I. Diagnostic criteria of hepatocellular carcinoma. 1. Pathological diagnostic criteria: HCC is diagnosed by biopsy or surgical excision of tissue specimens from occupied liver lesions or extrahepatic metastases, and this is the gold standard by pathological histological and/or cytological examination. 2. Clinical diagnostic criteria: Among all solid tumors, only HCC can be diagnosed using clinical diagnostic criteria, which are recognized domestically and externally as non-invasive, simple, convenient and operable, and are generally considered to depend mainly on three major factors, namely chronic liver disease background, imaging findings and serum AFP level; however, the understanding and specific requirements of the academic community vary and often change, and there are errors in practical application. Therefore, taking into account China’s national situation, previous domestic standards and clinical practice, the expert group proposed that a strict grasp and joint analysis is appropriate, requiring that the clinical diagnosis of HCC can be established when both (1)+(2)a or (1)+(2)b+(3) of the following conditions are met: (1) evidence of cirrhosis and HBV and/or HCV infection (HBV and/or HCV antigen-positive) (2) typical imaging features of HCC: simultaneous multi-row CT scan and/or dynamic contrast-enhanced MRI showing rapid heterogeneous vascular enhancement of the hepatic occupancy in the arterial phase with rapid elution in the venous or delayed phase. (1) HCC can be diagnosed if the diameter of liver occupancy is ≥2 cm and one of the two imaging examinations of CT and MRI shows that the liver occupancy has the features of hepatocellular carcinoma mentioned above; (2) If the diameter of liver occupancy is 1-2 cm, both imaging examinations of CT and MRI need to show that the liver occupancy has the features of hepatocellular carcinoma mentioned above before HCC can be diagnosed to enhance the specificity of diagnosis. (3) Serum AFP ≥ 400 μg/L for 1 month or ≥ 200 μg/L for 2 months, and can exclude other causes of elevated AFP, including pregnancy, germline embryonic-derived tumors, active liver disease and secondary hepatocellular carcinoma. 3. Precautions and instructions. (1) Several foreign guidelines (including AASLD, EASL and NCCN’s CPGs) emphasize that multi-row CT scan and/or dynamic contrast-enhanced MRI should be performed for hepatic occlusions and should be performed at an experienced imaging center; also, it is believed that a definitive imaging diagnosis of HCC requires a four-phase scan of plain phase, arterial phase, venous phase and delayed phase, and the lesion HCC is characterized by early arterial phase lesions that can be significantly enhanced with higher density than normal liver tissue, and rapid disappearance of enhancement in the venous phase with lower density than surrounding normal liver tissue. If the imaging features of liver occupancy are atypical, or if CT and MRI are inconsistent, liver puncture biopsy should be performed, but even if negative results do not completely exclude, follow-up observation is still needed. (2) In recent years, clinical observation and research results both at home and abroad suggest that serum AFP can be elevated in some patients with ICC and liver metastases from gastrointestinal cancer, and ICC is also often accompanied by cirrhosis. Although the incidence of ICC is much lower than that of HCC, both are commonly seen in patients with cirrhosis. Therefore, elevated AFP in liver-occupying lesions does not necessarily mean HCC and needs to be carefully differentiated. In China and most countries in the Asia-Pacific region, patients with markedly elevated AFP are more likely to have HCC, which still has a differential value compared with ICC, and is therefore used here as a diagnostic index for HCC. (3) For patients with serum AFP ≥ 400 μg/L and no liver occupancy on ultrasound, attention should be paid to exclude pregnancy, germline embryonic-derived tumors, active liver disease and gastrointestinal liver-like adenocarcinoma; if they can be excluded, multi-row CT and/or dynamic contrast-enhanced MRI scan must be performed promptly. The diagnosis of HCC is made if typical HCC imaging features are present (abundant vascularity in the arterial phase with regression in the portal or delayed phase); if the findings or vascularity are not typical, contrast-enhanced examination with other imaging modalities or liver biopsy of the lesion should be performed. Arterial phase enhancement alone without venous phase regression is not sufficient evidence for the diagnosis of HCC. If AFP is elevated but not at diagnostic levels, in addition to the above-mentioned conditions that may cause increased AFP should be ruled out, it is important to closely observe and follow the changes in AFP by reducing the interval between ultrasound examinations to 1-2 months and performing CT and/or MRI dynamic observation when needed. If hepatocellular carcinoma is highly suspected, further selective hepatic arteriography (DSA) is recommended, and liver aspiration biopsy may be performed if necessary and appropriate. (4) For those who have hepatic occupying lesions but no elevated serum AFP and no imaging features of hepatocellular carcinoma on imaging, if the diameter is <1 cm, they can be closely observed. If no vascular enhancement is seen in dynamic imaging of liver occupancy, it is unlikely to be malignant. If the occupancy gradually increases or reaches ≥2 cm in diameter, further examination such as ultrasound-guided liver aspiration biopsy should be performed. Even if the liver biopsy result is negative, it should not be easily dismissed and should be followed up; imaging follow-up should be performed at 6-month intervals until the lesion disappears, increases in size, or presents diagnostic features of HCC; if the lesion increases in size but still does not have typical HCC changes, repeat liver biopsy can be considered. (5) It should be noted that 5%-20% of patients with HCC in China do not have a background of cirrhosis, about 10% have no evidence of HBV/HCV infection, and about 30% have serum AFP consistently <200 μg/L. Also, most of the imaging features of HCC are richly vascular, but a few do show lack of vascularity. In addition, in Europe and the United States, patients with nonalcoholic steatohepatitis (NASH) can develop cirrhosis and then HCC (NASH-associated HCC), which has been reported more frequently, but there is a lack of data in China. Second, the differential diagnosis. 