Tutorial in Human Hepatocarcinogenesis, Part 1 (pre-malignant lesions)
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Transcript of Tutorial in Human Hepatocarcinogenesis, Part 1 (pre-malignant lesions)
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Tutorial in Human Hepatocarcinogenesis:Premalignant lesions and stem cells
Neil Theise, MDDepartments of Pathology and Medicine (Digestive Diseases)Mount Sinai Beth Israel Medical CenterNew York City
Icahn School of Medicine atMount Sinai
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Nodular dysplasias• Hepatocellular adenomas• Dysplastic nodules (only in CLD)
Cellular dysplasias• Small cell change• Large cell change
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Distinctive nodules which differ from the surrounding parenchyma in terms of:
size,color,texture, or degree of bulging from the cut surface…
Dysplastic Nodules
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Distinctive nodules which differ from the surrounding parenchyma in terms of:
size,color,texture, or degree of bulging from the cut surface…
…AND contain portal tracts.
Dysplastic Nodules
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Low GradeDysplasticNodules
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Features of Low Grade DNs:
Normal cytology or
Large cell change only
No architectural atypia
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High GradeDysplasticNodules
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Features of High Grade DNs:
Cytologic atypia e.g. small cell change
Clone-like domains e.g. Mallory body clustering, fatty or clear cell change, iron resistance, etc.
Architectural atypia e.g. pseudogland formation
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Incidence of DNs in Cirrhotic Livers
Location Source # Cirrhotic Livers
# w/ DNs (%)
Tokushima Autopsy 315 46 (14%)
New York Explant 44 11 (25%)
San Francisco Explant 110 17 (15%)
Kanazawa Autopsy 209 45 (21%)
New York Explant 155 32 (22%)
Bordeaux Explant 41 10 (24%)
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Chronic HepatitisHepatitis B and C Autoimmune hepatitis
Metabolic DiseaseGenetic hemochromatosis A-1-AT Deficiency
Chronic Biliary Tract Disease PBC, PSC
Toxic InjuryChronic alcoholic liver injury
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Chronic hepatitis
with fibrosis10-50 years
Natural History of Chronic Liver Disease
Cirrhosis
Normal liver
HepatocellularCarcnoma
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Increased proliferation
NodularHCC
Low gradedysplastic
nodule
Dysplasticnodule
containing early HCC
Genetic alteration
High gradedysplastic
nodule
Old Model
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Chronic hepatitis
with fibrosis10-50 years
Natural History of Chronic Liver Disease
Cirrhosis
Normal liver
HepatocellularCarcnoma
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SPREADINGMONOCLONAL
PROLIFERATION
CLONALDYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED HSC ACTIVATION
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SPREADINGMONOCLONAL
PROLIFERATION
NODULE-IN-NODULELESION
CLONALDYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED HSC ACTIVATION
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SPREADINGMONOCLONAL
PROLIFERATION
NODULE-IN-NODULELESION
CLONALDYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED HSC ACTIVATION
MATUREHEPATOCELLULAR
CARCINOMA
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Aihara T, et al.Clonal analysis of regenerative nodules in
hepatitis C virus-induced liver cirrhosis.Gastroenterology 1994; 107: 1805-11.
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XX
XX X
X
X
X
X
X
X
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XX
XX I
I
I
I
I
I
X
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IIII
IIII I
I
I
I
I
I
II
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IIII
II
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SPREADINGMONOCLONAL
PROLIFERATION
NODULE-IN-NODULELESION
CLONALDYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED HSC ACTIVATION
MATUREHEPATOCELLULAR
CARCINOMA
NL or INCREASED HSC ACTIVATION
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SPREADINGMONOCLONAL
PROLIFERATION
NODULE-IN-NODULELESION
CLONALDYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED HSC ACTIVATION
MATUREHEPATOCELLULAR
CARCINOMA
ADJACENT CLONAL CIRRHOTIC NODULES
NL or INCREASED HSC ACTIVATION
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SPREADINGMONOCLONAL
PROLIFERATION
NODULE-IN-NODULELESION
CLONALDYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED HSC ACTIVATION
MATUREHEPATOCELLULAR
CARCINOMA
ADJACENT CLONAL CIRRHOTIC NODULES
MULTIPLE, ADJACENTOr
DNs w/ INDISTINCT BORDERSMICROSCOPIC HCCs
NL or INCREASED HSC ACTIVATION
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Early HCC, vaguely nodular type
Early HCC, distinctly nodular type
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Hepatology 2009; 49: 658