Outcome of staged excision with pathologic margin control in high-risk basal cell carcinoma of the head region,

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Anais

Brasileiros

de

Dermatologia

www.anaisdedermatologia.org.br

INVESTIGATION

Outcome

of

staged

excision

with

pathologic

margin

control

in

high-risk

basal

cell

carcinoma

of

the

head

region

夽,夽夽

Reza

Kavoussi

a

_,

_Hossein

_Kavoussi

a,∗

_,

_Ali

_Ebrahimi

a

_,

_Nader

_Salari

b

_,

Seyed

Hamid

Madani

c

a_Department_of_Dermatology,_Kermanshah_University_of_Medical_Sciences,_Kermanshah,_Iran b_School_of_Health,_Kermanshah_University_of_Medical_Sciences,_Kermanshah,_Iran

c_Department_of_Pathology,_Kermanshah_University_of_Medical_Sciences,_Kermanshah,_Iran

Received18October2019;accepted27February2020

Availableonline12July2020

KEYWORDS

Mohssurgery; Pathology; Skinneoplasms

Abstract

Background: High-riskbasalcellcarcinomainvolvesasigniﬁcantrateofbasalcellcarcinoma

thatrequiresMohsmicrographicsurgeryfordeﬁnitivetreatment.Stagedexcisionwith

patho-logicmargincontrolisasimple,accessible,andcurativeproceduresuggestedforthetreatment

ofhigh-riskbasalcellcarcinoma.

Objective: Toevaluatetheresultsofstagedexcisionofhigh-riskbasalcellcarcinomainthe

headregion.

Methods: Thisinterventionalstudywasperformedonpatientswithhigh-riskbasalcell

carci-noma,whounderwentstagedexcisionuntilthemarginswerefreeoftumor.

Results: Atotalof122patients(47femalesand75males)withmeanageof57.66±9.13years

wererecruitedinthisstudy.Nasalandnodulartypeswerethemostcommonofbothclinical

andpathologicforms,respectively.Further,89.3%ofcaseswerecuredbystagedexcisionafter

fouryearsoffollow-up.Therewasasigniﬁcantrelationshipbetweentreatmentoutcomesand

recurrentlesions,multiplicityofriskfactors,long-standingdisease,andpathologictype.There

wasalsoasigniﬁcantassociationbetweenthenumberofsurgicalexcisionsandmultiplicityof

riskfactors,aswellasrecurrence,location,andsizeofbasalcellcarcinoma.

Studylimitations: Lackofmagneticresonanceimagingassessmentincasesofsuspected

per-ineuralinvasion.

夽 _How_to_cite_this_article:_Kavoussi_R,_Kavoussi_H,_Ebrahimi_A,_Salari_N,_Madani_SH._Outcome_of_staged_excision_with_pathologic_margin

controlinhigh-riskbasalcellcarcinomaoftheheadregion.AnBrasDermatol.2020;95:583---8.

夽夽_Study_conducted_at_the_Kermanshah_University_of_Medical_Sciences,_Kermanshah,_Iran. ∗_{Corresponding}_author.

E-mail:[email protected](H.Kavoussi).

https://doi.org/10.1016/j.abd.2020.02.009

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Conclusions: High-riskbasalcellcarcinomahadahighcureratebystagedexcision.Patients

withmoreriskfactorsandthosewithnasalandrecurrentbasalcellcarcinomarequiredmore

staged excisions.Failureoftreatment ismore probable inpatients withmore risk factors,

long-standinglesions,andhigh-riskpathologicandrecurrentbasalcellcarcinomas.

openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

Introduction

Basalcellcarcinomas(BCCs)arethemost common malig-nancy, with an increasing global incidence in recent decades.However,eventhough themortality ratedue to BCCsisverylow,treatment-relatedcostsimposean impor-tantburdenonthehealthcaresystem.1,2

AlthoughthemajorityofBCCsareeasilycured,high-risk basalcell carcinomas(HRBCCs), which representa signif-icant proportion of BCCs, require special attention tobe eradicated.2,3

Mohs micrographic surgery (MMS) is the treatment of choiceforHRBCCs,butthismethodrequiresspecial instru-mentsandboth surgical andpathologic experts;it is also expensive.4---6

Stagedexcisionwithpathologicmargincontrol(SEPMC) isasimpleandaccessibleprocedure withahighcurerate thatissuggestedforthetreatmentofspecialtypesofBCC orforspecialsitessuchasperiorbitalornasalareas.6---10

Considering thevery high prevalence ofBCCs, the rel-ativelyhighnumber ofHRBCCs,and thelack of accessto MMSatmostdermatosurgerycentersworldwide,thepresent studyevaluatedtheresultsofSEPMCinHRBCCsinthehead regionoversevenyears.

Methods

Studydesignandpopulation

Thisclinical,interventional,follow-upstudywasperformed on122 patientsover aperiodof eightyearsfrom2008 to 2016attheHajdaiedermatologyclinicofKermanshah Uni-versityofMedicalSciences,Iran.Abiopsywasperformedfor patientsclinicallysuspected ofBCC.Afterhistopathologic documentationof BCCs and their type, the patients with HRBCCcriteriawerechosenascandidatesforthistreatment modality.

