Many malignant pediatric neoplasms are histologically unique. In general, they tend to exhibit a primitive (embryonal) rather than pleomorphic-anaplastic microscopic appearance, and frequently they exhibit features of organogenesis specific to the site of tumor origin. Because of their primitive histologic appearance, many childhood tumors have been collectively referred to as small, round, blue-cell tumors. Sheets of cells with small, round nuclei characterize these tumors, which include neuroblastoma, lymphoma, rhabdomyosarcoma, Ewing sarcoma (peripheral neuroectodermal tumor), and some cases of Wilms tumor. Sufficient distinctive features usually are present to permit definitive diagnosis on the basis of histologic examination alone, but molecular studies are becoming increasingly useful, both for diagnosis and prognosis of childhood cancers. Three common tumors—neuroblastoma, retinoblastoma, and Wilms tumor—are described here to highlight the differences between pediatric tumors and those in adults.
The term neuroblastic includes tumors of the sympathetic ganglia and adrenal medulla that are derived from primordial neural crest cells populating these sites; neuroblastoma is the most important member of this family.
It is the second most common solid malignancy of childhood after brain tumors, accounting for 7% to 10% of all pediatric neoplasms, and as many as 50% of malignancies diagnosed in infancy. Neuroblastomas demonstrate several unique features in their natural history, including spontaneous regression and spontaneous or therapy-induced maturation. Most occur sporadically, but 1% to 2% are familial, with autosomal dominant transmission, and in such cases the neoplasms may involve both of the adrenals or multiple primary autonomic sites. Germline mutations in the anaplastic lymphoma kinase (ALK) gene have been linked to the familial predisposition to neuroblastoma. Somatic gain-of-function ALK mutations are also observed in 8% to 10% of sporadic neuroblastomas, and are markers of adverse prognosis. Clinical trials using inhibitors that target the mutated ALK tyrosine kinase are underway.
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Inchildhood,about40%ofneuroblastomasariseintheadrenal medulla. Theremainderoccuranywherealongthesympatheticchain,withthemostcommonlocationsbeingtheparavertebralregionoftheabdomen(25%)andposteriormediastinum(15%).Macroscopically,neuroblastomasrangeinsizefromclinicallysilentminutenodules(insitulesions)tolargemassesweighingmorethan1kg.Insituneuroblastomasarereportedtobe40timesmorefrequentthantumorswithclinicalsymptoms.Thegreatmajorityofthesesilentlesionsspontaneouslyregress,leavingonlyafocusoffibrosisorcalcificationintheadult.Someneuroblastomasaresharplydemarcatedwithafibrouspseudo-capsule,butothersareinfiltrativeandinvadesurroundingstructures,includingthekidneys,renalvein,andvenacava,andenveloptheaorta.Ontransection,theyarecomposedofsoft,gray-tan,brainliketissue.Largertumorshaveareasofnecrosis,cysticsoftening,andhemorrhage.
Histologically,classicneuroblastomasarecomposedofsmall,primitive-appearingcellswithdarknuclei,scantcytoplasm,andpoorlydefinedcellbordersgrowinginsolidsheets(