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Cancer Health Center

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Childhood Liver Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Cellular Classification


Histologically, small cell undifferentiated hepatoblastoma is typified by a diffuse population of small cells with scant cytoplasm resembling neuroblasts.[8] The chromosomal abnormalities reported for small cell undifferentiated hepatoblastoma are distinct from those occurring in other hepatoblastoma subtypes and are more similar to those observed in malignant rhabdoid tumors. These abnormalities include translocations involving a breakpoint on chromosome 22q11 and homozygous deletion at the chromosome 22q12 region that harbors the SMARCB1/INI1 gene.[5,9] Lack of detection of INI1 by immunohistochemistry is another characteristic shared by some small cell undifferentiated hepatoblastomas and malignant rhabdoid tumors.[5] A third characteristic shared between small cell undifferentiated hepatoblastomas and malignant rhabdoid tumors is the poor prognosis associated with each.[5,6,10] Patients with small cell undifferentiated hepatoblastoma whose tumors are unresectable have an especially poor prognosis.[5] Patients with stage I tumors appear to have increased risk of treatment failure when small cell elements are present.[11] For this reason, completely resected tumors composed of pure fetal histology or of mixed fetal and embryonal cells must have a thorough histologic examination as small foci of undifferentiated small cell histology indicates a need for aggressive chemotherapy.[11] Aggressive treatment for this histology is under investigation in the current COG study, COG-AHEP0731. Hepatoblastoma that would otherwise be considered very low or low risk is upgraded to intermediate risk if any small cell undifferentiated elements are found (refer to the Stage Information section of this summary for more information).

Hepatocellular Carcinoma

The cells of hepatocellular carcinoma are epithelial while hepatoblastoma has a less differentiated embryonal appearance. Hepatocellular carcinoma also differs from hepatoblastoma in that it often arises in a previously abnormal, cirrhotic liver. Both histologic types more commonly arise in the right lobe of the liver. Chronic hepatitis B is the leading cause of hepatocellular carcinoma in children in Asian and African countries; however, underlying liver disease can be identified in less than one-third of the children and adolescents with hepatocellular carcinoma in western countries.[12]

Fibrolamellar carcinoma

A distinctive histologic variant of hepatocellular carcinoma, termed fibrolamellar carcinoma, has been described in the livers of older children and young adults. This histology is characterized by a fusion transcript created by deletion of a 400 kb section of chromosome 19, which was found in 15 of 15 tumors that were tested.[13] Fibrolamellar carcinoma is thought to be associated with an improved prognosis and is not associated with cirrhosis.[14,15,16] The improved outcome in older studies may be related to a higher proportion of tumors being less invasive and more resectable in the absence of cirrhosis, because the outcome in recent prospective studies, when compared stage for stage, is not different from other hepatocellular carcinomas.[12,17]; [18][Level of evidence: 3iiA] Fibrolamellar hepatocellular carcinoma has also been reported in infants.[19]

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