Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study.

BACKGROUND: The aim of this study was to examine the association of a family history of cancer with the risk of testicular cancer in young adults. METHODS: This is a prospective cohort study including 1,974,287 males born 1951-2015, of whom 2686 were diagnosed with TC before the age of 30. RESULTS: A history of TC in male relatives was significantly associated with a diagnosis of TC among children and young adults, including brothers (6.3-fold), sons (4.7-fold), fathers (4.4-fold), paternal uncles (2.0-fold) and maternal uncles (1.9-fold). Individuals with a father diagnosed with a carcinoma or sarcoma showed an elevated risk (1.1-fold and 1.8-fold, respectively). A family history of mesothelioma was positively associated with a risk of TC [(father (2.8-fold), mother (4.6-fold) and maternal uncles and aunt (4.4-fold)]. Elevated risks were also observed when siblings were diagnosed with malignant melanoma (1.4-fold). The risk of TC was also increased when fathers (11.1-fold), paternal (4.9-fold) and maternal uncles and aunts (4.6-fold) were diagnosed with malignant neuroepithelial-tumours. CONCLUSION: We found an increased risk of TC among children and young adults with a family history of TC, carcinoma, mesothelioma, sarcoma, malignant melanoma and malignant neuroepithelial tumours. Hereditary cancer syndromes might underlie some of the associations reported in this study.

Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.

OBJECTIVE: An updated and comprehensive review on dysembryoplastic neuroepithelial tumor (DNET) focusing on differential diagnosis, atypical presentation, seizure outcome, and risk of malignant transformation. METHODS: A PubMed/MEDLINE-based literature search has been performed using "dysembryoplastic neuroepithelial tumor" as a keyword. Two treated cases characterized by an atypical presentation have been reviewed. RESULTS: Of 1162 articles, 200 relevant studies have been selected. DNET is a benign mixed neuronal-glial tumor causing drug-resistant epilepsy primarily in children and young adults. The typical radiological pattern is a magnetic resonance imaging (MRI) T1-hypointense, T2-, and fluid-attenuated inversion-recovery hyperintense multicystic lesion involving the cerebral cortex with no edema. Contrast enhancement may be present and a focal cortical dysplasia is commonly associated with it. MRI diffusion, perfusion, and spectroscopy have a paramount role in the differential diagnosis. The "specific glioneuronal elements" are pathognomonic. They are positive for S100 protein, synaptofisin, neuronal nuclei, oligodendrocyte transcription factor, neurite outgrowth inhibitor, and microtubule-associated protein 2, but negative for glial fibrillary acidic protein. As opposed to v-myb avian myeloblastosis viral oncogene homolog, isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutation and codeletion 1p-19q, fibroblast growth factor receptor 1 and BRAF V600E mutations are present. The effectiveness of surgery on seizure outcome has been established. Rare malignant transformations have been reported, especially in extra-temporal and complex forms. CONCLUSIONS: Advanced MRI techniques are fundamental in the differential diagnosis for DNET versus other low-grade gliomas. Immuno-phenotype assessment and search for fibroblast growth factor receptor 1 and BRAF V600E mutations limit the risk of misdiagnoses. A gross total tumor removal is generally associated with a seizure-free outcome. Recurrences and malignant transformations may rarely follow, legitimizing MRI surveillance in cases of subtotal tumor resection.

Malignant primary brain and other central nervous system tumors diagnosed in Canada from 2009 to 2013.

BACKGROUND: We present a national surveillance report on malignant primary brain and other central nervous system (CNS) tumors diagnosed in the Canadian population in 2009-2013. METHODS: Patients were identified through the Canadian Cancer Registry, an administrative dataset that includes cancer incidence data from all provinces/territories in Canada. Tumor types were classified by site and histology using the definitions from the Central Brain Tumor Registry of the United States (CBTRUS). Incidence rates (IRs) and 95% confidence intervals (CIs) were calculated per 100000 person-years (py) and age-standardized to the 2011 Canadian population for comparisons within Canada and to the 2000 United States population for comparisons with the US. RESULTS: Overall, 12515 malignant brain and other CNS tumors were diagnosed in the Canadian population in 2009-2013 (IR: 8.71/100000 py; 95% CI: 8.56, 8.86); 7085 were among males (IR: 10.06/100000 py; 95% CI: 9.82, 10.29) and 5430 among females (IR: 7.41/100000 py; 95% CI: 7.22, 7.61). Of these, 12115 were classifiable according to histological subgroups defined by CBTRUS. The most common histology was glioblastoma (IR: 4.06/100000 py; 95% CI: 3.95, 4.16). Among those aged 0-19 years, 1130 malignant brain and CNS tumors were diagnosed in 2009-2013 (IR: 3.36/100000 py; 95% CI: 3.16, 3.56). The most common histology among the pediatric population was embryonal tumor (IR: 0.74/100000 py; 95% CI: 0.65, 0.84). CONCLUSIONS: These data represent an initial detailed report on the frequency and distribution of primary malignant brain and other CNS tumors diagnosed in the Canadian population in 2009-2013. The reported distributions of tumor diagnoses by sex and age reflected expected patterns based on the literature from similar populations. A report incorporating data on nonmalignant primary brain tumors is forthcoming.

