Progesterone-receptor index in meningiomas: correlation with clinico-pathological parameters and review of the literature

For recurrent and untreatable meningiomas alternative therapies, such as anti-progesterone treatment, have been sought. However, the few clinical studies have not determined progesterone receptor (PgR) expression in most cases, and studies correlating quantitative PgR expression (PgR index) with clinico-pathological variables are scarce. The aim of our study was to assess the PgR indices in a consecutive series of meningiomas and correlate these values with clinico-pathological parameters. We analyzed immunohistochemically 82 consecutive meningioma specimens (73 primary and nine recurrent tumors) for PgR and Ki-67 antigen (MIB-1). The male/female ratio was 1:1.7, and median age at the time of surgery was 57 years (range 29–77 years). The series comprised 55 grade I (subtyped as 36 meningothelial, seven fibrous, nine transitional, two psammomatous, and one angiomatous), 23 grade II, and one grade III meningiomas. Nuclear immunostaining for PgR was positive in 56 meningioma specimens (71%). PgR index was 21.4±2.8% (mean ± SE; range 0–79%). Significantly higher expression was found in male patients in the age group <50 years than in those 60 years and in grade I meningothelial meningiomas than in fibrous and transitional subtypes. There was a trend to lower PgR indices in non-benign meningiomas. Cell proliferation rate (MIB-1 index) was 4.4±0.4% (mean ± SE; range 0.3–15.4%). Significantly higher MIB-1 indices were found in male than female patients,in recurrent than primary and in grade II than grade I meningiomas. We observed a trend to higher PgR indices in meningiomas with MIB-1 index <5%. In sum, the highest PgR index in our series was observed in patients under the age of 50 years with WHO grade I meningiomas of the meningothelial subtype and low cell proliferation indices. If hormonal therapy has a direct action on the PgR, these patients should respond best to anti-progesterone treatment. We conclude that PgR index is variable in meningioma, depending on clinical parameters and histopathological features. Stratification of anti-progesterone therapy trials on the basis of PgR index should be considered.     

Primary pulmonary malignant meningioma.

Fewer than 20 cases of primary pulmonary meningioma have been reported. Most of these cases have been histologically and clinically benign. We report an unusual case of primary pulmonary malignant meningioma with atypical histologic features and malignant behavior. A computed tomography scan of the head did not show evidence of tumor. The right upper lobe mass was resected and showed features of an atypical meningioma with loss of architectural pattern, mild nuclear pleomorphism, increased mitotic counts (up to 15 mitotic figures per 10 high power fields), and focally prominent nucleoli. Focally, cells with rhabdoid features were identified. The tumor's immunohistochemical and ultrastructural profiles were consistent with a meningioma. The tumor stained negative for estrogen and focally positive for progesterone receptors and had a MIB-1 labeling index (marker of cell proliferation) of 9.2%. Approximately 5 months after the initial resection, the patient experienced a tumor recurrence with multiple lymph node metastases, spread to the middle and lower lobes of the right lung, and metastasis to the diaphragm. Rarely, primary pulmonary meningiomas may present as high-grade malignant lesions.     

P53 Overexpression and Proliferative Potential in Malignant Meningiomas

Summary  Meningiomas are generally benign, but some meningiomas show malignancy with invasion and high recurrence rates. We investigated whether alterations in p53 protein may contribute to malignant progression in meningiomas. Immunostaining for p53 protein was performed on paraffin and frozen sections from 61 patients with different grades of meningiomas using monoclonal antibodies (mAbs) DO-1 and pAb240. Immunoblot analysis was performed to quantitate the amount of p53 protein. Mutations in p53 genes were assessed by single-strand conformational polymorphism (SSCP) analysis. MIB-1 immunostaining was used to detect proliferative potentials of meningiomas. We found an overexpression of p53 protein in all of five cases of anaplastic meningiomas by immunohistochemistry using DO-1 mAb. No p53 positive cells were recognized in atypical meningiomas, and several cells were weakly stained in only two of 52 benign meningiomas.  p53 staining index and immunoblot analysis indicated increasing amounts of p53 protein associated with subsequent recurrences of anaplastic meningiomas. The MIB-1 staining index was positively correlated with tumour grade and p53 protein overexpression. Immunostaining of frozen sections using the mutant-specific mAb pAb240, as well as mutation gene analysis by SSCP, indicate that the overexpressed p53 protein is not a mutant- but wild-type p53 protein. Four atypical meningiomas did not recur after surgical removal and radiation, while 4 anaplastic meningiomas with overexpressed p53 protein recurred repeatedly at short intervals even after radiation. Our results suggest that accumulation of p53 protein associated with highly proliferative potentials is a common and characteristic feature that may indicate malignant biological behaviour in meningiomas.     

