j0305257 Systemic pathology Nervous system j0305257 Brain swelling, ischemia j0305257 Brain swelling û generalised increase in the volume of brain (blood, water, ions) → clinical signs related to raised intracranial pressure / intracranial shift / herniation û û diffuse (vasodilatation, oedema – vasogenic, cytotoxic, interstitial) û focal (space-occupying lesions – inflammation, tumor, trauma, vascular lesion) û û herniations: ðsupracallosal – interhemispheric undex falx cerebri ðtranstentorial – temporal (3rd nerve, secondary braunstem haemorrhage) ðtonsillar – foramen magnum, vital centres compressed j0305257 Brain swelling ûgross: ðflattened gyri, narrow sulci, slit-like ventricles û ûmicro: ðneuropil vacuolation ðswelling of the cytoplasm and processes of astrocytes ðperivascular optically empty spaces ðmyelin less vividly colored j0305257 Diffuse brain swelling edém mozku.jpg j0305257 Diffuse brain swelling edém mozku mikro.jpg j0305257 Brain swelling - pathogenesis û main types: ðvasogenic • due to increased cerebral vascular permeability (esp. by neoangiogenesis) • adjacent to tumors, abscesses, haemorrage, ischemia ð ðcytotoxic • due to hypoxia / ischemia , toxic damage – cell membrane injury, ↑intracellular fluid ð ðinterstitial • due to damage of ventricular lining (hydrocephalus, CSF diffusion into the white matter) • û j0305257 Hydrocephalus û increased amonut of CSF, ↑ intracranial pressure û infants x older children, adults û û caused by: ðincreased CSF production ðdecreased CSF resorption • meningitis, subarachnoid haematoma ðobstruction to CSF flow • congenital x aquired – trauma, tumors, infection, blood coaguli, cyst ðhydrocephalus e vacuo (secondary/compensatory) û j0305257 Hydrocephalus j0305257 Encephalomalatia (cerebral infarction) ûcolliquative necrosis û„white“ ischemic x haemorrhagic – blood reflux, venous û û clinically: stroke or transient ischaemic attack – TIA û ûpathogenesis: ð arterial thrombosis (AS, arteritis, arteriopathy) ð thrombembolia ð venous thrombosis ð diffuse small vessel problems – spasm, vasculitis ð external pressure (haematoma) ð systemic hypoxia û ûthe size and distribution depends on: ðdiameter and localisation of affected artery ð closure promptness ðpossibilities of collateral circulation j0305257 Encephalomalatia ûgross: ðapprox. 24hours – affected tissue softened and swollen, loss of border between grey and white matter ð oedema ð infarcted tissue undergoes colliquative necrosis ð ûmicro: ðneuronal ischemia (loss of cytoplasmic basophilia, nuclei), endothelial + glial oedema ðneutrophils, after 2 days infiltration with macrophages (cytoplasm filled with the lipid products of myelin breakdown) ð reactive astrocytes and proliferating capillaries at the edge of the infarct • ðNecrotic tissue phagocytosed → fluid-filled pseudocystic cavity lined by glial tissue j0305257 Encephalomalatia (cerebral infarction) encefalomalácie.jpg encephalomalacia haemorrhage j0305257 Encephalomalatia (+ reactive macrophages) encefalomalacie starší 40x 01.jpg haemorrhagic infarction macrophages j0305257 Encephalomalatia encefalomalacie starší zrnéčkové bb 200x 02.jpg macrophages j0305257 Intracranial haemorrhage ûExtradural – epidural (haemorrhage between skull and dura mater) ð mostly due to skull fracture (rupture of a. meningea media) ð arterial, traumatic, acute, ð clinically: variable lucid interval later onset of signs - increased intracranial pressure û ûSubdural (haemorrhage between dura and arachnoid matter) ðrupture of venous sinuses or small bridging veins ðacute x chronic (particularly in elderly - headache, memory loss and confusion, personality