Category Archives: Neurooncology

Encephaloclastic cyst

Poorly circumscribed areas of parenchymal destruction associated with cystic components.

Encephaloclastic cysts provoked by intraventricular chemotherapy are very uncommon.

Rare complication of a malfunctioning methotrexate Ommaya reservoir 1) 2).


The pathogenesis may result from alterations in CSF pulsations with retrograde flow of intraventricular chemotherapy into the brain parenchyma and subsequent development of a local chemical encephalopathy.

Mella et al. report two rare cases of encephaloclastic cyst with intraventricular topotecan use. The patients were diagnosed and treated at The University of Texas MD Anderson Cancer Center. They consented to the publication of their laboratory results and imaging studies for educational purposes.

The patients presented with metastatic cancers (breast/lung) complicated by leptomeningeal disease. Ommaya reservoirs were placed in both cases and patients were initiated on intraventricular topotecan at 0.4 mg twice weekly. After approximately 12 intraventricular treatments, both patients developed confusion, seizures and headaches. MRI of the brain demonstrated cystic dilatation of the brain parenchyma around the catheter that connects to the reservoir dome and delivers the drug to the intraventricular space. The catheter was surrounded by vasogenic edema. Catheters were removed and analyzed and were found to be intact. CSF analyses showed no evidence of infection or malignancy. Intraventricular topotecan was discontinued and both patients demonstrated sustained clinical and radiological responses.

These cases highlight an atypical complication of intraventricular use of topotecan with successful management 3).


Chowdhary S, Chalmers LM, Chamberlain PA. Methotrexate-induced encephaloclastic cyst: a complication of intraventricular chemotherapy. Neurology. 2006 Jul 25;67(2):319. PubMed PMID: 16864827.

Lubomski M, Pell M, Lochhead A, Jude M. Encephaloclastic cyst: a rare complication of a malfunctioning methotrexate Ommaya reservoir. Intern Med J. 2018 Feb;48(2):224-226. doi: 10.1111/imj.13704. PubMed PMID: 29415363.

Mella DB, Kamiya-Matsuoka C, Liao B, Tummala S, de Groot J. Recurrent encephaloclastic cyst induced by intraventricular topotecan. J Neurol Sci. 2015 Feb 15;349(1-2):52-3. doi: 10.1016/j.jns.2014.12.024. Epub 2014 Dec 24. PubMed PMID: 25598491.

Update: Cerebellopontine angle pilocytic astrocytoma

Cerebellopontine angle pilocytic astrocytoma

A rare case of a 55-yr old patient of pilocytic astrocytoma of the cerebellopontine angle mimicking a vestibular schwannoma. The tumor protruded into the porus acusticus causing enlargement of the internal auditory meatus, which is quite an unusual feature of glial tumor 1).

Schneider et al. report a pilocytic astrocytoma of the cerebellopontine angle in a child presenting with auditory neuropathy spectrum disorder 2).

Mirone et al. describe a rare case of pediatric pilocytic astrocytoma presented as a right cerebellopontine angle (CPA) mass, completely separated from the brainstem and arising from the proximal VIII cranial nerve portion.

A 12-year-old boy, with no evidence of neurofibromatosis type 2, presented with progressive hearing loss at the right ear and headache. An initial enhanced magnetic resonance examination suggested the diagnosis of schwannoma. The tumor was resected by a suboccipital retrosigmoid approach.

The case seems to be the first report of a primary pediatric CPA pylocitic astrocytoma arising from the VIII nerve complex and presenting internal auditory canal enlargement. It represents the third reported case of a primary CPA pilocytic astrocytoma (the second pediatric case with the first arising from V nerve) and the eighth report of primary CPA glioma, overall 3).

A case of pilocytic astrocytoma of the cerebellum mimicking an acoustic schwannoma. The tumour protruded into the porus acusticus and enlarged the internal auditory meatus, which is a quite unusual characteristic of glial tumours 4).


Dutta G, Singh D, Singh H, Sachdeva D, Kumar V, Chaturvedi A. Pilocytic astrocytoma of the cerebellopontine angle mimicking vestibular schwannoma: report of a rare entity. Br J Neurosurg. 2017 Dec 26:1-3. doi: 10.1080/02688697.2017.1419163. [Epub ahead of print] PubMed PMID: 29278012.

Schneider F, Kompis M, Ozdoba C, Beck J, Caversaccio M, Senn P. Pilocytic astrocytoma of the cerebellopontine angle in a child presenting with auditory neuropathy spectrum disorder. Otol Neurotol. 2015 Apr;36(4):e101-3. doi: 10.1097/MAO.0000000000000355. PubMed PMID: 24781101.

Mirone G, Schiabello L, Chibbaro S, Bouazza S, George B. Pediatric primary pilocytic astrocytoma of the cerebellopontine angle: a case report. Childs Nerv Syst. 2009 Feb;25(2):247-51. doi: 10.1007/s00381-008-0690-9. Epub 2008 Aug 9. PubMed PMID: 18690462.

