Meningioma (ORPHA:2495)
A rare, mostly benign, neoplastic disease characterized by a primary tumor of the meninges, usually located intracranially (~90%) but spinal meningiomas occur as well. Clinical symptoms relate to the location of the tumor and may include seizures, focal neurological deficits (sensory-motor or visual symptoms, cranial nerve dysfunction), vascular complications (occlusion of cerebral blood vessels, deep venous thrombosis, pulmonary embolism), chronically increased intracranial pressure neurocognitive impairment and/or loss of bladder/anus sphincter control.
Epidemiology
In adults, intracranial meningiomas represent approximately 30% of central nervous system tumors. The male to female ratio is 1:3.5.
Clinical description
Whilst meningioma may appear at any age, it is predominantly diagnosed between the third and sixth decade of life. Meningiomas typically appear as oval or hemispheric lesions with broad dural attachment. They most frequently occur supratentorially at the calvaria or skull base meninges, along the falx and in the parafalcine location, but can also be found attached to the tentorium, in the cerebello-pontine angle, within the optic nerve sheath, intraventricularly, or in the spinal canal. Lesions are classified into grade I (benign, most frequent), II (atypical), III (malignant) based on local invasiveness, cellular features and mitotic activity. Osseous destruction is indicative of atypical or malignant meningioma. Hyperostosis of adjacent skull bone is highly suggestive of benign meningioma. There are 15 immunohistological subtypes; features are subtype dependent but typically include whorl formation, nuclear pseudo-inclusions, pseudo-syncytial growth, and strong somatostatin-receptor subtype 2 (SSTR2) and epithelial membrane antigen expression.
Etiology
The tumor most likely originates from arachnoid meningothelial cells. Several frequently mutated genes have been detected in meningiomas and include NF2, AKT1, SMO, PIK3CA, BAP1, TERT (promoter), SUFU, SMARCE1, and TRAF7.
Diagnostic methods
The radiological diagnosis is made using contrast-enhanced MRI. Contrast-enhanced CT may also be used and is valuable for the detection of calcification within the tumor, hyperostosis of adjacent bone, and intraosseous tumor growth, especially in skull-base meningiomas. PET-based imaging using SSTR ligands is a helpful additional diagnostic tool and can be used to discriminate the lesion from healthy tissue or other entities. If imaging strongly suggests meningioma, histological verification is not mandatory; however, exclusion of rare differential diagnoses such as metastasis is recommended. Moreover, current diagnostic methods are not able to predict tumor grade which may have therapeutic implications.
Differential diagnosis
The main differential diagnoses include other intracranial lesions, such as dural metastases, primary glial tumors that extend into the subarachnoid space, hematopoietic neoplasms (such as extra-axial non-Hodgkin lymphoma), pituitary neoplasms (e.g. adenomas or craniopharyngiomas), as well as inflammatory (rheumatoid arthritis, Wegener's granulomatosis, extra-axial neurosarcoidosis) and infectious diseases (tuberculosis, syphilitic gumma).
Genetic counseling
Genetic counseling should be considered for patients with multiple meningioma, particularly in combination with ependymoma or schwannoma (NF2-related), and multiple spinal clear-cell meningioma (SMARCE1-related).
Management and treatment
If treatment is required, surgery is the first option. Adjuvant therapies, mainly radiotherapy, may be required if location of the tumor is challenging, in case of significant residual disease or for grade III lesions. So far, there is no clear postoperative guideline for grade II meningiomas. Current systemic therapies have shown little or no response. Asymptomatic lesions (typically diagnosed incidentally) may be managed with observation and long-term follow-up with MRI until either symptoms develop, sustained growth occurs, or concerns of entrapment on sensitive structures arises.
Prognosis
Tumor grade and extent of resection (based on Simpson grading) are the most important predictors of progression-free survival. For completely resected grade I lesions, the risk of tumor recurrence is low. However, meningiomas may confer an aggressive clinical course with multiple recurrences and, infrequently, metastases to other organs. Of note, long-term sequelae (e.g. impairment of neurocognitive functioning and quality of life) following treatment have been reported.

                            Last update: 
                            October 2020


                            - Expert reviewer(s): 
                            Dr Christine JUNGK  - Dr Felix SAHM