[Primary Tumors of the Central Nervous System. Clinical Experience at a Third Level Center].

Background: Central nervous system (CNS) tumors are a group of neoplasms that originate from various cells in the CNS. The increasing incidence and prevalence of this type of tumor in developing countries are striking; however, there are few current studies in Latin America including Mexico estimating the impact of these pathological entities on the general population. Objective: The objective of the study was to study the characteristics of primary CNS tumors over a period of 52 years. Methods: A review of records from patients with a histopathological diagnosis of CNS neoplasm over a period of 52 years was conducted at a tertiary-care academic medical center. Patients were grouped by sex, age, and the tumor's anatomical location. Results: A sample of 9615 patients with tumor lesions was obtained; 51% were female, 49% were male, and their mean age was 42 years. The tumors with the highest prevalence were neuroepithelial tumors (38.6%), followed by meningeal tumors (22.8%). Neuroepithelial tumors accounted for 64% in the group of patients under 40 years of age and 56% among those above 40 years of age. The most frequently involved location was supratentorial, in 78.9% of cases. Conclusions: Although retrospective in nature and based on a small sample, this study reports the epidemiology and characteristics of primary brain tumors in the Mexican population.

Gliomatosis cerebri: a consensus summary report from the Second International Gliomatosis cerebri Group Meeting, June 22-23, 2017, Bethesda, USA.

Gliomatosis cerebri (GC) is an aggressive glioma characterized by an invasive growth pattern and a dismal prognosis. The low incidence and non-specific symptoms at presentation pose unique challenges for early diagnosis and disease-specific research. There is no standard of care for the treatment of patients with a GC phenotype. Understanding the biology of this entity is a critical step in determining effective treatments. Toward this end, the Second International GC Group convened at National Institutes of Health, Bethesda on June 22nd-23rd 2017. This paper summarizes the main conclusions and recommendations for research priorities to fight this fatal condition.

Age at epilepsy onset in patients with focal cortical dysplasias, gangliogliomas and dysembryoplastic neuroepithelial tumours.

PURPOSE: The age at epilepsy onset in patients with inborn or very early acquired brain lesions depends on the epileptogenic potential of the lesion and the patients' individual "susceptibility" to epileptic seizures. To gain insight into these determinants, we analysed the case history of patients with focal cortical dysplasias (FCDs) and neuroglial tumours. METHODS: In a systematic, retrospective analysis comprised of 233 patients who underwent surgery (116 with FCDs and 117 with neuroglial tumours), we evaluated the age at epilepsy onset according to histopathologic subgroups, lesion location and family history. RESULTS: Epilepsy onset was significantly earlier in patients with FCD than for those with neuroglial tumours (FCDs: 8.06 ±â€¯0.74 years, gangliogliomas: 15.86 ±â€¯1.24 years, dysembryoplastic neuroepithelial tumours (DNTs): 19.18 ±â€¯2.47 years; p < 0.00001). FCDs were most frequently located in the frontal, whereas neuroglial tumours most frequently in the temporal lobe. For FCD patients, the age at epilepsy onset was not dependent on lesion location, whereas DNTs in a temporal location were associated with a later epilepsy onset than gangliogliomas and extratemporal DNTs. A positive family history for epilepsy or epileptic seizures was found more frequently among patients with FCDs (FCDs: 20.4%, neuroglial tumours: 8.1%; p = 0.013). CONCLUSION: We postulate that the age difference at epilepsy onset between patients with FCDs and neuroglial tumours can be attributed - at least partially - to unidentified genetic factors underlying the epileptogenic potential of the brain tissue. Additionally, the large variance in the age at epilepsy onset is possibly also genetically determined.

