Innumerable Meningiomas Arising in a Patient With Tuberous Sclerosis Complex Decades After Radiation Therapy.

Meningioma is the most common radiation-induced brain neoplasm, usually occurring after a latency of 20 - 35 years, with multiplicity in 10% of cases. Radiation-induced meningiomas (RIMs) have not previously been reported in patients with tuberous sclerosis complex (TSC), unlike their well-known occurrence in other familial tumor predisposition syndrome patients. We report a TSC patient who developed numerous intracranial meningiomas twenty five year after radiation therapy for subependymal giant cell astrocytoma (SEGA). Autopsy examination showed innumerable, coalescent, benign, meningothelial meningiomas, WHO grade 1, ranging in size from 0.2 cm to 3.3 cm. Autopsy also showed small residual SEGA, radiation-induced cerebral vasculopathy, and classic TSC features including several small subependymal nodules ("candle gutterings"), white matter radial heterotopia, facial angiofibromas, dental enamel pitting, one ash leaf spot, and multiple hepatic and renal angiomyolipomas. Next-generation sequencing analysis utilizing a 500+ gene cancer panel demonstrated chromosomal loss involving the majority of chromosome 22, including the NF2 gene locus, as well as a truncating nonsense mutation in TSC1 p. R509*. While TSC patients rarely require radiation therapy, this striking case suggests that patients with TSC should be monitored closely if cranial therapeutic radiation is administered.

Dental x-rays and risk of meningioma.

BACKGROUND: Ionizing radiation is a consistently identified and potentially modifiable risk factor for meningioma, which is the most frequently reported primary brain tumor in the United States. The objective of this study was to examine the association between dental x-rays-the most common artificial source of ionizing radiation-and the risk of intracranial meningioma. METHODS: This population-based case-control study included 1433 patients who had intracranial meningioma diagnosed at ages 20 to 79 years and were residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 counties in Houston, Texas between May 1, 2006 and April 28, 2011 (cases). A control group of 1350 individuals was frequency matched on age, sex, and geography (controls). The main outcome measure for the study was the association between a diagnosis of intracranial meningioma and self-reported bitewing, full-mouth, and panorex dental x-rays. RESULTS: Over a lifetime, cases were more than twice as likely as controls (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4-2.9) to report having ever had a bitewing examination. Regardless of the age at which the films were obtained, individuals who reported receiving bitewing films on a yearly basis or with greater frequency had an elevated risk for ages <10 years (OR, 1.4; 95% CI, 1.0-1.8), ages 10 to 19 years (OR, 1.6; 95% CI, 1.2-2.0), ages 20 to 49 years (OR, 1.9; 95% CI, 1.4-2.6), and ages ≥40 years (OR, 1.5; 95% CI, 1.1-2.0). An increased risk of meningioma also was associated with panorex films taken at a young age or on a yearly basis or with greater frequency, and individuals who reported receiving such films at ages <10 years had a 4.9 times increased risk (95% CI, 1.8-13.2) of meningioma. No association was appreciated for tumor location above or below the tentorium. CONCLUSIONS: Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with an increased risk of intracranial meningioma. As with all sources of artificial ionizing radiation, considered use of this modifiable risk factor may be of benefit to patients.

Radiation-induced meningioma.

The long-term or delayed side effects of irradiation on neural tissue are now known to include the induction of new central nervous system neoplasms. However, during the first half of the 20th century, human neural tissue was generally considered relatively resistant to the carcinogenic and other ill effects of ionizing radiation. As a result, exposure to relatively high doses of x-rays from diagnostic examinations and therapeutic treatment was common. In the present article the authors review the literature relating to radiation-induced meningiomas (RIMs). Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. The incidence and natural history of RIMs following exposure to high- and low-dose radiation is presented, including latency, multiplicity, histopathological features, and recurrence rates. The authors review the typical presentation of patients with RIMs and discuss unique aspects of the surgical management of these tumors compared with sporadic meningioma, based on their clinical experience in treating these lesions.

Risk factors for gliomas and meningiomas in males in Los Angeles County.

Detailed job histories and information about other suspected risk factors were obtained during interviews with 272 men aged 25-69 with a primary brain tumor first diagnosed during 1980-1984 and with 272 individually matched neighbor controls. Separate analyses were conducted for the 202 glioma pairs and the 70 meningioma pairs. Meningioma, but not glioma, was related to having a serious head injury 20 or more years before diagnosis [odds ratio (OR) = 2.3; 95% confidence interval (CI) = 1.1-5.4], and a clear dose-response effect was observed relating meningioma risk to number of serious head injuries (P for trend = 0.01; OR for greater than or equal to 3 injuries = 6.2; CI = 1.2-31.7). Frequency of full-mouth dental X-ray examinations after age 25 related to both glioma (P for trend = 0.04) and meningioma risk (P for trend = 0.06). Glioma, but not meningioma risk, related to duration of prior employment in jobs likely to involve high exposure to electric and magnetic fields (P for trend = 0.05). This risk was greatest for astrocytoma (OR for employment in such jobs for greater than 5 years = 4.3; CI = 1.2-15.6). More glioma cases had worked in the rubber industry (discordant pairs 6/1) and more worked in hot processes using plastics (9/1). More meningioma cases had jobs that involved exposure to metal dusts and fumes (discordant pairs 13/5), and six of these cases and two controls worked as machinists. Finally, there was a protective effect among glioma pairs relating to frequency of use of vitamin C and other vitamin supplements (P for trend = 0.004); the OR for use at least twice a day was 0.4 (CI = 0.2-0.8).

