ASTROBLASTOMA: DOES IT REQUIRE DIFFERENT TREATMENT ?

Astroblastoma: Does it require different treatment ?

Verma YP, Additional Senior Medical Officer, Department of Radiation Oncology, PGIMS, Rohtak (India)

Pannu J, Resident, Department of Radiation Oncology, PGIMS, Rohtak (India)

Chauhan AK, Senior Professor, Department of Radiation Oncology, PGIMS, Rohtak (India)

ABSTRACT

Background- Astroblastoma is partially understood, poorly reported and rare in occurrence tumor with significant dilemma regarding cellular origin, diagnostic criteria, clinical behavior, and management protocol. Material and method- Thorough search of published English scientific literature was made with search word Astroblastoma through Google Search, PubMed,ResearchGate and Cochrane Library till June 2018. The reports thus collected were examined for data regarding age, gender, location and laterality of disease, pathological grade, treatment received, and outcome of treatment. Results- Data of 161 patients was retrieved from 72 publications. Median age at presentation was 18 years. Females were affected much more frequently than males. Most common site of involvement was the frontal lobe. Laterality data was inconsistent and sparingly reported. Most common presenting complaint was headache followed by history of seizure. Surgery was performed in majority of patients-79.6% of the patients underwent a gross total resection, 45% (44 out of 98 reported) had a high-grade tumor. Sixty patients received adjuvant radiation with a median dose of 54 Gy (Range 20-72), mostly for high grade, residual or recurrent disease. Adjuvant chemotherapy was used in 25 patients. Median follow-up was 43 months (range 1-238). Median overall survival was 138 months. Patients with a higher-grade tumor had significantly worse overall survival. Conclusion- Astroblastoma is rare but known to have two distinct grades, with higher-grade tumors bearing significantly poor survival. Maximal safe surgery is the standard. Though there is lack of consensus, adjuvant radiotherapy with or without Temozolamide should be considered in view of high rates of local recurrence.

Keywords: Astroblastoma, Brain tumor, Radiotherapy, Rare, Temozolamide

INTRODUCTION

First description of Astroblastoma in English literature dates back to 1926 by Bailey and Cushing.¹ Since then, limited number of cases have been described, mostly as case reports. Owing to rarity of the disease and limited published information, significant dilemma exists regarding cellular origin, diagnostic criteria, clinical behavior, and treatment protocol of this tumor. This work intends to review the available data on Astroblastoma to make our understanding better about it.

Materials and methods

Methodology

Thorough search of published English scientific literature was made with search word Astroblastoma through Google Search, PubMed,ResearchGate and Cochrane Library till June 2018. The reports thus collected were examined for data regarding age, gender, location and laterality of disease, pathological grade, treatment received, and outcome of treatment. References and cross references were carefully checked by arranging all published work in their order of publication year to rule outrepetition. Only the articles providing adequate information about demography, diagnosis, treatment and/ or outcome were considered. Available data were arranged in excel chart and analyzed.

Statistical analysis

Categorical variables were summarized by frequency (ratio and/ or percentage) and quantitative variables by median and/ or range. Overall survival (OS) was calculated from time of diagnosis. The Kaplan Meier method was used for survival analysis. Log rank test was used to find the impact of different prognostic variables and p value of ≤0.05 was taken as significant.

OBSERVATIONS

Patient Characteristics

Data of 161 patients with astroblastoma were retrieved from 72 publications, published over almost a century.^1-74 Most were case reports or small case series. Only four retrospective analyses had a sample size of more than hundred.^75-78

Patient’s characteristics are shown in Table 1.

Table 1: Patient characteristics (N= 161) (Studies= 72) (Study Period 1926- 2018 June)

Median age for the entire cohort was 18 years (Range 0- 73 years). More than half of the patients were in the first two decades of life (86/149; 57.7%). This frequency gets almost halved after consecutive two decades i.e. a gradual decline in frequency was observed (Fig 1).

Astroblastoma was observed more than twice as frequent in femalesas in males (69.7% versus 30.3%; M:F = 3:7).

The tumors were almost intracranial, the only case reported to involve spinal cord.Frontal lobe was involved most commonly (36%) followed by parietal (17%), temporal (15%) and occipital (10%); in that order. Only one patient with spinal astroblastoma was reported. Supra-tentorial part was involved much more commonly thanthe infra-tentorial(4:1). Laterality (left versus right) data was inconsistent and sparingly reported.

