Category Archives: Neurooncology

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).

Epidemiology

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.

Outcome

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).

Pathology

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.

Immunophenotype

GFAP positive

EMA positive

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

Treatment

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

Case reports

2017

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).

1)

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.

2)

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.

3)

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.

4)

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.

5)

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

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).

1)

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.

2)

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.

Update: Cerebellopontine angle metastases

Cerebellopontine angle metastases

Metastatic lesions in the cerebellopontine angle (CPA) are rare and are commonly associated with breast cancer or lung cancer.

In a retrospective series of 1345 patients with CPA lesions the common underlying diagnoses were VS (91.3%), meningiomas (3.1%), epidermoids (2.4%) and facial nerve schwannomas (1.2%). Other rare causes (2%) included lipomas, gliomas, dermoids, arachnoid cysts, hemangiomas, hemangioblastomas, medulloblastomas, chondrosarcomas, malignant teratomas and metastasis 1).

Clinical features

Isolated metastases to the CPA represent a diagnostic challenge to differentiate them from the more commonly occurring CPA lesions, particularly in the absence of metastatic disease 2).

In a small series of 14 patients with metastasis to the CPA, this was the initial presentation of the underlying malignancy in 4 (28%) 3).

Features suggestive of metastasis as opposed to schwannoma were acute onset, rapid progression of symptoms, associated seventh and/or eighth nerve deficits, bilateral involvement or systemic metastasis. Useful MRI findings included small and/or bilateral CPA enhancing lesions with relative isointensity to brain parenchyma on pre-contrast MRI and associated findings of multiple and/or bilateral cranial nerve and/or leptomeningeal lesions 4).

Case series

2017

Ten patients were reviewed for the period between 2008 and 2015. The clinical and neuroimaging features, and treatment outcomes were analyzed retrospectively. The average period during primary diagnosis through the diagnosis of CPA metastases was 42.4 months. Among the 10 cases, the primary tumors and metastases were found simultaneously in 3 cases, the metastases after primary tumor removal were found in 5 cases, and the metastases after stereotaxic radiosurgery were found in 2 cases. Only 4 patients presented with the symptoms and signs associated with CPA involving, one with hearing loss, one presenting facial paralysis, one suffering from tinnitus and one case with dizziness. There were 2 cases with the miliary metastases and 8 cases with massive metastases. There existed 3 cases with single CPA metastases, whereas 7 cases with multiple metastatic foci. Among the 8 cases of massive metastatic foci, 6 tumors presented the solid features and the other 2 cases exhibited cystic and solid features. In this cohort of cases, 4 cases were involved in the bilateral and 6 cases presented unilateral metastatic foci. The three CPA metastases were removed in this group, 6 case performed with radiotherapy, and 5 cases received chemotherapy. In the current group 5 patients have been dead, 3 patients kept stable and 2 cases experienced improvement. In spite of seldom previous reports regarding the metastases from CNS tumors occurring in the CPA are existent, this rare form of the disease should be considered in future evaluation as a differential diagnosis 5).

2002

A total of 174 cancer patients with inner ear-related symptoms such as vertigo, hearing loss, or tinnitus were seen at the university hospital from January 1994 to December 2000. All patients underwent a battery of audiologic and neurotologic tests. Magnetic resonance imaging was performed either when the clinical presentation suggested vertigo of central origin or when sensorineural hearing loss developed.

Magnetic resonance imaging confirmed tumors of the cerebellopontine angle in 6 (3%) of the 174 patients, including 3 men and 3 women. Their ages ranged from 46 to 80 years (mean 62 years). The final diagnoses were breast cancer with cerebellopontine angle metastasis (1), breast cancer with cerebellopontine angle epidermoid cyst (1), colon cancer with cerebellopontine angle metastasis (1), colon cancer with acoustic neuroma (1), nasopharyngeal carcinoma with cerebellopontine angle metastasis (1), and nasopharyngeal carcinoma with cerebellopontine angle benign tumor (1).

When a cerebellopontine angle tumor is discovered in a cancer patient, metastatic cancer should be suspected when the tumor presents with deficits of the VIIth and VIIIth cranial nerves of rapid progression or bilateral involvement, or extracranial systemic metastasis. Laboratory examinations such as cytologic study of the cerebrospinal fluid and serologic study can assist in the diagnosis 6).

