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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_186_библиотеки_им_акад_М_И_Перельмана
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approximately3hoursago.Shewasblow-dryingherhairwhenshenoticedthatshewas
havingdifficultygraspingthebrushwithherlefthand;shesaysherfingersfeltheavyand
clumsy,andshehadtroubleliftingherarmtoputthebrushaway.Herbloodpressureis
170/100.Herneurologicexaminationisnotablefor4/5strengthanddecreasedsensationof
herleftupperextremityandasubtleleftuppermotorneuronfacialdroop.Shealsoreportsa
headachethatbeganabout2weeksagobutbecamemuch,muchworsethismorning.What
isthenextstepinyourmanagement?
Inthischapter,wewillfocusmostofourattentiononthebrain,forthesimplereasonthatbraintumorsare
byfarthemostcommonoftheneurologicmalignancies.Manyofthesetumorscanbedevastating,butas
ourunderstandingoftheunderlyingtumorpathophysiologyandgeneticmake-uphasincreased,sohave
ourtreatmentoptions,andongoingclinicaltrialsoffermorehopeeachday.
AQuickWordonMassLesions
Braintumorsaremasslesions:theytakeupspaceinsidetheskull.Abscessesandhemorrhagesareother
examplesofmasslesions.Howtheselesionspresentisdependentononlytwothings:
1. Theirlocation.Sizematterstoo,ofcourse—bigtumorsdotendtobeworsethansmallones—butlocationusuallymattersmore.Tiny
tumors located in the brainstem, for instance, can present with sudden, dramatic symptoms affecting the cranial nerves, motor
pathways, andsensory pathways, whereas tumors located in the right frontal lobe—an area of the brain responsible for (relatively
speaking)verylittle—canremaincompletelyasymptomaticuntiltheygrowtobecomequitelarge.Corticallybasedtumorsoftenpresent
withseizures,whereastumorslocateddeeperinthebrainandcerebellumdonot.
2. The rate at whichthey grow.Slow-growingtumors typically presentinsidiouslyoverweeks to months withprogressive headache,
weightloss,andsubtle,progressive neurologic deficits whereasrapidly growingtumors can presentwithsymptomsthatdevelopover
daystoevenhours.
Theageofthepatientisalsosomethingtoconsider.Becausethebrainatrophiesovertime,older
patientstendtohavemorespaceinsidetheirskullandcantherefore“hide”masslesionsforlongerthan
youngerpatients,whohaveverylittleextraspaceandtendtobecomesymptomaticearlier.
Tumorscancausesymptomsbycompressingsurroundingbraintissue(eitherdirectlybythetumoritself
orasaresultofedemasurroundingthetumor)orbyobstructingtheflowofcerebrospinalfluid(CSF)if
thetumorislocatedwithin,orcompressesagainst,aventricle.Tumorscanalsobleed,andbloodcan
causecompressionorobstructionmuchmorerapidlythanthetumoritself.
Primarybraintumorscanmetastasizebutrarelydosooutsideofthecentralnervoussystem(CNS).
Moreoften,theycancausedistanteffects—forexample,backache,radiculopathies,cranialnervedeficits
—asaresultofspreadintotheleptomeningesandCSF(seeBox16.6onpage402).
Forthepurposesofthischapter,thereareonlyahandfulofthingstoknowabouteachtumor:itsorigin
(i.e.,thecellsfromwhichitderives),thepopulationittendstoaffect(children,adultsorboth),wherein
thebrainitlikestogrow(thiswilltellyouhowitpresents),andwhatitlookslikebothhistologicallyand
onimaging(soyoucanrecognizeitwhenyouseeit).Ifwedonotmentiononeorafewoftheabove
categoriesforagiventumor,itisnotbecauseweforgotbutbecausethedetailsareeitherclinically
unimportantorbeyondthescopeofthisbook;ineithercase,nothingforyoutoworryabout.Wewillalso
discussprognosisbutwillnotspendtoomuchtimeontreatment,sincemanyofthetreatmentoptionsand
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algorithms(particularlythenewertherapiesthataretargetedtoparticulartumormutations)areconstantly
changing.
PrimaryBrainTumors
Primarybraintumors(i.e.,tumorsthatoriginateinthebrain)areactuallysignificantlylesscommonthan
metastaticbraintumors(i.e.,tumorsthatoriginateelsewhereinthebody).Oftheprimarybraintumors,
meningiomasarethemostcommon,accountingforapproximately35%ofallprimaryintracranial
neoplasms.Glioblastomas1arethesecondmostcommon,makingupabout15%,followedby
schwannomas,whichaccountforapproximately8%.
