Radiation-induced Meningiomas Research Articles

Loss of 1p and 7p in radiation-induced meningiomas identified by comparative genomic hybridization

Cytogenetic and molecular studies of radiation-induced meningiomas (RIM) are rare and controversial. While comparative genomic hybridization (CGH) analysis identified monosomy 22 as the predominant change in RIM, occurring in frequencies comparable to those found in spontaneous meningioma (SM), molecular genetic analysis shows infrequent loss of chromosome 22 DNA markers. We have performed CGH analysis of six additional cases of RIM and detected an unbalanced genome in five of 6 cases. Loss of 1p and 7p was identified in the majority of RIM with an abnormal karyotype (4/5 cases), whereas loss of 6q occurred in three of five cases. Only one of five RIM had monosomy for chromosome 22. Loss of 7p is not frequently reported in SM and yet it was detected in four of 5 RIM with an abnormal karyotype in our study. Molecular and cytogenetic studies of chromosome 7 copy number should be attempted on a larger number of RIM to further investigate the role of 7p loss in RIM.

Radiation-induced meningioma: a descriptive study of 253 cases.

Ionizing radiation is the only established risk factor recognized today in the causation of meningioma. The aim of the present report is to describe the demographic and clinical characteristics of a large series of 253 patients with radiation-induced meningiomas (RIMs). These parameters were compared with those of 41 patients with meningiomas in whom there was no previous history of irradiation (non-RIM group) and with other series of patients presented in the literature. The cases of RIM were recruited from a cohort of approximately 11,000 individuals who had been treated with ionizing radiation during childhood for tinea capitis and from a group of individuals who, as adults, applied for compensation because of that treatment. The non-RIM group was identified through the Israeli Cancer Registry. Exposure to radiation was carefully validated among all cases of RIM and absence of previous irradiation was verified for all patients in the non-RIM group. Significantly, a lower patient age at diagnosis, higher prevalence of calvarial tumors, higher proportion of multiple meningiomas, and a nonsignificant higher recurrence rate were observed among patients with RIM compared with the non-RIM group. The mean latency period from date of radiation exposure to development of a meningioma among the RIM group was approximately 36 years. The findings of this study agree with those of other studies indicating the demographic, clinical, and even genetic variability between RIM and non-RIM cases. The existence of two different subtypes of meningiomas may have profound implications for screening, early diagnosis, and therapy of meningiomas.

Cytogenetic study of six cases of radiation-induced meningiomas

It is known that, following radiotherapy, secondary cancer may occur after a long latent period. Few cytogenetic studies have been reported on tumors of the central nervous system occurring after radiotherapy. We report the cytogenetic study of six cases of radiation-induced meningiomas. In all cases, we observed the same chromosome abnormality, der(1)(1qter→1p11::22q12→22pter). SKY and CGH techniques allowed us to identify the chromosomal abnormalities. We suggest that a gene localized on 1p13 is involved in radiation-induced meningiomas.

The clavicle: A vulnerable bone in pediatric oncology

The clavicle is frequently incorporated into the radiation field in the treatment of malignant tumors located in the head and neck. From 1954 to 1995, 499 pediatric patients were treated with moderate to high-dose radiation therapy to the head and neck at the University of Texas M.D. Anderson Cancer Center. The medical records of 312 of these patients were available and were reviewed. The period of observation ranged from 5 to 30 years. Five late radiation-induced abnormalities of the clavicle were encountered: osteosarcoma; osteochondroma; malignant fibrous histiocytoma; radionecrosis and impaired healing following trauma and radionecrosis and lysis. The doses of radiation therapy which induced the abnormalities varied from 35 to 60.5 Gy (median 34.75 Gy). The interval from radiation therapy to discovery of the complications varied from 6 to 11 years. Two patients died: one from malignant fibrous histiocytoma and another from a radiation-induced meningioma of the brain (which accompanied radionecrosis of the clavicle). We conclude that the incidence of radiation-induced abnormalities of the clavicle in pediatric long-term survivors is low (1.5%). However, some of the late sequela are potentially fatal. The clavicle should be considered a vulnerable bone to radiation therapy and should be monitored in long-term survivors of childhood cancer. The experience is compared to radiation-induced abnormalities recorded in the literature.

