Journal
of
Coloproctology
w w w . j c o l . o r g . b r
Original
article
Buschke-Loewenstein
Tumor:
a
case
series
from
Brazil
Maurilio
Toscano
de
Lucena
∗,
Luciana
Hora
Góis,
Aline
Apel,
José
Figueiroa
Filho,
Maurício
José
de
Matos
e
Silva,
Cláudia
Rosali
Esmeraldo
Justo,
Joaquim
Herbênio
Costa
Carvalho,
Fernando
Monteiro
HospitalBarãodeLucena,Recife,PE,Brazil
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f
o
Articlehistory:
Received26November2013 Accepted12August2014 Availableonline28October2014
Keywords:
Giantcondylomaacuminatum Buschke-LoewensteinTumor Verrucouscarcinoma Humanpapillomavirus
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Buschke-LoewensteinTumororgiantcondylomaacuminatumisadiseasecausedbyaDNA virus,theself-inoculablehumanpapillomavirus(HPV),beingsexuallytransmitted. Histo-logicallyBLTisabenigntumor,butwithmalignantclinicalbehaviorandahighpropensity forlocalrecurrenceandmalignantdegeneration.Theclinicalpictureconsistsofthe pres-enceofacauliflower-likebulkycondylomatousperianalmasswithmultiplefistuloustracts, whichcancausegreatdestructionoftheanalcanal,withinvasionofadjacenttissues. Bleed-ing,foulodor,localpainandweightlossarealsodescribed.Thediagnosisisestablished bybiopsy,thatshouldexcludethepresenceofmalignanttransformation,whichoccursin 30–50%ofcases.Associatedwithabiopsy,thehybridizationtestmaybeperformedto diag-noseHPVinfection,especiallysubtypes6and11,thatarecommonlyrelated.Thetreatment ofchoiceisradicalsurgicalexcision;however,thosepatientspresentingwithextensive fis-tulouslesionsmayrequireatemporarycolostomy.Someauthorsadvocatean abdominoper-inealresectionincasesofinfiltrationofthesphincterorrectum.Thisstudywasdesignedto evaluatetheexperienceoftheserviceofColoproctologyatareferralhospitalinNortheastern Brazilwiththisrareentity,contributingtoworldliteratureinaddressingthisdisease.
©2013SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.All rightsreserved.
Tumor
de
Buschke-Loewenstein:
uma
série
de
casos
brasileira
Palavras-chave:
Condilomaacuminadogigante TumordeBuschke-Loewenstein Carcinomaverrucoso
Papilomavírushumano
r
e
s
u
m
o
TumordeBuschke-Loewensteinoucondilomaacuminadogiganteéumadoenc¸acausada porum vírusde DNA,opapilomavírushumano(HPV),auto-inoculável,sendo transmi-tidosexualmente.Histologicamente,sãotumores benignos,porém,de comportamento clínicomaligno,apresentandoaltapropensãoàrecorrêncialocaleadegenerac¸ãomaligna. Oquadroclínicoconsistenapresenc¸adeumavolumosamassacondilomatosaperianal, comaspectodecouve-flor,comnumerosostrajetosfistulosos,podendoprovocargrande
∗ Correspondingauthor.
E-mail:mtlucena@superig.com.br,mtlucena@oi.com.br(M.T.Lucena). http://dx.doi.org/10.1016/j.jcol.2014.08.011
destruic¸ão do canalanal e invasão dos tecidos adjacentes. Sangramento, odor fétido, dorlocaleperdaponderalsãotambémdescritos.Odiagnósticoéfeitoporbiópsia,que deve afastar a presenc¸a de transformac¸ãomaligna, que ocorreem 30-50%dos casos. Associadoàbiópsia,podeserrealizadoumtestedehibridizac¸ãoparadiagnosticarainfecc¸ão porHPV,principalmenteossubtipos6e11quesãocomumenterelacionados.Otratamento deescolhaéa excisãocirúrgicaradical, entretanto,ospacientesqueapresentamlesão extensacomfístula,podemrequerercolostomiatemporária.Algunsautoresadvogama amputac¸ãoabdominoperinealdoretonoscasosdeinfiltrac¸ãodosesfíncteresoudoreto. Oestudofoidesignadoparaseavaliaraexperiênciadoservic¸odecoloproctologiadeum hospitaldereferêncianoNordestebrasileirocomestararaentidade,contribuindocoma literaturamundialnaabordagemdestaenfermidade.
