Walter F. Bierbaum, M.D.¹, Kar-Ming Fung, M.D., Ph.D.¹, Gregory N. Fuller, M.D., Ph.D.² Last update: June 30, 2003.

¹ Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, ² Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Clinical information: The patient was a 45 year old woman with a headache. MRI revealed a strongly enhancing dural based tumor of the falx cerebri. Edema was noted in the surrounding brain tissue but no mass effect was noted. Surgery yielded the following specimen.

Histopathology of the case:

A.	B.	C.	D.	E.	F.
G.	H.	I.

    Panel  A and B are low-magnification photographs taken at an area adjacent to the dura. Panel C, D, and E are taken from similar areas. Panel F, G, H, and I are taken from similar areas.

    The tumor was removed as multiple tissue fragments. At low-magnification, the lesion appeared as a cellular neoplasm (Panel A) with involvement of the dura (Panel B). There was a variation of histopathologic features in different areas of the specimen. In a number of areas, the histopathologic features were similar to those in Panel C, D, and E. In essence, the lesion was a cellular neoplasm with a pale blue myxomatous background. The tumor cells varied from round/polygonal to spindle-shaped (Panel D). The amount of pale blue myxomatous background also varied (compare Panel C and D). The tumor had small hyperchromatic and bland nuclei without prominent nucleoli. In some tumor cells, the cytoplasm contained several small vacuoles that gave them a bubbly appearance. In other tumor cells, the cytoplasm was dominated by one or two large vacuoles (Panel E).

    In other areas (Panel F, G, H, and I), the tumor had increased vascularity with sinusoidal vascular spaces. No anastomosing vascular channels were found (Panel F, G, and H). The volume of myxomatous background substance was reduced. The tumor cells appeared epithelioid and contained bubbly to clear cytoplasm. The nuclei had coarse to clumpy chromatin. Occasional intranuclear pseudoinclusions could be found (Panel H, and I). 

    Neither necrosis nor endothelial proliferation was noted in any part of the tumor. Mitotic figures were not readily seen.  Very little brain parenchymal tissue was adherent to the tumor and brain invasion could not be evaluated.

Discussion: General Information   Meningioma in general   Chordoid meningioma   Differential diagnosis

General Information    

    Meningiomas are neoplasms that display phenotypic features of arachnoid (meningotheliatous) cells. Most meningiomas are intracranial but about one-tenth of them occur in the spinal cord, very few of them arise from the ventricles. Some rare examples are found outside the central nervous system such as the lung, the mandible, and the scalp. Meningiomas are very common and comprise about one-fifth of all primary brain tumors. About one-tenth of meningiomas are multiple at the time of presentation. The peak incidence is between 45 to 55 years of age and there is a clear female predilection. Although meningiomas are seen in all age groups, they are uncommon in children and almost unknown in infants. When they occur in the very young, however, they tend to behave more aggressively.  In the 4 tier system of the World Health Organization (WHO) Classification of Tumors, three major histologic grades (WHO grade I, II, and III) for meningiomas with increase in anaplastic features and aggressive biological behavior from grade I to III. Recurrence of a WHO grade I meningioma after surgery is not uncommon. Meningiomas are seen in about half of the patients with neurofibromatosis 2 (NF2) but are not associated with neurofibromatosis 1 (NF1).

    The intracranial distribution of meniningiomas corresponds  with the distribution of the arachnoidal granulations. Most of them are found firmly affixed to the dura with half of all cases adjoining the sagittal sinus. The rest are predominantly seen in other convexities of the brain. Other common locations include olfactory grooves, the tubeculum sellae and parasellar region, the dural sheath of the optic nerve and the petrous bone. Meningiomas may also arise in the tela choroidae or in the stroma of the choroids plexus as intraventricular tumors. Spinal meningiomas are usually laterally situated, intradural, extramedullary tumors with a close relationship to the nerve roots. Macroscopically and radiographically, spinal meningiomas often raise the possibility of schwannoma.

