A report of nine newborns with congenital brain tumours

Background Although rare, brain tumours represent one of the relatively larger groups of congenital neoplasias. Most studies on congenital neoplastic disease deal with several types of neoplasms and are dominated by leukaemias, retinoblastomas and systemic solid tumours. Few studies are dedicated to congenital brain tumours. We present nine newborns (four boys and five girls) who were diagnosed with congenital brain tumours during the 8-year period 1 January 1992–31 December 1999 at our institution, which covers all paediatric neuro-oncology cases for Eastern Denmark.Epidemiology Two of the cases were referred from Western Denmark for surgery, and were therefore excluded from the calculation of incidence. During the same period, a total of 172 children below the age of 15 years were diagnosed as having primary central nervous system tumours. The seven remaining congenital cases thus represent 4% of all paediatric brain tumour cases in the area (95% confidence interval 1.7–8.3%). The population of the referral area is 2.383×10⁶, and based on the total number of living births, the incidence of congenital brain tumour was calculated to be 2.9 per 100,000 live births. The ages of the mothers were 28–33 years, corresponding to the present mean age of 31 years for Danish primipara. The gestational age varied between 35 and 42 weeks, and the birth weights were 3,044–4,790 g.Risk factors Two patients with p53-related glioblastoma multiforme (GBM) had relatives with p53-related neoplasms. In one case, the mother was treated for cancer of the ovary with surgery and chemotherapy 2 months before conception.Clinical features In five of the cases, brain abnormality was suspected antenatally. The clinical features of the newborns were limited to enlarged head circumferences, associated hydrocephalus, and asymmetric skull growth.Diagnosis and treatment Three babies were treated with complete tumour resection. In the remaining six cases, a guided or open biopsy to obtain histology was made after CT/MRI imaging. The histological diagnoses were teratoma in four cases, GBM in two cases, anaplastic astrocytoma in two cases and, finally, haemangioma capillare in one case.Outcome Four of the patients (44%) are still alive, including two patients with totally resected combined orbital/intracranial teratomas, one patient with a totally resected haemangioma and one patient with anaplastic astrocytoma who did not receive any treatment apart from supportive care. The survival lengths of the five neonates who died varied between 1 day and 51 days.A commentary on this paper is available at .     

Neuropathology and prognosis of foetal brain tumours

A survey of brain tumours that had been diagnosed prenatally by foetal sonography yielded 89 cases. The most commonly found tumour entities were teratomas (53.9%), glioblastomas (14.6%), lipomas (9.0%), plexus papillomas (7.9%) and craniopharyngiomas (5.6%). The mean gestational age at ultrasound diagnosis was 30.0 weeks, ranging between 25.4 weeks in craniopharyngiomas and 35.3 weeks in lipomas. Girls were more frequently affected (57.4%; P < 0.05). The average maximum tumour size at diagnosis was 6.5 cm, ranging between 1.6 cm in lipomas and 8.2 cm in teratomas. Tumours diagnosed between 1979– 1988 accounted for 29.2% of all cases and were larger when identified than the ones reported between 1989– 1998 (5.9 vs 8.4 cm; P = 0.08). Of all patients, only 18.8% were alive after the first week and 10.5% after the 1st year of life. Prognosis was particularly poor among foetuses with brain tumours detected before 30 weeks’ gestation of which 96.9% died. Significantly longer survival was found for lipomas (12.0 vs 3.8 months), tumour detection after gestational age of 30 weeks (6.3 vs 1.2 months) and in cases reported after 1988 (5.3 vs 2.9 months, all P < 0.05). Cytogenetic data was given for eight teratomas of which three showed a pathological and five cases a normal karyotype for both foetus and tumour. In conclusion, foetal brain tumours are rare neoplasms of whose cytogenetics little is known. They are mainly detected at the beginning of the third trimester of pregnancy with teratomas being the most common entity. Foetal brain tumours have a mainly unfavourable clinical outcome. However, their prognosis has improved in the last decade. Received: 16 June 1999 / Revised, accepted: 3 August 1999     

Multiple meningiomas consisting of fibrous meningioma and anaplastic meningioma.