Case reports

2016

A 61-year-old man, who visited an otorhinolaryngology clinic with complaints of rapidly progressing bilateral hearing impairment and facial palsy. The patient was referred to our hospital because tumorous lesions were suspected in the bilateral cerebellopontine angles on brain magnetic resonance imaging. Regarding tumor markers, the patient’s cancer antigen 19-9 and carcinoembryonic antigen levels were high, which suggested metastasis. However, no abnormal findings other than abdominal lymph node enlargement were detected on whole-body examination, and no primary lesion was identified. The tumor in the right cerebellopontine angle was excised using the lateral suboccipital approach and subjected to pathological examination. It was diagnosed as an adenocarcinoma; thus, both lesions were considered brain metastases from a malignant abdominal tumor, and radiochemotherapy was administered to the patient. Unfortunately, the patient died after 89 days of treatment, and a pathological autopsy revealed that the primary lesion was a common bile duct tumor. No dural metastasis was noted in the brain or spinal cord; however, tumors were detected in the epiarachnoid space during surgery. Metastasis to the bilateral cerebellopontine angles occurred in the same period, which was indicative of ascending metastasis through the vertebrobasilar artery. Hence, we suggest that progressive bilateral hearing impairment and facial palsy were a consequence of brain tumors that had metastasized bilaterally to the cerebellopontine angles 7).

2015

A 63-year-old male who underwent surgical resection of a poorly differentiated small cell carcinoma, likely from a small intestinal primary tumor that metastasized to the cerebellopontine angle (CPA). A 63-year-old male presented with mild left facial paralysis, hearing loss, and balance instability. MRI revealed a 15 mm mass in the left CPA involving the internal auditory canal consistent with a vestibular schwannoma. Preoperative MRI eight weeks later demonstrated marked enlargement to 35 mm. The patient underwent a suboccipital craniectomy and the mass was grossly different visually and in consistency from a standard vestibular schwannoma. The final pathology revealed a poorly differentiated small cell carcinoma. Postoperative PET scan identified avid uptake in the small intestine suggestive of either a small intestinal primary tumor or additional metastatic disease. The patient underwent whole brain radiation therapy and chemotherapy and at last follow-up demonstrated improvement in his symptoms. Surgical resection and radiotherapy are potential treatment options to improve survival in patients diagnosed with NET brain metastases. We present the first documented case of skull base metastasis of a poorly differentiated small cell carcinoma involving the CPA 8).

2005

This is the first formal case report of internal auditory canal and cerebellopontine angle metastasis from infiltrative ductal carcinoma of the breast. Only three previous cases have been reported of isolated metastasis in the cerebellopontine angle and internal auditory canal from breast cancer. Currently, no therapeutic guidelines for isolated metastasis from breast cancer in this location exist. We report a case and review the current literature in order to help characterize the clinicopathologic features and management. A 72-year-old female with a 5-year history of left infiltrative ductal carcinoma of the breast reported progressive left-sided facial palsy and ipsilateral hearing loss accompanied by the development of tinnitus and unsteadiness during the previous 3 months. MRI identified a lesion in the cerebellopontine angle and internal auditory canal. The lesion was completely excised via a retrosigmoidal approach and adjuvant radiotherapy was used subsequently. The patient remains well 18 months after treatment, with no evidence of recurrence on repeat MRI. The rapid evolution of symptoms involving the Vth, VIIth or VIIIth cranial nerve, or multiple cranial nerves, is suggestive of a malignant lesion of the cerebellopontine angle and/or internal auditory canal. A previous history of neoplasm is important due to the possibility of a metastasis. Cerebellopontine angle metastasis can be found many years after the initial diagnosis of breast neoplasm. Surgery and adjuvant radiotherapy seems to be a good choice for the treatment of patients with this specific type of metastasis9).


Bilateral cerebellopontine angle (CPA) tumors identified on MRI are considered bilateral acoustic neuromas, the definitive diagnostic criterion of neurofibromatosis 2 (NF-2). We report the case of a 67-year-old man with progressive bilateral hearing loss, vertigo, and imbalance. MRI revealed bilateral enhancing CPA lesions, which were suggestive of acoustic neuromas and a diagnosis of NF-2. However, autopsy showed metastatic adenocarcinoma of the lung. Therefore, metastatic carcinoma to the CPA can mimic bilateral acoustic neuromas; imaging studies alone may be insufficient to diagnose NF-2 10).

