Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update

World J Gastroenterol. 2016 Nov 14;22(42):9279-9287. doi: 10.3748/wjg.v22.i42.9279.


In 2010, a panel of Chinese pathologists reported the first expert consensus for the pathological diagnosis of primary liver cancers to address the many contradictions and inconsistencies in the pathological characteristics and diagnostic criteria for PLC. Since then considerable clinicopathological studies have been conducted globally, prompting us to update the practice guidelines for the pathological diagnosis of PLC. In April 18, 2014, a Guideline Committee consisting of 40 specialists from seven Chinese Societies (including Chinese Society of Liver Cancer, Chinese Anti-Cancer Association; Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Pathology, Chinese Anti-Cancer Association; Digestive Disease Group, Chinese Society of Pathology, Chinese Medical Association; Chinese Society of Surgery, Chinese Medical Association; Chinese Society of Clinical Oncology, Chinese Anti-Cancer Association; Pathological Group of Hepatobiliary Tumor and Liver Transplantation, Chinese Society of Pathology, Chinese Medical Association) was created for the formulation of the first guidelines for the standardization of the pathological diagnosis of PLC, mainly focusing on the following topics: gross specimen sampling, concepts and diagnostic criteria of small hepatocellular carcinoma (SHCC), microvascular invasion (MVI), satellite nodules, and immunohistochemical and molecular diagnosis. The present updated guidelines are reflective of current clinicopathological studies, and include a novel 7-point baseline sampling protocol, which stipulate that at least four tissue specimens should be sampled at the junction of the tumor and adjacent liver tissues in a 1:1 ratio at the 12, 3, 6 and 9 o'clock reference positions. For the purposes of molecular pathological examination, at least one specimen should be sampled at the intratumoral zone, but more specimens should be sampled for tumors harboring different textures or colors. Specimens should be sampled at both adjacent and distant peritumoral liver tissues or the tumor margin in order to observe MVI, satellite nodules and dysplastic foci/nodules distributed throughout the background liver tissues. Complete sampling of whole SHCC ≤ 3 cm should be performed to assess its biological behavior, and in clinical practice, therapeutic borders should be also preserved, even in SHCC. The diagnostic criteria of MVI and satellite nodules, immunohistochemical panels, as well as molecular diagnostic principles, such as clonal typing, for recurrent HCC and multinodule HCC were also proposed and recommended. The standardized process of pathological examination is aimed at ensuring the accuracy of pathological PLC diagnoses as well as providing a valuable frame of reference for the clinical assessment of tumor invasive potential, the risk of postoperative recurrence, long-term survival, and the development of individualized treatment regimens. The updated guidelines could ensure the accuracy of pathological diagnoses of PLC, and provide a valuable frame of reference for its clinical assessment.

Keywords: Diagnosis; Hepatocellular carcinoma; Intrahepatic cholangiocarcinoma; Liver cancer; Pathology; Practice guidelines.

Publication types

  • Consensus Development Conference
  • Practice Guideline
  • Review

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biopsy / standards*
  • Consensus
  • Humans
  • Immunohistochemistry / standards*
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / therapy
  • Molecular Diagnostic Techniques / standards*
  • Neoplasm Grading
  • Predictive Value of Tests
  • Reproducibility of Results


  • Biomarkers, Tumor