A 61-year-old woman presented with progressive dementia over a period of 4 months. Computed tomographic (CT) scans and magnetic resonance (MR) imaging showed 2 meningiomas located at the left parasagittal region and the left sphenoid ridge. These tumors had distinct MRI findings; the left parasagittal tumour showed a clear peritumoral CSF space without brain oedema, but the sphenoid ridge tumour was large with marked peritumoral oedema. Total excision of these 2 tumours was attempted with favourable clinical improvement and histological studies revealed meningiomas of different histological types. The left parasagittal tumour was a fibrous meningioma and the left sphenoid ridge tumour was an anaplastic meningioma with typical brain invasion. These tumours showed a MIB-1 staining index of 1% and 30%, respectively. There was also a difference in the immunohistochemical findings for neurofibromin (NF1 product) expression; the left parasagittal tumour expressed neurofibromin but the left sphenoid ridge tumour lacked neurofibromin expression, suggesting an NF1-gene mutation. This case may be a rare example of the simultaneous occurrence of meningiomas with distinct genotypes.     

Paediatric brain tumours treated at a single,tertiary paediatric neurosurgical referral centre from 1999 to 2010 in Australia

Paediatric brain tumours are the most common solid tumour of childhood and the most common cancer cause of death among children. A retrospective review of 313 histopathologically proven brain tumours over an 11-year period has been performed at the Children’s Hospital Westmead, New South Wales, Australia, to determine proportions and locations of different tumours, age distribution, survival rates and usage of various treatment modalities. Pilocytic astrocytoma was the most common paediatric brain tumour (29%) followed by medulloblastoma (12%) and ependymoma (6%). Most tumours were histologically benign (59%), and 42% of tumours were located in the posterior fossa. The average age at diagnosis was 7.9 years. About 50% of children were treated with surgery alone, whereas the other 50% had surgery or biopsy plus adjuvant treatment. The overall one-year survival rate was 89% and the five-year survival rate was 80%. The five-year survival rates for pilocytic astrocytoma was 91%; medulloblastoma, 75%; ependymoma, 82%; and high grade glioma, 15%. Thus, a large proportion of paediatric brain tumours were histologically benign and were treated with surgery alone, but a subset of benign tumours required adjuvant treatment and were associated with mortality (25%). The overall survival rates were high and are improving, although for some tumours, such as high grade glioma, the outlook remains poor.     

Short echo time 1 H magnetic resonance spectroscopy of childhood brain tumours

Aims To explore short echo time (30 ms) 1 H magnetic resonance spectroscopy (MRS) in children with brain tumours and determine the contributions to the characterization of these tumours of the metabolites inositol/myoinositol and glutamate/glutamine, which are not visible at long echo times (135 or 270 ms). Methods Over a 12-month period 86 single-voxel MRS investigations were performed on 59 children with various brain tumours on a Siemens Symphony 1.5-T Magnetom using point-resolved spectroscopy and echo time of 30 ms. Results The procedure was well tolerated, and good-quality data were obtained. N-Acetyl aspartate (NAA)/Choline (Cho) and creatine (Cr)/Cho concentration ratios were significantly (p<0.001) lower in tumour (0.95 and 1.63, respectively) compared with non-involved brain (3.68 and 3.98, respectively) in all histological types. Inositol/Myoinositol (Inos)/Cho ratios were significantly (p<0.05) lower in untreated tumours (1.91) than in treated tumours (3.93) and in non-involved brain (3.32). Inos/Cho ratios were high in diffuse pontine gliomas and low in medulloblastomas and supratentorial primitive neuroectodermal tumours (p<0.01). Glutamate/Glutamine (Glut)/Cho ratios were high in grade 1 astrocytomas (6.4) and unbiopsied optic gliomas (9.84) but low in diffuse pontine gliomas (2.44). Lipids and macromolecules were present in most tumours but in low quantities in non-involved brain. Conclusion Good-quality short echo time MRS data can be collected routinely on children with brain tumours. Inos and Glut levels show greater variability between tumour types than NAA, Cho and Cr present at long echo times, providing improved tumour characterization. Inos/Cho levels differ between untreated and treated tumours and may be useful for treatment monitoring.     

