Case 200 - Discussion

Uploaded: 2008-03-24, Updated: 2008-03-24

Fibrolamellar Hepatocellular Carcinoma
 

The Key Features

  • Young age, mean 23-27 years;

  • Central calcification and scar;

  • Large polygonal cells, bright eosinophilic cytoplasm, pale bodies and macronucleoli;

  • Abundant fibrous lamellar stroma;

  • EM: abundant cytoplasmic mitochondria.

 

CLINICAL FEATURES

  • An uncommon malignant neoplasm of the liver; distinctive clinical, histologic, and radiographic features that distinguish it from the relatively more common ordinary hepatocellular carcinoma (HCC); accounts for less than 10% of all cases of HCC;

  • Mean age: 23-27 years;

  • Etiology: typically not associated with underlying liver disease or elevated serum levels of AFP;

  • Clinical symptoms: nausea, vomiting, abdominal pain, malaise and weight loss. Rarely jaundice.

GROSS FINDINGS

  • Large (mean diameter10-20 cm), well-demarcated lobular mass;

  • Cut surface: light brown, white or tan, maybe bile-stained;

  • Central calcification (35-60%) and central stellate scar or fibrotic bands; Hemorrhage and necrosis are uncommon;

  • Regional lymph node metastases seen in 50-70% of patients at the time of initial diagnosis.

MICROSCOPIC FINDINGS

  • Characteristic triad: tumor cells with deeply eosinophilic cytoplasm, presence of macronucleoli, and abundant fibrous lamellar stroma;

  • Tumor cells:

    • in nests, sheets, cords, microtrabeculae or pseudoglandular pattern;

    • cells usually well-differentiated and larger than the normal hepatocytes;

    • polygonal or round containing brightly eosinophilic, coarsely granular cytoplasm;

    • nuclei are often large, hyperchromatic and vesicular;

    • macronucleoli;

  • Thick hyalinized bundles of lamellae form hypocellular collagen connective tissue that coalesces into the central scar;

  • The cytoplasm and tumor canaliculi may contain bile.

  • Pale bodies: pale staining, circumscribed areas in the cytoplasm of the tumor cells. Negative for hepatitis B surface antigen, but they are immunoreactive for fibrinogen. Present at 40% fibrolamellar carcinoma cases but not in common HCC.

DIFFERENTIAL DIAGNOSES

  • Focal nodular hyperplasia: thick-walled arteries, numerous ductules interposed between the septa and the hepatic parenchyma, cells resemble normal hepatocytes, lack the dense hyalinized lamellae;

  • Ordinary HCC:

 

Fibrolamellar HCC

Ordinary HCC

Clinical Features

 

 

    Mean age

27 years

50-70

    Gender

M=F

M>F

    Etiology

Unknown

Viral, alcoholic, aflatoxin, hemochromatosis, etc

    Surgical resectability

50-70%

10-20%

   Overall survival

32-68 months

< 6 months

Gross Features

 

 

    Nodule number

Often single

Single or multiple

    Consistency

Firm or hard

Soft or firm

    Fibrous septa

Often present

Absent

    Bile-stained areas

+/−

+/−

    Cirrhosis

Often absent

Often present

Histology Features

 

 

    Fibrous lamellae

+

    Trabeculae, pseudoglands

+

+

    Canaliculi

+

+

    Bile production

+

+

    Tumor cells

Large, polygonal

Small or large, polygonal, round or irregular

    Cytoplasm

Brightly eosinophilic, coarsely granular

Eosinophilic, fine granularity

    Nuclei

Macronucleoli ("owl" eye)

Variable size, prominent nucleoli

    Cytoplasmic inclusions

Pale bodies, globules

Globules, Mallory bodies

    Mitosis

Rare

Frequent or rare

Electron Microscopy

 

 

    Mitochondria

Numerous, back-to-back

Scattered

    Canaliculi

+

+

    Intracellular lumina

+

Immunoprofile

 

 

    CEA

+

+

    Hep-Par-1

+

+

    AFP

+

    CK7, 8, 18, 19

+/−

+/−

    CK20

Non-Neoplastic Liver

 

 

    Cirrhosis

+

    Dysplastic foci

+/−

 

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • Positive: alpha-1-antitrypsin, ferritin, fibrinogen, CEA, Her-Par-1, CK 8/18, CK7 and CK19;

  • Negative: AFP

ELECTRON MICROSCOPIC FINDINGS

  • Abundant cytoplasmic mitochondria, swollen, packed back-to-back

CYTOGENETIC STUDIES

 

TREATMENT AND PROGNOSIS

  • Fibrolamellar carcinoma has a better prognosis than ordinary HCC;

  • Overall survival, 66% at 5 years to 47% at 10 years;

  • Median survival for unresectable patients only 12 months.

REFERENCES

  • Outcome of patients with fibrolamellar hepatocellular carcinoma. Cancer, 106 (6): 1331 - 1338;
  • Clinicopathologic features and survival in fibrolamellar carcinoma: comparison with conventional hepatocellular carcinoma with and without cirrhosis. Modern Pathology (2005) 18, 14171423;
  • Rosai and Ackerman's Surgical Pathology, 9th edition;
  • AFIP, tumor of the liver and intrahepatic bile ducts, series 3.