    In computerized axial tomograph (CAT) scans, about three-quarter of meningiomas are hyperdense with calcifications found in about one-quarter of all cases. While they appear isointense with gray matter in T1-weighted non-contrast enhanced magnetic resonance imaging (MRI), they enhance brightly, and often homogenously. About slightly more than half of the cases have enhancement in the adjacent dura (the so-called “dural-tail”). A crest of cerebral spinal fluid (CSF) separating the tumor from the brain parenchyma (the so-called “CSF crest”) is often, but not always, present and is best detected in T2-weighed images. Edema in the brain parenchyma surrounding the tumor is quite variable. Invasion into the surrounding cranial bone is not an uncommon feature and is not an indication of biological malignancy. These cases, however, are more surgically challenging.  

Pathology of meningiomas in general

    Embryologically, the meninges are condensations of the mesenchymal elements around the neural tube. The telencephalic leptominges and the dermis of the upper face arise from the neural crest cells. The leptominges of the posterior brain and the spinal cord arise from the mesoderm. The role of the arachnoid cell in the cerebrospinal fluid circulation and its function as part of the brain coverings require both epithelial and mesenchymal properties.  This is clearly reflected in the morphologic features of arachnoid cells particularly at the ultrustructural level. As a family, there are probably no other tumors in the central nervous system that display a richer diversity in histopathologic features. The biological behavior can be correlated with some histologic variants. While the typical meningiomas are easy to diagnose, the uncommon variants often mimic other tumors and pose diagnostic difficulties. The rich diversity in histopathologic features may well be related to the diverse embryonic and biological features of arachnoid cells.  

    Most meningioms display more than one histologic pattern and rarely exist in one pure histologic pattern. The most common histologic types are the meningothelial type and mixed type. The fibrous (fibroblastic) type is less common. The meningothelial type has morphologic features similar to arachnoid cells. Typically, they are composed of bland syncytial epithelioid cells. The nuclei are oval, with distinct nuclear membrane, and fine chromatin. A single nuclear groove is seen sometimes. Pseudonuclear inclusions resulting from protrusion of cytoplasm into the nuclei are often present. Nucleoli are indistinct, if present. The neoplastic meningothelial cells tend to arrange in concentric whorls. The fibroblastic pattern has long spindle cells and fibroma like morphology. These features are illustrated in the box below. Ill-defined palisades of tumor cells suggestive of schwannoma may occur. With careful search, meningotheliomatous whorls that help confirm the diagnosis of meningioma are often found in fibrous meningiomas. The mixed type bears features of the meningothelial type and fibroblastic type. Psammoma bodies are often found at the center of the meningothelial whorls. When they are abundant, the term psammomatous meningioma is used. The psammoma bodies may become confluent and even ossified. Mesenchymal metaplastic changes including as osseous, cartilaginous, lipomatous, myxomatous and xanthoumatous changes can occur and complicate the otherwise classic meningiomas.

Click thumbnail to see meningothelial whorls in a meningioma.	Click thumbnail to see meningiothelial whorls in high-magnification. Note the nuclear pseudoinclusions (arrow).	Click thumbnail to see a meningothelial meningioma with epithelioid pattern ill-defined meningothelial whorls.	Click thumbnail to see a fibrous meningioma.

    Several other distinct morphologic variants of meningiomas are also recognized. While the angiomatous meningioma, microcystic meningioma, secretory meningioma, and lymphoplasmacyte-rich meningioma have distinctly different morphologic features, they have biologic behavior similar to that of the meningothelial, mixed, and fibrous meningioma and are WHO grade I tumors. In contrast, chordoid meningioma and clear cell meningioma (particularly those associated with an intracranial location) behave less favorably and are recognized as WHO grade II tumors. Papillary meningioma and rhabdoid meningiomas tend to behave aggressively and are recognized as WHO grade III tumors.

    Although some pleomorphism and mitotic activities may be noted in any of these variants, these features do not necessarily connote aggressive behavior. The WHO classification also recognizes atypical meningioma (WHO grade II) and anaplastic (malignant) meningioma (WHO grade III).  The diagnostic criteria of atypical and anaplastic meningioma are independent of the meningioma subtype. The WHO classification defined atypical meningioma as “A meningioma with increased mitotic activity or three or more of the following features: increased cellularity, small cells with high nucleus:cytoplasm ratio, prominent nucleoli, uninterrupted patternless or sheet-like growth, and foci of spontaneous or geographic necrosis.” Anaplastic meningioma is defined as “A meningioma exhibiting histological features of frank malignancy far in excess of the abnormalities present in atypical meningioma.” In our opinioin, a gray zone exists in between meningioma and atypical meningiomas.