Prognostic indicators in a range of astrocytic tumours: an immunohistochemical study with Ki-67 and p53 antibodies.

The treatment and prognosis of patients with cerebral astrocytic tumours are currently guided by histopathological classification. This study evaluates immunohistochemistry using Ki-67, an antibody to a nuclear protein expressed in proliferating cells, and DO-7, an antibody to the product of the tumour suppressor gene p53, as prognostic indicators for these tumours. Immunohistochemistry with Ki-67 has been correlated with the behaviour of many different tumours, but its value as a prognostic indicator in astrocytic tumours is diminished by the conflicting results of previous studies. Immunohistochemistry with antibodies to the p53 protein has been used as a prognostic indicator in melanomas and some carcinomas, but the relation between prognosis and accumulation of this protein in astrocytic tumours has not been clarified. We have tested the hypothesis that survival is correlated with Ki-67 immunolabelling indices (LIs) and patterns of p53 immunolabelling in the cerebral astrocytic tumours of a large cohort of patients (n = 123) for whom clinical indices were well documented. Astrocytic tumours were divided into three histological types: fibrillary astrocytoma (n = 24), anaplastic astrocytoma (n = 31), and glioblastoma (n = 68). Histological type and patient age were independent predictors of survival. Median Ki-67 LIs differed significantly (P < 0.0001) between the types of astrocytic tumour, and tumours with a Ki-67 LI < 2% had a significantly (P < 0.0001) better prognosis. Ki-67 LI as a continuous variable carried a significant (P = 0.0043) unadjusted hazard to survival which was lost when adjusted for other variables, notably histological type. By contrast, no relation was found between survival and three categories of p53 labeling (p53-negative, p53 LI < 40%, and p53 LI > 60%). The results indicate that, whereas Ki-67 immunohistochemistry predicts survival in patients with astrocytic tumours, conventional histological appraisal remains the best guide to prognosis, and immunohistochemistry for p53 has no value in the assessment of these tumours.     

Paediatric meningiomas in Singapore — Case series of a rare entity

Paediatric meningiomas are extremely rare. These tumours constitute only 2 to 3% of all childhood brain tumours. Despite similarities in histological features between PMs and their adult counterparts, there are important distinctions between them. In this case series, the authors describe their experience in paediatric meningiomas in Singapore’s 2 children’s hospitals from 1998 to 2018. The primary aim of this retrospective study is to evaluate the clinical, radiological and pathological characteristics, and associated outcomes of paediatric patients diagnosed with meningioma managed in our local institutions. Following that, the study’s findings are secondary aims are corroborated with published literature. A total of 10 patients (4 males and 6 females) were identified for this study within the period of 01 January 1998 to 31 December 2018. Their ages ranged from 1 year old to 18 years old (median age 10.5 years old). Two of the patients had NF1 and NF2 respectively. There were 9 intracranial and 1 intraspinal paediatric meningiomas. Seven patients achieved gross total resection and 3 patients had subtotal resection. Eight patients did not have tumour recurrence or increase in size of tumour remnant during the course of their follow-up. In congruency with the literature, up to 40% of our patients had higher grade meningiomas and 55.6% had large tumour volumes more than 30 cm³. Owing to the paucity of knowledge for this unusual tumour, the authors emphasize the need for closer surveillance and in-depth genomic studies to identify novel therapies for this challenging condition.     

