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CNS tumor classification.pptx
- 1. The 2021 WHOClassification of Tumors of the Central Nervous System: a summary By: David N Louis Neuro Oncol. 2021;23(8):1231-1251. PRESENTED BY: DR MUHAMMAD ZAMIL •
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- 3. CNS Tumor Taxonomy •The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) incorporates numerous molecular changes with clinicopathologic utility that are important for the most accurate classification of CNS neoplasms. • WHO CNS5 does not recommend specific methods for molecular assessment. • WHO CNS5 has grouped tumors according to the genetic changes that enable a complete diagnosis. • IDH (Astrocytoma, Oligodendroglioma and Glioblastoma) and H3 (Diffuse midline glioma, Diffuse hemispheric glioma). • Some by looser oncogenic associations. Like MAPK pathway alteration (Multinodular and Vacuolating Neuronal Tumor). • Some are classified by histological similarities even though molecular signatures vary. • Atypical teratoid/rhabdoid tumor, Ganglioglioma, Papillary glioneuronal tumor. • Many by using molecular features to define new types and subtypes. • Medulloblastoma. • The term “type" is used instead of “entity” and “subtype” is used instead of “variant".
- 4. CNS Tumor Nomenclature •The fifth edition of the WHO Classification of Tumors of the Central Nervous System follows the recommendations of the 2019 cIMPACT-NOW Utrecht meeting. • Names have been simplified, and only location, age, or genetic modifiers with clinical utility have been used. • Extra-ventricular neurocytoma vs Central neurocytoma. • The characteristics of tumors that are highly characteristic are included in tumor definitions and descriptions, even if they do not appear in the tumor name itself. • chordoid gliomas occurring in the third ventricle • Sometimes tumor names reflect morphologic features that are not present in every example, and they may also reflect historical associations. • Some myxopapillary ependymomas are minimally myxoid, and some may not be overtly papillary. • Xanthomatous change may be limited to a small fraction of cells in pleomorphic xanthoastrocytomas. • Medulloblast has not been identified in developmental studies, in cases of Medulloblastoma. • As they would be disruptive to clinicians and may lead to confusion, they were not changed. • Tumors are now graded within types, modifier terms like "anaplastic" are not routinely used.
- 5. Gene and ProteinNomenclature for CNS Tumor Classification • WHO CNS5 uses the HUGO Gene Nomenclature Committee (HGNC) system for naming gene symbols and gene name. • Gene symbols are presented in italics, but proteins and gene groups are not italicized • A sequence alteration relative to a transcript reference sequence is reported using a “c. ” prefix for the coding DNA sequence, followed by the nucleotide number and nucleotide change. The predicted protein sequence change then follows a “p.” prefix with the reference amino acid, the amino acid number, and the variant amino acid resulting from the mutation. • BRAF:c.1799T>A p.Val600Glu • For some genes like H3 Histone group are typically described in the context of the protein sequence lacks the initiating methionine, resulting in a single amino acid difference in numbering compared with the predicted sequence derived from the corresponding gene transcript. • To address this issue, the fifth edition uses the legacy protein numbering system in parentheses after the protein-level variant description. • H3-3A:c.103G>A p.Gly35Arg (G34R), or H3-3A:c.83A>T p.Lys28Met (K27M)
- 6. CNS Tumor Grading •2 Aspect of Grading have been changed. • Arabic Numerical • Use of Arabic numerical is now favored as Roman Numerical can be mixed with each other and an uncaught typographical error can result in unintended clinical consequences. • Grading within tumor types, has been extended to many categories. This is done due to following reasons: • To provide more flexibility in using grade relative to the tumor type. • To emphasize biological similarities within tumor types rather than approximate clinical behavior. • To conform with WHO grading in non-CNS tumor types. • WHO CNS5 has generally retained the ranges of grades used for tumor types in prior editions, for example IDH mutant Astrocytomas extend from CNS WHO grade 2-4 and Meningiomas from CNS WHO grade 1-3 • Molecular parameters have now been added as biomarkers of grading and for further estimating prognosis within multiple tumor types, for example, CDKN2A/B homozygous deletion in IDH mutant astrocytoma, TERT promoter mutation, EGFR amplification, and +7/−10 copy number changes in IDH-wildtype diffuse astrocytomas. • This allows a glioblastoma, IDH-wildtype CNS WHO grade 4 designation even in cases that otherwise appear histologically lower grade.
