**3. Summary and perspectives**

### **3.1 Prognostic factors**

*Pheochromocytoma, Paraganglioma and Neuroblastoma*

with pale staining nuclei [30, 31].

**2.3 Discussion**

**Figure 1.**

ganglion cells with a double nucleus, highly infiltrated and proliferated cells with dense chromatin [28, 29]. Further ganglioneuroblastomata have two histological subtypes: undifferentiated type has a small round to oval cells with hyperchromatic nuclei, and poorly differentiated type has a large round to oval spindle-shaped cells

*Various routes for entry of neuroblastoma cells, and its spread to and within CNS.*

Neuroblastoma is an enigmatic and one of the most common malignant solid tumour of the paediatric age group. Neuroblastoma is a disease with a grim prognosis, and the outcome has not changed significantly in the past two decades. Neuroblastoma teaches us essential aspects of CNS and neural crest development. Primary CNS Neuroblastoma (PCNS-NB) is a rare subtype of neuroblastoma with variable classification. It includes CNS neuroblastoma and ganglioneuroblastoma. In 2016 WHO classification of CNS tumours, PCNS-NB is classified as embryonal tumours. Embryonal tumours with the exception of medulloblastoma has been reclassified based on molecular alterations, for example atypical teratoid rhabdoid tumour (AT/RT) characterised by SMARCB1 or SMARCA4 inactivation, C19MC altered and/or LIN28A expressing embryonal tumour with multi-layered rosettes (ETANTR) and CNS neuroblastoma/Ganglioneuroblastoma without specific

histological features or molecular alterations [8]. Based on global transcriptional and methylation profiling four tumour entities have been proposed: CNS neuroblastoma with FOXR2 activation (NB-FOX-R2), High grade neuroepithelial tumour with MN1 alteration (HGNET-MN1), high grade neuroepithelial tumour with BCOR alteration (HGNET-BCOR), and Ewing sarcoma family tumour with CIC alteration (EFT-CIC) [18]. CNS neuroblastoma rarely contains GFAP positive cells which are usually reactive astrocytes and most of the NB-FOX-R2 tumours are neuroblastic differentiation and contains neurocytic cells with poorly differentiated neuropil rich stroma and embryonal architecture [32]. However, there are reports of CNS neuroblastoma with GFAP positive tumour cells demonstrating both neuronal and glial nature, though the clinical significance of such entity is unknown [32]. Since, PCNS-NB is a rare entity and usually present in younger age group, little is known about its treatment protocols, prognostic factors and patient risk stratification. Review of literature suggests that PCNS-NB preferentially occurs in the supratentorial space with involvement of frontal and parietal region [4]. Clinical presentation of PCNS-NB is usually as per the most common site of involvement. Since, most of the PCNS-NB prefers supratentorial location preferably in the frontal and parietal region, patients

**68**

Younger age group, a limited number of lesions, ganglioneuroblastoma subtype and surgical management, are found to be positive prognostic factors in PCNS-NB. Neuroblastoma has complex heterogeneous nature with varied prognosis, infants <1 year of age tend to have maximum overall survival with the tumour spontaneously regressing in some infants on the one hand and having widespread metastasis on the other hand [2, 12]. Studies have found best overall survival in infants <1 year of age and relatively less short term adverse events in age > 40 years with a 1-year survival of 57.2% [16].

#### **3.2 Management options**

In the population-based studies, patients with extensive disease, multiple lesions, and metastasis were more often offered conservative management as surgical excision was not feasible [16]. Surgical excision is often referred to as the first line of management in the treatment of PCNS-NB, whenever feasible [4]. Differentiation in ganglioneuroblastoma lies in between malignant neuroblastoma and benign ganglioneuroma. Ganglioneuroblastoma subtype is found to be associated with a good prognosis. Studies show that the ganglioneuroblastoma subtype rarely infiltrates and tends to be localised with less incidence of metastatic deposits [16, 34]. This explains that patients with this subtype are likely to be offered surgery and benefit from surgical excision with overall better survival. Ganglioneuroblastoma typically has a high invasive behaviour but slower multiplication rate and the asymptomatic period of up to 60 months has been reported after surgical excision [35, 36].
