Diagnosis and Classification of the Small Round-Cell Tumors of Childhood

Abstract

The small-round-cell tumors of childhood include neuroblastoma, the Ewing family of tumors, rhabdomyosarcoma, lymphoma, and desmoplastic small-round-cell tumor. Although classical histological features are generally highly suggestive of tumor type, on occasion these tumors may be indistinguishable by light microscopy, making a definitive diagnosis difficult. Accurate diagnosis of pediatric small-round-cell tumors has become increasingly crucial, as disparate approaches to therapy are used for distinct tumor types. In addition, because for many pediatric cancers, therapy is also tailored according to patient risk, it has become important to further classify tumors biologically, using cytogenetic or molecular studies to identify chromosome translocations, gene amplification, gene expression patterns, and/or mutations. In this issue of The American Journal of Pathology, Gilbert and colleagues used a reverse transcriptase polymerase chain reaction (RT-PCR) assay to analyze the expression of two genes involved in the catecholamine biosynthetic pathway, tyrosine hydoxylase and dopa decarboxylase, in 84 pediatric malignancies. 1 Their studies demonstrate that the expression of these two genes is highly specific for neuroblastoma. Of the 29 non-neuroblastoma tumor samples examined, only pheochromocytomas expressed clearly detectable levels of the genes. These results suggest that analysis of tyrosine hydoxylase and dopa decarboxylase expression may help distinguish neuroblastoma from other small-round-cell childhood tumors. Despite recent advances in immunohistochemistry and molecular pathology, some cases of small-round-cell tumors of childhood remain diagnostically problematic. Thus, additional diagnostic tools, such as the ones described by Gilbert and co-workers, are needed to ensure that every child with a small-round-cell tumor is diagnosed correctly. The value and limitations of current immunohistochemical, cytogenetic, and molecular studies as diagnostic aids for the small-round-cell tumors of childhood are highlighted below.