1)

Brackmann DE, Bartels LJ. Rare tumors of the cerebellopontine angle. Otolaryngol Head Neck Surg (1979). 1980 Sep-Oct;88(5):555-9. PubMed PMID: 6969383.

2)

Hamid B, Harris C, Spiess J. Metastatic adenocarcinoma in the cerebellopontine angle mimicking facial nerve Schwannoma. Am J Clin Oncol. 2007 Oct;30(5):566-7. PubMed PMID: 17921722.

3)

Yuh WT, Mayr-Yuh NA, Koci TM, Simon JH, Nelson KL, Zyroff J, Jinkins JR. Metastatic lesions involving the cerebellopontine angle. AJNR Am J Neuroradiol. 1993 Jan-Feb;14(1):99-106. PubMed PMID: 8427116.

4)

Chiong Y, Mulroy L, Fleetwood IG, Younis T. Isolated metastasis to the cerebellopontine angle secondary to breast cancer. Can J Surg. 2009 Oct;52(5):E213-4. PubMed PMID: 19865565; PubMed Central PMCID: PMC2769124.

5)

Zhang M, Wang Z, Zhang J, Zhang H, Gu C, Wang H, Yu C, Wu H. Metastases in cerebellopontine angle from the tumors of central nerve system. J Clin Neurosci. 2017 Aug;42:84-90. doi: 10.1016/j.jocn.2017.04.011. Epub 2017 Apr 22. PubMed PMID: 28442197.

6)

Huang TW, Young YH. Differentiation between cerebellopontine angle tumors in cancer patients. Otol Neurotol. 2002 Nov;23(6):975-9. PubMed PMID: 12438865.

7)

Node Y, Harada N, Masuda H, Kondo K, Nemoto M, Sugo N. [A Rare Case of Metastatic Brain Tumors in the Bilateral Cerebellopontine Angles]. No Shinkei Geka. 2016 Dec;44(12):1033-1038. Japanese. PubMed PMID: 27932747.

8)

Theodros D, Goodwin CR, Crane GM, Liauw J, Kleinberg L, Lim M. Metastatic extrapulmonary small cell carcinoma to the cerebellopontine angle: a case report and review of the literature. Case Rep Oncol Med. 2015;2015:847058. doi: 10.1155/2015/847058. Epub 2015 Feb 25. PubMed PMID: 25810937; PubMed Central PMCID: PMC4355812.

9)

Guilemany JM, Alobid I, Gastón F, Morrelló A, Bernal-Sprekelsen M. Cerebellopontine angle and internal auditory canal metastasis from ductal carcinoma of the breast. Acta Otolaryngol. 2005 Sep;125(9):1004-7. PubMed PMID: 16193592.

10)

Hariharan S, Zhu J, Nadkarni MA, Donahue JE. Metastatic lung cancer in the cerebellopontine angles mimicking bilateral acoustic neuroma. J Clin Neurosci. 2005 Feb;12(2):184-6. PubMed PMID: 15749427.

Update: Falcotentorial meningioma treatment

Falcotentorial meningioma treatment

The primary aim of surgical treatment for falcotentorial meningiomas is gross total excision. The vital surrounding brain structures make this a complex task.

Several surgical approaches have been described to treat falcotentorial meningiomas. These include infratentorial supracerebellar approachsuboccipital approachoccipital transtentorial approach, and combined supratentorial and infratentorial approaches 1) 2) 3).

There are two main issues in treating falcotentorial meningiomas. One is selecting the surgical approach, which includes design of the bone flap. The other main issue is whether main venous structures will be sacrificed for a radical tumor resection.

In all of the cases, Hong et al. tried to make an adequately sized bone flap, even when the tumor was quite large. Some authors have insisted on performing wide craniotomies for large falcotentorial meningiomas 4).

Quiñones-Hinojosa, et al. 5) described a bilateral occipital transtentorial/transfalcine approach for large falcotentorial meningiomas. They ligated and cut the transverse sinus after checking the patency of the occluded sinus, and used permanent aneurysmal clips to ligate the vein of Galenwhen the straight sinus was occluded. The area above and below the tentorium can provide wide exposure and reduce occipital lobe retraction during prolonged operation times. Moreover, this approach may allow surgeons some form of intraoperative flexibility in terms of their surgical plan.

