Abstract
Peripheral neuroblastic tumors (neuroblastoma, ganglioneuroblastoma and ganglioneuroma) are heterogeneous and their diverse and wide range of clinical behaviors (spontaneous regression, tumor maturation and aggressive progression) are closely associated with genetic/molecular properties of the individual tumors. The International Neuroblastoma Pathology Classification, a biologically relevant and prognostically significant morphology classification distinguishing the favorable histology (FH) and unfavorable histology (UH) groups in this disease, predicts survival probabilities of the patients with the highest hazard ratio. The recent advance of neuroblastoma research with precision medicine approaches demonstrates that tumors in the UH group are also heterogeneous and four distinct subgroups—MYC, TERT, ALT and null—are identified. Among them, the first three subgroups are collectively named extremely unfavorable histology (EUH) tumors because of their highly aggressive clinical behavior. As indicated by their names, these EUH tumors are individually defined by their potential targets detected molecularly and immunohistochemically, such as MYC-family protein overexpression, TERT overexpression and ATRX (or DAXX) loss. In the latter half on this paper, the current status of therapeutic targeting of these EUH tumors is discussed for the future development of effective treatments of the patients.
Highlights
The morphological and molecular characteristics of peripheral neuroblastic tumors (pNTs) are outlined for distinguishing tumors in the favorable histology (FH) group and unfavorable histology (UH) group according to the International Neuroblastoma Pathology Classification (INPC)
In order to predict a wide range of clinical behaviors of the patients with pNTs, there have been several risk grouping systems historically proposed by different cooperative groups, such as the International Society for Paediatric Oncology European Neuroblastoma (SIOPEN), the Gesellschaft für Paediatrische Onkologie und Haematologie (GPOH) and the Children’s Oncology Group (COG)
Two systems, the International Neuroblastoma Risk Group (INRG) and the COG risk classification system, are widely accepted; both are based on a combination of so-called prognostic factors, such as clinical stage, patient age at diagnosis, histopathology, and genetic and genomic/molecular properties
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. We believe that all ganglioneuromas were once neuroblastomas in their early stage of tumor development. Tumors in this group are known to present with a wide range of clinical behaviors, such as spontaneous regression, tumor maturation and aggressive progression refractory to intensive treatment. We understand that pNTs do not make a single disease entity; they are heterogeneous and their diverse clinical behaviors are closely associated with genetic/molecular properties of the individual tumors [2,3,4]. The morphological and molecular characteristics of pNTs are outlined for distinguishing tumors in the favorable histology (FH) group and unfavorable histology (UH) group according to the International Neuroblastoma Pathology Classification (INPC). We discuss precision medicine approaches for the extremely unfavorable histology groups (MYC, TERT and ALT subgroups)
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