Takada Y, Ohno K, Tamaki M, Hirakawa K. Cerebellopontine angle pilocytic astrocytoma mimicking acoustic schwannoma. Neuroradiology. 1999 Dec;41(12):949-50. PubMed PMID: 10639675.

Update: Medulloblastoma epidemiology

Medulloblastoma epidemiology

In children medulloblastoma comprise 15-20 % of intracranial tumor1).

30-55 % of posterior fossa tumors.

Medulloblastoma is the most common malignant pediatric intracranial tumor 2).

Medulloblastomas comprise < 1 % of adult brain neoplasms. Peak incidence during 1st. decade. Median age at diagnosis 5-7 years (75 % are diagnosed by age 15). Male:female ratio is 2:1. Familial cancer syndromes that include medulloblastoma: Gorlin syndromeTurcot syndrome.

Population-based data examining recent epidemiological trends in medulloblastoma, are limited. Therefore, Khanna et al. sought to examine recent population-level trends in medulloblastoma incidence and survival. Central Brain Tumor Registry of the United States (CBTRUS) data were analyzed from 2001 to 2013. Age-adjusted incidence rates (IR) and annual percent changes (APCs) with 95% confidence intervals (CI) were calculated by age, sex, and race. Relative survival rates were calculated by age, sex, and race using Surveillance, Epidemiology and End-Results (SEER) registries; subsets of CBTRUS data. Kaplan-Meier and Cox proportional hazards models were used to examine survival differences. Medulloblastoma incidence remained relatively stable from 2001 to 2013, with minor fluctuations from 2001 to 2009 (APC = 2.2, 95% CI 0.8, 3.5) and 2009-2013 (APC = -4.1, 95% CI -7.5, -0.6). Incidence was highest in patients aged 1-4 years at diagnosis, but patients aged 10-14 years showed increased incidence from 2000 to 2013 (APC = 3.2, 95% CI 0.6, 5.8). Males displayed higher IR relative to females (males: 0.16 vs. females: 0.12), except in patients <1 year-old. Compared to Whites, Blacks displayed a non-significant increase in incidence (APC = 1.7, 95% CI -0.4, 4.0) and in mortality risk (hazard ratio for survival = 0.74; p = 0.09). The current study reports no overall change in medulloblastoma incidence from 2001 to 2013. Male and female patients <1 year-old had equal medulloblastoma incidence rates and poor 5-year relative survival compared to other ages. Non-significant trends in the data suggest disparities in medulloblastoma incidence and survival by race. Thus, analysis of tumor-specific trends by demographic variables can uncover clinically informative trends in cancer burden 3).

A report aims to provide accurate nationwide epidemiologic data on primary brain and central nervous system (CNS) tumors in the Republic of Korea. Dho et al. updated the data by analyzing primary brain and CNS tumors diagnosed in 2013 using the data from the national cancer incidence database.

Data on primary brain and CNS tumors diagnosed in 2013 were collected from the Korean Central Cancer Registry. Crude and age-standardized rates were calculated in terms of gender, age, and histological type.

A total of 11,827 patients were diagnosed with primary brain and CNS tumors in 2013. Brain and CNS tumors occurred in females more often than in males (female:male, 1.70:1). The most common tumor was meningioma (37.3%). Pituitary tumors (18.0%), gliomas (12.7%), and nerve sheath tumors (12.3%) followed in incidence. Glioblastomas accounted for 41.8% of all gliomas. In children (<19 years), sellar region tumors (pituitary and craniopharyngioma), embryonal/primitive/medulloblastoma, and germ cell tumors were the most common tumors 4).


Laurent JP, Cheek WR. Brain tumours in children. J Pediatr Neurosci. 1985;1:15–32

Allen JC. Childhood brain tumors: current status of clinical trials in newly diagnosed and recurrent disease. Pediatr Clin North Am. 1985 Jun;32(3):633-51. Review. PubMed PMID: 3889800.

Khanna V, Achey RL, Ostrom QT, Block-Beach H, Kruchko C, Barnholtz-Sloan JS, de Blank PM. Incidence and survival trends for medulloblastomas in the United States from 2001 to 2013. J Neurooncol. 2017 Dec;135(3):433-441. doi: 10.1007/s11060-017-2594-6. Epub 2017 Aug 21. PubMed PMID: 28828582.

Dho YS, Jung KW, Ha J, Seo Y, Park CK, Won YJ, Yoo H. An Updated Nationwide Epidemiology of Primary Brain Tumors in Republic of Korea, 2013. Brain Tumor Res Treat. 2017 Apr;5(1):16-23. doi: 10.14791/btrt.2017.5.1.16. Epub 2017 Apr 30. PubMed PMID: 28516074; PubMed Central PMCID: PMC5433946.

Update: Ependymoma RELA fusion positive

Ependymoma RELA fusion positive

Ependymoma RELA fusion-positive is a accepted variant of ependymoma, only recognised in the World Health Organization Classification of Tumors of the Central Nervous System 2016 1).


They are the most common type of supratentorial ependymoma in children, and not found in the posterior fossa or spinal cord.

