who classification of meningioma.pptx

WHO CLASSIFICATION OF MENINGIOMA

1. WHO CLASSIFICATION OF CNS TUMOUR 1

2. WHO CNS TUMOUR CLASSIFICATION 2 Grading was done based on Histological /Morphological pattern Grade I - Tumour with low proliferative potential with possibility of cure after surgical resection Grade II - Tumour with cytological atypia (variation in nuclear shape / size with accompanying hyperchromasia ) alone. Grade III - Tumours with anaplasia and mitotic activity. Grade IV - Tumours with microvascular proliferation and /necrosis.

3. 3 WHO CNS TUMOUR CLASSIFICATION 2021 Grading based on both histologicalmorphological and molecular features Grading is done within tumour types (not across tumour types) Arabic numericals used ( instead of Roman numericals ) Based on biological elements (previously based on clinical outcomes) Grading not reflected in classification

4. CLASSIFICATION OF MENINGIOMA WHO/Mayo Clinic criteria broadly stratifies meningothelial tumors into three tiers of increasing biologic potential— Meningioma (WHO grade I) Atypical meningioma (WHO grade II) Anaplastic meningioma (WHO grade III) 4

5. ATYPICAL MENINGIOMA Atypical meningiomas are defined as: 1. containing four or more mitotic figures per 10 high-power microscopic fields (0.16 mm2) or 2. brain invasion, with tumor breaching beyond the pia or 3. exhibiting at least three of the following features: a. hypercellularity b. patternless , sheet-like growth c. macronucleoli d. small cell components with high nuclear:cytoplasmic ratio e. zones of spontaneous (i.e. noniatrogenic as seen after embolization) necrosis. 5

6. ANAPLASTIC MENINGIOMA Anaplastic meningiomas are defined as: 1. containing 20 or more mitoses per 10 high-power microscopic fields (0.16 mm2) or 2. exhibiting a loss of differentiated features resulting in carcinoma-melanoma-, or sarcoma-like appearances. 6

7. IMAGING Extra – axial mass with dural tail Uniformly contrast enhancing Extensive peritumoural edema , more common in subtypes namely angiomatous, microcystic secretory and lymphoplasmacyte rich Restricted diffusion on MRI,a finding often associated with increased cellularity associated with higher grade histology 7

8. 8 Meningioma: homogenous contrast enhancement and anchorage to dura . MRI image shows dural tail sign, suggestive not diagnostic of meningioma . Anaplastic Meningioma: on post contrast MRI, large tumour with irregular borders ,central areas of low signal intensity corresponding to foci of necrosis

9. EPIDEMIOLOGY Peak incidence : older adults .The risk increases with age. Females are afflicted more commonly than males (especially at spinal levels) The most common brain tumour in USA . 9

10. LOCALIZATION: Most meningiomas arise within the cranial cavity, are dura based and found in the vicinity of the superior sagittal sinus, over the cerebral convexities, or in contact with the falx cerebri. Basally positioned examples favor the sphenoid ridge, olfactory grooves, tuberculum sellae, and parasellar region. Still others are anchored to the petrous ridge, presenting as cerebellopontine angle tumors when posteriorly situated. Intracranial meningiomas may also originate within the stroma of the choroid plexus and rest entirely within the ventricular system. At spinal levels , meningiomas clearly favor the thoracic region, cervical examples being uncommon and lumbar lesions rare. E pidural and intra-osseous meningiomas as well as variants located entirely outside the craniospinal confines are also recognised . The latter are usually encountered in the head and neck region and include orbital (i.e. optic sheath), glabellar, sinonasal, oropharyngeal, subgaleal , juxtaparotid , and cutaneous examples. Rarely, ectopic meningiomas are situated e.g. in the mediastinum, lung,or brachial plexus). 10

11. PATHOPHYSIOLOGY Meningiomas driven by chromosome 22q alterations ( eg NF2,SMARCB1) arise in neural crest cell derived meninges, including convexities,falx,tentorium and spinal cord . Meningiomas driven by hedgehog signaling pathway,PI 3K signaling,TRAF7,KLF4 and POLR2A arise in the mesodermal derived meninges of the midline and paramedian anterior,central and ventral posterior skull base . 11

