Review Review of controversies in management of non-benign meningioma Iddo Paldor a,⇑ , Mohammed Awad a , Yuval Z. Sufaro a , Andrew H. Kaye a , Yigal Shoshan b a The Department of Neurosurgery, Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3052, Australia b The Department of Neurosurgery, Hadassah Medical Center, Ein-Kerem Campus, Jerusalem 91120, Israel article info Article history: Received 12 February 2016 Accepted 27 March 2016 Available online xxxx Keywords: Anaplastic meningioma Atypical meningioma Drug therapy Extent of resection Radiation therapy abstract Meningiomas are one of the most common brain tumors. World Health Organisation (WHO) Grade II and Grade III meningiomas are grouped together as non-benign meningioma (NBM). There are several contro- versies surrounding NBM management, including the significance of extent of resection and the efficacy of post-operative radiation and drug treatment. We reviewed the literature to develop recommendations for management of NBM. The questions we sought to answer were: Does gross total resection (GTR) improve patient outcome? Is radiation therapy (RT) warranted after complete or after incomplete resec- tion of NBM? What drug therapies have been proven to improve outcome in patients with NBM? We found that GTR improves outcome in WHO Grade II meningioma, and should be attempted whenever considered safe. GTR correlates less closely to outcome in Grade III meningioma compared to subtotal resection (STR). Extreme measures to completely resect Grade III meningioma are not warranted. RT fol- lowing GTR of Grade II meningioma does not improve patient outcome, and may be reserved for recur- rence. RT improves outcome following STR of Grade II meningioma. RT improves outcome after resection of Grade III meningioma. No drug therapy has been shown to improve outcome in NBM. This review elu- cidates recommendations for some of the controversies involving NBM. Ó 2016 Elsevier Ltd. All rights reserved. 1. Introduction Meningiomas are one of the most common brain tumors in adults [1]. According to the World Health Organization (WHO) 2007 classification of central nervous system tumors, there are nine subtypes designated grade I meningioma, three subtypes des- ignated grade II and three subtypes designated Grade III [2]. According to recent surveys, approximately 80% of meningiomas are benign tumors, designated WHO Grade I [3,4]. The rest are non-benign meningiomas (NBM). The term NBM encompasses both WHO Grade II and WHO Grade III meningioma, or malignant meningioma (MM). In order to satisfy the criteria for a Grade II meningioma, the tumor must fulfill one of the following criteria:  It may have a mitotic index of more than three mitoses per 10 high power fields (HPF).  It may be shown to invade brain.  It may have three of five specific atypical features. These fea- tures are spontaneous necrosis, macronucleoli, loss of normal architecture, hypercellularity or small cell changes.  It may have a predominantly chordoid morphology, It may have a predominantly clear cell morphology. In order for the tumor to be Graded WHO Grade III, it must have over 19 mitoses per HPF, or have a predominantly rhabdoid, or papillary, morphology. The 2007 WHO grading of meningiomas is described in Table 1 [2]. Demonstrative histology slides of NBM are shown in Figs. 1–3; Fig. 1 depicts some of the features of an atypical meningioma. Fig. 2 demonstrates a brain invasive WHO grade 2 meningioma. Fig. 3 is of an anaplastic meningioma. Fig. 4, 5 show imaging features of NBM: atypical meningioma in Fig. 4 and anaplastic meningioma in Fig. 5. The incidence of NBM varies between different races, genders and areas [5–7]. The introduction of the new WHO classification in 2000, and the newer classification in 2007, caused a shift in the epidemiology of benign meningioma as well as NBM [8,9]. The incidence of WHO Grade II meningioma increased, and that of WHO III meningioma did not significantly change [10]. Further- more, the new classification scheme correlates better with out- come compared to the previous grading system [8,11]. The management of meningioma involves resective surgery, radiation therapy (RT) and occasionally other salvage treatment options. The management of NBM has been a cause for controversy in the literature. The role of resective surgery, the significance of http://dx.doi.org/10.1016/j.jocn.2016.03.014 0967-5868/Ó 2016 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +61 3 93428219; fax: +61 3 93427273. E-mail address: iddo.paldor@mh.org.au (I. Paldor). Journal of Clinical Neuroscience xxx (2016) xxx–xxx Contents lists available at ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn Please cite this article in press as: Paldor I et al. Review of controversies in management of non-benign meningioma. J Clin Neurosci (2016), http://dx.doi. org/10.1016/j.jocn.2016.03.014