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InternationalJournalofSurgeryCaseReports11(2015)29–32ContentslistsavailableatScienceDirect
International
Journal
of
Surgery
Case
Reports
j o u r n al ho m e p a g e :w w w . c a s e r e p o r t s . c o m
A
unique
presentation
of
a
renal
clear
cell
carcinoma
with
atypical
metastases
Staderini
F.
∗,
Cianchi
F.,
Badii
B.,
Skalamera
I.,
Fiorenza
G.,
Foppa
C.,
Qirici
E.,
Perigli
G.
UnitofGeneralandEndocrineSurgery,DepartmentofSurgeryandTranslationalMedicine,UniversityofFlorence,Florence,Italya
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received27February2015
Receivedinrevisedform4March2015 Accepted4March2015
Availableonline9April2015
Keywords: Kidneycancer
Renalclearcellcarcinoma Metastases
Nephrectomy Metastasectomy Targetedtherapies
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INTRODUCTION:Renalcancerisarelativelycommonneoplasiawithrenalclearcellcarcinomabeingthe mostfrequenthistologicaltype.Thistumorhasastrongtendencytometastasizevirtuallytoallorgans. Today,newdiagnostictoolsallowphysicianstodistinguishbetweenthosepatientswith“incidental findings”andthosewithadvancedmetastaticdisease.
PRESENTATIONOFCASE:A70-year-oldmalewithmultipleindolentsubcutaneousmassesunderwent colonoscopyafterapositivefecalscreeningtestforcolorectalcarcinoma.Arectallesionwas discov-eredbutbiopsywasnegative.CTscanrevealedadvancedrenalcancerinvolvingtheperitonealcavity, retroperitoneumandlung.Biopsyofsubcutaneousmassesconfirmedthesuspectedmetastases.The patientunderwentsurgery(anopenleftnephrectomywithrectosigmoidresectionandmetastases debulking)becauseofahighriskofbowelobstructionandincreasinganemia.Afterthreeyearsof multi-targetedtherapyandfollow-up,thepatientisstillasymptomaticandingoodgeneralcondition. DISCUSSION:Treatmentofmetastaticrenalcancerisstillcontroversialevenifmorethan30%ofpatients havemetastasisatthetimeofdiagnosis.Recentlyintroducedtargetedtherapiesareencouragingbutstill presentproblemswithsideeffectsandanunlimitedperiodofefficacy.Althoughthereisnoconsensus, severalstudiesandguidelinesconsidermetastasectomytobeavalidoption.
CONCLUSION:Recentserieshighlightsurgeryasakey-pointinthemanagementofadvancedrenalclear cellcarcinoma.Ourcasedemonstratesthevalidityofasurgicalstrategysupportedbyamultidisciplinary approach.
©2015TheAuthors.PublishedbyElsevierLtd.onbehalfofSurgicalAssociatesLtd.Thisisanopen accessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
Renalcancerisarelativelycommonneoplasia,with approxi-mately11,800casesperyearinItaly,amountingto3%ofalladult malignancies[1].Renalclearcellcarcinoma(RCC)isthemost fre-quenthistologicaltype,representing60%ofcaseswiththehighest incidenceoccurringinindividualsbetween50and70yearsofage. Renalcanceristheurologicaltumorwiththehighestmortalityrate. Itsaggressivebehavior,duetoastrongtendencytometastasize (30%ofcasesaremetastaticattimeofdiagnosisorduring follow-up)isassociatedwith14,000estimateddeathsin2015intheUSA [2].
Whileinthepast,RCCtypicallypresentedashematuria,flank painorpalpablemassintheabdomen,mostcasestodayare asymp-tomaticattimeofdiscovery,duetotheavailabilityofmoreaccurate diagnostictools.Thistrendhasresultedin agreater separation betweencasespresentingas“incidentalfindings”andthosewith advancedmetastaticdisease.
∗ Correspondingauthor.Tel.:+393337240361. E-mailaddress:staderini.fabio@gmail.com(F.Staderini).
RCC’sstrongtendencytometastasizeismainlyduetocomplex andrichvascularizationanditslymphaticdrainage.Themajorsites ofmetastasisarelung[75%],bone[20%],lymphnodes[11%],liver [18%],andbrain[8%]butvirtuallyallorganscanbeaffected[3].
