Molecular and histopathological landscape of 131 meningiomas: a retrospective institutional study with insights from cIMPACT-NOW

Rola H. Ali^1*Abdulaziz Hassan²Hussain H. Jarkhi³Abdullah Alshawish⁴Mohamad Almanabri⁴Obada T Alhalabi⁵Ahmad R Alsaber⁶Nawal Y. Ali⁷Ehab Abdelnabi⁷Eiman M A Mohammed⁸Hiba Jama⁸Ammar Almarzooq⁸Zainab Alqallaf⁸Amir A. Ahmed⁸Shakir Bahzad⁸Stefan Hamelmann⁹Felix Sahm⁹Maryam Almurshed³

• ¹Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, Safat, 13110, Kuwait
• ²Department of Diagnostic Radiology, Jaber Alahmad Hospital, South Surra, Kuwait
• ³Department of Histopathology, Al Sabah Hospital, Shuwaikh, Kuwait
• ⁴Department of Neurosurgery, Jaber Alahmad Hospital, South Surra, Kuwait
• ⁵Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany
• ⁶Department of Management, College of Business and Economics, American University of Kuwait, Salmiya, Kuwait
• ⁷Department of Radiology, Ibn Sina Hospital, Shuwaikh, Kuwait
• ⁸Molecular Genetics Laboratory, Kuwait Cancer Control Center, Shuwaikh, Kuwait
• ⁹Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany

Background: Prognostication in meningiomas has traditionally relied on histopathological grading, which has inherent limitations, including interobserver variability, intratumoral heterogeneity, and inconsistent correlation with clinical behavior. While molecular profiling enhances diagnostic precision and risk stratification, it is not yet routinely adopted in clinical practice. To date, no molecular data on meningiomas have been published from our country. This study aims to address this gap by characterizing the molecular landscape of meningiomas at our institution, incorporating insights from recent cIMPACT-NOW updates.We retrospectively analyzed consecutive 131 meningiomas that underwent molecular sequencing at our institution between 2021 and 2023. Tumors were classified according to the latest WHO criteria. Next-generation sequencing (NGS) was performed using the Oncomine Comprehensive Assay, a targeted panel for solid tumors. Molecular findings were correlated with clinicopathological parameters.The cohort included 84 females and 47 males (median age: 51 years; range: 2-79). Tumor locations included the cerebral convexity (45.8%), skull base (38.2%), posterior fossa (3.1%), and spine (5.3%), with 7.6% being multifocal. CNS WHO grade 2 tumors were most common (58%), followed by grade 1 (35%) and grade 3 (7%). NF2 alterations (35%) were the most frequent, occurring across all grades but more prevalent in grades 2 and 3. Genotype (p = 0.004) and WHO grade (p = 0.002) were significantly associated with tumor location: NF2 alterations predominated in convexity and spine, while TRAKLS mutations (TRAF7, AKT1, KLF4, SMO) were enriched in lower-grade skull base tumors. High-risk homozygous CDKN2A/B deletions were identified in one grade 3 tumor, with hemizygous deletions, unexpectedly, in three grade 2 tumors.This study provides regional insight into the molecular landscape of meningiomas in our population. While routine molecular profiling adds value to classification and prognostication, broader implementation may be limited by cost and panel coverage constraints.