sign in sign up
<<
Home , Oncogenic osteomalacia

Copyright© ABE&M todos os direitos reservados. sed and mistreated inclinicalpractice.Theexactmech sed andmistreated 570 standing ofthis phosphate-wastingdisorder. Itseems tumorsledto new insightsinto the under factor-23 growth of fibroblast (FGF23)inoncogenic elusive.Recently,teomalacia remain theidentification anisms implicated in thepathogenesis of oncogenic os O INTRODUCTION Chicago, UnitedStates Northwestern University, andMolecular Metabolism São Paulo, SP, Brazil Federal deSãoPaulo (Unifesp), , Universidade Paulo (Unesp),Botucatu, SP, Brazil Universidade deSão Estadual Faculdade deMedicinaBotucatu, 3 2 1 case report Accepted onOct/26/2012 Received onMay/28/2012 [email protected] 01332-000 –SãoPaulo, SP, Brazil Rua Itapeva, 202,cj.129 Claudia V.Chang Correspondence to: Division ofEndocrinology, Department ofNeurologyand Department ofMedicine, life-threatening conditionmostoftenmisdiagno­ life-threatening butpotentially ncogenic osteomalaciaisarare muscle weakness.Hislaboratoryresultsmainlyshowedlowserumphosphate.Surgicalre present thecaseofa42-year-old manwithalong-termhistoryofundiagnosedprogressive factor 23.However, itispossiblethatthediseasemuch moremisdiagnosedthanrare. We Metab. 2012;56(8):570-3 Milla C. Bonates JoséV. Tagliarini de fosfato e baixos níveis de 1,25-di-hidroxivitamina D de 1,25-di-hidroxivitamina de fosfatoe baixos níveis A osteomalaciaoncogênicaéumdiagnósticoclínicodesafiador, caracterizadopelaperdarenal SUMÁRIO andonlyafteryears, adequatetreatmentarewarding outcomewas achieved. osteomalacia, thepatientsoughtmedicalhelpfromcountlessphysiciansconsecutive forfive to asymptom-freecondition.Eventhoughknowingtheunderlyingetiologywouldexplainhis earlier, years moval ofanasalhemangiopericytomathathadbeendiagnosedfive broughthim tamin D malacia causedbyrenalphosphatewasting andlowserumconcentrationof1,25-dihydroxyvi Diagnosing oncogenicosteomalaciaisstillachallenge. The disorderischaracterized byosteo SUMMARY Claudia V.Chang ser achave para evitar odiagnósticoincorreto Osteomalacia oncogênica: aperda defosfatemia pode the key to avoid misdiagnosis of mightbe : loss no decorrer doscincoanosatéquefossem instituídosodiagnósticoetratamentoadequados. clínicos enfatizam que,mesmocomaetiologiajáevidenciada,opaciente consultoudiversos tectado previamenteemcavidadenasallevou àresoluçãocompletadossintomas. Osautores defósforo. evidenciavam baixos níveis A remoçãocirúrgicadeumhemangiopericitoma porcincoanoserestriçãoàcadeiraderodas,semdiagnóstico.Seussiva exameslaboratoriais Arq BrasEndocrinolMetab. 2012;56(8):570-3 autores relatamocasodeumhomem42anoscomhistóricofraquezamuscularprogres trate muitomaisdeumafalhadiagnósticoclínicodoquepropriamentedoençarara.Os quese defatorcrescimentofibroblasto23.Noentanto,épossível produtor dealtosníveis 3 occurring inthepresenceofatumorthatproduceshighlevelsfibroblastgrowth 1 1 , GlauciaM. F. S. Mazeto , Andre C. Felicio 1 , Sandro J. Conde - - - tumor cells, is responsible forthelackofphosphatere tumor cells,isresponsible by that FGF23, a phosphatonin that is overexpressed tamin D lowlevelof1,25-dihydroxyvi with aninappropriately tubuleof the ,absorption inthe proximal along this disorder. indiagnosing highlightingthedifficulty overexpression, induced oncogenic osteomalacia with mRNAFGF23 Here, we report a case of confirmed tumor- acase of confirmed we report Here, 2 , SusanC. Lindsey 3 1 , Renata A. M. Luvizotto (1,2). 1 , Peter Kopp 3 , ocorrendo na presença de um tumor 1 Arq Bras Metab. Endocrinol 2012;56/8 , Flávia H. Moraes 3 , CéliaR. Nogueira 1 , Vânia S. Nunes Arq BrasEndocrinol 1 , 1

