The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide.

https://link.springer.com/content/pdf/10.1007%2Fs00401-007-0243-4.pdf

The 2007 WHO Classification of Tumours of the Central Nervous System

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control (CDC) and National Cancer Institute (NCI), is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors (malignant and non-malignant) and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates (incidence and mortality) are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non-malignant tumor was meningioma (38.3% of all tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.14. An estimated 83,830 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 23.5% and for a non-malignant brain and other CNS tumor was 82.4%.

CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011.

The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.

Identification of human brain tumour initiating cells

Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

/pdf/cancer-genome-landscapes-qmge4i5y2h.pdf

Cancer Genome Landscapes

background Epigenetic silencing of the MGMT (O 6 -methylguanine–DNA methyltransferase) DNArepair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.

/pdf/mgmt-gene-silencing-and-benefit-from-temozolomide-in-24olu5dmi6.pdf

MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma

✓ Two adults presented with frontal lobe masses. As visualized by computerized tomography, both lesions were large cysts with contrast-enhancing mural nodules and enhancing circumferential rims. En bloc resections of the mural nodules and cyst walls were performed. Pathological evaluation of each nodule disclosed a meningioma, and neoplastic cells were found in the distant cyst walls. Although the walls of large cysts associated with some meningiomas have been composed of reactive glia or collagen, the neoplastic character of the cysts in the present cases underscores the need for resection and careful pathological evaluation of the large cysts associated with meningiomas.

Meningiomas associated with large cysts with neoplastic cells in the cysts walls. Report of two cases.

Purpose
To test the efficacy of intra-arterial (IA) cisplatin versus intravenous (IV) PCNU for treating primary brain tumors, in a randomized trial (Brain Tumor Cooperative Group [BTCG] Trial 8420A).

Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative Group trial 8420A.

Meningioangiomatosis (MA) is a rare hamartomatous lesion of the cerebral cortex; to date only 18 cases with imaging findings have been reported in the English literature. The origin of MA is probably malformative, with possible association with neurofibromatosis. These lesions frequently cause seizures in young patients. We report two new cases seen at our institution and present their CT and MR findings clearly illustrating MA cortex infiltration. Gd-DTPA used in one of the two cases failed to cause enhancement.

Meningioangiomatosis: CT and MR findings.

Corrosion casts provide three dimensional replicas that can be examined readily by scanning electron microscopy (SEM). They are prepared by filling vascular networks with polymerizing plastic and then digesting away the tissue. As based on our studies of ocular vessels, this report describes the vascular anatomy, as well as the artifacts, that are encountered during SEM studies of such preparations.

Scanning electron microscopy of vascular casts

Classification of the glial subset of neuroepithelial tumours is based on the predominant cell type. Admixture of other neoplastic cells occurs quite frequently and should not, unless substantial, lead to an excessive diagnosis of mixed gliomas.

Peter C. Burger

Papers

Meningiomas associated with large cysts with neoplastic cells in the cysts walls. Report of two cases.

Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative Group trial 8420A.

Meningioangiomatosis: CT and MR findings.

Scanning electron microscopy of vascular casts

Definitions and Explanatory Notes