Available data revealed headache to be themost common presenting complaint (61%)followed by history of seizure (26%). Others had weakness, focal neurological deficits and occasionally incidental observation for intracranial bleed.

Treatment

Surgical details could be retrieved for 98 patients: 79.6% of the patients underwent a gross total resection (GTR), and the remainder had a decompression (Dcx), biopsy (Bx) or subtotal resection (STR) only. Forty-four out of 98 (45%) had a high-grade tumor. Sixty patients received radiotherapy for high grade, residual or recurrent disease; with a median dose of 54 Gy (range 20-72 Gy). Chemotherapy was used in 25 patients, Temozolamide being used in over half of those. Combination chemotherapy with Cisplatin, Etoposide,Vincristine, or Ifosfamide was used in others but one case, where Bevacizumab was added.

Radiotherapy and chemotherapy was found to be used mainly in setting of sub-optimal resection, high grade or recurrent disease. Since, bias was observed in use of treatment modalities, a head on comparison of results of surgery versus other modality or a combination was not found logical.

Outcome

Median follow up duration was 43 months (Range 1-238 months). Median overall survival was 138 months. Patients with a high grade tumor had significantly poor overall survival compared to low grade counterparts (Median OS- 53 months for high-grade tumors versus not reached for low-grade tumors; p = 0.001). Patients who underwent GTR had a 5-year OS of 76.2% compared to 18% of the patients with a STR. Other factors like age, gender, tumor location, adjuvant treatment (radiotherapy and/or chemotherapy) were not found to have significant impact on survival.

DISCUSSION

Astroblastoma have a controversial claim as a distinct entity, with no established WHO grade. These lesions are characterized by the presence of the perivascular pseudorosettes composed of tumour cells with a prominent process extending to a central blood vessel and perivascular hyalinization.

In publication of first case of Astroblastoma in 1926, Bailey and Cushing described ‘Astroblasts’ to be the embryonic, destined to become astrocytes, intermediate stage cells during development from spongioblasts to astrocytes.¹

The cell of origin was later described as a Spongioblast. Microscopic characteristics included- abundant thick blood vessels surrounded by plasma cells and lymphocytes. The perivascular tumor cells with broad footplates form a typical pseudorosette pattern as seen in ependymoma. Expression of glial fibrillary acidic protein (GFAP) and vimentin points towards an origin from astrocytes, while expression of epithelial membrane antigen (EMA) and cytokeratin (CK) positivity indicates ependymal differentiation.⁴

Russel and Rubenstein suggested that dedifferentiation of mature astro-glial cells could lead to the development of astroblastoma. They subcategorized the tumor into well-differentiated and anaplastic variants depending upon cellularity, mitosis and anaplasia.⁵

Another theory relates to its origin from Tanycyte, a cell intermediate between astrocytes and ependymal cells.¹⁵

On histology, it may simulate an ependymoma, especially when well differentiated, and can be differentiated by the presence of rarified bodies in between pseudorosettes.^8,53

While WHO 2000 classification was being followed, Louis et al claimed that most glioma classifications were derived from the seminal system of Bailey and Cushing. Bailey and Cushing, rather presciently for the 1920s, drew parallels between the histological appearances of glial tumors and putative developmental stages of glia. Thus, they reasoned that the cells of Astrocytoma microscopically most closely resembled astrocytes and those of oligodendroglioma histologically most mimicked oligodendrocytes. As these tumors became more malignant, they resembled less differentiated (i.e. earlier) precursor cells; hence, malignant astrocytomas were dubbed “astroblastomas.” Role of accurate classification of brain tumors, based on molecular and biological understanding and its importance in clinical decision making was also emphasized.⁷⁹

Navarro et al mentioned microscopic findings suggesting that anaplastic astroblasts have a tendency to evolve toward, or be associated with less differentiated cells, either neuro-epithelial or sarcomatous.²¹

In the WHO 2007 classification no formal grade was recommended, although well differentiated and malignant variants were recognized, possibly with clinical consequences. Astroblastoma was described to be positive for GFAP, S100 and Vimentin by IHC and frequently with focal expression of EMA. In the lack of consensus, Astroblastoma was classified as ‘other neuroepithelial tumours’.⁸⁰

