The incidence of neuroblastoma is 10.2 cases per million children under 15 years of age , and it is the most common cancer diagnosed during the first year of life
identifiable neuropil or rosettes . Tumour cells are small in size and have no discernible cytoplasm . The nuclei are round , have a salt-and-pepper appearance and may contain distinct nucleoli . In these undifferentiated tumours , immunohistochemistry shows a pattern compatible with a presumed immature ganglionic ( neuronal ) SNS lineage origin . These observations suggest that undifferentiated NB tumours may be locked at an early neuronal differentiation stage , without the capacity to differentiate in response to the factors driving normal sympathetic neuronal differentiation . GNB show well-defined microscopic foci of differentiating neuroblastic cells distributed in a ganglio-neuromatous tissue background . The neuroblastic component of GNB tumours expresses markers reflecting an advanced ganglionic ( neuronal ) development . GN are composed predominantly of mature Schwannian stroma and ganglion cells usually surrounded by satellite cells . Mature Schwann cells represent the dominant component of the tumour , characteristically forming multiple fascicles covered with perineurial cells . GN infrequently display neuroendocrine features and usually occurs after the age of four years . Both features suggest that it arises from mature neuronal sympathetic ganglia or adrenal medulla neuronal cells . 1 , 2
The incidence of neuroblastoma is 10.2 cases per million children under 15 years of age , and it is the most common cancer diagnosed during the first year of life . 3 , 4 Neuroblastoma is usually diagnosed in very young children ; the median age at diagnosis is 17 months . 5 The clinical
92 HHE 2018 | hospitalhealthcare . com presentation is highly variable , ranging from a mass that causes no symptoms to a primary tumour that causes critical illness as a result of local invasion , widely disseminated disease , or both . Usually the so-called primary tumour arises in the adrenal gland or paravertebral sympathetic ganglia . Two-thirds of neuroblastoma tumours have distant metastases in the bone , bone marrow , lymph nodes , liver or subcutaneous tissue upon diagnosis , whereas lung or central nervous system metastasis are extremely rare . 5 One-third of neuroblastoma present as localised with or without involvement of regional lymph nodes . These tumours do not distally metastasise . 6
There are different ways to stratify neuroblastoma ; nonetheless all investigators agree that age , presence or absence of distant metastasis , and MYCN amplification are key factors . Infants under 18 months of age always have a better prognosis compared with older children , not only because neuroblastoma present in young infants more frequently localised but also in the metastatic subgroup . By contrast , metastatic cases diagnosed beyond six years of age and in adolescents have a more indolent course that eventually will almost always be fatal . Patients with low-risk neuroblastoma have a very good prognosis with a five-year overall survival ( OS ) of 80 – 90 % treated with minimal or no therapy at all . 5 However , patients older than 18 months with metastases and / or patients of any age with MYCN-amplified tumours are considered HR , and their outcome is still poor despite intensive multimodal therapy with a five-year OS < 50 %. 5 Approximately 40 % of all neuroblastoma patients are classified as HR , and approximately half of them do not respond to first-line therapy or relapse during the first two years of treatment .
The traditional multi-modal therapeutic approach for HR neuroblastoma includes chemotherapy , surgical excision of the primary tumour and radiotherapy . These modalities are most frequently able to drastically reduce the tumour burden in the induction and consolidation phases and can lead to an apparent complete remission of the disease ( referred as minimal residual disease ( MRD )). Most cooperative groups would then include high-dose chemotherapy with autologous haemopoietic stem cell rescue as consolidation for HR neuroblastoma patients . HR neuroblastoma patients treated with this so-called standard schema have > 50 % recurrence rate , which indicates that most therapeutic failures nowadays occur during the stage of MRD . 7
After a variable period of quiescent ( mostly undetectable ) disease , many patients relapse , usually with metastatic foci resistant to cytotoxic therapies , and eventually undergo rapid and overwhelming progression . Thus , the major drawback of current therapies is the management of the limited number of cells that escape induction and consolidation therapies . These cells are able to undergo proliferation and / or migration , giving rise to the metastatic recurrence of neuroblastoma . Anti-GD2 immunotherapy is a promising treatment paradigm in this situation .
Immunotherapy The immune system can be divided into the