(A) Early diagnosis Early diagnosis is crucial. Since the 1970s to 1980s, the early diagnosis of PLC has been greatly facilitated by the gradual popularization and wide application of serum AFP, real-time ultrasound imaging and CT. As the early diagnosis rate has increased significantly, the surgical resection rate has increased and the prognosis has been improved significantly; therefore, the diagnosis of PLC, especially the early diagnosis, is the key to clinical treatment and prognosis. In terms of early diagnosis, full attention should be paid to the background of liver disease of patients. In China, 95% of PLC patients have a background of hepatitis B virus (HBV) infection, 10% have a background of hepatitis C virus (HCV) infection, and some patients have overlapping HBV and HCV infection. Special attention should be paid to the following risk groups: middle-aged and elderly men with high HBV load, HCV-infected patients, HBV and HCV overlapping infections, alcoholics, co-infected diabetics, and those with a family history of liver cancer. After the age of 35-40, these people should undergo regular screening (including serum AFP test and liver ultrasound) every 6 months; when there is elevated AFP or “occupying lesions” in the liver area, they should enter the diagnostic process immediately, observe closely and strive to make early diagnosis. (2) Laboratory diagnosis methods of hepatocellular carcinoma At present, the qualitative diagnosis of hepatocellular carcinoma in China is still mainly based on the detection of serum AFP, which should be highly regarded: (1) In China, more than 60% of hepatocellular carcinoma cases have serum AFP >400μg/L; (2) At present, there is no other tumor marker with specificity comparable to AFP; (3) AFP detection is less dependent on imaging equipment and new technology. (3) Imaging methods of hepatocellular carcinoma diagnosis In recent years, the progress of medical imaging methods has been obvious, which provides a reliable basis for clinical “four determinations” (localization, characterization, quantification and regularity) of PLC and the formulation of treatment plans. (1) Ultrasound examination: Ultrasound examination is non-invasive and has no adverse effects on human tissues, which is simple, intuitive, accurate, inexpensive, convenient, non-invasive and widely used for screening and post-treatment follow-up of liver cancer. Real-time ultrasonography has important clinical value for the differential diagnosis of liver cancer with diameter <3 cm, and is often used for the early detection and diagnosis of liver cancer, and is a good reference for the differential diagnosis of liver cancer, liver cysts and hepatic hemangioma, while intraoperative ultrasound directly explores the surface of the liver after opening, avoiding ultrasound attenuation and interference from the abdominal wall and ribs, and can detect intrahepatic lesions that are not detected by preoperative CT and ultrasound. However, ultrasound examination is easily limited by the experience, technique and meticulousness of the examiner. (2) Multi-layer spiral CT: The resolution of CT is much higher than ultrasound, and the image is clear and stable, which can reflect the characteristics of hepatocellular carcinoma comprehensively and objectively, and is used for routine diagnosis of hepatocellular carcinoma and follow-up examination after treatment. It is also important for diagnosing whether there are cancer emboli in portal vein, hepatic vein and inferior vena cava, whether there are metastases in hilar and abdominal lymph nodes, and whether liver cancer invades adjacent tissues and organs; it can also determine the severity of cirrhosis by showing the shape of liver, the size of spleen and the presence of ascites. In particular, thin layer and enhanced scan can help to further clarify the site, scope, intrahepatic metastasis and distant metastasis of liver cancer, which can significantly improve the detection rate of small liver cancer; CT scan after 3-4 weeks of hepatic artery iodine oil imaging can also effectively detect small liver cancer lesions. (3) Magnetic resonance imaging (MRI), with high tissue resolution, multi-parameter and multi-directional imaging, is another effective and non-invasive diagnostic method for liver cancer examination after CT, which is helpful for the differential diagnosis of liver cancer. The application of liver-specific MRI contrast can improve the detection rate of metastatic lesions and small hepatocellular carcinoma in the liver, and help to differentiate hepatocellular carcinoma from focal hyperplastic nodules and hepatic adenoma, etc. In addition, MRI may have higher clinical value than CT for the follow-up of