Incidence and survival of gliomatosis cerebri: a population-based cancer registration study.

Gliomatosis cerebri (GC) comprises a rare widespread infiltrating growth pattern of diffuse gliomas. We explored the incidence patterns and survival rates of GC in a population-based registration sample from the Surveillance, Epidemiology and End, Results database (1973-2012). GC cases (n = 176) were identified based on their International Classification of Diseases in Oncology (ICD-O-3) morphology code (9381). We calculated age-adjusted incidence rates (AIR) and evaluated temporal trends. Survival was assessed with Kaplan-Meier curves and Cox regression models. The annual AIR of GC was 0.1/million. We noted increasing trends in the preceding registration years (1973-2002; annually, + 7%) and a tendency of clinical/radiological approaches to substitute the gold-standard histological assessment for diagnosis. GC was diagnosed in the entire age spectrum (range 1-98 years), but higher incidence rates (0.43/million) were noted among the elderly (≥ 65 years). A slight male preponderance was identified (male-to-female ratio: 1.4). Median overall survival was 9 months with a 5 year survival rate of 18%. Increasing age, primary tumor location not restricted to the cerebral hemispheres and rural residence at diagnosis were identified as negative prognostic factors, whereas receipt of radiotherapy, surgical treatment, race and method of diagnosis were not associated with outcome. This first comprehensive overview of GC epidemiology exemplifies the rarity of the disease, provides evidence for male preponderance and increased incidence among the elderly and shows lower survival rates compared to the published single center reports. Expansion of registration to histological and molecular characteristics would allow emergence of clinical prognostic factors at the population level.

Epilepsy surgery of "low grade epilepsy associated neuroepithelial tumors": A retrospective nationwide Italian study.

OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. RESULTS: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012). SIGNIFICANCE: Our nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted.

Central nervous system tumours profile at a referral center in the Brazilian Amazon region, 1997-2014.

Tumours of the Central Nervous System (CNS) are an important cause of mortality from cancer. Epidemiological data on neoplams affecting the CNS are scarce in Brazil, especially in the Amazon region. The study aims at describing the histopathological profile of CNS tumours cases at a high-complexity referral cancer center. This study has described a 17-year-series profile of CNS tumours, registered at a high-complexity referral cancer center in Pará state, from January 1997 until July 2014 in the Brazilian Amazon Region. Data was gathered from histopathology reports kept in the hospital's cancer registry and 949 cases of CNS tumours were analyzed. The most common histopathology were neuroepithelial tumours (approx. 40%) and meningioma was the most frequent especific tumor histologic subtype (22.2%). Neuroepithelial tumours were more frequent in patients with ages ranging from less than a year to 19 years, whereas metastatic tumours were prevalent in patients over 40 years of age. It was not found temporal trends during the studied period. The knowledge of these tumours profile is valuable for the understanding of cancer epidemiology in the region, since its prevalence is currently underreported and more awareness on the disease is needed.

Pediatric solid tumors in Africa: different biology?

PURPOSE OF REVIEW: To review the recent literature regarding biologic characteristics of pediatric solid tumors in African children. RECENT FINDINGS: Data regarding pediatric solid tumors in Africa, while increasing, remain sparse when considering the ethnic and geographic diversity of the continent. Recent work, especially regarding nephroblastoma in Kenya, has identified some biologic variability among local tribes but also when compared with North American tumors. In general, reports from across the continent reveal markedly poorer survival for pediatric patients with solid tumors when compared with high-resourced regions. SUMMARY: Multiple resource-related and infrastructure-related challenges contribute to poorer outcomes, and these require systematic, multidisciplinary, and structured solutions. Socioeconomic factors and limited access to care currently seem to drive the survival outcomes in children with solid cancers in Africa.

[Gliomatosis Cerebri as a Clinical Entity].

Gliomatosis cerebri is a rare subtype of glioma involving more than three lobes of the central nervous system. Currently, diagnosis of gliomatosis cerebri can be confirmed pathologically, surgically, or with magnetic resonance imaging that shows high-signal areas expanding to the cerebral hemisphere, brain stem, cerebellum, and spinal cord. Although this disease has great clinical importance, it has recently been removed from the revised WHO classification of Tumors of the Central Nervous System (2016) owing to divergence between its morphological features and molecular profiles.

Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy.

Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4-11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3-10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4-0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3-8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population.

Dietary and Alcohol Intake and Central Nervous System Tumors in Adults: Results of the CERENAT Multicenter Case-Control Study.