Anaplastic meningioma with extremely rapid recurrence

A 62-year-old woman presented with an uncommon case of anaplastic meningioma manifesting as recent memory disturbance. Magnetic resonance imaging revealed a mass located in the right temporal lobe. She became unconscious because of uncal herniation and underwent urgent surgery. The tumor was completely resected, except for a lesion tightly attached to arteries. Histological examination indicated the presence of anaplastic meningioma with an extremely high MIB-1 labeling index (70%). After 43 days, the patient developed local recurrence and dissemination in the left temporal lobe. The exceptionally high MIB-1 labeling index corresponded with a short tumor doubling time (8.2 days). Whole-brain irradiation and linear accelerator surgery for disseminated lesions were performed, and the tumor growth halted. Although meningiomas rarely show malignant behavior, corresponding to World Health Organization grade III, it is necessary to consider malignant behavior when treating meningiomas.     

Malignant progression in meningioma: documentation of a series and analysis of cytogenetic findings

OBJECT: The malignant progression of benign tumors is well documented in gliomas and other systemic lesions. It is also well known that some meningiomas become progressively aggressive despite their original benign status. The theory of clonal evolution is widely believed to explain malignant progression in meningioma; however, the data used to explain stepwise progression have typically been derived from the cytogenetic analysis of different types of tumors of different grades and in different patients. In this study, the authors examined the data obtained in a group of patients with meningiomas that showed clear histopathological progression toward a higher grade of malignancy and then analyzed the underlying cytogenetic findings. METHODS: Among 175 patients with recurrent meningiomas, 11 tumors showed a histopathological progression toward a higher grade that was associated with an aggressive clinical course. Six tumors progressed to malignancy and five to the atypical category over a period averaging 112 months. Tests for MIB-1 and p53 and cytogenetic studies with the fluorescence in situ hybridization (FISH) method were performed in successive specimens obtained in four patients. The MIB-1 value increased in subsequent samples of tumors. Cytogenetic analysis with FISH showed deletions of 22, 1p, and 14q. In all but one case, these aberrations were also present in the previous specimen despite its lower hispathological grade. CONCLUSIONS: The authors documented the progression of meningiomas from benign to a higher histological grade. These tumors were associated with a complex karyotype that was present ab initio in a histologically lower-grade tumor, contradicting the stepwise clonal evolution model. Although it was limited to the tested probes, the FISH method appears to be more accurate than the standard cytogenetic one in detecting these alterations. Tumors that present with complex genetic alterations, even those with a benign histological grade, are potentially aggressive and require closer follow up.     

Noninvasive evaluation of the malignant potential of intracranial meningiomas performed using proton magnetic resonance spectroscopy

OBJECT: Controversy exists about correlations between histological tumor grade and magnetic resonance (MR) spectroscopy data. The authors studied single-voxel proton MR spectroscopy as a noninvasive way to evaluate grade of malignancy in intracranial meningiomas. METHODS: The authors compared the results of MR spectroscopy with those derived by the MIB-1 staining index (SI) in 29 meningiomas. Proton MR spectroscopy was performed using stimulated echo acquisition and volume-localized solvent-attenuated proton nuclear MR sequences before surgery or other therapy. Twenty-four tumors were histologically benign (13 meningothelial, three fibrous, four transitional, three angiomatous, and one chordoid); four were atypical (Grade II), and one was papillary (Grade III). The mean MIB-1 SI in the benign group was significantly lower than those in the other groups (p = 0.0041). The mean choline-containing compound (Cho)/ creatine and phosphocreatine (Cr) ratios in the benign and nonbenign groups were 2.56+/-1.26 and 7.85+/-3.23, respectively (p = 0.0002). A significant linear correlation was observed between the Cho/Cr ratio and the MIB-1 SI (r0.05 = 0.74, p<0.001). Necrosis was present histologically in four of the five meningiomas classified either as atypical or papillary. Magnetic resonance spectroscopy revealed a methylene signal in these meningiomas that was not detected in benign meningiomas. Of the five meningiomas in which only a lactate signal was observed, two were benign and the MIB-1 SI in these two benign meningiomas was higher than the mean value for the benign group. Alanine, detected in 12 of 30 meningiomas, did not correlate with either tumor grade or Cho/Cr ratio. CONCLUSIONS: Proton MR spectroscopy is a useful diagnostic method for determining the proliferative or malignant potential of meningiomas according to the Cho/Cr ratio. A lactate and/or methylene signal suggests a high-grade tumor.     