change) û ûSubarachnoid (haemorrhage between arachnoid matter and pia mater) ð inborn defect: aneurysm (saccular „berry“ aneurysm on the circle of Willisi) ð AS, hypertension, tumor, coagulative disorders û û j0305257 Intracranial haemorrhage ûIntracerebral ð nontraumatic arterial • hypertension + regressive vessel wall changes → rupture of blood vessel • AS • vasculitis, amyloid angiopathy, tumors ð traumatic û ðpremature newborn • extension into ventricular system, subarachnoid space - possible hydrocephalus ð û Intraventricular (haemocephalus) ðsecondary after haemorrhage extension into ventricular system j0305257 CNS infections ûetiology ðbacterial incl. tb, rickettsia ðviral ðfungal, parasitic (protozoan, etc.)… ð ð ð ð ðhaematogenous spread ðlocal extension – direct spread (adjacent inflammations) ðtrauma – direct implantation ðalong the peripheral nerves ðiatrogenic infection j0305257 Leptomeningitis ð ðchemical (irritation) ðacute pyogenic (bacterial) ðacute aseptic – lymphocytic (viral) ðchronic (granulomatous tuberculous; fungal) ð ðdirect spread x blood-borne ð j0305257 Bacterial leptomeningitis ûsymptoms: ð headache, joint + muscle pain ð sleepiness, fever, vomiting, loss of consciousness, convulsion ð petechial rash ð photophobia ð signs of meningeal irritation ð sepsis ð ð!! acute onset, rapid diagnosis + ATB therapy necessary j0305257 Bacterial leptomeningitis ûetiology: ðIn neonates: E. coli, Str. agalactiae, Listeria ð2-5 years.: Str. pneumoniae (Haemophilus now rare) ð5-30 years: Neisseria meningitidis (type B) ðover 30 years: Str. pneumoniae, staph., etc. ûGross: ðpia mater hyperemic, pus deposits ðopaque CSF ðbrain swelling, sometimes cortical necrosis j0305257 Bacterial leptomeningitis 01 j0305257 Bacterial leptomeningitis ûmicro: ðhyperemia, neutrophilic + macrophagic infiltrate, secondary phlebitis + thrombosis û û ûcomplications: ðcerebral abscess ðsubdural empyema ð cerebral infarction ðepilepsy ðleptomeningeal fibrosis, subarachnoid cysts, obstructive hydrocephalus j0305257 Bacterial leptomeningitis purulentní leptomeningitida 40x 01.jpg j0305257 Bacterial leptomeningitis purulentní leptomeningitida 100x 01.jpg Brain swelling granulocytes j0305257 Acute aseptic meningitis ûinfectious ð viral (mumps, coxackie, echoviruses, EBV, HSV) ðusually self-limited ðgross: hyperemic pia mater, slight edema ðmicro: lymphocytic infiltration û chemical or other irritant j0305257 Chronic meningitis ûgranulomatous ðMycobacterium tbc., granulomas, obliterative endarteritis ðmeningovascular neurosyphilis ðfungi: Cryptococcus neoformans, Aspergillus, etc. û chronic ðLyme disease – aseptic meningitis ð û immune deficiency ðAIDS, immunosuppression, cachexia ð j0305257 Tuberculous meningitis û etiology: mycobacterium tuberculosis û spread: usually hematogenous in primary pulmonary tuberculosis û AIDS (M. avium-intracellulare complex) û gross: exudative - thick gelatinous exudate, most marked at the base of the brain; û proliferative: small white granulomas û ð û û j0305257 tuberculous meningitis SurgicalPathologyOfTheNervousSystem_125-3 1 cerebellum 2 oblongata 3 gelatinous inflammatory infiltrate 1 2 3 j0305257 Encephalitis ûprimary ðneurotropic viruses ðanthropozoonozes - from animals transmitted to humans ûsecondary ð other underlying disease • viruses (HSV, enterovirus), rickettsie, parasites (toxoplasmosis…), spirochets (lues),.. û ûmicro (viral encephalitis): ðneuronal damage, reactive glial changes ðperivascular „cuff“ infiltrate of lymphocytes, plasma cell û j0305257 Viral encephalitis - myelitis û usually + meningitis û spread: haematogenous x neural (retrograde) û tropism - specific cell type or area involved û etiology: ðarthropod-borne (tick-borne), mumps, enteroviruses (poliomyelitis), HSV, CMV, EBV, HIV, rabies ð ûgross: ðhyperemic meninges, brain edema û ûmicro: ð perivascular, parenchymal mononuclear cell infiltrate, glial cell reaction, oedema, neuronophagia, viral inclusions ûpossibility of latency, immune-mediated disease, late sequelae ð j0305257 Viral encephalitis - myelitis Obrázek2.jpg j0305257 Viral encephalitis KBinfiltrát.jpg perivascular infiltrate of lymphocytes + plasma cell j0305257 Viral encephalitis ûwith the formation of inclusion bodies ðRabies ðHSV1, HSV2 ðPoliomyelitis ûWithout inclusion bodies ðtick-borne viral encephalitis ðHIV-associated encephalitis û j0305257 Encephalitis û Others ðAcute disseminated encephalomyelitis – immune-associated demyelinisation ðSubacute sclerosing panencephalitis (measles virus) ðTyphus fever - rickettsiae ðNeurosyphilis û û j0305257 Viral encefalitis with inclusion bodies ûrabies, lyssa ðincubation 3-8 weeks → with axonal retrograde flow to the brainstem, spinal cord, dorsal root ganglia, cerebral cortex, cerebellum, hippocampus ðmicro Negri bodies (eosinophilic inclusions of the size of red blood cells in the cytoplasm of neurons) û herpetic encephalitis (HSV1, HSV2) ðFrontal cortex, other parts of the gray matter ðhemorrhagic necrosis, intranuclear inclusions ðsevere (sometimes fatal) course j0305257 Viral encefalitis with inclusion bodies ûPoliomyelitis ð enteroviruses, coxsackie, ECHO ðpharyngitis, enteritis, myocarditis, myositis… ðapprox. in 10% affinity to the motoric neurons → anterior horns of the spinal cord, (gyrus precentralis) → symptoms of paralysis ðanterior horns of the spinal cord markedly swollen, hyperemic ðsmall intranuclear inclusions → neuronal necrosis → inflammatory reaction + neuronophagia → gliosis j0305257 Rabies GreenfieldsNeuropathology_047-1 Negri bodies, intracytoplasmatic inclusions copy j0305257 Herpetic encephalitis HSV encefalitis1.jpg intranuclear inclusions copy j0305257 HSV encefalitis2.jpg Herpetic encephalitis 1 1 necrotic neurons 2 edema 3 perivascular inflammatory infiltrate 2 3 copy j0305257 poliomyelitis acuta anterior 200x 02.jpg Poliomyelitis Necrotic neurons, inflammatory infiltrate j0305257 poliomyelitis acuta anterior 400x 03.jpg Poliomyelitis 1 1 intranuclear inclusions 2 perivascular inflammatory infiltrate 2 j0305257 Viral encephalitis without inclusion bodies ûTick-borne encephalitis (Middle Europe) ðmostly asymptomatic ðsymptoms rarely •convulsions, confusion, delirium, coma, often with focal neurological deficits such as reflex asymmetry ðmeningeal form, meningoencephalitic or encephalomyelitic form •both gray and white matter affected (panencefalitis) j0305257 Viral encephalitis without inclusion bodies ûHIV encephalitis ûHIV-associated dementia û ðacute aseptic meningitis in 10% of HIV + patients ðsubacute/chronic HIV encephalitis ðvacuolar myelopathy ðopportunistic encephalitis (herpetic, CMV, toxoplasmosis) û j0305257 Neurosyphilis ðdifferent CNS changes in the 2nd, 3rd stage ðmeningovascular form •chronic meningitis •obliterative (Heubner) endarteritis ðparenchymatous form • atrophic cortex + hemosiderin; gummata •progressive mental deficit → dementia •tabes dorsalis – sensory nerves of the dorsal roots j0305257 Neurosyphilis 02 1 cortical atrophy, red discoloration - progressive paralysis 2 initial stage 1 2 kopie j0305257 prion encephalopathy ûPrions (proteinaceous infectious particles) ðprotein particles capable of inducing conformational change of tissue PrPc to pathogenic PrPSc ð ðmicro: • spongiform encephalopathy – microscopic