Keywords
astroblastoma - malignant - cystic
Introduction
Astroblastomas are unusual tumors, constituting 0.45 to 2.8% of all neuroglial tumors.[1] The cell of origin of astroblastoma is controversial. It was considered to arise
from the embryonic cell programmed to become astrocyte. Presence of intermediate filament
on ultrastructure shows ependymal differentiation, along with positive staining for
glial fibrillary acidic protein (GFAP) and S100 suggesting the possibility of a cell
with features between astrocytes an ependymal cells. Because of the rarity and lack
of sufficient clinical-pathologic data, it has not been included in the World Health
Organization (WHO) grading system. They occur predominantly in the cerebral hemisphere
of young adults and children.[2] Existing literature is limited with few case reports.[3]
[4] We report a rare case of astroblastoma with recurrence after 1 year.
Case Report
A 28-year-old woman presented to us with holocranial headache and double vision for
2 months. Her neurologic examination was normal. Magnetic resonance imaging (MRI)
of the brain revealed well-demarcated, ring-enhancing solid cystic mass in right temporoparietal
lobe abutting superior surface of tentorium with mass effect. The patient underwent
gross total resection of the lesion through right temporoparietal craniotomy ([Fig. 1]). Histopathology showed a highly cellular papillary neoplasm composed of polygonal
cells with abundant eosinophilic cytoplasm and round to oval pleomorphic nuclei. Admixed
are several large multinucleate cells. The mitotic index was 5/10 HPF (high-power
field). There were areas of cystic change, hemorrhage, and infarct-like necrosis.
On immunohistochemistry, tumor cells were variably positive for GFAP; diffusely positive
for S100 and vimentin; and negative for synaptophysin, progesterone receptor (PR),
and P53. Epithelial membrane antigen (EMA) shows membrane positivity in focal areas,
staining group of cells. There was no dot positivity. MIB-1 labeling index was approximately
15% in the cellular zones. The histopathologic diagnosis of high-grade astroblastoma
was made ([Fig. 2]). The patient was advised for postoperative radiotherapy, but she lost to follow-up.
Fig. 1 First surgery: Contrast MRI of the brain showing solid cystic lesion in right temporoparietal
region abutting supratentorial surface in axial (a), sagittal (b), and coronal (c) views. (d) Postoperative CT scan (axial view) showing gross total excision of tumor.
Fig. 2 (a) Papillary tumor (10x H&E). (b) Fibrovascular core with hyalinization and perivascular arrangement of tumor cells
(20x H&E). Immunohistochemistry (IHC). (c) Diffuse expression of GFAP by tumor cells. (d) Focal positivity by EMA. (e) Diffuse positivity by S-100. (f) MIB-1 index is 15% in cellular areas.
After 1 year, the patient presented to us with headache only. MRI of the brain showed
recurrent tumor in the same location with infratentorial extension. She was reoperated,
and gross total excision of supra- and infratentorial tumor was done ([Fig. 3]). The recurrent tumor showed similar morphology but with increased pleomorphism,
multinucleation, and brisk mitotic figures of both typical and atypical forms with
an average of 15/10 HPF. There were large areas of hemorrhage and infarct-like necrosis.
Focal areas of calcification mostly involving small-caliber vessels and stromal sclerosis
are also noted. Immunohistochemistry revealed marked reduction in GFAP expression
of tumor cells compared with the initial tumor. Staining pattern of the remaining
markers (S100, vimentin, synaptophysin, progesterone receptor, and EMA) was same as
before. Cells were negative for pancytokeratin and desmin. MIB-1 labeling index was
approximately 25% in cellular zones. More than 50% of the cells showed nuclear positivity
for P53. The final diagnosis was that of high-grade astroblastoma with malignant transformation
based on the high proliferative index and expression of P53 in more than 50% of cells
([Fig. 4]). Postoperatively, she received radiotherapy and on regular follow-up.
Fig. 3 Second surgery: Contrast MRI of the brain showing recurrent tumor in right temporoparietal
region with infratentorial extension in axial (a), sagittal (b), and coronal (c) views. (d) Intraoperative image showing gross tumor excision in both supra- and infratentorial
locations (arrow). (e) Postoperative CT of the head showing gross total excision of tumor from both supra-
and infratentorial locations.
