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The meningioma is a tumor of the brain tumor which arrises from the dura mater, the tough outer covering of the brain. These tumors are most frequent along the parasagittal, falx cerebri, cerebral convexities, olfactory groove, sphenoid ridge, near the sella, foramen magnum, tentorium cerebelli, cerebellopontine angle, and spinal cord. Depending upon the location, the patient may present with a variety of neurological deficits. Multiple tumors may occur in 1-6% of cases. Tumors may also be associated with syndromes such as neurofibromatosis type 1. Meningiomas have a characteristic loss of chromosome 22 by cytogenetic analysis.

Under the microscope, there are a variety of patterns. Most contain meningothelial whorls, psammoma bodies (calcifications), and syncytial cells. Meningiomas are graded from I-III with grade III tumors the most pleomorphic and aggressive.


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Methylation of p14(ARF) gene in meningiomas and its correlation to the p53 expression and mutation.

Amatya VJ, Takeshima Y, Inai K.

1Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Mod Pathol. 2004 Jun;17(6):705-10. Abstract quote  

We have previously reported the statistically significant correlation of immunohistochemical expression of MIB-1 and p53 proteins among benign, atypical, and anaplastic meningiomas and p53 protein expression was high in atypical and anaplastic meningiomas.

In the present study, we analyzed 22 cases of meningiomas for mutation of p53 gene in its spectrum of exon 5 to 8 using automated genetic analyzer. We did not find any mutation of p53 in any of these cases, thus suggesting the p53 protein expression is wild type. We analyzed 72 cases of meningiomas for determining the methylation status of p14(ARF) gene and the immunohistochemical expression of MDM2 protein to explain p53 protein expression in these meningiomas.

We found methylation of p14(ARF) gene in five of 58 cases of benign meningiomas (8.6%), two of 10 cases of atypical meningiomas (20%), and two of four cases of anaplastic meningiomas (50%). In absence of p53 gene mutation, the high percentage of p14(ARF) gene methylation in high-grade meningioma may have been responsible for accumulation of wild-type p53 protein.

In addition, we also found the loss of MDM2 protein in high-grade meningiomas. These deregulations of p14-MDM2-p53 pathway may contribute to the malignant progression of meningioma.
Anaplastic Meningiomas

Am J Clin Pathol 2001;115:213-218

PS6K, a putative oncogene mapped to chromosome 17q23, encodes a serine/threonine kinase, which phosphorylates ribosomal subunit 6 and is part of the insulin receptor signal transduction pathway involved in the regulation of messenger RNA translation, protein synthesis, cell cycle progression, and cell size

Comparative genomic hybridization studies have detected 17q23 amplifications in a subset of meningiomas, particularly those with aggressive histologic features. PS6K amplifications have been reported in breast cancer, another hormonally driven neoplasm.

PS6K dosage in 94 archival paraffin-embedded meningiomas using dual-color fluorescence in situ hybridization

High-level PS6K amplifications in 3 of 22 anaplastic grade III meningiomas

Amplification was confirmed by differential polymerase chain reaction in 1 of these cases. In contrast, no amplifications were identified in 37 benign (grade I) and 35 atypical (grade II) meningiomas

Represents the first report of gene amplification in primary human meningiomas. Given its exclusive association with anaplastic meningiomas, PS6K amplification likely occurs during the malignant progression of a small subset of anaplastic tumors

Meningioma: a cytogenetic model of a complex benign human tumor, including data on 394 karyotyped cases.

Zang KD.

Institut fur Humangenetik, Universitat des Saarlandes, Homburg, Germany.

Cytogenet Cell Genet 2001;93(3-4):207-20 Abstract quote

Meningioma is the most frequent tumor of neuroectodermal origin in humans. It is usually benign. Only a minority of cases shows progression to an anaplastic tumor (WHO grade II and III). Meningioma is generally a sporadic tumor. Multiple and familial cases are rare and mostly associated with (hereditary) neurofibromatosis 2 (NF2). Meningiomas show an unexpectedly high recurrence rate. Also, completely removed low-grade tumors can recur. Recurrence and multiplicity are correlated with the formation of a peritumoral edema. On the cytogenetic level, meningioma is the best-studied tumor in humans. Grade I tumors show either uniform monosomy 22 or a diploid karyotype. The majority of high-grade, but only a minority of low-grade, meningiomas show loss of merlin, a cytoskeleton-cytoplasm-linker protein. Merlin is the product of the NF2 gene located on chromosome 22. A second tumor suppressor gene on chromosome 22 has not yet been detected.

In contrast to other solid tumors, progression of meningiomas is correlated with increasing hypodiploidy, showing characteristic clonal evolutions that mostly include chromosomes 14, 18, and 19 and, more rarely, 6 and 10. Structural aberrations are infrequent, except for the loss of the short arm of chromosome 1, which appears to be the decisive step for anaplastic growth.

Comparative histochemical and molecular cytogenetic studies point to the alkaline phosphatase gene (ALPL, liver-bone-kidney type) located on 1p36.1-->p34 as a candidate tumor suppressor gene. A model is proposed that tries to explain - with a minimum number of essential steps - the origin, progression, infiltration, and recurrence of meningiomas.


Loss of chromosome 22 and absence of NF2 gene mutation in a case of multiple meningiomas.

Lomas J, Bello MJ, Alonso ME, Gonzalez-Gomez P, Arjona D, Kusak ME, De Campos JM, Sarasa JL, Rey JA.

Department C. Experimental (Laboratorio de Oncogenetica Molecular), Hospital Universitario La Paz, Madrid; the Department of Neurosurgery, Hospital del Rio Hortega, Valladolid; and the Department of Pathology, Fundacion Jimenez Diaz, Madrid, Spain.

Hum Pathol 2002 Mar;33(3):375-8 Abstract quote

Multiple meningiomas are rare, and only 13 cases have been subjected to molecular genetic analysis to detect mutations of the tumor-suppressor gene neurofibromatosis type 2 (NF2) located on chromosome 22. Most of these cases display NF2 gene mutations parallel to loss of the chromosome 22 homolog, indicating that inactivation of this gene may represent an early event in the development of multiple meningiomas.

We report a case of a 61-year-old woman who developed multiple (dorsal and intracranial) meningiomas. Cytogenetic and molecular genetic studies demonstrated the loss of a copy of chromosome 22 in the 5 meningiomas studied and the absence of NF2 gene mutations in 4 of those available for this molecular analysis.

These findings, together with similar data from 2 previously reported cases, suggest the participation of a tumor-suppressor gene other than NF2 on chromosome 22 in the pathogenesis of a subgroup of multiple meningiomas.



The role of imaging in the follow up of meningiomas.

Hodgson TJ, Kingsley DP, Moseley IF.

Department of Radiology, National Hospital for Neurology and Neurosurgery, London, UK.

J Neurol Neurosurg Psychiatry 1995 Nov;59(5):545-7 Abstract quote

A retrospective study of 60 patients with meningiomas was conducted to evaluate the role of imaging in postoperative follow up.

Using case notes and imaging studies, requests were assessed with reference to the indications for imaging radiological findings and effect on patient management. Patients were divided into three groups: 34 who had undergone a macroscopically complete resection, 18 with known residual tumour, and eight in whom surgery was not performed. These 60 patients underwent a total of 165 CT and 11 MRI studies. In the complete resection group only two patients developed a recurrence, both having highly suggestive symptoms or signs.

It is concluded that routine imaging is not indicated in asymptomatic patients after complete tumour clearance. Both CT and MRI contribute to patient management in those with residual disease, MRI probably being the imaging method of choice.



Primary ear and temporal bone meningiomas: a clinicopathologic study of 36 cases with a review of the literature.

Thompson LD, Bouffard JP, Sandberg GD, Mena H.

Departments of Endocrine and Otorhinolaryngic-Head & Neck Pathology (LDRT) and Neuropathology and Ophthalmic Pathology (JPB, GDS, HM), Armed Forces Institute of Pathology, Washington, D.C.


Mod Pathol 2003 Mar;16(3):236-45 Abstract quote

"Primary" ear and temporal bone meningiomas are tumors that are frequently misdiagnosed and unrecognized, resulting in inappropriate clinical management.

To date, a large clinicopathologic study of meningiomas in this anatomic site has not been reported. Thirty-six cases of ear and temporal bone meningiomas diagnosed between 1970 and 1996 were retrieved from our files. Histologic features were reviewed, immunohistochemical analysis was performed (n = 19), and patient follow-up was obtained (n = 35). The patients included 24 females and 12 males, aged 10-80 years (mean, 49.6 years), with female patients presenting at an older age (mean, 52.0 years) than male patients (mean, 44.8 years). Patients presented clinically with hearing changes (n = 20), otitis (n = 7), pain (n = 5), and/or dizziness/vertigo (n = 3). Symptoms were present for an average of 24.6 months. The tumors affected the middle ear (n = 25), external auditory canal (n = 4), or a combination of temporal bone and middle ear (n = 7). The tumors ranged in size from 0.5 to 4.5 cm in greatest dimension (mean, 1.2 cm).

Radiographic studies demonstrated a central nervous system connection in 2 patients. Histologically, the tumors demonstrated features similar to those of intracranial meningiomas, including meningothelial (n = 33), psammomatous (n = 2), and atypical (n = 1). An associated cholesteatoma was identified in 9 cases.

Immunohistochemical studies confirmed the diagnosis of meningioma with positive reactions for epithelial membrane antigen (79%) and vimentin (100%). The differential diagnosis includes paraganglioma, schwannoma, carcinoma, melanoma, and middle ear adenoma. Surgical excision was used in all patients. Ten patients developed a recurrence from 5 months to 2 years later. Five patients died with recurrent disease (mean, 3.5 years), and the remaining 30 patients were alive (n = 25, mean: 19.0 years) or had died (n = 5, mean: 9.5 years) of unrelated causes without evidence of disease.