vacuolisation • numerical atrophy of neurons • reactive gliosis • missing inflammatory response!! ðlong incubation period, rapid progression (dementia) → L j0305257 prion encephalopathy ûCreutzfeldt-Jacob disease ðsporadic ðfamilial ðiatrogenic ðvariant (BSE?) j0305257 Creutzfeldt-Jacob disease SurgicalPathologyOfTheNervousSystem_425-8 j0305257 Neurodegenerative diseases j0305257 Neurodegenerative diseases ûloss of specific groups of neurons → typical clinical signs ðapoptosis + oxygen radicals – neuronal damage ðpathological protein aggregates •disease-specific – classification ðgenetic risk j0305257 Degenerative diseases ûcortex – Alzheimer disease – dementia û subcortical – Parkinson d. – tremor, dyskinesia, rigidity û amyotrophic lateral sclerosis – motor neurone loss û ûPick‘s disease ûHuntington‘s disease ûParkinson‘s disease, parkinsonism j0305257 Alzheimer´s disease û the most common neurodegenerative condition û pre-senile dementia ðpossible start at the age of 50 (or sooner) → slow progression (-> 8-10+ years) → death due to inanition, bronchopneumonia ðM:F 1:2 ð sporadic x familial (about 5%) û û j0305257 Alzheimer´s disease ûgross: ðmarked cortical atrophy (frontal, temporal) ðloss of cortical grey and white matter, secondary hydrocephalus ðlimbic system affected - hippocampus ûmicro: ðneuronal loss ðA-beta amyloid plaques and neurofibrillary tangles ðamyloid angiopathy - deposits in the wall of capillaries and arterioles ðnon-specific changes, only more pronounced û j0305257 Alzheimer´s disease 01 j0305257 Alzheimer´s disease SurgicalPathologyOfTheNervousSystem_428-8 1 senile plaques with amyloid core 2 neuron 3 neuroglia 1 2 3 j0305257 Frontotemporal dementias û similar clinical picture – language deterioration, personality changes ûmay have specific protein aggregates -deposits (tau) ûsporadic or rare familial ûapprox. 10% od dementias û j0305257 Pick‘s disease û5% of dementias, M>F ûgross ðmax. atrophy in the frontal and temporal lobe (foliate threads) - lobar atrophy ûmicro ðloss of neurons in the I.-III. cortical layers ðdemyelination in the white matter ðneuron‘s cytoplasm with Pick bodies (filamentous inclusions), Hirani bodies, granulovacuolar degeneration û j0305257 Pick‘s disease 05 copy j0305257 Pick‘s disease SurgicalPathologyOfTheNervousSystem_432-8 j0305257 Degenerative diseases of basal ganglia and brainstem ûmovement disorders ð rigidity ðabnormal posturing ðchorea ûreduction of voluntary movements ûincrease of involuntary movements j0305257 Huntington‘s disease ûAD ðgene on chromosome 4p – huntingtin protein •CAG triplet repeat, if> 35 → disease •↑ number of repeats → earlier onset, more rapid course ûbegins after age of 30 (4th, 5th decade) ûprogressive course (15-20 years) ûuncoordinated, jerky body movements, gradually dementia j0305257 Huntington‘s disease ûgross: ðAtrophy of n. caudatus a putamen ðdilated lateral + 3rd ventricle ðcortical atrophy ðbrain weight reduction of up to 30% ûmicro: ðloss of neurons ðfibrillary gliosis ð j0305257 Huntington‘s disease 08 copy 1 lateral ventricles dilatation 2 atrophy of caput nuclei caudati 1 2 j0305257 Parkinsonism ûclinical condition due to the damaged nigro – striatal dopaminergic system û↓ inhibitory neurotransmitter ûstiff facial expression, muscle rigidity, slowness of voluntary movements (bradykinesia), tremor ûforms: ðPrimary PS: •Parkinson's disease •multiple system atrophy, i. e striatonigral degeneration ðSecondary PS: •after encephalitis, in arteriosclerosis, after CO poisoning, other toxins, tumors, etc. j0305257 Parkinson‘s disease ûidiopatic ðmostly sporadic (exogenous, mitochondrial dysfunction?), minority