Download - Pathology of intracranial tumors lecture
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Pathology of intracranial tumours- a primer
E.E.U. AKANG, MBBS, FMCPath, FWACP
Consultant Pathologist, Department of Pathology, University College Hospital, Ibadan, Nigeria
National Postgraduate Medical College of Nigeria 2014 Revision Course in Pathology
FEBRUARY 14, 2014 LAGOS, NIGERIA
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E k’abo! Welcome to Lagos!
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Outline• Introduction• Historical background• Classification of
intracranial neoplasms• Neuroepithelial
neoplasms• Meningeal neoplasms• Sellar region neoplasms• Germ cell neoplasms• Lymphoid-Haematopoietic
neoplasms• Cranial/spinal nerve
neoplasms• Metastatic neoplasms• Paediatric CNS neoplasms• Clinical effects• Intraoperative
consultation• Concluding remarks
OBJECTIVES- Student should have a good grasp of the classification, clinical manifestations, gross and microscopic features of common intracranial neoplasms
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Introduction 1- Definition
Intracranial neoplasms are a diverse group of >130 primary CNS neoplasms, and numerous secondary neoplasms arising via either direct spread from neighbouring structures or haematogenous spread from distant sitesEach tumour entity has distinctive biology, treatment and prognosis
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Introduction 2- EpidemiologyMortality from CNS tumours in developed and developing nations is 3.6 and 2.9 per 100,000 yearly All intracranial neoplasms are potentially fatal (closed space and infiltrative properties)No known pre-malignant or in situ stages2/3 of 10 neoplasms are gliomas 2/3 of gliomas are astrocytic2/3 of adult neoplasms are supratentorial2/3 of paediatric neoplasms are infratentorial Cerebral/spinal cord tumour ratio is up to 12:1 10 CNS neoplasms only very rarely metastasiseMetastatic tumours > 10 CNS neoplasms
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Mostly sporadic, with cumulative mutations in oncogenes, tumour suppressor, DNA repair and apoptosis genesA few CNS neoplasms are familial (von Hippel Lindau, Turcot, Gorlin, Cowden, NF1, NF2, Li-Fraumeni)Clonal expansion of tumour stem cells
Introduction 3- Aetiopathogenesis
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Outline• Introduction
• Historical background
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Historical background•CNS tumours were believed to be rare in native Africans up until half a century ago•Expanding general/specialist medical services have led to increasing recognition of CNS tumours•Most of the early reports from the sub region have been clinical neurosurgery series
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Early African studies•1st CNS tumours reported from Africa were autopsy cases•Strachan, 1934- South Africa- less common in Bantus than other races•Davies, 1957- 6 gliomas among 2162 PMs- not uncommon•Jackson & Okubadejo, 1963-13 CNS tumours among 3489 PMs- uncommon
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Ibadan- 1991-2007Sahabi 2008, Ibadan-Progressive increase in CNS tumour rates356 histologically confirmed CNS neoplasms-264 (74.2%) adults & 92 (25.8%) childrenGliomas most common, followed by meningiomasFemale predominance in meningiomas; Relative decline of both metastases and choriocarcinoma
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
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Classification and grading of intracranial neoplasms (WHO)
Histological groups
• Neuroepithelial
• Meningeal
• Sellar region
• Germ cell
• Lymphoid-Haematopoietic
• Cranial/spinal nerve
• Metastatic
WHO grading•Grade 1- slow growing, non-malignant, with long-term survival•Grade 2- relatively slow-growing, recurrent, progress to higher grade•Grade 3- malignant, recur as higher grade•Grade 4- very aggressive malignant neoplasms
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Clinical categorization of CNS neoplasms
INTRA-AXIALNeuroepithelial tumoursMetastatic tumoursEXTRA-AXIAL• IntraduralMeningiomaSellar region tumoursCP angle tumoursNerve sheath tumoursMetastatic tumours• ExtraduralMetastatic tumours
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
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Neuroepithelial neoplasms
• Astrocytic tumours
• Oligoastrocytic tumours
• Oligodendroglial tumours
• Ependymal tumours
• Choroid plexus tumours
• Other neuroepithelial tumours
• Tumours of the pineal region
