Sphenoid Wing Meningioma

In 1614, Felix Plater first described meningiomas at an autopsy. In 1938, Cushing and Eisenhardt first used the term "meningioma" to describe these lesions and introduced it as a separate category of extraparenchymal tumors.[1, 2] Meningiomas are believed to arise from the meningothelial cell (arachnoid cap cell) and usually are attached to the inner surface of the dura mater.[3] The parasagittal region, cerebral convexities, skull base, and falx are the most common locations for meningiomas, although they may arise at any location where meninges exist.[4] See the image below.

Meningiomas account for approximately 13-20% of all brain tumors[5] and 34-36.4% of all primary brain tumors, making meningiomas the most common primary brain tumors.[6, 7] Meningiomas represent only 4% of all orbital tumors.[8] Of lesions in the supratentorial compartment, sphenoid wing meningiomas represent about 15-20% of all meningiomas. Sphenoid wing meningiomas also are known as “orbitosphenoid meningiomas,” “meningiomas en plaque of the sphenoid wing,” and “sphenoid wing meningiomas with osseous involvement.”[9] Sphenoid wing meningiomas may be associated with hyperostosis of the sphenoid ridge and may be very invasive, spreading to the dura of the frontal, temporal, and orbital regions.[9, 10, 11, 12]

This is a typical appearance of a sphenoorbital meningioma on the MRI. The image depicts a contrasted MRI of the brain which shows an enhancing mass along the sphenoid ridge, orbital apex, and even the temporalis muscle. The orbital involvement of the tumor causes significant proptosis of the affected eye.

Two different growing patterns of sphenoid wing meningioma have been described: meningioma en masse, forming a nodular space-occupying lesion, and meningioma en plaque, which is flat and demonstrates a carpet-like growth pattern.

Meningiomas of the anterior skull base are defined as arising anterior to the chiasmatic sulcus that separates the middle cranial fossa from the anterior cranial fossa.[13] Sphenoid wing meningiomas are the most common of the basal meningiomas. Medially, they may expand into the wall of the cavernous sinus, anteriorly into the orbit, and laterally into the temporal bone. Sphenoid wing meningiomas are categorized as lateral, middle, or medial (clinoidal), depending on the origin of the tumor along the sphenoid ridge.[14] Furthermore, medial (clinoidal) meningiomas are further differentiated into 3 subcategories based on their relation to the anterior clinoidal process.

Type I clinoidal meningiomas originate from the inferomedial surface of the clinoidal process proximal to the distal carotid ring. This type is very difficult to resect because of the absence of the arachnoid plane between the tumor and the internal carotid artery.

Type II clinoidal meningiomas originate from the superolateral surface, leading to widening of the sylvian fissure, and are relatively easy to remove.

Type III clinoidal meningiomas originate at the optic foramen and extend into the optic canal and thus present some difficulty in gross total removal.[15] Other frontal skull base meningiomas can arise from the olfactory groove or planum sphenoidale. Planum sphenoidale meningiomas arise 2 cm posterior to olfactory groove meningiomas, and they may be symmetrical around the midline or may extend to the side. Of these 2 subtypes, about 15-20% grow into the ethmoid sinuses.[16, 17]  

The most widely known risk factor for meningiomas is ionized radiation exposure.[18, 19, 20, 21, 22] For example, children with tinea capitis who are treated with an average single dose or multiple doses of 1.5 Gy have a relative 9.5% risk of developing meningioma.[23] Dental radiography is a common source of radiation in the United States. The risk of meningioma has been found to double after full-mouth series.[24] In addition, radiation-induced tumors may develop after previous radiation treatment of another lesion. In a recent pooled analysis, survivors of childhood cancer who received radiation treatment were 30 times more likely to develop meningioma later in life than those survivors who did not receive radiation treatment.[25] Cahan et al[26] were the first to propose criteria for identifying radiation-induced tumors, and these criteria have been applied to diagnose radiation-induced meningiomas. Radiation-induced tumors were defined as lesions arising after a latency period (4 years in the original article) within a previously irradiated field that have different histology than the radiated tumor.[26] These criteria have been augmented by others over the years with additional features, and the full set of criteria now includes the following[27, 28, 29] :

• The tumor must arise in the irradiated field.
• The histologic features must differ from those of any previous neoplasm in the region.
• The tumor must occur after an interval sufficient to demonstrate that the neoplasm did not exist prior to irradiation (usually years).
• This type of tumor must occur frequently enough after irradiation to suggest a causal relationship.
• This type of tumor must have a significantly higher incidence in irradiated patients than in an adequate control group.
• There must be no family history of a phakomatosis
• The tumor must not be recurrent or metastatic.