familial ðprogressive course (10 years), may be + dementia û ûgross: ðminor general changes, decolorization of substantia nigra ûmicro: ðloss of neurons → astrogliosis ðnumerous Lewy bodies (α-synuclein) in the cytoplasm of damaged neurons j0305257 Parkinson‘s disease - brainstem kopie 11 1 nucleus niger 2 atrophic nucleus niger with loss of pigment 1 2 j0305257 Degenerative diseases of spinal cord ûAmyotrophic lateral sclerosis ðloss of motor neurons ð ûSpinocerebellar hereditary ataxia ûSpinal muscular atrophy û û j0305257 Demyelinating diseases ûdisintegration of myelin sheaths ðaxonal regression ûprimary x secondary (after axonal damage) ð ûmultiple sclerosis ûprogressive multifocal leukoencephalopathy (JC virus) ûacute disseminated encephalomyelitis (after viral infection, rarely vaccination) û j0305257 Multiple sclerosis ûmore frequent in women between 20 and 40 ûunclear etiology ð autoimmune disorder triggered by exogenous factor (virus?) in susceptible host (genetics) ûprogressive course, episodic acute relapses with neurologic deficit ð variable presentation ðsensoric, sensitive, motor dysfunction ðends in severe psychomotoric disturbance + cachexia ð trophic ulcers, pressure sores, sepsis j0305257 Multiple sclerosis ûgross: ð white (less commonly gray) matter with multiple, well-demarcated, gray-tan solid lesions – plaques •variable size mm-cm ðMostly periventricular, but also in optic fasciculus…. û ûmicro: ðActive plaques, early (pink, softer) •myelin reduction, perivascular monocytic infiltrate + activation of macrophages → axonal destruction ðInactive plaques: •disappearance of oligodendrocytes and myelin, reactive gliosis, persistence of numerous nerve fibers without inflammation û j0305257 Multiple sclerosis ûAcute form ðfatal within a few weeks / months ðmay be in children ðpink lesions (plaques) in white matter of the brainstem, spinal cord ð ûNeuromyelitis optica ðfasciculus opticus → bilateral blindness ðnecrotic centre of plaques • û j0305257 Multiple sclerosis SMmakro.jpg active (pink) plaques j0305257 Tumors of the nervous system j0305257 neuroectodermal tumors ûtumors of the central nervous system ûperipheral neuroectodermal tumors ûtumors of the autonomic nervous system ûmelanocytic tumors j0305257 INTRACRANIAL TUMORS j0305257 Intracranial tumors ûprimary extracerebral (meningioma, schwannoma, neurofibroma) ûprimary intracerebral (gliomas – astrocytoma, oligodendroglioma, ependymoma, neuronal tumors, primitive neuroectodermal tumors PNET – medulloblastoma, endocrine t., vascular t., lymphomas ûsecondary tumors – metastases, leukemic infiltration û j0305257 Intracranial tumors û focal signs according to the localisation (excitation, later loss of function) û general raised intracranial pressure (seizures, headache, visual defects, nausea etc.) û ûhistologically benign brain tumors can kill the patient – growing in a position where they cannot be completely resected ! j0305257 Metastatic tumors of the CNS û CNS metastases in 25% of cancer deaths ûmost common origin in adults ðlung ca (small cell, adenocarcinoma) ðbreast ca ðmelanoma ðrenal ðcolorectal û most common origin in children ðleukaemia, lymphoma ðosteosarcoma, rhabdomyosarcoma j0305257 Biologic potential ûpossible infiltrating growth of histologically benign tumors ûlocalisation highly important (grave consequences even in benign tumors) ûrare metastases outside the CNS j0305257 Age factor ûin chidren - mostly primary intracerebral incl. PNET; infratentorially (posterior fossa) ûin adults – number of secondary t. rises with age; mostly supratentorially j0305257 classification of intracranial tumors