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

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.

Radiation-induced meningioma: a distinct molecular genetic pattern?

Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors.

Multiple skull base meningioma: case report

BACKGROUND The incidence of multiple skull base meningiomas varies from 1 to 3% in different series. Skull base meningiomas are rare. The pathogenetic role of low-dose radiation seems to be fairly well established in the oncogenesis of meningiomas. Calvarial location and multiplicity seem to be among the distinctive features of radiation-induced meningiomas. Skull base location is a very rare occurrence, mainly because the path of irradiation does not significantly involve this region. CASE REPORT We describe a rare case of simultaneous occurrence of two skull base meningiomas in a 66-year-old female. This patient underwent low-dose irradiation for tinea capitis when she was 8 years old. The patient complained of nuchal pain, paresthesias in both hands, and progressive weakness on her right side. She was admitted to the hospital in September 1994. An MRI showed two masses, one located at the level of the tuberculum sellae and the other at the foramen magnum. These seemed very likely to be multiple meningiomas. The latter lesion, which was more symptomatic and dangerous, was operated on first. Six months later, elective treatment of the suprasellar meningioma was performed with success. CONCLUSION The actual role of previous head irradiation in the oncogenesis of the present meningiomas remains somewhat unclear. Proper management and judicious use of skull base surgery techniques were key factors in the successful treatment of the patient.

Meningiomas after radiotherapy for tinea capitis--still no history.

To review the clinical, radiological and histological findings of 19 patients with radiation-induced intracranial meningiomas treated at our neurosurgical department between 1981 and 1996. The records of 18 patients with intracranial meningiomas who underwent low-dose radiation for tinea capitis in childhood, and of one patient irradiated for pituitary adenoma, were analyzed in respect of the previously reported features of postradiation meningiomas. The mean age of the patients with low-dose radiation-induced meningiomas was 58 years and the mean shortest onset latency was 48 years. The male to female ratio was 1.1:1. Forty-seven percent of patients presented with mental changes and/or focal neurological signs, 21% with signs of increased intracranial pressure and 26% with seizures. Calvarial location of the meningiomas was found in 54% of patients and in one patient the tumor arose from the skull base. Multiple tumors were present in 15% of patients and 29% of the meningiomas displayed malignant features on histological examination. A significantly lower meningioma recurrence rate was found in our series compared to the recurrence rate in the reported series of postradiation meningiomas. Five patients had a history of a second neoplasm other than meningioma. Our series of low-dose radiation-induced meningiomas represents one of the largest of its kind in the English literature. The patients did not differ substantially in sex ratio, tumor localization, multiplicity and histological features from the previously reported postradiation meningioma patients, except for the significantly lower tumor recurrence rate. It would seem that over the next years we will be further witnessing the deleterious effects of low-dose radiation administered in childhood.

Dosimetric and cytogenetic studies of multiple radiation-induced meningiomas for a single patient

No criteria are currently available to determine the spontaneous or radiation-induced origin of a malignant tumor occurring in a previously irradiated area. This study presents the dosimetric and cytogenetic analysis of meningiomas diagnosed in irradiated brain areas from a single patient and a discussion of the karyotypes of spontaneous meningiomas and radiation-induced tumors published in the literature.

High-dose radiation-induced meningiomas

Numerous neoplasms within the CNS have been reported as radiogenic in origin; radiation-induced meningiomas are at least five times more numerous than gliomas or sarcomas in the world literature. The authors review 10 cases of cerebral meningiomas following high-dose radiotherapy in patients operated for neoplasm of the nervous system. The pathologic and clinical aspects of this unusual complication are analyzed in all cases in the world literature. There is a female predominance (F-M ratio: 3:2) and the patients are young (mean age: 33.1 years; median: 29 years). The average latency period is 14.4 years (range: 9-21 years). The first disease is acute lymphocytic leukemia (ALL) in 40% of cases. Radiation induced meningiomas are atypical in four cases. Recurrence was observed in one case without malignant transformation. High-dose radiation-induced meningiomas have the following characteristics: (1) children appear particularly sensitive to the development of this tumor; (2) there is a female predominance, otherwise than is observed in low-dose meningioma; (3) these tumors present a peak frequency in the third decade of life; and (4) frequently, these tumors are atypical and recur. Finally, it is essential that every new case be reported to throw light on this particular pathologic correlation with its many grey areas.

