Simple SummaryThe shape of meningiomas has been suggested as a potential indicator of the WHO grade. Medial sphenoid wing meningiomas are surgically challenging skull base tumors regarding the preservation of cranial nerve functioning. The present study investigates the impact of tumor shape on neuropathology, progression-free survival, and cranial nerve functioning. The present investigation shows that irregular shape is significantly associated with new postoperative cranial nerve deficits and a shorter time to tumor progression. From a pathological point of view, irregular shapes may result from areas with increased proliferative activity. A systematic review and pooled data analysis that included the present study revealed that an irregular shape is associated with a higher MIB-1 labeling index. Tumor shape should be considered in the preoperative surgical planning regarding the preservation of cranial nerve functioning. Further research is required to examine the molecular basis of irregular meningioma shape.AbstractMedial sphenoid wing meningiomas (MSWM) are surgically challenging skull base tumors. Irregular tumor shapes are thought to be linked to histopathology. The present study aims to investigate the impact of tumor shape on postoperative functioning, progression-free survival, and neuropathology. This monocentric study included 74 patients who underwent surgery for primary sporadic MSWM (WHO grades 1 and 2) between 2010 and 2021. Furthermore, a systematic review of the literature regarding meningioma shape and the MIB-1 index was performed. Irregular MSWM shapes were identified in 31 patients (41.9%). Multivariable analysis revealed that irregular shape was associated with postoperative cranial nerve deficits (OR: 5.75, 95% CI: 1.15–28.63,p= 0.033). In multivariable Cox regression analysis, irregular MSWM shape was independently associated with tumor progression (HR:8.0, 95% CI: 1.04–62.10,p= 0.046). Multivariable regression analysis showed that irregular shape is independently associated with an increased MIB-1 index (OR: 7.59, 95% CI: 2.04–28.25,p= 0.003). A systematic review of the literature and pooled data analysis, including the present study, showed that irregularly shaped meningiomas had an increase of 1.98 (95% CI: 1.38–2.59,p< 0.001) in the MIB-1 index. Irregular MSWM shape is independently associated with an increased risk of postoperative cranial nerve deficits and a shortened time to tumor progression. Irregular MSWM shapes might be caused by highly proliferative tumors.