WHO 2016 Classification of Tumors of Central Nervous System describes malignant astroblastoma as having focal or multiple foci of high cellularity, anaplasia, increased mitotic activity (>5 mitoses per HPF), elevated proliferative index (typically >10%), microvascular proliferation and necrosis.⁸¹

Brat et al suggested that Astroblastoma may have a characteristic cytogenetic profile in addition to their distinctive clinical, radiographic, and histopathologic features.¹²

Molecular studies are being carried to make understanding more clear. Recently, they have been described to overlap with a newly-discovered group of tumours described as ‘high-grade neuroepithelialtumour with MN1 alteration’ (CNS HGNET-MN1), defined by global methylation patterns and strongly associated with gene fusions targeting MN1, so providing opportunity to understand the evolutionary history and provide novel therapeutic targets for astroblastoma/ CNS HGNET-MN1.⁷¹

            So far reported as rare brain tumors, Astroblastoma predominates in children and young adults, with incidence range 0.45% to 2.8% of all glioma.⁸Though cases have been reported in adults, overall incidence has not been commented upon. Only 11 cases have been reported from India, so far.

Demographics are helpful in differentiating Astroblastoma from other tumors. From this analysis, it seems that Astroblastoma tends to occur early in life (childhood and teenage), with gradual decline in frequency over the ages. This is in contrast to glioblastomamultiforme (GBM), meningioma, and oligodendroglioma, which affect older adults, while ependymoma and atypical teratoidrhabdoid tumor (ATRT) are often found in younger children. While most large studies endorse similar pattern,^76-78 a bimodal distribution was reported by Shugrue et al.⁷⁵But, if we examine data of latter as well, a gradual decline of frequency with every decade of age group is found which is compliant with our observation.

In the present analysis, incidence in female was much more than in males (M:F = 3:7). Female predominance, with M:F ranging from1:3 to 1:11,has been reportedby reviews.^31,66,72 Unlike majority of reports showing a female preponderance, SEER data analysis reported equal incidence in males and females.⁷⁶

We found the disease located in supra-tentorial area more than infra-tentorial area (4:1). This ratio has been found to range from 4.4:1 to as high as 11:1in earlier published reports.^75-78

Present analysis found the tumorinvolving the frontal lobe most commonly,in nearly one third of the cases. Parietal and temporal lobe cases almost equaled to rank next, followed by occipital lobe. This finding corresponds to most reviews except slight change in middle order.^75-78

Headache is themost common presenting complaint (61%)followed by history of seizure (26%) in this study, others being weakness, focal neurological deficits and incidental intracranial bleed. Most other studies found headache to be the commonest presentation instead of focal neurological deficits.

Because of rarity, Astroblastoma presents a challenge as to its diagnosis and treatment. No level I-III clinical evidence exists to guide treatment, so the optimal therapy remains disputed and possibly extrapolation of principles of astrocytoma management is applied.

Imaging may support early diagnosis and good prognosis. Astroblastoma often demonstrate T1 and T2‑prolongation relative to white matter, with well‑demarcated boundaries and heterogeneous contrast enhancement; different from meningioma, which tends to exhibit a homogeneous enhancement. Supra-tentorial location differentiates it from ependymoma, which usually occupies the posterior fossa. Calcifications are a consistent imaging finding, and would be unusual for GBM and ATRT. Astroblastoma tend to be peripherally oriented and may involve or arise primarily from the ventricular system. Although rim enhancement seen around its cystic components may resemble that of a necrotic GBM, Astroblastoma usually have minimal peri-tumor white matter T2‑prolongation. The extent of peri-tumor edema is considered an unfavorable radiological feature that suggests early recurrence or progression in Astroblastoma.^31,53

Cunningham et al reviewed radiological features of Astroblastoma and observed that imaging often shows a supra-tentorial, superficial, well-defined, cystic-solid enhancing mass. On CT, most are hyper-attenuated, have calcifications, and may remodel adjacent bone if superficial. MRI characteristically reveals a hypointense mass on T1-W and T2-W sequences with restricted diffusion. MR spectroscopy, PET and catheter angiography findings are nonspecific.⁷⁷

TREATMENT

The clinical behavior of Astroblastoma is unpredictable and prognosis has been described as intermediate between that of low grade astrocytoma and glioblastoma.