BACKGROUND: Little is known about the relationship between diet and central nervous system (CNS) tumors, especially in terms of their histological subtypes. This study investigated the overall associations between food groups, alcohol intake and CNS tumors, and in particular about the associations between neuroepithelial tumors and meningiomas. METHODS: Data were collected through the CERENAT (CEREbral tumors: a NATional study) case-control study conducted in France during the period 2004-2010. Data were available for 1,479 subjects (494 cases, including 201 neuroepithelial tumors, 193 meningiomas, 100 other CNS tumors, and their 985 matched controls). Conditional logistic regressions for matched sets were adjusted based on the participants' educational level, occupation, smoking status and frequency of food group consumption. RESULTS: A heavy consumption of grilled meat and poultry was associated with neuroepithelial tumors in a dose-related relationship (ORQ4vsQ1 = 3.72, 95% CI 1.62-8.52, p = 0.005). Higher fruit and vegetable intake was inversely associated with meningiomas (for fruits: ORQ4vsQ1 = 0.38, 95% CI 0.17-0.87, p = 0.06, for vegetables ORQ4vsQ1 = 0.26, 95% CI 0.11-0.62, p = 0.007). Consumption of alcohol on a daily basis was inversely associated with CNS tumors especially for meningiomas (ORQ4vsQ1 = 0.33, 95% CI 0.18-0.61, p = 0.001). CONCLUSIONS: Results obtained in terms of grilled meat, fruits and vegetables consumption were in line with those published in epidemiological literature. Contradictions in results between neuroepithelial tumors and meningiomas confirmed the need to analyze the effects of dietary factors on the basis of the histological subtypes of CNS tumors.

Gliomatosis cerebri: A consensus summary report from the First International Gliomatosis cerebri Group Meeting, March 26-27, 2015, Paris, France.

Gliomatosis cerebri (GC) is a universally fatal extensive and diffuse infiltration of brain parenchyma by a glial tumor. Many aspects of this phenomenon remain unknown. The First International Gliomatosis cerebri Group Meeting had the following goals: refine the clinical and radiologic diagnostic criteria for GC, suggest appropriate diagnostic procedures, standardize tissue manipulation for histologic and molecular characterization, and prioritize relevant preclinical projects. Also, general treatment recommendations were outlined for the pediatric population. Importantly, this meeting was the starting point for meaningful collaborative international research projects. This review is a consensus summary of discussions shared and conclusions derived from this meeting.

Astroblastomas: a Surveillance, Epidemiology, and End Results (SEER)-based patterns of care analysis.

OBJECTIVE: This study sought to report patient characteristics, risk factors, and trends in management for astroblastoma patients. METHODS: A retrospective analysis was conducted utilizing the Surveillance, Epidemiology and End Results Program of the National Cancer Institute. RESULTS: Two hundred and thirty-nine patients were identified, with 206 patients receiving treatment. The median age at diagnosis was 35 years (range 0 to 84 years). Tumor location was available for 177 patients, and the majority were supratentorial (n = 144, 81.3%). The median overall survival and cause-specific survival for the cohort receiving treatment was 55 and 65 months, respectively. On univariate analysis, patients receiving surgery alone compared to only radiotherapy displayed improved overall survival (OS) and cause-specific survival (CSS) with a 5-year OS of 62.2% vs. 27.3%, P < .001, and CSS of 67.3% vs. 31.9%, P = .003. Supratentorial tumor location was associated with worse survival, with an estimated 5-year OS of 44.9% for supratentorial tumors compared to 75% for infratentorial tumors (hazard ratio 3.41 [95% CI, 1.76 to 6.62]; P < .001) and CSS of 47.5% (supratentorial) to 82% (infratentorial) (hazard ratio 3.95 [95% CI, 1.81 to 8.62]; P = .001). Age >60 years at diagnosis and treatment before 1990 were correlated with decreased survival on both the univariate and the multivariate analyses. CONCLUSIONS: To our knowledge, this is the largest report of astroblastoma patients described in the literature. Supratentorial tumor location, older age, and treatment prior to 1990 were poor prognostic factors.

Intramedullary spinal cord neoplasia in 53 dogs (1990-2010): distribution, clinicopathologic characteristics, and clinical behavior.

