Histopathologic Prognostic Factors in Neuroblastic Tumors: Definition of Subtypes of Ganglioneuroblastoma and an Age-Linked Classification of Neuroblastomas

Abstract

Histopathologic prognostic factors of 295 pretreatment tumors of a total 641 neuroblastomas and ganglioneuroblastomas were studied with the use of the following proposed tumor classification. The tumors were divided into 2 groups: stroma-poor (235 cases) and stroma-rich (60 cases) according to their organizational pattern (stromal development). The stroma-poor group was classified further into 2 subgroups: favorable stroma-poor (84% survival) and unfavorable stroma-poor (4.5% survival) according to the patient's age at diagnosis, degree of maturation, and nuclear pathology [mitosis-karyorrhexis index (MKI)] of the neuroblastic cells. The stroma-rich group was further classified into 3 subgroups: well differentiated (100% survival), intermixed (92% survival), and nodular (18% survival) on the basis of morphology of the immature element in the tumor tissue without regard to patient's age or quantitative maturation. Favorable stroma-poor and well-differentiated and intermixed stroma-rich groups seem to make good prognosis groups (87% survival), which show gradual progression along a maturational sequence according to the age of the patient. Unfavorable stroma-poor and nodular stroma-rich groups form poor prognosis groups (7% survival) and show morphological evidence of malignant or aggressive behavior, such as inappropriate immaturity for age, higher MKI, and gross nodule formation by immature neuroblasts.

Favorable prognostic significance of high-level retinoic acid receptor β expression in neuroblastoma mediated by effects on cell cycle regulation

“…High-level RARb expression in the primary tumor occurred at a higher frequency in Neuroblastoma tumor tissue is composed of primitive neuroblasts, more di erentiated mature ganglion cells and interstitial neuropil (Brodeur et al, 1997). Moreover, a high degree of ganglion cell maturation within a tumor correlates with a better patient prognosis (Shimada et al, 1984). We, therefore, wanted to identify whether RARb was selectively expressed in particular cell types within the neuroblastoma tumor tissue.…”

Proliferation marker KI-S5 discriminates between favorable and adverse prognosis in advanced stages of neuroblastoma with and without MYCN amplification

“…15 In accordance with this idea, a form of proliferation assessment in terms of the mitosis-karyorrhexis index has become an integrative constituent of several grading systems for neuroblastoma. 26,[41][42][43][44] The usefulness of these grading systems in incontestable. However, the evaluation of cell renewal and decay without distinction between the two components seems less informative than the PI alone, 45 which was shown to identify subsets of cases with distinct prognosis in Shimada's group with unfavorable histology in accordance with a previous investigation.…”

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

“…1,2 A number of prognostic parameters for the disease have been identified, including age, loss of heterozygosity at chromosome 1p36, DNA ploidy, histopathologic stage and amplification of the N-myc proto-oncogene. [3][4][5][6][7][8] The latter condition is strongly correlated with advanced disease, insensitivity to chemotherapy and poor outcome. 9 -12 N-myc and other members of the myc family encode transcription factors that control the expression of genes involved in cell growth, differentiation and survival.…”