12. ETIOLOGY Radiation exposure is a risk factor . eg ionizing cranial irradiation, full mouth Dental xray series . growth of meningiomas is subject to hormonal influence. Coupled with their frequent expression of progesterone (and less commonly, estrogen as well as androgen) receptors and the rapid enlargement of some examples during pregnancy or the luteal phase of the menstrual cycle . The association of multifocal meningiomas with NF2 is noteworthy, the genetic locus for which resides on chromosome 22q12. Allelic loss involving this band is a frequent feature of meningiomas . Germline mutation in SMARCB1,SMARCE1 Craniocerebral trauma although less common . 12

13. CLINICAL FEATURES Clinical features are due to tumour compression , most commonly headache, seizure ,focal neurological deficit. Based on cranial nerves involvement ,most commonly involve facial nerve , can extend upto trigeminal nerve , vesticulocochlear nerve and glossopharyngeal, vagus , spinal accessory nerve also. Features of raised ICT due to development of hydrocephalus while tumour size is more than 6 cm . 13

14. MORPHOLOGY On g ross assessment, the typical meningioma is a solid, lobulated, or globose mass that is broadly anchored to the dura mater. Cystic variants, although uncommon . the term meningioma en plaque , the occasional lesion that presents (usually over the sphenoid ridge) as a poorly delimited, carpet-like growth , insidiously permeate the neighboring skull, provoking a highly characteristic form of osteoplastic expansion and bony remodeling known as hyperostosis or, if chronically neglected, come to attention as visible masses in the scalp. 14

15. None of these findings brand a meningioma as atypical or anaplastic, although involvement of the cranial floor greatly prejudices matters against the neurosurgeon and so predisposes to tumor recurrence and progression following attempted resection. T he lesion that cannot be easily separated from the adjacent brain or spinal cord, as this may imply transgression of the pia-arachnoid and invasion of the neuroparenchyma proper—nevertheless, the surgeon’s gross impression of brain invasion does not correlate well with microscopic confirmation, likely due to some cases adhering to pia rather than truly invading parenchyma. 15

16. 16 Meningioma :the broad dural base depicted here is characteristic

17. Morphological subtypes Meningothelial hyperplasia Fibrous meningioma Transitional meningioma psammomatous meningioma microcystic meningioma secretory meningioma Chordoid type Lymphoplasmacytic type Metaplastic Angiomatous Clear cell type Rhabdoid Papillary 17

18. MORPHOLOGICAL SUBTYPES Meningotheliomatous variant Most classic /typical . Grade 1 tumour characterized by a lobular microarchitecture populated by cells having delicate round or oval nuclei, inconspicuous nucleoli, lightly eosinophilic cytoplasm, and indistinct cytoplasmic borders ( “syncytial” meningiomas). tumor cells concentrically wrapped in tight whorls, nuclear clearing (“holes”) and pale nuclear “ pseudoinclusions ” consisting of invaginated cytoplasm, the lamellated calcospherules known as psammoma bodies 18

19. fibrous (or fibroblastic ) meningiomas adopt a mesenchymal profile variably collagenized consisting of spindled tumor cells in fascicular array . Grade 1 tumour 19 Fascicular pattern

20. Transitional meningioma Features of both meningothelial and fibrous type maintaining a lobular arrangement but having a tendency to cellular elongation and streaming. Meningothelial with fibrous with conspicuous whorls and psammoma bodies . 20

21. psammomatous meningioma Tumors of this type characteristically occur in middle-aged to elderly women Often thoracic 21

22. The microcystic meningioma is named for its content of variably sized intercellular vacuoles these often appearing empty but in some instances containing a lightly PAS-positive fluid Cobweb like background the common finding of severe peritumoral cerebral edema on preoperative neuroradiological study. 22 Cobweb like pattern results from extracellular fluid accumulation

23. The secretory meningioma distinguished by its content of “ pseudopsammoma bodies”—globular hyaline inclusions that are eosinophilic, intensely PAS positive, and diastase Peritumoural edema on neuroimaging 23 Eosinophilic globules

24. Chordoid type Cords or trabeculae of eosinophilic often vacuolated cells set in mucoid matrix like chordoma. Peritumoral lymphoplasmacytic infiltrates with germinal center formation presentation in childhood or adolescence with manifestations of the Castleman syndrome —polyclonal dysgammaglobulinemia , iron-refractory anemia, hepatosplenomegaly, and retarded growth and sexual maturation. Ribbon like architecture ,vacuolated cytoplasm ,mucinous stromas

25. The lymphoplasmacyte -rich meningioma tumor infiltrated by chronic inflammatory elements, at times so heavily overshadowing meningothelial cells. An association with hypergammaglobulinemia and/or anemia has been occasionally noted 25 Brisk inflammatory infiltrate ,later one an immunostain for somatostatin receptor 2a

