Wikipedia

Meningioma

Meningioma,also known asmeningeal tumor,is typically a slow-growingtumorthat forms from themeninges,the membranous layers surrounding thebrain and spinal cord.[1]Symptoms depend on the location and occur as a result of the tumor pressing on nearby tissue.[3][6]Many cases never producesymptoms.[2]Occasionallyseizures,dementia,trouble talking, vision problems, one sided weakness, orloss of bladder controlmay occur.[2]

Meningioma
Other namesMeningeal tumor[1]
An MRI of the brain, demonstrating the appearance of a meningioma
SpecialtyNeurosurgery,Neuro-oncology
SymptomsNone,seizures,dementia,trouble talking, vision problems, one sided weakness[2]
Usual onsetAdults[1]
TypesWHO Grade 1, 2, or 3[1]
Risk factorsIonizing radiation,family history[3]
Diagnostic methodMedical imaging[2]
Differential diagnosisHaemangiopericytoma,lymphoma,schwannoma,solitary fibrous tumour,metastasis[4]
TreatmentObservation, surgery,radiation therapy[2]
MedicationAnticonvulsants,corticosteroids[2]
Prognosis95% ten year survival with complete removal[5]
Frequencyc. 1 per 1,000 (US)[3]

Risk factors include exposure toionizing radiationsuch as duringradiation therapy,a family history of the condition, andneurofibromatosis type 2.[2][3]They appear to be able to form from a number of different types ofcellsincludingarachnoidcells.[1][2]Diagnosis is typically bymedical imaging.[2]

If there are no symptoms, periodic observation may be all that is required.[2]Most cases that result in symptoms can be cured by surgery.[1]Following complete removal fewer than 20%recur.[2]If surgery is not possible or all the tumor cannot be removed,radiosurgerymay be helpful.[2]Chemotherapyhas not been found to be useful.[2]A small percentage grow rapidly and are associated with worse outcomes.[1]

About one per thousand people in the United States are currently affected.[3]Onset is usually in adults.[1]In this group they represent about 30% ofbrain tumors.[4]Women are affected about twice as often as men.[3]Meningiomas were reported as early as 1614 byFelix Plater.[7]

Signs and symptoms

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Meningioma seen at autopsy, as a tumor of thedura materextending into the cranial cavity, and can be detached from the bone along with the rest of the dura mater

Small tumors (e.g., < 2.0 cm) usually are incidental findings atautopsywithout having caused symptoms. Larger tumors may cause symptoms, depending on the size and location.[citation needed]

  • Focal seizuresmay be caused by meningiomas that overlie thecerebrum.
  • Progressive spastic weakness in legs and incontinence may be caused by tumors that overlie the parasagittal frontoparietal region.[citation needed]
  • Tumors of theSylvian aqueductmay cause myriad motor, sensory, aphasic, and seizure symptoms, depending on the location.
  • Increased intracranial pressureeventually occurs, but is less frequent than ingliomas.
  • Diplopia(Double vision) or uneven pupil size may be symptoms if related pressure causes a third and/or sixth nerve palsy.

Causes

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The causes of meningiomas are not well understood.[8]Most cases are sporadic, appearing randomly, while some arefamilial.Persons who have undergoneradiation,especially to thescalp,are more at risk for developing meningiomas, as are those who have had a brain injury.[9]Atomic bomb survivors fromHiroshimahad a higher than typical frequency of developing meningiomas, with the incidence increasing the closer that they were to the site of the explosion.Dental X-raysare correlated with an increased risk of meningioma, in particular for people who had frequent dental X-rays in the past, when the X-ray dose of a dental X-ray was higher than in the present.[10]

Having excess body fat increases the risk.[11]In 2020, theEuropean Medicine Agencyissued a warning that high doses ofcyproterone acetatemay contribute to risk of meningioma, and to use the minimum dosage or alternative treatment for most indications, with the exception of prostate carcinoma.[12]

A 2012 review found that mobile telephone use was unrelated to meningioma.[13]

People withneurofibromatosistype 2 (NF-2) have a 50% chance of developing one or more meningiomas.[14]

92% of meningiomas are benign. 8% are either atypical or malignant.[7]

Genetics

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The most frequent genetic mutations (~50%) involved in meningiomas are inactivation mutations in theneurofibromatosis 2gene(merlin) onchromosome 22q.[14]