Hong et al. do not suggest routine application of wide craniotomies, such as the combined supratentorial and infratentorial approach. This is because wide craniotomies may increase the total amount of bleeding, prolong the operation time, and increase the risk of cerebral cortex injury. Moreover, it is possible to completely remove huge falcotentorial meningiomas without neurological deficit via relatively small craniotomies.

A catheter for CSF drainage was inserted into the ventricle or cisternal space through the safest area in each patient. They also designed small craniotomies through which the possible access area covered the entire tumor territory. Thus, if a CSF drain is possible, then appropriately designed small craniotomies are sufficient to achieve complete tumor resection without cortex injury 6).

There are some reports that have described usage of ligation and sectioning of the transverse sinus with or without reanastomosis 7) 8).

Although many authors have reported safe ligation of the transverse-sigmoid sinus, some complications have been described 9) 10).

Every venous structure should be preserved even if they seem to lack significant function. This will help prevent complications associated with delayed lobar parenchymal hemorrhage that can be attributed to venous infarction.

In conclusion, surgical approaches should be tailored to each patient according to the origin and direction of tumor growth, feeding arteries, and the surrounding venous drainage system.

Hong et al. found that a relatively small craniotomy was sufficient to completely remove each tumor. Moreover, they found that the most important factors for avoiding surgical complications were to preserve vital deep neurovascular structures, as well as flow through the venous sinuses.

The results showed that falcotentorial meningiomas could be cured via single-stage operations without complications by applying careful perioperative planning and a delicate microsurgical technique 11).

Videos


In this operative video, the authors demonstrate an illustrative step-by-step technique for endoscopic-assisted microsurgical resection of a falcotentorial meningioma using the posterior interhemispheric retrocallosal transfalcine approach for a superiorly positioned falcotentorial meningioma. The surgical nuances are discussed, including the surgical anatomy, gravity-assisted interhemispheric approach in the lateral position, retrocallosal dissection, transfalcine exposure, tumor removal, and preservation of the vein of Galen complex. In summary, the posterior interhemispheric retrocallosal transfalcine approach is a useful surgical strategy for select superiorly positioned falcotentorial meningiomas.

Case series

2009

From 2001 to 2005, 9 patients underwent operation for meningiomas arising from the falcotentorial junction, with some extending to and/or invading the torcula. All patients were assessed preoperatively with magnetic resonance neuroimaging and cerebral angiography. Furthermore, preoperative embolization was attempted in all cases. A supratentorial/infratentorial torcular craniotomy technique was used in all but 1 of these cases.

The average dimensions of the falcotentorial meningiomas were 5.1 x 4.4 x 4.2 cm. The angiograms revealed that these tumors were fed by branches of the internal carotid artery, choroidal arteries, branches of the meningohypophyseal trunk, and branches of the posterior cerebral artery. Preoperative embolization was achieved in only 2 patients. Five patients had gross total resection (Simpson grade 1), and 4 had subtotal resection (Simpson grade 4). Two of the tumors (22%) recurred during a mean follow-up period of 49 months (range, 17-88 months). The most common complication after surgery was cortical blindness, but all postoperative visual deficits had fully recovered at the last follow-up evaluation within several months.

An excellent outcome can be expected with detailed preoperative neuroimaging and knowledge of the nuances of the surgical technique that we describe in detail in the article 12).

2006

Goto et al. evaluated their surgical experience over 20 years with 14 treated falcotentorial meningiomas.

In the past 20 years, 14 patients with falcotentorial junction meningiomas were surgically treated. There were seven men and seven women, whose ages ranged from 34 to 79 years. On the basis of neuroimaging studies, the authors analyzed the influence of the anatomical relationship of the tumor to the vein of Galen, patency of the vein of Galen, tumor size, and the signal intensities on the magnetic resonance images to determine possible difficulties that might be encountered during surgery and to prognosticate the outcome of surgery. Depending on the relationship with the vein of Galen, tumors were labeled as either a superior or an inferior type. All tumors were resected via an occipital transtentorial approach. The surgical outcome in eight patients was excellent; in the remaining six patients, it was fair. Of the prognostic factors, tumor location especially seemed to be the most important (p < 0.01, Fisher exact test). The outcome associated with the inferior type of tumor was significantly less optimal probably due to the relationship to the deep veins and the brainstem. In this series, the occlusion of deep veins did not significantly influence outcome.