The most commonly reported radiation-induced tumor is meningioma.[27, 29] The Childhood Cancer Survivor Study in the United States reported a cumulative incidence of 3.1% and a relative risk of 2.7% for meningioma development at 30 years after the primary tumor diagnosis.[21] Radiation-induced meningiomas develop more frequently over the convexities than the skull base, at a ratio of 1.9:1 for both high-dose and low-dose radiation.[29]

Radiation-induced meningiomas more commonly occur as multiples and in younger age groups than do spontaneous meningiomas.[29] Some authors reported that these tumors exhibit more malignant behavior, as indicated histologically by high cellularity, pleomorphism, multinucleation, and giant cell pseudoinclusions.[30] These findings have not yet been confirmed by others.[29]

There is a wide variation in the literature regarding the latency period for the development of radiation-induced meningioma.[27, 30, 31] It has been suggested that this variation is related to variation in the radiation dose, with a short latency for high doses and long latency for low-dose radiation.[27] The recognized latency period can be as short as 14 months and as long as 63 years, although the average latency period is 30-40 years in most cases.[29, 30, 31]

Aside from radiation, other factors that have been studied as potential causes of meningioma include genetic abnormalities, hormonal factors, and viral infections.

In cytogenetic studies, the most commonly reported genetic abnormality is the loss of NF2 tumor suppressor gene on long arm of chromosome 22 (monosomy 22). This genetic alteration leads to loss of expression of NF2 protein product (neurofibromin) and has been reported in 40-70% of meningiomas.[32, 33, 34]  Seventy-five percent of NF2 patients develop meningioma during their lifetime. Ten percent of these are multiple lesions.[35, 36]  Other commonly reported genetic alterations in meningioma include deletion of short arm of chromosome 1; loss of chromosomes 6, 10, 14, 18, and 19; and gain of 1q, 9q, 12q, 15q, 17q, and 20q.[32]  

Hormonal factors (eg, estrogen, progesterone, androgen, steroid) have been studied extensively as risk factors for meningiomas because of the striking predominance of meningiomas in women; the female-to-male ratio is 2:1 for intracranial tumors and 10:1 for spinal meningiomas.[32] Other evidence to substantiate the implication of sex-specific hormones comes from data showing increased growth of meningiomas during pregnancy and hormonal replacement therapy.[37] Estrogen receptor (ER) has been found in 30% of meningiomas in 1 series, predominantly the ER-beta receptor isoform.[38]

The progesterone receptor is the best candidate among the sex-specific factors as a cause for meningiomas. Progesterone receptors have been shown to be expressed in 81% of women and 40% of men with meningiomas.[39, 40] Other studies indicate that progesterone binds to meningiomas in 50-100% of tested specimens.[39] Although progesterone receptor expression has been observed more frequently in benign meningioma (96%) than the malignant type (40%), no relation has been found between progesterone receptor status and age, sex, location of tumor, or menopausal state.[5, 40] These findings have prompted researchers to develop antiprogesterone medications, such as mifepristone (RU-486), which appears to inhibit tumor growth in vitro and in vivo.[41]

Androgen receptors also have been found in approximately 50% of meningiomas, but their receptor expression is variable, making them less likely candidates in the pathophysiology of meningiomas.[42] Similarly, meningiomas vary in expression of receptors for other hormones (eg, vascular endothelial growth factor receptor [VEGFR], epidermal growth factor [EGF], platelet-derived growth factor [PDGF], fibroblast growth factor, and insulin-like growth factor-1 [IGF-1]), making them less likely candidates for oncogenesis of meningiomas. It has been suggested that the direct stimulatory effect of EGF on PDGF or PDGF itself may be partially responsible for angiogenesis and even oncogenesis in meningiomas. PDGF is a particularly attractive candidate because it has structural homology with the product of c-sis oncogene on chromosome 22.[36]

Some viruses have been found within meningiomas, including polyoma virus, simian vacuolating virus 40 (SV-40), and adenovirus. A suggested role for these viruses or parts of viruses is related to the proteins involved in the induction or maintenance of tumor growth and transformation.[18] However, this association has not been proven.

