Blatt J, Hamilton R L
Division of Hematology/Oncology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Cancer. 1998 Apr 15;82(8):1603-8. doi: 10.1002/(sici)1097-0142(19980415)82:8<1603::aid-cncr24>3.0.co;2-7.
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.
病例报告显示，神经母细胞瘤（一种源自胚胎神经嵴的癌症）与先天性无神经节性巨结肠和Ⅰ型神经纤维瘤病有关。本研究的目的是检验神经母细胞瘤是神经发育整体缺陷一部分这一假说。
回顾了1980 - 1995年间在匹兹堡儿童医院死于神经母细胞瘤的儿童尸检的神经病理学发现，以查找宏观和微观异常情况。作为对照，还研究了同期死于其他原发性颅外癌症的儿童的尸检情况。查阅了有尸检资料的神经母细胞瘤患者的病历，以寻找先前存在的非恶性神经疾病的临床证据。
在145名被诊断为神经母细胞瘤的儿童中，49名已经死亡，其中13名进行了不限脑部检查的尸检。在1名已知智力发育迟缓但无明确综合征的患者中发现了宏观解剖异常（小脑小且胼胝体缺失）。在该患者以及其他12名患者中的3名患者中发现了细胞结构的微观异常（局灶性皮质发育异常[fcd]，n = 3；软脑膜异位，n = 1；发育不全的脑沟或脑回变平，n = 2）。仅存在微观异常的3名患者中，没有一人有神经发育问题的临床证据。在可进行完整尸检的26名患有非神经母细胞瘤癌症的儿童中，1名婴儿有大脑的主要宏观结构异常。这些患者均无微观异常（P < 0.01）。
神经母细胞瘤患儿的脑细胞结构异常发生率增加，尤其是fcd。这些异常通常无症状且通过组织学检查诊断。此类异常不能归因于化疗，在其他非中枢神经系统肿瘤患儿中未观察到。这些发现与神经母细胞瘤可能发生在神经发育更广泛缺陷背景下的概念一致。需要对更多病例进行盲法回顾以验证这些数据。