1 , ------Arq Bras Metab. Endocrinol 2012;56/8 areas attheendof theclavicles. Figure 1. Scoliosis, convextotheleft, inthethoracic region. Radiolucent of 851.64mg/24h(400-1,300mg/24h),andlowtu phosphaturia normal (11-65 pg/mL),inappropriately mmol\L (RV:0.81-1.45 mmol/L),PTH:53.3pg/ml of0.51 phosphorus dL (61.88μmol/L),lowserum (RV:2.1-2.6 levelof0.7mg/ mmol/L),creatinine on allfourlimbs. wasgradedIV/V Musclestrength duction ofreflexes. examination showedre beats perminute.Neurological at 78 was120/85mmHg,andpulse regular sure of metabolic disease. sorption, and no family history bone. He had no symptoms ofmalab oid and immature ofoste areas bonetissuewithirregular showing mature out, (second hospitalization)abonebiopsywascarried 1).Atthatmoment (Figure significant bonedeformity heightloss,and wasprogressive There fragility fracture. was awheelchair-user, andwasdiagnosedwithfemur disability. progressive Emergency Roomreporting He failed. toms repeatedly ficulty.relief hissymp attemptsto Severaltreatment walking dif gradually worsened, leading to progressive basically ofgeneral muscle weakness andpain, which Meanwhile, he visited countless complaining notrequested. were phosphorus, ofserum surement tests,suchasthemea sults. Hence,otherlaboratory tocheckthere consecutive yearsanddidnotreturn Unfortunately, thepatientmissedfollow-upsfor five toanasalhemangioperycitoma. tumor corresponded thatthe biopsied andthehistologicalanalysisrevealed evalua­ Clinical sodic eventsofepistaxisandnasalobstruction. Unitduetoepi ted toourOtorhinolaryngological At theageof37,thisBrazilian-whitemanwasadmit CASE REPORT His laboratory testsshowedcalciumof2.3mmol/L His laboratory thathis blood pres Physical examinationrevealed Five yearslater, atthe thepatientwasre-admitted tion revealed amassinthenasalcavity,tion revealed whichwas ------and sphenoid bone, and L lamina papyracea were ob and sphenoidbone,L lamina papyraceawere sinus,ethmoid theLmaxillary bonewallsfrom Eroded intravenous contrast. on the left with heterogeneous whole left(L)nasalcavitywithsolidethmoidalcells moral mass.Anexpandinglesionoccupiedalmostthe ofthetu thepresence imagingconfirmed resonance cavity massusingcomputertomographyandmagnetic oncogenic osteomalaciawasconsidered. bsorption ofphosphate,thehypothesisunderlying ­ gether with hyphophosphatemia and low tubular rea and pain,theradiologicalevidenceofosteomalacia,to muscle weakness the clinical complaint of progressive andtakingintoconside­ sal hemangioperycitoma, D droxyvitamin but 1,25-dihy D was normal, His 25-hydroxyvitamin phosphate wasting. 78-98%), thus indicating renal range ofphosphateat72%(normal bular reabsorption sive improvement of his muscle strength. ofhismuscle strength. sive improvement andhenoticed progres normalized, parameters were laboratory cytoma, thepatientbecame symptom-free, 2). tissue(Figure tonormal tissue compared of FGF23mRNAinthetumor showed overexpression ABI user’smanual(AppliedBiosystems).Thisassay bytheCtmethoddescribedin determined were inexpression cyclophilin mRNAlevels,anddifferences tothe normalized duplicate. ThemRNAcontentswere in performed Allassayswere mRNAexpression. trol) tatively measure sciences, Boston,MA,USA)wasemployedtoquanti tems). AnABIPrism7700system(PerkinElmerLife