Peripheral neuroblastic tumors occur on a histologic spectrum from benign ganglioneuromas to malignant neuroblastomas, but even within the latter category, there is extensive heterogeneity in morphologic appearance and genetic composition. The International Neuroblastoma Pathology Committee classification has traditionally been used to successfully categorize tumors with favorable or unfavorable histology, but morphology must be supplemented with the results of additional testing. While MYCN amplification, diploid DNA content, and 11q loss have long been known to be negative prognostic factors, a new group of molecular biomarkers has emerged that define discrete high-risk categories. These include MYCN/MYC overexpression, dysregulated telomere maintenance mechanisms (both increased expression of telomere reverse transcriptase and alternate lengthening of telomeres), and ALK aberrations. Testing for these biomarkers and an integrated classification scheme may lead to improved risk stratification and selection of emerging targeted therapies.