We conclude that extracranial ear and temporal bone meningiomas are rare tumors histologically similar to their intracranial counterparts. They behave as slow-growing neoplasms with a good overall prognosis (raw 5-y survival, 83%). Extent of surgical excision is probably the most important factor in determining outlook because recurrences develop in 28% of cases.


Primary intrathoracic meningioma: histopathological, immunohistochemical and ultrastructural study of two cases.

Falleni M, Roz E, Dessy E, Del Curto B, Braidotti P, Gianelli U, Pietra GG.

Department of Pathology, School of Medicine, University of Milan, San Paolo Hospital, Italy.

Virchows Arch 2001 Aug;439(2):196-200 Abstract quote

Meningiomas are common, usually benign slow-growing neoplasms of the central nervous system thought to arise from meningocytes capping arachnoid villi. Primary ectopic meningiomas are exceedingly rare extracranial and extraspinal tumors of controversial origin; they are usually limited to the head and neck region or to the paravertebral soft tissues. Only one mediastinal ectopic meningioma and few pulmonary ectopic meningiomas have been described in the literature until now.

Because of their rarity and their intriguing pathogenesis, we report here a second case of primary mediastinal meningioma and an additional case of primary pulmonary meningioma. Their possible origin and differential diagnosis are discussed.


Meningioangiomatosis. A comprehensive analysis of clinical and laboratory features.

Wiebe S, Munoz DG, Smith S, Lee DH.

Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.

Brain 1999 Apr;122 ( Pt 4):709-26 Abstract quote

Meningioangiomatosis (MA) is a rare, benign, focal lesion of the leptomeninges and underlying cerebral cortex characterized by leptomeningeal and meningovascular proliferation. It may occur sporadically or in association with neurofibromatosis type 2. Previous reports have emphasized histological and imaging features. Data on the management of these patients are sparse, and electrophysiological features of MA lesions have not been published.

We assessed the clinical, electrophysiological, histopathological and imaging features as well as the surgical outcome in MA, and compared MA with and without neurofibromatosis. Seven patients with MA at our centre were investigated and their outcome was assessed. A review of the literature is included.

MA exhibits a wide range of clinical, imaging, histopathological and electrophysiological features, making the diagnosis difficult. Sporadic MA cases are not associated with neurofibromatosis and the two disorders are genetically distinct. Medically refractory, localization-related epilepsy is the commonest presentation in sporadic cases, but atypical presentations also occur. Unlike sporadic cases, MA with neurofibromatosis is often found incidentally, does not produce seizures, occurs less frequently (ratio of 1:4), and is multifocal. MRI findings in MA correspond to the histological picture. However, the appearance on imaging is non-specific and may suggest cystic atrophy, angioma and tumours. Several abnormalities have been found in close proximity to MA lesions, i.e. meningioma, oligodendroglioma, arteriovenous malformation, encephalocoel and orbital erosion. In spite of histopathological diversity, MA lesions are either predominantly cellular or vascular. Immunohistochemical results are inconsistent among cases, add little to the diagnosis, and do not support a meningeal origin.

Electrocorticographic recordings from the surface and within MA lesions revealed a spectrum of electrophysiological expressions. Intrinsic epileptogenicity of MA lesions was documented in some cases. Epileptogenicity was confined to the perilesional cortex in some patients and it was complex (extralesional, multifocal, generalized) in others. Only 43% of our patients became seizure-free postoperatively compared with 68% previously reported, and >70% of our patients and those in the literature continued to require antiepileptic drugs.

This is in keeping with the diverse electrophysiology of MA and suggests a less optimistic postoperative outcome than previously recognized.

Meningioangiomatosis Occurring in a Young Male Without Neurofibromatosis With Special Reference to Its Histogenesis and Loss of Heterozygosity in the NF2 Gene Region

Yukio Takeshima, M.D. ; Vishwa Jeet Amatya, M.B.B.S. ; Fumio Nakayori, B.S. ; Tomohiro Nakano, C.T. ; Kazuhiko Sugiyama, M.D. ; Kouki Inai, M.D.

From the Second Department of Pathology (Y.T., V.J.A., F.N., T.N., K.I.) and the Department of Neurosurgery (K.S.), Hiroshima University School of Medicine, Hiroshima, Japan.

Am J Surg Pathol 2002;26:125-129 Abstract quote

A 16-year-old young male experienced persistent headache, and brain computed tomography and magnetic resonance imaging showed an abnormal mass with calcification in the right temporal lobe of the cerebrum. The tumor was located in the leptomeninges and cerebral cortex. In the leptomeninges, multiple calcified–fibrous nodules were noted.

In this area spindle-shaped cells were arranged in a fascicular or storiform pattern. A few meningioma-like nodules were also present. With continuity of this leptomeningeal lesion, a diffuse infiltrative lesion composed of proliferating perivascular cells and hyalinized small vessels was also present in the cerebral cortex. The proliferating vessels were small and narrowed by proliferation of surrounding spindle-shaped cells. Immunohistochemically, the spindle-shaped cells had strong to moderate positivity for vimentin and CD34 and weak positivity for epithelial membrane antigen and S-100 protein. The maximum Ki67 labeling index was 0.3%. The spindle-shaped cells showed loss of heterozygosity on D17S929 and D17S282 microsatellite markers flanking the NF2 gene.

These histopathologic and genetic findings are consistent with meningioangiomatosis, and meningioangiomatosis has been thought to be a neoplastic lesion of meningothelial cells. This is the first report of a genetic alteration in a case of meningioangiomatosis.


Meningiomas of the central nervous system occurring below the age of 17: report of 24 cases not associated with neurofibromatosis and review of literature.

Amirjamshidi A, Mehrazin M, Abbassioun K.

Department of Neurosurgery, Tehran University of Medical Sciences, Sina Hospital, Iran.

Childs Nerv Syst 2000 Jul;16(7):406-16 Abstract quote

The objective of this work was to gain more insight into the controversial characteristics of meningiomas occurring during childhood and adolescence. Management of meningiomas is an important field in pediatric neurosurgery. Every pediatric neurosurgeon has tried to resolve the problems relating to the clinical characteristics, biological behavior and outcome of this interesting and almost benign pathology, which rarely occurs in the first two decades of life.

The records on central nervous system (CNS) tumors held by the two major neurosurgery centers of Tehran Medical University and Arad General Hospital were prospectively collected during last 15 years. Complete medical records are available for all 24 cases, and long-term follow-up was achieved 19 patients. All the cases were diagnosed and treated after the introduction of computed tomographic (CT) scanning. Angiography and magnetic resonance imaging (MRI) were performed as complementary studies in some cases. The sample consisted of 13 girls and 11 boys. The age range at the time of diagnosis varied between 2 and 17 years, with a mean of 9.47 and standard deviation of 3.43. Fifteen patients were below 10 years of age (62.5%), and 9 of them were between 10 and 17 years old (37.5%).

The most common presenting symptoms, in declining order of frequency, were headache, epilepsy and focal neurological deficits. Similar cases associated with neurofibromatosis either at the time of presentation with meningioma or during the follow-up period were excluded (5 cases). The size of the presenting tumor was more than 5 cm in diameter in 17 cases. The locations of the lesions, taken as the site of the presumed widest dural base in each case were: spinal, orbital, ethmoidal and sphenoethmoidal in 1 case each, petroclival in 2, and tentorial or supratentorial in 18 patients. The only predisposing factor in this series of childhood meningiomas was whole-axis irradiation for previous malignancy in the case presenting with cervical intradural meningioma. There have been no surgical deaths, and gross total excision of the lesions was achieved in 21 cases. Tumor recurrence was observed during the follow-up period in 6 cases (25%). The follow-up period varied between 2 and 165 months, with a median interval of 130.2 months.

This series of pediatric CNS meningiomas comprises almost 1.08% of all meningiomas operated on by the authors during the last 15 years and it also accounts for about 1.1% of all pediatric CNS tumors encountered. This series of patients has certain characteristics regarding sex distribution, unusual size, peculiar localizations, special histological features and benign clinical behavior distinguishing it from other series reported in the literature.

Extracranial Sinonasal Tract Meningiomas
A Clinicopathologic Study of 30 Cases With a Review of the Literature

Lester D. R. Thompson, M.D., LCDR, MC, USNR; Kymberly A. Gyure, M.D.

From the Departments of Endocrine and Otorhinolaryngic-Head & Neck Pathology (L.D.R.T.) and Neuropathology (K.A.G.), Armed Forces Institute of Pathology, Washington, DC, U.S.A.


Am J Surg Pathol 2000;24:640-650 Abstract quote

Extracranial meningiomas of the sinonasal tract are rare tumors. These tumors are frequently misclassified, resulting in inappropriate clinical management. To date, there has been no comprehensive study to evaluate the clinicopathologic aspects of meningioma in these anatomic sites.

Thirty cases of sinonasal tract meningiomas diagnosed between 1970 and 1992 were retrieved from the files of the Otorhinolaryngic Registry of the AFIP. Histologic features were reviewed, immunohistochemical studies were performed, patient follow up was obtained, and the results were statistically analyzed.

The patients included 15 females and 15 males, aged 13 to 88 years (mean, 47.6 yrs). Patients presented clinically with a mass, epistaxis, sinusitis, pain, visual changes, or nasal obstruction, dependent on the anatomic site of involvement. Symptoms were present for an average of 31.1 months. The tumors affected the nasal cavity (n = 14), nasopharynx (n = 3), frontal sinus (n = 2), sphenoid sinus (n = 2), or a combination of the nasal cavity and ethmoid, frontal, sphenoid, and/or maxillary sinuses (n = 9). The tumors ranged in size from 1.0 to 8.0 cm in greatest dimension (mean, 3.5 cm). Radiographic studies demonstrated a central nervous system connection in six cases. The tumors often eroded the bones of the sinuses (n = 18) and involved the surrounding soft tissues, the orbit, and occasionally the base of the skull.

