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