tumors of the childhood - warszawski uniwersytet...
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Tumors of the childhood AgnieszkaWegnerMD,PhDDepartmentofPediatricNeurologyMedicalUniversityofWarsaw
Children tumors Tumor-incorrect,palpableorvisiblestructure
Thetumor’seDologyØ congenitalØ inflammatoryØ cancerous
TodifferenDateØ interviewØ physicalexaminaDonØ knowledgeofthetendencytolocalizetumorsinaparDcularlocaDonataspecificpopulaDon(age,gender,etc)
Ø addiDonaltests:imaging,histopathological,immunochemical,etc
Examina6on InterviewØ Howlongitlast
Ø Alergies,diet,skinchangesØ Drugs,vaccinaDons
Ø Contactwithanimals
Ø Weightloss
Ø Changesinchildcharacter
PhysicalexaminaDon-thetumorandits:
Ø localizaDon(local/generalized,symmetrical/asymmetrical)
Ø sizeandshape
Ø consistency,splashing
Ø soreness,swelling,appearanceoftheskinØ nodes-single/packages
Tumors BENIGN
Ø Lipoma
Ø Fibroma
Ø Hemangioma
Ø NerveDssuetumors(neurofibromas,schwannoma)
Ø Teratoma
MALIGNANT
Ø Leukemia
Ø Lymphomas
Ø CNStumors
Ø Sarcomas
Ø Neuroblastoma
Ø ReDnoblastoma
Children’s oncology 1. Around1childin500developscancerby15yearsofage.
2. Childhoodcancercomprise2%ofallmalignanttumoursbuttheyaretheleadingcauseofdeathinthisagegroup
3. Bothbenignandmalignanttumorsoccurinchildhood.
4. Benigntumorsaremorecommonthanmalignanttumorsbuttheyaregenerallyofli_leimmediateconsequence
5. MostmalignanttumorsinchildrenarisefromhematopoieDc,nervousandsoaDssues.
6. The5-yearsurvivalofchildrenwithallformsofcancerisabout75%,mostofwhomcanbeconsideredcured,althoughcureratesvaryconsiderablyfordifferentdiagnoses.
Differences between pediatric and adults cancers
Pediatriccancers AdultcancersIncidence • Rare
• Dependsonage• RelaDvelycommon• Increasedincidencewithincreasingage
LocalizaDon • HematopoieDcsystem• NeuralDssue• SoaDssue
• Epithelialorgin-carcinomas(lungcancer,coloncancer,skincancer)
Regression • Tendencytoregressspontaneously/mature
Histology • PrimiDve/embryonalappearance • Pleomorphic-anaplasDcappearence
GeneDcs • Simplekaryotype • Complexkaryotypes
Management • Curable-chemotherapy/radiotherapy• Evenresectablemayneedchemo• Maydevelopsecondmalignancy
• Oaenchemo-insensiDve• Lowstage-surgicallycurable
Frequency of different kind of cancer
Predsposing factors Ø GeneDc-mutaDons,neurocutaneousdisorders,chromosomalabnormaliDes
Ø Immunodeficiencies
Ø InfecDons–EBV,HIVØ Environmental
Ø Chemotherapy
Ø IonisingradiaDonØ ElectromagneDcradiaDon
Leukemia ACUTE(95%)
ALL–acutelymphocy6c/lymphoblas6cleukemia
- 80-85%allchildishleukemia
- Thepeakincidenceat3-6yearsofage,mostlyboys
- ShortduraDonofthedisease-2-6weeks
ANLL–acutenonlymphocy6cleukemia(acutemyeloidanemia,AML)
- Thesameincidenceinbothsexes
- 8typeswithdifferentclinicalcourseandresponsefortreatment(M0-M7)
CHRONIC(5%)
CML–chronicmyeloidleukemia
- RareincidenceinchildrenpopulaDon
- PossibilitytotransformtoALLaaer3-5years
- ClassifytomyelodysplasDcdisorders
ALL ALL-symptomsØ IniDallynonspecific-anorexia,irritability,lethargy,lossofapeDte,lossofweightØ PallorØ BleedingØ PetechiaeØ FeverØ Lymphadenopathy,splenomegaly,hepatomegalyØ BonepainandarthralgiaØ RarelyheadacheandvomiDng