• Embryonal tumours (medulloblastoma, CNS Primitive Neuroectodermal Tumour/PNET, atypical teratoid/rhabdoid tumour)
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Astrocytic neoplasmsGrouped by:•Topography (supratentorial vs. infratentorial)•Differentiation (fibrillary, protoplasmic, gemistocytic)•WHO grade1- (Pilocytic astrocytoma, chordoid glioma, desmoplastic astrocytoma, pituicytoma), 2- (Well-differentiated- low cellularity/ minimal pleomorphism, no vascular proliferation or necrosis), 3- (Anaplastic- or malignant- high cellularity, marked pleomorphism, no vascular proliferation or necrosis) 4- (Glioblastoma- high cellularity, marked pleomorphism with microvascular proliferation and/or necrosis)•Growth pattern (Expansile (WHO grade 1 and PXA- grade 2) vs. Diffuse (WHO grades 2 to 4))
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Pilocytic astrocytomaWHO grade 1 neoplasms of childhoodOccur in cerebellum, sellar region, brainstem and optic nerveCerebellar neoplasms have an excellent prognosisGrossly cystic neoplasms with mural noduleBiphasic pattern (solid and microcystic foci with bipolar cells associated with Rosenthal fibres and eosinophil granular bodies)
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Astrocytoma, grade 2Low cellularity, mild pleomorphism, no vascular proliferation and no necrosisMay progress to grade 3 astrocytomaMedian survival 6 years; peak 5th decade of lifeFibrillary astrocytomaSmall stellate, elongated cells with fibrillary processesGemistocytic astrocytomaLarge, plump cells with abundant glassy eosinophilic cytoplasm and peripheral nuclei
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Anaplastic astrocytoma, grade 3Acquisition of additional mutations compared to grade 2 astrocytomaMay progress to secondary glioblastomaHigh cellularity, significant pleomorphism, but no microvascular proliferation and no necrosisMedian survival times of 2 years and peak in the 5th decade of life
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Glioblastoma
Grade 4 neoplasm showing cellularity, pleomorphism and vascular proliferation and or necrosisPeak in 6th decade, but any age. Median survival of 1 year
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Glioblastoma - 2 molecular pathways
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OligodendrogliomaHemispheric gliomas of young/middle aged adultsFrontal, temporal, parietal and occipital lobes in ratio 3:2:2:1Calcification on X-ray/CT Histology shows uniform cells with perinuclear haloes (fried egg) with chicken-wire capillaries. Better prognosis than astrocytoma (mean survival- 20yr grade 2 and 10yr grade 3). Surgery, chemotherapy, and radiotherapyDel 1p/19q has good prognosis
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Cancer stem cell theory applied to gliomas (Louis, 2006)
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EpendymomaMost sporadic; few familial in type 2 neurofibromatosisArise from lining of fourth (children) and lateral (adult) ventricles. Commonest spinal cord neoplasms Grade 1- Subependymoma: rare incidental tumour; and myxopapillary ependymoma: cauda equinaGrade 2- well differentiated ependymomaGrade 3- anaplastic ependymoma
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Ependymoma
Histological features: 1. Perivascular pseudorosettes2. True rosettes with central lumen having a limiting membraneCiliary basal bodies (blepharoplasts) can be demonstrated on electron microscopy
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Ependymoma-Bony (left) and cartilaginous (right) metaplasia
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Anaplastic ependymoma-A- Perivascular pseudorosettes, B- ependymal true rosettes, C-
papillary differentiation, D- microvascular proliferation, E-pseudopalisading necrosis
A
B
C
D
E
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Choroid plexus neoplasmsChoroid plexus papilloma (CPP) Grade 1 childhood tumours of lateral ventricle. Grossly, pink cauliflower like massCause hydrocephalus mainly by obstruction of flow, but also rarely, by overproduction of CSF.Histologically are papillary neoplasms that recapitulate normal choroid plexusAtypical CPP- Grade 2CP carcinoma- Grade 3Hyperdiploidy, multiple gains
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MedulloblastomaMalignant, invasive embryonal cerebellar tumour of children with neuronal differentiation, and tendency to spread via CSFCommonest malignant paediatric CNS neoplasmMost are sporadic but familial cases with nevus basal cell carcinoma (Gorlin) or Turcot syndromes may occurDel 17p and isochromosome 17qPTCH (Gorlin), APC (Turcot)Variants- classical, large cell, anaplastic, desmoplastic
