Bone Marrow Infiltration in Neuroblastoma: Characteristics of Infiltrating Cells and Role of the Microenvironment

Abstract

Neuroblastoma (NB) is a pediatric tumor that arises from peripheral nervous system. The clinical presentation of NB is highly heterogeneous, ranging from asymptomatic tumor masses requiring little, if any, treatment to metastatic disease requiring intensive multimodal therapies (see [1] for review). Also the outcome of NB patients is highly variable. The 5-years overall survival ranges from 98-100% for stage 1 infants without MYCN amplification to less than 20% for children with stage 4 MYCN amplified tumors [2]. The main prognostic factors are indeed stage, age at diagnosis and MYCN oncogene status [3]. At diagnosis, about 50% of cases present metastatic spread that mainly involves vascularized tissues, such as bone marrow (BM) and bone. According to the International Neuroblastoma Staging System (INSS [4]), patients with metastatic disease are categorized as stage 4, whereas in the absence of metastatic spread patients are categorized as stage 1, 2 and 3, depending on the extent of the primary tumor (within or across the midline), the involvement of ipsilateral or controlateral lymph nodes, and the surgical possibility of resection. Recently, the INSS has been replaced by the International Neuroblastoma Risk Group-Stage System (INRG-SS) based on image-defined surgical risk [5]. According to the INRG-SS criteria, patients with metastatic spread have stage M disease, while patients with localized disease have stage L1 or L2, depending on the level of surgical risk. ©