Epidemiology of paediatric central nervous system tumours in Queensland,Australia

Within Australia, there is little epidemiologic information regarding paediatric central nervous system (CNS) tumours. This study examined the epidemiology of childhood CNS tumours at Queensland Children’s Hospital (QCH), the major paediatric referral centre for Queensland and northern New South Wales. We assessed the data from 221 newly diagnosed childhood CNS tumours across a five-year period from 2015 to 2019. Recurrent tumours were excluded. Data was collected on patient age, gender, histopathological diagnosis, tumour grade, anatomical site, and residential geographical location. The incidence within this period ranged from 2.65 to 3.85 cases per 100,000 children. The median symptom interval was 30 days (IQR 14–122) with presenting features similar to previous studies. The symptom interval was shorter for children zero to three years compared to children four years or older. The most frequent tumour was pilocytic astrocytoma, followed by medulloblastoma and Langerhans cell histiocytosis. The posterior fossa was the most frequent anatomical location for tumours. Our study demonstrated a shorter symptom interval in comparison to previous literature. The study was able to determine the incidence and presenting features within an Australian population.     

Intracranial tumours in the first 18 months of life

There are few population-based studies of intracranial tumours in children. This study examines 93 brain tumours in children up to 18 months of age from over 800 childhood central nervous system tumours reported to the Manchester Children's Tumour Registry during the period 1953–1987. The incidence was 1 per 25 000 live births. Of these tumours, 85% were malignant. The three most common tumours were medulloblastoma, ependymoma and juvenile astrocytoma. Eighteen percent of the tumours were in the axial region. Twenty-five percent were connected to the ventricles. The tumour was supratentorial in two-thirds of the children under 6 months of age. A high incidence of tumours in the families of these children was found; tumours were noted in two sets of siblings.     

Posterior fossa tumours in children and adolescents. A clinicopathological study of 216 cases

Posterior fossa tumours are characteristics of paediatric population. This report is a study of 216 consecutive cases of neuropathologically verified brain tumours in children under the 18th year of age, who underwent surgery at the Polish Mother Memorial Hospital in Lód?, Poland, between 1990 and 2003. Children with posterior fossa tumours constituted 47% of all paediatric patients with brain tumours. Male-to-female ratio was 1.35:1, and the major peak in the incidence of tumours was observed between 4 and 6 years of age. The most common locations were the cerebellum along with the fourth ventricle (61.5%), cerebellar hemispheres (27.5%), and brain stem (7.5%). Astrocytic tumours (predominantly pilocytic astrocytomas) were the most common group of neoplasms (41.5%) followed by embryonal tumours (all but one medulloblastomas--34.5%), ependymal tumours (13%), and mixed neuronal-glial tumours (5.5%). Altogether, nineteen histological types of brain tumours were diagnosed in the analysed population. The location of tumours, age and sex were compared with those of previously published series of paediatric posterior fossa tumours.     

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case–control study of 410 patients with 8 years post-operative follow-up

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case–control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.     

Brain tumours result in sleep disorders in children and adolescents

Background and objectivesSleep disturbances are frequently reported in children with brain tumours. The objective of our cross-sectional study was to systematically examine sleep in these children. We hypothesised that children with tumours involving the sleep-wake-regulatory areas have an altered sleep-wake-regulation.MethodsSixty-one patients aged 0–18 years and with a diagnosis of a primary brain or cervical medullary tumour were included. They were categorised based upon tumour location into two groups – those affecting the sleep-wake regulatory regions, i.e. brain stem, basal forebrain, hypothalamus, thalamus, and posterior fossa compressing the brain stem and those that did not. Sleep history, questionnaire surveys, polysomnography, and multiple sleep latency test were used, as indicated clinically. Surveys included Pediatric Daytime Sleepiness Scale, Children's Sleep Habits Questionnaire, Strengths and Difficulties Questionnaire, and Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale and Generic Core Scale.ResultsPatients with tumours involving the sleep-wake regulatory areas were sleepier/more fatigued (p = 0.03). Sleep apnoea was observed in 86% of all the patients and comorbid narcolepsy in 8%, without group differences (p ≥ 0.12). Patients with tumours involving the sleep-wake-regulatory areas had more emotional problems (p = 0.04), were more affected by mental health problems (p < 0.001), and had poorer quality of life (p ≤ 0.03).ConclusionsMany children with brain tumours suffer from disturbed sleep, poor mental health, and low quality of life. We recommend that systematic sleep evaluation is included in their routine care along with psychological and social support.     