2. Presentationofcase
The patient, a 70-year-old man witha history of hyperten-sion,diabetesandmultipleindolentsubcutaneousmasses,after apositivescreeningfecaltestforcolorectalcarcinoma,underwent colonoscopy.Thepatientwasasymptomatic,withneitherrectal bleedingnorhematuria.
Theendoscopistdescribedasmoothflatlesionoccupying one-third ofthecoloniclumenextendingfor5cm, characterizedby richsuperficialvascularizationwithnomucosalulceration,20cm fromtheanalverge.Biopsysamplesshowednon-specific lympho-cyticinflammationwithedemaofthecolonicmucosalwall.The maintumormarkerswerenormal:CEA1ng/mL,Ca19-93.1U/mL, PSA0.39ng/mL,CA-72.41.1U/mL.Renalfunctionwasconserved. ThepatientunderwentwholebodyCTscanwhichrevealed mul-tiplenodularmassesoccupyingtheentireperitonealcavity,pelvis andretroperitoneum,rangingfromafewmillimetersupto4cm intheretroperitonumand8cminthepelvis(Fig.1).Specifically, http://dx.doi.org/10.1016/j.ijscr.2015.03.009
2210-2612/©2015TheAuthors.PublishedbyElsevierLtd.onbehalfofSurgicalAssociatesLtd.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
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30 F.Staderinietal./InternationalJournalofSurgeryCaseReports11(2015)29–32
Fig.1.AbdominalCTscan.
theposterioraspectoftheleftkidneywasoccupiedbyanexpansive processpenetratingthepara-andperirenalspacewithamaximum transversediameterof11cm.Thelungswereinvolvedwithlesions ofsecondaryaspectwithintensecontrastenhancementand subcu-taneoustissuewascharacterizedbymultiplelumpsrangingfrom1 to10cm.Surprisingly,theliver,pancreas,spleenandbladderwere freeofpathologicfindings.
FollowingtheCTscan,thepatientwassenttoourdepartment forsurgicalevaluation.Physicalinspectionconfirmedthepresence of palpable masses in the leftabdomen and multiple subcuta-neouslesionsofparenchymatousconsistencyinthepatient’sarms, backandchestthathereportedashavinghadforyearsandthat werealwaysconsideredasbenignlipomas.Wedecidedtobiopsy onesubcutaneouslesion,locatedintheleftchestwall, and his-tologyidentifieditasclearcellcarcinomaofpossiblerenalorigin (AE1/AE3+,CDK7−/+,Vimentin+,CD10+,TTF1−).
Althoughthereisnosureevidenceofmajorclinicalbenefitof surgeryin metastaticrenal cancer[4]afterconsultingwiththe pathologistandtheoncologist,wedecidedtoproceedtosurgery mainlybecauseofahighriskofbowelobstructionandincreasing anemiaduetorecurrentrectalbleeding.Anotherpurposewasto permitsubsequentchemotherapyaftermassivecytoreductionof theneoplasiawithpossiblybetterefficacy[5,6].
Theoperationperformedwasanopenleftnephrectomywith rectosigmoid resection, because of two hypervascularized soft massesof5and7cminvolvedintherectosigmoidjunction.We alsoproceededwithdebulkingofthreeomentalmacrometastases ofabout5cmeach (Fig.2).Peritonealmultiplemetastasectomy
Fig.2.Omentalmetastases.
completedtheprocedure(Fig.3).Nomacroscopicradicality(R0) wasachieved.
Surgicalspecimenexaminationrevealedthattheposteriorof thekidneywascompletelysubstitutedbyasmooth hypervascular-ized10cmmassinvolvingperirenalfatandretroperitonealspace (Fig.4).Definitivehistologyconfirmeda10cmrenalclearcell car-cinomainfiltratingperirenalfat,theleftadrenalgland,omentum, sigmoidcolon (Fig. 5), subdiaphragmatic stromas and subcuta-neoustissues.Therenalpediclewasfreeofmetastaticinfiltration asweresurgicalmarginsoftheexcisedrecto-sigmoidtract;pT4, pNx,pM1(AJCC,TNM-2010).