©2013SociedadeBrasileiradeColoproctologia.PublicadoporElsevierEditoraLtda. Todososdireitosreservados.
Introduction
In 1894, Buschke drew attention to the existence of a variety of condyloma acuminatum of the penis, whose clinical behavior was invasive.1–5 Later, in 1925, the same
BuschkeandLoewensteindescribedtheconditionasa well-definedclinicalentity,thegiantcondylomaacuminatum,that received,sincethen,thenameofBuschke-LoewensteinTumor (BLT).6–10
BLTisaself-inoculablediseasecausedbyaDNAvirus,the humanpapillomavirus (HPV),and is sexually transmitted. Histologically,thesearebenigntumors,butwithmalignant clinicalbehavior,withahighpropensityforlocalrecurrence andmalignantdegeneration.5
Sincethedescriptionofthefirstcaseofthisdiseaseinthe analregionin1963byKnoblichandFailig,until2003only52 caseshadbeenreportedintheEnglishliterature.10–12
ThereisnotreatmentdefinedfortheBuschke-Loewenstein Tumor;topicalagents,immunotherapy,surgeryand chemora-diotherapyaretentativelyused.Surgery,aloneorin conjunc-tionwithothermethods,involvesextensiveresections;andin casesofinvasionoftheanalsphincter,anabdominoperineal resectionoftherectumisrequired.13–15
Thisstudywasdesignedtoevaluatetheexperienceofthe serviceofColoproctologyatareferralhospitalinNortheastern Brazilwiththisrareentity,contributingtoworldliteraturein addressingthisdisease.
Method
Thisisa retrospectivelongitudinalstudy, aseries ofcases treated atthe Hospital of Coloproctology Barão de Lucena – SES/PE through the medical records of all patients who underwentbiopsyforsuspicionofanalcondyloma,obtained fromthesurgeryregisterintheperiodfromFebruary1996to February2006.Theauthorsidentifiedsixcasesdiagnosedas Buschke-LoewensteinTumor.Then,ananalysisoftheclinical picture,treatmentinstitutedandpatientoutcomewascarried out.
Thosepatientslosttofollow-upwere contactedthrough telegrams,phonecallsorbyanactivesearchoftheirhome.
Clinicalcase1
A48-year-oldmalepatientwithahistoryofperianaltumor andpurulentdischargefromtheperineum,painandweight lossfor±2months.Onphysicalexamination,anulcerated lesionintheanalmarginwasobserved,invadingtherectum andanal canalupto±6cmfrom theanalmargin,with fis-tulizationtotheperineum.Laboratorytests:VDRL–negative; HIV–negative;CEA=2.0ng/mL,wholeabdomenUSG– nor-mal.Thehistopathologywassuggestiveofanalcondylomaof viraloriginwithsecondarysuppurativechronicinflammation inthecorium.
Intralesionalinterferonhasbeenproposed,butthepatient refusedtreatment,returningtotheoutpatientcliniconlyafter aperiodof4months.Onthisoccasion,heshowedprogression ofthelesion,withtherectum andanal canalalmost com-pletelyobstructedbyanulcerative-vegetativetumor,invading theprostaticcavityandischiorectalfossa,withmultiple fis-tulae tothe perineum and gluteal region. The upperlimit ofthetumorwasnotreachedbytheexaminer’sfinger.This patientalsohadsevereleukocytosis(30,000cells/mm3)with
aleftshift.Antibioticsanddrainageofabscessesandfistulae, includingthescrotum,wereestablishedandanewbiopsywas performed, that was consistent with Buschke-Loewenstein Tumor.
Then,weproposedanabdominoperinealresection,butit wasdecidedthatonlyaterminalsigmoidcolostomywouldbe performed,becausethetumorwasconsideredunresectable. The patient was discharged and his last contact with the servicewasattheurgencyunit,whenhewasseenwith com-plaintsoffever anddysuria, beingmedicatedand released home.
