Histopathological features of pretreatment neuroblastoma are of limited clinical significance following adjustment for clinical and biological marker status

Neuroblastic tumours are morphologically classified into broad categories according to defined criteria, with further histopathological features described which may provide prognostic information, such as calcification, mitotic rate and the mitoses-karyorrhexis index; these may be combined with patient age and other factors to indicate high-risk and low-risk groups. However, recently, a range of biological molecular markers have proved to be of major prognostic importance in neuroblastic tumours, including MYCN amplification, 1p deletion, and 17q gain. It is therefore hypothesised that traditional histopathological features are now of limited clinical significance after adjustment for known clinical and biological pregnostic markers. Evidence to evaluate this hypothesis was obtained via a literature search to identify studies reporting on prognostic significance of histopathological features in multivariate analysis after adjustment for biological marker status. Thirteen studies were included of which four (1642 subjects) reported an independent effect of histopathological findings, whereas nine (2385 subjects) reported no significant independent effect. All four studies examining both MYCN and other markers such as 1p, 11q or 17q status, reported no significant independent effect of histological parameters. Histopathological diagnosis remains the gold standard for the diagnosis and evaluation of paediatric tumours but in the evolving era of molecular evaluation of tumours, the role of traditional morphological assessments is likely to become increasingly obsolete, and diagnostic paediatric pathology departments must respond to the changing understanding of the biological basis of childhood malignancies towards routinely providing both diagnostic and molecular prognostic data from these small samples.