2021 WHO Classification of brain tumours.pptx

Classification of CNS tumours, Classification of brain tumours, WHO 2021 Classification, 2007 WHO Classification, 2016 WHO Classification

1. Classification of brain tumours Department of Neurosurgery Dr RE Anto 18/03/2022

2. Contents Introduction Epidemiology Risk factors Etiology Hereditary sx Clinical presentation Classification systems Benign vs Malignant Tumour locations WHO Classification System Main changes References

3. Introduction Brain tumour is an abnormal mass of tissue intracranially, in which cells grow and multiply uncontrollably, seemingly unchecked by the mechanisms that control normal cells. Multiple classification systems Primary vs. Secondary Type of cell origin Location Grading (Benign or Malignant)

4. Epidemiology Primary brain tumours are relatively rare: 2% of all cancers in adults NOTE: In paeds : 15-20 % of paediatric cancers Great variance in degree of incidence between 1 st world and developing countries May be due to differences in resources like imaging modalities and better registration and data capture systems Incidence rises with age Males: Female (1.5:1) – except meningiomas (female > male)

5. Davis FG, McCarthy BJ. Current epidemiological trends and surveillance issues in brain tumours. Expert Rev Anticancer Ther2001;1:395–401.

6. Risk factors D evelop as a consequence of accumulated genetic alterations that permit cells to evade normal regulatory mechanisms and destruction by the immune system Seizures may herald development of cerebral tumours by years! Risk for any cerebral tumour after first admission for epilepsy is increased 20-fold Highlights the need for continued surveillance of patients with new-onset seizures

7. Etiology Some epidemiological studies suggest increased incidence of astrocytomas Petrochemicals eg vinyl chloride Electromagnetic radiation High dose ionizing radiation 10 times risk of meningiomas 2.5 times risk for gliomas Primary CNS lymphoma Viruses eg EBV Immunocompromised (transplant patient, AIDS)

8. Hereditary syndromes < 5% of all primary CNS tumours Neurofibromatosis I and II (MPNST, Optic n glioma, Meningiomas, Vestibular schwannoma) Von-Hippel Lindau sx ( Haemangioblastoma ) Tuberous sclerosis (SEGA, Cortical tubers) Li-Fraumeni sx (Malignant gliomas, PNET, Medulloblastoma) MEN I (Multiple endocrine neoplasia) ( Pituitary adenomas, Malignant schwannoma) Turcot sx (GBM, Medulloblastoma) Werner’s sx (Meningioma)

9. Clinical Presentation Generalized or focal signs. Epilepsy: focal or generalized tonic clonic seizures Frontal lobe: Anosmia Dementia Urinary incontinence Conjugate deviation of eyes Aphasia

10. Clinical Presentation Temporal lobe: Temporal lobe epilepsy Auditory hallucinations Memory difficulties Parietal lobe: Hemisensory changes Sensory apraxia Occipital lobe: Visual field changes Chiasmatic lesions: Visual field changes

11. Clinical Presentation Posterior fossa lesions: CN Palsies Long tract signs Obstructive HCP Sellar lesions Hormone dysfunction Acromegaly Hyperprolactinemia Hypopituitarism Hypocortisolemia Visual disturbances

12. Classification systems Primary: Arise from the brain tissue or surrounding meninges itself Glial Non-glial (in structures in the brain including nerves, vessels, glands) Secondary: Arises from other tumours in the body and migrate to the brain 5-10 times more common than primary CNS tumours (most common tumours in adults)

13. Benign vs Malignant This distinction is less significant than for other systems Benign Slow-growing tumours Low cellularity Few mitosis No necrosis No vascular proliferation However, location of these tumours can have lethal consequences despite its histological classification Eg : FM meningioma causing compression of the medulla and causing cardiorespiratoy arrest

14. Malignant Not malignant “metastasize” out of CNS (rare) Morphological Features: 1. Nuclear atypia 2. Mitosis 3. Endothelial Proliferation 4. Necrosis Daumas-Duport C, Scheithauer B, O'Fallon J, Kelly P (1988). Grading of astrocytomas . A simple and reproducible method. Cancer 62: 2152-2165.