Epilepsy and brain tumours in children

Although epilepsy is one of the clinical manifestations of brain tumour in one out of three children, such tumours are only found in 1 to 2% of epileptic children explored. When epilepsy reveals the tumour, the latter is benign in 9 out of 10 cases: usually an astrocytoma, an oligodendroglioma or a mixed oligoastrocytic tumour. These tumours accounted for 84% of benign tumours of the cerebral hemispheres among children treated by surgery in our department at the Enfants Malades hospital, Paris; 76% of them had been revealed by epileptic seizures. Among other lesions responsible for epilepsy were 2 cavernous angiomas and 6 thrombotic angiomas. Brain tumours were located in the temporal lobe in almost one half of the cases. The type of epileptic attack was variable, but complex partial seizures were the majority (47%). Several types were associated in 30% of the cases. Surgery was the only treatment in view of the very low recurrence rate. In 80% of the case, removal of the tumour was sufficient to suppress epilepsy. 71% of the children operated upon have an IQ of more than 80; 77% have normal schooling.     

Tumour vascularity is of prognostic significance in adult, but not paediatric astrocytomas

Astrocytomas are the commonest type of brain tumours in adults and children. Although the most reliable prognostic indicators have been shown consistently to be patient age and tumour histological grade, biological progression in these tumours is inevitable and the overall prognosis has remained poor. Due to the evidence that vascular changes are important histological features of astrocytomas, the aim of this study was to investigate prognostic significance of tumour vascularity in paediatric and adult astrocytomas. Study population consisted of 70 patients (45 adult and 25 children) with histologically proven diagnosis of astrocytoma with no history of previous therapy. Histological quantification of tumour vascularity was performed using three different methods: microvessel density, vascular grading and Chalkley counting. Histological classification and grading were also assessed using the World Health Organization system. In contrast to the results in paediatric astrocytomas, tumour vascularity in adult tumours correlated significantly with postoperative survival by univariate analysis (P < 0.05). Microvessel density appeared to be an independent indicator of prognosis by multivariate analysis (P = 0.001). Likewise, patients with microvessel density of 70 or greater had significantly shorter survival than the remaining group (P < 0.001). Patient age and tumour histological grade were also correlated with survival. We conclude that histological quantification of tumour vascularity is a significant prognosticator in adult astrocytomas, but not in children. Our data do not support the validity of applications of antiangiogenic agents in paediatric astrocytic tumours, particularly pilocytic astrocytomas.     

Hypofractionated stereotactic radiotherapy for oligometastases in the brain: a single-institution experience

The treatment of brain metastases is changing. Many different radiotherapy options are now available and under clinical evaluation. As part of this effort, we retrospectively evaluated the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) in patients with up to three brain metastases. Sixty-five patients with 81 lesions were treated with hypofractionated radiotherapy. Median dose was 24 Gy in three fractions. Median follow-up was 24.6 months. Actuarial tumour control was 75 and 45% at 9 months and 24 months after treatment, respectively. Median survival time was 7.5 months, and 32% of the patients died from brain tumour progression. Actuarial overall survival was 75% at 3 months and 25% at 12 months. Recursive partitioning analysis class was the only significant prognostic factor. Neoadjuvant whole-brain radiotherapy (in 29 patients) had no impact on survival or local control. Neurological status improved in 42 patients (65%). Adverse events were rare and usually mild. This experience suggests HSRT should be considered as an alternative approach in the treatment of one to three metastatic lesions in selected patients.     