Clinicalcase2
Thehistopathologydemonstratedanabsceded,fistulous, nonspecificchronicinflammation.HIVandVDRLtestswere negative. The patient underwent a loop colostomy, retur-ningmonthslaterwithworseningofthedisease,whenwas evidencedavegetating, abscededand ulceratedtumorthat beganat±7cmfromtheanalmarginexternally,reachingthe righthemicircumferenceoftherectumandwithinvasioninto theischiorectalfossa.Thehistopathologyrevealedcondyloma acuminatumwithareasofulcerationandhyperplasic granu-lationtissue.
Thepatient underwent localexcision, and the resultof thehistopathologicalexaminationwasconsistentwitha ker-atinizing,vegetativeandinfiltratingsquamouscellcarcinoma oftheanalmargin,showingmoderatedifferentiation.
We opted for radiation and chemotherapy with 5-fluorouracil at a dose of 1g/m2 of body surface area/day/
continuousinfusionfor4days,startingonthe1stand 21st daysofradiationtherapy,andcisplatinatadoseof75mg/m2of
bodysurfacearea/infusionof2honthe2ndand22nddaysof radiationtherapy.Thetotaldoseofradiotherapywas4500cGy with180cGy/dayfor28days.Thepatientwasdischargedafter thesecondcycle;however,shediedathomebeforebeing eval-uatedastothetreatmentoutcome.
Clinicalcase3
A38-year-oldfemalepatientwithapictureofrectal bleed-ing,eliminationofpurulentdrainageassociatedwithperianal tumor,painand weightlossof5kgabout6monthsago.A physicalexaminationidentifiedalargeulcerated, hardand brittlelesion,whichextendedupto2cmfromtheanal mar-gin,occupyingtheentirerighthemicircumference,withthe presenceof pus,blood and cellulitis in the gluteal region. ThepatientwashospitalizedandunderwentendovaginalUS, whenabulkymasstotherightoftheanalcanalmeasuring 4.1cm×2.4cmwasdemonstrated,withnosignsofabscess. The histopathological examination revealed presence of a giant condyloma of Buschke-Loewenstein. The lesion was affectingpartoftherightglutealregionandanalcanalinright lowerquadrant(RLQ)andrightupperquadrant(RUQ).Then, wedecidedbyperformingaloopcolostomy.Thepatient devel-opedapericolostomicabscess,whichwasdrainedpriortoher discharge.
Thepatientwasre-admittedafter2monthswithaweight lossof15kgandsevereanemia(Hb=8.1mg/dlandHt=27%), being treated with hemotransfusion; then, she underwent a local resection of part of the gluteal region bilaterally, perianalregion, posteriorwallofthe vaginaand coccyx,in amonoblockprocedure.Thehistopathologicalexamination confirmedpresenceofgiantcondylomaacuminatumandan abscededchronicinflammation.
Thepatientiswellafterafollow-upof20months,withher woundhealedandwithonlyoneparacolostomichernia,for whichsherefusesasurgicalcorrection.
Clinicalcase4
A 36-year-old male patient presenting perianal vegetating lesioninvolvingtheentiresphinctermuscle,associatedwith painforabout5months.
Fig.1–Extensivecondylomatouslesionwithlargetissue destructionintheglutealregion,perineumandbaseofthe scrotum;multiplefistulasandpurulentdischarge.
The patient underwent partial resection of the lesion (superficial hygienic resection). The histopathological find-ingswereconsistentwithverrucouscarcinoma.Onemonth later,thepatientwasseenwithextensiveandinvasive condy-lomatouslesionwithimportantanteriorfixation,withfetid odorandapurulentdrainageandmyiasis(Fig.1).On physi-calexamination,thelesionwasconsideredunresectable;on that occasion,thepatient receivedlocalcareand was pre-scribedabloodtransfusion.Afterdefiningtheunresectability, the patient was dischargedand sent forcare ataSupport Homewithoutpatientfollow-up.Thepatientreturnedafter 7monthsinastateofimportantcachexia,dehydrationand anemia,withavegetatinggiantlesioncausinggreat destruc-tionoftheanalsphincterandglutealregion,withfistulization and several necrotic areas with an extremely foul odor. The histopathology demonstrated a verrucous carcinoma (Fig. 2). The patient died before performing the scheduled colostomy.
