TNM Classification for Hepatocellular Carcinoma

Staging systems for hepatocellular carcinoma (HCC) have not been universally adopted. One system implemented is the American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classification system. The TNM classification system takes into account tumor characteristics including size, number, and vascular invasion, as well as lymph node involvement and metastatic disease.^{[1, 2]}

Table 1. TNM Classification for Hepatocellular Carcinoma (Open Table in a new window)

Primary tumor (T)
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
T1	Solitary tumor < 2 cm, or >2 cm without vascular invasion
T1a	Solitary tumor < 2 cm
T1b	Solitary tumor > 2 cm without vascular invasion
T2	Solitary tumor > 2 cm with vascular invasion; or multiple tumors, none > 5 cm
T3	Multiple tumors, at least one of which is > 5 cm
T4	Single tumor or tumors of any size involving a major branch of the portal vein or hepatic vein, or tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum
Regional lymph nodes (N)
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Regional lymph node metastasis
Distant metastasis (M)
M0	No distant metastasis
M1	Distant metastasis

Table 2. Anatomic stage/prognostic groups (Open Table in a new window)

Stage	T	N	M
IA	T1a	N0	M0
IB	T1b	N0	M0
II	T2	N0	M0
IIIA	T3	N0	M0
IIIB	T4	N0	M0
IVA	Any T	N1	M0
IVB	Any T	Any N	M1

Table 3. Histologic grade (Open Table in a new window)

Histologic grade (G)
GX	Grade cannot be accessed
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated
G4	Undifferentiated

In addition to the TNM staging for HCC, other systems have been proposed to help guide therapeutic strategies. One of these validated systems is the Barcelona-Clinic Liver Cancer staging system (BCLC). The BCLC system stratifies HCC patients based on tumor size, extent, liver function, and performance status. The BCLC staging system is thought to be better than other staging systems for determining prognosis, given the inclusion of liver function and performance status.^{[3, 4]}

Table 4. Barcelona-Clinic Liver Cancer staging system (Open Table in a new window)

Stage	Performance Status	Tumor Stage	Okuda Stage	Liver function
A: Early HCC
A1	0	Single, < 5 cm	I	No portal hypertension, normal bilirubin
A2	0	Single, < 5 cm	I	Portal hypertension, normal bilirubin
A3	0	Single, < 5 cm	I	Portal hypertension, abnormal bilirubin
A4	0	3 tumors, < 3 cm	I-II	Child-Pugh A-B
Stage B: Intermediate HCC	0	Large, multinodular	I-II	Child-Pugh A-B
Stage C: Advanced HCC	1-2	Vascular invasion or extrahepatic spread	I-II	Child-Pugh A-B
Stage D: End-Stage HCC	3-4	Any	I-II	Child-Pugh C
Stage A and B: All criteria need to be fulfilled Stage C: At least one of the following criteria needs to be filled: performance status 1-2 or vascular invasion/extrahepatic spread. Stage D: At least one of the following criteria needs to be filled: performance status 3-4 or Okuda Stage III/Child Pugh C.

Cirrhosis is an important component of HCC staging. Cirrhosis is not only an independent predictor of survival but also guides management decisions and determines candidacy for different therapies. The Child-Pugh score can be used to classify the prognosis based on the degree of cirrhosis and therefore can help in determining operative risk

Another consideration in determining stage and prognosis in patients with HCC is the degree of liver fibrosis. There are many different scoring systems used to determine the degree of liver fibrosis. With one such scoring system, the Ishak fibrosis staging system, stages 1 through 5 had no direct correlation with survival, however, stage 6 was associated with poor overall survival ^[5]

Table 5. Ishak fibrosis score (Open Table in a new window)

Architectural Change	Score
No fibrosis	0
Fibrous expansion of some portal areas, with or without short fibrous septa	1
Fibrous expansion of most portal areas, , with or without short fibrous septa	2
Fibrous expansion of most portal areas, with occasional portal-to-portal bridging	3
Fibrous expansion of portal areas with marked bridging as well as portal-central	4
Marked bridging (portal-to-portal and/or portal-central) with occasional nodule (incomplete cirrhosis)	5
Cirrhosis, probable or definite	6

Questions & Answers

Overview

What is the TNM classification for hepatocellular carcinoma (HCC)?

What is the Barcelona-Clinic Liver Cancer staging system for hepatocellular carcinoma (HCC)?

How is the degree of cirrhosis determined in hepatocellular carcinoma (HCC)?

How is the Ishak fibrosis score used in the staging of hepatocellular carcinoma (HCC)?

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Table 1. TNM Classification for Hepatocellular Carcinoma

Primary tumor (T)
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
T1	Solitary tumor < 2 cm, or >2 cm without vascular invasion
T1a	Solitary tumor < 2 cm
T1b	Solitary tumor > 2 cm without vascular invasion
T2	Solitary tumor > 2 cm with vascular invasion; or multiple tumors, none > 5 cm
T3	Multiple tumors, at least one of which is > 5 cm
T4	Single tumor or tumors of any size involving a major branch of the portal vein or hepatic vein, or tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum
Regional lymph nodes (N)
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Regional lymph node metastasis
Distant metastasis (M)
M0	No distant metastasis
M1	Distant metastasis

Table 2. Anatomic stage/prognostic groups

Stage	T	N	M
IA	T1a	N0	M0
IB	T1b	N0	M0
II	T2	N0	M0
IIIA	T3	N0	M0
IIIB	T4	N0	M0
IVA	Any T	N1	M0
IVB	Any T	Any N	M1

Table 3. Histologic grade

Histologic grade (G)
GX	Grade cannot be accessed
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated
G4	Undifferentiated

Table 4. Barcelona-Clinic Liver Cancer staging system

Stage	Performance Status	Tumor Stage	Okuda Stage	Liver function
A: Early HCC
A1	0	Single, < 5 cm	I	No portal hypertension, normal bilirubin
A2	0	Single, < 5 cm	I	Portal hypertension, normal bilirubin
A3	0	Single, < 5 cm	I	Portal hypertension, abnormal bilirubin
A4	0	3 tumors, < 3 cm	I-II	Child-Pugh A-B
Stage B: Intermediate HCC	0	Large, multinodular	I-II	Child-Pugh A-B
Stage C: Advanced HCC	1-2	Vascular invasion or extrahepatic spread	I-II	Child-Pugh A-B
Stage D: End-Stage HCC	3-4	Any	I-II	Child-Pugh C
Stage A and B: All criteria need to be fulfilled Stage C: At least one of the following criteria needs to be filled: performance status 1-2 or vascular invasion/extrahepatic spread. Stage D: At least one of the following criteria needs to be filled: performance status 3-4 or Okuda Stage III/Child Pugh C.

Table 5. Ishak fibrosis score

Architectural Change	Score
No fibrosis	0
Fibrous expansion of some portal areas, with or without short fibrous septa	1
Fibrous expansion of most portal areas, , with or without short fibrous septa	2
Fibrous expansion of most portal areas, with occasional portal-to-portal bridging	3
Fibrous expansion of portal areas with marked bridging as well as portal-central	4
Marked bridging (portal-to-portal and/or portal-central) with occasional nodule (incomplete cirrhosis)	5
Cirrhosis, probable or definite	6