Classification of the tumor location by preoperative neuroimaging studies can be helpful in estimating the surgical difficulty that might be encountered in treating the falcotentorial junction meningioma 13).

2003

Meningiomas arising from the falcotentorial junction are rare. As a result, their clinical presentation and surgical management are not well described. During the past 3 years, the authors have treated six patients with falcotentorial meningiomas.

Most patients presented with symptoms related to raised intracranial pressure, including headaches, papilledema, and visual and gait disturbances. Magnetic resonance imaging revealed a smooth, oval, or round mass, which was typically homogeneously enhancing. Angiography was useful in evaluating arterial supply for embolization, when possible, and determining the status of venous collateral supply and sinus patency. The authors detail the surgical technique used in all six patients. Postoperatively, patients experienced transient cortical blindness, which in all cases spontaneously resolved during the course of several days to weeks. They provide a comprehensive description of the presentation and surgical management of falcotentorial meningiomas.

An excellent outcome can be expected when surgery is predicated on detailed preoperative neuroimaging and knowledge of the nuances of the surgical technique 14).

2001

Okami et al. present four surgical cases. An occipital transtentorial approach was used in three cases, and a combined midline occipital and suboccipital approach in one case. Total tumour excision was impossible in two cases because of engulfing deep venous structures including the great vein of Galen. Postoperative Gamma knife radiosurgery was performed in these two cases. On the other hand, a posteriorly located tumour was relatively easy to remove, and macroscopic total removal was accomplished. In conclusion, precise microvascular anatomical knowledge is indispensable to satisfactorily excise meningiomas in the falcotentorial area without significant morbidity 15).

1995

Asari et al. describe the clinical features, neuroimaging studies, and results of surgical treatment of meningiomas of the falcotentorial junction and clarify the characteristics of this lesion based on a review of the literature and seven patients treated at their institution. The most common symptoms resulted from intracranial hypertension. Upward-gaze palsy appeared in only one patient. Computerized tomography (CT) showed no specific findings, but there was no evidence of edema around the tumor. Magnetic resonance (MR) imaging revealed a round, smooth-bordered mass with a peritumoral rim, without edema, and showing marked contrast enhancement. The multiplanar capability of MR imaging delineated the relationship between the tumor and adjacent structures better than did CT. Detailed knowledge of the vascular structures, especially evidence of occlusion of the galenic venous system and the development of collateral venous channels, is critical for successful surgery; stereoscopic cerebral angiography is necessary to achieve this aim. The seven patients described developed five types of collateral venous channels: through the basal vein of Rosenthal to the petrosal vein, through the veins on the medial surface of the parietal and occipital lobes to the superior sagittal sinus, through superficial anastomotic veins, through veins of the posterior fossa to the transverse or straight sinus, and through the falcian veins to the superior sagittal sinus. The first three types mainly developed after occlusion of the galenic system. The tumors were removed through the occipital transtentorial approach with a large window at the posterior part of the falx. A favorable prognosis for patients undergoing surgical treatment of falcotentorial junction meningiomas can be expected if detailed neuroimaging studies and microsurgical techniques are used 16).


The tumors were removed subtotally or totally via an occipital interhemispheric transtentorial approach and/or infratentorial supracerebellar approach. The postoperative courses were uneventful, and no neurological deficit was detected postoperatively. Pineal region tumors with a maximum diameter of 5 cm or larger should be operated on via a unilateral or bilateral occipital interhemispheric transtentorial approach, regardless of the angiographic findings, because this permits a wide operative field and can be followed, if necessary, by an infratentorial supracerebellar approach. Selection of the operative approach for a relatively small pineal region tumor should depend on the angiographic findings: downward displacement of the bilateral internal cerebral veins and the great vein of Galen indicates an occipital interhemispheric transtentorial approach, whereas upward displacement indicates an infratentorial supracerebellar approach 17).