The patient was referred to the oncologists for adjuvant chemotherapy.After6monthsofselectivemulti-targetreceptor tyrosinekinaseinhibitortherapy(Pazopanib),thewholebodyCT scandemonstratedadiffusereductionofthoraco-abdominal resid-ualdisease.Afteranother6monthsofthesametherapy,anew CTscanrevealednodimensionalvariationinthelesions.Almost 3yearsaftersurgery,thepatientisstillasymptomatic,receiving homechemotherapy(Sunitinib)andisingoodgeneralcondition. HismostrecentCTscanconfirmedthestabilityofhisneoplasia. 3. Discussion
Metastaticrenalcancerisarelativelycommoneventwithmore than30%ofpatientspresentingwithametastasisatthetimeof diagnosis,evenwithnon-palpableandasymptomaticrenalmass. AsexplainedbyKrumermanandGarret[7],thepatternofspread isalmostalwaysunpredictable,mainlyduetodeepangioinvasion
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Fig.4.Leftkidney.
andcomplexlymphaticdrainage.However,thereisapredilection forcertainmetastaticsitessuchasthelung[75%],bone[20%],liver [18%],cutaneoussites[8%]andcentralnervoussystem[8%][3].As aresult,atypicalmetastasesareconsideredthoselocalizedinasite otherthanthoracic,skeletal,hepatic,adrenalorencephalic[8].The peritoneum,gut,mesenteryandomentumareatypicalsitesand extremelyrare,affectingonly1%ofpatientswithmetastaticrenal canceruponautopsyexamination.Peritonealandretroperitoneal diffusionisassociatedwithpoorprognosis[9–11].Ourreviewof theliteraturewasunabletofindanycasesofindolentdiffuserenal cancersimultaneouslyinvolvingtheperitoneum,retroperitoneum, omentum,lung,subcutaneoustissue,colonandadrenalglandbut withnoliverandboneinvolvement.Ourcaseisprobablyoneofthe firstreported.Insuchcases,itisalwayschallengingtodecidewhich therapyisthebestchoice,especiallywhenasurgeonisrequested toperforma non-codified surgicalprocedure. Thetreatmentof metastaticrenalcancerisstillcontroversialsincelargeseriesof metastasectomiesarereportedintheliterature,butlittleisknown aboutthemanagementofmetastasisinatypicalsites[8,12].
Althoughthereisstillnoclearconsensusabouttheuseof metas-tasectomy,thiswouldbeavalidoption,assupportedbyseveral studiesandrecent guidelines[8,4,13]and bythefactthatuntil today,thetreatmentofmetastaticrenalcarcinomawithsystemic therapyhasbeenratherunsuccessful.Recentlyintroducedtargeted therapiesareproblematicbecauseofsideeffectsandtheirneedto
Fig.5. Sigmoidcolonmetastases.
betakenforanunlimitedperiodoftime[14,15].Ongoingphase3 studiesontargetedtherapiesarerecruitingpatientsbuttheresults areprematureandrequireconfirmation[16–18].
Cytoreductivemetastasectomyassociatedwithnephrectomyis anoptionbutthemainlimitationsaretheneedofgoodoverall healthandfunctionalstatusofthepatient.Patientswithasingle kidney,poorrenal functionorcavalinvolvementarenot candi-datesforsurgery.Inouropinion,thereisarationaleforsurgeryin associationwithtargetedtherapiesinthetreatmentofmetastatic RCC,althoughthetimingandtreatmentsequence arestilltobe established.
Availablestudiesdemonstratethepotentialoflong-term sur-vivalaftercompletesurgicalresectionofmultiplemetastasesin patientswithmetastaticRCCaswellasclinicalbenefitevenwith incompletesurgicalresection.Five-yearsurvivalrateswere45%, 23%and8%inoneseriesand49.4%,23.7%and8.9%inanotherseries forpatientswhounderwentcompletesurgicalresection, incom-plete surgical resection, and noresection, respectively [13,19]. Surgicalresectionremainsacriticalmodeofachievingcontrolof long-termdiseaseinmetastaticRCCpatients.However,prospective studiesarerecommendedtodefinesurgicalindications.
4. Conclusion
Ourcasedemonstratesthevalidityofthisapproachwiththe clinicalevidenceofoursurgicalandmedical strategy.We hope thatamultidisciplinaryapproach,withtheadventofnewtargeted therapies,associatedwithcompletesurgicalresectionofthe pri-marytumorandmetastaseswillleadtoadvancedmetastaticRCC becomingamoreindolentandchronicdisease[20].
Conflictsofinterest No. Funding No. Ethicalapproval Yes. Consent
Thepatientsignedawrittenconsentapprovingthetreatment ofhispersonalmedicaldataforscientificpurpose.
Authorcontribution
Eachauthorcontributedinthepreoperative,operativeor post-operativemanagementofthepatient.
Guarantor
Prof.GiulianoPerigli. References
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