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
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MeningiomaOrigin from meningothelial arachnoid cells of convexities, parafalcine, sphenoid, olfactory and suprasellar regions, optic nerve and choroid plexusCommoner in blacks (30-40%) than Caucasians (10-15%)Females (steroid receptors)Most sporadic; Familial in NF2Recurrence rate is 11%WHO grade 1- benign (del 22q)Grade 2- atypical (del 14q)Grade 3- malignant (del 1p)Co-express EMA and vimentin
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Meningeal neoplasmsSahabi, 2008
HISTOLOGICAL TYPES
HISTOLOGICAL SUBTYPES
WHO GRADETOTAL
I II III
Meningioma
Transitional 45 0 0 45
Meningothelial 21 0 0 21
Fibroblastic 8 0 0 8
Psammomatous 5 0 0 5
Secretory 3 0 0 3
Angiomatous 2 0 0 2
Atypical 0 3 0 3
Anaplastic 0 0 7 7
Mesenchymal tumours
Haemangiopericytoma 0 3 1 4
Other Haemangioblastoma 3 0 0 3
TOTAL 87 6 8 101
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
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Pituitary adenomaSellar neoplasms are commoner in Nigeria (20-28%), than other parts of Africa (7.5-13.4%)Pituitary adenomas comprise 2/3 of sellar neoplasmsClinically manifest with1. Mass effect (headache, vomiting, papilloedema)2. Bitemporal hemianopsia3. Pituitary hormone dysfunction(panhypo- or selected hyper- function)Best grouped by immune or by EMAtypical adenoma and pituitary carcinoma are uncommon
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CraniopharyngiomaAwelimobor, 2011
Majority originate from Rathke cleft remnants. Commonest childhood sellar region tumour. Common in Nigeria and Japan.Benign cystic locally invasive neoplasms with dark oily fluid and calcific material. Epithelial islands with peripheral palisading and central stellate reticulum. Express steroid receptors. Mutation of beta-catenin (CTNNB1) gene. Recurrence in 10-62%
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
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Germ cell neoplasms
Origin from aberrant migrating germ cells in midline (pineal and suprasellar regions) Rare (except in Taiwan and Japan)
GerminomaTeratoma (mature, immature, with malignant transformation)Yolk sac tumourEmbryonal carcinomaChoriocarcinomaMixed germ cell tumour
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
• Lymphoid-Haematopoietic
neoplasms
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Lymphoid-haematopoietic neoplasmsCNS may be involved in advanced systemic NHL (e.g. Burkitt), Hodgkin disease, plasmacytoma or myelomaPrimary CNS lymphoma (PCNSL) occurs in both immunosuppressed and immunocompetent individualsNHL most common (particularly high grade B cell NHL)EBV associated with PCNSLMay present as solitary or multiple parenchymal nodules or with diffuse meningeal infiltration
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
• Lymphoid-Haematopoietic
neoplasms
• Cranial/spinal nerve neoplasms
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Vestibular schwannoma-Cerebellopontine angle
Antoni A
Antoni B
Vestibular part of VIII nerveSporadic (unilateral in 95% of cases) or familial (bilateral in NF2)Cellular (Antoni A) and loose (Antoni B) areas
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
• Lymphoid-Haematopoietic
neoplasms
• Cranial/spinal nerve neoplasms
• Metastatic neoplasms
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Metastatic CNS neoplasmsOutnumber 10 CNS neoplasms by ratio of 10:14-30% of intracranial neoplasms in PM seriesPrimary sources include choriocarcinoma, lung, breast, prostate, soft tissue, lymphoid, GIT and female genital tract malignanciesUsually multiple and located at grey-white matter junction
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
• Lymphoid-Haematopoietic
neoplasms
• Cranial/spinal nerve neoplasms
• Metastatic neoplasms
• Paediatric CNS neoplasms
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Paediatric CNS neoplasms
•ASR is 25-40 per 106 in developed and <15 per 106
in developing nations•Due partly to under ascertainment and partly to racial factors•Previous Nigerian and African series have shown prominence of astrocytoma, medulloblastoma, ependymoma and craniopharyngioma•There is need for population based registries to assess true burden of these neoplasms, particularly in Africa
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Intracranial Tumours: adults vs. children