Clinicalcase5
A 23-year-old male patient withcomplaints of small peri-analtumorsabout7monthsago,showedsignificantbleeding in stools in recent days, pain and difficulty to evacuate. HIV-positive,asymptomatic,onantiretroviraltreatment.On physical examination, a cauliflower-like vegetative mass bleeding easily to the touch, with drainage and fistuliza-tion was observed, affecting the entire anal margin in a radialextentof±15cm(Fig.3A).Treatedwithlocalresection withelectrocautery,afterinfiltrationwithadrenalinesolution (Fig.3B).
The histopathological examination confirmed the pres-enceofcondylomaacuminatum(Fig.4).
Thepatienthadbeenreceivingoutpatienttreatmentwhen, after4months,sufferedarecurrenceofthelesionintheanal margin of±8cm in diameter,extending tothe entire anal canal.Anewlocalresectionwasperformed,withpreservation oftheanalsphincter(Fig.5AandB).
Fig.2–(AandB)Stromalinvasion(ofcorium)withinflammatoryreactionisdemonstrated.(C)Hyperkeratosisand parakeratosis,hyperchromasiaandirregularity,binucleation,changeinnucleus/cytoplasmratioandkoilocytesare evidenced(HEstain,10×).
Fig.3–(A)Cauliflower-likegiantcondylomaacuminatum(GCA)inassociationwithmicrosatellitelesionsandwith spontaneousbleeding.(B)Thefinalappearanceafterelectrofulguration.
Fig.5–(A)Diseaserecurrence4monthsafterthefirstsurgery;(B)postoperativeappearanceafteranewlocalresection.
Fig.6–Recurrence5monthsafterthelastsurgery.
pruritusfor±60days.Onphysicalexamination,avegetating lesionof±3cmindiameterwasobservedintheanalmargin, occupyingtherighthemicircumference,exactlyatthe anoder-maljunctionwithoutapparentinvolvementoftheanalcanal
(Fig.6).Anewsurgicalresectionwasperformedand,todate, thepatienthasnosignsofrecurrence.
Clinicalcase6
A27-year-oldmalepatientwithperianallesionswithbloodin stools,painanddifficultytodefecate,unawareoftheduration ofthesesymptoms. Thepatientexhibitedcognitive impair-ment,andthecommunicationbetweenfamilymembersand himselfwasmarkedlyimpaired.
On physical examination, a bulky, vegetative, bleeding, condylomatouslesionaroundthe analcanalwasobserved, withnosignsofinvasionofdeepstructures.PatientHIV-and VDRL-negative.Alocalresectionofthetumorwithamargin of±2cmwasperformed,savingthesphinctermusclesand leavingthewoundopen.
Thehistopathologicalexaminationrevealedagiant condy-loma(Buschke-LoewensteinTumor)(Fig.7).
Thirteenmonthsaftersurgery,thepatientreturnedtothe clinicwithnocomplaintsandwithcomplete healingofhis wound,withoutdeformityorretraction,anintactsphincter and inastateofcontinence.On theother hand,exhibited
Fig.8–Finalappearanceafterlocalresectionandhealing bysecondaryintention.
Oxiurusinhisanalmargin,whichwastreatedwith Albenda-zole(Fig.8).
Table1summarizes themaindemographic data, symp-toms, physical examination, therapeutic regimens and evolutionofthesixcases.
Discussion
Sincethefirstdescriptionofagiantcondylomaby Buschke-Loewenstein,fewcaseshavebeenreportedintheperianaland anallocation.5
Althoughtherearenoprospectiverandomizedstudieson giantcondylomaacuminatum,numerouscasereportsexistin theliterature.Fromthese,speculationsaboutthebest treat-mentstrategyhavebeendrawn.10
Inthepresentstudy,thepatients’agerangedfrom23to 48years,predominantlyinthethirddecadeoflife(3cases). Accordingtotheliterature,GCAisfoundintheagegroupfrom 18to70years,withameanageof43years,especiallybetween the4thand6thdecadesoflife.1,6,12Studieshaveshowna
ten-dencytoGCAonsetinanincreasinglyearlyage,10whichwas
alsoobservedinourstudy.