Histologically, the tumors demonstrated features similar to intracranial meningiomas. The majority were of the meningothelial type (n = 23), although there were three atypical meningiomas. Immunohistochemical studies confirmed the diagnosis of meningioma with positive reactions for epithelial membrane antigen (EMA) and vimentin (all tested). The differential diagnosis includes paraganglioma, carcinoma, melanoma, psammomatoid ossifying fibroma, and angiofibroma. Surgical excision was used in all patients. Three patients died with recurrent disease (mean, 1.2 yrs), one was alive with recurrent disease (25.6 years), and the remaining 24 patients were alive or had died of unrelated causes (mean, 13.9 yrs) at the time of last follow up (two patients were lost to follow up).

Extracranial sinonasal tract meningiomas are rare tumors which need to be considered in the differential diagnosis of sinonasal tumors. A whorled growth pattern and psammoma bodies, combined with positive EMA and vimentin immunohistochemical reactions, can confirm the diagnosis of meningioma. The overall prognosis is good, without a difference in outcome between benign and atypical meningiomas.


Chordoid Resemble chordoma

Chordoid Meningioma A Clinicopathologic Study of 42 Cases

M. E. Couce, M.D., Ph.D.; F. V. Aker, M.D.; B. W. Scheithauer, M.D.

From the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, U.S.A.

Am J Surg Pathol 2000;24:899-905 Abstract quote

The term chordoid meningiomas was first used by Kepes et al. in 1987 to describe a meningeal tumor in young patients associated with microcytic anemia and/or dysgammaglobulinemia. Such tumors were composed of spindle or epithelioid cells disposed in chordoma-like clusters and cords in a myxoid matrix and often featured a prominent lymphoplasmacellular infiltrate.

Our study includes 42 chordoid meningiomas that represented 0.5% of all meningiomas operated at Mayo Clinic during the interval 1975 to 1997.

The male to female ratio was 1:1 and the age range was 12 to 77 years (mean, 47.4 yrs). Only two (5.2%) occurred in children. The majority (88%) were large and supratentorial. No manifestation of systemic disease was noted. Chordoid elements comprised 10% to 100% of the tumors; 34 (81%) were more than 50% chordoid. Thirty-seven tumors (88%) were classified as typical and five as atypical. Lymphoplasmacytic infiltrates varied, being moderate in 10 cases (23.8%), mild in 15 (35.7%), and absent in 17 (40.5%). In 14 (42%) of the 33 cases with available follow up, one or more recurrences were noted. All but one recurrent tumor had been subtotally resected. In 86% of recurrent tumors, the primary lesion was more than 50% chordoid in pattern and contained little or no inflammatory infiltrate.

In our experience, chordoid meningiomas are primarily tumors of adults, lack sex predilection, are unassociated with systemic manifestations, and uniformly recur when subtotally excised.

Fibroblastic May resemble schwannomas with benign spindle cells
Hemangioblastic, Angioblastic, Angiomatous Resembles a vascular malformation

Angiomatous Meningioma: A Clinicopathologic Study of 38 Cases

Hasselblatt, Martin MD; Nolte, Kay Wilhelm MD; Paulus, Werner MD

From the Institute of Neuropathology, University Hospital Münster, Münster, Germany.

American Journal of Surgical Pathology : Volume 28(3) March 2004 pp 390-393 Abstract quote

To characterize histopathological and clinical features of angiomatous meningioma, 38 cases of angiomatous meningioma, ie, meningiomas whose vascular component exceeded 50% of the total tumor area, are reported. In addition to histologic examinations, clinical characteristics as well as follow-up data were compiled. Angiomatous meningiomas constituted 2.1% of all meningiomas.

Histologic signs of atypia or anaplasia were not observed in any tumor. The mean MIB-1/Ki67 proliferation index was 2.4%. Based on vessel size, two distinct histologic subtypes were identified, which differed in localization but not with regards to sex, age, presence of peritumoral edema, MIB-1/Ki67 proliferation index, or progesterone receptor status. In patients with gross tumor resection, no recurrences occurred. To conclude, angiomatous meningiomas share histologic and clinical features of benign meningiomas.

Since all angiomatous meningiomas examined here were grade 1 tumors, the diagnosis of angiomatous meningioma may have prognostic implications. Therefore, the existence of this rare subgroup of meningioma appears justified.

Psammomatous Numerous psammoma bodies

Lipomatous Meningioma A Clinicopathologic Study of 18 Cases With Special Reference to the Issue of Metaplasia

Federico Roncaroli, etal.

Am J Surg Pathol 2001;25:769-775 Abstract quote

We report 18 cases of lipomatous meningioma occurring in patients aged 14 to 79, most being females (72%).

Sixteen were supratentorial and 2 involved the spinal meninges. Follow-up ranged from 1 to 120 months. Fifteen patients were cured with surgery alone and 3 (17%) experienced a recurrence at 7, 8 and 24 months. Of these, one died with disease 4 years after resection of the primary lesion.

Histologically, 12 tumors were meningothelial, 3 transitional, 2 showed myxoid stromal changes and 1 was microcystic. The 2 spinal tumors were atypical. The proportion of fatty cells ranged from 10 to 90%. These resembled mature adipocytes or less commonly lipoblasts. Xanthomatous meningothelial cells were also noted in 6 tumors (30%). Both conventional meningothelial as well as lipid-laden cells exhibited epithelial membrane antigen immunoreactivity. In addition, occasional cells resembling mature adipocytes showed reactivity for S-100 protein. Ultrastructurally, lipidization of neoplastic cells varied from intracytoplasmic lipid droplets to a single massive globule. Moreover, lipid-laden meningothelial cells featured interdigitating cell membranes and well-formed desmosomes. Lipid droplets were not membrane-bound.

In that metaplasia denotes differentiation of one mature cell type to another, lipid accumulation in meningiomas cannot be considered true metaplasia since their lipid-laden cells retain the immunophenotype and ultrastructural features of meningothelium. We suggest that this distinctive subset of meningiomas be termed ``lipidized meningiomas'' rather than being included in the metaplastic category.

Meningothelial or Syncytial Small clusters of meningothelial cells

Secretory meningiomas: clinical and immunohistochemical observations.

Buhl R, Hugo HH, Mihajlovic Z, Mehdorn HM.

Department of Neurosurgery, University of Kiel, Germany.

Neurosurgery 2001 Feb;48(2):297-301; discussion 301-2 Abstract quote

OBJECTIVE: Secretory meningiomas are a rare histological subtype of these benign intracranial tumors. Few reports have been published regarding their tendency to develop peritumoral edema.

METHODS: Between July 1994 and February 1999, 11 patients with secretory meningiomas underwent operations in the Department of Neurosurgery, University of Kiel, Kiel, Germany. The clinical notes and radiological data (computed tomographic and magnetic resonance imaging scans) were reviewed. Immunohistochemistry was used to examine the expression of carcinoembryonic antigen and epithelial membrane antigen as well as progesterone and estrogen receptors.

RESULTS: Secretory meningiomas were found in 11 (5%) of 214 patients with intracranial meningiomas who were operated on in that period. All 11 patients were women. These patients' mean age was 65 years (range, 51-87 yr). The localization of these tumors was at the convexity in seven patients, at the sphenoid ridge in two patients, and in the olfactory groove and petroclival region in one patient each. Two meningiomas had no edema surrounding them, two meningiomas had a small amount of edema, two had moderate edema, and five had severe edema. No recurrences were observed during the mean follow-up period of 26 months (range, 8-65 mo). Immunohistochemically, all tumors contained pseudopsammoma bodies and reacted with epithelial membrane antigen and carcinoembryonic antigen. The MIB-1 antibody staining index showed a mean of 2% (range, 0-7%).

CONCLUSION: Secretory meningiomas are rare tumors, and they are mainly localized at the frontal convexity and the sphenoid ridge. They are surrounded by more edema than usual. The preponderance of female patients with this presentation is striking. The expression of carcinoembryonic antigen and epithelial membrane antigen is a characteristic feature of secretory meningiomas. These meningiomas are also positive for progesterone receptors, which has been shown to be a good prognostic factor.

Transitional Composed of syncytial and fibroblastic cells
Anaplastic Lobulated and circumscribed with malignant cytologic features such as high mitotic index, necrosis, and brain invasion
Atypical More cellularity and cytologic atypia than grade I tumors
Clear cell Mixture of clear cells and meningothelial cells
Common at the lumbar and cerebellopontine angles

Clear cell meningioma of the fourth ventricle.

Carlotti Jr CG, Neder L, Colli BO, Dos Santos MB, Garcia AS, Elias Jr J, Chimelli LC.


Am J Surg Pathol 2003 Jan;27(1):131-5 Abstract quote

Clear cell meningioma (CCM) has been identified and included in the World Health Organization classification of CNS tumors recently. CCMs are histologically characterized by sheets of polygonal cells with clear cytoplasm, which is the expression of high glycogen concentration. Compared with other variants of meningiomas, CCMs occur in younger patients and usually are located in the spinal canal and posterior fossa, the last ones mainly in the cerebellopontine angle. Some reports suggest that CCMs have high recurrence rate and potentially aggressive behavior. Poor outcome has been shown in intracranial and spinal tumor location, but indicators that predict outcome have not been established.

The authors present two cases of intracranial CCMs, with excellent outcome in patients harboring tumor location (restricted to the fourth ventricle) and some clinical particular features (young age, gender, obesity, and moderate impairment of intellectual capacity).

To the best of our knowledge, these are the two first reported cases of clear cell meningioma located primarily in the fourth ventricle.