Case reports

2017

One representative case of falcotentorial meningioma treated through an anterior interhemispheric transsplenial approach is also described. Among the interhemispheric approaches to the pineal region, the anterior interhemispheric transsplenial approach has several advantages. 1) There are few or no bridging veins at the level of the pericoronal suture. 2) The parietal and occipital lobes are not retracted, which reduces the chances of approach-related morbidity, especially in the dominant hemisphere. 3) The risk of damage to the deep venous structures is low because the tumor surface reached first is relatively vein free. 4) The internal cerebral veins can be manipulated and dissected away laterally through the anterior interhemispheric route but not via the posterior interhemispheric route. 5) Early control of medial posterior choroidal arteries is obtained. The anterior interhemispheric transsplenial approach provides a safe and effective surgical corridor for patients with supratentorial pineal region tumors that 1) extend superiorly, involve the splenium of the corpus callosum, and push the deep venous system in a posterosuperior or an anteroinferior direction; 2) are tentorial and displace the deep venous system inferiorly; or 3) originate from the splenium of the corpus callosum 18).

2006

Kawashima et al. reported, in anatomic studies, a occipital transtentorial approach: the occipital bi-transtentorial/falcine approach, to treat such lesions. Gusmão et al. present a patient with a large falcotentorial meningioma, located bilaterally in the posterior incisural space. The occipital bi-transtentorial/falcine approach allowed an excellent surgical exposure and complete tumor removal with an excellent patient outcome 19).

References

1) , 15)

Okami N, Kawamata T, Hori T, Takakura K. Surgical treatment of falcotentorial meningioma. J Clin Neurosci. 2001 May;8 Suppl 1:15-8. Review. PubMed PMID: 11386819.
2)

Raco A, Agrillo A, Ruggeri A, Gagliardi FM, Cantore G. Surgical options in the management of falcotentorial meningiomas: report of 13 cases. Surg Neurol. 2004 Feb;61(2):157-64; discussion 164. PubMed PMID: 14751629.
3) , 7)

Sekhar LN, Goel A. Combined supratentorial and infratentorial approach to large pineal-region meningioma. Surg Neurol. 1992 Mar;37(3):197-201. PubMed PMID: 1536024.
4) , 6) , 11)

Hong CK, Hong JB, Park H, Moon JH, Chang JH, Lee KS, Park SW. Surgical Treatment for Falcotentorial Meningiomas. Yonsei Med J. 2016 Jul;57(4):1022-8. doi: 10.3349/ymj.2016.57.4.1022. PubMed PMID: 27189300; PubMed Central PMCID: PMC4951445.
5) , 12)

Quiñones-Hinojosa A, Chang EF, Chaichana KL, McDermott MW. Surgical considerations in the management of falcotentorial meningiomas: advantages of the bilateral occipital transtentorial/transfalcine craniotomy for large tumors. Neurosurgery. 2009 May;64(5 Suppl 2):260-8; discussion 268. doi: 10.1227/01.NEU.0000344642.98597.A7. PubMed PMID: 19287325.
8)

Hwang SK, Gwak HS, Paek SH, Kim DG, Jung HW. Guidelines for the ligation of the sigmoid or transverse sinus during large petroclival meningioma surgery. Skull Base. 2004 Feb;14(1):21-8; discussion 29. PubMed PMID: 16145581; PubMed Central PMCID: PMC1151668.
9)

Al-Mefty O, Fox JL, Smith RR. Petrosal approach for petroclival meningiomas. Neurosurgery. 1988 Mar;22(3):510-7. PubMed PMID: 3362317.
10)

Hitselberger WE, House WF. A combined approach to the cerebellopontine angle. A suboccipital-petrosal approach. Arch Otolaryngol. 1966 Sep;84(3):267-85. PubMed PMID: 5296435.
13)

Goto T, Ohata K, Morino M, Takami T, Tsuyuguchi N, Nishio A, Hara M. Falcotentorial meningioma: surgical outcome in 14 patients. J Neurosurg. 2006 Jan;104(1):47-53. PubMed PMID: 16509146.
14)

Quinones-Hinojosa A, Chang EF, McDermott MW. Falcotentorial meningiomas: clinical, neuroimaging, and surgical features in six patients. Neurosurg Focus. 2003 Jun 15;14(6):e11. Review. PubMed PMID: 15669786.
16)

Asari S, Maeshiro T, Tomita S, Kawauchi M, Yabuno N, Kinugasa K, Ohmoto T. Meningiomas arising from the falcotentorial junction. Clinical features, neuroimaging studies, and surgical treatment. J Neurosurg. 1995 May;82(5):726-38. Review. PubMed PMID: 7714596.
17)

