oncologic issues in the neonate (read-only) · 1. what is the diagnosis? 2. ... neuroblastoma •...

OncologicIssuesintheNeonate

BillSlaytonM.D.

Babywithbumps

YouareaskedtoevaluateababyinNICU3whodoesnotseemrighttothenurseintheunit.Baby’stoneisdecreasedandhasbrachcephaly.Babyalsohashepatosplenomegaly.…

Bloodwork

• WBC55,000,HGB7,Plt 117with80%blasts.

Questions?

1. Whatisthediagnosis?2. Whatistheprognosis?3. Whatarethesepatientsatriskforinthe

future?

TransientMyeloproliferativeDisorderoftheNeonate

• AssociatedwithDownSyndrome• Somebabiesaremosaic’swithsubtlephenotypes

• Morphologicfeaturesareconsistentwithcongenitalleukemia

• Spontaneousremissionoccurs

Complications

• Respiratorycomplicationsfrommassivehepatomegaly

• Hyperleukocytosis leadingtopoortissueperfusion

• Hepaticfibrosiscanleadtoliverfailure• 20-30%ofpatientsgoontodevelopacutemyeloidleukemialaterinlife

Pathophysiology

• InvariablyduetomutationsoftheGATA1gene.• LeadtotruncatedGATA1isoformthatfunctionsasdominantnegativeinhibitingGATA1’seffectonmegakaryocytedifferentiation

• GATA1mutationsarerarelyfoundinpatientswhodon’thavedownsyndrome

• AdditionalmutationsnecessaryforpatientswithTMDtodevelopacutemyeloidleukemia

Treatment

• Wehaveanopenbiologicstudyhere• Mostpatientsdonotneedtreatment• ChemotherapygiventopatientswithWBC>100,000massivehepatosplenomegaly,hydrops,pleuraleffusions,pericardialeffsuions,ascites,orlifethreateningliverdisease

• Chemotherapyisverymildandtypicallyshortcourse(cytarabine)

Thisbabyhasabigspleen!

Youarecalledtoassessababywhohasawebbedneckandasyouassessthebabyyounotepectusexcavatum.4extremitybloodpressuressuggestacoarctation oftheaorta.Babyhasanenormousspleenwhichisrockhardandpalpableinthepelvis.

Peripheralbloodcounts

CBCWBC77,000,platelets149,000,HGB11Smear:10%monos,60%polys,8%metamyelocytes,5%promyelocytes,5%eosinophils

JuvenileMyelomonocytic Leukemia

• Associatedwithneurofibromatosis,Noonan’ssyndrome

• Presentwithpallor,infection,bleeding,orsymptomsfromorganomegaly

• ElevatedWBCwithabsolutemonocytosisusuallypresent

• Maculopapularskinrashcommon

JMML-LikePictureandNoonan’sSyndrome

• Seeninupto10%ofbabieswithNoonan’ssyndrome

• Diagnosedduringfirstfewmonthsoflife(incontrasttopatientswithJMMLmedianage1.8years)

• Spontaneousregressionusuallyoccurs,butcanprogresstofataldisease

• AssociatedwithPTENandRASmutations

Abighonkin’liver

• Youareaskedtoevaluateatermnewbornwhohasanenormouslivermass.

• Babyhavingdifficultybreathingandisintubated

Neuroblastoma

• Canariseatanysitealongthesympatheticchain

• Mosttumorsariseinabdomen,oftentheadrenal

• Primarycan’tbefoundin1%ofcases• MassiveinvolvementoflivercausingrespiratorycompromiseiscommonininfantswithStageIV-Sdisease

Diagnosis

NeuroblastomaStaging

Prognosis

• Agelessthan18months—betterprognosis• Histology• NMyc amplificationStage• 4Sdiseasehasgoodprognosis,evenwithouttherapy

StageIVSNeuroblastoma

• Symptomaticpatientsneedemergentmedicalintervention

• Safebiopsy• Myc status(N-Myc amplifiedgettherapy)• Patientswhoareasymptomaticcanbeobservedclosely—until3months

Ourpatient

• Receivedemergentradiationtherapy• Nextmorningpatientisanuric• Creatinine>2.0

Whatdoyouthinkhappened?

