Glf

Fig. 8.51 Pure fetal hepatoblastoma. A Cuboidal cells form trabeculae. B Immunoreactivity for alpha-fetoprotein is present in most tumour cells. A cluster of hematopoietic cells is present at lower center.

classification is based on the epithelial or mixed epithelial/mesenchymal components present.

Small cell undifferentiated

Hepatoblastomas composed entirely of noncohesive sheets of small cells resem-

Fig. 8.52 Fetal and embryonal epithelial hepatoblas-toma. Fetal epithelial cells with a high cytoplasmic lipid concentration are separated by a band of fibrous connective tissue from a vascular mass of embryonal cells.

bling the small blue cells of neuroblas-toma, Ewing sarcoma, lymphoma, and rhabdomyosarcoma are called small cell undifferentiated hepatoblastomas and amount to about 3% of the tumours. This type is believed to represent the least differentiated form of hepatoblastoma {602}.

While often difficult to identify as hepatic in origin, the presence of small amounts of glycogen, lipid and bile pigment, along with cytoplasmic cytokeratin, helps separate this lesion from metastatic small cell tumours. The cells are arranged as solid masses with areas of cellular pyknosis and necrosis and high mitotic activity. Sinusoids are present but decreased in amount compared to the fetal epithelial pattern, and there is pronounced intracellular expression of extracellular matrix proteins and large numbers of fibers immunoreactive for collagen type III {1629}.

Mixed epithelial and mesenchymal The largest number of hepatoblastomas (44%) display a pattern combining fetal and embryonal epithelial elements with primitive mesenchyme and mesenchy-mally derived tissues. Of these mixed tumours, 80% have only immature and

Fig. 8.53 Fetal and embryonal hepatoblastoma. Embryonal epithelial cells occur singly and in glandlike structures.

mature fibrous tissue, osteoid-like tissue and cartilaginous tissue, in addition to the epithelial cells. The other 20% contain additional elements. The mesenchymal elements of the 'simple' mixed tumour are interspersed with the fetal and embryonal epithelial elements. The primitive mesenchymal tissue consists of a light myxomatous stroma containing large numbers of spindle-shaped cells with elongate nuclei. The cells may display a parallel orientation with collagen fibers and cells resembling young fibroblasts. More mature fibrous septa with well differentiated fibroblasts and collagen may also be seen. Islands of osteoid-like tissue composed of a smooth eosinophilic matrix containing lacunae filled with one or more cells are the hallmark of the mixed lesion. Rarely, they are the only 'mesenchymal' component noted in a predominantly fetal epithelial hepatoblastoma. In fact, the 'osteoid' material is positive for alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha fetoprotein, carcinoembryonic antigen, chromogranin A, epithelial membrane antigen, vimentin and S-100 protein, suggesting an origin from epithelial cells {10, 2058, 1629}. The cells within the lacunae, while 'osteoblast-like' with angu-lated borders, abundant eosino-philic cytoplasm and one or more round or oval nuclei, may in some areas blend with adjacent areas of embryonal epithelial cells, further supporting their epithelial origin. Cartilaginous material may also be present.

Mixed with teratoid features

In addition to the features noted in the 'simple' mixed epithelial/mesenchymal hepatoblastoma, about 20% of lesions will display additional features, including striated muscle, bone, mucinous epithelium, stratified squamous epithelium, and melanin pigment {1839}. These tissues may occur separately or be admixed with others. It is important to differentiate these teratoid features from a true ter-atoma, which does not contain fetal and embryonal epithelial hepatoblastoma areas. There is, however, a single case report of a discrete cystic teratoma contiguous to a hepatoblastoma {331}.

Staging

These is no official TNM classification for hepatoblastoma but a TNM-type system has been proposed {332}. The Children's

Fig. 8.54 Pure fetal epithelial hepatoblastoma. Clusters of small, dark haematopoietic cells are present.

Cancer Study Group (CCSG) classification is widely used. While 40-60% of patients are considered inoperable at the time they are first seen and 10-20% have pulmonary metastases, preoperative chemotherapy and transplantation for the more extensive lesions have resulted in resectability for nearly 90% of cases.

Precursor lesions and benign tumours

Precursor lesions of hepatoblastoma have not been identified, but hepatoblastoma must be differentiated from other liver tumours and pseudotumours that occur in the same age period. Infantile haemangioendothelioma, the most commonly occurring benign tumour of the liver, is seen almost exclusively in the first year of life and presents as an asymptomatic mass or, less frequently, as congestive heart failure due to rapid shunting of blood through the liver {1708}. MRI and arteriography are helpful in establishing the diagnosis. Mesenchymal hamartoma, another benign lesion, occurs during the first 2-3

Fig. 8.55 Fetal and embryonal hepatoblastoma. The embryonal cells may resemble other blastemal cells, e.g. those encountered in nephroblastoma or neuroblastoma.
Fig. 8.56 Macrotrabecular hepatoblastoma. On the left, the tumour consists of macrotrabeculae. The one to two-cell thick trabeculae of fetal epithelial hepatoblastoma pattern are seen on the right.

Fig. 8.57 Mixed epithelial and mesenchymal hepatoblastoma. Areas showing mesenchymal tissue and foci of osteoid-like material are present, together with areas of epithelial hepatoblastoma.

years of life and presents as a rapidly enlarging mass due to accumulation of fluid within cysts formed in the mesenchymal portion of the lesion {1841}. CT and MRI are useful in defining the cystic nature of the lesion. Focal nodular hyperplasia and nodular regenerative hyperplasia may be seen in the first few years of life but are more common in older children {1839}. Hepatocellular adenoma is rarely seen in the first 5-10 years of life, but may be difficult to differentiate from a pure fetal epithelial hepatoblastoma.

Genetic susceptibility

Congenital anomalies are noted in approximately 5% of patients (Table 8.04) and include renal malformations such as horseshoe kidney, renal dysplasia and duplicated ureters, gastrointestinal malformations such as Meckel diverticulum, inguinal hernia and diaphragmatic her-

nia, and other disparate malformations such as absent adrenal gland and het-erotopic lung tissue. Other syndromes with an increased incidence of hepato-blastoma include Beckwith-Wiedemann syndrome, trisomy 18, trisomy 21, Acardia syndrome, Goldenhar syndrome, Prader Willi syndrome, and type 1a glycogen storage disease {1585}. Hepatoblastoma and familial adenoma-tous polyposis (FAP) are associated due to germline mutation of the adenomatous polyposis coli (APC) gene. FAP kindreds include patients with hepatoblastoma who have an APC gene mutation at the 5' end of the gene {267, 578}. Alterations in APC have also been noted in cases of hepatoblastoma in non-familial adenomatous polyposis patients {1390}.

Molecular genetics

Cytogenetic abnormalities include tri-

somy for all or parts of chromosome 2, trisomy for chromosome 20 and loss of heterozygosity (LOH) for the telomeric portion of 11 p (11 p15.5). The material lost on 11p is always of maternal origin {43}. LOH has also been observed on the short and long arms of chromosome 1 with a random distribution of parental origin for chromosome arm 1p and a paternal origin for chromosome arm 1q {970}. TP53 overexpression has been described in several cases, but TP53 mutations in exons 5 to 9 are infrequent {1406}. Increased copy numbers of c-met and K-sam proto-oncogenes and cyclin D1 genes have been described in a case of hepatoblastoma in an adult patient {977}.

The presence of oval cell antigen has been demonstrated in hepatoblastomas, which supports the stem cell origin of these tumours {1631}.

Was this article helpful?

0 0

Post a comment