Fig. 4 (a) Recurrent tumor with similar morphology and (b) sclerosis of the papillary core (10x H&E). (c) Higher magnification showing mitosis (20x H&E). (d) Patchy areas of necrosis (10x H&E). Immunohistochemistry (IHC). (e) Decreased expression of GFAP by the tumor cells. (f) EMA. (g) Expression of P53 by the tumor cells. (h) MIB-1 labeling index is 30% in cellular areas.
Discussion
Bailey and Cushing[5] first described these lesions in 1926, and Bailey and Bucy[6] supported their statistical analysis in 1930. They believed that astroblastoma originated
from astroblasts, an intermediate stage between glioblasts and astrocytes. These are
rare glial tumors usually located in the cerebral hemisphere. However, tumor invasion
has also been reported into the corpus callosum, cerebellum, brainstem, and optic
nerve.[7] The studies performed till date show striking female preponderance with a male-to-female
ratio of 1:11.[8] Most commonly patients present with features of raised intracranial tension, drowsiness,
and seizures. Astroblastomas are mostly reported in children and young adults, but
congenital cases have also been reported rarely.[1]
Bell et al[8] in a series of 12 cases of astroblastomas reported that astroblastomas are almost
exclusively reported supratentorially and they are peripheral in location with both
solid and cystic components. Largest series till date by Ahmad et al[9] described supratentorial tumor location, older age, and treatment prior to 1990
as poor prognostic factors. Another series by Asha et al[10] reported single-institute series of nine cases with recurrence in one case after
12 months after first surgery as in our case. Our case showed typical solid cystic
lesion with ring enhancement similarly. Based on imaging, the differential diagnoses
for astroblastomas include high-grade astrocytoma, pilocytic astrocytoma, primitive
neuroectodermal tumor, ependymoma, and atypical teratoid-rhabdoid tumor. Unlike in
high-grade tumors, perilesional edema is usually less in astroblastomas, including
high-grade variant.
Astroblastomas are defined histologically by the presence of perivascular pseudorosettes
and prominent perivascular hyalinization.[11] They may resemble astrocytic tumors, ependymomas, and non-neuroepithelial tumors
due to their astroblastic components. Lack of fibrillarity is an essential feature
in distinguishing astroblastomas from other glial neoplasms. Immunohistochemically,
astroblastomas are immunoreactive for GFAP, S100 protein, vimentin, and majority display
a focal cytoplasmic immunoreactivity for EMA. Similar immunophenotypes were noted
in the initial as well as recurrent tumor in the case of concern.
Astroblastomas along with gliomatosis cerebri and polar spongioblastoma are included
in neuroepithelial tumors of uncertain origin and are grade 4 tumors as per 2007 contrary
to grade 1 in WHO classification of brain tumors. Bonnin and Rubinstein[7] reported two distinct histologic types: A low-grade type with better differentiated
pattern and favorable postoperative prognosis and a high-grade type showing more anaplastic
microscopic features with short postoperative survival. High-grade lesions show focal
or multifocal regions of high cellularity, anaplastic nuclear features, elevated mitotic
indices, vascular proliferation, and necrosis with pseudopalisading. Our case was
considered in high-grade group. However, pseudopalisading and microvascular proliferation
were not present.
The present case of concern had proliferative indices exceeding the cutoff values
for high-grade tumor as per WHO 2016 in both primary and in recurrent tumors. Apart
from the high proliferative index, recurrent tumor showed additional features patchy
areas of necrosis and expression of p53. However, the effect of the high proliferative
index on outcome is still not clear.
Natural history of astroblastoma seems to place it in between astrocytoma and glioblastoma.[12] Total resection is the best way of treating an astroblastoma.[13] Favorable prognosis is almost always associated with well-circumscribed tumors,
which permits total resection.[14] Given the peripheral location of astroblastomas, total resection seems a goal easier
to achieve than in other gliomas. Regular follow-up is required even in low-grade
variants due to unpredictable behavior. Adjuvant radiotherapy is recommended for high-grade
and recurrent cases.[15] Caroli et al[14] reported a high-grade astroblastoma with a 5-year survival without recurrence after
total resection, radiation therapy, and temozolomide usage. The lack of enough information
about the natural history favors the use of adjuvant radiotherapy from the beginning.
Conclusion
Astroblastomas are very rare. Complete excision without radiotherapy and close follow-up
is required in low-grade variants. High-grade and recurrent tumors should receive
adjuvant radiotherapy. As per WHO 2016, gross total resection of even high-grade astroblastoma
may result in favorable outcome.
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