QuantitectRT-PCR(SYBR Green Kit,AppliedBiosys method Ichemistry outusingtheSYBRGreen carried RT-PCR Thereal-time FGF23 mRNAexpression. was (RT) Cat.no.:18080-051). PCR(Invitrogen, First-Strand SynthesisSystemforReverseTranscription with SuperScript III total RNAwasreverse-transcribed using Trizol of Onemicrogram (Invitrogen). reagent ment, andtotalRNAofthetumoralmasswasextracted at thatmo case. The tumorwascompletelyremoved lacia, weoptedtouseamolecularbiologytoolinthis totumor-inducedabout otherfactorsrelated osteoma level data, or information access to either fgf23 serum Sincewedidnothave the interiorofrhinopharynx. 7X4X6 cm and extended to The mass measured served. (26 pg/mL;RV:9-52 pg/mL). A new evaluation of the previously detectednasal A newevaluationofthepreviously After complete resection ofthenasalhemangioperi After completeresection PCRwasused tostudy Quantitative real-time As the biopsy performed 5 years earlier showeda na As the biopsy performed 3 level was also inappropriately normal normal levelwasalsoinappropriately , and cyclophilin (internal con FGF23, and cyclophilin (internal Phosphorus inoncogenicosteomalacia ration 571 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. (Student’s ttest;p<0.05). 572 tolocatethetumorsite, andwork difficult usual­ly very (4).Itis region and lessofteninthecranio-cervical placed inthelower(45%)or upper(17%)extremities, generally sible foroncogenicosteomalacia. Theyare capacity ofthepatient. tumor-resection the functional may completely restore should eagerlyseektolocatethetumorsitebecause ofthisdisorder, oftheparaneoplasticnature aware and osteomalacia. Moreover, physiciansshouldbe treating byoncogenic phosphateinpatientsafflicted low serum Thebiochemicalassessmentreveals pain/fractures. complaintsofmuscleweaknessorbone long-term cia shouldbetakenintoconsiderationinpatientswith thatoncogenicosteomala reinforces This casereport causeofosteomalacia. rare avery malacia isconsidered disease(3).Oncogenicosteo renal tion, andchronic and X-linkedhypophosphatemicrickets),malabsorp (autosomaldominanthypophosphatemicrickets, errors metabolism lead toosteomalacia.Theyincludeinborn achieved. outcomewas arewarding only afteradequatetreatment countless physicians for five consecutive years,and from explained hisosteomalacia,hesoughtmedicalhelp knownunderlyingetiologythat couldhave previously disease.Eventhoughthe patient had a another rare acaseofmisdiagnosis thanof might bemuchmore here diseases,butthepatientpresented asrare sidered inclinicalmedicinecon severalcasereports are There DISCUSSION Differences inexpressionweredeterminedbytheCtmethod(2 qPCR, andcyclophilinwasusedtonormalizeFGF23expression. tissues (hemangyopericitoma). The mRNAexpressionwasquantifiedby Figure 2. RelativeFGF23expressionfornormal(nasaltissue)andaffected Phosphorus inoncogenicosteomalacia Relative gene expression Most commonly, respon mesenchymaltumorsare that isarangeofmetabolicbonedisorders There FGF23/cyclophilin 0 1 2 3 4 5 mRNA FGF23relativeexpression Normal p <0,001 Aftected DDCt ------) the autosomal dominanthypophosphatemic (1), thinwalls(6). channels withvery vascular tightlypacked,andsurrounding shape thatare bysmallcellsofuniform formed tologic architecture, of aspecialhis toma ismainlybasedonthepresence ing, painlessmasses.Thediagnosisofhemangiopericy asslow-grow usuallypresent stillunknown(3). ratesare incidence andprevalence themostcommonneoplasms,but probably mas are