26. Metaplastic meningiomas can contain bone, cartilage, or adipocytic elements. Progressive xanthomatous change, that is, nonspecific cytoplasmic lipidization , rather than true metaplasia seems to account for so-called lipomatous meningiomas . 26

27. angiomatous meningioma Numerous blood vessels,often more endothelial cells than meningothelial cells. tendency to cause conspicuous edema of the adjoining cerebrum and sometimes marked degenerative nuclear atypia. 27 Hypervascularity,degenerative nuclear atypia

28. Clear cell type Composed of glycogen-rich, water-clear cells that are often disposed in patternless sheets traversed by bands of perivascular collagen these unusual tumors typically manifest little or nothing in the way of classic meningothelial attributes (e.g. whorls) 28 Cytoplasmic clearing, collagenous bands,absence of whorls

29. Rhabdoid type WHO grade III tumour Rhabdoid cells ie plump cells with eccentric nuclei ,open chromatin,prominent nucleoli and eosinophilic cytoplasm . 29 Rhabdoid features, later one shows IHC for vimentin

30. Papillary type WHO CNS GRADE III Perivascular psudopapillary pattern Loss of cell cohesion Resembles pseudorosettes . 30

31. NEW ENTITIES - WITHIN RED BOX

32. Microscopy General classic findings: Oval nuclei with delicate chromatin Frequent intranuclear pseudoinclusions Syncytial tumour cells with abundant eosinophilic cytoplasm. Numerous whorls Occasional psammoma bodies. 35

33. IMMUNOHISTOCHEMISTRY Positive Somatostatin Receptor 2A (SSTR2A) is the most specific,sensitive . Positive EMA,Vimentin,PR ± S100 Ki67 often varies with grade 36

34. DIFFERENTIAL DIAGNOSIS The first differential diagnosis comes into a surgeon’s mind is vestibular swannoma , presenting with ipsilateral facial palsy . On the basis of seizure,visual disturbance and constitutional symptoms ,meningioma must be differentiated from other tumours -Oligodendroglioma -Astrocytoma -Pituitary adenoma -Primary CNS lymphoma -medulloblastoma -Ependymoma -Craniopharyngioma -Pinealoma -Brain metastasis OTHERS : - AV malformation - Brain aneurysm - Bacterial brain abcess -Tuberculosis - Toxoplasmosis - Hydatid cyst -CNS cryptococcosis -CNS aspergillosis 37

35. Meningothelial meningioma Usually a single mass Meningothelial hyperplasia Can be upto 100 cell layers thick Discontinuous growth pattern Never invades dura 38

36. Fibrous meningioma STAT6 – SOMATOSTATIN RECEPTOR 2a + Solitary fibrous tumour/Hemangiopericytoma STAT6 + SOMATOSTATIN RECEPTOR 2a - 39

37. Fibrous meningioma Uniform cellular SSTR2a + SOX 10+ S 100 variable Swannoma Biphasic( Antoni A,B) Verocay body SSTR2a - SOX 10+ S 100 + 40

38. Chordoid meningioma SSTR2a + EMA + S100 – GFAP – Brachyury - Intracranial myxoid neoplasm CHORDOMA CHORDOID GLIOMA CHONDROSARCOMA INTRACRANIAL MYXOID MESENCHYMAL TUMOURS 41

39. Clear cell meningioma SSTR2a + CA 9 - Metastatic clear cell renal cell carcinoma SSTR2a – CA9 + RCC + PAX 8 + 42

40. Angiomatous and microcystic subtype SSTR2a + Inhibin - Hemangioblastoma SSTR2a – Inhibin + 43

41. PROGNOSIS Extent of surgery and WHO grading Estimated 10 year overall survival for non malignant meningiomas is 81.4% Rate of recurrence is 50% for grade II, 90% for grade III 44

42. TREATMENT Observation ,if asymptomatic . Gross total resection is usually curative. Post operative radiation if incompletely excised or WHO grade 2 or 3. Pre operative ventriculoperitoneal shunting done if hydrocephalus develops . 45

43. CONCLUSION Meningioma is a benign slow growing tumour, rarely malignant also. To summarise , it is a common yet intriguing brain tumour that demands attention and awareness . Understanding its characteristics, its diagnosis and treatment options ,we can better manage this condition. To conclude ,meningioma is a treatable condition with early detection ,precise diagnosis, personalised treatment , we can significantly improve patient’s survival rate and reduce morbidity. 46

44. 47 THANK YOU