Papillary-Grade II-III High rate of local recurrence and metastasis
Papillary proliferation with fibrovascular core
Hemangiopericytoma (Hemangiopericytic)-Grade II Histologically identical to hemangiopericytoma of the soft tissue
80% recurrence
23% metastasize
Rhabdoid Abundant eosinophilic cytoplasm resembling rhabdoid tumor

Primary Meningeal Sarcomas With Leiomyoblastic Differentiation A Proposal for a New Subtype of Primary Meningeal Sarcomas

Yasuo Sugita, M.D.; Minoru Shigemori, M.D.; Hiroshi Harada, D.D.S.; Yoshihiro Wada, M.D.; Itsurou Hayashi, M.D.; Minoru Morimastu, M.D.; Yuji Okamoto, M.D.; Kazunori Kajiwara, M.D. Bigner DD, McLendon RE, Bruner JM, eds. Graham DI, Lantos PL eds. Russell DS, Rubinstein LJ, eds.

From the Departments of Pathology and Neurosurgery, Kurume University School of Medicine, Kurume, and the Department of Neurosurgery, Saiseikai Yahata General Hospital, Kitakyushu, Japan.

Am J Surg Pathol 2000;24:1273-1278 Abstract quote

Two cases of primary meningeal sarcoma with leiomyoblastic differentiation are presented.

In case no. 1, the tumor showed anaplastic spindle cell tumor components intermingled with anaplastic meningothelial components. Meningothelial tumor cells gradually became transformed into spindle tumor cells. Spindle tumor cells reacted with antisera to muscle actin (HHF-35) and -smooth muscle actin. However, unchanged meningothelial tumor cells did not react with the antisera to HHF-35 and -smooth muscle actin. Electron microscopy showed condensations of cytoplasmic fibers and pinocytotic vesicles in spindle tumor cells similar to those seen in smooth muscle cells. In case no. 2, the tumor cells consisted predominantly of sheets of round or polygonal cells as seen in an epithelioid leiomyosarcoma. The neoplastic cells had frequent nuclear inclusions, such as those seen in meningiomas. Immunohistochemically, the tumor cells reacted with antisera to desmin and to HHF-35. Electron microscopy showed a basal lamina around the cytoplasm of tumor cells. Intranuclear inclusions with various cytoplasmic organelles were frequently observed in the tumor cells, as in meningiomas. Interdigitating cytoplasmic processes and intercellular junctional complexes, however, were not found in the tumor cells. Two possible hypotheses explain the occurrence of leiomyoblastic characteristics of these cases. In case no. 1, leiomyoblastic cells originated from meningothelial cells with the advancement of meningothelial anaplasia. In case no. 2, pluripotential mesenchymal cells in the meninges differentiated into meningothelial and smooth-muscle cell lines at the time of tumor growth.

With consideration of previous publications on primary meningeal sarcoma, these cases are the first reported primary meningeal sarcoma with leiomyoblastic and meningothelial differentiation.

Leukemic infiltrate within a meningioma Am J Surg Pathol 2001;25:127-130

Meshy meningioma: a potential novel variant.

Yamanouchi H, Yokoo H, Yoshida T, Kamiya M, Sasaki A, Hirato J, Nakazato Y.

First Department of Pathology, Gunma University School of Medicine, Maebashi, Japan.

Neuropathology 2001 Sep;21(3):236-40 Abstract quote

A potential novel variant of meningioma is reported. The tumor was solid, hard, white-colored, well circumscribed in a fibrous capsule and fixed to the dura, showing no invasion into the brain parenchyma.

Histopathological study presented a sparsely cellular tumor composed of cells with fine reticular or mesh-like cytoplasm, each containing an oval nucleus. Mitotic figures were rarely seen. Immunohistochemical studies of tumor cells showed positive immunoreactivity for vimentin and epithelial membrane antigen but were negative for GFAP, desmin, neurofilament, keratin, S-100, CD34 and CEA. Bipolar neoplastic cells and long processes were noted on ultrastructural observation; these were attached side by side to each other by desmosomes, resulting in a mesh-like configuration. Perinuclear cytoplasm and processes were rich in intermediate filaments and rough endoplasmic reticulum.

These microscopic and ultrastructural features have never before been reported among the variants of meningioma. The name 'meshy meningioma' is proposed for this novel variant.

Lack of alkaline phosphatase activity predicts meningioma recurrence.

Bouvier C, Liprandi A, Colin C, Giorgi R, Quilichini B, Metellus P, Figarella-Branger D.

Department of Pathology, Faculty of Medicine, Timone Hospital, Marseille, France.
Am J Clin Pathol. 2005 Aug;124(2):252-8. Abstract quote  

Meningiomas usually are benign intracranial tumors. However, some recur despite gross total resection, invade surrounding structures, or, rarely, metastasize. Reduced expression of the nonspecific tissue-type alkaline phosphatase (Pal) has been reported in high-grade meningiomas.

To search for a predictor for recurrence, we studied Pal expression by histoenzymology in a series of 54 meningiomas with gross total removal. Pal expression was mostly altered in grades II and III meningiomas (P = .000014) and meningiomas with high MIB-1 values (P = .001). Pal expression correlated with cytogenetic data (P = .000033) and with recurrence (P = .0064); all tumors that recurred had abnormal Pal expression (13/13). In univariate analysis, Pal expression was the only variable correlated with recurrence-free survival (P = .035).

Histochemical detection of Pal is a useful, easy, and low-cost technique to predict recurrence in meningiomas.
IMMUNOPEROXIDASE Progesterone receptors on the cells.
The cells are also positive for EMA, vimentin, and variable staining for S-100.

Immunohistochemical study of anaplastic meningioma with special reference to the phenotypic change of intermediate filament protein.

Ikeda H, Yoshimoto T.


Ann Diagn Pathol. 2003 Aug;7(4):214-22. Abstract quote

The phenotypic changes in the transformation of classic or atypical meningioma to anaplastic meningioma were investigated.

Among nine patients with anaplastic meningioma, four men and five women ranging in age from 32 to 75 years, four cases were identified as anaplastic meningioma at the first operation (de novo type), while five cases were identified as classic or atypical meningioma at the first operation but at recurrence had transformed to anaplastic meningioma (secondary type).

Immunohistochemical analysis was performed with the avidin-biotin complex method using monoclonal antibodies for glial fibrillary acidic protein, cytokeratin, alpha-internexin, neurofilament proteins (70 kd, 168 kd, and 200 kd), desmin, vimentin, CD34, Ki-67, epithelial membrane antigen, and S-100 protein. Immunohistochemical analysis showed positive immunoreactivity for cytokeratin, alpha-internexin, neurofilament proteins, vimentin, and glial fibrillary acidic protein during the course of progression. Expression of epithelial membrane antigen decreased with malignant progression. Marked expression of cytokeratin was observed in anaplastic meningioma. Ki-67 labeling index increased at every recurrence of both the de novo and secondary types.

The major phenotypic changes in the transformation of meningioma from the classic to the anaplastic type are loss of meningioma architecture, decreased expression of epithelial membrane antigen, increased expression of vimentin, and metaplastic expression of alpha-internexin and neurofilament triplet proteins.


Immunohistochemical expression of cathepsin D in meningiomas.

Castilla EA, Prayson RA, Abramovich CM, Cohen ML.

Department of Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA.


Am J Clin Pathol 2003 Jan;119(1):123-8 Abstract quote

We retrospectively studied the expression of cathepsin D by immunohistochemical analysis in 86 meningiomas (World Health Organization [WHO] grade I, n = 44; WHO grade II, n = 21; WHO grade III, n = 21) and correlated the results with tumor grade and outcome.

Staining was scored semiquantitatively based on distribution among neoplastic cells as follows: 0, no staining; 1+, 5% or less of the cells; 2+, 6% to 20%; 3+, 21% to 50%; and 4+, more than 50% of the cells. Cathepsin D expression was observed as follows: 0, 10 cases (12%); 1+, 25 cases (29%); 2+, 15 cases (17%); 3+, 12 cases (14%); and 4+, 24 cases (28%). A higher degree of cathepsin D immunostaining was associated with low tumor grade (P = .0014), low mitotic count (P < .0001), low apoptotic count (P < .0001), and the development of recurrence (P = .035). There was no correlation with outcome or MIB-1 proliferation index.

Cathepsin D expression by immunohistochemical analysis was identified in the majority (88% [76/86]) of meningiomas studied. A greater degree of immunoreactivity was observed in the WHO grade I group.

Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics.

Hahn HP, Bundock EA, Hornick JL.

Department of Pathology, Brigham and Women's, Hospital and Harvard Medical School, Boston, MA.

Am J Clin Pathol. 2006 Feb;125(2):1-6. Abstract quote  

The histologic distinction between meningiomas and other tumors of the central nervous system occasionally can be difficult. Claudin-1 is a tight junction-associated protein recently shown to be expressed in anaplastic meningiomas.

The purpose of this study was to determine whether immunohistochemical staining for claudin-1 could help distinguish meningiomas from histologic mimics, compared with commonly used markers. Tissue sections from 10 meningothelial meningiomas, 20 fibrous meningiomas, 10 atypical meningiomas, 7 solitary fibrous tumors of the meninges, 5 meningeal hemangiopericytomas, and 7 vestibular schwannomas were stained immunohistochemically for claudin-1, epithelial membrane antigen, S-100 protein, CD34, and glial fibrillary acidic protein. In total, 21 (53%) of 40 meningiomas were immunoreactive for claudin-1, whereas none of the other tumors were positive. In contrast, there was considerable overlap in the distribution of the other antibodies evaluated.

Claudin-1 seems to be a specific marker for meningiomas in this context. Although its sensitivity is relatively low, claudin-1 may be helpful in a panel of immunostains to distinguish meningiomas from histologic mimics.
Expression of cytokeratin by malignant meningiomas: diagnostic pitfall of cytokeratin to separate malignant meningiomas from metastatic carcinoma.

Liu Y, Sturgis CD, Bunker M, Saad RS, Tung M, Raab SS, Silverman JF.

Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Pittsburgh, PA 15212, USA.
Mod Pathol. 2004 Sep;17(9):1129-33. Abstract quote  

Based on clinical and histologic features, differentiating metastatic carcinomas from benign or malignant meningiomas usually is not difficult. Occasionally, however, in some patients without a clinical history of carcinoma, malignant meningiomas can morphologically simulate metastatic carcinoma, necessitating an immunohistochemical study for cytokeratin to make a correct diagnosis. However, the utility of immunohistochemical markers to separate malignant meningioma from metastatic carcinoma has not been investigated.

The immunoperoxidase method with antigen retrieval was used to characterize the expression of three cytokeratins (AE1/AE3, CAM 5.2, and Pan cytokeratin), EMA, CEA, Ber-EP4, CD 15, and B72.3 in 12 previously diagnosed malignant meningiomas, 20 benign meningiomas, and 20 metastatic carcinomas. Cytokeratin expression was detected in 75% of malignant meningiomas, 0% of benign meningiomas, and 100% of metastatic carcinomas. While epithelial markers of Ber-EP4, CEA, B72.3 and CD-15 were positive in 90, 80, 70 and 65% of the metastatic carcinoma, respectively, they were negative in all 12 malignant meningioma examined. Vimentin immunoreactivity was seen in all benign and malignant meningiomas, and in 20% of metastatic carcinomas.

Our results indicated that cytokeratin is not a reliable immunohistochemical marker to separate a malignant meningioma from metastatic carcinoma. A panel of epithelial markers including Ber-EP4, CEA, B72.3 and CD-15, and vimentin may be needed to separate malignant meningioma from metastatic carcinoma.

Cytokeratin expression can be a potential pitfall for confusing a malignant meningioma with a metastatic carcinoma.

Mapping of the keratin polypeptides in meningiomas of different types: An immunohistochemical analysis of 463 cases.

Miettinen M, Paetau A.

Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC and the Department of Pathology, Haartman Institute of University of Helsinki, Helsinki, Finland.

Hum Pathol 2002 Jun;33(6):590-8 Abstract quote

Keratins are known to be expressed in some meningiomas, and they have been consistently reported in secretory meningiomas. However, the expression of individual keratin polypeptides has not yet been systematically explored, and such a study could provide important information for the differential diagnosis of meningioma and other tumors, particularly metastatic carcinomas.

In this study we analyzed the keratin polypeptide patterns of 463 meningiomas of different types using well-characterized monoclonal antibodies specific to 11 individual keratins and 3 additional antibodies that recognize more than 1 keratin. Archnoid tissues from autopsies were examined for comparison. Secretory meningiomas showed consistent positivity for all simple epithelial keratins K7, K8, K18, and K19, usually limited to the slender spindle cells lining the gland-like lumina. Other keratins variably detected in a minority of gland-like structures were K5/6, K14, K16, and K17. Among other meningiomas, keratin 18 was commonly present in a significant number of tumor cells in different subtypes (30% to 80% of cases), often extensively. The K18 positivity of meningiomas paralleled that observed in normal arachnoids, which were negative for K7, K8, K19, and AE1. Only rare meningiomas, other than the secretory ones, had significant positivity for K7, K8, K19, and other keratins than K18. The concentric spindle cells around psammoma bodies and few other spindle cell foci were often focally positive for K7 and to lesser degree for K8, K14, and K19. The complex pattern of keratins in meningiomas has to be considered in the differential diagnosis of meningioma and metastatic carcinoma. In this context, antibodies to K7, K8, and K19 and the antibodies AE1 and AE3 are useful, because they only rarely label significant numbers of meningioma cells but are positive in a great majority of carcinomas.

Careful histologic analysis is necessary to differentiate anaplastic meningiomas and metastatic carcinomas, which have overlapping patterns of several keratins except K20, which was never present in any type of meningioma.


Occurrence, regulation, and significance of progesterone receptors in human meningioma.

Blankenstein MA, Verheijen FM, Jacobs JM, Donker TH, van Duijnhoven MW, Thijssen JH.

Department of Endocrinology, KE 03_139.2, University Medical Center Utrecht, P.O. Box 85090, NL 3508 AB, Utrecht, The Netherlands.

Steroids 2000 Oct-Nov;65(10-11):795-800 Abstract quote

The abundant expression of progesterone receptors (PR) in human meningiomas is well established. It is unknown, however, how PR expression is regulated, especially since estrogen receptors (ER) are virtually absent in these tumors.

At the mRNA level, ER splice variants occur in meningioma but these appear not to be involved in the apparently autonomous PR expression. In an earlier study, because other ER-inducible proteins were either not expressed at all (pS2) or were expressed at a very low level compared to their expression in breast cancer (Cathepsin-D), the authors have postulated that the autonomous PR expression in meningioma is PR promoter-related rather than ER-related and have studied PR expression in cultured meningioma cells. PR levels appeared to decrease rapidly in vitro in monolayer as well as in three dimensional spheroid cultures. Culture conditions thus are not yet sufficient for the quantitative evaluation of PR expression. To evaluate whether PR deterioration is associated with cell turnover (meningiomas grow much faster in vitro than in vivo), the relationship between expression of the apoptotic proteins Bcl-2 and Bax and PR expression was investigated. Bcl-2 expression was found to be highest in meningioma with low PR levels, and in breast cancer tissue with high PR levels. Bax expression was not related to PR expression in any of the two tissues.

Given the potential benefit of antiprogestin treatment and the occurrence in meningiomas of a protein capable of binding to the estrogen-responsive element, the expression of PR in meningioma remains a fascinating phenomenon which requires further investigation.



Dural lesions mimicking meningiomas.

Johnson MD, Powell SZ, Boyer PJ, Weil RJ, Moots PL.

Department of Pathology, Vanderbilt Medical School, Nashville, TN 37232, USA.

Hum Pathol 2002 Dec;33(12):1211-26 Abstract quote

Recently, a number of neoplastic and nonneoplastic entities have been reported that radiographically and clinically mimic meningiomas. Because these lesions occur infrequently and may resemble a meningioma during intraoperative analysis, they may not be considered in the differential diagnosis.

This review (and case illustrations) considers some of the newly recognized and notable lesions that can mimic meningiomas, including solitary fibrous tumors, gliosarcomas, leiomyosarcomas, hemangiopericytomas, melanocytomas, Hodgkin's disease, plasmacytomas, inflammatory pseudotumors, neurosarcoidosis, plasma cell granulomas, Rosai-Dorfman disease, Castleman's disease, xanthomas, rheumatoid nodules, and tuberculomas.

Awareness that these lesions involve the dura may facilitate intraoperative recognition and, in some cases, preclude unnecessary additional surgery.


Meningioangiomatosis. A comprehensive analysis of clinical and laboratory features.

Wiebe S, Munoz DG, Smith S, Lee DH.

Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.

Brain 1999 Apr;122 ( Pt 4):709-26 Abstract quote

Meningioangiomatosis (MA) is a rare, benign, focal lesion of the leptomeninges and underlying cerebral cortex characterized by leptomeningeal and meningovascular proliferation. It may occur sporadically or in association with neurofibromatosis type 2. Previous reports have emphasized histological and imaging features. Data on the management of these patients are sparse, and electrophysiological features of MA lesions have not been published.

We assessed the clinical, electrophysiological, histopathological and imaging features as well as the surgical outcome in MA, and compared MA with and without neurofibromatosis. Seven patients with MA at our centre were investigated and their outcome was assessed. A review of the literature is included. MA exhibits a wide range of clinical, imaging, histopathological and electrophysiological features, making the diagnosis difficult. Sporadic MA cases are not associated with neurofibromatosis and the two disorders are genetically distinct. Medically refractory, localization-related epilepsy is the commonest presentation in sporadic cases, but atypical presentations also occur. Unlike sporadic cases, MA with neurofibromatosis is often found incidentally, does not produce seizures, occurs less frequently (ratio of 1:4), and is multifocal. MRI findings in MA correspond to the histological picture. However, the appearance on imaging is non-specific and may suggest cystic atrophy, angioma and tumours. Several abnormalities have been found in close proximity to MA lesions, i.e. meningioma, oligodendroglioma, arteriovenous malformation, encephalocoel and orbital erosion. In spite of histopathological diversity, MA lesions are either predominantly cellular or vascular. Immunohistochemical results are inconsistent among cases, add little to the diagnosis, and do not support a meningeal origin. Electrocorticographic recordings from the surface and within MA lesions revealed a spectrum of electrophysiological expressions. Intrinsic epileptogenicity of MA lesions was documented in some cases. Epileptogenicity was confined to the perilesional cortex in some patients and it was complex (extralesional, multifocal, generalized) in others. Only 43% of our patients became seizure-free postoperatively compared with 68% previously reported, and >70% of our patients and those in the literature continued to require antiepileptic drugs.

This is in keeping with the diverse electrophysiology of MA and suggests a less optimistic postoperative outcome than previously recognized.


Characterization of Chromosome 14 Abnormalities by Interphase In Situ Hybridization and Comparative Genomic Hybridization in 124 Meningiomas
Correlation With Clinical, Histopathologic, and Prognostic Features

María Dolores Tabernero, MD, PhD, etal.
Am J Clin Pathol 2005;123:744-751 Abstract quote

We analyzed quantitative chromosome 14 abnormalities in 124 meningiomas by interphase fluorescence in situ hybridization (iFISH) and confirmed the nature of abnormalities by comparative genomic hybridization (CGH).

