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