BACKGROUND: Intramedullary neoplasms of the canine spinal cord are infrequently reported. OBJECTIVE: To describe distribution, clinicopathologic characteristics, radiographic findings, and clinical features of canine intramedullary spinal tumors. METHODS: Retrospective series of histologically confirmed canine intramedullary spinal tumors. Contingency tables were generated for categorical variables (breed, sex, treatment, pain, chief complaint, localization, histology, imaging, and site). Associations were assessed by Fisher's exact, Wilcoxon rank sum test, t-test, and one-way ANOVA. RESULTS: Intramedullary spinal cord tumors comprised 16% (53/331) of all tumors of the spinal cord. Primary tumors were diagnosed in 66% (35/53) of cases, with neuroepithelial-origin tumors comprising 51% (18/35) of all primary neoplasms. Intraparenchymal metastases of transitional cell carcinoma and hemangiosarcoma accounted for 66% (6/18 each) of all secondary tumors. Primary tumors were more likely to affect younger dogs. Dogs with intramedullary metastases were most commonly presented for primary myelopathic signs (8/18, 44%). The majority of all tumors (52.8%) occurred in the T3-L3 spinal cord segments. All dogs with cervical neurolocalization had primary tumors. Dogs with metastatic lesions had a shorter duration of clinical signs before presentation, but there was no difference in survival time between dogs with primary as compared with secondary tumors. CONCLUSIONS: Intramedullary spinal cord tumors are uncommon. Primary intramedullary spinal cord tumors are more common than secondary intramedullary spinal cord tumors and tend to occur in the cervical spinal cord of younger dogs. Intramedullary metastases occur in older dogs, are rarely asymptomatic, and neurologic dysfunction is a common clinical presentation. Dogs with primary tumors may have a protracted clinical course compared with those with intramedullary metastases.

Primary brain tumour epidemiology in Georgia: first-year results of a population-based study.

A population-based cohort study was initiated in Georgia in March 2009 to collect epidemiologic data of malignant and non-malignant primary brain tumours. During the first year, 473 incident cases were identified. For a population of 4.3 million, the annual incidence rate was 10.25 per 100,000 inhabitants, age-standardized to the year 2000 US population. Non-malignant tumours constituted about 66 % of all tumours. Males accounted for 40 % and females for 60 % of the cases. Crude incidence rates by histology were highest for meningiomas (2.92/100,000), pituitary adenoma (1.16/100,000) and glioblastomas (0.64/100,000), which was in agreement with the frequency of reported histology: meningiomas--45.2 %, pituitary adenoma--18.0 % and glioblastomas--9.9 %. The age-standardized incidence rates were higher among females than males for all primary brain tumours (11.05 vs. 8.44/100,000) as well as for individual histologies except for glioblastoma and several other neuroepithelial tumours. Some differences compared with 2004-2005 Central Brain Tumor Registry of the United States data may be explained by a higher percentage of unclassified tumours (37 %) in our study. We suggest further studies to clarify the nature of this discrepancy.

Albumin storage in neoplastic astroglial elements of gangliogliomas.

PURPOSE: Low-grade neuroepithelial tumors are frequent neuropathological findings in patients with pharmacoresistant epilepsies. Little is known regarding epileptogenic mechanisms in this group of neoplasms with gangliogliomas (GG) as the most common entity. Presence of hemosiderin deposits in GG points to impairment of the blood-brain barrier (BBB). Therefore, we hypothesized a potential role of BBB dysfunction and astrocytic albumin uptake as potential epileptogenic factor in GG. METHODS: Prussian blue staining and fluorescent double-immunohistochemistry with antibodies against albumin, GFAP, CD34 and GLUT-1 were used to analyze hemosiderin deposits and astroglial albumin accumulation in tumor and adjacent pre-existing brain tissue of GG (n=10) and several control groups, i.e. dysembryoplastic neuroepithelial tumors (DNT; n=5), focal cortical dysplasia with balloon cells (FCD IIb; n=10), astrocytomas WHO grade II (n=5) and clear renal cell carcinoma brain metastases (RCCM, n=6). RESULTS: Our results revealed strong hemosiderin deposits in GG. Intriguingly, we noted substantial albumin uptake exclusively in neoplastic glial cell components of GG and DNT, whereas no significant albumin was present in perilesional reactive astrocytes. Strikingly, we did not observe substantial albumin uptake in further controls. CONCLUSION: Glial albumin uptake was restricted to long-term epilepsy associated, vasculature-containing tumors. Intratumoural BBB dysfunction in concert with subsequent accumulation of albumin by neoplastic glial cell elements represent a new putatively epileptogenic mechanism for long-term epilepsy-associated tumors.