Matsuda Y, Inagawa T. Surgical removal of pineal region meningioma–three case reports. Neurol Med Chir (Tokyo). 1995 Aug;35(8):594-7. PubMed PMID: 7566392.
18)

Yağmurlu K, Zaidi HA, Kalani MY, Rhoton AL Jr, Preul MC, Spetzler RF. Anterior interhemispheric transsplenial approach to pineal region tumors: anatomical study and illustrative case. J Neurosurg. 2017 Jan 13:1-11. doi: 10.3171/2016.9.JNS16279. [Epub ahead of print] PubMed PMID: 28084911.
19)

Gusmão S, Oliveira MM, Arantes A, Ulhoa TH, Morato EG. Occipital bi-transtentorial/falcine approach for falcotentorial meningioma: case report. Arq Neuropsiquiatr. 2006 Mar;64(1):136-8. Epub 2006 Apr 5. PubMed PMID: 16622571.

Update: Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumors of the cerebrum (MVNT) are superficial neuronal tumors in adults that were first documented in 2013 1)

It is a new pattern of neuronal tumour included in the World Health Organization Classification of Tumors of the Central Nervous System 2016, as a unique cytoarchitectural pattern of gangliocytoma.

There are fifteen reports in the literature to date. They are typically associated with late onset epilepsy.

Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 2).

Differential diagnosis

Dysembryoplastic neuroepithelial tumor – DNET can appear similar but usually is mostly cortical (rather than subcortical) often has bright FLAIR rim focal cortical dysplasia (Type II) high T2 signal deep to cortex is in the same location but is usually associated with a radial glial band (transmantle sign) and with thickened abnormal overlying cortex perivascular spaces location can be similar usually more elongated along vessel long axis fully attenuating on FLAIR 3).

Treatment

MVNTs appear to be benign tumours with very indolent biological behaviour which can, if asymptomatic, be followed with imaging alone. In symptomatic patients (epileptic) surgical resection often controls seizures, with no tumour regrowth reported 4) 5) 6) 7).

Case series

2017

Thom et al. present a series of ten cases and compare their pathological and genetic features to better characterised epilepsy associated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy associated tumours (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi-gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre-operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 8).


Nunes et al. report 33 cases of presumed multinodular and vacuolating neuronal tumor of the cerebrum that exhibit a remarkably similar pattern of imaging findings consisting of a subcortical cluster of nodular lesions located on the inner surface of an otherwise normal-appearing cortex, principally within the deep cortical ribbon and superficial subcortical white matter, which is hyperintense on FLAIR. Only 4 of the cases are biopsy-proven because most were asymptomatic and incidentally discovered. The remaining were followed for a minimum of 24 months (mean, 3 years) without interval change. They demonstrate that these are benign, nonaggressive lesions that do not require biopsy in asymptomatic patients and behave more like a malformative process than a true neoplasm 9).

2013

Huse et al. report 10 cases of a non-neurocytic, purely neuronal tumor affecting adults. Situated in the cerebral hemispheres, with 7 of 10 confined to the temporal lobes, most presented with seizures as their principal clinical manifestations. On magnetic resosnance imaging (MRI), the tumors generally appeared solid and non-contrast enhancing with minimal diffuse infiltration, edema, or mass effect. Six examples demonstrated internal nodularity. Microscopically, the tumor cells were largely distributed into discrete and coalescent nodules exhibiting varying degrees of matrix vacuolization, principally within the deep cortical ribbon and superficial subcortical white matter. Populating elements ranged from morphologically ambiguous to recognizably neuronal, with only two cases manifesting overt ganglion cell cytology. In all cases, tumor cells exhibited widespread nuclear immunolabeling for the HuC/HuD neuronal antigens, although expression of other neuronal markers, including synaptophysin, neurofilament and chromogranin was variable to absent. Tumor cells also failed to express GFAP, p53, IDH1 R132H, or CD34, although CD34-labeling ramified neural elements were present in the adjoining cortex of seven cases. Molecular analysis in a subset of cases failed to reveal DNA copy number abnormalities or BRAF V600E mutation. Follow-up data indicate that this unusual neuronal lesion behaves in benign, World Health Organization (WHO) grade I fashion and is amenable to surgical control 10).