Histopathologic features predicting recurrence of meningiomas following subtotal resection

Histopathologic features that predict recurrence of meningiomas following subtotal resection were identified by reviewing the initial surgical specimens from 82 patients (38 with tumor recurrence and 44 without) treated at the Massachusetts General Hospital between 1962 and 1984. There was no correlation between histologic subtype and tendency toward tumor recurrence; however, the few examples of hemangiopericytoma, angioblastic meningioma, or sarcomatous meningioma were observed almost exclusively in patients with recurrent tumors. Seven histopathologic features were positively correlated with recurrence of meningiomas, including the following: hypervascularity of tumors, hemosiderin deposition, growth of tumor cells in sheets rather than the usual growth patterns of meningiomas, prominent nucleoli, mitotic figures, single-cell and small-group necrosis, nuclear pleomorphism, and overall atypical or malignant tumor grade (all p less than 0.005). In addition, sheeting of tumor cells, prominent nucleoli, and the presence of less than 10% meningothelial pattern were correlated with significantly abbreviated progression-free survival, i.e., more rapid progression of tumor with shorter intervals between treatment and tumor recurrence. These findings suggest that the presence of features such as large prominent nucleoli, tumor growth in sheets, individual-cell necrosis, and nuclear pleomorphism may be used to predict recurrence of subtotally resected meningiomas that would not be classified as malignant by traditional criteria.     

MIB-1 staining index of pediatric meningiomas

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.     

Radiosurgery for Atypical and Anaplastic Meningiomas: Histopathological Predictors of Local Tumor Control

Objectives: We investigated the radiosurgical outcomes of patients with nonbenign meningiomas retrospectively and sought to identify prognostic factors for local tumor control after radiosurgery with an emphasis on histopathology. Methods: Between 1998 and 2010, 35 patients with 49 atypical or anaplastic meningiomas were treated with radiosurgery. The mean tumor volume and marginal irradiation dose were 3.5 cm(3) (range 0.3-25.3) and 16 Gy (range 12-21), respectively. Results: The actuarial local tumor control rates for patients with atypical meningiomas at 1, 2 and 3 years after radiosurgery were 78, 53 and 36%, respectively, whereas those for anaplastic meningiomas were 35% at 1 year and 10% at 2 years. Multivariate analysis revealed that the mitotic count (≤8 per 10 high-power fields; HPF) and the MIB-1 proliferation marker labeling index (LI; ≤8%) were significant favorable prognostic factors for the radiosurgical outcomes of patients with nonbenign meningiomas (p = 0.014 and p = 0.012, respectively). Conclusions: Radiosurgery could be a treatment option for patients with atypical meningiomas, but more aggressive treatments are needed for those with anaplastic meningiomas. Histopathological factors such as mitotic count and MIB-1 LI are significant prognostic factors for the radiosurgical outcomes of patients with nonbenign meningiomas and should be considered before radiosurgery.     