Merfeld et al observed overall survival at 5 years to be 79.5% and emphasized that Astroblastoma be treated with curative intent.⁷²

Surgery and extent

Sughrue et al observedsurvival trends in a cohort (n=116), and found statistically significantdifference (p=0.011) in 5-year progression-free survival for patients treated with GTR as compared to STR (83% versus 55%).⁷⁵

Ahmed et al in review ofSEER data also revealed similar patterns of survival; patients treated with surgery alone compared to radiation therapy alone showed improved 5-year overall survival (62.2% versus 27.3%; p<0.001) and cause-specific survival (67.3% versus 31.9%; p< 0.003). But the possibility of treatment bias can’t be ruled out.⁷⁶

In analysis by Mallick et al, patients treated with GTR were found to have better survival, with a trend to statistical significance (p = 0.0649) compared to those treated with a STR.⁷⁸

Radiotherapy

No report could be found with radiotherapy given in neo-adjuvant setting.

The role of adjuvant radiotherapy to the tumor bed has been debatable. Adjuvant radiotherapy may not be necessary in low-grade astroblastoma tumors, particularly after radical surgery (i.e., GTR).

Bonnin et al reviewed and found two distinct histological types: low-grade and high-grade. In low-grade tumors, survival from 3 to 20 years after treatment was reported whereas in high grade, it was an exception beyond 3 years. Best clinical results were obtained after total or subtotal resection of the tumor, followed by radiotherapy.⁷⁴

Janz et al presented a case in which there was early recurrence of a low‑grade variant that warranted postoperative radiotherapy with no further recurrence.⁵³

Lau et al, Yao et al and Samples et al have described low‑grade Astroblastoma treated with GTR that recurred early, warranting another operation and adjuvant radiotherapy; thus advocating implementation of adjuvant radiotherapy even for low grade neoplasm.^22,57,66

Mangano et al analyzed outcomes and treatment strategies in low and high grade Astroblastoma.Among the patients with high‑grade tumors, those who received surgery and radiotherapy, had the highest survival rate.²⁷

Ahmed suggested that surgery was superior to radiation alone and the combination of both did not improve survival.⁷⁶

Mallick et al pointed that 65% of the patients required a salvage surgery and 50% underwentsalvage radiation. Ultimately, 68% of the patients received radiation either as adjuvant or in salvage therapy. Observations justified the addition ofadjuvant radiation to optimize the treatment outcome.⁷⁸

Focal radiotherapy has been suggested largely in patients with high-grade tumors, tumors with STR, or in the setting of tumor recurrence.^{8,12,37,68,72}

Chemotherapy

Though, isolated reports have used chemotherapy and shown its benefit in adjuvant setting, no large review has ever endorsed its benefit. Few studies have advocated the use of Temozolamide, but that seems to be extrapolation of experience with GBM.^36,44

Combination of Cisplatin, Etoposide,Vincristine, or Ifosfamide was used in some. Bevacizumab has also been tried.

Words of caution come from Merfeld et al, who reported no benefit of chemotherapy.Rather hazard ratio of 2.516 was reported with use of adjuvant chemotherapy.⁷²

PROGNOSIS

Prognosis of Astroblastoma appears to directly correlate with its histological grade. In general patients with high grade disease survive poor than those with low grade.^17,27,64,78

Extent of surgery is another factor. Astroblastoma, as stated above, treated with GTR have relatively better prognosis.^75-78

Tumor site has also been associated with clinical outcome. The 5-year OS for tumors located at infra and supra-tentorial has been estimated to be 75% and 44.9% (p<0.001), respectively.⁷⁶

The age and gender of the patient also seems to be of prognostic significance.^37,68 A strong correlation between age and OS- the worse OS correlated with older age- has been reported.^76,78

CONCLUSION

Astroblastoma is a rare tumor and hence not amenable to study in a prospective setting. In absence of clinical guidelines, patient’s treatment should be customized. This review should help in clinical decision making. Maximal safe resection is the standard and adjuvant radiotherapy is worth considering, in view of high local recurrence rate. Temozolamide may be considered in high grade Astroblastoma, proven otherwise.

Compliance with ethical standards

Conflict of interest Nil

REFERENCES

1. Bailey P, Cushing H. A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis. J.B. Lippincott Co., Philadelphia (1926).

