Liver and intrahepatic bile ducts - tumor
Hepatocellular carcinoma
Fibrolamellar variant

Author: Deepali Jain, M.D. (see Authors page)

Revised: 30 November 2017, last major update February 2012

Copyright: (c) 2002-2017,, Inc.

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

Cite this page: Jain, D. Fibrolamellar variant of hepatocellular carcinoma. website. Accessed March 19th, 2018.
Definition / general
  • Common variant in young adults 20 - 40 years with better prognosis than classic HCC, characterized by well differentiated oncocytic cells in background of dense acellular collagen bundles
  • Some consider a distinct entity due to different clinical and histologic features (eMedicine: Fibrolamellar Carcinoma [Accessed 28 November 2017])
  • Etiology unknown but not associated with cirrhosis
Clinical features
  • < 10% of HCC but 35% of patients < 50 years old; no gender preference
  • Similar symptoms to classic HCC
  • Rarely associated with gynecomastia and Budd-Chiari syndrome
  • Not associated with hepatitis B virus, cirrhosis or metabolic abnormalities
  • 5 year survival is 60 - 75%, better than classic hepatocellular carcinoma (Cancer 2006;106:1331)
  • Metastasizes to abdominal lymph nodes, peritoneum and lung
  • Serum alpha fetoprotein elevated in only 10% vs. 60% of classic HCC
Radiology description
  • Xray: central scar (similar to focal nodular hyperplasia); often calcified (uncommon with FNH)
Case reports

Clear cell variant:
Gross description
  • Single (75%), large (mean 13 cm), hard, scirrhous, well circumscribed, bulging, white brown tumor with fibrous bands throughout and central stellate scar
  • Only liver tumor that is more common in left lobe but may involve both lobes
  • Variable bile staining, hemorrhage and necrosis
Gross images

Images hosted on other servers:

Various images

Clear cell variant:

Well circumscribed tumor

Microscopic (histologic) description
  • Nests, sheets or cords of well differentiated oncocytic cells in background of dense, acellular collagen bundles arranged in parallel lamellae that may contain small, thick walled vessels
  • Cells are large and polygonal with well defined cell borders, abundant granular and eosinophilic cytoplasm due to abundant mitochondria, often pale bodies (ground glass cells) or PAS+ hyaline globules, vesicular nuclei and prominent nucleoli (Adv Anat Pathol 2007;14:217)
  • Vascular invasion and necrosis common; fibrotic tissue coalesces into central scar; remaining liver is unremarkable
  • Radiologic calcification corresponds to necrosis with foreign body type reaction
  • Variable: focal nuclear pleomorphism, conventional hepatocellular carcinoma, trabecular, adenoid or pelioid patterns
Microscopic (histologic) images

Images hosted on PathOut server:

Various images

Pale bodies








Images hosted on other servers:

Large, polygonal, densely eosinophilic tumor cells

Separated from the
native liver paren-
chyma (right) by a
thin fibrous capsule

Cords and clusters of tumor cells

Acinar structures, bile production

Foci of trabecular and acinar architecture

Tumor cells embedded in loose, myxoid stroma

Various images (figs e - h)

Various images

Clear cell variant:

Classic fibrolamellar foci and clear cell foci

Antimitochondrial antibody stain

Cytology description
  • Discohesive cells with inconspicuous strands of collagen; may contain bile
Cytology images

Images hosted on other servers:

Various images

Positive stains
Negative stains
Electron microscopy description
  • Numerous mitochondria
  • Pale bodies contain fibrinogen and are associated with intracytoplasmic luminal / bile canaliculi or accumulation of rough endoplasmic reticulum
  • May have dense core neuroendocrine-like granules but are not neuroendocrine
Electron microscopy images

Images hosted on other servers:

Clear cell variant:

Distended membrane
bound vesicles
represent dilated

Molecular / cytogenetics description
  • Often diploid
  • Overall fewer chromosomal abnormalities than classic HCC; tumors with no cytogenetic changes may be less aggressive (Mod Pathol 2009;22:134)
Differential diagnosis