We correlated the abnormalities with clinical, histopathologic, and prognostic factors.
Of 124 cases, 50 (40.3%) showed loss (14.5%) or gain (25.8%) of the 14q32 chromosome region by iFISH. Most corresponded to numeric abnormalities: monosomy (12.9%), trisomy (1.6%), or tetrasomy (24.2%); in only 2 cases (1.6%), chromosome 14 loss did not involve the whole chromosome and was restricted to the 14q31-q32 region (confirmed by CGH). Cases with gain or monosomy corresponded more frequently to histologically malignant tumors (P = .009). Patients with monosomy 14/14q–, but not those with gain, more often were male (P = .04) and had a greater incidence of recurrence (P = .003) and shorter relapse-free survival (P = .03). The 2 patients with loss limited to 14q31-q32 had histologically benign tumors and no relapse after more than 5 years' follow-up.

Most meningiomas with chromosome 14 abnormalities have numeric changes, with interstitial deletions of 14q31-q32 present in few cases. Of the abnormalities detected, only monosomy 14 showed an adverse prognostic impact.
The Mitosis-Specific Antibody Anti-Phosphohistone-H3 (PHH3) Facilitates Rapid Reliable Grading of Meningiomas According to WHO 2000 Criteria.

Ribalta T, McCutcheon IE, Aldape KD, Bruner JM, Fuller GN.

From the Departments of daggerPathology and double daggerNeurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, TX; and the *Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Suner, Universitat de Barcelona, Barcelona, Spain.
Am J Surg Pathol. 2004 Nov;28(11):1532-1536. Abstract quote  

Mitotic figure (MF) counting is the most objective criterion for grading of meningiomas according to the 2000 World Health Organization (WHO) classification. However, the search for the area(s) of highest mitotic activity is tedious, and there is high interobserver variability in differentiating MF from apoptotic cells.

We tested the utility of the mitosis-specific marker phosphohistone-H3 (PHH3) to enhance rapid recognition of MFs and quick reliable grading of meningioma. Fifty-four archival meningiomas (26 benign, 20 atypical, 8 anaplastic) were reclassified according to current WHO criteria. PHH3-immunostained MFs were counted the same way as in hematoxylin and eosin-stained sections. Anti-PHH3-labeled MFs were easily seen and permitted quick identification of the area(s) of highest mitotic activity. Count results (mean) show a strong correlation between both methods: benign, hematoxylin and eosin 1.4, PHH3 2.2; atypical, hematoxylin and eosin 9.0, PHH3 15.9; anaplastic, hematoxylin and eosin 22.4, PHH3 34.1. PHH3 counting yielded greater sensitivity and in 12 cases (22.2%) suggested a change in grade (increased 9; lowered 3). All cases in which PHH3 lowered the grade were from older blocks, suggesting a loss of antigen preservation.

PHH3 immunostaining facilitates the rapid reliable grading of meningiomas by focusing attention on the most mitotically active areas and by allowing easy and objective differentiation of MFs from apoptotic nuclei.
Prognostic value of HER2 expression in meningiomas: an immunohistochemical and fluorescence in situ hybridization study.

Loussouarn D, Brunon J, Avet-Loiseau H, Campone M, Mosnier JF.

Department of Pathology, University Hospital of Nantes, France.

Hum Pathol. 2006 Apr;37(4):415-21. Abstract quote  

The aggressiveness of meningiomas is unpredictable. HER2 represents a well-known prognostic factor in various tumors such as breast carcinomas.

This work was designed to study HER2 protein expression and HER2 gene amplification in meningiomas and to evaluate their prognostic value. Frozen sections of 35 meningiomas were immunostained for HER2, estrogen receptor, progesterone receptor, E-cadherin, and MIB-1. Meningiomas immunostained for HER2 were further examined for the HER2 gene amplification by dual-color fluorescence in situ hybridization using probes for centromere 17 and 17q11.2-q12. Complete clinical information was obtained in all cases.

The study included 15 atypical meningiomas, 3 anaplastic meningiomas, and 17 classic meningiomas. Five atypical/anaplastic meningiomas and 5 classic meningiomas of the whole 35 (28.5%) meningiomas expressed HER2 protein. This was considered as an overexpression in comparison with negative normal meninges. Fluorescence in situ hybridization demonstrated more HER2 gene copy in 4 of these 10 HER2-positive meningiomas. At equivalent histologic grading, meningiomas with HER2 overexpression exhibited similar immunohistochemical parameters of prognostic value than their HER2-negative counterparts; however, the rate of tumor recurrence was significantly higher in meningiomas with HER2 overexpression than in HER2-negative meningiomas.

Conversely, HER2 amplification was not associated with recurrence. Some meningiomas exhibit HER2 protein overexpression in part induced by gene amplification. However, only HER2 overexpression could represent an independent prognostic factor in meningiomas.

MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors.

Abramovich CM, Prayson RA.

Department of Anatomic Pathology, Cleveland Clinic Foundation, OH 44195, USA.

Hum Pathol 1998 Dec;29(12):1420-7 Abstract quote

Predicting tumor behavior in meningiomas based on histology alone has been problematic.

This study retrospectively compares histology and MIB-1 (cell proliferation marker) labeling indices (LI) in benign, aggressive, and malignant meningiomas. Six histological features, including mitoses, necrosis, loss of pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared in 90 meningiomas (Fisher's exact test). Tumors with two or more of the above features were designated as aggressive meningiomas. Malignant meningiomas were characterized by brain invasion or metastasis. The MIB-1 LIs (% positive tumor cell nuclei) were compared between the three groups (Kruskal-Wallis test, Wilcoxon two-sample test).

Of the benign meningiomas (n=37; mean age, 54 years), 41% had one of the six histological features, with nuclear pleomorphism (n=10) being the most frequent. The aggressive tumors (n=29; mean age, 61 years) were characterized by nuclear pleomorphism (n=28), mitoses (n=20), necrosis (n=16), loss of pattern (n=16), prominent nucleoli (n=6), and hypervascularity/hemosiderin deposition (n=5). Malignant tumors (n=24; mean age, 59 years) were characterized by nuclear pleomorphism (n=22), mitoses (n=21), loss of pattern (n=21), necrosis (n=21), nucleoli (n=17), and hypervascularity/hemosiderin deposition (n=3). Significant differences were found between the aggressive and malignant groups with regard to loss of pattern, necrosis, and nucleoli (P=.0043, .011, and .00029, respectively). Mean MIB-1 LIs for the benign, aggressive, and malignant groups were 1.0% (range, 0 to 5.5%),5.5% (range, 0.1 to 32.5%), and 12.0% (range, 0.3 to 32.5%), respectively. Differences in the mean MIB-1 LI between groups were statistically significant, with P values of <.0001 (benign v aggressive) and .0012 (aggressive v malignant). Mean MIB-1 LIs for recurrent versus nonrecurrent tumors were 7.1% (range, 0 to 32.5%) versus 3.8% (range, 0 to 20.9%) (P=.32). The mean MIB-1 LI for patients who were alive with or without tumor was 6.2% (range, 0 to 32.5%) versus a mean MIB-1 LI of 14.2% (range, 2.8% to 32.5%) for patients who died of or with tumor (P=.0013).

In conclusion, (1) There is a statistically significant difference in the increasing MIB-1 LI means between benign, aggressive, and malignant meningiomas and between patients who were alive versus those who died; (2) there is some overlap in MIB-1 LI ranges between groups, which warrants caution in interpreting an individual MIB-1 LI in a given tumor.

Histopathologic features and MIB-1 labeling indices in recurrent and nonrecurrent meningiomas.

Abramovich CM, Prayson RA.

Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Arch Pathol Lab Med 1999 Sep;123(9):793-800 Abstract quote

BACKGROUND: Predicting the behavior of meningiomas based on histopathologic features alone has remained problematic.

DESIGN: This study retrospectively compared several histopathologic features and MIB-1 labeling indices (LIs) in recurrent meningiomas with those of nonrecurrent meningiomas. Six histopathologic features, including mitoses, necrosis, loss of architectural pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared between 32 recurrent and 27 nonrecurrent meningiomas using Fisher exact tests. MIB-1 LIs (% positive tumor cell nuclei) were compared using the Wilcoxon rank sum test.

RESULTS: The patients in the recurrent group included 26 women (mean age, 55 years), who developed 1 to 5 recurrences. Time intervals to the first recurrence ranged from 5 to 183 months (mean, 55 months). The nonrecurrent group included 21 women (mean age, 56 years), with follow-up ranging from 88 to 124 months (mean, 109 months). Of the histopathologic features evaluated, statistically significant differences between the recurrent and nonrecurrent groups were found only with respect to prominent nucleoli (P =.024) and nuclear pleomorphism (P <.001), both of which were more common in the recurrent group. In the recurrent group, 9 tumors were considered malignant (defined by brain invasion or metastasis) versus 2 of the nonrecurrent meningiomas. Nineteen percent of nonrecurrent tumors versus 41% of recurrent tumors had 2 or more of the 6 histopathologic features. MIB-1 LIs in the nonrecurrent group ranged from 0 to 8.3 (mean, 1.5) and were generally lower than those in the recurrent group (range, 0-32.5; mean, 5.4); no statistical difference was identified between these groups. No statistically significant difference with regard to histology or MIB-1 LIs was noted between the initially excised recurrent tumor and the most recently resected recurrence.

CONCLUSIONS: Of the histopathologic features examined, only prominent nucleoli and nuclear pleomorphism were found to be statistically more common in recurrent than nonrecurrent meningiomas. The mean MIB-1 LI was higher in the recurrent than in the nonrecurrent group, although there was no statistical difference between means and there was clear overlap with regard to MIB-1 LI ranges.

MIB-1 staining index of pediatric meningiomas.

Sandberg DI, Edgar MA, Resch L, Rutka JT, Becker LE, Souweidane MM.

Division of Neurosurgery, New York Presbyterian Hospital and the Weill Medical College of Cornell University, New York, USA.