2. Yamashita J, Handa H, Yamagami T, Haebara H. Astroblastoma of pure type. Surg Neurol. 1985;24(2):218-22.

3. Husain AN, Leestma JE. Cerebral astroblastoma: immunohistochemical and ultrastructural features. Case Report J Neurosurg. 1986;64(4):657-61.

4 Hoag G, Sima AA, Rozdilsky B. Astroblastoma revisited: a report of three cases. ActaNeuropathol. 1986;70(1):10-6.

5. Rubinstein LJ, Herman MM. The astroblastoma and its possible cytogenic relationship to the tanycyte. An electron microscopic, immunohistochemical, tissue and organ-culture study. ActaNeuropathol. 1989;78(5):472-83.

6. Cabello A, Madero S, Castresana A, Diaz-Lobato R. Astroblastoma: electron microscopy and immunohistochemical findings: case report. Surg Neurol. 1991;35(2):116-21.

7. Jay V, Edwards V, Squire J, Rutka J. Astroblastoma: report of a case with ultra-structural, cell kinetic and cytogenetic analysis. PediatrPathol. 1993;13(3):323-32.

8. Pizer BL, Moss T, Oakhill A, Webb D, Coakham HB. Congenital astroblastoma: an immunohistochemical study. Case report J Neurosurg. 1995;83(3):550-5.

9. Yunten N, Ersahin Y, Demirtas E, Yalman O, Sener RN. Cerebral astroblastoma resembling an extra-axial neoplasm. J Neuroradiol. 1996;23(1):38-40.

10. Thiessen B, Finlay J, Kulkarni R, Rosenblum MK. Astroblastoma: does histology predict biologic behavior? J Neuro-Oncol. 1998;40(1):59-65.

11. Mierau GW, Tyson RW, McGavran L, Parker NB, Partington MD. Astroblastoma: ultrastructural observations on a case of high-grade type. UltrastructPathol 1999;23(5):325-32.

12. Brat DJ, Hirose Y, Cohen KJ, Feuerstein BG, Burger PC. Astroblastoma: clinicopathologic features and chromosomal abnormalities defined by comparative genomic hybridization. Brain Pathol. 2000;10(3):342-52.

13. Shuangshoti S, Mitphraphan W, Kanvisetsri S, Griffiths L, Navalitloha Y, Pornthanakasem W et al. Astroblastoma: report of a case with microsatellite analysis. Neuropathology. 2000;20(3): 228-32.

14. Sugita Y, Terasaki M, Shigemori M, Morimatsu M, Honda E, Oshima Y. Astroblastoma with unusual signet-ring-like cell components: a case report and literature review. Neuropathology. 2002;22(3):200-5.

15. Port JD, Brat DJ, Burger PC, Pomper MG. Astroblastoma: radiologic-pathologic correlation and distinction from ependymoma. AJNR Am J Neuroradiol. 2002;23(2):243-47.

16. Sener RN. Astroblastoma: diffusion MRI, and proton MR spectroscopy. Comput Med Imaging Graph. 2002;26(3):187-91.

17. Caroli E, Salvati M, Esposito V, Orlando E R, Giangaspero F. Cerebral astroblastoma. ActaNeurochir. 2004;146(6):629-33.

18. Kim DS, Park SY, Lee SP. Astroblastoma: a case report. J Korean Med Sci. 2004;19(5):772-6.

19. Kim BS, Kothbauer K, Jallo G. Brainstem astroblastoma. PediatrNeurosurg. 2004;40(3):145-6.

20. Huhn SL, Yung Y, Cheshier S, Harsh G, Ailles L, Weissman I et al. Identification of phenotypic neural stem cells in a pediatric astroblastoma. J Neurosurg. 2005;103(5 Suppl):446-50.

21. Navarro R, Reitman AJ, de León GA, Goldman S, Marymont M, Tomita T. Astroblastoma in childhood: pathological and clinical analysis. Childs Nerv Syst. 2005;21(3):211-20.

22.  Lau PP, Thomas TM, Lui PC, Khin AT. Low-grade’ astroblastoma with rapid recurrence: a case report. Pathology. 2006;38(1):78-80.

23. Kaji M, Takeshima H, Nakazato Y, Kuratsu J. Low-grade astroblastoma recurring with extensive invasion. Neurol Med Chir. 2006;46(9):450-4.

