Pathology of peripheral neuroblastic tumors

Neuroblastoma is the most prevalent extracranial solid tumor in pediatric age populations worldwide and the most common neoplastic disease diagnosed in the first year of life. The term neuroblastoma often encompasses all peripheral neuroblastic tumors (pNTs including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma) of neural crest origin. Since pNTs demonstrate a wide range of clinical behaviors, including spontaneous regression, tumor differentiation/maturation, and aggressive progression refractory to even intensive treatment modalities, these tumors are believed to be distinguished into different biological/molecular groups. For the practical purpose, risk classification systems have been developed based on combinations of so-called prognostic factors.In this review of pNTs, we describe a history of pathology, summarize epidemiology and clinical features, and outline International Neuroblastoma Pathology Classification (INPC). Then we discuss advantages and limitations of core needle biopsy and conventional biopsy of neuroblastoma. Besides the INPC, we also describe other prognostic factors, such as age at diagnosis, clinical stage, and molecular/genetic factors, since they are included in widely used Risk Classification Systems. Additionally, we discuss further molecular abnormalities closely associated with highly aggressive neruoblastomas. Towards the end, we touch on rapidly advancing technologies for establishing an artificial intelligence-assisted INPC system.