Meningiomas and Melanocytic Lesions
Main Text
Preamble
Meningiomas are the most common of all brain tumors, accounting for > 1/3 of all primary intracranial neoplasms and nearly 40% of nonmalignant tumors. The 5th edition WHO separates meningiomas into a single family of neoplasms that are separated by grade into three groups: CNS WHO grades 1, 2, and 3 (formerly benign or typical meningioma, atypical meningioma, and anaplastic meningioma, respectively).
In contrast to prior editions of the WHO classification of meningiomas, the 5th edition defines diagnostic criteria by tumor grade. Following a brief overview, we consider all three grades of meningioma in this chapter.
Following our focused and detailed discussion of meningiomas, we briefly discuss melanocytic tumors, which were assigned their own major tumor group in the 5th edition.
Meningiomas
Preamble
Meningiomas have a wide morphologic spectrum that includes numerous histopathologically defined subtypes. The 5th edition lists 15 subtypes of meningiomas (meningothelial, fibrous, transitional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic, chordoid, clear cell, rhabdoid, and papillary meningiomas) plus atypical meningiomas (AMs) and anaplastic (malignant) meningiomas.
The WHO, 5th edition diagnostic criteria for meningioma include classic histopathologic features matching at least one of the meningioma subtypes, or suggestive histopathologic features combined with biallelic inactivation of NF2 or other classic drivers of conventional meningioma (TRAF7, AKT1, KLF4, SMO, PIK3CA), clear cell meningioma (SMARCE1), or rhabdoid meningioma (BAP1), or (2) suggestive histopathologic features combined with a defined DNA methylation class of meningioma. The WHO, 5th edition also notes that the diagnosis of meningioma frequently requires matching of several of the above criteria.
Recent studies suggest dividing meningiomas into four consensus molecular groups: Two benign groups largely dichotomized by neurofibromatosis type 2 (NF2) status, and two clinically aggressive groups defined by their hypermetabolic transcriptome &/or their preponderance of proliferative, cell-cycling pathways.
In contrast to CNS WHO grade 1 meningiomas, CNS WHO grades 2 and 3 are associated with more aggressive clinical behavior and less favorable outcomes. We discuss each of these three members of the meningioma family in sequence.
Meningioma, CNS WHO Grade 1
Meningioma is a benign lesion with nonaggressive growth and a low recurrence risk. Histologically and biologically benign meningiomas correspond to WHO grade 1 and are by far the most common type, accounting for 70-80% of all meningiomas.
Etiology
Meningiomas arise from progenitor cells that give rise to arachnoid meningothelial (“cap”) cells positioned outside the thin arachnoid layer that covers the brain and spinal cord (27-1) (27-2) (27-3).
Monosomy of chromosome 22, an early event in meningioma tumorigenesis, is the most frequent genetic abnormality. NF2 mutations are detected in most meningiomas associated with NF2 and are found in 40-60% of sporadic meningiomas. NF2 mutations occur in approximately equal frequency among all three WHO grades.
Mutations in non-NF2 meningiomas include TRAF7, KLF4, AKT1, and SMO or POLR2A. These are found in ~ 1/4 of meningiomas. Most meningiomas with these non-NF2 mutations are benign.
Higher grade meningiomas exhibit more complex genetic changes with losses on multiple chromosomes. Heterozygous or homozygous deletions of CDKN2A&/or CDKN2B and TERT promoter mutations are poor prognostic, grade 3-defining parameters.
Pathology
Location
Tumor location is strongly associated with mutation spectrum. Although meningiomas can occur at virtually any site within the CNS, > 90% are supratentorial (27-4). The most common location is parasagittal/convexity, accounting for ~ 1/2 of all meningiomas. The majority of these carry a 22q deletion &/or NF2 mutations. Parasagittal/falx meningiomas also commonly exhibit SMARCB1 mutations, while some convexity meningiomas have BAP1 mutations.
Between 15-20% are located along the skull base, including the sphenoid ridge (27-5). Most of these are non-NF2 meningiomas. Non-NF2 meningiomas have mutations in other “driver genes.” Several mutations (TRAF7, KLF4, AKT1, SMO, &/or PIK3CA) have been identified. These non-NF2 meningiomas are also usually benign and originate from the central or anterior skull base.
Less common supratentorial sites include the ventricles (usually in the choroid plexus glomus) and pineal region (tentorial apex).
Approximately 8-10% of intracranial meningiomas occur in the posterior fossa. Here, the cerebellopontine angle is by far the most common infratentorial site followed by the jugular foramen and foramen magnum, usually from the clivus or craniocervical junction. Meningiomas rarely arise from the squamous portion of the occipital bone.
Between 1-2% of meningiomas are entirely extracranial. Sites include the orbit (optic nerve sheath), paranasal sinuses, and nose. A few typical meningiomas (TMs) arise within the skull (“intradiploic” or “intraosseous” meningioma) and are most common where arachnoid granulations occur.
Size and Number
Meningiomas vary widely in size. Most are small (< 1 cm) and found incidentally at imaging or autopsy. Some—especially those arising in the anterior fossa from the olfactory groove—may attain large size before causing symptoms.
Meningiomas can be solitary (90%) or multiple. Multiple meningiomas occur in NF2as well as in multiple meningiomatosis syndrome.
MENINGIOMA: LOCATION
General
• Supratentorial (90%), infratentorial (8-10%)
• Multiple [10%; neurofibromatosis type 2 (NF2), meningiomatosis]
Sites
• Most common (60-70%)
Parasagittal (25%)
Convexity (20%)
Sphenoid ridge (15-20%)
• Less common (20-25%)
Posterior fossa (8-10%)
Olfactory groove (5-10%)
Parasellar (5-10%)
• Rare (2%)
Intraventricular
Pineal region/tentorial apex
Extracranial (optic nerve sheath, sinuses, nose)
Intraosseous (diploic space, often associated with arachnoid granulations)
Gross Pathology
Meningiomas have two general configurations: A round (“globose”) (27-5) (27-6) (27-7) (27-8)and a flat, sheet-like or carpet-like (“en plaque”) appearance (27-16). Most meningiomas are well-demarcated, firm, rubbery, or gritty masses that have a broad base of dural attachment. As they grow, meningiomas typically invaginate toward adjacent brain. A CSF-vascular “cleft” is often present between the tumor and underlying cortex (27-6) (27-7).
In contrast to higher grade meningiomas, most CNS WHO grade 1 meningiomas displace and compress, but do not invade, adjacent brain.
Meningiomas often cause reactive nonneoplastic thickening of the adjacent dura (dural tail sign on imaging) (27-9) (27-10). They commonly invade dural venous sinuses and may extend through the dura to involve the skull, inducing calvarial hyperostosis (27-17).
Although small intratumoral “microcysts” are not uncommon, gross cystic change is rare. Frank hemorrhage is uncommon, occurring in only 1-2% of cases (27-20).
Rarely, metastasis from an extracranial primary to a meningioma occurs. Here, one primary tumor is the recipient and another tumor is the donor. Meningioma is the most common tumor to harbor metastases. Tumor-to-tumor metastasis, a.k.a. “collision tumors, “are typically lung or breast metastases to a histologically benign meningioma.
Microscopic Features
Meningiomas exhibit a wide spectrum of histologic appearances with 15 subtypes identified in the 2021 WHO classification. Of these subtypes, the most common are the meningothelial, fibrous, and transitional variants.
By definition, CNS WHO grade 1 meningiomas carry a low risk of recurrence &/or aggressive growth. Their mitotic index is low with MIB-1 usually < 1%. Brain invasion is absent.
Features of brain invasion &/or more aggressive growth can arise in any meningioma subtype. Histologically benign-appearing meningiomas that show unequivocal brain invasion (not isolated perivascular spread or indentation of the brain without pial breach) are designated as CNS WHO grade 2 neoplasms.
Because two specific histologic subtypes—chordoid and clear cell meningiomas—have a higher likelihood of recurrence, they are also assigned CNS WHO grade 2.
Clinical Issues
Epidemiology
Recent epidemiologic data suggest that meningioma is the most frequently diagnosed primary brain tumor, accounting for > 1/3 of all reported CNS tumors. Grade 1 meningiomas account for 80-85% of these tumors.
Many meningiomas are small and discovered incidentally, often at imaging or autopsy. The lifetime risk of developing meningioma is ~ 1%; meningiomas are found in 1-3% of autopsies.
Multiple meningiomas are common in patients with NF2 and non-NF2 hereditary multiple meningioma syndromes (27-8). Sporadic multiple (i.e., not syndromic) meningiomas occur in ~ 10% of cases.
Demographics
Meningiomas are classically tumors of middle-aged and older adults. Peak occurrence is in the sixth and seventh decades (mean = 65 years). Although meningioma accounts for slightly < 3% of primary brain tumors in children, meningioma still represents the most common dura-based neoplasm in this age group. Many (but by no means all) are related to NF2. NF2-related meningiomas occur at a significantly younger age compared with nonsyndromic meningiomas.
Meningioma is one of the few brain tumors that exhibits a female predominance. Women are almost twice as likely men to develop CNS WHO grade 1 meningiomas. The F:M ratio varies with age, peaking at 3.5-4:1 in premenopausal women in the 35- to 44-year age group.
Presentation
Symptoms relate to size and tumor location. Less than 10% of meningiomas become symptomatic.
Natural History
Longitudinal studies have demonstrated that most meningiomas < 2.5 cm grow very slowly—if at all—over five years. The majority of small, asymptomatic, incidentally discovered meningiomas show minimal growth and are usually followed with serial imaging.
Malignant degeneration of a CNS WHO grade 1 meningioma into an atypical or anaplastic variant is rare. Extracranial metastases are exceptionally rare, occurring in 1 in 1,000 cases. When they do occur, metastases are generally to the lung or axial skeleton. Metastases from both benign and atypical/malignant meningiomas have been reported.
Treatment Options
Stratified treatment risk:benefit ratios vary, not just with tumor type and grade, but also with size and location, vascular supply, and presence or absence of a brain/tumor cleavage plane.
Image-guided surgery with resection of symptomatic lesions can be curative. The major factor associated with meningioma recurrence is subtotal resection.
Stereotactic radiosurgery or chemotherapy with progesterone antagonists may be options in patients with meningiomas in critical locations, such as the cavernous sinus.
MENINGIOMA: CLINICAL ISSUES
Epidemiology
• Most common intracranial primary neoplasm
36% of all primary CNS neoplasms
• Most are asymptomatic
Found incidentally at imaging/autopsy (1-3%)
• Solitary (> 90%)
Multiple in NF2, meningiomatosis
Demographics
• F:M = 2:1
Sex difference greatest prior to menopause
• Median age at diagnosis = 65 years
• Rare in children unless NF2
Natural History
• Grows slowly
• Rarely metastasizes
Imaging
General Features
The general appearance of a CNS WHO grade 1 meningioma is a round or lobulated, sharply demarcated, extraaxial, dura-based mass that buckles the cortex inward. A discernible CSF-vascular “cleft” is often present, especially on MR.
Unequivocal parenchymal invasion—not just perivascular spread or indentation of the brain without breaching the pia—is uncommon. When present, it upgrades the tumor to atypical meningioma (AM), CNS WHO grade 2.
Meningioma-associated cysts are found in 4-7% of cases. These can be intra- or extratumoral. Occasionally, pools of CSF are trapped between the tumor and adjacent brain (creating the CSF-vascular “cleft”). Partially or almost completely cystic meningiomas occur but are rare.
CT Findings
NECT
Almost 3/4 of meningiomas are mildly to moderately hyperdense compared with cortex (27-14A). About 1/4 are isodense (27-12) (27-15A). Hypodense meningiomas occur but are uncommon (27-19A) (27-13). Frank necrosis or hemorrhage is rare (27-20A).
Peritumoral vasogenic edema, seen as confluent hypodensity in the adjacent brain, is present in ~ 60% of all cases.
Approximately 25% of TMs demonstrate calcification (27-11). Focal globular or more diffuse, sand-like (“psammomatous”) calcifications occur.
Bone CT may show hyperostosis that varies from minimal to striking (27-17). Hyperostosis is often but not invariably associated with tumor invasion. Striking enlargement of an adjacent paranasal sinus may occur with skull base meningiomas (27-18). Bone lysis or frank destruction can also occur. Bone involvement by meningioma occurs with both benign and malignant meningiomas and is not predictive of tumor grade.
CECT
The vast majority of meningiomas enhance strongly and uniformly (27-12) (27-14).
MR Findings
General Features
The majority of meningiomas are isointense with cortex on all sequences (27-14). Between 10-25% of cases demonstrate changes suggestive of cyst formation or necrosis (27-13), although frank hemorrhage is uncommon.
T1WI
Meningiomas are typically iso- to slightly hypointense compared with cortex. Predominant hypointensity on T1WI and hyperintensity on T2WI suggest the microcystic subtype of TM (27-19).
T2WI
Most meningiomas are iso- to moderately hyperintense compared with cortex (27-23A). These are associated with a “soft” consistency at surgery, whereas T2-/FLAIR-hypointense tumors tend to be “hard” and somewhat gritty. Densely fibrotic and calcified meningiomas (appearing as “brain rocks” on NECT) can be very hypointense.
The CSF-vascular “cleft”(27-6)is especially well delineated on T2WI and is seen as a hyperintense rim interposed between the tumor and brain (27-21D) (27-23A). A number of “flow voids” representing displaced vessels are often seen within the “cleft.”
Sometimes, a sunburst pattern that represents the dural vascular supply to the tumor can be identified radiating toward the periphery of the mass (27-22).
FLAIR
Meningioma signal intensity varies from iso- to hyperintense relative to brain (27-14E). FLAIR is very useful for depicting peritumoral edema, which is found with ~ 1/2 of all meningiomas (27-21E). Peritumoral edema is related to the presence of pial blood supply and VEGF expression, not tumor size or grade. Some small meningiomas incite striking peritumoral edema, whereas some very large masses exhibit virtually none.
Pools of CSF trapped in the cleft between tumor and brain (nonneoplastic “peritumoral cysts”) are usually proteinaceous and may not suppress completely on FLAIR.
T2* (GRE, SWI)
T2* sequences are helpful to depict intratumoral calcification. “Blooming” secondary to intratumoral hemorrhage is rare.
T1 C+
Virtually all meningiomas, including densely calcified “brain rocks” and intraosseous tumors, demonstrate at least some enhancement following contrast administration. Over 95% enhance strongly and homogeneously (27-15B) (27-14F).
A dural “tail” is seen in the majority of meningiomas and varies from a relatively focal area adjacent to the tumor (27-9)to dural thickening and enhancement that extends far beyond the site of tumor attachment. The dural “tail” often enhances more intensely and more uniformly than the tumor itself. A dural tail sign is not pathognomonic of meningioma, as it occasionally occurs with schwannomas or pituitary macroadenomas.
Most of the enhancing dural “tail” represents benign, reactive dural thickening, although small tumor foci can be seen adjacent to the main tumor mass (27-10). Tumor extending 1 cm beyond the base of the tumor is rare.
Nonenhancing intratumoral cysts are seen in 5% of cases (27-13). Nonneoplastic peritumoral cysts do not enhance. Enhancement around the rim of a cyst suggests the presence of marginal tumor in the cyst wall, so complete cyst resection is recommended if technically feasible.
DWI
Most meningiomas do not restrict on DWI.
Perfusion MR
Perfusion MR may be helpful in distinguishing CNS WHO grade 1 tumors from atypical/malignant meningiomas. High rCBV in the lesion or in the surrounding edema suggests a more aggressive tumor grade.
MRS
Alanine (Ala; peak at 1.48 ppm) is often elevated in meningioma although glutamate-glutamine (Glx; peak at 2.1-2.6 ppm) and glutathione (GSH; peak at 2.95 ppm) may be more specific potential markers.
Angiography
CTA, MRA/MRV
CTA is very helpful in detecting dural venous sinus invasion or occlusion. Although it may be helpful in depicting the general status of the vascular supply to a meningioma (27-21B), DSA is best for detailed delineation of tumor vascularity prior to embolization or surgery. Tumor invasion of major dural venous sinuses is especially well depicted on MRV.
DSA
The classic angiographic appearance of a meningioma is a radial “sunburst” of vessels extending from the base of the tumor toward its periphery (27-22). Dural vessels supply the core or center of the lesion, radiating outward from the vascular pedicle of the tumor (27-24A). Pial vessels from internal carotid artery branches may become “parasitized” and supply the periphery of the mass (27-24C).
A prolonged vascular “blush” that persists late into the venous phase is typical. In some cases, arteriovenous shunting with the appearance of “early draining” veins occurs (27-24B). Careful examination of the venous phase should be conducted to detect dural sinus invasion or occlusion.
Preoperative embolization with tumor devascularization may substantially reduce operative time and blood loss. Careful delineation of tumor blood supply, including “dangerous” extra- to intracranial anastomoses, is essential to procedure success.
MENINGIOMA: IMAGING
General
• Round or flat (“en plaque”), dura based
• Extraaxial mass with “cleft” between tumor, brain
CT
• Hyperdense (70-75%)
• Calcified (20-25%)
• Cysts (peri- or intratumoral) (10-15%)
• Hemorrhage rare
• > 90% enhance
MR
• Usually isointense with gray matter
• CSF-vascular “cleft”
• ± vascular “flow voids”
• Strong, often heterogeneous, enhancement (> 98%)
• Dural “tail” (60%)
Angiography
• “Sunburst” vascularity
• Dural arteries to outside, pial to inside
• Prolonged, dense vascular “blush”
Differential Diagnosis
The major differential diagnosis of TM is AM or anaplastic (malignant) meningioma. Although there are no pathognomonic imaging features that reliably distinguish grade 1 tumors from these more aggressive variants, they are statistically far more common. Anaplastic meningiomas typically invade the brain and may exhibit a “mushrooming” configuration (27-28).
Dural metastasis, usually from a breast or lung primary, may be virtually indistinguishable from meningioma on imaging studies.
Rare entities that can closely resemble meningioma include hemangioma and solitary fibrous tumor. A hemangioma of the dura or venous sinuses is a true vasoformative neoplasm that can resemble meningioma. Most hemangiomas are very hyperintense on T2WI, whereas most meningiomas are iso- to mildly hyperintense. Delayed slow centripetal “filling in” of the mass on dynamic contrast-enhanced MR is suggestive of hemangioma.
Intracranial solitary fibrous tumor is relatively rare. Most are found adjacent to the dura, venous sinuses, or choroid plexus. There are no specific imaging features that reliably distinguish solitary fibrous tumors from meningiomas.
Other meningioma mimics include granuloma (TB, sarcoid) and focal idiopathic hypertrophic pachymeningitis. Solitary dural granulomas are rare. Idiopathic hypertrophic pachymeningitis is uncommon. Most cases are found in or around the skull base, particularly the orbit, cavernous sinus, and posterior fossa (clivus/cerebellopontine angle). Idiopathic hypertrophic pachymeningitis can invade bone and may be virtually indistinguishable from “en plaque” meningioma.
Intracranial mesenchymal tumor, FET::CREB fusion-positive (sometimes called angiomatoid fibrous histiocytoma) is a rare extraaxial neoplasm attached to the meninges or dura that can exhibit a dural “tail,” mimicking meningioma. Most occur in children or young adults, although cases in middle-aged adults have been reported.
Extramedullary hematopoiesis (EMH) can present as confluent or multifocal dura-based disease resembling “en plaque” solitary or multiple meningiomatosis. EMH occurs in the setting of chronic anemia or marrow depletion disorders.
MENINGIOMA MIMICS
Common
• Metastasis
Most common = breast, lung, colon, prostate
• Lymphoma
Less Common
• Granuloma
TB, sarcoid most common
Other (less common) = plasma cell granuloma, Rosai-Dorfman disease
Rare but Important
• IgG4-related disease
• Dural/venous sinus hemangioma
• Solitary fibrous tumor
• Intracranial mesenchymal tumor, FET::CREB fusion-positive
• Extramedullary hematopoiesis
Meningioma, CNS WHO Grade 2
While metastasis of meningiomas is extremely rare, tissue invasion is common and has wide implications for the treatment and clinical course of these tumors. In the 2016 WHO, 4th edition, breach of the “brain-meningioma interface” (i.e., brain invasion) led to acceptance of brain invasion as a standalone grading criterion for grade 2 meningioma. In the 2021 WHO, 5th edition, brain invasion must be unequivocal (i.e., not just perivascular spread or indentation of brain without pial breach) to establish the diagnosis of a CNS WHO grade 2 tumor.
Terminology
Atypical meningioma (AM) is an intermediate-grade meningioma with specific diagnostic criteria that can be applied across all meningioma subtypes (see below).
Etiology
There is a significant correlation between the number of inactivating NF2 mutations and tumor grade. The rate of NF2 mutations in high-grade meningiomas is 80%. Chromosomal abnormalities beyond chromosome 22 deletions are also much more common in high-grade meningiomas.
AMs demonstrate NF2 loss, genomic instability, mutations in SMARCB1, and a hypermethylated subtype.
Biallelic SMARCE1 inactivation and activating TERT promoter are rare mutations that are restricted to AM, CNS WHO grade 2 tumors. Most are clear cell subtypes.
Pathology
Location
Most atypical and anaplastic (malignant) meningiomas arise from the calvaria. The skull base is a relatively uncommon location for these more aggressive lesions.
Gross Pathology
Approximately 1/2 of all AMs invade the adjacent brain. In such cases, there is no intervening layer of leptomeninges between the invading tumor and underlying parenchyma. Brain invasion is also strongly correlated with the presence of other histopathologic criteria of atypia or anaplasia (see below).
Microscopic Features
The 2021 WHO, 5th edition established specific criteria that must be met for a diagnosis of AM, CNS WHO grade 2. These include 4-19 mitoses in 10 consecutive HPF or unequivocal brain invasion (not only perivascular spread or indentation of brain without pial breach) or specific morphologic subtype (chordoid or clear cell). Extension along the perivascular spaces does not constitute brain invasion per se because the perivascular spaces are lined by pia.
A meningioma can be also designated as a grade 2 tumor with at least three of the following five features: Increased cellularity, small cells with high nuclear:cytoplasmic ratio, prominent nucleoli, sheeting (uninterrupted patternless or sheet-like growth), or foci of spontaneous (i.e., noniatrogenic) necrosis.
Clinical Issues
Epidemiology
AMs represent 10-15% of all meningiomas.
Demographics
AMs tend to occur in slightly younger patients compared with grade 1 meningiomas and display a slight male predominance. Pediatric meningiomas also tend to be more aggressive.
Male patients with SMARCE1- inactivating mutations develop tumors in childhood, whereas carrier female patients develop tumors in adolescence or early adulthood.
Natural History
AMs are generally associated with a higher recurrence rate (25-30%) and shorter recurrence-free survival compared with TMs. The Simpson and modified Shinsu grading systems are the best predictors of recurrence after resection. Grade I represents macroscopically complete tumor removal, including excision of its dural attachment and any abnormal bone. Grades II-IV represent progressively less complete resection, and grade V is simple decompression, with or without biopsy.
Imaging
General Features
A good general rule is that it is difficult, if not impossible, to predict meningioma grade on the basis of imaging findings (27-30). However, because brain invasion is a frequent (but not always visible) feature of AMs, the CSF-vascular “cleft” typically seen in CNS WHO grade 1 meningiomas (27-23)is often compromised or absent (27-25).
CT Findings
AMs are usually hyperdense with irregular margins. Minimal or no calcification is seen, and frank bone invasion with osteolysis is common. Tumor may invade through the skull into the scalp.
MR Findings
Tumor margins are usually indistinct with no border between the tumor and the underlying cortex. A CSF-vascular “cleft” is often absent or partially effaced. Peritumoral edema and cyst formation are common but nonspecific findings (27-25). Contrast enhancement is strong but often quite heterogeneous.
ADC is significantly lower in atypical and malignant meningiomas compared with grade 1 lesions. Perfusion MR may show elevated rCBV, especially in the peritumoral edema (27-27). MRS often shows elevated choline (27-27D).
Differential Diagnosis
Because it is difficult to determine meningioma tumor grade on the basis of imaging findings alone, the major differential diagnosis of AM is CNS WHO grade 1 meningioma. Dural metastasis and anaplastic (malignant) meningioma, CNS WHO grade 3, can also be indistinguishable from AM. Solitary fibrous tumor can mimic meningiomas of all grades on imaging studies.
Meningioma, CNS WHO Grade 3
Terminology
Meningioma, CNS WHO grade 3, was formerly known as anaplastic or malignant meningioma. These uncommon tumors exhibit overtly malignant cytomorphology (anaplasia) &/or markedly elevated mitotic activity.
Etiology
High-grade meningiomas often harbor a diverse and variable group of somatic mutations. Several genes have been associated with malignant progression in meningioma. Homozygous deletions or mutations of the tumor suppressor genes CDKN2A (ARF) and CDKN2B are found in most anaplastic meningiomas. A new meningioma-associated tumor suppressor gene, NDRG2, is downregulated in anaplastic meningioma and AMs with aggressive clinical behavior.
Pathology
AM corresponds histologically to CNS WHO grade 3. Grossly, most AMs display extensive necrosis and often exhibit frank brain invasion (27-28).
Either a markedly elevated mitotic index (≥ 20 mitoses/10 HPF) or histologic features of frank anaplasia (e.g., sarcoma-, carcinoma-, or melanoma-like appearance) is sufficient for the diagnosis of anaplastic meningioma. As the presence of TERT promoter mutation or homozygous deletion of CDKN2A&/or CDKN2B confers a high recurrence risk and short interval to progression, these molecular features designate a CNS WHO grade 3 tumor irrespective of other histologic features.
In the past, the rhabdoid meningioma subtype was designated a grade 3 anaplastic/malignant meningioma based on the presence of rhabdoid cells alone without fulfilling other criteria for a CNS WHO grade 3 designation. Recent studies have demonstrated that patient outcome is correlated with CNS WHO grade independent of rhabdoid features.
Similarly, focal papillary architecture—once considered indicative of an AM or anaplastic meningioma—does not itself suffice for designating tumors as CNS WHO grade 2 or 3. Therefore, histomorphologic features of a rhabdoid or papillary subtype alone do not designate a tumor as CNS WHO grade 2 or 3.
A subset of rhabdoid &/or papillary meningiomas arise in patients with BRCA (br east ca ncer gene)-associated protein 1 (BAP1) mutations and the BAP1 tumor predisposition syndrome. Loss of BAP1 expression is associated with aggressive clinical behavior consistent with CNS WHO grade 3 tumors.
Clinical Issues
Epidemiology
Anaplastic (malignant) meningiomas are rare, representing only 1-3% of all meningiomas. Malignant meningiomas have a striking male predominance.
Natural History
Prognosis is poor. Recurrence rates following tumor resection range from 50-95%. Survival times range from 2-5 years and vary depending on resection extent.
Imaging
General Features
The imaging triad of extracranial mass, osteolysis, and “mushrooming” intracranial tumor is present in most, but not all, cases of anaplastic meningioma (27-28) (27-31). Calcification is rare, and contrast enhancement is typically heterogeneous (27-29).
Differential Diagnosis
The major differential diagnosis of anaplastic meningioma is AM. AMs can be indistinguishable from malignant meningiomas on imaging studies alone, as brain invasion may occur in both.
Metastases, solitary fibrous tumors, and sarcomas, such as meningeal fibrosarcoma, can all mimic anaplastic meningioma.
Primary Melanocytic Lesions
Preamble
By far the most frequent of all melanocytic CNS lesions are metastases from extracranial malignant melanomas (see Fig. 31-15). Primary melanocytic tumors of the CNS are a very rare, broad, and diverse group of entities with an estimated incidence of 0.9 per 10 million. These tumors can be circumscribed or diffuse and benign or malignant.
Primary CNS melanomas are thought to originate from leptomeningeal melanocytes, which are preferentially located at the base of the brain, ventral medulla, and along the upper cervical spinal cord. They can present as focal nodules or diffuse leptomeningeal infiltrates. Diffuse leptomeningeal melanotic infiltrates also occur in meningeal melanocytosis/melanomatosis [neurocutaneous melanosis (NCM)](27-32) (27-33).
Focal primary CNS melanotic masses span a morphologic spectrum from low-grade melanocytoma to the rare primary malignant melanoma. The 5th edition WHO specifies diagnostic criteria for circumscribed/localized primary melanocytic neoplasms in the meninges.
Melanocytomas have limited cytologic atypia, almost/no mitoses, no necrosis, and no CNS parenchymal invasion. For intermediate-grade melanocytomas, mitotic count of 0.5-1.5 mitoses/mm² (up to 5/HPF) &/or CNS invasion may be present, but cytologic atypia is limited and necrosis is absent. Melanomas should have > 5 mitoses/HPF &/or necrosis. Marked cytologic atypia is common.
Melanocytoma and Melanoma
Melanocytomas account for < 0.1% of all CNS neoplasms. Molecular analyses have shown that melanocytomas carry GNAQ/GNA11 mutations and present with copy number variants in chromosomes 3 and 6. Methylation profiling is especially useful in recognizing these neoplasms and distinguishing them from other pigmented CNS tumors.
Melanocytomas are solitary, darkly pigmented, low-grade tumors that do not invade adjacent brain. Preferred sites are the posterior fossa (skull base, cerebellopontine angle), temporal lobe, Meckel cave (with nevus of Ota), and spinal cord/nerve roots. Melanocytomas rarely undergo malignant transformation.
Melanomas frequently demonstrate TERT promoter mutations and frequently harbor additional oncogene mutations.
Prognosis is variable for melanocytic tumors of intermediate differentiation and poor for melanoma.
Imaging findings for melanocytic tumors depend largely on intrinsic melanin content and range from small, well-circumscribed focal lesions to diffuse meningeal involvement. Melanotic lesions are hyperdense on NECT and enhance strongly on CECT. The paramagnetic properties of melanin cause T1 shortening, so hyperintensity on T1WI and hypointensity on T2WI are characteristic (27-35) (27-36).
The major differential diagnosis for primary melanocytic lesions of the brain is metastatic malignant melanoma.
Diffuse Meningeal Melanocytosis/Melanomatosis
Diffuse leptomeningeal melanocytosis and melanomatosis are usually features of NCM, a rare neurocutaneous syndrome of childhood. Most patients present with numerous congenital melanotic nevi of the skin and neurologic dysfunction.
Diffuse melanocytic lesions appear as dense, thick, black confluent aggregates that fill the subarachnoid spaces and coat the pia (27-32) (27-33). The amygdala, pons, and cerebellum are most commonly involved but melanosis can be seen anywhere in the CNS.
Bilateral T1-hyperintense foci in the amygdala is an early sign of NCM (27-34A). Diffuse leptomeningeal enhancement (27-34B)and extension into the brain parenchyma via the perivascular spaces can occur and usually indicate malignant transformation with poor prognosis.
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