Allparticipantswereinformedaboutthisprocedureand wereaskedfortheirconsent.Then,theywererecruitedin thestudy.

The exclusioncriteriaincludedlesionswithadiameter largerthan5cm,penetrationof malignantcells intodeep subcutaneous area or cartilage involvement, extension of tumortospecialsites suchasconjunctiva, stagedsurgery more than four times, pregnancy, comorbidities such as immunodeﬁciency,andgeneticsusceptibilitytoBCCssuch asxerodermapigmentosumandrepairabnormalities.

Demographicdata,site,clinicalandpathologic charac-teristicsofBCCs,typeandnumberofriskfactors,treatment outcome,andcomplicationswererecordedonthe question-nairesusedinthisstudy.

CriteriaforHRBCCs

HRBCCswereconsideredtobelesionsinhigh-risklocations, pathologicandclinicaltypes,lesionslargerthan2cm,those withperineuralinvasion,thosewithindeterminateborders, recurrentlesions,andthoseinpatientsless than30years old.

Proceduralmethods

BCC lesionswere assessed underappropriate lighting and 2.5×loupe magniﬁcation; their marginswere determined byasurgicalmarker.Inthecaseoflesionswithundeﬁned margin,adisposableandsharpcurettewasusedunderlocal anesthesiatoremovethefragileandabnormaltumoral tis-sueinordertodeterminethemargin.

Afterdeterminingthetumorborderandlocal anesthet-ics,theBCCswereexcisedwitha4to6mmsurgicalmargin basedonthenumberofriskfactorsfor BCCs.Theexcised tumoral tissue wasmarked with suture or a different ink colorinthesuperiorandinferiordirections.

The excised and marked sample was ﬁxated in 10 % formaldehydesolutionandsubmittedtoapathology labo-ratory.Thepathologydepartmentwasinstructedtopresent thehistopathologicalresultsassoonaspossible.

Subsequent tissue excision was advanced 2 to 3mm at each stage based on the histopathologic report if the resectionmarginswerefoundtobehistopathologically pos-itive,or when themargin wastoo narrowin theinvolved areas. Therewere two-to-fourday intervalsbetween sur-gical stages.In ordertopreventsecondary infection,oral antibioticswereprescribed.

Finally,whenallsurgical marginsweretumor-free,the repairapproachwasestablishedbasedonthesize,location, andotherfactorsoftheremainingdefect.

The number of surgical stages and probable complications duringthe surgical processwasrecorded in thequestionnaire.

Pathologicassessment

The specimens were received in 10% formaldehyde solu-tionandwereorientedaccordingtotheirlabels.Then,thin representative pieces were takenfrom the labeledtissue margin to diagnose the tumoral tissueinvolvement. After preparation of slides, staining was done by hematoxylin-eosinmethod.Ifanyofthemarginswereinvolvedaccording tothelabels,thelocationoftheinvolvementsitewasgiven to the dermatosurgeon and subsequent excision was rec-ommendeduntilfreemarginswereobtained.The margins status was reported as soon as possible, not more than 48hours.

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Table1 Characteristicsofthestudypopulation.

Percent Frequency Variables

38.5 47 Female Sex 61.5 75 Male 58.2 71 <60 Age(years) 41.8 51 ≥60 74.6 91 _≤20 Size(mm) 25.4 31 >20 53.3 65 _≤48 Duration(months) 46.7 57 >48

56.6 69 Negative Personalhistoryof

BCC

43.4 53 Positive

25.4 31 TypeII Skinphenotype

61.5 75 TypeIII 13.1 16 TypeIV 40.2 49 Nose Site 15.6 19 Periorbital 8.2 10 Forehead 7.4 9 Cheek 5.7 7 Post-auricular 4.9 6 Ear 4.9 6 Lateralofface 3.3 4 Chin 3.3 4 Periorificial 3.3 4 Nasolabialfold 3.3 4 Scalp 60.7 74 Defined Border 39.3 48 Undefined 63.1 77 Yes Previous treatment 36.9 45 No

82.0 100 Nodular Clinicaltype

8.2 10 Superﬁcial

9.8 12 Morpheaform

55.7 68 Nodular Pathologictype

17.2 21 Inﬁltrative 9.8 12 Morpheaform 9.0 11 Micronodular 8.2 10 Superﬁcial 13.9 17 I Numberofrisk factors 47.5 58 II 25.4 31 III 13.1 16 IV 7.4 9 I Numberof excisionstages 45.9 56 II 30.3 37 III 16.4 20 IV 89.3 109 Cure Outcomeof treatment 10.7 13 Failure

BCC,basalcellcarcinoma.

Ethicalconsiderations

This study wasapprovedby theEthics Committeeof Ker-manshahUniversityofMedicalScienceandregisteredinthe IRCT database(IRCT201412196403N5). Patientinformation waskeptconﬁdential.