•ADULTS: 2/3 supratentorial–meningioma–pituitary adenoma–malignant astrocytoma/glioblastoma•CHILDREN: 2/3 posterior fossa–pilocytic astrocytoma–medulloblastoma–ependymoma
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
• Lymphoid-Haematopoietic
neoplasms
• Cranial/spinal nerve neoplasms
• Metastatic neoplasms
• Paediatric CNS neoplasms
• Clinical effects
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Clinical effects•Clinical effects of intracranial neoplasms are those of raised ICP (headache, projectile/effortless vomiting and papilloedema) and are modified by anatomical location of the neoplasm•There may be seizures, localizing signs, behavioural abnormalities, cognitive deficits and endocrinopathies
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HERNIATIONS
A- cingulate
B- uncal
C- tonsillar
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With bilateral
uncal
herniation there
is stretching and
then rupture of
penetrating
branches of the
basilar artery
supplying the
midbrain and
upper pons
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
• Lymphoid-Haematopoietic
neoplasms
• Cranial/spinal nerve neoplasms
• Metastatic neoplasms
• Paediatric CNS neoplasms
• Clinical effects
• Intraoperative consultation
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Intraoperative consultationA primary role of pathologist in patient management
-Gross examination
-Frozen section
-Cytology
Awelimobor 2011-
100% concordance rate between cytological and frozen section diagnosis, as well as between frozen section and routine paraffin embedded tissue diagnosis
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Glioblastoma- cytology, Frozen section and permanent section
Awelimobor, 2011
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Pituitary adenoma- cytology and frozen sectionAwelimobor, 2011
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Meningioma- cytology, Frozen section and permanent section
Awelimobor, 2011
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Outline• Introduction
• Historical background
• Classification of intracranial neoplasms
• Neuroepithelial neoplasms
• Meningeal neoplasms
• Sellar region neoplasms
• Germ cell neoplasms
• Lymphoid-Haematopoietic
neoplasms
• Cranial/spinal nerve neoplasms
• Metastatic neoplasms
• Paediatric CNS neoplasms
• Clinical effects
• Intraoperative consultation
• Concluding remarks
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Concluding remarks
•Biological characteristics of intracranial neoplasms have been discussed•These neoplasms may originate froma. Brain structure and its coveringsb. Neighbouring tissues by direct invasionc. Distant sites by haematogenous spread• Clinical effects are those of raised ICP and are modified by the anatomical location of the neoplasm
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Further reading(1) J Neurol Sci (Turk) 2007;24(3):212-8.(2) CA Cancer J Clin 2011;61(2):69-90.(3) West Afr Med J Niger Pract 1967;16(1):31-42.(4) Asian Pac J Cancer Prev 2008;9(2):267-70.(5) Neurosurgery in Africa. Ibadan: Ibadan University Press; 1989.(6) West Afr Med J 1963;12:251-63.(7) Cancer 1980;46(10):2322-4.(8) East Afr Med J 2000;77(1):4-8.(9) National Postgraduate Medical College of Nigeria; 2008.(10) Arch Pathol Lab Med 2009;133(1):78-82.(11) Pediatr Pathol Lab Med 1996;16(5):791-800.(12) Ann Trop Paediatr 2002;22(2):159-63.(13) J Neurol Neurosurg Psychiatry 2004;75 Suppl 2:ii2-11.(14) WHO Classification of Tumours of the Central Nervous System. Lyon: IARC; 2007.(15) WHO Classification of Tumours of the Central Nervous System. Lyon: IARC; 2013.(16) Afr J Med Sci 1973;4(2):143-59.(17) Afr J Med Sci 1973;4(2):99-106.(18) Afr J Med Sci 1973;4(2):178-86.(19) J Natl Cancer Inst 1975;55(2):281-4.
(20) J Clin Neurosci 2006;13(6):649-54.(21) West Afr Med J 1963;12:251-63.(22) Afr J Med Med Sci 1976;5(3):181-4.(23) Cancer in Africa: epidemiology and prevention. Lyon: IARC Press; 2003.(24) Childs Nerv Syst 1985;1(1):39-44.(25) Childs Nerv Syst 2010;26(8):1021-7.(26) Trop Doct 2004;34(4):223-5.(27) Robbins and Cotran pathologic basis of disease. Philadelphia: Saunders Elsevier; 2010.(28) Robbins basic pathology. Philadelphia: Saunders Elsevier; 2013.(29) Greenfield’s neuropathology. London: Edward Arnold; 2008.(30) Escourolle and Poirier manual of basic neuropathology. Philadelphia: Butterworth Heinemann, 2004.(31) Modern surgical neuropathology. Cambridge: Cambridge University Press, 2009.(32) Neuropathology. Pathology Articles. Medscape. http://emedicine.medscape.com/pathology
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Thanks for listening!
O d’abo!