Clinical and histological features
Primary CNS neuroblastoma mostly occur in the first decade, with 26% of cases in children under 2 years old; it is rarely reported in adults. It is located in the cerebral hemisphere, most often in the parietal and frontal lobes.5,6
The World Health Organization 2016 classification of CNS tumors defined primary CNS neuroblastoma as an embryonal tumor characterized by poorly differentiated neuroepithelial cells, groups of neurocytic cells, and variable neuropil-rich stroma.1
Based on their histological features and clinical behavior, these tumors are considered highly malignant tumors.7
However, in the literature disease-related mortality is 12.5%, lower than generally reported for other embryonal tumors.4
In line with its preferential supratentorial location, the clinical presentation of CNS neuroblastoma varies from signs and symptoms related to focal mass effects (neurological deficits), seizures, and neurocognitive impairment, to signs of increased intracranial pressure due to impairment of cerebrospinal fluid pathways such as headache, vomiting, and abnormal head circumference growth8 9,10
Due to the rarity of these malignancies, data regarding their optimal therapeutic management are inconclusive. However, most authors recommend surgery as the first line of treatment for primary CNS neuroblastoma with the aim of complete tumor resection whenever possible.13
Adjuvant management of primary CNS neuroblastoma remains controversial. Lu et al used the SEER (Surveillance, Epidemiology, and End Results) database to identify patients diagnosed with primary CNS neuroblastoma from 1973 to 2013, including 300 patients;2
however, data regarding adjuvant treatment were insufficient and therefore not included in the analysis. Earlier reports showed high rates of local failure with surgery alone, suggesting the potential benefit of adjuvant radiotherapy in local control improvement.13-15
In our case, the treatment protocol we adopted was detailed.
Radiotherapy as an adjuvant method for the primary site is a standard procedure for high-risk extracranial neuroblastomas, which could effectively reduce recurrence of the primary site,15
but its effects in patients with primary CNS neuroblastoma have not been evaluated. In addition, data regarding target volumes and optimal doses are lacking, and reported radiotherapy modalities are inconsistent. Our patient had 30.6 Gy to the whole brain with a 23.4 Gy boost to the initial tumor bed. In the absence of any evidence of the tumor’s spread in the supine MRI and spinal tap, we decided to omit spinal axis radiotherapy and avoid the increased chance of radiation toxicity. Bennett et al suggested that prophylactic whole-brain and spinal irradiation was probably justified because of the propensity of primary site recurrence and cerebrospinal metastases.16
The side effects of radiotherapy on the CNS remain an important problem, especially for younger patients with underdeveloped CNS. Problems such as parenchymal radionecrosis could disable late cognitive function and result in other side effects, such as to the lung, heart, or kidneys.17,18
Berger et al showed that receiving radiation therapy as an adjuvant treatment improved overall survival in their 11-case series.19
Chemotherapy has been performed most frequently as adjuvant treatment. Due to their histological aggressiveness and brain location, CNS neuroblastoma are treated according the supratentorial primitive neuroectodermal tumor protocols.20
Chemotherapy combined with radiotherapy has occasionally been used in early series, and favorable clinical responses were obtained.21
Berger et al recommended chemotherapy for patients whose tumors were subtotally resected.19
For nonmetastatic tumors, therapy with multiple chemotherapeutic agents is considered. The most common ones are vincristine, lomustine, cisplatin, and etoposide. In our case, the protocol used associated VP1-6 and carboplatin. This protocol was poorly tolerated by our patient, who developed grade 3-4 neutropenia; the interruption of chemotherapy was necessary. Other less-toxic protocols need to be evaluated.
In the other hand, radiotherapy was completed at 54 Gy with good outcomes and late tolerance, including tumor stability after 14 months and the absence of cognitive impairment. When compared with the efficacy of radiation in managing high-risk neuroblastoma, adjuvant radiotherapy should be considered for primary CNS neuroblastoma, especially in patients with high-grade tumors and subtotal resection.