Hepatocellular carcinoma classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]

Overview

Hepatocellular carcinoma (HCC) may be classified into different histological subtypes based on the microscopic features. The TNM staging system is widely used for the staging of hepatocellular carcinoma, the Cancer of the Liver Italian Program (CLIP) system is used widely because it is adapted from the original Okuda classification system that takes cirrhosis into account.

Classification

Classification based on histological features

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatocellular carcinoma
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fibrolamellar carcinoma
 
Undifferentiated carcinoma
 
 
Sarcomatoid HCC
 
Combined HCC-CC*
 
 
Lymphoepithelioma
 
Scirrhous HCC
 
 
 

Abbreviations: Combined HCC-cholangiocarcinoma (HCC-CC)*

Classification based on TNM staging

According to the TNM staging system, there are four stages of hepatocellular carcinoma based on the tumor size, lymph node involvement, and distant metastasis. Although the TNM staging system is widely used for the staging of hepatocellular carcinoma, the Cancer of the Liver Italian Program (CLIP) system is preferable because it is adopted from the original Okuda classification system that takes cirrhosis into account.

TNM staging system

According to the TNM staging system, there are four stages of hepatocellular carcinoma based on the tumor size, lymph node involvement, and distant metastasis.[4]

Primary tumor

Primary tumor Interpretation
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 A single tumor with no invasion into the blood vessels of the liver
T2 A single tumor with invasion into the blood vessels or multiple tumors, none more than 5 cm in size
T3a Multiple tumors, with any tumor larger than 5 cm
T3b The tumor has grown into either the portal or hepatic vein
T4 The tumor has grown into nearby organs (other than the gallbladder) or the tumor has grown into the layer of tissue that covers the organs in the abdomen (visceral peritoneum)

Regional lymph node

Lymph node involvement Interpretation
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis

Distant metastasis

M0 No distant metastasis
M1 Distant metastasis

Clip and Okuda staging systems for hepatocellular carcinoma

Cancer of the Liver Italian Program (CLIP) system is used widely because it is adopted from the original Okuda classification system that takes cirrhosis into account.

CLIP Classification

Variable Points
0 1 2
i.Tumor number (%) Single Multiple
Hepatic replacement by tumor <50 <50 >50
ii. Child-Pugh score A B C
iii. α fetoprotein level (ng/mL) <400 ≥400
iv.Portal vein thrombosis (CT) No Yes
CLIP stages (score = sum of points): CLIP 0, 0 points; CLIP 1, 1 point; CLIP 2, 2 points; CLIP 3, more than 3

points.

OKUDA Classification

OKUDA Classification
Tumor extenta Bilirubin (mg/dL) Albumin (g/L) Ascites
≥50% <50 ≥ 3 <3 ≤3 >3 +
(+) (−) (+) (−) (+) (−) (+) (−)
Okuda stages: stage 1, all (−); stage 2, 1 or 2 (+); stage 3, 3 or 4 (+)

a. Liver span occupied by the tumor.

Adopted from Harrison's Textbook of Medicine*

References

  1. Shafizadeh N, Kakar S (2013). "Hepatocellular Carcinoma: Histologic Subtypes". Surg Pathol Clin. 6 (2): 367–84. doi:10.1016/j.path.2013.03.007. PMID 26838979.
  2. Matsuura S, Aishima S, Taguchi K, Asayama Y, Terashi T, Honda H, Tsuneyoshi M (2005). "'Scirrhous' type hepatocellular carcinomas: a special reference to expression of cytokeratin 7 and hepatocyte paraffin 1". Histopathology. 47 (4): 382–90. doi:10.1111/j.1365-2559.2005.02230.x. PMID 16178893.
  3. Drebber, U.; Dienes, H. P. (2006). "Diagnose und Differenzialdiagnose des hepatozellulären Karzinoms". Der Pathologe. 27 (4): 294–299. doi:10.1007/s00292-006-0842-1. ISSN 0172-8113.
  4. Canadian Cancer Society.http://www.cancer.ca/en/cancer-information/cancer-type/liver/staging/?region=ab

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