Two-thirds of supratentorial (ST) ependymomas harbor oncogenic fusions of RELA.


The protein product is the principal effector of canonical Nuclear factor kappa signaling. RELA fusion proteins activate signaling for tumor proliferation and malignant progression, resulting in poorer prognoses in these patients compared to those in patients with other ST ependymomas.

In a study, Nakamura et al. encountered a case of C11orf-RelA fusion-positive ST anaplastic ependymoma that was diagnosed in first tumor resection surgery of multi-staged gross total resection with molecular evidence. In ependymomas, regardless of tumor location or pathological grade, subtotal resection is associated with higher rates of mortality compared with GTR 2).

In posterior fossa ependymoma group A (PF-EPN-A) tumors, telomerase activity varied and was significantly associated with dismal overall survival, whereas telomerase reactivation was present in all supratentorial RelA fusion-positive (ST-EPN-RELA) ependymomas 3).


These tumours can be both grade II or III and demonstrate a variety of histological morphologies, although clear cells and prominent vascularity are common.

The presence of the RELA fusion gene can be assessed with FISH.


GFAP positive

EMA positive

L1CAM positive correlates closely with the presence of RELA fusion not exclusive to ependymomas.


Actinomycin D could constitute a promising therapeutic option for Ependymoma RELA fusion positive, whose tumours frequently exhibit p53 inactivation 4).

Case reports


A case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of Ependymoma RELA fusion positive, showing aggressive behavior 5).


Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016 Jun;131(6):803-20. doi: 10.1007/s00401-016-1545-1. Epub 2016 May 9. Review. PubMed PMID: 27157931.


Nakamura T, Fukuoka K, Ikeda J, Yoshitomi M, Udaka N, Tanoshima R, Tateishi K, Yamanaka S, Ichimura K, Yamamoto T. Encouraging option of multi-staged gross total resection for a C11orf-RelA fusion-positive supratentorial anaplastic ependymoma. Brain Tumor Pathol. 2017 Oct;34(4):160-164. doi: 10.1007/s10014-017-0297-5. Epub 2017 Aug 22. PubMed PMID: 28831588.


Gojo J, Lötsch D, Spiegl-Kreinecker S, Pajtler KW, Neumayer K, Korbel P, Araki A, Brandstetter A, Mohr T, Hovestadt V, Chavez L, Kirchhofer D, Ricken G, Stefanits H, Korshunov A, Pfister SM, Dieckmann K, Azizi AA, Czech T, Filipits M, Kool M, Peyrl A, Slavc I, Berger W, Haberler C. Telomerase activation in posterior fossa group A ependymomas is associated with dismal prognosis and chromosome 1q gain. Neuro Oncol. 2017 Sep 1;19(9):1183-1194. doi: 10.1093/neuonc/nox027. PubMed PMID: 28371821; PubMed Central PMCID: PMC5570194.


Tzaridis T, Milde T, Pajtler KW, Bender S, Jones DT, Müller S, Wittmann A, Schlotter M, Kulozik AE, Lichter P, Peter Collins V, Witt O, Kool M, Korshunov A, Pfister SM, Witt H. Low-dose Actinomycin-D treatment re-establishes the tumoursuppressive function of P53 in RELA-positive ependymoma. Oncotarget. 2016 Sep 20;7(38):61860-61873. doi: 10.18632/oncotarget.11452. PubMed PMID: 27556362; PubMed Central PMCID: PMC5308696.


Kim SI, Lee Y, Kim SK, Kang HJ, Park SH. Aggressive Supratentorial Ependymoma, RELA Fusion-Positive with Extracranial Metastasis: A Case Report. J Pathol Transl Med. 2017 Nov;51(6):588-593. doi: 10.4132/jptm.2017.08.10. Epub 2017 Nov 15. PubMed PMID: 29161788.

Update: GLARIUS trial


The GLARIUS trial which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) as compared to standard temozolomide (TMZ) in the first-line therapy of MGMT promoter methylation glioblastoma showed that progression free survival was significantly prolonged by BEV/IRI while overall survival was similar in both arms 1).

A report focusses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease.

Patients (n=170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard TMZ. At least every three months KPS was determined and QoL was measured using the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. A generalized estimating equation model (GEE) evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration was analyzed separately.

In all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation.

GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM 2).


Herrlinger U, Schäfer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hänel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tüttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol. 2016 May 10;34(14):1611-9. doi: 10.1200/JCO.2015.63.4691. Epub 2016 Mar 14. PubMed PMID: 26976423.


Schäfer N, Proescholdt M, Steinbach JP, Weyerbrock A, Hau P, Grauer O, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Grau S, Hänel M, Schnell O, Krex D, Vajkoczy P, Tabatabai G, Mack F, Schaub C, Tzaridis T, Nießen M, Kebir S, Leutgeb B, Urbach H, Belka C, Stummer W, Glas M, Herrlinger U. Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma. Neuro Oncol. 2017 Nov 7. doi: 10.1093/neuonc/nox204. [Epub ahead of print] PubMed PMID: 29121274.