Neurosurgery 2001 Mar;48(3):590-5; Abstract quote

OBJECTIVE: For adult meningiomas, the staining index (SI) for the anti-Ki-67 monoclonal antibody MIB-1 is well correlated with histological atypia and tumor recurrence. MIB-1 SIs for meningiomas in the pediatric population have not been previously reported. Meningiomas tend to be more histologically aggressive and to recur more frequently in children, compared with adults. The objectives of this study were to determine whether MIB-1 SIs are correlated with pathological atypia and recurrence among pediatric meningiomas and to compare the MIB-1 SIs of pediatric meningiomas with those of adult meningiomas.

METHODS: MIB-1 SIs were assessed on paraffin-embedded sections of 14 pediatric meningiomas (patient age, 2-17 yr), 5 of which contained atypical or malignant features. For comparison with benign pediatric meningiomas, MIB-1 SIs were also assessed on paraffin-embedded sections of 14 adult meningiomas (patient age, 38-90 yr), none of which displayed atypical or malignant features or recurred within a 5-month median follow-up period.

RESULTS: MIB-1 SIs of pediatric meningiomas ranged from 1.2 to 31.6% (median, 9.1%). Significant differences were observed between the MIB-1 SIs for tumors with atypical or malignant features (median, 12.3%; range, 7.0-31.6%) and those for tumors without atypia (median, 7.0%; range, 1.2-12.6%; P = 0.045). There were six recurrences after gross total resection, during a 36.5-month median follow-up period. All five of the tumors with pathological atypia recurred; one tumor without atypia recurred. Significant differences were observed between MIB-1 SIs for nonrecurrent tumors (median, 6.6%; range, 1.2-12.2%) and those for recurrent tumors (median, 12.5%; range, 7.0-31.6%; P = 0.012). The median MIB-1 SI for adult control specimens was 8.8% (range, 1.2-19.3%), which did not differ significantly from that for pediatric meningiomas without atypia (P = 0.68).

CONCLUSION: For this cohort of pediatric meningiomas, pathological atypia and the tendency to recur were correlated with elevated MIB-1 SIs. The median MIB-1 SI for pediatric meningiomas without histological atypia did not differ significantly from that for adult meningiomas without atypia, suggesting that the more aggressive clinical features of meningiomas in children may be attributable to factors other than the rate of cellular proliferation.

Significance of MIB-1 Staining Indices in Meningiomas Comparison of Two Counting Methods

Satoshi Nakasu, etal.

Am J Surg Pathol 2001;25:472-478 Abstract quote

The authors evaluated the predictability of MIB-1 immunohistochemistry for growth and recurrences of meningiomas using two different counting methods: 1) in the area of the highest MIB-1 labeling (HL method) and (2) in randomly selected fields (RS method). The MIB-1 staining indices (SIs) determined by the HL method were approximately twice as high as those by the RS method, and the correlation coefficient between them was high (R = 0.86) in 139 meningiomas when transformed logarithmically.

The differences in SIs in histologic grades were significant with either method. Tumor doubling time (Td) was calculated in 22 meningiomas from serial radiologic examinations. The RS method yielded a slightly higher correlation coefficient between log Td and log SI than the HL method. When the authors examined the predictability of recurrence in 112 totally removed meningiomas, the RS method distinguished the recurrent group more definitively. Several benign meningiomas with low SIs by the RS method exhibited focal accumulation of MIB-1-positive cells. Although they were assigned high MIB-1 values by the HL method, these meningiomas did not recur, and therefore obscured the prognostic importance of the MIB-1 value with the HL method.

Focal accumulation of MIB-1-positive cells in meningiomas is not likely to correlate with their biologic aggressiveness.

Immunohistochemical study of Ki-67 (MIB-1), p53 protein, p21WAF1, and p27KIP1 expression in benign, atypical, and anaplastic meningiomas

Vishwa Jeet Amatya, MBBS
Yukio Takeshima, MD Kazuhiko Sugiyama, MD Kaoru Kurisu, MD Takashi Nishisaka, MD Toshiyuki Fukuhara, MD Kouki Inai, MD

Hum Pathol 2001;32:970-975 Abstract quote

Histologic grading of meningiomas has prognostic and clinical therapeutic implications. Meningiomas were histologically classified into 3 different World Health Organization grades. Grade II, an atypical meningioma, was defined by major and various minor histologic criteria. However, these histologic criteria sometimes are not fulfilled, and other criteria are necessary.

We studied and analyzed the immunohistochemical expression of MIB-1, p53, p21WAF1, p27KIP1 proteins in 146 cases of meningiomas, including 109 benign, 27 atypical, and 10 anaplastic meningiomas. Most of the benign meningiomas expressed low MIB-1 labeling index (mean, 1.5%), and fewer cases had p53 protein expression. In contrast, the anaplastic meningiomas had a high labeling index of MIB-1 (mean, 19.5%) and always expressed p53 protein, with a mean labeling index of 6.3%. The atypical meningiomas had MIB-1 and p53 labeling indexes in the range between benign and anaplastic meningiomas, with mean labeling indexes of 8.1% and 3.5%, respectively. These expressions were statistically significant among benign, atypical, and anaplastic meningiomas (P < .001).

We conclude that the immunohistochemistry of MIB-1 and p53 protein will be valuable in discriminating atypical meningiomas from benign or anaplastic meningiomas, at least in histologically borderline cases. In addition, we also found direct correlation of p21 and inverse correlation of p27 expressions in meningiomas with increasing histologic grade and proliferative index.


DNA Topoisomerase II-alpha and Cyclin A Immunoexpression in Meningiomas and Its Prognostic Significance.

Korshunov A, Shishkina L, Golanov A.

Departments of Neuropathology (Dr Korshunov and Dr Shishkina) and Neuro-oncological Surgery (Dr Golanov), Burdenko Neurosurgical Institute, Moscow, Russia.


Arch Pathol Lab Med 2002 Sep;126(9):1079-86 Abstract quote

Context.-Routine pathologic examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Therefore, numerous efforts have been made to evaluate the meningioma growth fraction and its prognostic value. However, a universally applicable proliferative marker for meningioma outcome is not yet a reality.

Objective.-To investigate the prognostic utility of 3 proliferative markers, namely, Ki-67, DNA topoisomerase II-alpha (topoII), and cyclin A in a representative series of intracranial meningiomas.

Design.-Two hundred sixty-three adult patients with intracranial meningiomas (208 benign, 42 atypical, and 13 anaplastic) were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to Ki-67 (MM-1), topoII, and cyclin A. A computerized color image analyzer was used to count immunostained nuclei.

Results.-The topoII and cyclin A scores exhibited a close correlation with Ki-67 immunostaining. Significant differences between the indices for all 3 markers were noted among the 3 grades of meningiomas. The scores for all 3 markers were significantly different between recurrent and nonrecurrent meningiomas, including benign tumors that were treated with gross total resection. Recurrence-free survival was significantly reduced for cases with a Ki-67 labeling index (LI) of 4.4% or greater, a topoII LI of 3.2% or greater, and a cyclin A LI of 3.1% or greater. Multivariate analysis revealed that the risk of recurrence for the entire meningioma cohort was significantly associated with tumor grade (hazard ratio = 2.7; P =.004), topoII LI of 3.2% or greater (hazard ratio = 5.5; P <.001), and a cyclin A LI of 3.1% or greater (hazard ratio = 2.4; P =.01).

Conclusions.-There is a close correlation in the expression of these 3 proliferative markers in meningiomas, and all of the markers showed a significant association with tumor grade, recurrence rate, and recurrence-free survival. Consequently, in addition to Ki-67, immunoexpression of topoII and cyclin A is available for predicting meningioma recurrence. Moreover, the topoII and cyclin A staining scores were found to be more sensitive predictors for meningioma progression than Ki-67 and, therefore, either of these 2 markers may prove to be clinically informative and useful.


Secondary intracranial meningiomas after high-dose cranial irradiation: report of five cases and review of the literature.

Strojan P, Popovic M, Jereb B.

Department of Radiotherapy, Institute of Oncology, Ljubljana, Slovenia.

Int J Radiat Oncol Biol Phys 2000 Aug 1;48(1):65-73 Abstract quote

PURPOSE: To review cases of secondary intracranial meningiomas following high-dose cranial irradiation (>/= 10 Gy) identified in Slovenia between 1968 and 1998, to determine their histological profile and to review the literature on this topic.

METHODS AND MATERIALS: Personal files of patients treated for secondary intracranial meningioma during a 31-year period were reviewed. In cases which met the criteria for radiation-induced tumors, steroid hormone receptor and Ki-67 status were analyzed. For the literature review, computerized database systems and reference lists from respective publications were used.

RESULTS: Five patients (2 females, 3 males), 3-11 years old at the time of cranial irradiation, developed secondary meningioma after a latency period of 9.5-31.5 years. Three patients had multiple tumors and 2 developed recurrent disease. Of 9 histologically examined tumors, 5 were graded as benign and 4 as atypical meningiomas, with Ki-67 proliferative index 3.2 +/- 3.6 and 10 +/- 6, respectively. The ratio between positive and negative meningiomas regarding immunostaining for progesterone and estrogen receptors was eight-to-one and six-to-three, respectively. Cumulative actuarial risk of secondary meningioma in a cohort of 445 children 16 years or younger treated with high-dose cranial irradiation between 1968 and 1990 in Slovenia at 10, 20, and 25 years was 0.53%, 1.2%, and 8.18%, respectively. Out of 126 cases of radiation-induced meningiomas reported, 57% were females and 43% were males, with mean age at presentation 33 +/- 17.3 years. The majority (68%) of patients was irradiated during childhood. The latency period was significantly shorter in those who aged 5 years or less at the time of cranial irradiation (p = 0.04), and in those with atypical/anaplastic tumor (p = 0.01). Correlation between radiation dose and latency period could not be found.

