Results:
- 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).
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.