5/24/2013
Variants of Hepatocellular
Carcinoma: Practical Issues
Disclosures
I have nothing to disclose.
Raga Ramachandran, MD, PhD
UCSF Pathology
May 24, 2013
Features of classic HCC
HCC with different architectural patterns
• Hepatocellular proliferation arranged in
trabeculae or acinar/pseudoglandular
groups.
• Lack of normal portal tracts
• Increased arterialization within lesion
• Bile production
• Reticulin loss or intact reticulin outlining
tumor cells in irregular architectural
groupings
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Bile production in HCC
Problem patterns of HCC to address
today
• HCC with clear-cell change
• HCC with fibrosis
• HCC with glandular/pseudoglandular
architecture
• Prognosis and treatment of HCC variants may
differ from that of classic (conventional) HCC
HCC with focal clear-cell change
• HCC with clear-cell change
• HCC with fibrosis
• HCC with glandular/pseudoglandular
architecture
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HCC with diffuse clear-cell change
Steatohepatitis-like HCC
Steatohepatitis-like HCC
Steatohepatitis-like HCC
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Key considerations with clear-cell morphology
Differential for clear-cell HCC
• Metastatic renal cell carcinoma
• Metastatic adrenocortical carcinoma
• Neuroendocrine carcinoma with clear-cell
features
• “Balloon cell” melanoma
• Epithelioid angiomyolipoma
• Epithelioid mesenchymal tumors including
epithelioid GIST
MOC31 +
MOC31 –
Hep Par 1 +
None*
HCC
Hep Par 1 –
• RCC (subset)
• Neuroendocrine
tumor
• HCC with aberrant
immunophenotype
(rare)
Keratin +
• RCC
• Neuroendocrine tumor
• Epithelioid GIST (rare)
Keratin –
• Melanoma
• Adrenocortical carcinoma
• Epithelioid
angiomyolipoma
• Epithelioid sarcomas
Differential for HCC with fibrosis
• HCC with clear-cell change
• HCC with fibrosis
• HCC with glandular/pseudoglandular
architecture
•
•
•
•
Fibrolamellar carcinoma
Scirrhous HCC
Cirrhosis-like HCC
Combined HCC-cholangiocarcinoma
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Identifying fibrolamellar carcinoma
Fibrolamellar carcinoma
• large polygonal tumor cells with abundant
eosinophilic granular cytoplasm
• prominent macronucleoli
• lamellar fibrosis
Fibrolamellar carcinoma
Pale bodies are not specific for a diagnosis
of fibrolamellar carcinoma
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Scirrhous HCC
Cirrhosis-like HCC
Cirrhosis-like HCC
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Reticulin
Cirrhosis-like HCC
CD34
Cirrhosis-like HCC: incidental finding at explant
Pale nodules are HCC
Cirrhosis-like HCC (in cirrhosis)
• Diagnostic problem both clinically and
microscopically
• May also have large dominant mass and
smaller, cirrhosis-like satellite lesions
Jakate….Ferrell, et al. Diffuse Cirrhosis-like HCC.
AJSP 2010; 34:935-941.
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HCC: Courtesy of Dr. Shriram Jakate, Rush Univ
Cirrhosis-like HCC explant
Little or no difference between tumor nodules
and cirrhotic nodules
• HCC with clear-cell change
• HCC with fibrosis
• HCC with glandular/pseudoglandular
architecture
Differential for HCC with
pseudoglandular architecture
• Pseudoglandular HCC
• Combined HCC-cholangiocarcinoma
• Pure cholangiocarcinoma
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CK7
Hep Par 1
Goodman et al. classification of HCCcholangiocarcinoma (HCC-CC)
• Type I – collision tumor with apparently
coincidental HCC and CC in the same liver
• Type II – transitional tumor with elements of HCC
closely associated with and apparently transitioning
to elements of CC
• Type III – fibrolamellar type, resembles
fibrolamellar HCC but with mucin-producing
pseudoglands
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Hep Par 1
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Hep Par 1
CK19
Summary
• Common morphologies of HCC include
trabecular/solid growth, acinar patterns
• Common problem patterns of HCC include
– HCC with clear-cell change
– HCC with fibrosis
– HCC with glandular/pseudoglandular architecture
• Use limited tissue strategically (H&E, reticulin,
unstaineds)
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