ûAstrocytic tumors û ûOligodendroglial tumors û ûEpendymal tumors û ûChoroid plexus tumors û ûNeuronal/glioneuronal tumors û ûPineal tumors û ûEmbryonal tumors û j0305257 Astrocytic tumors ûDiffuse (fibrillary) astrocytoma (Grade II) û ûAnaplastic astrocytoma (Grade III) û ûGlioblastoma (Grade IV) û û ûPilocytic astrocytoma (Grade I) û ûPleomorphic xanthoastrocytoma (Grade II) û ûsubependymal giant cell astrocytoma (Grade I) j0305257 Astrocytic tumors Diffuse (fibrillary) astrocytoma û low grade - grade II/IV (WHO) û slow growth, high degree of differentiation û !! intrinsic tendency for malignant progression to anaplastic astrocytoma → glioblastoma û û in all age groups ðmostly young adults, M>F û ûAnywhere in the brain - poorly demarcated or infiltrative tumor û û j0305257 Astrocytic tumors Diffuse (fibrillary) astrocytoma ûmicro: ðwell-differentiated fibrillary, germistocytic (mass of eosinophilic cytoplasm), rare protoplasmic astrocytes ðslightly increased cellularity in comparison with normal tissue tumor ð stroma often microcystic ðusually no mitotic activity ðwithout necrosis or microvascular proliferation j0305257 Diffuse (fibrillary) astrocytoma astrocytom WHO GII 100x j0305257 Diffuse (fibrillary) astrocytoma astrocytom WHO GII 200x j0305257 Astrocytic tumors Glioblastoma ûgrade IV/IV (WHO) – anaplastic glioma û most common and most malignant primary brain tumor û û typically in adults, usually 45-75 years of age û mostly de novo – primary glioblastoma ðshort history, >60 years of age ûpossible transformation from preexisting astrocytoma gr. II or III – secondary glioblastoma, ð history 1-10 yrs, around 45 years of age ûrapidly growing, infiltrative (very poor prognosis) û û gross: ðvariable appearance – white and firm regions, yellow and soft parts, foci of necrosis, cysts, hemorrhages ð j0305257 Astrocytic tumors Glioblastoma ûmicro: ð pleomorphic tumor cells - severe cellular and nuclear atypia ðtumor is regionally heterogeneous • alternatition of pleiomorphic and more regularly arranged areas ðhigh mitotic rate ðconspicuous microvascular proliferation and / or necrosis ð pseudopalisading of tumor cells around necrotic areas j0305257 Glioblastoma 20 j0305257 Glioblastoma glioblastom 40x 02 1 psudopalisading around areas of necrosis 2 necrosis 1 2 j0305257 Glioblastoma glioblastom 100x 01 1 2 1 1. pseudopalisading around areas of necrosis 2 necrosis j0305257 Glioblastoma glioblastom 100x 03 Pleiomorphic tumor cells j0305257 Astrocytic tumors Pilocytic astrocytoma ûgrade I (WHO) ûgrows very slowly ûgrowth begins in childhood - clinical signs manifest around age of 20 (and later); in cerebellum or near III. and IV. ventricle, resection posssible ûmicro: ðbiphasic structure solid / cystic • compact region with bipolar tumor astrocytes with eosinophilic Rosenthal fibers • microcystic, sparsely cellular areas with multipolar tumor cells with granular eosinophilic bodies and eosinophilic globules ðdegenerative atypia and calcification ð infrequent mitosis, sm. nuclear pleiomorphism and hyperchromasia ð glomeruloid vascular endothelial proliferation often ðsmall necrosis possible • j0305257 Pilocytic astrocytoma Hermanova_OBR4B (1) bipolar tumor astrocytes with granular eosinophilic bodies and Rosenthal fibers j0305257 Pilocytic astrocytoma Hermanova_OBR4A Microcystic areas with multipolar tumor cells j0305257 Oligodendroglial tumors ûOligodendroglioma (Grade II/IV) û û Anaplastic oligodendroglioma (Grade III) û Mixed oligoastrocytomas (Grade II, III) j0305257 Oligodendroglial tumors Oligodendroglioma ûgrade II (WHO) û û in adults; slow growth ûMicro: ðuniform tumor cells with