Primary hepatocellular carcinoma is divided into two main categories: hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
Histologic grading of hepatocellular carcinoma
The degree of differentiation of hepatocellular carcinoma is graded according to the internationally used Edmondson-Steiner quadruple classification, which is based on the nucleus and cellular anisotropy, from mild to severe: grade I (highly differentiated), grade II (moderately differentiated), grade III (poorly differentiated), and grade IV (undifferentiated).
Grade I (highly differentiated)
Early-stage small hepatocellular carcinoma less than 2 cm in diameter with mildly anisotropic nuclei, mainly of the fine beam and pseudoglandular duct types, and common steatosis.
Grade II (intermediate differentiation)
Common in tumors larger than 3 cm in diameter, round nuclei and distinct nucleoli are seen, mainly showing thickened trabecular and pseudoglandular structures.
Grade III (hypofractionated)
Clearly heterogeneous pleomorphic nuclei are common, mainly showing solid mass-like growth.
Grade IV (undifferentiated)
Cancerous tumor cells contain only a small amount of cytoplasm, and highly heterogeneous or spindle-shaped cells are seen as solid growth.
Histologic grading of intrahepatic cholangiocarcinoma
Intrahepatic cholangiocarcinoma is classified from mild to severe differentiation into grade I (highly differentiated), grade II (moderately differentiated), and grade III (poorly differentiated).
Most intrahepatic cholangiocarcinomas present as highly differentiated ductal adenocarcinomas, moderately differentiated adenocarcinomas are those in which the ducts are fused into sieves or strips, and hypofractionated adenocarcinomas are those in which the ducts are markedly distorted and have cellular anisotropy.
Frequently asked questions about histologic grading of hepatocellular carcinoma
Next, we answer common questions about histologic grading of hepatocellular carcinoma.
Can the same tumor have a different histologic grade?
Can the same tumor be graded differently histologically?
Most carcinoma nodules less than 1 cm in diameter show uniform and consistent hyperdifferentiation.
Cancerous nodules 1 to 3 cm in diameter may have tumor tissue of different histologic grade, usually with less differentiated cancer tissue centrally located and more highly differentiated cancer tissue peripherally located.
What is meant by cellular anisotropy?
Tumor tissue has a different degree of cellular morphology and histology compared to normal tissue, called tumor heterogeneity.
Cellular heterogeneity is manifested by tumor cells that are usually larger than normal cells, tumor cells that are not uniform in size and shape, tumor cells that are increased in size, tumor cells that have an increased ratio of nucleus to cytoplasm, tumor cells that have distinct nucleoli, and tumor cells that may have a nuclear fission phase.
What is highly differentiated hepatocellular carcinoma and hypofractionated hepatocellular carcinoma?
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Highly differentiated hepatocellular carcinoma is common in small early-stage tumors less than 2 cm in diameter. The tumor cells have mildly anisotropic nuclei with a slightly increased nucleoplasmic ratio, mainly exhibiting a fine-beam and pseudoglandular ductal growth pattern, and fatty changes are common, appearing as faint nodules to the naked eye, with poorly defined tumor and surrounding tissue. The incidence of microvesicular carcinoma thrombi and satellite nodules is low.
Lowly differentiated hepatocellular carcinoma is rarely seen within small early-stage tumors. Tumor cells are markedly pleomorphic, varying in size and morphology, with giant cells visible, a markedly increased nucleoplasmic ratio, and solid mass-like growth.