Among the other potential factors for inducing meningiomas that have not been proven are head trauma and electromagnetic field exposure. Head trauma and skull fractures have been suggested as a risk factor for meningioma development by some authors.[43] However, a large population-based 2014 study from Taiwan found no association between head injury and meningioma development in 2 cohorts of patient with and without head injury.[44]

Similarly, electromagnetic field exposure, especially with the widespread use of cell phones, has generated interest in relation to the pathophysiology of brain tumors. Many studies suggest that little, if any, evidence supports the implications of cell phone use on meningioma development, although there generally is a lack of well-conducted studies to date and a significant amount of debate in this regard.[5]  

According to the most recently published Central Brain Tumor Registry of the United States (CBTRUS) report, meningioma is the most common nonmalignant brain and central nervous system (CNS) tumor, making up 37.6% of reported tumors (7.86 per 100,000 population).[45] The CBTRUS report also indicates that meningioma is the second most frequently reported brain and CNS tumor overall in adolescents and young adults (age 15-39 years), accounting for 15.9% of tumors. It is the most common tumor in patients aged 35-39 years, accounting for 25.1% of tumors, and is least common in patients aged 15-19 years, accounting for 4.9% of tumors. These numbers increase steadily with age.[46]

The annual incidence of meningiomas can be as low as 0.74 per 100,000 individuals younger than 34 years and as high as 18.86 per 100,000 individuals older than 85 years. It is 2.5 times more common in females than in males and 1.1% more common in Blacks than in Whites.[6, 47] In children, meningioma accounts for 4.6% of all primary brain tumors.[32, 48] Incidental meningioma is found in 0.52-0.9% of brain images.[49, 50]  

Frequency

United States

Meningiomas account for approximately 13-20% of all brain tumors.

International

Worldwide, meningiomas account for approximately 13-20% of all brain tumors.

Mortality/Morbidity

In a 2016 study of 1549 operated meningiomas, the overall perioperative complication rate was 17.8-18.8%; of these, the morbidity rate was 1.2-2.2%.[51]

Among patients with skull base meningiomas, a 2016 study reported the overall mortality rate was 5%, with transient cranial nerve deficits occurring in 32% of cases, definite cranial nerve lesions in 18%, and cerebrospinal fluid (CSF) leak in 14%.[52] Another study reported an overall mortality rate of 5.8%, transient cranial nerve deficit rate of 11.7%, definitive morbidity of 5.8%, and second recurrence rate of 5.8%.[53]

Potential complications include bleeding, deep venous thrombosis and embolism, air embolism, venous infract, wound-healing deficits, paresis, sensory deficits, cranial nerve palsy, aphasia, seizures, brain edema, hygroma, CSF fistula hydrocephalus, ischemia, and pituitary insufficiency. These complications vary depending on preoperative morbid conditions, age, and tumor size and location.

Race

Previous studies argued that there is variability in the prevalence of meningiomas among Whites, Africans, African-Americans, and Asians and greater incidence among Blacks than Whites.[7, 54]  A more recent report indicated that benign and malignant meningioma were more commonly found in African Americans compared with Caucasians in the United States.[45]

Sex

The incidence rate of meningioma is higher in females (10.87 per 100,000 population) than in males (4.98 per 100,000 population).[46]

No sexual predilection was found among Africans.[54]

Age

The average age at onset is 63 years. The incidence of meningiomas increases steadily thereafter.[51]

A 1983 study showed that recurrence-free survival rates after complete surgical removal in 114 patients (60% of which were sphenoid wing meningioma) at 5, 10, and 20 years were 80%, 70%, and 50%, respectively.[55] The extent of surgical resection and histological grade are very important prognostic factors.

In 1957, Simpson classified meningiomas based on the extent of resection as follows[56] :

• Grade I - Macroscopically complete removal of the tumor with excision of its dural attachment and of any abnormal bone
• Grade II - Macroscopically complete removal of the tumor and of its visible extensions with endothermy coagulation of its dural attachment
• Grade III - Macroscopically complete removal of the intradural tumor without removal or coagulation of its dural attachment or extradural extensions
• Grade IV - Partial removal of the tumor
• Grade V - Simple decompression with or without biopsy

The 10-year risk for recurrence for grades I through IV were 9%, 19%, 29%, and 44%, respectively.[56]

The relevance of this system in the current era of microsurgical procedures advancement has been questioned by some authors53; however, a 2016 study of 458 patients with World Health Organization (WHO) grade I meningioma indicated that the extent of surgical resection based on Simpson grading is an important predictor of tumor recurrence.[57] Moreover, Borovich et al[58]  introduced the idea of Simpson grade 0, which includes Simpson grade I resection plus an additional several cm of dural resection as a margin. This stemmed from the discovery that clusters of microscopic or even macroscopic tumor cells were observed in surrounding dura, as far as 4 cm from the margin of the tumor.[59]  To corroborate this, Kinjo et al[60]  observed no meningioma recurrence after 5 years for all of their Simpson grade 0 resections when they removed a 2-cm margin of dura. The overall tumor recurrence rates for Simpson resection grades I, II, III, and IV were 5%, 22%, 31%, and 35%, respectively.[57] When WHO histological grading of meningiomas is considered regarding survival, a 2016 study of 905 patients demonstrated that the 5-year overall survival rate was 85-90% for WHO grade I, 75-78% for WHO grade II, and 30-35% for WHO grade III tumors.[51] Recurrence rates of tumors graded according to the 2007 WHO classification of tumors of the central nervous system were 7-25% for WHO grade I, 29-52% for WHO grade II, and 50-94% for WHO grade III.[61]

Studies on the prognosis of sphenoid wing meningioma and spheno-orbital meningioma have generally showed good outcomes.