Case reports

2015

Fukushima et al. report a case of MNVT involving a 37-year-old man who presented with an epileptogenic, superficial solid lesion in the left parietal lobe. Histomorphology of the resected specimen was characterized by nodular lesions with vacuolation. Nodules comprised irregular proliferation of neuronal cells, which ranged from ganglion-like forms to those with indistinct lineage. Immunohistochemical analysis showed that the lesional cells stained positively for HuC/HuD, synaptophysin, and Olig2, and negatively for NeuN, neurofilament, chromogranin A, GFAP, CD34, IDH1(R132H), and BRAF(V600E). Eighteen months following surgery, the patient is well and without neurological deficits. MVNTs are distinctive tumors that should be differentiated from ganglion cell tumors, dysembryoplastic neuroepithelial tumors, and malformation of cortical development 11).

2014

Bodi et al. report the findings in two cases with similar features, a surgical resection and the other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical resection for a multinodular non-enhancing frontal white matter lesion causing intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the age of 71 and MRI scanning revealed extensive multinodular non-enhancing white matter lesions in the temporal lobe. There was no history of epilepsy and post mortem histology confirmed MND.Macroscopically multiple small grey well-formed, discrete and coalescent nodules were seen in the deep cortex and subcortical white matter. On histology, mature-looking neurons with large cytoplasmic vacuoles were distributed in a fibrillary background, where vacuoles were also noted. In the resected tumour scattered oligodendroglia-like cells were present. No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP, IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic vacuoles in the neurons and in some neuronal processes. The seizures recurred in Case 1.Some clinicopathological features of this lesion suggest a possible relationship with dysembryoplastic neuroepithelial tumour (DNT) although the morphological features are not typical of DNT. Case 2 demonstrates that MVNT may remain asymptomatic 12).

References

1) , 6) , 10)

Huse JT, Edgar M, Halliday J, Mikolaenko I, Lavi E, Rosenblum MK. Multinodular and vacuolating neuronal tumors of the cerebrum: 10 cases of a distinctive seizure-associated lesion. Brain Pathol. 2013 Sep;23(5):515-24. doi: 10.1111/bpa.12035. Epub 2013 Feb 1. PubMed PMID: 23324039.
2) , 8)

Thom M, Liu J, Bongaarts A, Reinten RJ, Paradiso B, Jäger HR, Reeves C, Somani A, An S, Marsdon D, McEvoy A, Miserocchi A, Thorne L, Newman F, Bucur S, Honavar M, Jacques T, Aronica E. MULTINODULAR AND VACUOLATING NEURONAL TUMOURS IN EPILEPSY: DYSPLASIA OR NEOPLASIA? Brain Pathol. 2017 Aug 19. doi: 10.1111/bpa.12555. [Epub ahead of print] PubMed PMID: 28833756.
4) , 12)

Bodi I, Curran O, Selway R, Elwes R, Burrone J, Laxton R, Al-Sarraj S, Honavar M. Two cases of multinodular and vacuolating neuronal tumour. Acta Neuropathol Commun. 2014 Jan 20;2:7. doi: 10.1186/2051-5960-2-7. PubMed PMID: 24444358; PubMed Central PMCID: PMC3899932.
5) , 11)

Fukushima S, Yoshida A, Narita Y, Arita H, Ohno M, Miyakita Y, Ichimura K, Shibui S. Multinodular and vacuolating neuronal tumor of the cerebrum. Brain Tumor Pathol. 2015 Apr;32(2):131-6. doi: 10.1007/s10014-014-0198-9. Epub 2014 Aug 22. PubMed PMID: 25146549.
7) , 9)

Nunes RH, Hsu CC, da Rocha AJ, do Amaral LLF, Godoy LFS, Watkins TW, Marussi VH, Warmuth-Metz M, Alves HC, Goncalves FG, Kleinschmidt-DeMasters BK, Osborn AG. Multinodular and Vacuolating Neuronal Tumor of the Cerebrum: A New “Leave Me Alone” Lesion with a Characteristic Imaging Pattern. AJNR Am J Neuroradiol. 2017 Jul 13. doi: 10.3174/ajnr.A5281. [Epub ahead of print] PubMed PMID: 28705817.