15. WHO Classification 1979 : 1 st edition – Histological typing of CNS tumours 1993: 2 nd edition – Reflected advances in immunohistochemistry 2000: 3 rd edition – Started introduction pathology and genetics 2007: 4 th edition – used up until 2015 (Youmans 6 th edition) 2016: Revised 4 th edition – substantial revision of 4 th edition

16. WHO Classifications (2007/2016)

17. WHO Classifications (2007/2016) Formulating concept of how CNS tumours diagnoses are structured in the molecular era Restructured diffuse gliomas, medulloblastomas and incorporated genetically identified entities. Embryonal tumours (removal of PNET) Ependymoma genetic variants introduced

18. WHO Classifications (2007/2016) Addition of newly recognized entities, variants and patterns: IDH-wildtype and IDH-mutant glioblastoma (entities) Diffuse midline glioma, H3 K27M–mutant (entity) Embryonal tumour 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) Multinodular and vacuolated pattern of ganglion cell tumor (pattern)

19. WHO Classifications (2007/2016) Deletion of former entities, variants and terms: Gliomatosis cerebri Protoplasmic and fibrillary astrocytoma variants Cellular ependymoma variant “Primitive neuroectodermal tumor” Addition of brain invasion as a criteria for atypical meningioma Restructuring of solitary fibrous tumour and hemangiopericytoma (SFT/HPC) as one entity and adapting a grading system to accommodate this change Expansion and clarification of entities included in nerve sheath tumors , with addition of hybrid nerve sheath tumors and separation of melanotic schwannoma from other schwannomas Expansion of entities included in hematopoietic/lymphoid tumors of the CNS (lymphomas and histiocytic tumors

20. 2021 WHO Classification 5 th edition of WHO Classification of Tumours of the Central Nervous System (CNS) Sixth version of the international standard for the classification of brain and spinal cord tumours Build on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy ( cIMPACT -NOW)

21. cIMPACT -NOW Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy – Not Officially WHO Seven updates from 2016-2020

22. Gliomas, glioneuronal tumors, and neuronal tumours Adult-type diffuse gliomas Astrocytoma, IDH-mutant Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Glioblastoma, IDH-wildtype Pediatric-type diffuse low-grade gliomas Diffuse astrocytoma, MYB- or MYBL1-altered Angiocentric glioma Polymorphous low-grade neuroepithelial tumor of the young Diffuse low-grade glioma, MAPK pathway-altered Pediatric-type diffuse high-grade gliomas 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

23. Gliomas, glioneuronal tumors, and neuronal tumours Circumscribed astrocytic gliomas Pilocytic astrocytoma High-grade astrocytoma with piloid features Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma Chordoid glioma Astroblastoma, MN1-altered

24. Glioneuronal and neuronal tumours Ganglioglioma Desmoplastic infantile ganglioglioma (DIG) / desmoplastic infantile astrocytoma Dysembryoplastic neuroepithelial tumor Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (provisional inclusion) Papillary glioneuronal tumor Rosette-forming glioneuronal tumor Myxoid glioneuronal tumor Diffuse leptomeningeal glioneuronal tumor Gangliocytoma Multinodular and vacuolating neuronal tumor Dysplastic cerebellar gangliocytoma ( lhermitte-duclos disease) Central neurocytoma Extraventricular neurocytoma Cerebellar liponeurocytoma

25. Ependymal tumours Supratentorial ependymoma Supratentorial ependymoma, ZFTA fusion-positive Supratentorial ependymoma, YAP1 fusion-positive Posterior fossa ependymoma Posterior fossa ependymoma, Group PFA Posterior fossa ependymoma, Group PFB Spinal ependymoma Spinal ependymoma, MYCN-amplified Myxopapillary ependymoma Subependymoma

26. Choroid Plexus tumours Choroid plexus papilloma Atypical choroid plexus papilloma Choroid plexus carcinoma

27. Embryonal tumours - Medulloblastoma Medulloblastomas, molecularly defined Medulloblastoma, WNT-activated Medulloblastoma, SHH-activated and TP53-wildtype Medulloblastoma, SHH-activated and TP53-mutant Medulloblastoma, NON-WNT/NON-SHH Medulloblastomas, histologically defined

28. Other CNS Embryonal tumours Atypical teratoid/rhabdoid tumor Cribriform neuroepithelial tumor (provisional inclusion) Embryonal tumor with multilayered rosettes (ETMR) CNS neuroblastoma, FOXR2-activated CNS tumor with BCOR internal tandem duplication CNS embryonal tumor

29. Pineal tumours Pineocytoma Pineal parenchymal tumor of intermediate differentiation Pineoblastoma Papillary tumor of the pineal region Desmoplastic myxoid tumor of the pineal region, smarcb1-mutant

30. Cranial and Paraspinal nerve tumours Schwannoma Neurofibroma Perineurioma Hybrid nerve sheath tumor Malignant melanotic nerve sheath tumor Malignant peripheral nerve sheath tumor Paraganglioma