- 7. NOS (Not Otherwise Specified) and NEC(Not Elsewhere Classified) Diagnoses. • NOS: the diagnostic information (histological or molecular) necessary to assign a specific WHO diagnosis is not available. • NEC: That the necessary diagnostic testing has been successfully performed but that the results do not readily allow for a WHO diagnosis.
- 8. Novel Diagnostic Technologies • Over thepast decade, methylome profiling has emerged as a powerful approach to CNS tumor classification, as detailed in a variety of publications over the past few years. • Methylome profiling is the use of arrays to determine DNA methylation patterns across the genome.
- 9. Integrated and Layered Diagnoses •The fifth edition of the WHO Classification of Tumors of the Central Nervous System follows, The International Society of Neuropathology—Haarlem consensus guidelines.
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- 11. Gliomas, Glioneuronal Tumors, and Neuronal Tumors •Divided into 6 different categories. • Adult-type diffuse gliomas • Pediatric-type diffuse low-grade gliomas • Pediatric-type diffuse high-grade gliomas • Circumscribed astrocytic gliomas • Glioneuronal and neuronal tumors • Ependymomas
- 12. Gliomas, Glioneuronal Tumors, andNeuronal Tu mors • 14 Newly recognized types have been added. • For some these, integrating histological appearances and molecular features is required to arrive at a diagnosis. • There have also been some nomenclature changes to existing entities. • Diffuse Midline Glioma H3 K27- altered from H3 K27M- mutant • Division of diffuse gliomas into adult-type and pediatric type.
- 13. Gliomas, Glioneuronal Tumors,and Neuronal Tumors • Simplification of the classification of common, adult type, diffuse gliomas. • It Includes 3 types. • Astrocytoma, IDH-mutant • Oligodendroglioma, IDH-mutant and 1p/19q-codeleted • Glioblastoma, IDH-wildtype. • Gliosarcoma and Giant Cell Glioblastoma are not listed in the classification, they're discussed in their respective chapters. • Nomenclature and grading of common, adult-type, diffuse astrocytic gliomas. • All IDH mutant diffuse astrocytic tumors are considered a single type, Astrocytoma, IDH-mutant. It is then graded as 2, 3 or 4. • Grading is no longer entirely histologic, e.g. CDKN2A/B homozygous deletion results in a CNS WHO grade of 4, even in the absence of microvascular proliferation or necrosis. • 3 genetic parameters are used as criteria for a diagnosis of Glioblastoma, IDH-wildtype. • TERT promoter mutation • EGFR gene amplification • Combined gain of entire chromosome 7 and loss of entire chromosome 10
- 14. Gliomas, Glioneuronal Tumors, and NeuronalTumors Pediatric-type low-grade and high-grade diffuse gliomas. • The low grade group includes. • Diffuse astrocytoma, MYB- or MYBL1-altered • Angiocentric glioma • Polymorphous low-grade neuroepithelial tumor of the young • Diffuse low-grade glioma, MAPK pathway-altered • The high grade group includes. • Diffuse midline glioma, H3 K27-altered • Diffuse hemispheric glioma, H3 G34-mutant. • Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH- wildtype • Infant-type hemispheric glioma. Neuronal and Glioneuronal Tumor • 3 new types have been added. • Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (Provisional) • Myxoid glioneuronal tumor • Multinodular and vacuolating neuronal tumor
- 15. Gliomas, Glioneuronal Tumors,and Neuronal Tumors • Ependymomas • Classified by combination of histopathological, molecular features and anatomic site. • Divided into molecular groups. • Supratentorial • Supratentorial ependymoma • Supratentorial ependymoma, ZFTA fusion-Positive • Supratentorial ependymoma, YAP1 fusion-Positive • Posterior fossa (PF) • Posterior fossa ependymoma • Posterior fossa group A (PFA) ependymoma • Posterior fossa group B (PFB) ependymoma • Spinal compartments • Spinal ependymoma, MYCN-amplified • Myxopapillary Ependymoma is now considered WHO Grade 2 rather than 1 • Papillary, clear cell, and tanycytic morphological variants are no longer listed as subtypes of ependymoma. • Graded as WHO grade 2 or 3 , anaplastic ependymoma is no longer listed.
