Results:
  1. Patients’ characteristics : Age ranged from 1 year to 28 years with median age of 4 years and M:F ratio of 1.5:1 (Figure 1a). Majority were less than 18 years (80%) with three patients being more than 18 years (Figure 1b) (Table 1).
  2. Location : Tumors arising in the supratentorial compartment was seen in majority (n=8 cases, 53.3%), while in 6 cases, tumor occurred in posterior fossa (40%). A single case of spinal tumor (at L1 location) was seen (Figure 1c).
  3. Imaging : All the tumors were intra-axial in location having large size but were well demarcated. The posterior fossa lesions showed compression on peduncles (Figure 1S, supplementary ). These masses showed no to mild enhancement following contrast administration and had mild to moderate perilesional oedema with significant mass effect. Diffusion restriction was seen in the solid component of the lesions.
  4. Management and clinical outcome : Gross total excision was achieved in 11 cases while in 4 cases only a near total resection could be achieved owing to the proximity to vital structures. Intraoperatively, most tumors were well defined and fleshy. The follow-up period ranged from 1-31 months; thirteen patients died with overall median survival of 6.4 months. Though the sample size was small, we attempted to calculate difference in median survival amongst the three patterns (ETANTR versus EBL versus others (including MEPL, embryonal tumor, NOS and ETANTR+EBL). The median survival of ETANTR was 1.3 months, while for EBL was 9.2 months and for others was 11.4 months (p=0.23, not significant ) (Figure 1d). All patients succumbed to the disease with two patients being alive, one month and 14 months after diagnosis, respectively. Two patients had metastatic disease at presentation with cerebrospinal fluid (CSF) being positive. Nine patients were found to be eligible for adjuvant treatment following surgery. Four patients completed the planned cranio-spinal irradiation (CSI) to a dose of 36Gy in 20 fractions followed by tumor bed boost of 9-18 Gy in 5-10 fractions and six cycles of platinum-based chemotherapy while one patient has recently completed first cycle of chemotherapy. Two patients received only radiotherapy (CSI and focal radiotherapy in one patient each to a total dose of 54 Gy in 30 fractions). Rest of the two patients were planned for adjuvant chemo-radiotherapy but deteriorated during radiotherapy (RT) and thus could not complete the further treatment.
  5. Histology : Diverse histological patterns were noted with ETANTR pattern identified in 6 cases; EBL pattern was seen in 6 cases; mixed ETANTR and EBL pattern and MEPL was identified in one case each, while in a single case the tumor displayed sheets of undifferentiated cells with occasional rosettes, the cells were strongly and diffusely positive for LIN 28A. The tumor was categorized as embryonal tumors, NOS (Table 1). On performing immunohistochemistry, all tumors revealed retained nuclear expression for INI-1 (strong and diffuse). Synaptophysin, NFP, and Neu N expression was observed more in the neuropil in cases of ETANTR. GFAP was largely negative in all cases, except for rare areas with positivity. All cases expressed LIN 28A, the expression was restricted mainly to rosettes forming cells in cases of ETANTR, while in EBL and MEPL it was more widespread highlighting the poorly differentiated embryonal cells of EBL and tubular and papillary structures of MEPL.
  1. ETANTR pattern (n=6): Typical case revealed cellular islands interspersed by swathes of neuropil wherein the classic multilayered rosettes were abruptly encountered (Figure 2,3). The characteristics multilayered rosettes was identified as multilayering of mitotically active neuroepithelial cells clustered around a central lumen. The central portion of some rosettes were filled with nuclear debris or a lumina could be identified. The cellular islands consisted of embryonal cells in sheets, cords or as clusters set in a fine fibrillar matrix.
  2. EBL pattern (n=6): The tumors within this pattern featured poorly formed ependymoblastic rosettes which were numerous in large portions while the neuropil content was relatively less (Figure 4). Mitoses was readily identified.
  3. MEPL pattern (n=1): A single example of this tumor at spinal location (L1) was encountered in a teenage girl who presented with low backache. On histology, the tumor demonstrated papillary and tubular arrangement of neoplastic cells reminiscent of neuroepithelium and forming primitive neural tube (Figure 5). Neuropil content was low throughout the tumor. Adjacent areas comprised of sheets of embryonal cells with presence of rare multilayered ependymoblastic rosettes. No other differentiation pattern was observed. Focal expression of cytokeratin was noted.
  4. Undifferentiated embryonal sarcoma, NOS (n=1): The tumor comprised of sheets of densely packed, immature cells, with a high nuclear to cytoplasmic ratio and round, oval, or angulated hyperchromatic nuclei. Occasional rosettes were identified. The cells were variably immunopositive for synaptophysin and OLIG2, while GFAP was negative. LIN 28A was widely expressed.
All morphological patterns showed numerous mitotic figures and abundant apoptotic bodies. Ki67 was uniformly high and it brilliantly highlighted the multilayered rosettes amidst the neuropil islands when central lumina were poorly defined. Tumor recurrence post-therapy was seen in a single case 9months following gross-total resection of the primary tumor. The recurrent tumor consisted of areas of epithelioid and rhabdoid morphology characterized by large cells with abundant dense eosinophilic cytoplasm, large pleomorphic vesicular nuclei and conspicuous nucleoli. GFAP immunostain highlighted areas with glial differentiation; however, no neuronal differentiation was observed. Also, INI-1 was widely expressed by the neoplastic cells.