24.  Hata N, Shono T, Yoshimoto K, Mizoguchi M, Kawamura T, Nagata S et al. An astroblastoma case associated with loss of heterozygosity on chromosome 9p. J Neuro-Oncol. 2006;80(1):69-73.

25. Miranda P, Lobato RD, Cabello A, Gómez PA, Martínez de Aragón A. Complete surgical resection of high-grade astroblastoma with long time survival: case report and review of the literature. Neurocirugia.2006;17(1):60-3.

26. Kubota T, Sato K, Arishima H, Takeuchi H, Kitai R, Nakagawa T. Astroblastoma: immunohistochemical and ultrastructural study of distinctive epithelial and probable tanycytic differentiation. Neuropathology. 2006;26(1):72-81.

27. Mangano FT, Bradford AC, Mittler MA, Valderrama E, Schneider SJ. Astroblastoma. Case report, review of the literature, and analysis of treatment strategies. J Neurosurg Sci. 2007;51(1):21-7 discussion 27.

28. Bannykh SI, Fan X, Black KL. Malignant astroblastoma with rhabdoid morphology. J Neuro-Oncol. 2007;83(3):277-8.

29. Tumialán LM, Brat DJ, Fountain AJ, Barrow DL. An astroblastoma mimicking a cavernous malformation: case report. Neurosurgery. 2007;60(3):E569-70 discussion E570.

30. Alaraj A, Chan M, Oh S, Michals E, Valyi-Nagy T, Hersonsky T. Astroblastoma presenting with intracerebral hemorrhage misdiagnosed as dural arteriovenous fistula: review of a rare entity. Surg Neurol. 2007;67(3):308-13.

31. Bell JW, Osborn AG, Salzman KL, Blaser SI, Jones BV, Chin SS. Neuroradiologic characteristics of astroblastoma. Neuroradiology. 2007;49(3):203-9.

32.  Eom KS, Kim JM, Kim TY. A cerebral astroblastoma mimicking an extra-axial neoplasm. J Korean Neurosurg Soc. 2008;43(4): 205-8.

33. Denaro L, Gardiman M, Calderone M, Rossetto M, Ciccarino P, Giangaspero F et al. Intraventricular astroblastoma. Case report J NeurosurgPediatr. 2008;1(2):152-5.

34. Fathi AR, Novoa E, El-Koussy M, Kappeler A, Mariani L, Vajtai I. Astroblastoma with rhabdoid features and favorable long term outcome: report of a case with a 12-year follow-up. Pathol Res Pract. 2008;204(5):345-51.

35. Notarianni C, Akin M, Fowler M, Nanda A. Brainstem astroblastoma: a case report and review of the literature. Surg Neurol. 2008;69(2):201-5.

36. Unal E, Koksal Y, Vajtai I, Toy H, Kocaogullar Y, Paksoy Y. Astroblastoma in a child. Childs Nerv Syst. 2008;24(2):165-8.

37. Salvati M, D’Elia A, Brogna C, Frati A, Antonelli M, Giangaspero F et al. Cerebral astroblastoma: analysis of six cases and critical review of treatment options. J Neuro-Oncol. 2009;93(3):369-78.

38.  Kemerdere R, Dashti R, Ulu MO, Biçeroğlu H, Demiröz AS, Albayram S et al. Supratentorial high grade astroblastoma: report of two cases and review of the literature. Turk Neurosurg. 2009;19(2):149-52.

39. Ganapathy S, Kleiner LI, Mirkin DL, Broxson E. Unusual manifestations of astroblastoma: a radiologic-pathologic analysis. PediatrRadiol. 2009;39(2):168-71.

40. Kantar M, Ertan Y, Turhan T, Kitis O, Anacak Y, Akalin T et al. Anaplastic astroblastoma of childhood: aggressive behavior. Childs Nerv Syst. 2009;25(9):1125-9.

41. Grundy RG, Wilne SH, Robinson KJ, et al. Primary postoperative chemotherapy without radiotherapy for treatment of brain tumours other than ependymoma in children under 3 years: results of the first UKCCSG/SIOP CNS 9204 trial. Eur J Cancer. 2010;46(1):120-33.

