Brain Tumors

After a mass is first identified in a patient’s brain, one of the usual first steps is a near-immediate surgery to remove as much of the mass as possible. During this operation, the neurosurgeon will typically take a sample of tissue from the mass – or biopsy – and send it to the hospital’s “pathology” department, which is in charge of analyzing the sample of tissue/cells and determining the exact diagnosis. Pathology answers questions such as: is the mass really a tumor or something else, like an infection or cyst? If it is a tumor, is the tumor benign or malignant? Is it an oligodendroglioma, meningioma, astrocytoma, or another tumor type? What grade is the tumor? These answers will then play a critical role in determining a patient’s subsequent treatment plan. Will the patient need radiation? Will they need chemotherapy? Both? Will doctors take a “wait-and-watch” approach? Historically, pathologists analyze biopsy samples by examining the tissue under microscopes and produce a report (pathology report or surgical pathology report) on the tumors’ grade and diagnosis from an observable set of standard characteristics that define the different “classifications” of brain tumors. This microscope-based approach is called “histopathology.” However, because of the biological diversity of tumors, there can be some uncertainty and variability in obtaining an accurate diagnosis. New studies over recent years demonstrate that molecular alterations in tumor cells define different groups of brain tumor types (including gliomas) that have distinctive characteristics. These studies also suggest that analyzing a tumor for mutations or deletions in certain genes or regions of chromosomes can provide a deeper level of understanding of each tumor’s make-up. By using molecular markers, doctors can more accurately define and classify brain tumors compared to current pathology methods. These findings have begun to move the neuro-oncology field toward a more informed and precise classification for the many different types, and subtypes, of brain tumors, which may better inform how patients should be treated. “Unfortunately, classifying a tumor only by [microscopic] appearance and grade has not provided sufficient information about the way the tumor is likely to behave, how it will respond to treatment, or the patients' likely survival time,” said Dr. Margaret Wrensch of UCSF. “These markers will potentially allow us to predict the course of gliomas more accurately, treat them more effectively, and identify more clearly what causes them in the first place.” Thus, in mid-2014 a group of top neuropathologists – who specialize in the pathology of brain tumors – began discussing how to integrate the latest science and the most accurate techniques into the current classification system of brain tumors, which was last updated in 2007. And after two years of work, the group – in conjunction with the World Health Organization, the international organization charged with setting standard grades and categories for tumors – has published a new standard classification system for brain tumors that incorporates molecular information alongside traditional histopathology, establishing “integrated diagnoses” that should lead to improvements in diagnostic consistency, prognostic estimation, and therapeutic prediction. The 2016 World Health Organization Classification of Tumours of the Central Nervous System (the “Blue Book”) is based on years of research and culminated with a consensus meeting of top international neuropathologists in 2015. OVERVIEW – TUMOR CLASSIFICATIONS*

Periodic revisions of tumor classifications have important effects on many aspects of individual and population health. Based on the latest knowledge from molecular characterization studies, researchers have come to better understand how brain tumors are a heterogeneous group of molecularly distinct entities, with some tumors sharing common characteristics and others based on very different sets of alterations and mutations. As such, the groups charged with producing the new 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) sought to answer the following questions:

• Can an entity (brain tumor type) be defined on the basis of histology and genetics? o If so, what should a histologically similar tumor without the corresponding genetic findings be called?

• Are there “new” entities to add?

• Are there “old” entities to delete?

• After reviewing all the latest scientific information on brain tumors, the consensus was that: Major restructuring of diffuse gliomas, with the incorporation of genetically defined entities

• Major restructuring of medulloblastomas, with the incorporation of genetically defined entities

• Major restructuring of other embryonal tumors, with the incorporation of genetically defined entities and removal of the term “primitive neuroectodermal tumor”

• Incorporation of a genetically defined ependymoma variant

• Novel approach distinguishing pediatric look-alikes, including designation of novel, genetically defined entity

• Addition of newly recognized entities, variants and patterns Glioblastoma, IDH-wildtype and Glioblastoma, IDH-mutant (entities) Diffuse midline glioma, H3 K27M–mutant (entity) Embryonal tumor with multilayered rosettes, C19MC-altered (entity) Ependymoma, RELA fusion-positive (entity) Diffuse leptomeningeal glioneuronal tumor (entity) Anaplastic PXA (entity) Epithelioid glioblastoma (variant) Glioblastoma with primitive neuronal component (pattern) The multinodular and vacuolated pattern of ganglion cell tumor (pattern)

• Deletion of former entities and variants Gliomatosis cerebri Protoplasmic and fibrillary astrocytoma variants Cellular ependymoma variant

(*The above descriptions and tables are taken from lectures by Dr. David N. Louis, the lead editor of the 2016 CNS WHO classification.)

OVERVIEW – DIAGNOSIS/PROGNOSIS/TREATMENT

Based on the new edition of WHO brain tumor classifications, a percentage of brain tumor diagnoses will now be based on BOTH microscopic analysis AND molecular analysis. Previously, diagnosis and classification was based on just microscopy.

This means diagnoses for many brain tumors will be much more precise and give the treating physician a better idea of what treatment course to take.

However, not every tumor in the new classification will have molecular information included; sometimes the traditional microscopic analyses (which is based on what’s called “phenotype,” or the observable traits of a cell) will remain the most important information for classification.

In instances where genotype (the tumor’s collection of genes) trumps phenotype, or both molecular and histological information is needed, diagnoses for brain tumors will take on an “integrated” and “layered diagnosis.” With the new integrated and layered diagnoses, diagnostic pathology reports will now have four lines of information based on the integration of molecular analysis:

1. Integrated diagnosis

2. Histological (microscopic) diagnosis

3. WHO (histological) grade

4. Molecular information

Patients will still receive their traditional microscope-based diagnosis within a week, but it may take 3-4 weeks for the full, integrated diagnosis with the molecular information to come in. The 2016 World Health Organization Classification of Tumours of the Central Nervous System will have a significant impact in terms of how physicians both diagnose and plan therapies by providing more accurate information on an individual patient’s tumor characteristics.

Source:https://braintumor.org/wp-content/assets/WHO-Re-Classification-2016_FINAL