1, serum AFP positive, HCC should be differentiated from the following diseases: (1) chronic liver disease: such as hepatitis, liver cirrhosis, the patient's serum AFP level should be dynamically observed. When liver disease is active, AFP is mostly active in the same direction as ALT and is mostly transient or fluctuates repeatedly, usually not more than 400 μg/L and for a short period of time. If the curves of AFP and ALT are separated, AFP rises while SGPT falls, i.e., AFP and ALT are heterogeneously active and/or AFP is persistently high, then the possibility of HCC should be alerted. (2) Tumors such as pregnancy, gonadal or embryonic type: Identification is mainly by medical history, physical examination, abdominopelvic ultrasound and CT examination. (3) Gastrointestinal tumors: Some adenocarcinomas of the gastrointestinal and pancreatic glands can also cause elevated serum AFP, called hepatoid adenocarcinoma. In addition to detailed medical history, physical examination and imaging, the determination of serum AFP heterogeneity can help to identify the origin of the tumor. For example, in the case of gastric liver-like adenocarcinoma, AFP is predominantly of the lentil agglutinin unbound type. When serum AFP is negative, HCC should be differentiated from the following diseases: (1) Secondary hepatocellular carcinoma: mostly seen in metastatic GI tract tumors, but also common in lung and breast cancer. Patients may have no background of liver disease, but their medical history may show GI tumor manifestations such as blood in stool, fullness and distension, anemia and weight loss, and normal serum AFP, while GI tumor markers such as CEA, CA199, CA50, CA724 and CA242 may be elevated. (2) The typical image of metastasis is "bull's-eye sign" (a halo around the mass and hypoechoic or hypointense in the center due to the lack of blood supply); (3) Enhanced CT or DSA imaging shows that the tumor is less vascular and the blood supply is not as rich as that of HCC; (4) GI endoscopy or X-ray imaging may reveal the tumor. or X-ray imaging may reveal the primary cancerous lesion in the gastrointestinal tract. (2) Intrahepatic cholangiocarcinoma (ICC): it is a rare pathological type of primary hepatocellular carcinoma, with a predilection for age 30-50 years, non-specific clinical symptoms and no background of liver disease. However, the most meaningful CT scan shows that the blood supply to the liver is not as rich as that of HCC, and the fibrous component is more, with delayed enhancement and "fast-in, slow-out" characteristics. Sometimes irregular dilatation of intrahepatic bile ducts can be seen; there can also be localized atrophy of the liver lobe and invagination of the liver envelope, and sometimes there are linear high-density shadows in the parenchyma of liver tumor (linear sign). The diagnostic rate of imaging examination is not high, and it mainly depends on pathological examination after surgery. (3) Hepatic sarcoma: often without a background of liver disease, imaging shows a homogeneous solid occupancy with abundant blood supply, which is not easily distinguished from AFP-negative HCC. (4) benign liver lesions: including: ① hepatic adenoma: often without a background of liver disease, more women, often with a history of oral contraceptive use, and not easily distinguished from highly differentiated HCC, the more meaningful test for differentiation is 99mTc nuclear scan, hepatic adenoma can take up nuclear, and the delayed phase shows a strong positive image; ② hepatic hemangioma: often without a background of liver disease, more women, CT-enhanced scans can be seen from the periphery of the occupancy reinforcement filling (iii) liver abscess: often with a history of dysentery or septic disease and no history of liver disease Ultrasound examination is often confused with hepatocellular carcinoma when the abscess is not liquefied or pus thick, and after liquefaction, it shows liquid dark area, which should be distinguished from central necrosis of hepatocellular carcinoma; DSA imaging does not have tumor vessels and staining. If necessary, fine needle aspiration can be performed at the pressure point. Anti-amoebic test treatment is a better differential diagnosis method. The clinical manifestations can be very similar to liver cancer; however, the disease generally has a long course, often with a history of many years, and progresses more slowly. The Casoni test is a specific test with a positive rate of 90-95%. Ultrasound examination reveals strong echogenicity of floating cysts in the cystic space, and CT sometimes reveals calcified head nodes in the cyst wall. Puncture biopsy is not recommended because of the serious allergic reaction that can be induced. Third, pathologic diagnosis. Pathological histological and/or cytological examination is the basis for the gold standard diagnosis of hepatocellular carcinoma, but it is still necessary to pay attention to the combination with clinical evidence when making pathological