The results of a retrospective study of 25 patients who underwent surgical resection and orbital reconstruction with an average of 5 years of follow-up showed that a gross-total resection was achieved in 70% of patients, with surgery limited by the superior orbital fissure and the cavernous sinus. Proptosis improved in 96% of patients, with 87% improvement in visual function. Ocular paresis improved in 68%, although 20% of patients experienced temporary ocular paresis postoperatively. Overall, 95% of patients reported an improved functional orbit. There were no perioperative deaths or morbidity related to the surgical approach or reconstruction. Tumor recurrence occurred in 8% of patients.[62]

In another series of 67 patients with sphenoorbital meningioma who underwent surgical resection with orbital wall reconstruction, a total removal was achieved in 14 cases (82.3%), with only 1 recurrence (7.1%) over a mean follow-up period of 36 months. Proptosis was corrected in all cases, and visual acuity improved in 7 (70%) of 10 cases. Radical resection was followed by cranio-orbital reconstruction to prevent enophthalmos and to obtain good cosmetic results. No deaths or serious complications occurred in association with surgery. Revision of the orbital reconstruction was required because of postoperative enophthalmos (2 cases) or restricted postoperative ocular movement (1 case).[63]

A 2016 series of 33 patients with spheno-orbital meningioma who underwent resection without formal orbital wall reconstruction (mean follow-up, 4.5 years) showed improved proptosis in all patients, and only 2 patients had tumor recurrence at the orbit that required surgery.[9]  An extension of this series evaluated visual outcomes of 33 subsequent patients with spheno-orbital meningioma. This study demonstrated that 86% of the patients had stable or improved vision, 100% had improved proptosis; and 0% developed pulsatile enophthalmos, even after no rigid orbital reconstruction.[64]

The authors of these studies emphasize aggressive removal of the hyperostotic bone to achieve satisfactory results and to decrease the risk for recurrence. For example, a study of 47 patients with spheno-orbital meningioma who underwent surgery via the frontotemporal approach without orbital wall reconstruction showed that complete resection was achieved in 51% of cases. At a mean follow-up of 52 months, proptosis normalized in 90.9% and improved in the remaining patients, visual acuity normalized in 20.8% and improved in 45.8% patients, and cranial nerve deficit subsided in all but 2 cases. The recurrence rate was 29.7%.[65] According to the authors, the high recurrence rate in this study was likely related to the incomplete removal of the invaded bone to minimize perioperative morbidity. 

Some useful information is provided by the American Brain Tumor Association.

The classic triad of sphenoid (spheno-orbital) wing meningioma is proptosis,(86%) which may be painless; visual impairment (78%); and ocular paresis (20%).[62, 63] Headache also is a common manifestation[63]  and sometimes ptosis. Patients may present with retro-orbital pain or a sensation of pressure. Proptosis is often the first presentation. It is gradual and easily detectable on a review of previous photographs.

Slowly growing scalp masses have been reported.

Transient ischemic attack–like presentation has been reported.[66]

Variants of the clinical syndrome include the following:

• Eye swelling and hearing loss secondary to compression of the eustachian tube ^[67]
• Blindness and optic atrophy in 1 eye, sometimes with papilledema of the other eye (Foster Kennedy syndrome) ^[68]
• Mental changes
• Increased intracranial pressure and intracranial hemorrhage secondary to bony hyperostosis and stretching of underlying venous structures ^[69]

Sphenoid wing meningiomas can be associated with various cranial nerve dysfunction due to superior orbital fissure involvement and foraminal encroachment of cranial nerves located at the skull base.[70] Swelling of the sphenoid bone and exophthalmos are common examination findings.

Spheno-orbital meningiomas that present with proptosis will have a “woody proptosis.” On retropulsion, the globe and orbital tissues will be firm, compared with the softer proptosis seen with orbital tumors like hemangiomas, dermoids, etc. The slow, progressive orbital pressure also often presents with chemosis and conjunctivochalasis, often with associated lagophthalmos and symptoms of corneal exposure.