Brain and salivary gland tumors related to prior dental radiography: implications for current practice.

Five epidemiological studies of brain, cranial meninge, and salivary gland tumor sites reviewed implicate prior dental radiography with increased risk of subtentorial intracranial meningiomas and tumors of the parotid gland. Diagnostic radiography (medical and dental) was the most important risk factor identified for parotid gland cancers; among Los Angeles County residents, about 85% of the cumulative parotid dose from diagnostic radiography came from dental examinations. Irradiation of patients during dental radiography declined substantially from 1920 to 1988; it is uncertain whether current low doses increase risk. Recommendations for exposure reduction are made.

Efficacy and safety of intrathecal liposomal cytarabine for the treatment of meningeal relapse in acute lymphoblastic leukemia: experience of two pediatric institutions.

The treatment of meningeal relapse in acute lymphoblastic leukemia (ALL) remains a challenging clinical problem. Liposomal cytarabine (DepoCyte) permits to decrease frequency of lumbar punctures, without loss of efficacy, because intrathecal levels of the drug remain cytotoxic for up to 14 days. We investigated the efficacy and safety of intrathecal DepoCyte in six children with meningeal relapse, treated in two pediatric institutions. DepoCyte was well tolerated in all patients, who achieved complete clearance of blasts from the cerebrospinal fluid after the first three intrathecal drug administrations. Five of the six patients were concurrently treated with high-dose administration of systemic cytarabine, without additional neurological side effects. Our results suggest that DepoCyte is a valid option for children with ALL experiencing meningeal relapse; it deserves further investigation in intensive treatment regimens, taking into due consideration potential neurotoxicity.

Medical and dental x rays as risk factors for recently diagnosed tumors of the head.

We used epidemiologic data on 2 tumor sites, the intracranial meninges and the parotid gland, to evaluate the importance of medical and dental x rays as risk factors for radiogenic tumors of the head diagnosed among residents of Los Angeles County in recent years. Exposures to x-ray treatment to the head and to full-mouth dental x-ray series before 1960 appear to be risk factors for both meningiomas and parotid tumors. Evidence from both descriptive and analytic studies suggests that the female over male excess of meningiomas, which is greatest from ages 25 to 54 years, may be partially explained by the excess exposure of young women to dental x rays. Study participants' ability to recall diagnostic x rays accurately is also evaluated by our comparisons of interview data to those available from dental charts. Recall of these events appears to be unbiased and accurate enough to justify the use of interview data in investigations of these risk factors.

Epidemiology and etiology of intracranial meningiomas: a review.

The frequency of meningiomas has been the topic of relatively few reports. Hospital-based brain tumor series indicate that the incidence is approximately 20% of all intracranial tumors; population-based studies indicate an overall incidence of 2.3/100,000. Although intracranial tumors as a whole show a higher prevalence in males than in females, meningiomas have a 2:1 female-to-male ratio. Between Caucasians and Africans, African-Americans, and Asians, certain differences also have been noted. Meningiomas in children are rare and differ from those in adults and other childhood tumors; they are even more rare in infants. Several features indicating etiologic factors have been identified, among which are ionizing radiation, head injury, hormones, and other receptor binding sites, genetic factors, and viruses. The most common source of exposure of the head to ionizing radiation is dental radiographic examination. Since 1922, head trauma has been considered a possible risk factor, but recent large studies do not support this link. Several factors have prompted studies of estrogens and progestogens as risk factors for meningiomas. Other studies have sought to determine if certain individuals have an inherited predisposition for developing a meningioma and/or if viruses, which may act alone or with other mutagens, figure into the formation of a meningioma. The most promising studies are those of cytogenetics, and future elucidation of factors associated with the loss of one copy of chromosome 22, another phenomenon that has been identified in meningiomas, may lead to screening tests and gene therapy.

Epidemiology of intracranial meningioma.

Intracranial meningiomas arise from the meninges and typically have benign histologic findings. They constitute approximately 20% of all intracranial tumors. Their incidence increases with age, and they affect women more commonly than men. The annual incidence per 100,000 people ranges from two to seven for women and from one to five for men. Since the first study was published in 1970, only eight major epidemiologic studies have been done that attempted to identify risk factors for meningioma. Ionizing radiation and head trauma have emerged as the most promising etiologic risk factors. In these studies, radiation doses as low as 1-2 Gy have been associated with increased risk. The role of dental radiographs has been suggested in some studies but not supported in others. An explanation for the apparent excess of meningiomas in women remains obscure. The potential effects of endogenous or exogenous sex hormones on tumor induction or growth remain unexplored in epidemiologic studies. More should be learned about the risk factors for meningioma in search of opportunities for prevention.