|
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.
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|
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.
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|
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.
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|
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
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ELECTRON MICROSCOPIC FINDINGS |
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CYTOGENETIC STUDIES |
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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,
1417–1423;
- Rosai and Ackerman's Surgical Pathology, 9th edition;
- AFIP, tumor of the liver and intrahepatic bile ducts, series
3.
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