Long-term changes induced by high-dose irradiation of the head and neck region: imaging findings.

High-dose irradiation is an effective treatment for tumors in the head and neck. Radiation-induced complications are uncommon but may result in chronic, progressive symptoms months or years after therapy. In 19 (1%) of 1,950 patients who underwent successful high-dose irradiation of head and neck tumors over a 5-year period, delayed radiation-induced changes were documented with imaging. These changes can be categorized as soft-tissue, bone, and cartilage necrosis; fibrosis leading to functional disorders; arteriopathy; central nervous system reactions, delayed myelopathy, and cranial nerve palsies; and the development of meningiomas. Radiologic features of radiation-induced soft-tissue, bone, and cartilage necrosis include inflammatory swelling adjacent to the area of involvement; deep gas-containing ulcerations; sclerotic appearance of the involved cartilages; fragmentation and sloughing of necrotic bone or cartilage; and abscess and fistula formation. Masticator muscle fibrosis appears as an area of diffusely increased signal intensity on T2-weighted images and of enhancement on postcontrast T1-weighted images. Radiation arteriopathy may manifest as occlusion, subocclusive sclerotic or atheromatous plaque, localized mural thrombus, aneurysm, or, rarely, spontaneous rupture. In central nervous system reactions, imaging findings include demyelination foci in the white matter, focal radiation necrosis, and severe brain atrophy. Radiation-induced meningiomas display the same imaging features as non-radiation-induced meningiomas at computed tomography, magnetic resonance imaging, and angiography, although follow-up examinations may reveal their more aggressive biologic behavior. Knowledge of the radiologic appearance of radiation-induced changes may prevent misinterpretations and facilitate treatment.

Radiation-induced meningioma following radiation therapy for pituitary adenoma

The authors report the long-term result of treatment of a presumed pituitary adenoma with external-beam radiation therapy, which appears to be the development of a radiation-induced meningioma. Of the post radiation neoplasms that have been reported, meningiomas constitute a large proportion of these lesions.

Radiation-Induced Meningioma

A case of radiation-induced meningioma that appeared in a 27-year-old woman, 12 years after treatment of a childhood-onset posterior fossa medulloblastoma, is reported from the Department of Neurosurgery, Bretonneau Hospital, Tours, France.

Intracranial meningiomas following irradiation--a growing problem?

We present 10 cases of meningiomas occurring after high-dose irradiation for other brain tumours. These constitute 3.7% of 272 patients with meningiomas treated in our unit over 10 years. The clinical and pathological features of the 10 cases were added to those of 69 previous cases documented in the literature and compared with the features of our 262 spontaneous meningiomas. The literature on 119 cases of low-dose radiation-induced meningiomas was also reviewed. Malignant histological features and multiplicity were more common in the radiation-induced meningiomas (p < 0.01). Increasing long-term survival rates following radiotherapy for primary intracranial tumours, particularly in childhood, may lead to an increased incidence of postirradiation meningiomas.

Meningiomas: genetics, malignancy, and the role of radiation in induction and treatment. The Richard C. Schneider Lecture.

The author reviews the molecular genetics, pathology, and cell kinetics of meningiomas and the role that regional multiplicity in the dura mater may play in their recurrence. Malignant and radiation-induced meningiomas are discussed, with summaries of series of 60 patients with frankly malignant lesions treated over a period of 22 years at the University of California, San Francisco, and of 10 patients with meningiomas induced by high-dose radiation therapy. Reviewing a 23-year series of 140 patients with subtotally removed meningiomas who were treated post-operatively with radiation, the author recommends that, with meticulous technique, irradiation is effective in preventing the regrowth of subtotally removed benign meningiomas and of all malignant meningiomas. Adoption of both the microscopical cytological grading system proposed by Jääskeläinen's group in Helsinki and the classification of operations proposed by Donald Simpson is also recommended. Wide removal of dura adjacent to meningioma reduces the risk of recurrence, and determination of the bromodeoxyuridine labeling index provides a valid basis for planning treatment and follow-up evaluations. Increased awareness is necessary for early recognition of radiation-induced meningiomas in patients at risk for developing such tumors. For meningiomas in such sites as the parasellar region and the posterior fossa, conservative removal of tumor followed by irradiation is advocated in preference to a radical operation that may cause neurological injury without being curative.