42. Johnson KA, Bonnin JM, Boaz JC, Douglas-Akinwande AC, Hattab EM. Anaplastic astroblastoma presenting as massive, sudden-onset, intraparenchymal hemorrhage. PediatrNeurosurg. 2010;46(6):457-61.

43. Mastrangelo S, Lauriola L, Coccia P, Puma N, Massimi L, Riccardi R. Two cases of pediatric high-grade astroblastoma with different clinical behavior. Tumori. 2010;96(1):160-3.

44. Bergkåsa M, Sundstrøm S, Gulati S, Torp SH. Astroblastoma- a case report of a rare neuroepithelial tumor with complete remission after chemotherapy. ClinNeuropathol. 2011;30(6):301-6.

45. Binesh F, Akhavan A, Navabii H, Mehrabaniyan M. Anaplastic astroblastoma: a rare glial tumour. BMJ Case Rep. 2011 Sep 28;2011.

46. Weintraub D, Monteith SJ, Yen CP, Schlesinger D, Rich T, Sheehan J. Recurrent astroblastoma treated with gamma knife radiosurgery. J NeuroOncol. 2011;103(3):751-4.

47. Bhattacharjee S, Pulligopu AK, Uppin MS, Sundaram C. Astroblastoma with bone invasion. Asian J Neurosurg. 2011;6(2):113-5.

48. Agarwal V, Mally R, Palande DA, Velho V. Cerebral astroblastoma: a case report and review of literature. Asian J Neurosurg. 2012;7(2):98-100.

49. Khosla D, Yadav BS, Kumar R, Agrawal P, Kakkar N, Patel FD et al. Pediatric astroblastoma: a rare case with a review of the literature. PediatrNeurosurg. 2012;48(2):122-5.

50. Yao K, Li TF, Zhu MW, Duan ZJ, Liu CQ, Wang JQ et al. Mixed astroblastoma-arteriovenous malformation complex: a case report. Neurol India. 2013;61(4):439-42.

51. Nasit JG, Trivedi P. Recurrent low-grade astroblastoma with signet ring-like cells and high proliferative index. Fetal PediatrPathol. 2013;32(4):284-92.

52. Singh DK, Singh N, Singh R, Husain N. Cerebral astroblastoma: a radiopathological diagnosis. J PediatrNeurosci. 2014;9(1):45-7.

53. Janz C, Buhl R. Astroblastoma: report of two cases with unexpected clinical behavior and review of the literature. ClinNeurolNeurosurg. 2014;125:114-24.

54. Paul S, Narad SR, Vaishya S, Vasdev N, Munshi A, Sarkar B. Cerebral astroblastoma. Clin Cancer Investig J. 2014;3:432-4.

55. De la Garma VH, Arcipreste AA, Vázquez FP, Aguilar RR, Castruita UO, Guerra RM. High-grade astroblastoma in a child: report of one case and review of literature. SurgNeurol Int. 2014;5:111.

56. Sabharwal P, Sadashiva N, Unchagi A, Mahadevan A, Pandey P. Intraventricular Astroblastoma in an infant: a case report and review of the literature. PediatrNeurosurg. 2015;50(6):325-9.

57. Yao K, Wu B, Xi M, Duan Z, Wang J, Qi X. Distant dissemination of mixed low-grade astroblastoma- arteriovenous malformation after initial operation: a case report. Int J ClinExpPathol. 2015;8(6):7450-6.

58. Samkari A, Hmoud M, Al-Mehdar A, Abdullah S. Well differentiated and anaplastic astroblastoma in the same patient: a case report and review of the literature. ClinNeuropathol. 2015;34(6):350-8.

59.  Narayan S, Kapoor A, Singhal MK, Jakhar SL, Bagri PK, Rajput PS et al. Astroblastoma of cerebrum: a rare case report and review of literature. J Cancer Res Ther. 2015;11(3):667.

60. Mellai M, Piazzi A, Casalone C, Grifoni S, Melcarne A, Annovazzi L et al. Astroblastoma: beside being a tumor entity, an occasional phenotype of astrocyticgliomas? Onco Targets Ther. 2015;8:451-60.

61. Barakat MI, Ammar MG, Salama HM, Abuhashem S. Astroblastoma: case report and review of literature. Turk Neurosurg. 2016;26(5):790-4.

