Brain invasion in meningiomas-clinical considerations and impact of neuropathological evaluation: a systematic review

Abstract

With the release of the 2016 edition of the World Health Organization (WHO) Classification of Central Nervous System Tumors, brain invasion in meningiomas has been added as a stand-alone criterion for atypia and can therefore impact grading and indirectly adjuvant therapy. Regarding this rising clinical importance, we have reviewed the current knowledge about brain invasion with emphasis on its implications on current and future clinical practice. We found various definitions of brain invasion and approaches for evaluation in surgically obtained specimens described over the past decades. This heterogeneity is reflected by weak correlation with prognosis and remains controversial. Similarly, associated clinical factors are largely unknown. Preoperative, imaging-guided detection of brain invasion is unspecific, and intraoperative assessment using standard and new high-magnification microscopic techniques remains imprecise. Despite the increasing knowledge about molecular alterations of the tumor/ brain surface, pharmacotherapeutic options targeting brain invasive meningiomas are lacking. Finally, we summarize the impact of brain invasion on histopathological grading in the WHO classifications of brain tumors since 1979.In conclusion, standardized neurosurgical sampling and neuropathological analyses could improve diagnostic reliability and reproducibility of future studies. Further research is needed to improve pre- and intraoperative visualization of brain invasion and to develop adjuvant, targeted therapies.

Keywords: brain invasion; grading; meningioma; prognosis; resection.

Fig. 1

Flowchart showing the selection process of relevant studies. In addition to 707 PubMed results identified through database searching, 42 records including quotations, 5 editions of the WHO classification of brain tumors, and recent studies known to the authors were screened. In 182 excluded cases, the abstracts did not provide detailed information about methods and results and full texts were lacking (*). Moreover, 24 full texts could not be considered, since they were not written in English (**).

Fig. 2

Examples of different microscopic patterns of brain invasion. Although finger-like invasion is mostly described (A, arrows), several studies also showed meningioma cell clusters/islands in the adjacent CNS parenchyma distant from the main tumor (B, arrow) or single tumor cells diffusely infiltrating the brain (arrows). (A–C) Hematoxylin and eosin staining; *brain tissue; **main meningioma tissue.

Fig. 3

Illustrative cranial MRI of a patient with a brain invasive meningioma. (A) Preoperative, axial post-gadolinium (GD) T1-weighted MRI revealing a large right frontal, contrast-enhancing meningioma. (B) Axial T2-weighted image shows the distinct peritumoral edema. In neuropathological analyses, the tumor showed finger-like invasion into the adjacent brain tissue (C; hematoxylin and eosin staining); *meningioma; **peritumoral brain edema; BT, brain tissue.

Fig. 4

Risk of tumor recurrence comparing brain invasive and non-invasive meningiomas. In most studies, brain invasion was significantly (black graphs) correlated with an increased hazard ratio of tumor recurrence in uni- (dashed lines) or multivariate (solid lines) analyses. However, no statistically significant correlation between tumor recurrence and brain invasion was found in some studies (gray graphs). For this figure, studies without information about hazard ratios and confidence intervals were excluded.