Tumors of the childhoodAgnieszkaWegnerMD,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 WeightlossØ Changesinchildcharacter

 PhysicalexaminaDon-thetumorandits:Ø localizaDon(local/generalized,symmetrical/asymmetrical)

Ø sizeandshape

Ø consistency,splashing

Ø soreness,swelling,appearanceoftheskinØ nodes-single/packages

TumorsBENIGN

Ø LipomaØ Fibroma

Ø HemangiomaØ NerveDssuetumors(neurofibromas,schwannoma)

Ø Teratoma

MALIGNANT

Ø LeukemiaØ Lymphomas

Ø CNStumorsØ Sarcomas

Ø Neuroblastoma

Ø ReDnoblastoma

Children’s oncology1.  Around1childin500developscancerby15yearsofage.2.  Childhoodcancercomprise2%ofallmalignanttumoursbuttheyaretheleadingcauseof

deathinthisagegroup

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 factorsØ GeneDc-mutaDons,neurocutaneousdisorders,chromosomalabnormaliDesØ Immunodeficiencies

Ø InfecDons–EBV,HIVØ Environmental

Ø Chemotherapy

Ø IonisingradiaDonØ ElectromagneDcradiaDon

LeukemiaACUTE(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 ALLTheaimistoinducealasDngremission,definedastheabsenceofdetectablecancercellsinthebody.Ø ChemotherapyØ SteroidsØ RadiaDontherapyØ Bonemarroworstemcelltransplants

Prognosisoverallcurerate80%.Itisassumedthatthe5-yeardisease-freesurvival(countedfromtheendoftherapy)issynonymouswithcurethechild.AaerthisperiodofALLrelapsearealreadyveryrare.

ALL- prognosisWorseprognosis

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 EnlargednodesandhepatosplenomegalyØ GingivalhyperplasiainAMLM4iM5

 Inves6ga6on:

 Anemia,trombotythopenia,neutropenia WBCcountinmostcasesenlarged

 Presenceofblastcellsonperipheralsmear Diagnosis:25%myeloblastsinbonemarrow

Treatment Chemotherapy Radiotherapy

 BonemarrowtransplantaDon

 Worseoutcomes:noresponceaaerinducDontherapy

 M5type

Non Hodgkin lymphomaØ 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 diseaseØ Sign-painless,firm,cervicalorsupraclavicularadenopathyØ Rarelyhepatosplenomegaly

Ø Lesscommon:Pruritus,lethargyandanorexiaØ 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

NeuroblastomaSecondmostcommonsolidtumorofinfants(upto2years)

metastasistobonemarrow

2/3ofthecases,thediagnosisof

NBL symtomsabdominalmasslossofappeDte,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- symptomsØ recurrentsymptomsofurinarytractinfecDonØ hematuriaØ hypertension(reninsecreDon)Symptomsofatumorintheabdomen:

Ø AbdominaldistensionØ abdominalpain,nausea,vomiDng,abnormalintesDnaltransitØ 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 classifica6onLocalisaDon• 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 tumoursØ 3-3.7%ofallmalignanciesinchildrenØ benignormalignantØ M:F-1:2-4Ø 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-Wiedemansydrome,WAGR,neurofibromatosis

2.  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 tumorsMalignantbonetumoursareuncommonbeforepuberty.

OsteogenicsarcomaismorecommonthanEwingsarcoma,butEwingsarcomaisseenmoreoaeninyoungerchildren.

Bothhaveamalepredominance

Osteosarcoma:§  Themostcommonmalignantbonetumorinchildren§  Thepeakincidence15-19yearsofage§  ThemostcommonlocaDon-metaphysealdistalfemurand

proximalDbiametaphyseal

Bone tumorsEwingsarcoma§  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 pa6entsAsquickaspossible!

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

 Slideshare.net