CONCLUSION: Secondary meningiomas following high-dose cranial irradiation are characterized by younger age at presentation, by higher male-to-female ratio and by biologically more aggressive variants compared to primary spontaneous meningiomas. Latency period correlated with the age at the time of cranial irradiation and with tumor grade but not with irradiation dose. Ki-67 immunoreactivity correlated with histological grade. The progesterone and estrogen receptor immunoreactivity was high. The risk for development of secondary meningioma after high-dose cranial irradiation was increasing with the time of follow-up.


Surgical management of clinoidal meningiomas.

Lee JH, Jeun SS, Evans J, Kosmorsky G.

Department of Neurosurgery, The Cleveland Clinic Foundation, Ohio 44195, USA.

Neurosurgery 2001 May;48(5):1012-9; Abstract quote

OBJECTIVE: Surgical outcome has been less than desirable in the management of patients with clinoidal meningiomas in the past, and little attention has been directed at improving their visual function. The purpose of this article is to advocate an available cranial base technique for removing these difficult tumors and to delineate the technique's advantages that aid in achieving an improved extent of tumor resection and enhancing the patients' overall outcome, particularly their visual outcome.

METHODS: A retrospective analysis was performed on 15 consecutive patients with clinoidal meningiomas (including a patient with hemangiopericytoma) who underwent surgical resection at the Cleveland Clinic Foundation between June 1995 and January 2000. A cranial base technique consisting of extradural anterior clinoidectomy, coupled with optic canal unroofing and optic sheath opening, was used in 13 patients, and standard pterional craniotomy was used in 2. Eight of 15 patients had significant visual deficits preoperatively. All patients had thorough preoperative and postoperative ophthalmological evaluations. The follow-up period ranged from 6 to 60 months (mean, 37.2 mo).

RESULTS: Total resection was achieved in 13 (86.7%) of the 15 patients in this series, and the majority of the patients with preoperative visual impairment experienced significant improvement (6 of 8 patients; 75%).

CONCLUSION: In the majority of patients with clinoidal meningiomas, total resection may be achieved with minimal complications. For large tumors encasing the optic nerve and internal carotid artery, or for those tumors causing preoperative visual impairment, use of the cranial base technique delineated in this study may lead to significant improvement in the patients' visual and overall outcomes.

RADIATION Localized irradiation in smaller tumors

Gamma knife radiosurgery in the management of cavernous sinus meningiomas.

Roche PH, Regis J, Dufour H, Fournier HD, Delsanti C, Pellet W, Grisoli F, Peragut JC.

Service de Neurochirurgie, CH St. Marguerite, Marseille, France.

J Neurosurg 2000 Dec;93 Suppl 3:68-73 Abstract quote

OBJECT: The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS).

METHODS: Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6-71 years). The mean tumor volume was 5.8 cm3 (range 0.9-18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12-50 Gy), delivered with an average of eight isocenters (range two-18). The median peripheral isodose was 50% (range 30-70%).

RESULTS: Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12-79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred.

CONCLUSIONS: Gamma knife radiosurgery was found to be an effective low morbidity-related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.

Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy.

Hug EB, Devries A, Thornton AF, Munzenride JE, Pardo FS, Hedley-Whyte ET, Bussiere MR, Ojemann R.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

J Neurooncol 2000 Jun;48(2):151-60 Abstract quote

OBJECTIVE: Atypical and malignant meningiomas are at high risk for local failure. The role of radiation therapy (RT) and dose levels required to improve tumor control are poorly defined. This study reviews our experience with RT.

MATERIAL AND METHODS: Thirty-one patients underwent fractionated RT for atypical (AM, 15 patients) or malignant meningioma (MM, 16 patients) of the cranium. Sixteen patients presented with primary and 15 with recurrent disease. Eight patients received RT following total resection, 21 patients after subtotal resection and 2 patient following biopsy only. RT was given using megavoltage photons in 15 patients and combined photons and 160 MeV protons in 16 patients. Total target doses ranged from 50 to 68 (AM, mean 62) and from 40 to 72 (MM, mean 58) Gy or CGE (= cobalt-gray-equivalent).

RESULTS: With mean observation time of 59 months (range: 7-155 months) actuarial local control rates at 5- and 8-years were similar for both histologies (38% and 19% for AM and 52 and 17% for MM). However, significantly improved local control was observed for proton versus photon RT (80% versus 17% at 5 years, p = 0.003) and target doses > or = 60 Gy for both, atypical (p = 0.025) and malignant meningioma (p = 0.0006). At time of analysis, 14/15 patients (93%) with AM and 6/16 (38%) with MM were alive. Three patients (19%) with MM developed distant metastasis. Actuarial 5- and 8-year survival rates for MM were significantly improved by use of proton over photon RT and radiation doses > 60 CGE. Three patients developed symptomatic radiation damage after 59.3, 68.4 and 72 Gy/CGE.

CONCLUSION: Conformal, high dose RT resulted in significant improvement of local control for atypical and malignant meningiomas. Increased local control resulted also in improved rates of survival for patients with malignant meningioma.

Gamma knife radiosurgery for skull base meningiomas.

Pollock BE, Stafford SL, Link MJ.

Department of Neurological Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.

Neurosurg Clin N Am 2000 Oct;11(4):659-66 Abstract quote

Radiosurgery has been proven to be a safe and effective management strategy for skull base meningiomas either primarily or for tumor recurrence or progression after prior microsurgical resection. With its steep radiation falloff, radiosurgery provides long-term tumor growth control without the complications associated with conventional fractionated radiation therapy. Stereotactic MR imaging has allowed better definition of the tumor margin for precise multiisocenter conformal dose planning, and our current radiation dose prescription has decreased the incidence of new cranial nerve deficits after radiosurgery to less than 10%. Tumor growth control after radiosurgery remains greater than 90%; patients with subsequent growth typically have tumor outside the irradiated volume or a histologic diagnosis of atypical or malignant meningioma. Still, longer follow-up is needed to ensure that tumor growth control remains permanent after radiosurgery. For patients with large tumors of the skull base, radiosurgery can be part of a staged approach with microsurgery. Initially, the tumor is debulked without an attempt at resection involving the cranial nerves or basal vessels. Radiosurgery can then be performed for the small remaining tumor volume with little risk of cranial nerve deficits. Such multimodality treatment should result in reduced patient morbidity, with long-term tumor control.


A phase II evaluation of tamoxifen in unresectable or refractory meningiomas: a Southwest Oncology Group study.

Goodwin JW, Crowley J, Eyre HJ, Stafford B, Jaeckle KA, Townsend JJ.

Ozarks CCOP, Springfield, MO.

J Neurooncol 1993 Jan;15(1):75-7 Abstract quote

Twenty-one patients with nonresectable refractory meningiomas were registered on a study giving tamoxifen 40 mg per M2 b.i.d. for four days, then 10 mg b.i.d. thereafter. Nineteen were eligible and evaluated for response.

One patient (5%) achieved an MRI-documented partial response while two had a minor response measured on CT scan which was of short duration (4 and 20 months). Six patients (32%) remained stable for a median duration of 31 + months while ten (53%) demonstrated progression. Twenty-two percent (22%) reported subjective improvement though this did not correlate with objective improvement in all cases.

At present, a definite recommendation for the use of tamoxifen in refractory meningiomas cannot be made. Further evaluation of hormonal therapy of meningiomas with a consensus for definition of endpoints for evaluation of response in view of the difficulty of evaluating radiologic findings with clinical outcome, is needed.

Hydroxyurea for treatment of unresectable and recurrent meningiomas. II. Decrease in the size of meningiomas in patients treated with hydroxyurea.

Schrell UM, Rittig MG, Anders M, Koch UH, Marschalek R, Kiesewetter F, Fahlbusch R.

Department of Neurosurgery, University of Erlangen-Nurnberg, Germany.

J Neurosurg 1997 May;86(5):840-4 Abstract quote

In this paper the authors present the first evidence that meningiomas respond to treatment with hydroxyurea. Hydroxyurea was administered as an adjunct chemotherapeutic treatment in patients with recurrent and unresectable meningiomas. Hydroxyurea was used because experimental data demonstrated that it inhibits growth of cultured human meningioma cells and meningioma transplants in nude mice by inducing apoptosis.

The authors therefore treated four selected patients with hydroxyurea. All patients had undergone multiple gross resections and all except one received radiotherapy. Three patients with recurrent Grade I meningiomas assessed according to World Health Organization (WHO) guidelines received hydroxyurea because of an increased tumor growth rate, documented by magnetic resonance (MR) imaging, within a 6- or 12-month interval. A fourth patient with a malignant meningioma (WHO Grade III) began a course of treatment with hydroxyurea immediately after his sixth palliative operation without waiting for another relapse to be demonstrated on MR imaging. Because of their location and invasive growth behavior none of the meningiomas could have been removed completely by surgical intervention. All patients received hydroxyurea at a dosage level of 1000 to 1500 mg/day (approximately 20 mg/kg/day). In a man with a large sphenoid wing meningioma invading the right cavernous sinus and the temporal base, the intracranial tumor mass was reduced by 60% during 6 months of treatment. A woman with a large ball-shaped meningioma of the right sphenoid wing invading the cavernous sinus exhibited a 74% decrease of the initial tumor volume in 10 months of treatment with oral hydroxyurea. Serial MR images obtained monthly revealed that the process of size reduction was continuous and proportionate. The shrinkage of the tumor was accompanied by a complete remission of symptomatic trigeminal neuralgia after 2 months and by improved abducent paresis after 5 months. The third patient had a slowly growing meningioma that exhibited a 15% reduction in mass when reassessed after 5 months of hydroxyurea treatment. The fourth patient with the malignant meningioma in the left cerebellopontine angle has had no recurrence for 24 months.

Long-term treatment with hydroxyurea may result in full remission of tumors in meningioma patients. The preliminary data indicate that hydroxyurea provides true medical treatment in patients with unresectable and recurrent meningiomas, replacing palliative surgery and radiotherapy in the management of this disease.

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