Liver Cancer (Hepatocellular Carcinoma): Classification

Several classifications can be distinguished for hepatocellular carcinoma (hepatocellular carcinoma; HCC):

Eggel macroscopic classification

  • Diffuse – about five percent of cases
  • Expansive – up to 20% of cases.
  • Mixed type – in up to > 40% of cases.
  • Infiltrative – circa 33% of cases.

Microscopic classification

  • Acinar type (pseudoglandular) – with glandular structures.
  • Solid type (compact) – with poorly differentiated liver cells.
  • Trabecular type – with highly differentiated tumor cells, similar to liver cells.
  • Cirrhotic type (cell-poor).

CLIP score (Cancer of the Italian Liver Program).

Parameters 0 points 1 point 2 points
Tumor node Singular Multiple
Affected liver in % < 50 < 50 > 50
Child-Pugh score A B C
α-Fetoprotein <400 ng/ml ≥ 400 ng/ml
Portal vein thrombosis on CT No Yes

CLIP 0 – 0 points CLIP 1 – 1 point CLIP 2 – 2 points CLIP 3 – 3 points

Okuda classification

Extent of affected liver Ascites Albumin in g/l Bilirubin in mg/dl
≥ 50 % < 50 + ≤3 > 3 ≥ 3 < 3
(+) (-) (+) (-) (+) (-) (+) (-)

Okuda stage 1 – all (-) Okuda stage 2 – 1-2 x (+) Okuda stage 3 – 3-4 x (+)

TNM classification

T Infiltration depth of the tumor
T1 No vascular invasion
T2 Vascular invasion or multiple tumors <5 cm
T3 Multiple tumors > 5 cm or involvement of a branch of the hepatica/V. portae vein
T4 Invasion of an adjacent organ (not gallbladder!) or perforation of visceral peritoneum
N Lymph node involvement
N0 No lymph node metastases
N1 Regional lymph node metastases
M Metastases
M0 No distant metastases
M1 Distant metastases

UICC/TNM classification for staging (increasingly rarely used).

UICC stage TNM stages
I T1 N0 M0
II T2 N0 M0
IIIa T3 N0 M0
IIIb T4 N0 M0
IIIc Any T N1 M0
IIId each T Each N M1

Milan criteria (Milan criteria)

Patients transplanted within the Milan criteria have better long-term survival (75% at four years). The Milan criteria are defined as follows:

  • A lesion smaller than 5 cm
  • Up to three lesions, each smaller or no larger than 3 cm
  • No extrahepatic manifestation
  • No vascular invasion (e.g., tumor thrombosis of the portal vein or hepatic veins)

Consideration of AFP may complement the Milan criteria: AFP concentration (= proliferation marker of HCC) of less than 100 ng/ml lowered the five-year recurrence risk from 47.6% ± 11.1% to 14.4% ± 5.3% (p = 0.006). AFP concentrations greater than 1,000 ng/ml increased the five-year recurrence risk (37.1% ± 8.9% vs. 13.3% ± 2.0%).