An increased incidence of meningiomas has been reported in patients with neurofibromatosis type II and in those with abnormalities of chromosome 22, as follows[32, 35, 36] :

• Deletions on chromosome 22 have been demonstrated in 40% of meningiomas. These deletions seem to be associated mainly with the terminal portions of the long arm of chromosome 22.
• Loss of heterozygosity has been reported in at least 1 locus of chromosome 22 in 60-65% of patients with benign meningiomas. The incidence of an abnormality on chromosome 22 increases in atypical and malignant meningiomas. The possible culprit may be a 664-kb gene on this locus coding for an N-acetylglucosaminyltransferase gene. This gene codes for an amino acid glycosyl transferase enzyme, and absence of this enzyme may lead to abnormal glycosylation of proteins and lipids, resulting in tumor formation.
• Other chromosomal abnormalities have been reported in association with chromosome arms 1p, 7p, 14p, 18q, and 6q and chromosome 10.

Various viruses that have been described in association with primary brain tumors, including SV-40, adenovirus, and papovavirus, have been identified in meningiomas.[18]

Hormonal factors, namely estrogen and progesterone, have been implicated in the pathophysiology of meningiomas. Both estrogen and progesterone receptors have been reported in a large majority of meningiomas, with a greater percentage of meningiomas expressing active progesterone receptors than estrogen receptors.[32, 38, 40]

The beta-receptor beta subtype of PDGF was identified in 100% of meningiomas in 1 study.[36]

In vitro, PDGF appears to enhance cell proliferation of meningioma cells. The medium in which meningioma cells are grown in vitro has been shown to contain PDGF, and supplementary addition of PDGF to cultured meningioma cells appears to stimulate their growth.[36]

Vascular endothelial growth factor also seems to play a role in the biology of meningiomas. The degree of peritumoral edema on T2-weighted MRI has been correlated directly with the degree of staining intensity of the meningioma in vitro.[36]

Epidermal growth factor has been described in a large percentage of meningiomas in tissue culture.[71]

Head trauma was suggested as a possible etiology for meningiomas, but recent prospective studies have shown no increased incidence of meningiomas in patients with head trauma. 

The complexity of skull base approaches, proximity of the cranial nerves, poor accessibility, dural attachments, and involvement of the extracranial compartment, especially the nasal sinuses for skull base meningiomas, makes the complication frequency for these lesions higher than with other locations.[72]

Depending on the exact location of the meningioma, a different subset of neural structures may become involved.

For medial sphenoid wing meningiomas, visual loss and abnormalities of cranial nerves III, IV, VI, V1, and V2 may occur because the meningioma may have some degree of encasement of these structures as they pass through the cavernous sinus.

Seizures, paresis, and sensory loss may occur, depending on potential damage to adjacent brain parenchyma among patients with lateral sphenoid wing meningiomas. 

Meningioma can present a different set of clinical symptoms based on its size, location, and its intrinsic aggressiveness. Besides some nonspecific symptoms such as headache, a convexity meningioma in close proximity to motor/sensory areas of the brain may manifest motor/sensory disturbances or seizures. On the other hand, olfactory groove meningioma may present with loss of smell, personality changes, or visual deficit. Spheno-orbital meningioma may present with unilateral proptosis and/or visual deficit. Therefore, it is important to realize the normal surrounding structures that may be affected by the tumor. Appropriate work-up should focus on testing the structural and functional integrity of those normal intracranial, or sometimes extracranial, structures.

Clinical examination should include a detailed neuro-ophthalmic assessment, together with a dilated fundal examination of the optic nerve head and retina. Orbito-sphenoid meningiomas recurrences often are associated with involvement of the optic nerve.[78]

Laboratory studies may be indicated to rule out other differential diagnoses (eg, metabolic panel including calcium, bone-specific alkaline phosphatase, urine hydroxyproline).

Plain radiography of the skull

Abnormalities have been found in 30-60% of patients with sphenoid wing meningioma. Hyperostosis, thinning of bone, and irregular foci of calcification can be seen.[79]

CT scanning of the bone window

CT scanning of the bone window typically shows thick, hyperdense, intradiploic lesion expanding the calvaria and destroying the cortical layers of the skull. The bony expansion and ground-glass appearance of sphenoid wing meningioma complicates differentiation from fibrous dysplasia71; however, the inner table of the skull looks smooth in fibrous dysplasia, whereas sphenoid wing meningiomas often demonstrate irregularity of the inner table associated with a dural reaction. Clinically, fibrous dysplasia usually presents in younger individuals and stops growing after puberty, in contrast to meningioma, which typically develops in older individuals. Among sphenoid wing meningiomas, 59% are osteoblastic, 10-35% are osteolytic, and 6% are a mixed picture of both osteolytic and hyperostosis.[75, 80]

CT scan brain bone window showing intraosseous meningioma involving left sphenoid wing, lateral orbital, superior orbital fissure, and the anterior part of the middle fossa floor.