1
Althoughglioblastomasarethesecondmostcommonprimarybraintumor,theyarethe
mostcommonprimarymalignantbraintumor,accountingforoverhalfofallmalignant
CNStumors.
GlialTumors
Glialcellsarethenon-neuronalcellsoftheCNS.Theyincludeastrocytes(whichformpartofthebloodbrainbarrierandhavearoleinneurotransmittermetabolismaswellastheformationofglialscars),
oligodendrocytes(whichmyelinateCNSneurons),andependymalcells(whichlinetheventricles).
Microglia(whichactasCNSmacrophages)arealsogliabutarenotrelevanttothischapterforthe
simplereasonthattheydonotformtumors.Allglialcellscontainglialfibrillaryacidicprotein(GFAP),
andthereforetumorsformedfromglialcellswillstainpositiveforGFAPonhistology.
Box16.1TheWorldHealthOrganizationTumorGradingSystem
Untilrecently,theWHOgradedCNStumorsbasedlargelyontheirhistologicalfeatures(such
ascellularityandmitoticactivity)buthasnowbeguntofocusonmolecularmarkersaswell
asawaytoimproveourunderstandingofeachindividualtumorandtargetpotential
therapeuticoptions.TheWHOgradingscalehelpsprimarilywiththediagnosisandprognosis
ofCNStumors.Thedifferentgradesarecomplicated,butthechartbelowshouldhelptogive
ageneralsenseofwhattheymean.Weexcludedthenewermolecularmarkerinformation
fromthistablebecauseitgoesbeyondthescopeofthisbook.
TheWHOTumorGradingSystem
GradeI Welldifferentiatedcellswithlowproliferativepotential;maybecuredwithsurgeryalone
GradeIIModeratelydifferentiatedcells;lowrecurrenceratebutcantransformtohighergradetumors
Grade
III
Poorlydifferentiatedandinfiltrativecells;highrecurrenceratefollowingtreatment
GradeIVPoorlydifferentiatedandinfiltrativecellswithapropensitytospreadthroughouttheCNSandbecomenecrotic;poorprognosis
despitetreatment
Thereareseveralmajortypesofglialtumors:
Ependymomas are derived from ependymal cells. They are most commoninchildrenand young
adults and are often located within the fourth ventricle (although they can be supratentorial2 and
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cord-basedaswell).Histologyshowsperivascularpseudorosettes,whichareclustersoftumorcells
thatsurroundbloodvessels.Dependingontheirspecific molecularmake-up,ependymomascanbe
WHOgradeIIorIII.
Oligodendrogliomasaremalignantbutslow-growingtumorsderivedfromoligodendrocytes.They
are relatively rare, most often diagnosed in young adults, and have a predilection for the frontal
lobes. “Fried egg” cells (cells witha darkcentersurroundedbya pale halo) and“chicken wire”
capillariesaretheclassicfindingsonhistology.TheseareWHOgradeIIorIII.
Astrocytomasarederived fromastrocytes, andthere aremultiple types.Discussedbelowarethe
twoyoushouldknow.
Pilocytic astrocytomas are the most common primary brain tumor in children. They are most often infratentorial (i.e.,
cerebellar).Onhistology,theyarecharacterizedbyRosenthalfibers(corkscrew-appearingeosinophilicprocessesofastrocytes).
Onimaging,theyclassically appearas cystic lesionswith smallenhancingnodulesinside.TheyareclassifiedasWHO gradeI
and,ifcompletesurgicalresectionispossible,areoftencompletelycurable.
(A)Thecharacteristiccys ticappearanceofanas trocytomaonMRI,withasm allenhancingmuralnodule(note
that,althoughthisastrocytomais supratentorial,theyaremos tofteninfratentorial)and(B)Rosenthalfiberson
his tology(blackarrows).(A,reprintedfromStrayerDS,RubinE.Rubin’sPathology,7thed.WoltersKluwer;2014;
andB,m odifiedfromSchniederjanMJ.BiopsyInterpretationoftheCentralNervousSystem,2nded.Wolters
Kluwer;2017.)