round nuclei and perinuclear halos ðmicrocalfications (X-ray) ðareas of mucoid degeneration ðabundant branching capillaries j0305257 Oligodendroglioma oligodendrogliom.jpg j0305257 Ependymal tumors ûEpendymoma (grade II) û ûAnaplastic ependymoma (grade III) û û ûMyxopapillary ependymoma (grade I) û ûSubependymoma (grade I) j0305257 Epemdymal tumors Ependymoma ûgrade II (WHO) û ûin children - usually around IV. vetricle, in adults - spinal cord, with neurofibromatosis type 2 û ûmicro: ð fusiform cells with long processes,uniform round to oval nuclei ðfine fibrillary background ðcanalicular formations, perivascular pseudorosettes ðsporadic or no mitotic figures j0305257 ependymom 100x.jpg Ependymoma Perivascular pseudorosettes, uniform population of tumor cells j0305257 Ependymoma ependymom 200x.jpg Perivascular pseudorosettes, uniform population of tumor cells j0305257 Tumors of the choroid plexus ð ûChoroid plexus papilloma (grade I) ûAtypical choroid plexus papilloma (grade II) û ûChoroid plexus carcinoma (grade III) j0305257 Embryonal tumors ûPrimitive aggressive malignant tumors of childhood û ûTumors "of small blue cells" grade IV ð Medulloblastoma ð ðSupratentorial primitive neuroectodermal tumor ð ðEpendymoblastoma ð ðRetinoblastoma ð… j0305257 Embryonal tumors Medulloblastoma ûgrade IV (WHO) û ûtumor of first two decades of life ûhighly malignant but radiosensitive ûin cerebellum, midline in children ð local infiltration, meningeal and CSF spread → hydrocephalus ðgross – focal pink/grey tumor û ûmicro: ðhighly cellular ðsmall hyperchromatic nuclei, carrot-shaped ð neuroblastic Homer-Wright‘s rosettes ð high mitotic activity ðdifferentiation to neuronal / other cells possible j0305257 Medulloblastoma mbl, 200x.jpg j0305257 Medulloblastoma C:\Documents and Settings\jirka\Plocha\dejavu - mbl, paragangliom\MBL\Brož\BrožHE.jpg j0305257 Tumors of the meninges ûMeningioma (Grade I) ð(Syncytial (+) ðFibroblastic (+) ðTransitional (+) ðPsammomatous ðAngioblastic ðMicrocystic) û û(Atypical meningioma, chordoid and clear cell (Grade II) û ûRhabdoid, papillary, anaplastic (Grade III) û û+ solitary fibrous tumor of meninges, (hemangiopericytoma), sarcomas,…. ) j0305257 Tumors of the meninges Meningioma ûgrade I (WHO classification) ûusually benign, common (20% of all intracranial tumors), adults ûpredominantly on the hemispheral convexity û origin from arachnoidal cap cells û ûgross: ðusually solitary , well demarcated, firm, whorl-like pattern on cut surfaces ðattached to the dura, cortical compression, rare skull invasion û micro: ð highly variable ð whorls, bundles ðcommon laminated calcific concretions – psammoma bodies (X-ray) j0305257 Meningioma 27 1.Lobular meningioma 2.Flat meningiomas 3.Dura mater 4.Falx cerebri 1 2 3 4 j0305257 Meningioma meningiom 40x 01 1.whorl formations of meningothelial cells 2.psammoma bodies 3.vessels 1 2 3 j0305257 Meningioma meningiom 100x 01 1 2 1. whorl formations of meningothelial cells 2. psammoma bodies j0305257 Peripheral nerve sheat tumors j0305257 Benign tumors û Schwannoma û ûneurofibroma (solitary; multiple - neurofibromatosis type 1 ) û ûperineurioma û ûneurothecoma û ûgranulosa cell tumor j0305257 Schwannoma •peripheral myelinisation û in connection with peripheral nerve ûintracranial - cerebellopontine angle – VIII. nerve „acoustic neuromas ûcompression (excitation, later loss of function) û ûgross: ðwell-circumscribed encapsulated lesion, may be attached to the nerve ûmicro: ðcellular areas of densely packed spindle cells (Antoni A pattern, Verocay bodies – nuclear palisading) ðintermixed with looser, myxoid regions (Antoni B pattern) û j0305257 