the efficacy of TACE treatment for PLC patients. MRI has unique features and can be used as a supplement to CT. (4) Positron emission computed tomography-CT (PET-CT) is a functional molecular imaging system that integrates PET and CT into one, which can reflect the detailed molecular information (biochemical metabolism) of liver occupancy by PET functional imaging and precise anatomical localization of lesions by CT morphological imaging, and the whole-body scan can understand the overall condition and evaluate the metastatic situation. In addition, CT morphological imaging can be used for precise anatomical localization of the lesion, and simultaneous whole-body scan can understand the overall condition and evaluate the metastasis, so as to achieve early detection of the lesion and diagnose the disease, which has the characteristics of sensitivity and accuracy, high resolution and good intuition, and has a certain role in the diagnosis of liver cancer. (5) Selective hepatic arteriography is an invasive examination, and iodine oil angiography also has therapeutic effect, which can clearly show small lesions in the liver and their blood supply, and it is applicable when the diagnosis cannot be confirmed after other examinations. (4) Pathological diagnosis of hepatocellular carcinoma Pathological examination is the gold standard for the diagnosis of primary hepatocellular carcinoma, but special attention should be paid to the clinical aspects. Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and mixed hepatocellular carcinoma are the three main types of pathological histology. Fibrous lamellar carcinoma is a special type of HCC, which is commonly seen in adolescents, mostly without cirrhosis, with slow growth; the prognosis is better. In view of the differences between hepatocellular carcinoma and intrahepatic cholangiocarcinoma in terms of pathogenesis, biological characteristics, clinical manifestations, treatment methods and prognosis, attention should be paid to differentiation and corresponding diagnosis and treatment protocols should be formulated respectively. The main diagnostic bases are as follows: (1) HCC is mostly characterized by polygonal arrangement, with polygonal cells, eosinophilic cytoplasm, round nuclei, and blood sinusoids lining between the cords, but it can also have various cytological and histological special types, such as common pseudoglandular duct structures, which require careful differential diagnosis. Representative immunohistochemical stains: hepatocyte antigen (Hep Par1) shows positive cytoplasm, polyclonal carcinoembryonic antigen (pCEA) shows positive cell membrane (capillary bile ducts), and CD34 shows diffuse positive microvasculature. (2) For the general typing of HCC, we can refer to the "five large and six subtypes" classification developed by the Chinese Hepatocellular Carcinoma Pathology Research Collaborative Group in 1979, and the degree of differentiation of cancer cells can refer to the Edmondson-Steiner four-grade classification. (3) ICC is predominantly glandular ductal arrangement, with cuboidal or low columnar shape, lightly stained or basophilic cytoplasm and abundant interstitial fibers, but there can be various cytological and histological special types, which require careful differential diagnosis. Representative immunohistochemical stains: cytokeratin 19 (CK19) and mucoglycoprotein-1 (MUC-1) show positive cytoplasm. (4) The general types of ICC can be classified as nodular, peritubular infiltrative and nodular infiltrative, and the degree of cancer cell differentiation can be classified as good, moderate or poor. (5) Mixed hepatocellular carcinoma is the presence of both hepatocellular carcinoma and bile duct carcinoma in one hepatocellular carcinoma nodule, and the biological characteristics are between the two types. Small hepatocellular carcinoma is not exactly equal to the concept of early hepatocellular carcinoma. Some small hepatocellular carcinomas can have tiny metastases in early stage, and their surgical resection treatment may not be very effective; in addition, early stage hepatocellular carcinoma does not exactly mean that liver function is in a compensated state, nor does it mean that they are all resectable. The content of the pathological diagnosis report should include: the location, size, number, cell and histological type, differentiation, vascular and envelope invasion, satellite and metastatic foci, as well as liver tissue lesions adjacent to the cancer. The pathological diagnosis report can also be accompanied by the results of immunohistochemistry and molecular markers related to drug-targeting molecules, biological behavior and prognosis of liver cancer for clinical reference.