Intro to premalignant liver lesions (emphasis on dysplastic nodules) for radiology group.

1. Tutorial in Human Hepatocarcinogenesis:
Premalignant lesions and stem cells
Neil Theise, MD
Departments of Pathology and Medicine (Digestive Diseases)
Mount Sinai Beth Israel Medical Center
New York City
Icahn School of Medicine at
Mount Sinai

2. Nodular dysplasias
• Hepatocellular adenomas
• Dysplastic nodules (only in CLD)
 Cellular dysplasias
• Small cell change
• Large cell change

3. Distinctive nodules which differ from
the surrounding parenchyma in terms of:
size,
color,
texture,
or
degree of bulging from the cut surface…
Dysplastic Nodules

8. 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

10. Low Grade
Dysplastic
Nodules

11. Features of Low Grade DNs:
Normal cytology
or
Large cell change only
No architectural atypia

14. High Grade
Dysplastic
Nodules

15. 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

20. 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%)

21. Chronic Hepatitis
Hepatitis B and C
Autoimmune hepatitis
Metabolic Disease
Genetic hemochromatosis
A-1-AT Deficiency
Chronic Biliary Tract Disease
PBC, PSC
Toxic Injury
Chronic alcoholic liver injury

25. Chronic
hepatitis
with fibrosis
10-50 years
Natural History of Chronic Liver Disease
Cirrhosis
Normal liver
Hepatocellular
Carcnoma

26. Increased proliferation
Nodular
HCC
Low grade
dysplastic
nodule
Dysplastic
nodule
containing
early HCC
Genetic
alteration
High grade
dysplastic
nodule
Old Model

27. Chronic
hepatitis
with fibrosis
10-50 years
Natural History of Chronic Liver Disease
Cirrhosis
Normal liver
Hepatocellular
Carcnoma

40. SPREADING
MONOCLONAL
PROLIFERATION
CLONAL
DYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED
HSC ACTIVATION

41. SPREADING
MONOCLONAL
PROLIFERATION
NODULE-IN-NODULE
LESION
CLONAL
DYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED
HSC ACTIVATION

42. SPREADING
MONOCLONAL
PROLIFERATION
NODULE-IN-NODULE
LESION
CLONAL
DYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED
HSC ACTIVATION
MATURE
HEPATOCELLULAR
CARCINOMA

43. Aihara T, et al.
Clonal analysis of regenerative nodules in hepatitis C
virus-induced liver cirrhosis.
Gastroenterology 1994; 107: 1805-11.

45. X
X
XX X
X
X
X
X
X
X

46. X
X
XX I
I
I
I
I
I
X

47. II
II
IIII I
I
I
I
I
I
II

48. IIII
II

50. SPREADING
MONOCLONAL
PROLIFERATION
NODULE-IN-NODULE
LESION
CLONAL
DYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED
HSC ACTIVATION
MATURE
HEPATOCELLULAR
CARCINOMA
NL or INCREASED
HSC ACTIVATION

51. SPREADING
MONOCLONAL
PROLIFERATION
NODULE-IN-NODULE
LESION
CLONAL
DYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED
HSC ACTIVATION
MATURE
HEPATOCELLULAR
CARCINOMA
ADJACENT CLONAL
CIRRHOTIC NODULES
NL or INCREASED
HSC ACTIVATION

52. SPREADING
MONOCLONAL
PROLIFERATION
NODULE-IN-NODULE
LESION
CLONAL
DYSPLASTIC NODULE
DEVELOPING CIRRHOSIS
DIMINISHED
HSC ACTIVATION
MATURE
HEPATOCELLULAR
CARCINOMA
ADJACENT CLONAL
CIRRHOTIC NODULES
MULTIPLE, ADJACENT
Or
DNs w/ INDISTINCT BORDERS
MICROSCOPIC HCCs
NL or INCREASED
HSC ACTIVATION

53. Early HCC, vaguely nodular type
Early HCC, distinctly nodular type

54. Hepatology 2009; 49: 658