osteomalacia. Amongthesetumors,hemangiopericyto teoblastomas) have been associated with oncogenic giopericytomas, hemangiomas, giant cell tumors, os the managementofourpatient. facilitated ustoestablishthediagnosisofmass,and identified,afactthatgreatly mor hadbeenpreviously tumors. Fortunately, thetu here, inthecasepresented imaging, itisnoteasytobothlocateandidentifythese techniquesofmolecular ties (5).Evenwithmodern andmodali imagingprocedures numerous up requires . was reported relevant tothis article nopotential conflictofinterest Disclosure: phate-wasting disorder. sis ofthistricky, phos and ofteninefficiently-handled, thediagno support FGF23 levelsmayfurther serum of easy diagnosisofthiscondition.Themeasurement levelsandhighphosphatoninenablesaquite phorus phos tial diagnosis.Thedocumentationoflowserum include oncogenicosteomalaciaintheirlistofdifferen andshould muscle weaknessandpain/bonefractures, complaintsof inpatientswithlong-term awareness lesion. tumor,ence ofresidual oranadditionaloccultcausative ated oncogenicosteomalaciamaybeduetothepres the associ to normalize Failure is complete resection. osteomalacia (7). diagnosis andmanagementofpatientswithoncogenic causative tumormightbeusefulclinicalmarkersforthe intheneoplastic tissue)ofthe or mRNAexpression level,immunostaining specific studyofFGF23(serum ofthecausativetumor.ze afterresection Additionally, ­ sera ofpatientswithoncogenicosteomalacianormali ele­ studies haveshownthat ic osteomalacia (2). Previous but it is also involved in the pathogenesis of oncogen vated FGF23 concentrations found in preoperative vated FGF23 concentrations foundin preoperative FGF23 was originally identified as responsible for FGF23 wasoriginallyidentifiedas Soft tissueandbonetumorsofvarioustypes(heman In conclusion,physiciansshouldhaveheightened ofchoice Once thetumorislocated,treatment Arq Bras Metab. Endocrinol 2012;56/8 ------

Arq Bras Metab. Endocrinol 2012;56/8 3. 2. 1. REFERENCES

mors are a single histopathologic entity: an analysis of 32 cases mors Cho JY, etal.Mostosteomalacia-associatedmesenchymal tu- Folpe AL, Fanburg-Smith JC,BillingsSD, BiscegliaM,Bertoni F, Endocr Rev. 2006;27(3):221-41. cellular phosphoglycoprotein,andfibroblastgrowthfactor23. phosphate homeostasis:frizzledrelatedprotein-4,matrixextra- involvedplicated ascirculatingfactors innormalanddisordered White KE,Larsson TE, EconsMJ. The rolesofspecificgenesim- 2001;86(2):497-500. thatcausephosphate wasting.tumors JClinEndocrinolMetab. rickets (ADHR)geneisasecretedpolypeptideoverexpressed by Mannstadt M,etal. The autosomaldominanthypophosphatemic White KE,Jonsson KB,CarnG,HampsonSpector TD, 7. 6. 5. 4.

2003;88(9):4088-94. foroncogenicosteomalacia.JClinEndocrinolMetab. marker Clinical caseseminar:fibroblastgrowthfactor23:anewclinical Nelson AE, BlighRC,MiramsM,Gill A, Au A, Clarkson A, etal. a nasalhemangiopericytoma.JClinRheumatol.2003;9(6):373-9. et al.Oncogenichypophosphatemic osteomalaciaassociatedwith Fuentealba C, Pinto D, Ballesteros F, Pacheco D, Boettiger O, Soto N, docrinol Metab.2011;96(12):3599-600. of wholebodyimagingintumor-induced osteomalacia.JClinEn- Chong WH, Yavuz S,Patel S,ChenCC,CollinsMT. The importance 1984;77(3):501-12. literature of42casesandreport oftwonewcases. Am JMed. Ryan EA,Reiss E.Oncogenousosteomalacia.Review oftheworld 2004;28(1):1-30. reviewoftheliterature. and acomprehensive Am JSurgPathol. Phosphorus inoncogenicosteomalacia 573

Copyright© ABE&M todos os direitos reservados.