LabtestØ Anemia,thrombocytopenia,increaseserythrocytesedimentaDonrateØ WBCNØ PresenceofblastcellsonperipheralsmearØ Bonemarrow–leukemiclymphoblasts
DifferenDaldiagnosisØ AplasDcanemiaØ MyelofibrosisØ InfecDonsmononucleosis
Treatment ALL TheaimistoinducealasDngremission,definedastheabsenceofdetectablecancercellsinthebody.Ø ChemotherapyØ SteroidsØ RadiaDontherapyØ Bonemarroworstemcelltransplants
Prognosisoverallcurerate80%.Itisassumedthatthe5-yeardisease-freesurvival(countedfromtheendoftherapy)issynonymouswithcurethechild.AaerthisperiodofALLrelapsearealreadyveryrare.
ALL- prognosis Worseprognosis
1. Agechildbelow12months
2. WBCcountlessthen50000/ul
3. ChromosomaltransacDonst(22:9),t(4:10),Downsyndrome
4. Gender-male
5. CancerspreadintotheCentralnervoussystem(brainorspinalcord)
6. Morphological,immunological,andgeneDcsubtypes
7. PaDent'snoresponsetoiniDaltreatment
Acute myeloid leukemia Symptoms:
Ø Pallor,faDgue,peDchae,
Ø Enlargednodesandhepatosplenomegaly
Ø GingivalhyperplasiainAMLM4iM5
Inves6ga6on:
Anemia,trombotythopenia,neutropenia
WBCcountinmostcasesenlarged
Presenceofblastcellsonperipheralsmear
Diagnosis:25%myeloblastsinbonemarrow
Treatment Chemotherapy
Radiotherapy
BonemarrowtransplantaDon
Worseoutcomes:noresponceaaerinducDontherapy
M5type
Non Hodgkin lymphoma Ø Abdominalform(B)andmediastinalform(T)
Ø asymmetricalenlargementoflymphnodes,mainlysupraclavicular(figuremediasDnal),someDmesextranodalsite
Ø rareininfants,increasingincidenceaaer3years
Ø Burki_'slymphomavirus(EBV)
Ø ahugerateofchange(days!)andlargemalice(CNSandbonemarrow)
DIAGNOSIS uricacidlevels
LDHacDvityreflectsthesizeofthetumor
Treatment:mainlychemotherapy(fewindicaDonsforradiotherapy)
Hodgkin lymphoma- Hodgkin disease Ø Sign-painless,firm,cervicalorsupraclavicularadenopathy
Ø Rarelyhepatosplenomegaly
Ø Lesscommon:Pruritus,lethargyandanorexia
Ø AddiDonaltests:mildanemia,reducednumberofeosinophiliccells,elevatedESR
Ø Hispatologically:Reed-Sternbergcells
Ø Treatment:TheassociaDonofchemotherapyandradiotherapy
Oral lesions in the hematopoie6c and lympha6c diseases Causeoftheoccurencethechangesintheoralcavity:Ø thepresenceofneoplasDclesionsØ peripheralbloodcytopeniaØ immunedeficiency
Thechangesintheoralcavity:Ø gingiviDsØ periodonDDsØ bleedingØ gingivalhyperplasiaØ petechiaeØ erosionsØ ulcersofthemucousmembranes
Changes in oral cavity Gingivialhyperplasia-cause:Ø leukemicinfiltrates(paDentswithchronicmyelomonocyDcleukemia(CML)oracuteleukemianonlymphocyDc(ANLL-M4andM5))
Ø primaryneoplasDcproliferaDonoriginaDngfromthelymphaDcsystem(rare)
Ø drug-inducedgingivalhyperplasia(phenytoin,cyclosporinA,calciumchannelblockers)
Ø agranulocytosiscancauseinflammatorychangesand/orfungalinfecDonsoftonsilsandoralmucosa
Ø thrombocytopenia->developmentofthrombocytopenicbleedingswithsymptomsofbleedinggumsandpetechiaeoftheoralmucosa
Ø anemia->palemucousmembranes
PaDentswithNHL(usuallyfrommatureBcells)->increasebacterialandfungalinfecDonsintheoralcavity,drymucousmembranes,decreasedsalivasecreDon,viralvesicularlesionsonthemucousmembranesofthemouth,onthehardpalate,soaposteriorwallofthepharynx.
EBV-developmentofpost-transplantlymphoproliferaDvesyndrome(PTLD)-localorgeneralizedinpaDentwithimmunedeficiencyØ varyingdegreesofseverity(fromreacDvehyperplasia,tothedevelopmentoflymphoma);thecauseofhairyleukoplakia,erosions,ulcers
HPV–oncogenicvirusØ clinicalpicturemaybeasymptomaDc,ormaybethecauseofchangeofsquamouspapilloma(7-8%oftumorsinchildren)
Changes in oral cavity
Neuroblastoma Secondmostcommonsolidtumorofinfants(upto2years)
metastasistobonemarrow
2/3ofthecases,thediagnosisof<5yearsofage(meanageofonset2.5years)
themostcommonmalignanttumorinneonatalage(34-54%)
LocaDon:retroperitonealspace(70-75%)RearmediasDnum(20%)neck(5%)
metastaDcformofthediseasein70%oftheDmeofdiagnosis
Diagnosis-CT,MRI→tumormass,Tumormarkers→HVA,VMA,Biopsy
Treatment:surgicalchemotherapyandradiotherapy
NBL symtoms abdominalmasslossofappeDte,weightlossfeverabdominalpain,bonepainmulDplesubcutaneousnodulesexophthalmosHorner'ssyndrome(notcharacterisDc)overproducDonofcatecholamines:
Diarrhea(escapepotassiumoverproducDonVIP)EpisodesofsweaDngskinrednessHypertension
Wilms tumor- nephroblastoma derivedfromrenalDssuewithlowdiffernDaDon thepeakincidenceof3-4yearsofage 7-10%ofchildhoodcancers cancoexistwithothercongenitaldefects bilateralWilmstumor GeneDcpredisposiDon:◦ WAGRsyndrome-Wilms,aniridia,genito-urinarymalformaDons,mentalretardaDon,del11p13
◦ Beckwith-Wiedemannsyndrome-omphalocoele,macroglossia,giganDsm,hepatoblastoma,nephroblastoma,gonadoblastoma,del11p15
◦ Denys-Drashsyndrome-nephropaDa,nephroblastoma,pseudohermaphrodiDsm,pointmutaDonsintheWT1gene
Wilms tumor- symptoms Ø recurrentsymptomsofurinarytractinfecDon
Ø hematuria
Ø hypertension(reninsecreDon)Symptomsofatumorintheabdomen:
Ø Abdominaldistension
Ø abdominalpain,nausea,vomiDng,abnormalintesDnaltransit
Ø bulgeofabdominalwall
Diagnosis-USG,CT,ChestX-ray,CT Treatment-surgicalremoval,chemotherapy:VincrisDne,acDnomycin&doxorubicin,Radiotherapy
Re6noblasoma Symptoms:leukocoria,strabismus,orbitalinfalmaDon,pain◦ Monocularform,unifocaloccurssporadically,diagnosedbetween3-4yearsofage,60%ofallcases
◦ MulDfocalform,predominantlyintheformofabinocularhereditaryrecognizedinmostcasesin1yroflife,25%ofallcases
developsintraocularly,theninvadesthestructureofperiocularandpenetratesintothecranialcavity
Itcangivedistantmetastases.