Glioblas tomas (previouslyknown as glioblastoma multiforme, orGBM)are classifiedasWHO grade IV.Theygrowrapidly,
are largely resistant to treatment, andhave a poor prognosiswith an average survival of approximately15months. Theyare
typically hemisphericandcharacteristicallycross thecorpuscallosum toinvade thecontralateralhemisphere,appearingasbig,
irregular butterfly lesions on imaging with variable enhancement, significant surrounding edema, and often hemorrhagic
components. Histology reveals pleomorphic tumor cells with brisk mitotic activity, prominent microvascular proliferation, and
areas of necrosis and hemorrhage surrounded by pseudopalisading tumor cells (see image on the next page). Treatment is
typicallywith surgicalresectionfollowedbyconcurrentradiationandchemotherapy(temozolomide,analkylatingagent,isfirstline).Ongoingclinicaltrialsareevaluatingdozensofotherpotentialtherapeutics,includingotheralkylatingagents,anti-angiogenic
treatments,targetedmutationaldrugs,andimmunotherapy.
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(A)A“butterfly”glioblas tom aonMRIand(B)afocioftumornecros is s urroundedbyahypercellularcuffoftumor
cells(“pseudopalis adingnecrosis ;”seeblackarrows )onhis tology.(A,reprintedfromGriggs RC,JoyntRJ.Baker
andJoynt’sClinicalNeurologyonCD-ROM.Wolters Kluwer;2014;andB,modifiedfromSchniederjanMJ,Brat
DJ.BiopsyInterpretationoftheCentralNervousSystem.Wolters Kluwer;2011.)
2
Supratentorialreferstoanywhereinthebrainabovethetentoriumcerebelli(i.e.,
anywhereabovethecerebellum).Infratentorialreferstoanywhereinthebrainbelow
thetentoriumcerebelli(i.e.,inthecerebellum).Thesetermsareoftenusedtodescribe
CNStumors.
NeuronalTumors
Tumorsderivedfromneuronsarelesscommonthanthosederivedfromglialcells.Synaptophysin(a
transmembraneglycoproteininvolvedinsynaptictransmission)isacommonhistologicalmarkerfor
neuronaltumors(justasGFAPisamarkerforglialtumors).
Neuroepithelialtumorsarederivedfromneuroepithelialcells,whichareundifferentiatedcellsof
theCNSthatcanultimatelybecomeeitherneuronsorglia.
Ce ntralne urocytomasaremostcommoninyoungadults.TheyareclassifiedasWHOgradeII,areusuallylocatedwithinthe
ventricles(ofteninvolvingtheseptumpellucidum,thethinmembranethatseparatestheanteriorhornsoftheleftandrightlateral
ventricles),andappearasuniformcellswith“saltandpepper”chromatinonhistology.
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(A)AcentralneurocytomaonMRIand(B)thesaltandpepperappearanceonhis tology.(A,reprintedfromSanelli
P,SchaeferP,LoevnerL.Neuroim aging:TheEssentials.Wolters Kluwer;2015;andB,reprintedfromKiniSR.
CytopathologyofNeuroendocrineNeoplasia.WoltersKluwer;2013.)
Dysembryonic neuroepithelialtumors (DNETs) are morecommon inchildren. Theyare rare, benign, andslow-growing,
classifiedasWHOgradeI.Theyhaveapredilectionforthetemporallobeandclassicallypresentwithintractablefocalseizures.
Onimaging,theyhaveacharacteristic“soapbubble”appearanceandappearasmucin-richbubblynodulesonhistology.
(A)ADNETonMRI(blackarrow)and(B)thesoap-bubbleappearanceonhistology.(A,m odifiedfromZamoraC,
Cas tilloM.NeuroradiologyCom panion,5thed.WoltersKluwer;2016;andB,reprintedfrom SchniederjanMJ.
BiopsyInterpretationoftheCentralNervousSystem,2nded.Wolters Kluwer;2017.)
Primitive neuroectodermaltumors (PNETs) area subtypeofsmall roundbluecell tumors (i.e.,
theystainbluewithstandard staining techniques) that tendto be highlyaggressive. Both cerebral
neuroblastomasandmedulloblastomasareWHOgradeIV.
Ce rebralneuroblastomas are mostcommoninchildrenandtendtobesupratentorial. Noncerebral neuroblastomasaremost
often located in the adrenal medulla but can also grow anywhere along the sympathetic chain. Neuroblastomas appear as
clusters ofsmall round blue cells onhistology,oftenin the formof Homer–Wrightrosettes (darkblue cells surrounding pale
fibrils,seeimageonthenextpage).
Medulloblas tomas are the most commonmalignant tumor seen in children but can alsooccur in adults. They tend tobe
infratentorial, located within the cerebellar vermis or fourth ventricle. They appear similar to cerebral neuroblastomas on
histology.
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Hom er-WrightRos ettescom posedofclustersofsmallroundbluecellssurroundingpalefibrils(agoodexample
canbeseenwithintheblackcircle).(ModifiedfromMulhollandMW.Greenfield’sSurgery,6thed.WoltersKluwer;
2016.)
OtherPrimaryBrainTumors
Meningiomasarethemostcommonprimarybraintumorinadults.Theyarederivedfromarachnoid
cells and are intradural (most of the time; rarely, they canbe extradural) but extra-axial: inother
words,theygrowbeneaththedurabutoutsideofthebrainparenchyma,withintheconcavitiesofthe
hemispheres,nearbone,andoftenappearattachedtotheduraviathickenedduralsegmentsknownas
dural tails. The vast majority of meningiomas are WHO grade I (although they can range up to
gradesIIandIII),butthatdoesnotmeantheycannotcauseproblems:themajorityareasymptomatic,
but as theygrowtheycancompressandirritatebraintissue,causingfocalneurologic deficits and
seizures. Characteristic histologic findings include psammoma bodies and whorled cells (see
imagesbelow).Onimaging,meningiomasarevividlyanduniformlyenhancingandhaveasmooth,
circularappearance.Treatmentiswithsurgicalexcision.
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(A)Aparasagittalmeningiomawithduraltails;(BandC)Characteristicpsammomabody(B)andwhorled
cells(C)onhistology.(A,reprintedfromTangC,FarooqiA.PocketRadiationOncology.WoltersKluwer;
2019;BandC,reprintedfromRubinR,StrayerDS,RubinE.Rubin’sPathology,6thed.WoltersKluwer;
2011.)
Schwannomas are WHO grade I tumors that are derived from schwann cells (the cells that
myelinate peripheralnerves) and—logically—grow along peripheral nerves, includingthe cranial
nervesandspinalroots.CN8schwannomas(i.e.,acousticschwannomas)arethemostcommonand
presentwithprogressivehearinglossandtinnitus.Especiallywhenbilateral,acousticschwannomas
areassociatedwithneurofibromatosistype2(seeChapter17).Theyarecharacterizedbyalternating
areas of hypercellular “antoni A” tissue (often with verocay bodies, see image B below) and
hypocellular“antoniB”tissue.
(A)Anacousticschwannoma(asterisk)growingalongtheeighthcranialnervewhereitexitsthe
brainatthecerebellopontineangleand(B)aclose-upofaverocaybody,characterizedbyrowsof
palisadingnuclei(bluedots)separatedbyareasofacellularpinkmembrane.(A,reprintedfrom
BarkerLR,FiebachNH,KernDE,ThomasPA,ZiegelsteinRC,ZievePD.PrinciplesofAmbulatory
Medicine,7thed.WoltersKluwer,2006;andB,modifiedfromRequenaL,RequenaL,KutznerH.
CutaneousSoftTissueTumors.WoltersKluwer;2014.)
Craniopharyngiomas are WHO grade I tumors derived from embryonic pituitary tissue (i.e.,
remnantsofRathkepouch)thatgrowwithinthesellaturcicaandcanpresentwithendocrinopathies
and bitemporal hemianopia (see Box 16.2 on Sellar and Suprasellar Tumors). There are two
common age peaks—young children and adults in their 50s and 60s—and two subtypes—
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adamantinomatous(whichaccountforapproximately90%ofthesetumorsandappearascysticand
oftencalcified masses filled with oilyfluid) andpapillary(massesofmetaplastic squamouscells,
notcalcified).
Histologyfrom(A)adamantinomatousand(B)papillarycraniopharyngiomas.(A,reprintedfrom
BiopsyInterpretation:TheFrozenSection,2nded.WoltersKluwer;2013;andB,reprintedfromMills
SE,GreensonJK,HornickJL,LongacreTA,ReuterVE.Sternberg’sDiagnosticSurgicalPathology,
6thed.WoltersKluwer;2015.)
Box16.2SellarandSuprasellarTumors
Thesellaturcicaisasaddle-shapeddepressionwithinthesphenoidbonethatcontainsthepituitarygland.Tumorsthat
ariseherecancausebothbitemporalhemianopia,duetocompression oftheopticchiasm(remember,lightreceived
from thelateral or temporalhalfof the worldfallson the nasalhalf of each retinaandthenasalretinal fibers come
together to cross in the chiasm [see page 432]), and endocrinopathies, due to compression of pituitary tissue. In
children, the most commonsellar andsuprasellar tumors includecraniopharyngiomas and other gliomas (including
hypothalamicandopticnervegliomas);inadults,pituitaryadenomasandmeningiomasaremorecommon.