Radiation-Induced Meningiomas

High dose radiation-induced meningiomas are a rare, severe and late complication of craniospinal radiotherapy for brain tumors. Radiation-induced meningiomas are, according to the literature, several times more frequent than radiogenic gliomas and sarcomas. It is suggested that every new case of radiogenic meningioma has to be reported to elucidate this particular pathologic entity with its many grey areas. In addition to high dose radiation-induced meningiomas, intracranial meningiomas were observed in patients who underwent low-dose radiation for tinea capitis in childhood, applied en mass to immigrants coming to Israel from the North Africa and the Middle East during the 1950. Authors summarize the data on radiogenic meningiomas from the literature and, as the previous radiotherapy may confer a low, but life-long risk for meningioma occurrence, they suggest that surveillance MRI after high dose cerebrospinal radiotherapy should be extended to several (3-5) decades after radiotherapy.

Childhood intracranial meningiomas after high-dose irradiation

Irradiation, either alone or in association with other factors, is thought to play a role in the causation of intracranial meningioma. The authors report two 15-year-old patients with convexity meningiomas as a result of high-dose irradiation received at a young age and review the English language literature reports of 13 pediatric patients with meningiomas after high-dose irradiation. The clinical characteristics of the 15 patients are presented. There were nine girls and six boys. The mean age at the time of irradiation was 2.5 years (2 months-9 years), and the mean age at diagnosis of meningioma was 13 years (5-15.5 years). The mean radiation dose was 4154 cGy (1500-8000 cGy). In 11 of the 15 patients, the meningioma was located in the calvarial area. Only 1 of 15 had multiple tumors, and only two of the tumors were clearly malignant at diagnosis. In ten patients, gross total resection was recorded, and two patients underwent subtotal resection. Three died of recurrent/disseminated meningiomas. This study suggests that meningiomas after high-dose radiation in children are mostly calvarial in location, rarely multiple, mostly benign in histologic type, and that complete removal is possible in most patients. The age at the time of radiation is young (mean age, 2.5 years) and the latent period is short (mean, 10.8 years). Although the clinical course of radiation-induced meningiomas in childhood generally is benign, high doses of radiation at a young age are to be avoided, and other means of therapy should be used if possible.

Chromosome 22 monosomy in a radiation-induced meningioma

We report for the first time on the cytogenetics of a radiation-induced meningioma, in a patient without neurofibromatosis. Chromosome 22 monosomy was found in more than 50% of the cells examined. These findings seem to suggest that the same kind of chromosomal aberrations are found in both "idiopathic" and radiation-induced meningiomas and that a common etiopathogenetic mechanism might be at work in meningiomas of whatever origin.

Radiation-induced meningiomas: experience at the Mount Sinai Hospital and review of the literature

From the records of The Mount Sinai Hospital, seven cases which met established criteria for radiation-induced meningiomas were identified. This represents the largest series of radiogenic meningiomas documented in North America and includes both intracranial and intraspinal tumors. The records and pathological specimens were reviewed and these data analyzed with other cases retrieved from the world literature. This study reveals that radiation-induced meningiomas can be categorized into three groups based on the amount of radiation administered: 1) low dose; 2) moderate dose and miscellaneous; and 3) high dose. The overwhelming majority of cases had received low-dose irradiation (800 rad) to the scalp for tinea capitis and the second largest group resulted from high-dose irradiation for primary brain tumors (greater than 2000 rad). The unique features distinguishing radiation-induced meningiomas from other meningiomas are reviewed. Although histologically atypical tumors were common in this series, overt malignancy was not encountered. The preoperative management of these lesions should include angiography to evaluate for large-vessel occlusive vasculopathy, a known association of meningiomas induced by high-dose irradiation. Given the propensity these tumors possess for recurrence, a wide bony and dural margin is recommended at surgical resection.

Radiation-induced meningioma

Radiation-induced meningioma