New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges

• Molecular typing of HCC and ICC is helpful for predicting drug effects and prognosis.
• The clonality of recurrent or multifocal HCC is related to the personalized strategy.
• High genomic instability of HCA is a sign of high risk of malignant transformation.
• DPHCC new type with high infiltration can only be diagnosed by molecular detection.
• Using new tools for molecular pathology will bring precision and efficacy of therapy.

Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies.