Epidemiology and Clinical Characteristics of Chordoid Meningiomas

Chordoid meningiomas are rare tumors, representing approximately 0.5-2% of all intracranial meningiomas; they demonstrate an age distribution that is somewhat younger than conventional meningiomas. While typical meningiomas show peak incidence in the sixth and seventh decades of life, chordoid variants often present in the fourth to sixth decades, with a mean age at diagnosis typically in the mid-40s to mid-50s. Cases associated with Castleman disease or Neurofibromatosis Type 2 may present even earlier, sometimes in the third or fourth decade of life. The sex distribution of chordoid meningiomas differs notably from conventional meningiomas. While typical meningiomas show a strong female predominance with a female-to-male ratio of approximately 2-3:1, chordoid meningiomas demonstrate a more balanced sex distribution or even a slight male predominance in some series.

Epidemiology and Clinical Characteristics of Chordoid Meningiomas

Chordoid meningiomas are rare tumors, representing approximately 0.5-2% of all intracranial meningiomas; they demonstrate an age distribution that is somewhat younger than conventional meningiomas. While typical meningiomas show peak incidence in the sixth and seventh decades of life, chordoid variants often present in the fourth to sixth decades, with a mean age at diagnosis typically in the mid-40s to mid-50s. Cases associated with Castleman disease or Neurofibromatosis Type 2 may present even earlier, sometimes in the third or fourth decade of life.  The sex distribution of chordoid meningiomas differs notably from conventional meningiomas. While typical meningiomas show a strong female predominance with a female-to-male ratio of approximately 2-3:1, chordoid meningiomas demonstrate a more balanced sex distribution or even a slight male predominance in some series.

Anatomical Location and CNS Site Predilection

These tumors occur most commonly in supratentorial locations, with particular frequency along the cerebral convexities, parasagittal region, and falcine areas. Chordoid meningiomas demonstrate a relatively increased occurrence in the skull base, including the sphenoid wing, cavernous sinus region, and cerebellopontine angle.

Clinical Presentation and Presenting Symptoms

The clinical presentation of chordoid meningiomas depends primarily on tumor location, size, and growth rate. Because these are Grade 2 tumors with relatively aggressive growth characteristics, patients may present with a shorter duration of symptoms compared to slow-growing benign meningiomas. The symptoms at presentation reflect mass effect, compression of adjacent neural structures, and occasionally edema in surrounding brain parenchyma.

Patients with supratentorial convexity or parasagittal chordoid meningiomas commonly present with headaches, which may be progressive and associated with features of increased intracranial pressure in larger tumors. Seizures represent another common presenting symptom for supratentorial lesions, occurring in 20-40% of cases depending on tumor location. Motor or sensory deficits may develop if the tumor compresses the motor cortex or sensory pathways. Cognitive changes or personality alterations can occur with frontal lobe lesions, though these symptoms may be subtle and develop gradually.

Skull base chordoid meningiomas present with location-specific symptoms. Tumors in the cerebellopontine angle typically cause progressive hearing loss, tinnitus, facial numbness or weakness (cranial nerves VII and VIII), and balance difficulties. Cavernous sinus lesions may present with diplopia, facial pain or numbness, and other cranial neuropathies affecting nerves III, IV, V, and VI. Suprasellar chordoid meningiomas can cause visual field defects (classically bitemporal hemianopsia from chiasmal compression), visual acuity loss, and occasionally pituitary dysfunction, though the latter is less common than with pituitary adenomas.

Radiological Findings

The neuroimaging characteristics of chordoid meningiomas share many features with conventional meningiomas but also demonstrate some distinctive findings related to their histological composition. On computed tomography (CT), chordoid meningiomas typically appear as well-demarcated, extra-axial masses with a broad dural base. They are usually isodense to slightly hyperdense relative to brain parenchyma on non-contrast CT. Calcification is less common than in some other meningioma variants, though it can occur. Bone changes at the site of dural attachment, including hyperostosis or bone erosion, may be present but are variable.

On MRI T1-weighted sequences, chordoid meningiomas typically appear isointense to slightly hypointense relative to gray matter. The T2-weighted and FLAIR sequences often show a characteristic feature: areas of hyperintensity within the tumor corresponding to the myxoid matrix component.

Following gadolinium administration, chordoid meningiomas demonstrate strong, relatively homogeneous enhancement, similar to other meningiomas. enhancement may occasionally be seen, potentially corresponding to myxoid or mucoid degeneration.

An important radiological feature of chordoid meningiomas is the presence of significant perilesional vasogenic edema in the adjacent brain parenchyma. This edema is often more extensive than would be expected for the tumor size and is seen in a higher proportion of chordoid meningiomas compared to benign variants

Intraoperative Findings

The surgical encounter with chordoid meningiomas reveals several characteristic features that distinguish them from conventional meningiomas. The gross appearance at surgery typically shows a firm to moderately soft, well-circumscribed extra-axial mass with a broad dural attachment. The tumor surface may appear smooth or slightly lobulated, and the color is often described as tan, gray, or yellowish-white. The consistency can be somewhat softer or more gelatinous than fibrous meningiomas, reflecting the abundant myxoid matrix component.

One of the most significant intraoperative findings is the increased vascularity of chordoid meningiomas. These tumors tend to be more vascular than typical benign meningiomas, with prominent feeding vessels from the dura and sometimes from pial vessels. The increased vascularity can lead to more substantial intraoperative bleeding, requiring meticulous hemostatic technique. The tumor-brain interface may show greater adherence to adjacent structures compared to some benign meningiomas, and there may be some encasement of blood vessels, particularly in skull base locations, making complete resection more challenging.

Histological Features

The histological appearance of chordoid meningiomas is distinctive and represents the defining characteristic of this variant. Under light microscopy, these tumors demonstrate a unique architectural pattern that resembles chordoma, hence the name "chordoid." The tumor cells are arranged in cords, trabeculae, and clusters embedded within an abundant myxoid or mucoid extracellular matrix. This matrix-rich appearance gives the tumor its characteristic chordoid quality and is essential for diagnosis.

The tumor cells themselves are epithelioid in appearance, with moderate to abundant eosinophilic cytoplasm that is often vacuolated. These vacuoles may be small and multiple or occasionally large, giving some cells a signet-ring appearance. The nuclei are typically round to oval with vesicular chromatin and small nucleoli. The cells may appear somewhat plasmacytoid or histiocytoid, with eccentric nuclei in some cases. Nuclear pleomorphism is generally mild to moderate, though it can occasionally be more pronounced. Importantly, the chordoid pattern must constitute a significant proportion of the tumor—typically at least 50% in most classification schemes—to warrant classification as a chordoid meningioma, as focal chordoid areas can occasionally be seen in otherwise conventional meningiomas.

The myxoid matrix that surrounds and separates the tumor cell cords is a hallmark feature. This matrix appears pale blue to amphophilic on hematoxylin and eosin staining and creates the appearance of tumor cells floating in a sea of mucoid material. The matrix is rich in glycosaminoglycans, particularly hyaluronic acid, and gives the tissue a loose, edematous quality. The amount of matrix can vary from case to case, but it is always a prominent component.

An important associated finding is the presence of lymphoplasmacytic infiltrates within and around the tumor. Collections of mature lymphocytes and plasma cells are commonly observed in the stroma and can sometimes be quite prominent. This inflammatory component is not unique to chordoid meningiomas but is seen more frequently in this variant than in many others. Occasionally, lymphoid follicles with germinal centers may be present, and in rare cases, the lymphoplasmacytic infiltrate can be so prominent that it raises consideration of a lymphoplasmacyte-rich meningioma. However, the presence of the chordoid architecture and myxoid matrix distinguishes the chordoid variant.

Mitotic activity in chordoid meningiomas is variable. Some tumors show very low mitotic counts (fewer than 4 per 10 high-power fields), while others may demonstrate more brisk mitotic activity. Importantly, chordoid meningiomas receive a WHO Grade 2 classification regardless of mitotic count, distinguishing them from atypical meningiomas where increased mitotic activity (4 or more mitoses per 10 high-power fields) is required for Grade 2 designation. This reflects the recognition that the chordoid phenotype itself confers more aggressive biological behavior independent of proliferative activity.

Necrosis is typically absent or minimal in chordoid meningiomas, and its presence should raise consideration of a higher-grade lesion or alternative diagnosis. Brain invasion, if present, would further influence grading and prognosis but is not a defining feature of chordoid meningiomas. The vascular pattern shows typical meningioma-type blood vessels, sometimes with hyalinization, though the vascularity may be increased compared to benign variants.

Immunohistochemical Profile

The most important positive markers are those that confirm meningothelial differentiation. Epithelial membrane antigen (EMA) shows strong, diffuse membranous staining in the vast majority of chordoid meningiomas, similar to other meningioma variants. This is typically one of the most reliable markers for meningioma diagnosis. Progesterone receptor (PR) expression is variable in chordoid meningiomas and is often negative or only weakly/focally positive, in contrast to many conventional meningiomas that show strong, diffuse PR positivity.

Vimentin staining is typically diffusely positive, as expected for mesenchymal tumors. SSTR2A (somatostatin receptor 2A) immunostaining is usually positive and can be useful both diagnostically and for identifying patients who might benefit from somatostatin receptor-targeted imaging or therapy. More recent studies have shown that many meningiomas, including chordoid variants, express claudin-1, a tight junction protein, which can be helpful in confirming meningothelial differentiation.

Chordoid meningiomas frequently show focal to diffuse positivity for cytokeratins, particularly low molecular weight cytokeratins such as CAM5.2, CK8, and CK18. This cytokeratin expression can be seen in both the tumor cells and in the vacuolated cells. S100 protein staining in chordoid meningiomas is typically negative or only weakly/focally positive in scattered cells..

Ki-67 proliferation index is variable but is often in the range of 3-10%, consistent with a Grade 2 lesion. Higher Ki-67 indices (>15-20%) may indicate more aggressive behavior and increased recurrence risk.

Special Stains

Alcian blue stain is particularly useful and demonstrates strong positivity in the abundant extracellular mucoid matrix that surrounds the tumor cell cords. Alcian blue highlights acidic mucopolysaccharides (particularly glycosaminoglycans like hyaluronic acid) and renders the matrix a characteristic blue color, making the chordoid architecture more apparent.

Mucicarmine stain may show variable positivity in chordoid meningiomas, with focal staining sometimes seen in the vacuoles within tumor cells and occasionally in the extracellular matrix. However, mucicarmine positivity is typically less pronounced than Alcian blue staining.

Periodic acid-Schiff (PAS) stain may show variable positivity, particularly in cell membranes and in some of the matrix material. PAS with diastase digestion (PAS-D) can help determine if glycogen is present in tumor cells, though this is not a defining feature. Reticulin stains typically show a pericellular pattern around individual cells or small groups of cells, reflecting the lobular architecture and the presence of basement membrane-like material around tumor cell nests.

Differential Diagnosis

Chordoma represents the single most important differential diagnostic consideration, particularly for skull base lesions. Chordomas arise from notochordal remnants and typically occur along the midline axis, most commonly in the clivus (intracranially) or sacrococcygeal region (spinally). Histologically, chordomas display a remarkably similar appearance to chordoid meningiomas, with cords and clusters of epithelioid cells with vacuolated, physaliphorous (bubble-bearing) cytoplasm embedded in a myxoid matrix. Both tumors are Alcian blue positive and may show cytokeratin expression, making them nearly indistinguishable on routine histology and these stains alone.

The key distinguishing features are immunohistochemical. Chordomas show strong, diffuse nuclear positivity for brachyury, which is the gold standard marker for chordoma and is negative in chordoid meningiomas. Additionally, chordomas demonstrate strong, diffuse cytoplasmic S100 protein positivity, whereas chordoid meningiomas are S100 negative or only weakly/focally positive. Chordomas typically show less robust or more variable EMA expression compared to the strong, diffuse EMA positivity seen in chordoid meningiomas.

Metastatic carcinoma, particularly from kidney (renal cell carcinoma) or other sites, enters the differential diagnosis because metastases can show vacuolated cells, mucin production, and epithelial features. Renal cell carcinomas, especially clear cell type, can demonstrate cells with clear to eosinophilic cytoplasm and may occur in the meninges. However, metastatic carcinomas typically lack the characteristic chordoid architecture with cords of cells in myxoid matrix. Immunohistochemically, renal cell carcinomas are positive for PAX8 often CD10, while being negative for EMA (or showing only weak, variable staining) and lacking meningothelial markers. The clinical history of a known primary malignancy is obviously important, though meningiomas can occasionally represent the first presentation of metastatic disease. Metastatic mucinous adenocarcinomas from gastrointestinal or breast primaries may also show abundant mucin but typically demonstrate glandular architecture, lack meningothelial markers, and are positive for site-specific markers (CDX2 for colorectal, GATA3 for breast, etc.).

Lymphoplasmacyte-rich meningioma can enter the differential diagnosis when a chordoid meningioma contains prominent lymphoplasmacytic infiltrates. Lymphoplasmacyte-rich meningiomas are characterized by abundant inflammatory cells that can sometimes obscure the underlying meningothelial component. However, these tumors lack the distinctive chordoid architecture and abundant myxoid matrix seen in chordoid variants. Careful examination typically reveals more conventional meningioma patterns (meningothelial, transitional, or fibrous) within lymphoplasmacyte-rich variants, whereas chordoid meningiomas maintain their distinctive epithelioid cells arranged in cords within myxoid stroma. Both may show similar immunoprofiles for meningothelial markers, but the histological architecture is the distinguishing feature.

Secretory meningioma is a distinctive variant characterized by intracellular and extracellular eosinophilic, PAS-positive, hyaline inclusions (pseudopsammoma bodies) and may show vacuolated cells. However, secretory meningiomas lack the abundant myxoid matrix and chordoid architecture, and the secretory inclusions are distinctive. These inclusions contain immunoglobulin and are surrounded by a corona of epithelial cells. Secretory meningiomas also tend to have a more lobular architecture and prominent edema, but the histological pattern is different from chordoid variants.

Clear cell meningioma can show cells with clear cytoplasm and may have a patternless or sheet-like architecture that differs from typical meningioma. However, clear cell meningiomas lack the abundant myxoid matrix and chordoid cords characteristic of chordoid variants. Clear cell meningiomas also have distinct molecular features, including SMARCE1 mutations in many cases, and have a predilection for the cerebellopontine angle and spine in younger patients. Both are WHO Grade 2 tumors.

Genetic Alterations and Chromosomal Instability

Chordoid meningiomas demonstrate a complex pattern of genetic alterations that reflects their more aggressive nature. Like many meningiomas, loss of the NF2 gene on chromosome 22q is frequently observed, though this is not universal. The NF2 gene encodes merlin, a tumor suppressor protein, and its inactivation through deletion or mutation represents a key pathogenic mechanism.  Studies have shown that chordoid meningiomas often harbor multiple chromosomal losses beyond 22q, including deletions on chromosomes 1p, 14q, and 18q. This pattern of multiple chromosomal losses suggests significant genomic instability, which likely underlies the more aggressive clinical behavior of these tumors. The chromosomal instability in chordoid meningiomas approaches or exceeds that seen in other Grade 2 (atypical) meningiomas, providing molecular justification for their Grade 2 classification even in the absence of increased mitotic activity or brain invasion.

Copy Number Alterations

Comparative genomic hybridization and array-based studies have revealed that chordoid meningiomas typically show more complex copy number alteration profiles compared to benign meningiomas. Beyond simple chromosomal losses, these tumors may demonstrate gains on certain chromosomes and complex patterns of genomic rearrangement. The presence of multiple copy number alterations has been associated with higher recurrence rates and may serve as a molecular prognostic marker.

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