Schwannoma j0305257 Schwannoma 1 neurinom 100x 01 2 Textové pole: 1 1 3 1.Antoni A 2.Antoni B 3. nuclear palisading j0305257 Schwannoma neurinom 100x 02 1 2 1.Antoni A 2.nuclear palisading j0305257 Neurofibroma û peripheral nerve sheath tumor û solitary x multiple (neurofibromatosis I. , II. type) ûcutaneous x plexiform (along nerves, possible malignant transformation) ð ûgross: ðunencapsulated soft roundish nodules ð ûmicro: ðspindle cells, „S“ and „C“ shaped ðextracellular loose myxoid or collagenous matrix ðsporadic small vascular lumina j0305257 neurofibroma neurofibrom1 Bundles of spindle cells in collagenous stroma j0305257 neurofibroma neurofibrom2 wavy „S“ shaped nuclei j0305257 Neurofibromatosis (type I) û von Recklinghausen‘s disease ð AD, frequency 1:3000, chromosome 17, defect of tumor suppressor gene û multiple neurofibromas, mostly on skin , in any localisation - retroperitoneum, orbit, tongue, GIT, melanin- containing variants û hyperpigmented skin lesions (café-au-lait spots), pigmented iris hamartomas (Lisch nodules) û û in approx. 3% of patients malignant transformation û↑ risk of development of other tumors (optic gliomas, meningiomas, pheochromocytomas) j0305257 Neurofibromatosis (type I) Obrázek6.jpg j0305257 Malignant tumors û malignant peripheral nerve sheath tumor (MPNST) ð „neurogennic sarcomas“ arising from the peripheral nerve sheath ð 50% occur in patients with neurofibromatosis type 1, adults ðagressive, recurrent, metastases (lung, bones) ð gross: foci of necrosis, hemorrhage ð micro: fibroblast-like cells with elongated nuclei, frequent mitotic figures, areas of necrosis û û primitive neuroectodermal tumors (PNET) ðbone tumor û j0305257 MPNST irregular bundles, sm. fibrosarcoma-like j0305257 MPNST Hyperchromatic nuclei of spindle cells Mitoses (arrows) j0305257 TUMORS OF THE AUTONOMIC NERVOUS SYSTEM j0305257 Tumors of the parasympathetic system ûparaganglioma, chemodectoma ð originate from extraadrenal paraganglia • glomus tympanicum and jugulare, vagal bodies, carotid bodies, laryngeal, aorticopulmonary –pressure changes: ↓PaO2, ↑PaCO2 a ↑pH → reflex stimulation of respiratory and cardiovascular system ðmicro: • organoid (solid alveolar) formation ofcells: – chief cells - polygonal to oval; in distinctive cell nests, „Zellballen“) –supporting (sustentacular) spindle cells • separated by thin fibrovascular stroma • • j0305257 Paraganglioma paragangliom, 200ax.jpg j0305257 Paraganglioma paragangliom, 400x.jpg 1 2 1Zellbalen 2Sustentacular cells j0305257 Tumors of the sympatoadrenal system û Paragangliomas û û Pheochromocytoma ð Adrenal medullary paraganglioma ð Gross:, circumscribed lessions, usually confined to the adrenal , yellow-tan (hemorrhage, necrosis) ð 10% associated with familial syndromes (MEN 2A,2B,..), 10% extra-adrenal, in adrenal location 10% bilateral, 10% biologically malignant) ð û Neuroblastoma → ganglioneuroblastoma→ ganglioneuroma ðspontaneous or chemotherapy-induced maturation ðeven regression possible ðvariable prognosis, according to age and stage - j0305257 Neuroblastoma ûmost common extracranial solid tumor in chidhood ûusually sporadic, 1% germline mutation of ALK (anaplastic lymphoma kinase)-gene ûmostly in adrenal medulla, paravertebral sympathetic ganglia ûlarge tumors haemorrhagic, necrotic j0305257 Neuroblastoma ûMicro: ðsmall round cells, hyperchromatic nuclei („small blue cells“) ðextracellular eosinophilic fibrillary stroma ðHomer-Wright rosettes ðcommonly high mitotic acitivity, caryorrhexis j0305257 Neuroblastoma Necrotic haemorrhagic adrenal tumor j0305257 Neuroblastoma 1 j0305257 Neuroblastoma 1 Homer-Wrigh rosettes