TRAF7mutations are present in about one-fourth of meningiomas. Mutations in theTRAF7,KLF4,AKT1,andSMOgenes are commonly expressed in benign skull-base meningiomas. Mutations in NF2 are commonly expressed in meningiomas located in the cerebral and cerebellar hemispheres.[15]

Pathophysiology

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Histopathology of a typical WHO grade 1 meningioma,H&E stain.It is of the meningothelial histologic type, which is the most common meningioma type. It shows its typical findings:
- A woven architectural pattern
-Psammoma bodies(spheroid calcifications)
- Syncytial cells (having indistinct cell membranes) with eosinophilic (pink) cytoplasms
- Round uniform nuclei
-Whorls(concentric cell arrangements)[16]
Micrographof a meningioma showing the characteristic whorling,HPS stain
Micrographof a meningioma with brain invasion (WHO Grade II). The tumour (bottom/right of image) has the typical "pushing border" invasion into the cerebral cortex (top/left of image),HPS stain.

Meningiomas arise fromarachnoidalcap cells,[17]most of which are near the vicinity of thevenous sinuses,and this is the site of greatest prevalence for meningioma formation. Some subtypes may arise from the pial cap cells that migrate during the development together with blood vessels into the brainparenchyma.[18]They most frequently are attached to the dura over the superior parasagittal surface of frontal andparietal lobes,along thesphenoid ridge,in theolfactorygrooves, the Sylvian region, superiorcerebellumalong thefalx cerebri,cerebellopontine angle,and thespinal cord.The tumor is usuallygray,well-circumscribed, and takes on the form of the space it occupies. They usually are dome-shaped, with the base lying on thedura.[citation needed]

Locations

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Other uncommon locations are thelateral ventricle,foramen magnum,and the orbit/optic nerve sheath.[7]Meningiomas also may occur as aspinal tumor,more often in women than in men. This occurs more often in Western countries than Asian.[citation needed]

Micrograph of apsammoma bodyin the centre of the field in a meningioma of brain.H&Estain.

Histologically, meningioma cells are relatively uniform, with a tendency to encircle one another, forming whorls andpsammoma bodies(laminated calcific concretions).[19]As such, they also have a tendency to calcify and are highly vascularized.[citation needed]

Meningiomas often are considered benign tumors that can be removed bysurgery,but most recurrent meningiomas correspond to histologic benign tumors. The metabolicphenotypeof these benign recurrent meningiomas indicated an aggressivemetabolismresembling that observed for atypical meningioma.[20]

Diagnosis

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A meningioma that previously had been operated on, with surrounding edema
MRI image of a meningioma with contrast
Low-grade and high-grade meningioma. H&E stain.[21]
Histologic variants of meningioma, H&E stain[22]

Meningiomas are visualized readily with contrastCT,MRIwithgadolinium,[23]and arteriography, all attributed to the fact that meningiomas are extra-axial and vascularized. CSF protein levels are usually found to be elevated whenlumbar punctureis used to obtain spinal fluid.[citation needed]On T1-weighted contrast-enhanced MRI, they may show a typicaldural tail signabsent in some rare forms of meningiomas.[18]

Although the majority of meningiomas are benign, they may have malignant presentations. Classification of meningiomas are based upon the WHO classification system.[24]

  • Benign (Grade I) – (90%) – meningothelial, fibrous, transitional, psammomatous, angioblastic
  • Atypical (Grade II) – (7%) – chordoid, clear cell, atypical (includes brain invasion)
  • Anaplastic/malignant (Grade III) – (2%) – papillary, rhabdoid, anaplastic (most aggressive)

In a 2008 review of the latter two categories, atypical and anaplastic-meningioma cases, the mean overall survival for atypical meningiomas was found to be 11.9 years vs. 3.3 years for anaplastic meningiomas. Mean relapse-free survival for atypical meningiomas was 11.5 years vs. 2.7 years for anaplastic meningiomas.[25]

Malignant anaplastic meningioma is aggressive. Although anaplastic meningioma has higher chances of distant metastasis than the other two types, the overall incidence of meningioma metastasis is only 0.18%; which is considered rare.[26]Even if, by general rule, neoplasms of the nervous system (brain tumors) cannot metastasize into the body because of theblood–brain barrier,anaplastic meningioma can. Although they are inside the cerebral cavity, they are located on the bloodside of the BBB, because meningiomas tend to be connected to blood vessels. Thus, cancerized cells can escape into the bloodstream, which is why meningiomas, when they metastasize, often turn up around the lungs.[citation needed]