Association between absence of epidermal growth factor receptor immunoreactivity and poor prognosis in patients with atypical meningioma

OBJECT: The clinical behavior of meningiomas is variable. Because multiple growth factor receptors have been identified in these tumors, the authors sought to assess the capacity of the expression patterns of a subset of these receptors to stratify meningioma cases. METHODS: Eighty-four meningiomas were analyzed, including 36 benign, 29 atypical, and 19 malignant lesions. Immunohistochemical staining was performed for epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR)-beta, basic fibroblast growth factor receptor (BFGFR), and MIB-1. Survival analyses were performed using follow-up data obtained in patients with newly diagnosed tumors. Immunoreactivity for EGFR was observed in 47% of benign, 48% of atypical, and 42% of malignant tumors. Staining for BFGFR was identified in 89% of benign, 97% of atypical, and 95% of malignant lesions. Immunostaining for PDGFR-beta was evident in all the lesions assessed. Mean MIB-I indices for benign, atypical, and malignant cases were 3.6 (range 0.5-15.3), 8.2 (range 1.5-23.1) and 18.3 (range 1.0-55.8), respectively. Overall mean follow-up duration was 9.0 years (range 5.1-18.8 years). Lack of EGFR immunoreactivity was identified as a strong predictor of shorter overall survival in patients with atypical meningioma (p = 0.003, log-rank test). This association was not evident in cases of benign or malignant meningiomas. CONCLUSIONS: There is a significant association between EGFR immunoreactivity and prolonged survival in patients with atypical meningioma. Given the variable behavior of atypical meningiomas, EGFR assessment could improve existing strategies for patient stratification and treatment.     

Rhabdoid transformation of recurrent meningioma in the cervical cord: a case report

We report a case of persistent local recurrence of rhabdoid meningioma in the cervical spinal cord. Recently, the meningioma has been reported to be undergoing rhabdoid transformation, but the clinical course is still unclear. Histopathological examination of the tumor showed that it was composed of both meningothelial cells and rhabdoid cells. At each recurrence of the tumor, the population of the rhabdoid cells had increased and the ability to grow had also increased, confirmed by the MIB-1 labeling index. This case showed that phenotypic change of the cells with rhabdoid morphology may affect meningiomas and that such changes are associated with aggressive biological and clinical behavior. This newly classified tumor should be recognized in the differential diagnosis of meningioma.     

Angiomatous meningioma: a clinicopathologic study of 38 cases

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.     

Recurrence in meningeal hemangiopericytomas

BACKGROUND Meningeal hemangiopericytomas are more aggressive than typical meningiomas, with a high rate of recurrence and distant metastases. The question of whether a correlation exists between prognosis and histologic features remains controversial.

CASE DESCRIPTION

We report two cases of recurrent meningeal hemangiopericytomas. Although local growth control of the tumor was obtained by tumor removal and irradiation in a 38-year-old male patient (Case 1) with a recurrent tentorial tumor, the tumor disseminated and metastasized extracranially within a short period after treatment, leading to rapid deterioration. Another 38-year-old female patient (Case 2) with a recurrent orbital tumor had a favorable outcome after tumor removal. The Ki-67 proliferative index using the MIB-1 monoclonal antibody increased as the tumor recurred in Case 1 (2.5%, 7.9%, and 15.7%), but did not change between primary and recurrent tumors of Case 2 (4.2%, 3.1%). Immunostaining for p53 protein in Case 1 was negative at the first resection, and became positive at the second and third resections, whereas in Case 2, it was negative in both the primary and recurrent tumors.

CONCLUSIONS Our results suggest that p53 protein accumulation with a high proliferative potential is a useful marker to estimate malignant progression in meningeal hemangiopericytomas.     

Surgical resection and permanent brachytherapy for recurrent atypical and malignant meningioma

OBJECTIVE: Recurrent atypical and malignant meningiomas are difficult to treat successfully. Chemotherapy to date has been unsuccessful, and radiosurgery is limited to smaller tumors. Reoperation alone provides limited tumor control and limited prolonged survival. The addition of brachytherapy at the time of operation is an option. Here, we report the results of our series of patients with recurrent malignant meningioma treated with resection and brachytherapy with permanent low-dose (125)I. METHODS: The charts of patients in our database with recurrent atypical and malignant meningiomas treated by surgical resection and permanent (125)I brachytherapy at the University of California, San Francisco, between 1988 and 2002 were selected for this study. Calculations of disease-free survival and overall survival curves were made by the Kaplan-Meier actuarial method. Univariate analysis between Kaplan-Meier curves was based on the log-rank statistic, with a significance level set at a value of P 相似文献   