SMART syndrome: a late reversible complication after radiation therapy for brain tumours

With intensified treatment leading to longer survival, complications of therapy for brain tumours are more frequently observed. Regarding radiation therapy, progressive and irreversible white matter disease with cognitive decline is most feared. We report on four patients with reversible clinical and radiological features occurring years after radiation for brain tumours, suggestive for the so called SMART syndrome (stroke-like migraine attacks after radiation therapy). All four patients (males, age 36–60 years) had been treated with focal brain radiation for a primary brain tumour or with whole-brain radiation therapy for brain metastases. Ranging from 2 to 10 years following radiation therapy patients presented with headache and focal neurological deficits, suggestive for tumour recurrence. Two patients also presented with focal seizures. MRI demonstrated typical cortical swelling and contrast enhancement, primarily in the parieto-occipital region. On follow-up both clinical and MRI features improved spontaneously. Three patients eventually proved to have tumour recurrence. The clinical and radiological picture of these patients is compatible with the SMART syndrome, a rare complication of radiation therapy which is probably under recognized in brain tumour patients. The pathophysiology of the SMART syndrome is poorly understood but bears similarities with the posterior reversible encephalopathy syndrome (PRES). These four cases underline that the SMART syndrome should be considered in patients formerly treated with radiation therapy for brain tumours, who present with new neurologic deficits. Before the diagnosis of SMART syndrome can be established other causes, such as local tumour recurrence, leptomeningeal disease or ischemic disease should be ruled out.     

The incidence trends of primary brain tumors in Saskatchewan from 1970 to 2001

OBJECTIVE: There has been a paucity of information on the epidemiology of primary brain tumors (BTs) in Canada. This study documents epidemiology of primary BTs in Saskatchewan over three decades to define their current state, changing pattern over years and relative distribution in two geographically defined areas of the province. METHODS: Data on all primary BTs from 1970 to 2001 from the Brain Tumor Registry in Saskatchewan was collected. The aggregate data on primary BTs including the time-series for incidence, age, geographic location and sex were statistically analyzed using SPSS 13. Poisson regression was used to model the incidence as a function of decade of diagnosis and age at the time of diagnosis. RESULTS: The average annual incidence of primary BTs was 11.1 per 100,000 person-years (male 12.5 per 100.000 and female 9.8 per 100.000). Males constituted 54.5% of all these tumors. The age distribution of tumors was bimodal with peaks at 5 years and 65 years. During this time, the incidence of primary BTs has increase predominantly in non-malignant types. No difference was found in the rate of all the diagnosed primary BTs combined, meningioma and lymphoma between the northern part (Regina) and southern part (Saskatoon) of the province. CONCLUSIONS: The incidence of BTs in Saskatchewan is more than previously reported in Canada. There is a temporal trend in increasing incidence of some of the BTs predominantly in the non-malignant types. No spatial difference in the incidence of primary BTs was shown in this province. These data will provide useful information to guide the future studies on BTs changing patterns, possible etiologies and efficient resource allocation for management of these diseases.     

On the changing epidemiology of hydrocephalus

Purpose  The purpose of this study is to evaluate the changing epidemiology of paediatric hydrocephalus over the past three decades in a single institution. Methods  All children treated for newly diagnosed hydrocephalus during the 1985–1990 (group A) and the 2000–2005 periods (group B) were enrolled and classified according to the associated cause of hydrocephalus. Results  A significant 8.8% decrease of the incidence of hydrocephalus was noticed between the two time periods, resulting from the reduction of hydrocephalus associated to myelomeningocele, aqueduct stenosis (p = 0.04), CNS infection (p = 0.03), cranio-cerebral malformation and head injuries; post-haemorrhagic hydrocephalus remained stable, while the tumour-associated one increased (p < 0.0001). No consistent differences in terms of rate of adjunctive surgery (30.3% versus 23.9%) and number revision procedures (200 versus 104) were recorded. Conclusions  The present study confirmed data from the literature about the declined incidence of paediatric hydrocephalus, which mainly results from the decrease of congenital malformations. In spite of the recent advances in neuroendoscopy and in the shunting valve design, the impact of hydrocephalus in the paediatric neurosurgical practice remains high. All the authors approve the present submission and declare that this paper has not been published before and it is not under consideration elsewhere.     

