Neurodevelopmental anomalies in children with neuroblastoma

Case reports have associated neuroblastoma, a cancer derived from the embryonal neural crest, with aganglionosis coli and neurofibromatosis type I. The aim of the current study was to test the hypothesis that neuroblastoma is part of a global defect in neurodevelopment.

Neuropathologic findings from autopsies of children who died of neuroblastoma during the period 1980-1995 at the Children's Hospital of Pittsburgh were reviewed for macroscopic and microscopic abnormalities. As controls, autopsies of children who had died of other primary extracranial cancers over the same time period also were studied. Medical records of neuroblastoma patients for whom autopsies were available were reviewed for clinical evidence of preexisting nonmalignant neurologic disease.

Of 145 children diagnosed with neuroblastoma, 49 had died, and autopsies not restricting examination of the brain had been performed on 13. Macroscopic anatomic abnormalities (a small cerebellum and the absence of the corpus callosum) were noted in one patient who was known to have been mentally retarded without having a defined syndrome. Microscopic abnormalities of cytoarchitecture were noted in that patient as well as 3 of the 12 other patients (focal cortical dysplasia [fcd], n = 3; leptomeningeal heterotopia, n = 1; abortive sulcation or flattened gyri, n = 2). None of 3 patients with only microscopic abnormalities had clinical evidence of problems with neurodevelopment. Of the 26 children with nonneuroblastoma cancers for whom complete autopsies were available, 1 infant had major macroscopic structural abnormalities of the brain. None of these patients had microscopic abnormalities (P < 0.01).

Children with neuroblastoma have an increased incidence of abnormalities of brain cytoarchitecture, particularly fcd. These abnormalities are generally asymptomatic and are diagnosed by histologic examination. Such abnormalities cannot be attributed to chemotherapy and are not observed in other children with non-central nervous system tumors. These findings are consistent with the concept that neuroblastoma may occur in the setting of a more global defect in neurodevelopment. A blinded review of larger numbers of cases will be needed to verify these data.