Classic neuroblastoma: Histopathologic grading as a prognostic indicator. The Shimada system and its progenitors

Classic neuroblastoma of adrenal or extraadrenal origin is one of the most common solid malignancies in children. Since the 19th century when the earliest pathologic descriptions of neuroblastoma became available, clinical, biochemical, pathologic, and molecular biologic studies have appeared in increasing numbers. Many basic and important observations have been made, but unfortunately there have been few major advances in therapy and prognosis during the past 25 years. Histopathologic grading of neuroblastomas evolved as it became apparent that neuroblasts have the potential to differentiate into ganglion cells and Schwann cells. This capacity has served as the basis for the original clinicopathologic studies. Because most neuroblastic tumors have variable histologic features, these grading systems were subject to sampling errors and interobserver differences. It was generally acknowledged that the ganglioneuroblastoma has a more favorable prognosis than the undifferentiated neuroblastoma, but the number and maturity of the ganglion cells in a particular tumor, needed to designate a tumor as a ganglioneuroblastoma, were problematic. The classification of Shimada and co-workers has provided several morphologic alternatives to circumvent the difficulties of the earlier pathologic grading systems. This article discusses the classification proposed by Shimada as the most recent effort in a succession of studies. Whether this classification surpasses its progenitors is a judgment that should be reserved for the future. It must contend with the possibility that all histopathologic classifications may become obsolete or irrelevant in light of recent cytogenetic and molecular biologic findings.