diagnosis, and to fully understand the patient's HBV/HCV infection, the results of serum AFP and other tumor markers, as well as the imaging features of liver occupancy. Currently, new modern molecular biology-based tests such as genomics, proteomics and metabolic enzymology are being established and applied, which will have higher specificity and accuracy and may help predict tumor response to treatment, propensity for metastatic recurrence, and prognosis. In pathological diagnosis, the following three main pathological types should be defined as well as other rare types of cancer should be noted: 1. Hepatocellular carcinoma (HCC): It accounts for more than 90% of primary liver cancer and is the most common type of pathology. (1) Gross typing: It can be divided into nodular, massive and diffuse types; also refer to the classification of "five large and six subtypes" developed by the Chinese Hepatocellular Carcinoma Pathology Research Collaborative Group in 1977. The tumor diameter <1 cm is called microscopic cancer, 1-3 cm is called small liver cancer, 3-5 cm is called medium liver cancer, 5-10 cm is called large liver cancer, >10 cm is called massive liver cancer, and small foci scattered throughout the liver (similar to cirrhotic nodules) are called diffuse liver cancer. At present, the criteria for small hepatocellular carcinoma in China are: the maximum diameter of a single cancer nodule is ≤3cm; the number of multiple cancer nodules does not exceed 2, and the total maximum diameter of these nodules is ≤3cm. small hepatocellular carcinoma is small in size, mainly grows in a single nodular and swelling manner, and has clear demarcation with surrounding liver tissues or has envelope formation, which has the characteristics of slower growth, lower malignancy, less possibility of metastasis and better prognosis. (2) Histologic features: the cancer cells are polygonal in shape, with eosinophilic cytoplasm and round nuclei, and blood sinusoids lining between the beams and cords. The degree of differentiation of cancer cells can be classified by the classical Edmondson-Steiner four-grade grading method for hepatocellular carcinoma, or into good, intermediate and poor grades. (3) Representative immunohistochemical markers: hepatocyte antigen (Hep Par1) shows positive cytoplasm, polyclonal carcinoembryonic antigen (pCEA) shows positive cell membrane capillaries, CD34 shows diffuse distribution of hepatic sinusoidal microvessels, and phosphatidylinositol protein-3 (GPC-3) is usually expressed in the cytoplasm of HCC cancer cells. Histopathological examination of liver biopsy for small lesions should be performed and evaluated by an experienced pathologist; GPC-3, heat shock protein 70 (HSP) and glutamine synthetase (GS) staining can be performed, and if two of the three are positive, HCC can be diagnosed. 2. Intrahepatic cholangiocarcinoma (ICC): less common, originating from the epithelial cells of the intrahepatic bile ducts far from the secondary branches of the bile ducts, generally accounting for only It generally accounts for only Q5% of primary hepatocellular carcinoma. (1) General typology: It can be divided into nodular, periductal infiltrative, nodular infiltrative and intraductal growth type. (2) Histological features: adenocarcinoma structure is the main feature, and the cancer cells are arranged into a glandular lumen similar to bile ducts, but the glandular lumen does not contain bile but secretes mucus. The cancer cells are rectangular or low columnar in shape, with lightly stained cytoplasm, transparent cytoplasm and abundant fibrous interstitium, i.e. the cancer cells are surrounded by more fibrous tissue. There are also several cytologic and histologic specific types, and if there is beam-like arrangement, it may resemble hepatocellular carcinoma, which needs to be distinguished. The degree of differentiation of cancer cells can be classified as good, moderate or poor. (3) Representative markers: immunohistochemical examination of cytokeratin 19 (CK19) and mucoglycoprotein-1 (MUC-1), which can show positive cytoplasm. 3.Mixed hepatocellular carcinoma: i.e. HCC-ICC mixed hepatocellular carcinoma, which is relatively rare. Within a liver tumor nodule, both HCC and ICC components are present, and the two are mixed in distribution with unclear boundaries, expressing their respective immunohistochemical markers. 4. Other types. There are some rare types of primary hepatocellular carcinoma, such as clear cell type, giant cell type, sclerosing type and hepatic fibrous lamellar carcinoma. Among them, FLC is a special and rare histological subtype of HCC; its characteristics are that it is mostly seen in young patients under 35 years of age, usually without hepatitis B virus infection and hepatic sclerosis background, less malignant than HCC, and the tumor is often more limited, so this disease usually has the chance of surgical resection and better prognosis. Most of the tumors are located in the left lobe of the liver, often single, with clear boundaries, scalloped edges and hard textures. 5.Main contents of pathology report. The pathological report of hepatocellular carcinoma emphasizes standardization and standardization. The contents should include tumor size and number, growth pattern, pathological staging, vascular cancer thrombus, histological type, differentiation degree, envelope invasion, satellite foci, surgical margins, paracancerous liver tissue (pathological grading and staging of chronic hepatitis and type of cirrhosis), immunohistochemistry and molecular pathology indexes. In addition, the results of molecular markers related to drug-targeted therapy, biological behavior and prognosis of hepatocellular carcinoma are also available for clinical reference.