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(A)ApituitarymacroadenomaonsagittalpostcontrastMRI.(B)Adrawingdemonstratinghow
sellarmassescancompresstheopticchiasmandresultinbitemporalhemianopia.(A,reprinted
fromCheng-ChingE,BaronEP,ChahineL,Rae-GrantA.ComprehensiveReviewinClinical
Neurology,2nded.WoltersKluwer;2016.)
Hemangioblastomas are WHO grade I tumors that originate from stromal cells in small blood
vessels and are most often located within the cerebellum, brainstem, or spine.About 25% of the
time, they are associated with von Hippel–Lindau disease (see Chapter 17); in these cases, the
average age of thoseaffected is 20 to 40 years. Whenhemangioblastomas are sporadic (i.e., not
associatedwithvonHippel–Lindau),the averageageismucholder,closerto50 to70.Histology
reveals highly vascularized tissue with foamy cells. Hemangioblastomas can be associated with
secondarypolycythemiaduetoerythropoietinproductionbythetumorcells.
PrimaryCNSlymphomaisrelativelyrare,accountingforapproximately5% ofallprimary CNS
tumors. It usually occurs in immunocompromised individuals—HIV and iatrogenic
immunosuppressionareimportantriskfactors—butcanoccursporadicallyinhealthyindividualsas
well.Whenitaffectsimmunocompromisedpatients,primaryCNSlymphomaisoftenassociatedwith
anunderlyingEBVinfection,butinthemajorityofnonimmunocompromisedpatientsnoevidenceof
EBVcanbefound.PrimaryCNSlymphomacanbehemisphericbutisoftenperiventricular,located
within thedeep gray matter.Like glioblastomas, it can also cross the corpus callosum. OnMRI,
primaryCNSlymphomauniformlyenhancesandcanrestrictdiffusionondiffusion-weightedimaging
(DWI) due to the high cellularity of these tumors. First-line treatment involves steroids,
chemotherapy,and—ifHIV-related—antiretroviraltherapy.Steroidscanreducethediagnosticyield
on biopsy and should be delayed if possible until the biopsy is completed. Modern high-dose
methotrexate-basedchemotherapyregimenshavesignificantlyprolongedsurvivaltime;however,the
relapserateishigh.Thesurvivalrateislikelyworseinimmunocompromisedindividuals.Surgical
resectionis not recommended becauseithasnot been shown toincrease overall survival. Whole
brainradiationisgenerallyusedasasalvagetherapy;itcanbeeffectivebutisassociatedwithearly
relapseandasignificantsideeffectprofileincludingoftendebilitatingcognitivedysfunction.
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PrimaryCNSlymphoma.(A)AxialCTshowsmultiplemassesalongthelateralventricles.(B)These
lesionsavidlyenhanceonpostcontrastMRI.(ReprintedfromPinaSanelli;PamelaSchaefer;Laurie
Loevner.Neuroimaging:TheEssentials.WoltersKluwer;2015.)
Box16.3MetastaticBrainTumors
Metastaticbraintumorsareactuallymorecommonthanprimarybraintumorsandtendtobelocated
supratentoriallyalongthegraymatter/whitematterjunction.Lungcanceristhemostlikelytometastasizeto
thebrain,followedbybreastcancerandmelanoma.Allbrainmetastasescanbleed,butlungcancer,
melanoma,renalcellcancer,choriocarcinoma,andthyroidcancermetastasesarethemostlikelytodoso.
Cysts
Acystisamembranouspocketthatisfilledwithsomething—itcanbeair,CSF,blood,etc.Theytendto
bebenignbutcanoccasionallywreakhavocinthebrainduetocompressionofthesurroundingtissueor,
evenmorerarely,cystrupture.Amongthemostcommoncystsare:
Colloidcystsarebenignmucus-filledmassesthatarelocatedwithintheforamenofMonroorthird
ventricle.Theyareusuallyasymptomaticbutcanoccasionallycausesuddenheadache,dropattacks,
rapidneurologicdecline,andevenherniationanddeath.Thesesymptomsoccurwhenthecystshifts
so that it obstructs the ventricular system, resulting in acute hydrocephalus and a rapid rise in
intracranialpressure.Small,asymptomaticcystscanbemonitoredwithserialimaging.Forlargeror
rapidlygrowingcysts,surgicalexcisioniscurative.
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