Regardinggender, ourseriesconsistedof4malesand 2 females,withamale-femaleratioof2:1.Thepredominance ofmalesisinagreementwithmoststudies,showingahigher incidenceinmales,witharatioof2.2:1.1,6,12
Themostfrequentsymptomswere:presenceofperianal massandpain,whichwereobservedinallpatients,discharge ofpus(fourpatients),bleeding(threepatients),difficultyof defecation(threepatients), weightloss(threepatients)and rash(onepatient).Thesefindingsweresimilartothosefound inmostseries,thatreport:perianalmassin47%ofcases, peri-analpainin32%,fistulaorabscessin32%,bleedingin18%, weightlossin10%andrashin4%.10
In this series, fistulas were present in five cases, with invasionoftheanalcanaldemonstratedinfivepatientsand invasionoftherectuminthree,besidesotherstructures (scro-tum,perineum,prostaticcavity,ischiorectalfossa,gluteusor vagina),beingconsideredlocallyadvancedinfourpatients. Asthe literatureshows,theclinical courseofperianalGCA
canbeveryaggressive,causingfistulasandinfiltrationofdeep tissues,11asshowninmostofourpatients.
Diagnoseswereobtainedbasedonhistopathological exam-inations, withmany patients requiring multiple studies to confirmthediagnosis.Thankstoitsappearanceandsize,the Buschke-LoewensteinTumorcanbeconfusedwithmalignant tumorsoftheperianalregion.Therefore,thehistological diag-nosisisveryimportant.Whenamalignanttumorisnotfound, thereisatrendtoobtainanewbiopsytoconfirmtheabsence ofneoplasia,becauseoffearthatthematerialmaynothave beenrepresentative.Inthesametumor,onecanfindavery widespectrum,fromareasofcondylomaacuminatum,severe dysplasiaandcarcinomainsitu,toafranklyinvasive squa-mouscellcarcinoma.
The difficulty for the establishment of a diagnosis lies primarily in the importance in ruling out the presenceof malignant transformation,because theconfirmationofBLT does not necessarily exclude the possibility of squamous cell carcinoma. Given this, multiplebiopsies involving the entiredepthofthelesionshouldbemade,becausesuperficial samplesmaycoveronlyinflammatorytissueormaybe condy-lomatoustissue,withsuperficialthickening,withoutoffering thepathologisttheopportunitytoassessapossibleinvasion ofthebasallamina.
Themalignanttransformationisrevealedintheareasthat show thesquamouscell carcinomaassociatedwith condy-loma,whichwasobservedononeofourpatients.According totheliterature,the malignanttransformationof Buschke-LoewensteinTumorhasbeenreportedin30–56%ofcases.3,6,7,9
Thegiantcondylomaappearstobehistologicallysimilar tosimplecondylomaacuminatum.1,8,12,16Aninvasiveclinical
behavioristhecriticalfactorforthediagnosis.Manyauthors considertheBuschke-LoewensteinTumorasavariantofthe verrucouscarcinoma,butothersbelieveitisjustadifferent nomenclatureforthesamedisease.Thisconfusionregarding nomenclatureisanotherdifficultyforitsdiagnosis.Oftenthe resultofhistopathologyisaverrucouscarcinoma(asinour patients),butweonlyconsiderthepresenceofmalignancyif thereisaninvasionofthebasallamina.
There are several treatments that can be used in GCA, from topical agents (podophyllin,ATA, 5-fluorouracil) to immunotherapy,interferon,radiotherapy, chemotherapy, cryotherapy,laser,electrocauteryandsurgery(localexcision oramputationoftherectumandanus).Thechoicewilldepend onthenumberoflesions,theirextent,degreeofinfiltration, theinvolvementoftheanalcanalorrectumandthepresence (ornon-presence)ofmalignanttransformation.17
The standard approach tothe giant condyloma acumi-natum isradical surgical excision. Patients with extensive lesions,complicatedbyseverelocalinfection,requirea tem-porarycolostomy.Theabdominal-perinealamputationofthe rectum is reserved forthose patients with invasionof the rectumandanalsphincter,especiallytheexternalsphincter muscle.6,16
Inthosecaseswherethereisamalignanttransformation, theoptimaltreatmentisnotwelldefined;however, studies haveshown thatchemoradiotherapycan beusedpriorthe radicalsurgicaltreatment.2,3,6Inthesinglecaseofmalignant
Table1–Demographicdata,symptoms,lesioncharacteristics,therapeuticregimensandpatientoutcomes.