TumorLysisSyndrome

• Resultofreleaseofnuclearandcytoplasmicdegradationproducts

• Potassium,principleintracellularcation,increasesandcanbeworsenedbyrenalinsufficiency.

• Uricacidcomesfrombreakdownofnucleicacids• Crystalsprecipitateincollectingductsofrenaltubules

• Phosphateandcalciumcrystalizecausingsecondaryhypocalcemia

TreatmentofTumorLysisSyndrome

• Hydration(atleast1.5Xmaintenance)• Alkalinization nolongerstandardofcareduetoconcernaboutcalciumandphosphateprecipitation.

• Allopurinol• Rasburicase

Sacrococcygeal massinnewborn

Sacrococcygeal Teratoma inNewborn

• Mostcommongermcelltumorofchildhood• Mostfrequentlyrecognizedneoplasmsinfetusesandneonats

• 75%ofpatientsarefemales• Mostareexophytic andvisable onexam• 80%diagnosedwithinfirstmonthoflife• Oneinfivehavemalignantcomponent

Sacrococcygeal Teratoma Treatment

• IfdetectedonUltrasound,growthvelocityshouldbeobserved

• Ifthreatensfetalsurvival,prematuredeliverywarranted

• Earlyandcompleteexcisionmainstayofmanagement

• Halfofrecurrencesassociatedwithmalignantyolksaccomponent

• Mostimportantriskfactorincompleteresection

Neonatewithmultiplecongenitalanomalies

Babyisbornwithanalatresia,VSD,atracheo-esophagealfistula,arenalanomaly,andmalformedthumbs.

1. Whatclassicpediatricblooddisordermightthispatienthave?

2. Howdoyouworkthisup?

Fanconi’sAnemia

• Firstcoinedtodescribefamilialaplasticanemiaandphysicalanomalies

• Nowknownthatpatientswhoappeartobenormalcanhavethedisorder.

• Fordiagnosis,necessarytohavechromosomalbreakswithclastogenic stress

• Meanageofdiagnosis8years

FanconiAnemiaAgeDistribution

Fanconi’sAnemia:PhysicalExamination

• ClassicFanconi’s:shortstature,thumbabnormalities,caféaulait andhypopigmented spots,characteristicfacialfeatures

• InThromocytopenia absentradii(TAR)syndrome,radiiabsentbutthumbspresent,whereasthumbsabnormalinFA

• TheVACTERL-Hassociation(Vertebralanomalies,analatresia,cardiacdefect,tracheoesophagealfistiula,renaldefects,limbanomalies,hydrocephalus)shouldmakeyouthinkofFanconi’s

• Atleast25%ofFApatientsdonothavephysicalanomalies

FanconiAnemiaAnomalies

PatientswithFAhaveincreasedSensitivity toclastogenic(causeDNABreaks)agentssuchasmitomycinCanddiepoxybutane(DEB)

ComplementationGroupsinFanconi’sAnemia

FusingcelllinesfromIndividualswithFArescuedcellsfromclastogenicsensitivity

FAGenesare“CaretakerGenes”

VariousFAgenesencodeproteinsthatformacomplex.ThisComplexubiquinatesFanc-DWhichtheninteractswithBRCA1inDNAdamagedcells,RegulatingDNArepair,apoptosis,Andprogression intocellcycle.

ResultofMutations

• Frequentlydevelopaplasticanemia• Highrateofmyelodysplasia• HighrateofAML• Highrateoflivertumors• Highrateofepithelialmalignancies(headandneckcancers,cervicalcancer,skincancer)

Fanconi’sAnemia:WhotoEvaluate

• Screeningrecommendedforallchildrenwithaplasticanemia

• Anypatientwithunexplainedmacrocytosisandbirthdefect

• VACTERLH-likesyndromesorstructuraldefectsofGUsystem

• Unusualsensitivitytochemotherapy