62. Bale TA, Abedalthagafi M, Bi WL, Kang YJ, Merrill P, Dunn IF et al. Genomic characterization of recurrent high-grade astroblastoma. Cancer Genet. 2016;209(7-8):321-30.

63. Yeo JJ, Low YY, Putti TC, Koh KM. Adult intraventricular astroblastoma. Singap Med J. 2016;57(1):53-4.

64. Yuzawa S, Nishihara H, Tanino M, Kimura T, Moriya J, Kamoshima Yet al. A case of cerebral astroblastoma with rhabdoid features: a cytological, histological, and immunohistochemical study. Brain Tumor Pathol. 2016;33(1):63-70.

65. Singla N, Dhandapani SS, Kapoor A, Chatterjee D, Vashishta RK. Hemorrhage in astroblastoma: an unusual manifestation of an extremely rare entity. J ClinNeurosci. 2016;25:147-50.

66. Samples DC, Henry J, Bazan C, Tarasiewicz I. A case of astroblastoma: radiological and histopathological characteristics and a review of current treatment options. Surg. Neurol. Int. 2016;7(Suppl. 40):S1008-12.

67. Palled SR, Thimmaya N, Jagadheesan S, Khaleel I. Astroblastoma: a rare case report. Journal of Radiotherapy in Practice. 2016;15:107-10.

68. Lehman NL, Hattab EM, Mobley BC, Usubalieva A, Schniederjan MJ, McLendon RE et al. Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults. NeuroOncol. 2017;19(1):31-42.

69. Payne C, Batouli A, Stabingas K, Alcindor D, Abdel AK, Pu C, et al. A pediatric tumor found frequently in adult population: a case of anaplastic astrocytoma in an elderly patient and review of the literature. Case Rep Neurol Med. 2017:1607915.

70. Sadiq M, Ahmad I, Shuja J, Ahmad Z, Ahmed R, Ahmad K. Astroblastoma in a Young Female Patient: A Case Report and Literature Review of Clinicopathological, Radiological and Prognostic Characteristics and Current Treatment Strategies. Brain Tumor Res Treat. 2017;5(2):120-6.

71. Burford A, Mackay A, Popov S, Vinci M, Carvalho D, Clarke M, et al. The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelialtumour with MN1:BEND2 fusion. Scientific Reports. 2018;8:1032.

72. Merfeld EC, Dahiya S, Perkins SM. Patterns of care and treatment outcomes of patients with astroblastoma: a National Cancer Database analysis. CNS Oncol. 2018 Apr;7(2):CNS13.

73. Yamada SM, Tomita Y, Shibui S, Takahashi M, Kawamoto M, Nobusawa S, et al. Primary spinal cord astroblastoma: case report. Journal of Neurosurgery: Spine, June 2018;28(6):642-6.

74. Bonnin JM, Rubinstein LJ. Astroblastomas: a pathological study of 23 tumors, with a postoperative follow-up in 13 patients. Neurosurgery. 1989 Jul;25(1):6-13.

75. Sughrue ME, Choi J, Rutkowski MJ, Aranda D, Kane AJ, Barani IJ et al. Clinical features and post-surgical outcome of patients with astroblastoma. J ClinNeurosci. 2011 Jun;18(6):750-4.

76. Ahmed KA, Allen PK, Mahajan A, Brown PD, Ghia AJ. Astroblastomas: a Surveillance, Epidemiology, and End Results (SEER)-based patterns of care analysis. World Neurosurg. 2014;82(1-2):e291-7.

77. Cunningham DA, Lowe LH, Shao L, Acosta NR. Neuroradiologic characteristics of astroblastoma and systematic review of the literature: 2 new cases and 125 cases reported in 59 publications. PediatrRadiol. 2016;46(9):1301-8.

78. Mallick S, Benson R, Venkatesulu B, Melgandi W, Rath GK. Patterns of care and survival outcomes in patients with astroblastoma: an individual patient data analysis of 152 cases. Childs Nerv Syst. 2017;33:1295-302.

79.  Louis DN, Holland EC and Cairncross JG. Glioma classification- a molecular reappraisal. Am J Pathol. 2001 Sep;159(3):779-86.

80. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO Classification of Tumours of the Central Nervous System. ActaNeouropathol. 2007;114:97-109.

81. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. World Health Organization  histological classification of tumours of the central nervous system. International Agency for Research on Cancer, France: 2016.