Diagnostic challenges in meningioma

Abstract

Advances in molecular profiling and the application of advanced imaging techniques are currently refreshing diagnostic considerations in meningioma patients. Not only technical refinements but also sophisticated histopathological and molecular studies have the potential to overcome some of the challenges during meningioma management. Exact tumor delineation, assessment of tumor growth, and pathophysiological parameters were recently addressed by "advanced" MRI and PET. In the field of neuropathology, high-throughput sequencing and DNA methylation analysis of meningioma tissue has greatly advanced the knowledge of molecular aberrations in meningioma patients. These techniques allow for more reliable prediction of the biological behavior and clinical course of meningiomas and subsequently have the potential to guide individualized meningioma therapy. However, higher costs and longer duration of full molecular work-up compared with histological assessment may delay the implementation into clinical routine.This review highlights the diagnostic challenges of meningiomas from both the neuroimaging as well as the neuropathological side and presents the latest scientific achievements and studies potentially helping in overcoming these challenges. It complements the recently proposed European Association of Neuro-Oncology guidelines on treatment and diagnosis of meningiomas by integrating data on nonstandard imaging and molecular assessments most likely impacting the future.

Keywords: MRI; PET; diagnosis; meningioma; molecular markers; neuropathology.

Fig. 1

Standard plus advanced MRI in a large bifrontal meningioma. MR images of a 67-year-old man with a 4-month history of progressive frontal headaches associated with decreased motivation and personality changes. (A) T1-weighted contrast-enhanced MR image shows a large meningioma bifrontally with intense, relatively inhomogeneous enhancement. (B) Axial T2-weighted sequence shows high signal intensity of the tumor with very little peritumoral edema. (C) MR spectroscopy shows a prominent resonance from choline (black arrow) and creatine (blue arrow) and an inverted doublet peak at 1.45 ppm, corresponding to alanin as a typical marker for meningiomas (red arrow). (D) In MR perfusion there is increased blood volume at the periphery of the lesion due to pial blood supply and heterogeneous blood volume in the tumor center.

Fig. 2

Molecular versus histological diagnosis in meningioma. (A) A meningioma with widely inconspicuous histology and low mitotic activity may harbor (B) a small area of elevated proliferation. If this area is included in the 10 HPF for assessment of mitotic activity, it might surpass the threshold for WHO grade II. However, if this area is regarded as nonrepresentative and excluded from assessment of mitotic activity, or not even present in the section due to sampling bias, the identical tumor might be assigned WHO grade I. (C) Detection of an AKT1 mutation associated with WHO grade I and slow or no progression, or (D) of a TERT promoter mutation, indicating a higher risk of recurrence, gives additional objective information on the tumor biology. Scale bar represents 100 µm.

Fig. 3

⁶⁸Ga-DOTATATE PET for the differentiation of meningioma from tumor-free tissue and postoperative changes. (A) Preoperative imaging. MR and PET images of a 55-year-old male patient who presented with therapy-resistant left frontal headache for the past 6 months. T1-weighted MR images show subtle contrast enhancement at the skull base without exact delineation of tumor borders. The fluid attenuated inversion recovery sequence shows diffuse signal changes. In contrast, ⁶⁸Ga-DOTATATE PET (DOTA-(Tyr3)-octreotide) is able to differentiate between meningioma and tumor-free tissue with an excellent tumor-to-background contrast. Fusion images were used for surgical planning. (B) Imaging at recurrence. Histological grading revealed a WHO grade II meningioma. After subtotal surgical resection (Simpson grade IV), the patient underwent radiation therapy. Follow-up imaging after 2 years revealed further tumor growth/recurrence. The T1-weighted image shows diffuse contrast enhancement at the skull base, difficult to be differentiated from postoperative changes. ⁶⁸Ga-DOTATATE PET in contrast is consistent with meningioma tissue in this region with additional retrobulbar tumor growth.