Long-term exposure to ambient air pollution and incidence of brain tumours: The Danish Nurse Cohort

BackgroundAir pollution has been considered a potent environmental risk factor for neuropathology through neuroinflammation and oxidative stress, which might also cause brain tumour formation. However, epidemiological evidence on the association between air pollution and brain tumours in humans is sparse, with no data on exposure to particles. In this study we aim to examine associations between long-term exposure to ambient air pollution and risk for development of brain tumours.MethodsWe used the Danish Nurse Cohort with 28,731 female nurses (age ≥ 44 years) recruited in 1993 or 1999 when self-reported information on lifestyle was collected. We obtained data on the incidence of brain tumours until 2013 from the Danish Cancer Register, and estimated annual mean concentrations of particulate matter with diameter < 2.5 μm (PM_2.5), particulate matter with diameter <10 μm (PM₁₀), nitrogen oxides (NO_x) and nitrogen dioxide (NO₂) at the residence since 1990 using an atmospheric integrated chemistry-transport models system, and examined the association between the 3-year running mean of pollutants and brain tumour incidence using time-varying Cox regression, separately for total brain tumours, and for tumour subtypes by location (brain or meninges), and by malignancy (malignant or benign), and estimated hazard ratios and 95% confidence intervals per increase in interquartile range of exposure.ResultsOf 25,143 tumour-free nurses at recruitment, 121 developed brain cancer during 15.7 years of follow-up. We found a weak positive association between total brain tumours and PM_2.5 (1.06; 0.80–1.40 per 3.37 μg/m³), NO₂ (1.09; 0.91–1.29) per 7.5 μg/m³, and NO_x (1.02; 0.93–1.12 per 10.22 μg/m³), and none with PM₁₀ (0.93; 0.70–1.23 per 3.31 μg/m³). Associations with PM_2.5 and NO₂ were stronger for tumours located in meninges than in brain, and for benign than for malignant tumours. Finally, association of total brain tumours with PM_2.5 was modified by BMI, and was statistically significantly enhanced in obese women (2.03; 1.35–3.05).ConclusionWe found weak evidence for association between risk of brain tumours and long-term exposure to air pollution in women older than 44 years. However, we present novel results that obese women may be susceptible, as well as a positive tendency towards elevated risk for meninges and benign tumours, which require further investigation.     

Primary intracranial haemangiopericytoma: Comparison of survival outcomes and metastatic potential in WHO grade II and III variants

Primary intracranial haemangiopericytomas (HPC) are rare, highly vascular tumours with a high propensity for local recurrence and distant metastasis. Optimal treatment includes maximal surgical resection followed by adjuvant radiotherapy. In 2007, new histopathological grading criteria were introduced to differentiate between high grade (World Health Organization [WHO] grade III) and low grade (WHO grade II) tumours. Given the rarity of this tumour, there is a paucity of information regarding the prognostic significance of histological grade. We conducted a retrospective review of our 20 year experience in treating 27 patients with HPC at our institution. Statistical analysis to compare overall survival, local recurrence rate and metastatic potential between the two grades were conducted using Kaplan–Meier analysis. The estimated median survival for grade II HPC was 216 months and for grade III tumours was 142 months. On multivariate analysis, grade II tumours were associated with better survival than grade III lesions (hazard ratio = 0.16, 95% confidence interval 0.26–0.95; p = 0.044). During the study period, 33% of grade III tumours developed local recurrence compared to 21% of grade II tumours. Metastases were found in 36% of grade II patients and 25% of grade III patients. There was no significant statistical difference in local recurrence rate and metastasis between the two grades. Higher histological grading in HPC is associated with worse overall survival. However based on our series higher histological grading is not associated with higher local recurrence or distant metastatic rates.