Our results indicate that specific combinations of genetic changes in neuroblastoma tumors contribute to distinct morphologic and clinical features. Furthermore, the identification of two genetically and morphologically distinct types of progressing tumors suggests that possibilities for different therapeutic regimens should be investigated.

A child with bilateral Wilms' tumors is reported. The left renal tumor showed nephroblastoma with several tissues of apparent mesenchymal derivation and tubules with diverse epithelial differentiation. The right‐sided tumor showed the more familiar triphasic pattern of nephroblastoma. Initial percutaneous renal biopsy of the left tumor did not reveal nephroblastoma but showed tubules with various epithelia and mesenchymal elements, and led to a diagnosis of teratoma. The pathogenesis of this complex neoplasm is discussed, and argument is presented that primitive renal blastema may be capable of more diverse differentiation than has previously been realized. A comparison is drawn between this neoplasm and some cases of hepatoblastoma. Certain cases reported as renal teratoma may be similar in nature.

Infantile myofibromatosis, congenital fibrosarcoma and congenital/infantile haemangiopericytoma are generally considered distinct entities. Overlapping microscopic features between infantile myofibromatosis and congenital fibrosarcoma, and between infantile myofibromatosis and congenital/infantile haemangiopericytoma, however, have been noted, but not formally reported. This report concerns six neonatal tumours, each exhibiting more than one of the above patterns, supporting a histogenetic relationship among these entities. Immunohistochemistry for smooth muscle actin was found to be useful in the diagnosis of congenital/infantile haemangiopericytoma, and also served to support a histogenetic relationship with the other two entities under consideration.

Aberrant cytoplasmic sequestration has been reported as an alternative mechanism of p53 inactivation to mutation in neuroblastoma. We hypothesized that p53 localization and function in neuroblastoma is related to differentiation status. Eighty-two untreated and 24 paired pre and post-chemotherapy neuroblastomas were studied by immunocytochemistry for p53, p21(WAF1), BAX, Bcl2 and Ki67. Predominantly nuclear p53 was detected in undifferentiated neuroblastoma, and both nuclear and cytoplasmic p53 in differentiating neuroblastoma. The nuclear p53 labeling index (LI) correlated with the Ki67 LI (r = 0.51, p <0.001), and weakly with p21(WAF1) (r = 0.37), but not with BAX or Bcl2. There was a significant reduction in p53, p21(WAF1) and Ki67 LI after chemotherapy (p < 0.01), an increase in BAX (p <0.05), but no change in Bcl2. p53 localization and function were examined in two p53 wild-type undifferentiated and 9-cis retinoic acid differentiated neuroblastoma cell lines. Using immunocytochemistry, immunofluorescence and cell fractionation, p53 was found to be predominantly nuclear in both undifferentiated and differentiated cells. Following irradiation, there was upregulation of p53, p21(WAF1) and MDM2, but less induced PARP and caspase 3 cleavage in differentiated cells, suggesting intact p53 transcriptional function, but resistance to apoptosis. p53 function in undifferentiated and differentiated cells was confirmed by upregulation of p21(WAF1) and MDM2 following Nutlin-3 treatment. In conclusion, p53 is predominantly nuclear and functional in neuroblastoma regardless of differentiation status.

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