- 16. Choroid Plexus Tumors This familyof tumors has been separated from the category of primary neuroepithelial tumors. Classification is largely unchanged.
- 17. Medulloblastomas 4 principal moleculargroups. • Medulloblastoma, WNT-activated • Medulloblastoma, SHH-activated and TP53-wildtype • SHH-1 • SHH-2 • SHH-3 • SHH-4 • Medulloblastoma, SHH-activated and TP53-mutant • Medulloblastoma, non-WNT/non-SHH • 8 Molecular sub-groups (Group ¾ Subgroup 1-8). Histopathological Classification listed in 2016 has now been described as morphological patterns of Medulloblastoma, histologically defined.
- 18. Other Embryonal Tumors Includes: • Atypical teratoid/rhabdoidtumor. • AT/RT-SHH • AT/RT-TYR • AT/RT-MYC • Embryonal tumor with multilayered rosettes. • Embryonal tumor with multilayered rosettes, C19MC-altered • Embryonal tumor with multilayered rosettes, DICER1-mutated • Cribriform neuroepithelial tumor (Provisional). • CNS neuroblastoma, FOXR2-activated. • CNS tumor with BCOR internal tandem duplication. • CNS embryonal tumor NEC/NOS.
- 19. Pineal Tumors Pineocytoma Pineal parenchymaltumor of intermediate differentiation Pineoblastoma Pineoblastoma, miRNA processing-altered_1 Pineoblastoma, miRNA processing-altered_2 Pineoblastoma, RB1- altered (pineal retinoblastoma) Pineoblastoma, MYC/FOXR2-activated Papillary tumor of the pineal region Desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant
- 20. Meningiomas • Considered asingle type. • Broad morphological sub-types, 15 subtypes. • Choroid and Clear cell Meningioma have higher rate of recurrence, hence assigned WHO Grade 2. • Grading should not be done on the basis of a rhabdoid cytology or papillary architecture alone. • Several molecular biomarkers are also associated with classification and grading of meningiomas • SMARCE1 --- clear cell subtype. • BAP1 --- rhabdoid and papillary subtypes • KLF4/TRAF7 --- secretory subtype • TERT promoter mutation and/or homozygous deletion of CDKN2A/B --- CNS WHO grade 3 • H3K27me3 loss of nuclear expression --- potentially worse prognosis • Methylome profiling --- prognostic subtyping
- 21. Mesenchymal, Non-Meningothelial Tumors •Only those entities that occur uniquely in the CNS. • Common soft tissue tumors, found in the CNS are no longer included given that their diagnostic features are identical to their soft tissue counterparts, e.g. Leiomyoma. • New Types include • Intracranial mesenchymal tumor, FET-CREB fusion-positive (Provisional). • CIC-rearranged sarcoma • Primary intracranial sarcoma, DICER1-mutant
- 22. Nerve Tumors • Paragangliomaare now included in nervous tumor. • The paraganglioma of the cauda equina/filum Terminale region is now recognized as a distinct tumor type as, Cauda equina neuroendocrine tumor (previously paraganglioma). • Melanotic schwannoma name has been changed to Malignant melanotic nerve sheath tumor. • A new subtype has been added to the neurofibroma section: Atypical neurofibromatous neoplasm of unknown biological potential (ANNUBP)
- 23. Lymphomas and HistiocyticTumors • Includes those lymphoid and histiocytic tumor entities that occur relatively often in the CNS or that have special histological or molecular features when they occur in the CNS.
- 24. Tumors of theSellar Region • Adamantinomatous craniopharyngioma and Papillary craniopharyngioma are now considered separate tumor types. • Pituicytoma, Granular cell tumor, and Spindle cell oncocytoma are included in 1 section as a related group of tumor types. • The new term Pituitary neuro-endocrine tumor (PitNET) is introduced. • Pituitaryblastoma has been added as tumor type.
- 25. Metastatic Tumors • Divided in2 categories • Metastases to the brain and spinal cord parenchyma • Metastases to the meninges
- 26. Genetic Tumor Syndromes •This section has been expanded, now covering 8 disorders not covered in the prior Blue Book. • Carney complex • DICER1 syndrome • Familial paraganglioma syndrome • Melanoma-astrocytoma syndrome • Familial retinoblastoma • BAP1 tumor predisposition syndrome • Fanconi anemia • ELP1-medulloblastoma syndrome
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