Anaplastic meningioma andhemangiopericytomaare difficult to distinguish, even by pathological means, as they look similar, especially, if the first occurrence is a meningeal tumor, and both tumors occur in the same types of tissue.[citation needed]

Although usually benign a "petro-clival" menigioma is typically fatal without treatment due to its location. Until the 1970s no treatment was available for this type of meningioma; however, since that time a range of surgical and radiological treatments have evolved. Nevertheless, the treatment of this type of meningioma remains a challenge with relatively frequent poor outcomes.[27]

Prevention

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The risk of meningioma can be reduced by maintaining a normal body weight,[28]and by avoiding unnecessary dental x-rays.[29]

Treatment

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Observation

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Observation with close imaging follow-up may be used in select cases if a meningioma is small and asymptomatic. In a retrospective study on 43 patients, 63% of patients were found to have no growth on follow-up, and the 37% found to have growth at an average of 4 mm / year.[30]In this study, younger patients were found to have tumors that were more likely to have grown on repeat imaging; thus are poorer candidates for observation. In another study, clinical outcomes were compared for 213 patients undergoing surgery vs. 351 patients under watchful observation.[31]Only 6% of the conservatively treated patients developed symptoms later, while among the surgically treated patients, 5.6% developed persistent morbid condition, and 9.4% developed surgery-related morbid condition.[citation needed]

Observation is not recommended in tumors already causing symptoms. Furthermore, close follow-up with imaging is required with an observation strategy to rule out an enlarging tumor.[32]

Surgery

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Meningiomas usually can be surgicallyresected(removed) and result in a permanent cure if the tumor is superficial on theduralsurface and easily accessible. Transarterialembolizationhas become a standard preoperative procedure in the preoperative management.[33]If invasion of the adjacent bone occurs, total removal is nearly impossible. It is rare for benign meningiomas to becomemalignant.[citation needed]

The probability of a tumor recurring or growing after surgery may be estimated by comparing the tumor's WHO (World Health Organization) grade and by the extent of surgery by the Simpson Criteria.[34]

Simpson Grade Completeness of Resection 10-year Recurrence
Grade I complete removal including resection of underlying bone and associated dura 9%
Grade II complete removal and coagulation of dural attachment 19%
Grade III complete removal without resection of dura or coagulation 29%
Grade IV subtotal resection 40%
Grade V simple decompression ± biopsy n/a

Radiation therapy

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Radiation therapy may include photon-beam or proton-beam treatment, orfractionated external beam radiation.Radiosurgery may be used in lieu of surgery in small tumors located away from critical structures.[35]Fractionated external-beam radiation also can be used as primary treatment for tumors that are surgically unresectable or, for patients who are inoperable for medical reasons.[citation needed]

Radiation therapy often is considered for WHO grade I meningiomas after subtotal (incomplete) tumor resections. The clinical decision to irradiate after a subtotal resection is somewhat controversial, as no class I randomized, controlled trials exist on the subject.[36]Numerous retrospective studies, however, have suggested strongly that the addition of postoperative radiation to incomplete resections improves both progression-free survival (i.e. prevents tumor recurrence) and improves overall survival.[37]

In the case of a grade III meningioma, the current standard of care involves postoperative radiation treatment regardless of the degree of surgical resection.[38]This is due to the proportionally higher rate of local recurrence for these higher-grade tumors. Grade II tumors may behave variably and there is no standard of whether to give radiotherapy following a gross total resection. Subtotally resected grade II tumors should be radiated.[citation needed]

Chemotherapy

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Likely, current chemotherapies are not effective.Antiprogestinagents have been used, but with variable results.[39]A 2007 study of whetherhydroxyureahas the capacity to shrink unresectable or recurrent meningiomas is being further evaluated.[40]

Epidemiology

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Many individuals have meningiomas, but remain asymptomatic, so the meningiomas are discovered during an autopsy. One to two percent of all autopsies reveal meningiomas that were unknown to the individuals during their lifetime, since there were never any symptoms. In the 1970s, tumors causing symptoms were discovered in 2 out of 100,000 people, while tumors discovered without causing symptoms occurred in 5.7 out of 100,000, for a total incidence of 7.7/100,000. With the advent of modern sophisticated imaging systems such asCT scans,the discovery of asymptomatic meningiomas has tripled.[citation needed]