MRI

MRI allows better delineation of the soft tissue component of the tumor and dural involvement, as well as delineation of intraorbital extension or growth. There might be no dural tail in sphenoid wing meningioma, especially the en plaque variant.[81]

MRI brain T2W (left) and T1W Fat-Sat (right) sequences showing involvement of the left sphenoid wing associated with dural thickening and the periorbita. Notice proptosis of the left globe secondary to left orbital wall thickening.

Angiography

Angiography is not necessary in sphenoid wing meningioma. When performed, it usually shows tumor blush of the en masse component and tortuous external carotid artery feeders.[81]

C-PiB and F-FDG positron-emission tomography scanning

Two patients who had undergone contrast-enhanced MRI scans that revealed extra-axial tumors next to the sphenoid wing were examined using C-PiB and F-FDG positron-emission tomography (PET) scanning. The researchers concluded that C-PiB could be used as a meningioma marker.[82]  

Other tests may include the following:

• Preoperative evaluation of patients with anterior basal meningiomas, including formal visual field and acuity testing.
• Metastatic work-up, such as CT scanning of the chest, abdomen, and pelvis; skeletal survey; radionucleotide scanning; and PET scanning
• Intraoperative radiodetection of somatostatin receptors is feasible, especially in bone-invasive meningiomas using gamma probe. ^[83]

According to the WHO, in 2007 and 2016, 3 types of meningiomas exist based on malignant behavior, as follows[61, 84, 85] :

• Grade I (benign), with a recurrence rate of 7-25%, does not meet atypical or malignant meningioma criteria. Despite involvement of the adjacent bony structures, grade I meningiomas do not invade the brain parenchyma. Grade I meningiomas include 9 histologic subtypes: meningothelial, fibrous, transitional, psammomatous, angiomatous, macrocystic, secretory, lymphoplasmacyte-rich, and metaplastic.
• Grade II (atypical), with a recurrence rate of 29-52%, includes atypical, clear cell, and chordoid histologic subtype or increased mitotic activity (4-19 mitoses per 10 high-powered fields) or brain invasion, or 3 or more of the following features: increased cellularity, small cells with a high nuclear:cytoplasmic ratio, prominent nucleoli, uninterrupted patternless or sheetlike growth, or foci of spontaneous or geographic necrosis.
• Grade III (malignant), with a recurrence rate of 50-94%, includes anaplastic, papillary, and rhabdoid histologic subtypes. Anaplastic meningiomas have 20 or more mitoses per 10 high-powered fields or malignant characteristics resembling carcinoma, sarcoma, or melanoma.

Malignant transformation is rare. Originally, malignancy was seen in anaplastic tumors, but they may arise from any of the meningioma variants or atypical meningiomas. Papillary histopathology is associated with local aggressiveness and an increased incidence of late distant metastasis. The papillary type is considered malignant by definition and is encountered more frequently in children.[86]

Earlier classification schemes used the term angioblastic meningioma for what is now considered to be a hemangiopericytoma. This neoplasm is distinctly separate from a meningioma, and it shows extremely high propensity for recurrence and metastasis. Hemangiopericytoma is a sarcoma in the new WHO classification.[85, 87]

Meningiomas generally are slow growing. Growth patterns of meningioma in a 2011 series of incidentally diagnosed meningioma included no growth, linear growth, or exponential growth. The presence of calcification, T2-weighted MRI tumor hypointensity, and older age at onset were associated with slower growth rate.[88]

In a large series of 603 asymptomatic meningiomas, 63% did not increase in size, and only 6% of patients eventually experienced symptoms over a mean follow-up of 3.9 years.[89]

Another series of 273 incidental meningiomas in 244 patients with a mean follow-up period of 3.8 years observed a 2 mm or greater increase in maximum diameter in 120 tumors (44% of the cases).[90]

True metastases are extremely uncommon, and dissemination usually is believed to occur hematogenously, with the lungs as the most common site.[91]

Bony invasion is not evidence of malignancy in meningiomas, and invasion of mesenchymal components (eg, bone, muscle, dura) can occur with benign meningiomas.[92]  

The operative approach for meningioma depends largely on the tumor location, size, shape, and involvement of the critical neurovascular structures. In general, the operative procedure to remove meningioma requires opening of the skull (craniotomy) in the most accessible location where it can facilitate removal of the meningioma without aggressive retraction of the brain. For instance, convexity meningioma typically will require a craniotomy directly over the tumor. The margin of the craniotomy should be larger than the tumor in order to completely resect the tumor. Tumors involving the anterior/middle skull base (meningioma of tuberculum sella, planum sphenoidale, sphenoid wing, clinoidal) typically can be approached via a standard frontotemporal approach. With the advancement of endoscopic techniques and technologies, expanded endoscopic endonasal approaches are being popularized for removal of these tumors. However, tumors that are saddling the petrous and the clival bone (also known as petroclival meningioma) may require additional skull base drilling (such as partial or complete petrosectomy) in order to gain access.[93]  Olfactory groove meningioma may require bifrontal craniotomy and subfrontal approach for resection.