Case Age(years) Gender Symptoms Lesioncharacteristics Treatment Outcome
1 48 M Tumor+perianalpain+ purulentdrainage±2 monthsago
Ulcerovegetativefistulized tumorintheanalmargin, extendingtotheanalcanal andrectumforabout6cm
Drainageof abscesses+ATB+ colostomy
Persistswith disease,follow-up foroneyearafter diagnosis 2 27 F Perianaltumor+local
pain+difficultyto evacuate+drainageof pus±8monthsago
Bulkyulcerovegetativetumor withabscessesandfistulasto therectum,ischiorectalfossa andsuprasphinctericspace, withpartialstenosisaffecting theanalcanal
Colostomy+local excision+ radiotherapyand chemotherapy
Died8monthsafter thediagnosis
3 38 F Perianaltumorandpain +rectalbleeding+ drainageofpus±6 monthsago
Ulcerated,hardandbrittle lesionwithlocalcellulitis extendingforabout2cmand whichoccupiedtheright hemicircumferenceoftheanal canal
ATB+colostomy+ localexcision
Goodevolution,with nosignsof
recurrenceafter follow-upfor20 months
4 36 M Perianaltumorand pain±5monthsago
Vegetatingtumorinanal margin,perineumandgluteal regionwithfistulasand impairedsphinctermuscle
Partialexeresis+ abscessdrainages+ fistulotomies
Deathafter±two yearsofdiagnosis
5 23 M Perianaltumors+pain anddifficultyto evacuate+local bleeding±7monthsago
Exophyticlesionswitha condylomatousaspect throughouttheperianal circumferenceandwith involvementoftheanalcanal
Localresection Recurrenceofthe lesion;thepatient wassubmittedtoa newlocalexcision; inoutpatient follow-upfor20 months 6 27 M Perianaltumor
associatedwith bleeding,localpainand difficultytoevacuate; patientunawareofthe durationofsymptoms
Bleeding,condylomatous, bulkyvegetativelesion, affectingtheentireanalcanal
Localresection Nosignsof recurrenceafter12 months’follow-up
welladvancedandthepatientdiedshortlyaftertheendof treatment.
According to the literature, mortality occurs in 20% of patients and relapse in 50% of cases treated with radical surgery.Inourstudy,deathoccurredintwopatients(33.3%), amongthoseregularlyfollowed,intheperiodof8monthsand 2yearsafterdiagnosis,respectively.Recurrencewasobserved in one patient among the three who underwent curative surgery.Inthissamepatient,thereweretworecurrencesat ameantimeof4.5months.Thefollow-uptimeforthethree patientswhounderwentcurativesurgerywas11,13and20 months.Twopatientswerelosttofollow-up,anditwasnot possibletoassesstheactualnumberofdeathsandrelapses.
Theaggressivebehaviorofthetumor,withinvasionof adja-centtissues,determined,inmostofourpatients,difficulties inhandlingtheinjury.Theprimaryfactorimplicatedforthis behaviorwastheslownessbetweentheonsetofsymptoms, thefirstconsultationandtheinitiationoftreatment.
Conclusions
Ascan beseenfrom this review,the Buschke-Loewenstein Tumorisararediseaseinwhichonlysixcaseswerediagnosed within10years.
Althoughconsideredabenignlesion,BLTislocally aggres-sive,withfistulizationandinvasionofadjacenttissues,with theoutstandingfeatureofhighratesofrelapse,whichwas observedinonethirdoftheoperatedcases.Ahighmortality rate(1/3ofpatients)amongthosepatientsregularlyfollowed wasobservedinthissurvey,asalsoreportedintheliterature.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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