31. Meningioma Meningothelial Fibrous Transitional Psammomatous Angiomatous Microcystic Secretory Lymphoplasmacyte -rich Metaplastic Chordoid Clear Cell Atypical Papillary Rhabdoid Anaplastic

32. Mesenchymal, non-meningothelial tumours – Soft tissue tumours Fibroblastic and myofibroblastic tumors Solitary fibrous tumor Vascular tumors Hemangiomas and vascular malformations Hemangioblastoma Skeletal muscle tumors Rhabdomyosarcoma Uncertain differentiation Intracranial mesenchymal tumor, FET-CREB fusion-positive (provisional inclusion) CIC-rearranged sarcoma Primary intracranial sarcoma, dicer1-mutant Ewing sarcoma

33. Chondro-osseous tumours Chondrogenic tumors Mesenchymal chondrosarcoma Chondrosarcoma Notochordal tumors Chordoma (including poorly differentiated chordoma)

34. Melanocytic tumours Diffuse meningeal melanocytic neoplasms Meningeal melanocytosis Meningeal melanomatosis Circumscribed meningeal melanocytic neoplasms Meningeal melanocytoma Meningeal melanoma

35. Hematolymphoid tumours - Lymphomas CNS lymphomas Primary diffuse large b-cell lymphoma of the CNS Immunodeficiency-associated CNS lymphoma Lymphomatoid granulomatosis Intravascular large b-cell lymphoma Miscellaneous rare lymphomas in the CNS MALT lymphoma of the dura Other low-grade b-cell lymphomas of the CNS Anaplastic large cell lymphoma (ALK+/ALK−) T-cell and NK/t-cell lymphomas

36. Germ cell tumors Mature teratoma Immature teratoma Teratoma with somatic-type malignancy Germinoma Embryonal carcinoma Yolk sac tumor Choriocarcinoma Mixed germ cell tumor

37. Tumors of the sellar region Adamantinomatous craniopharyngioma Papillary craniopharyngioma Pituicytoma, granular cell tumor of the sellar region, and spindle cell oncocytoma Pituitary adenoma ( pitNET ) Pituitary blastoma

38. Metastases to the CNS Metastases to the brain and spinal cord parenchyma Metastases to the meninges

39. Main changes in 5 th edition Builds on prior version by placing greater emphasis on molecular markers in terms of classification and grading Heterogenous classification Layered report structure Integrated diagnosis Histopathological classification CNS WHO Grade Molecular information

40. Grading Within tumour types Unlike other WHO classification systems that graded each tumor based on its own features (i.e. the most low-grade version of a particular tumor was given grade 1) This approach has been abandoned, in favour of grading tumours within “type” Example: No Grade 1 Diffuse Astrocytoma, IDH Mutant (only 2,3 or 4) Glioblastoma, IDH-wildtype – can only be Grade 4 Arabic numerals Previously – I,II,III,IV (Roman numerals) Replaced by Arabic Numerals – 1,2,3,4 Example: Meningioma, CNS WHO Grade 1

41. Grading Anaplastic modifier The term anaplastic, used extensively in the prior classifications has been dropped in favour of grading only. Thus what was previously known as an "anaplastic astrocytoma" is now referred to as an "astrocytoma, IDH-mutant, CNS WHO grade 3 Molecular grading For the first time, molecular features have been explicitly added to the grading schema May supersede histological features. Example: an IDH-wildtype astrocytoma with low-grade histologic features can be considered Grade 4 (Glioblastoma) in the presence of EGFR amplification, TERT promoter mutation or the combined gain of chromosome 7 and loss of chromosome 10

42. Other changes NOS (Not Otherwise Specified) Diagnostic information (histological or molecular) needed to assign a specific WHO diagnosis is not available Example: not enough tissue available or no resources available NEC (Not Elsewhere Classified) Results do not readily allow for a WHO diagnosis Clinical, histological, or molecular mismatch

43. References Louis D, Perry A, Wesseling P et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A Summary. Neuro-Oncology. 2021;23(8):1231-51. doi:10.1093/ neuonc /noab106 Louis D, Perry A, Reifenberger G et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary. Acta Neuropathol . 2016;131(6):803-20. doi:10.1007/s00401-016-1545-1 – Pubmed International Agency for Research on Cancer, Otmar D. Wiestler . WHO Classification of Tumours of the Central Nervous System. (2016) ISBN: 9789283244929 GreenBerg 9 th edition Davis FG, McCarthy BJ. Current epidemiological trends and surveillance issues in brain tumours. Expert Rev Anticancer Ther2001;1:395–401.

44. Thank you