Staging typically is not done for meningioma, which is confined to areas within the meninges and typically does not metastasize to distant organs.

Management of the meningioma largely is divided into observation, surgery, or radiation, alone or in combination. Small meningiomas in patients who otherwise are asymptomatic may be monitored with serial imaging to document growth. Tumors that demonstrate growth or cause symptoms may be considered for surgical removal and histopathologic evaluation. Adjuvant radiation may be considered for high-grade or recurrent tumors. Primary radiation may be considered for patients when surgical removal is not deemed possible.[94]

Total microsurgical resection of sphenoid wing meningioma usually is curative. A recurrence risk approaching 30% has been reported when incomplete removal is attempted.[65, 95] Depending on the bony involvement and the soft tissue component of the tumor, the principles of resecting a sphenoid wing en plaque meningioma are complete removal of all the involved bone, including the sphenoid wing, orbital roof, and orbital lateral wall; decompression of optic nerve; and decompression of the superior orbital fissure, and maxillary branch of the trigeminal nerve posteriorly to foramen rotundum.

The skin incision is made 0.5-1 cm anterior to the tragus at the level of the zygomatic arch and extended behind the hairline toward the widow peak. It can be curved back across the midline toward the contralateral superior temporal line, if needed. Care must be taken not to injure the temporal branch to the frontalis muscle or the facial nerve that passes anterior to it. The temporalis muscle, along with the superficial and the deep fascial layers, are incised in similar fashion from the skin down to the bone. The musculocutaneous flap is reflected anteriorly using a periosteal elevator. Avoid cauterizing the blood supply and innervation to the temporalis muscle to prevent future muscle atrophy.

After elevation of the myocutaneous flap; note the underlying bone is infiltrated with tumor.

Once the muscle is elevated and reflected anteriorly, lateral sphenoid wing hyperostosis is usually apparent, and any tumor noticed during elevation of the temporal muscle is excised.

Multiple bur holes then are made around the invaded or hyperostotic bone to prevent excessive bleeding and dural tear. The drill is used to connect the bur holes and to remove the invaded bone. 

A frontotemporal craniotomy is performed to elevate the affected bone. Underlying it, dura is seen. The dura is also infiltrated with the tumor.

This process continues until all hyperostotic tissue is removed from the sphenoid wing down to the meningo-orbital band. The meningo-orbital band is then coagulated and cut sharply, followed by dural stripping from the superior orbital fissure and the anterior part of the lateral wall of the cavernous sinus, exposing the middle fossa floor laterally to the foramen spinosum and posteriorly to the foramen rotundum. 

The tumor debulking is performed using the micro-instruments and high-speed diamond drill bit.

Hyperostotic tissue then is removed in a similar manner from the orbital roof and lateral walls of the orbit. The superior orbital fissure is completely decompressed. The optic nerve in the canal is unroofed, and anterior clinoidectomy is performed.

Once the bone removal is complete, attention is focused on resecting the intradural portion of the tumor, and the dura is resected beyond the enhanced dural tail.

The dura is opened. Any intradural portion of the tumor is resected, if any. The involved dura is cut and discarded.

The intraorbital extension with involvement of the periorbita and extraocular muscles should also be removed.

Important neurovascular structures are decompressed including the orbit, orbital apex, superior orbital fissure. The tumor has also infiltrated the periorbita. Some periorbital fat can be seen.

After gross total resection of the tumor (star = orbit, circle = frontal lobe, triangle = temporal lobe).

Abdominal fat or temporalis fascia with or without pericranial flap can be used to repair the frontal, maxillary, and ethmoid sinuses if they have been opened to prevent postoperative development of a CSF leak and rhinorrhea. A duraplasty is performed using a dural substitute.

