like growth without intervening fibrous bands, pseudoglandular or pelioid patterns
Microscopic (histologic) images

Contributed by Rondell P. Graham, M.B.B.S.

Fibrolamellar



Case #161

Pale bodies

Trichrome

CK7

HepPar

Ki67



Images hosted on other servers:

Various images

Cytology description
  • Individual cells with ample cytoplasm, open nuclear chromatin and prominent nucleoli; may contain bile
Cytology images

Contributed by Rondell P. Graham, M.B.B.S.

Fibrolamellar



Images hosted on other servers:

Various images

Negative stains
  • Liver fatty acid binding protein (LFABP)
  • In rare cases PRKAR1A; often individuals with the Carney complex
Electron microscopy description
  • Numerous mitochondria
  • Abundant endoplasmic reticulum membranes with concentric whorls
  • Internalized canaliculi lined by microvilli (Mod Pathol 2017;30:892)
Molecular / cytogenetics description
  • > 95% of cases are characterized by DNAJB1-PRKACA fusion gene; diagnostic tests exist
  • Rare cases characterized by biallelic PRKAR1A loss (mostly in patients with the Carney complex) instead of the above fusion gene (Hepatology 2018;68:1441)
  • Single case characterized by PRKACA amplification without the above genomic changes has been identified (Surg Pathol Clin 2018;11:377)
  • Transcriptome has been published and revealed multiple insights (Proc Natl Acad Sci U S A 2015;112:E5916)
  • Overall fewer chromosomal abnormalities than classic hepatocellular carcinoma (Mod Pathol 2009;22:134)
Sample pathology report
  • Liver, segment 3, resection:
    • Fibrolamellar hepatocellular carcinoma (see synoptic report and comment)
    • Comment: A trichrome stain shows no significant fibrosis. An iron stain is unremarkable.
Differential diagnosis
Board review style question #1
What is the characteristic status of the nonneoplastic liver in patients with fibrolamellar carcinoma?

  1. Chronic viral hepatitis C without advanced fibrosis
  2. Cirrhosis due to chronic viral hepatitis B
  3. Glycogen storage disease
  4. Normal
  5. Steatohepatitis
Board review style answer #1
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