Gliomas in the 2016 WHO Classification of CNS Tumors
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1 Gliomas in the 2016 WHO Classification of CNS Tumors Hindi N Al-Hindi, MD, FCAP Consultant Neuropathologist and Head Section of Anatomic Pathology Department of Pathology and Laboratory Medicine King Faisal Specialist Hospital & Research Center 11th SANS and 2nd APNS Joint Annual Conference Burj Rafal Hotel Kempinski, Riyadh April 8, 2017
2 Basic Considerations Why the need for a tumor classification system? Classification (histogenesis vs. differentiation) Prognosis (grade and stage) Prediction of response to therapy History of CNS Tumor classification WHO classifications
3 Gliomas Histopathological diagnosis is the gold standard for classification and prognostication. H%E, > 100 years: histological type and grade EM: cell differentiation IHC, ~30 years: cell differentiation Molecular Tech., years: diagnostic, prognostic and/or predictive WHO 2016: integration of histologic and molecular diagnoses.
4 WHO Classification of CNS Tumors 1st Ed nd Ed rd Ed th Ed th Ed. Rev 2016 Classification solely based on morphologic features Integration of morphologic & molecular features for Dx
5 Histological Dx of Glial and GN Tumors- Decision Tree WHO 2007 Perry & Wesseling. Handbook of Clin Neurol. 2016; 134:71-95
6 Histological Diagnosis of Glioms - Limitations Inadequate and limited tissue specimens Tumor heterogieniey Mixed and overlapping features Imprecise diagnostic criteria. Confounding factors, e.g. necrosis in post therapy sample Inherent limitation of histology in representing the biology of tumor.
7 WHO s Next?: A Colloquium to Guide Next Steps in Brain Tumor Classification and Grading Brain Pathology 24 (2014) Major Question: How can non-histological criteria (eg, molecular, imaging, clinical, etc.) be used to enhance typing and grading of human brain tumors?
8 Adult DG Diagnosis- Paradigm Shift *Perry & Wesseling. Handbook of Clin Neurol. 2016; 134:71-95
9 WHO 2016 It is hoped that this phenotype-genotype integration will result in: More objectivity Narrowly defined entities More accuracy and reproducibility Improved patient management prognostication and prediction of response to therapy. Louis D, et al. Acta Neuropathol (2016) 131:
10 WHO 2016 Summary of Major Changes
11 WHO 2016-Diffuse Gliomas Restructuring of diffuse gliomas, with incorporation of genetically defined entities and the addition of newly recognized entities, variants and patterns IDH-mutated and IDH-wild type DA and AA (entities) IDH-mutated and 1p/19q codeleted O and AO (entities) IDH-wildtype and IDH-mutant glioblastoma (entities) Epithelioid glioblastoma (variant) Glioblastoma with primitive neuronal component (pattern)
12 WHO 2016-Diffuse Gliomas Novel approach distinguishing pediatric look-alikes, including designation of novel, genetically defined entity Diffuse midline glioma, H3 K27M mutant (entity)
13 Diffuse Astrocytoma, IDH-mutant Young adults IDH1 codon 132 in 90% of cases (IHC) IDH2 codon 172 in 10% of cases Other alterations P53: 94% ATRX: 86% (IHC) MGMT: 50% 1p/19q co-deletion: 0% (regardless of morphology) Progression in 75% of cases (AA & GBM-IDH-m)
14 Diffuse Astrocytoma, IDH-wild type Rare Less favorable outcome Especially with 7q+ and 10q-
15 Dx of DG - Decision Tree WHO 2016
16 WHO Glioblastoma
17 Pediatric Diffuse Gliomas Morphologically similar, but genetically distinct from adulttype counterparts Genetic alterations MYB, BRAF V600E (IHC), FGFR1, KRAS, H3 K27M (IHC) Lacks alterations in IDH1/2, p53 and ATRX Cerebral hemispheres and thalami Anaplastic transformation is rare
18 Pediatric High-Grade DA Include glioblastoma and anaplastic A in pts. <20 yrs old Almost all are de novo ( primary ) Midline: pons, thalamus H3 K27M (IHC) Cerebral hemispheres (older pts.) H3.3 G34R Genetic alterations: p53, ATRX, SETD2, CDKN2A, PDGFRA Rarely IDH1, TERT, EGFR
19 Diffuse midline glioma, H3 K27M-mutant Predominate in children Brain stem, thalamus and spinal cord WHO Grade IV: 2-yr survival <10% In 10% no anaplastic features In 25% mitosis only Can have oligo-like morphology
20 Oligodendroglioma, IDH-mutated and 1p/19q codeleted By definition IDH1/2 mutation AND 1p/19q whole-arm codeletion Other genetic alterations TERT promotor methylation Lacks ATRX mutation Other
21 Oligodendroglioma, NOS Small minority of oligodendrogliomas Diffusely infiltrating glioma Classic oligodendroglial morphology Combined IDH mutation and 1p/19 q codeletion could not be completed or was inconclusive IDH+/ATRX retained IHC is supportive In adults, molecular workup to r/o GBM, IDH-wt
22 Pediatric-type Oligodendroglioma Lacks IDH mutation and 1p/19q codeletion Majority of oligos in children and adolescents; uncommon in adults Should rule out histologic mimics; unlikely with typical histology Overlaps genetically with other diffuse gliomas of childhood
23 Oligoastrocytoma Strongly discouraged in the WHO 2016 Cab be reclassified as astrocytoma or oligodendroglioma by molecular tests OA, NOS and AOA, NOS (provisional entities) True OA is rare
24 Diffuse Gliomas WHO 2007 WHO 2016
25 WHO Other astrocytomas Addition of newly recognized entity Anaplastic PXA (entity) replacing PXA with anaplastic features Pilomyxoid astrocytoma should not be graded; formerly automatically given WHO grade II
26 WHO Ependymomas Incorporation of a genetically defined ependymoma variant Ependymoma, RELA fusion positive (entity) Majority (70%) of supratentorial ependymomas in children; uncommon in adults Deletion of former entities, variants and terms Cellular ependymoma variant
27 WHO 2016: Challenges Phenotype genotype discordance- rare Can we use genotype alone? not in the near future. Histology needed for diagnosing and grading DA Unavailability of molecular tests or their IHC surrogates in many labs around the world.
28 The category Not Otherwise Specified A group of lesions that cannot be classified into any of the more narrowly defined groups Insufficient information to assign a more specific code Have not been fully tested for the relevant genetic parameter(s) tested but do not show the diagnostic genetic alterations. The category Not Otherwise Specified WHO 2016: Work in progress 5th edition coming soon
29 Thank You
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