There is no clear consensus in the literature regarding whether to reconstruct the orbit. Orbital wall reconstruction has been recommended whenever the orbital floor or more than 1 wall has been resected or the periorbita was resected to prevent occurrence of pulsatile enophthalmos postoperatively.[96] However, studies have concluded that this complication is uncommon and that orbital reconstruction is unnecessary except in rare occasions when the orbital rim is resected.[9, 97, 98]

When orbital reconstruction is needed, the area can be reconstructed using mesh, dural substitute, or split bone if only the superior and lateral walls of the orbit have been removed. The cranial flap is placed back if it was not involved by the tumor, or a piece of Medpor can be used to cover the cranial defect, making sure to cover the keyhole area. The temporal muscle is reattached, and the skin is closed in 2 layers. 

After closing the dura with a synthetic dural substitute, cranium is replaced and secured with titanium hardware. Medpore cranioplasty (white plates) are placed for further reconstruction and to restore cosmesis.

Anecdotal reports have described using antihormonal agents in the treatment of meningiomas. Medical treatment is reserved for atypical and malignant meningiomas as an adjunct to surgery.

The complexity of skull base approaches; proximity of the cranial nerves; poor accessibility; dural attachments; and involvement of extracranial compartment, especially the nasal sinuses for skull base meningiomas, makes the complication frequency for these lesions higher compared with other locations.[72]

Depending on the exact location of the meningioma, a different subset of neural structures may become involved.

• For medial sphenoid wing meningiomas, visual loss and abnormalities of cranial nerves III, IV, VI, V1, and V2 may occur because the meningioma may have some degree of encasement of these structures as they involve the cavernous sinus.
• Seizures, paresis, and sensory loss may result depending on potential damage to adjacent brain parenchyma for patients with lateral sphenoid wing meningiomas.

Patients are typically monitored for a significant length of time. Patients with asymptomatic meningioma may be monitored with serial imaging, sometimes indefinitely. Postsurgical patients may be seen at 1-, 3-, and 6-month and 1- and 2-year intervals to observe growth (if subtotal resection) or recurrence. Immediate postoperative care usually involves pain control, incision care, and setting up oncologic appointment based on histopathology.

Tamoxifen, an antiestrogen hormone, inhibits the effects of estrogen by competitively binding to estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. Its use has been reported in small series of patients with refractory or unresectable meningiomas; in 1 study, 19 patients were included in a phase II trial. Results showed partial MRI response in 3 patients, 6 patients remained stable for a median duration of 31 months, and 10 patients had progression.[99]

Mifepristone, RU-486 (Mifeprex), is an antiprogesterone agent. A 2015 systematic review of all studies reporting on this medication provided no evidence for benefit beyond preclinical uses.[100]

Hydroxyurea is a chemotherapeutic agent that selectively inhibits ribonucleoside diphosphate reductase and induces apoptosis. Small case series of patients with recurrent grade II and III meningiomas have been published. Some of the these studies suggest clinical stabilization of the disease with radiologic response except in 1 patient.[101]

Sunitinib is a tyrosine kinase inhibitor that targets VEGFR and PDGF receptor. A prospective, multicenter, single-arm phase II trial of 36 patients with recurrent WHO II and III meningioma found 42% progression-free survival at 6 months, with 5.2 months median progression-free survival and 24.6 months median overall survival. This study demonstrated that expression of VEGFR2 predicted progression-free survival of a median of 1.4 months in VEGFR2-negative patients versus 6.4 months in VEGFR2-positive patients, suggesting that VEGFR2 might be an important prognosticator in WHO II/III meningioma.[102]

Other systemic therapies have been evaluated for recurrent meningioma, including cytotoxic chemotherapies (temozolomide, irinotecan, and combination therapy with cyclophosphamide, doxorubicin, and vincristine), biologics (interferon alfa-2b), and targeted therapies (erlotinib, gefitinib, somatostatin analogs, sunitinib, valatinib, imatinib, bevacizumab).

Class Summary

Inhibit effects of estrogen by competitively binding to estrogen receptor.

Tamoxifen (Soltamox)

Competitively binds to estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects.

Class Summary

RU-486 has been used experimentally in the treatment of this medical condition.

Mifepristone, RU-486 (Korlym, Mifeprex)

Experimental antiprogesterone agent. Used in patients with recurrent benign meningiomas; in one study of 14 patients, tumor regression was reported in 5 of 14 patients.

Class Summary

Agents in this class inhibit cell growth and proliferation and exhibit antiangiogenic properties.

Sunitinib (Sutent)

This agent shows antitumor and antiangiogenic effects. May inhibit multiple-receptor tyrosine kinases, including platelet-derived growth factors, vascular endothelial growth factors, FMS-like tyrosine kinase-3, colony-stimulating factor type 1, and glial cell-line–derived neurotrophic factor receptor. Studies have shown that VEGFR2-positive patients may achieve progression-free survival of up to 6.4 months.