Diagnosis→Opthalmology–orbitalUSGandCT
Treatment–u/lenucleaton
LaserphotocoagulaDon,cryotherapy,radiotherapy B/l→enucleaDonofthemoreseveraleffectedeye.
Thereisasignificantriskofsecondmalignancy(especiallysarcoma)amongsurvivorsofhereditaryreDnoblastoma.
Brain tumors Themostcommonsolidtumors(20-25%ofallcancers)
Theaverageageof7years10months.
EDology:◦ Hereditary:neurofibromatosistypeIandII,tuberoussclerosis,Li-Fraumenisyndrome,Gardener,Turcot,vonHippel-Lindau
◦ Environmentalfactors:pesDcides,nitrosamines,exposuretoionizingradiaDon,electromagneDc◦ Primaryandsecondaryimmunedeficiencies
Diagnosis:◦ neuroimaging–MRI◦ Cerebrospinalfluid◦ Biochemicaltests(AFP,hCG)
Treatment-surgery,radioandchemiotherapy
Brain tumors classifica6on LocalisaDon• Supratentorial(gliomas,ependymomas,PNETtumors,midline-germcelltumors,pinealtumors)
• Infratentorial->thecerebellum(medulloblastoma),Brainstem(gliomas)
• Astrocytoma(~40%)–variesfrombenigntohighlymalignant(glioblastomamul,forme)
• Medulloblastoma(~20%)–arisesinthemidlineoftheposteriorfossa.MayseedthroughtheCNSviatheCSFandupto20%havespinalmetastasesatdiagnosis
• Ependymoma(~8%)–mostlyinposteriorfossawhereitbehaveslikemedulloblastoma
• Brainstemglioma(6%)
• Craniopharyngioma(4%)–adevelopmentaltumourarisingfromthesquamousremnantofRathkepouch.Itisnottrulymalignantbutislocallyinvasiveandgrowsslowlyinthesuprasellarregion.
ThesupratentorialglioblastomamulDforme
ThejuvenilepilocyDcastrocytomaofthecerebellum
Brain tumors- symtoms Posteriorfossatumors◦ theincreaseinintracranialpressure◦ ataxia◦ headache◦ nausea◦ vomiDng
Supratentorialtumors◦ Seizures◦ hemiparesis◦ focalsymptoms
Tumorsmidline◦ Visualfielddefect◦ visualacuity,◦ diabetesinsipidus◦ growthdisorders
Rhabdomyosarcoma ThemostcommonformofsoaDssuesarcomainchildhood-2-6yearsofage,moreboys
Headandneckarethemostcommonsitesofdisease(40%),
Clinicalsymptoms:Ø exophthalmos,squint,narrowingoftheeyelidØ nasalspeech,difficultyswallowingØ occupaDonofthemiddleearwiththeleakandpolypsintheexternalauditorycanalØ intracranialpressure,cranialnervepalsies
Genitourinarytumoursmayinvolvethebladder,paratesDcularstructuresorthefemalegenitourinarytract.
SymptomsincludeØ dysuriaandurinaryobstrucDon,Ø scrotalmassØ bloodstainedvaginaldischarge.
MetastaDcdisease(lung,liver,boneorbonemarrow)ispresentinapproximately15%ofpaDentsatdiagnosisandisassociatedwithaparDcularlypoorprognosis.
MulDmodalitytreatment(chemotherapy,surgeryandradiotherapy)
Germ cell tumours Ø 3-3.7%ofallmalignanciesinchildren
Ø benignormalignant
Ø M:F-1:2-4
Ø TheyarisefromtheprimiDvegermcellswhichmigratefromyolksacendodermtoformgonadsintheembryo.
Ø Benigntumoursaremostcommoninthesacrococcygealregion,andmostmalignantgermcelltumoursarefoundinthegonads.
Ø Serummarkers(αFPandβ-HCG)areinvaluableinconfirmingthediagnosisandinmonitoringresponsetotreatment.
Ø Twoincidencepeaks:1. 0-3yr(mainlytumorsofsacrococcygealregion,tesDnaltumors)2. >12yearsofage(mainlyovarytumors)
Ø Goodresponsetochemotherapy
Liver tumors 0.5-2%ofcancersdevelopmentalage
Primarymalignantlivertumoursare:1. hepatoblastoma(65%),thepeakincidence1yrs,geneDcfactors-Beckwith-Wiedeman
sydrome,WAGR,neurofibromatosis2. hepatocellularcarcinoma(25%),thepeakincidence12yearsofage,HBVinfecDon,
tyrosinemia,billaryatresia
Symtoms:lossofappeDte,weightloss,vomiDng,abdominaltumor,hepatomegaly
Elevatedserumα-fetoprotein(αFP)isdetectedinnearlyallcasesofhepatoblastomaandinsomecasesofhepatocellularcarcinoma.
Diagnosis-USG,CT,MRI,biopsy
Managementincludeschemotherapy,surgeryand,ininoperablecases,livertransplantaDon.
Themajorityofchildrenwithhepatoblastomacannowbecured,buttheprognosisforchildrenwithhepatocellularcarcinomaisworst.
Computedtomogramofhepatoblastoma
Computedtomogramofhepatocarcinoma
Bone tumors Malignantbonetumoursareuncommonbeforepuberty.
OsteogenicsarcomaismorecommonthanEwingsarcoma,butEwingsarcomaisseenmoreoaeninyoungerchildren.
Bothhaveamalepredominance
Osteosarcoma:§ Themostcommonmalignantbonetumorinchildren§ Thepeakincidence15-19yearsofage§ ThemostcommonlocaDon-metaphysealdistalfemurand
proximalDbiametaphyseal
Bone tumors Ewingsarcoma§ Itcanoccuratayoungerage§ ThemostcommonlocaDon-flatboneofthepelvis,shoulder,ribs,longbones-femur,Dbia,arrow
§ thereisoaenasubstanDalsoaDssuemass§ 1/3paDentsatdiagnosisismetastaDctothelung,bone
Treatment-combinaDonchemotherapygivenbeforesurgery.Wheneverpossible,amputaDonisavoidedbyusingenblocresecDonoftumourswithendoprostheDcresecDon.
InEwingsarcoma,radiotherapyisalsousedinthemanagementoflocaldisease,especiallywhensurgicalresecDonisimpossibleorincomplete,e.g.inthepelvisoraxialskeleton.
Dental care on the oncological pa6ents Asquickaspossible!
Chemotherapy:miniumumoneweekearlier
Radiotherapy:amin2weeksearlier
Oralhygiene:useasoatoothbrush-toothpasteforchildren
Liquidtomouth:saline,bakingsoda,infusionsofchamomile,
Removalofbraces
RestricDvediet
Complica6ons of chemotherapy and radiotherapy AgeneralizedinflammaDonoftheoralmucosa(mouthwasheswithpainkillers,anDfungal,steroids)
reducedsalivasecretion(pilocarpine,Vit.A) opportunisDcinfecDons(FluconazoleprophylacDcally)
toothcaries,necroDcboneinflammaDonbecauseofradiaDon
periodonDDs Trismus
dysgeusia,dysphagia
Refferences and sources NelsontextbookofPediatrics,19thEdiDon,Kliegman,Behrman,Schor,Stanton,St.Geme
Pediatria,Kawalec,Grenda,PZWL,Warszawa2013
IllutratedtextbookofPediatrics,4thEdiDon h_p://www.cancer.gov/types/childhood-cancers/hp/unusual-cancers-childhood-pdq
Google.com
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