Meningiomas are more likely to appear in women than men, though when they appear in men, they are more likely to be malignant. Meningiomas may appear at any age, but most commonly are noticed in men and women age 50 or older, with meningiomas becoming more likely with age. They have been observed in all cultures, Western and Eastern, in roughly the same statistical frequency as other possible brain tumors.[7]

History

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Theneoplasmscurrently referred to as meningiomas were referred to with a wide range of names in older medical literature, depending on the source. Various descriptors included "fungoid tumors", "fungus of the dura mater", "epithelioma", "psammoma", "dural sarcoma", "dural endothelioma", "fibrosarcoma", "angioendothelioma", "arachnoidal fibroboastoma", "endotheliosis of the meninges", "meningeal fibroblastoma", "meningoblastoma", "mesothelioma of the meninges", "sarcoma of the dura", and others.[citation needed]

The modern term of "meningioma" was used first byHarvey Cushing(1869–1939) in 1922, to describe a set of tumors that occur throughout theneuraxis(brain and spinal cord), but have various commonalities.[41][42]Charles Oberling then separated these into subtypes based on cell structure and, over the years, several other researchers have defined dozens of different subtypes as well. In 1979, theWorld Health Organization(WHO) classified seven subtypes, upgraded in 2000 to a classification system with nine low-grade variants (grade I tumors) and three variants each of grade II and grade III meningiomas.[42]The most common subtypes are Meningotheliomatous (63%), transitional or mixed-type (19%), fibrous (13%), and psammomatous (2%).[7]

The earliest evidence of a probable meningioma is from a skull approximately 365,000 years old, which was found in Germany. Other probable examples have been discovered in other continents around the world, including North and South America, and Africa.[citation needed]

The earliest written record of what was probably a meningioma is from the 1600s, whenFelix Plater(1536–1614) of theUniversity of Baselperformed an autopsy on Sir Caspar Bonecurtius.[41]Surgery for removal of a meningioma was first attempted in the sixteenth century, but the first known successful surgery for removal of a meningioma of the convexity (parasagittal) was performed in 1770 by Anoine Luis.[43]The first documented successful removal of a skull base meningioma was performed in 1835 by Zanobi Pecchioli, Professor of Surgery at theUniversity of Siena.[7]Other notable meningioma researchers have beenWilliam Macewen(1848–1924), andWilliam W. Keen(1837–1932).[41]

Improvements in meningioma research and treatment over the last century have occurred in terms of the surgical techniques forremovalof the tumor, and related improvements inanesthesia,antisepticmethods, techniques to control blood loss, better ability to determine which tumors are and are not operable,[44]and to effectively differentiate between the different meningioma subtypes.[45]

Notable cases

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  • Leonard Wood(1860–1927), underwent successful surgery by Dr.Harvey Cushingfor a meningioma circa 1910, a major advance in neurosurgery at the time.[41]
  • Crystal Lee Sutton(1940–2009), American union organizer and inspiration for the filmNorma Rae,died of a malignant meningioma.[46][47]
  • Elizabeth Taylor(1932–2011), American actress, underwent surgery in February 1997 to remove a benign meningioma.[48]
  • Kathi Goertzen(1958–2012), television news anchor in Seattle who underwent a very public battle with recurring tumors. She died on August 13, 2012, of complications related to her treatment.[49]
  • Eileen Ford(1922–2014), American model agency executive and co-founder ofFord Models.Died on July 9, 2014, from complications of meningioma andosteoporosis.[50]
  • Mary Tyler Moore(1936–2017), American actress, underwent surgery in May 2011 to remove a benign meningioma.[51][52]
  • Jack Daulton(1956–), American trial lawyer and art collector, underwent three surgeries in 2011–2012 in connection with the removal of a golf-ball-size benign meningioma over his left motor cortex; he fully recovered without disability or recurrence.[53]
  • Simone Giertz(1990–), Swedish inventor and professional YouTuber, underwent surgery to remove a grade I meningioma in 2018 and radiation therapy after tumor regrowth in 2019.

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