Neuroblastoma Cellular Heterogeneity

Many of the cell phenotypes characteristic of the developing neural crest - neuroblasts, non-neuronal (Schwann, perineurial, or satellite) cells, and even melanocytes -are evident in the same NB (Shimada et al. 1999). Moreover, cellular heterogeneity and extent of maturation (e.g., stroma-rich and stroma-poor tumors or high- and low-risk tumors based on histological grade) correlate with clinical behavior and are useful for prognostication of the disease (see Chap. 7; Shimada et al. 1999).

This same cellular heterogeneity is seen in NB cell lines. Three distinct cellular phenotypic variants have been described (Rettig et al. 1987; Biedler et al. 1988, 1997): sympathoadrenal (N-type) neuroblasts; large flattened, substrate-adherent (S-type) cells; and morphologically intermediate (I-type) cells (Fig. 6.1). Studies over the past 25 years have shown that each phenotype represents a particular lineage within the neural crest. The availability of cell lines of the three cell types has led to an increased understanding of the differentiation and malignant potentials of each.

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