ACRT Journal

Introduction

According to the World Health Organization (WHO) 2021 on Central Nervous System (CNS) tumors, neuroblastoma is considered an embryonal neoplasm, characterized by the activity of the transcription factor FOXR2 with chromosomal structural rearrangement [1] gains in chromosome 1q have been found more frequently in about 83-100% of cases [2-4]. Others are in 3q, 8p, 8q, 17q and losses in 3p, 6q, 10q and 16q [5]. Histologically characterized by poorly differentiated cells with round, hyperchromatic nuclei with scant cytoplasm, Homer Wright rosettes and areas of necrosis. Neurocytic differentiation and mature ganglion cells may be present and intense mitotic activity may be present. Immunohistochemistry studies show immunoreactivity to Olig2 and some embryonic cells may show positivity to synaptophysin and Ki67 is usually high [1]. Clinical manifestations present a varied spectrum due to the predominantly supratentorial location of the neoplasm, from focal neurological deficits, irritative signs such as seizures to neurological deterioration [6]. We submit a case of neuroblastoma (NBs) located in the cerebellum and a review of the literature.

Case Presentation

A 9-year-old male, admitted with the complaint of headache, nausea, vomit and ataxia, previously treated as vertigo. After a month and clinical deterioration, a head tomography was performed, and evidence of a cerebellum tumour was found, involving the fourth ventricle with dimensions of 1.2x0.6x0.4 cm in the rostrocaudal, ventrolateral and transverse planes and cerebral edema, for which a ventricle-peritoneal bypass valve was placed. A mid-suboccipital craniotomy was performed with partial resection of 50% of the tumour. He was sent to the HPCMNSXXI for chemotherapy treatment (ifosfamide, carboplatin and etoposide) and radiotherapy. The Pathology service received slides that included routine stains and immunohistochemistry (synaptophysin, GFAP, CD99, Ki67) without paraffin blocks, therefore it was not possible to perform other immunohistochemistry markers or the identification for the transcription factor FOXR2 (forkhead box R2).

An embryonic, hypercellular tumor, consisting of undifferentiated, small and hyperchromatic cells, densely packed with Homer Wright rosettes, which alternated with well-differentiated areas with multiple ganglion cells in different stages of maturation on a fibrillar background was identified. With areas of palisade necrosis and dystrophic calcifications. Immunohistochemistry was positive for synaptophysin in tumor cells, GFAP positive in neuropil, Ki67 positive 95% in neoplastic cells.The diagnosis of Neuroblastoma NOS, grade 4 (WHO 2021), was issued. (Figure 1)

Figure 1: A) HE, Photomicrograph showing a neoplasm consisting of two differentiation components with evidence of embryonic neoplasia alternating with differentiated hypocellular areas 10X

Figure 1: B) Presence of embryonic component with apoptosis and mitosis as well as evidence of multinucleated cell with neuronal differentiation. C) Close-ups in which a fibrillar background is observed with the presence of multiple cells with differentiation neuroblastic or neuronal. (HE, 40x).

Magnetic resonance imaging was performed in April 2023 with the presence of residual lesion in the fourth ventricle that caused a volume effect on the ventricle and adjacent structures (Figure 2). She was followed for 17 months with chemotherapy and radiotherapy treatment, with a torpid evolution followed by death.

Figure 2: A) Sagittal section in T 1, contrasted with evidence of neoplasm located on the posterior edge of the pons and fourth ventricle that is heterogeneously reinforced. B) Coronal section in T2 showing a hyperintense and heterogeneous midline lesion in the posterior fossa, with few areas with signal intensity similar to CSF.

Material and Methods

A systematic review of published cases in the Web of Science (WOS), SCOPUS, Google Scholar, TripDatabase, Science Direct and PudMed was carried out without using language restrictions, and the search strategy included all known descriptors on CNS neuroblastoma and FOXR2, with no date limit.

The main parameters that were considered eligible for the study were: primary location in CNS and paediatric population.

Other parameters that were included: sex, clinical presentation, surgical treatment, medical treatment, survival time.

The exclusion parameters that were considered for the study were: duplicate cases, CNS metastasis, non-paediatric population, case report, without clinical data of the patients.

The selection process was carried out using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, which is summarized in (Figure 3) the studies in this systematic review were carried out between 1966 and 2024, resulting in a final study cohort of 197 patients including our patient.

Figure 3: Flow diagram of study identification

Results

(Table 1) shows the summary of the cases found. The criteria were met in 26 publications, plus 6 articles that were not obtained, but the case information was obtained from the publication of Ahdevaara et al., 1976, with a total of 197 cases of NBs from CNS, of which 111 (56.34%) cases were female, and 86 (43.65%) cases were male, with a male:female ratio of 1:1.2.

Only 66 cases (33.5%) documented the most frequent clinical symptoms, those secondary to increased intracranial pressure (headache, nausea, vomiting, convulsions, papilledema), with only ataxia being added in the identified cerebellar case [7].

Of the total number of cases, 195 were supratentorial; 49 frontal, 14 fronto-parietal, 7 fronto-temporal, 2 fronto-temporo-parietal, 9 temporal, 6 temporo-parietal, 3 temporo-parieto-occipital, 23 parietal, 13 parieto-occipital and 6 occipital cases. In the basal nuclei and thalamus 4 cases, intraventricular with 5 cases and 3 cases in other locations. A total of 51 cases were identified as supratentorial lesion, without specifying the affected area. In infratentorial location, a single case was identified located in the right cerebellar lobe and our case, with intraventricular presentation, both cases of the same age at diagnosis and with similar histopathological findings.

Treatment was reported in 92/197 cases (46.7%); 65/92 cases had surgery 33 cases with partial resection and 32 cases with total resection. Chemotherapy was received in 52 cases and 80 cases received radiotherapy. The authors Schmincke 1914*, Horten and Rubinstein 1976, Bennett and Rubinstein 1983, Holsten et al, 2021 and Tietze et al. 2022, with more than 50% (105 patients) of cases included, do not report information on surgical, chemotherapeutic and/or radiotherapy treatment. [8-11]

Of the total number of cases, 62 were reported alive at the time of publication, and the rest were lost and dead as our case. In 102/165 cases, the mean survival was 3 years (0.5 months-14 years), and surgical resection could not be correlated with survival.

Table 1: Literature review of reported cases of primary CNS neuroblastoma

M: male F: female ND: not available a: years m: months s: weeks

*The papers were not gotten and the cases. Were referenced in Ahdevaara et al., 1976.