A case of recurrent convexity meningioma with malignant transformation 26 years after total tumor removal

Meningiomas are common intracranial tumors, the majority of which are considered benign. However, they sometimes show altered biologic behavior, associated with local aggressiveness and late distant metastasis. We report a patient with a convexity meningioma, which recurred as a malignant transformation 26 years after a total tumor removal. A 75-year-old man was transferred to a local hospital because of general convulsions and left hemiparesis. The patient had had an operation for the total removal of a right frontal convexity meningioma at the age of 46 and had been free of its effects until the age of 72. Brain magnetic resonance imaging (MRI) showed a recurrent tumor located in the anterior area of the previous craniotomy. Over the following two and a half years, MRI revealed rapid enlargement and infiltration of the tumor into the brain parenchyma. The primary tumor was nodular, macroscopically well demarcated from the surrounding brain tissue and, histologically, was a transitional type of meningioma without any atypical features. In contrast, the recurrent tumor, whose border was ill-defined, had invaded the neighboring brain. A histological specimen of the recurrent tumor showed highly malignant features such as necrosis, intracerebral infiltration, dense cellularity, and high proliferating activity as demonstrated by a cell kinetic study using the MIB 1 staining index. We should be mindful that recurrence from common benign type meningiomas may occur as malignant transformations after more than two decades.     

Proliferative activity of meningiomas as evaluated by bromodeoxyuridine uptake examination

Summary Proliferative activity of meningiomas was examined in 12 consecutive cases by administering bromodeoxyuridine (BrdU) before surgical removal and by immunohistochemical staining of the removed tumours using anti-BrdU monoclonal antibody (anti-BrdU MAb) to detect BrdU-labelled tumour cells. The 12 cases consisted of 6 with a primary tumour and 6 with a recurrent tumour. All of the tumours contained labelled cells and the labelling index (LI) was obtained in each tumour. The highest average LI was 13.6% and the second highest was 9.0% both in recurrent cases of histologically malignant meningothelial meningioma. The high LIs of both cases were thought to correspond well with the rapid recurrence of the tumour. The average LI of a case of recurrent haemangiopericytic tumour was 2.0%, and that of a case of meningioma associated with von Recklinghausen disease was 1.5%. The other 8 meningiomas showed the average LIs ranging from 0.1 to 0.9%, which were considered to be the LIs of usual benign meningiomas.The results of the BrdU uptake examination was considered to reflect well the clinical behaviour of meningiomas. The usefulness of the BrdU uptake examination in brain tumours, which can be employed in the clinical practice without any serious side-effects, is stressed.     

Detection of chromosomal imbalances in spinal meningiomas by comparative genomic hybridization

Little is known about genetic mutations during the malignant progression of spinal meningiomas. This study investigated genomic changes across the entire genome in spinal meningioma samples to determine possible mechanism(s) of tumorigenesis. Paraffin-embedded tissue sections of 16 spinal meningiomas were analyzed by the comparative genomic hybridization (CGH) technique. Lymphocytes of the patients were evaluated as controls. Genomic change was detected in 11 samples. Complete or partial loss of chromosome 22 was the most commonly seen abnormality in eight cases. Chromosome losses on 1p, 9p, and 10q and gains on 5p and 17q were the other abnormalities. These changes are all frequently seen in meningiomas, but are mostly specific to atypical and anaplastic meningiomas. However, in the present study, copy number changes on chromosomes 9p (3 samples), 17q (2 samples), and 1p (2 samples) were seen even in the benign tumors. Our results suggest that in addition to the neurofibromatosis type 2 tumor suppressor gene, other cancer-related genes located on 1p, 9p, 10q, and 17q might be involved in the etiology of spinal meningiomas.     

Clinical and radiological features related to the growth potential of meningioma

Clinical and radiological features that help predict the growth potential of meningioma would be beneficial. The purpose of this study is to clarify the characteristics related to proliferating potential using the MIB-1 staining index. We analyzed the relationship of MIB-1 staining indices to characteristics of 342 consecutive patients with meningioma surgically removed between 1995 and 2004 by logistic regression analysis. One hundred and forty-nine of the patients with meningioma were ≥60 in age; 89 male; 48 recurrent; 203 symptomatic; 157 at the skull base; 124 over 20 cm³; 24 multiple; 136 with edema; 117 with calcification. The MIB-1 staining index in 56 of 296 grade I meningiomas in WHO classification was ≥ 3.0; in 27 of 28 grade II; and in 17 of 18 grade III, respectively. Logistic regression analysis demonstrated that male (odds ratio [OR], 2.374, p=0.003), recurrence (OR, 7.574, p=0.0001), skull base (OR, 0.540, p=0.035), calcification (OR, 0.498, p=0.019) were independent risk factors for a high MIB-1 staining index (≥3.0); age, symptomatic, volume, multiple, edema were not. Male, recurrence, non-skull base, absence of calcification are independent risk factors for a high proliferative potential. These should be taken into consideration when managing meningiomas.     

Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningioma

OBJECT: The management of certain meningiomas of the skull base and those involving the dural venous sinuses remains a challenge. In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas. The authors report their experience in using hydroxyurea for the treatment of patients with recurrent or unresectable meningiomas. METHODS: Hydroxyurea was administered at a dosage of approximately 20 mg/kg/day to 11 women and nine men (median age 59 years, range 31-75 years) with recurrent or unresectable intracranial meningiomas (12 basal, two parasagittal, and six multiple). In 16 patients the meningiomas were benign, in three they had atypical features, and in one the meningioma was malignant. All patients had measurable residual disease. Four patients with benign meningiomas had previously received radiotherapy (two were treated with conventional fractionated radiotherapy and two with stereotactic radiosurgery), three with atypical meningiomas received conventional fractionated radiotherapy, and the one with a malignant meningioma received conventional radiotherapy with additional stereotactic radiosurgery. Tumor enlargement was documented in all patients on neuroimages obtained before initiation of hydroxyurea therapy. All patients were evaluable for response to therapy. In 12 patients with benign meningiomas, the disease had stabilized on neuroimages obtained posttreatment (median duration of treatment 122 weeks, range 8-151 weeks), and two of these showed clinical improvement. One patient with a benign meningioma experienced a minor partial response that was noted after 39 weeks of treatment and was confirmed on neuroimaging and clinical evaluations. In three others with benign meningiomas, progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks, respectively: the 1-year freedom from progression rate was 0.93 (standard error 0.07) in patients with benign meningiomas. In three patients with atypical meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and 45 weeks, respectively. In the patient with a malignant meningioma, progression was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been reasonably well tolerated, although one patient discontinued therapy because of moderate myelosuppression. CONCLUSIONS: Although tumor regression appears uncommon, these results indicate that hydroxyurea may arrest progression of unresectable or recurrent benign meningiomas.     

Radiation-induced meningiomas: clinical, pathological, cytokinetic, and cytogenetic characteristics

OBJECT: Radiation-induced meningiomas are known to occur after high- and low-dose cranial radiation therapy. The goal of this study was to discern the distinguishing findings and characteristics of radiation-induced meningiomas. METHODS: The records of 16 patients (seven men and nine women) who fulfilled the criteria for radiation-induced meningiomas were retrospectively reviewed. Clinical, histopathological, cytokinetic, and cytogenetic findings as well as the patients' outcome were analyzed. The mean age of the patients was 38.8 years and the mean tumor latency was 26.5 years. Five patients had multiple meningiomas in the irradiated field. The recurrence rate was 100% after the initial resection; 62% of patients had a second recurrence and 17% had a third recurrence. Thirty-eight percent of patients had atypical or malignant histopathological findings. The presence of progesterone receptors and low proliferation indices in these patients did not correlate with benign tumor behavior. Cytogenetic analysis showed multiple clonal aberrations in all tumors studied. The most frequent aberrations were found on chromosomes 1p, 6q, and 22. Derivative, lost, or additional chromosome 1p was found in 89% of cases and loss or deletion on chromosome 6 was found in 67%. CONCLUSIONS: The age of patients at presentation with meningioma and the latency period of radiation-induced meningiomas are dose related. These tumors are more aggressive and are certain to recur, have a higher histopathological grade, and are associated with complex cytogenetic aberrations particularly involving 1p and 6q.