Statisticalanalysis

DataanalysiswasperformedbySPSS(v.16)usingdescriptive andinferentialstatistics.

Asforthedescriptivestatistics,thecentraltendencyand thedispersionalongwithtableswerereported.

Regardinginferentialstatistics,thechi-squaredtestand multiplelogisticregressionanalysiswereapplied.Multiple logisticregressionmodelswerecreatedtoexaminethe rela-tionshipbetweenstudyvariablesandoutcomeandnumber ofexcisionstepstoprovidetheoddsratio(OR)witha95% conﬁdenceinterval(95%CI).The levelofsigniﬁcance was setat0.05.

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Table2 Univariatelogisticregressionanalysisbasedontreatmentoutcomesandnumberofexcisionsteps.

Outcome Univariate Numberofexcisionstages Univariate

95%CI OR p-value ≤2 >2 95%CI OR p-value --- 1 0.545 30(63.8) 17(36.2) --- 1 0.066 0.198---2.35 0.682 35(46.7) 40(53.3) 0.954---4.26 0.496 --- 1 0.264 31(47.7) 34(52.3) --- 1 0.188 0.602---6.37 0.510 34(59.6) 23(40.4) 0.301---1.26 1.62 --- 1 0.106 21(42.9) 28(57.1) --- 1 0.006 0.115---1.23 2.56 44(60.3) 29(39.7) 0.237---1.03 2.02 --- 1 0.388 43(47.3) 48(52.7) --- --- 0.025 0.813---8.65 1.99 22(71.0) 9(29.0) 1.13---6.56 2.7 --- 1 0.031 46(70.8) 19(29.2) --- --- 0.065 0.059---0.873 0.227 19(33.3) 38(66.7) 0.096---0.445 0.207 --- 1 0.057 40(58.0) 29(42.0) --- --- 0.236 0.087---1.03 0.301 25(47.2) 28(52.8) 0.315---1.33 0.647 --- 1 0.001 37(54.4) 31(45.6) --- --- 0.778 0.928---11.03 0.313 28(51.9) 26(48.1) 0.667-1.03 1.1 --- 1 0.052 9(40.9) 13(59.1) --- --- 0.203 0.086-1.01 3.3 56(56.0) 44(44.0) 0.720---4.69 1.8 --- 1 0.017 62(80.5) 15(19.5) --- --- 0.005 0.063---0.760 0.219 3(6.7) 42(93.3) 0.005---0.063 0.017 --- 1 0.167 41(55.4) 33(44.6) --- --- 0.559 1.16---13.9 0.248 24(50.0) 24(50.0) 0.389---1.66 0.805 --- 1 0.006 48(63.2) 28(36,8) --- --- 0.006 0.038---0.571 0.148 17(37.0) 29(63.0) 0.160---0.730 0.342

OR,oddratio;95%CI,95%conﬁdenceinterval.

Results

Atotalof122patients,47(38.5%)femalesand75(61.5%) males,wererecruitedinthisstudy.Theagerangeofthe par-ticipantswas38---81years,withameanageof57.66±9.13 years(Table1).

Thenasalareawasthemostcommonsiteoftreatment 49(40.2%),andtheperiorbitalarea19(15.6%)andforehead 10(8.4%)wereothercommonlytreatedareas(Table1).

Clinically, 100 (82.0%), 12 (9.8%), and 10 (8.2%) BCCs manifested as nodular, superﬁcial, and morphoeic types, respectively(Table1).

Pathologic assessment of lesions revealed 44 (36.1%) high-riskand78(73.9%)low-riskpathologictypes(Table1). Seventy-seven(63.1%) patients presented withprimary BBCsand 45(36.9%)patientshadrecurrent BCCsasarisk factor,whohadbeenpreviouslysubjectedtoinappropriate procedures(Table1).

Moreover, one-, two-, three-, and four-stage surgical excisionsweredoneinnine(7.4%),56(45.9%),37(30.3%), and20(16.4%)lesions,respectively(Table1).

Outof 122lesions,109lesions(89.3%) werecuredand only13lesions(10.7%)showedrecurrenceduringthe follow-upperiod(Table1).

Other demographic and clinical characteristics of the patientsarepresentedinTable1.

Nocomplications, includinginfectionin thesurgical or para-surgicalsitesandbleeding,wereseenduringthe sur-gicalandfollow-upperiods.

To better quantify the relationship between the study variables andthe number of surgical excisions and

treat-ment outcomes, a more concise classiﬁcation of some of thevariableswasperformed(Table2).

Theresultsoflogisticregressionanalysisshoweda signif-icantrelationshipbetweenthenumberofsurgicalexcisions andtumorlocation,multiplicityofriskfactors,tumorsize, andrecurrentlesions(p<0.05;Table2).

Theresultsoflogisticregressionalsoshowedasigniﬁcant relationship between treatment outcome and pathologic type,recurrentcases ofBCCs,multiplicity ofrisk factors, anddiseaseduration(p<0.05;Table2).

Discussion

This study showed a 89.3% cure rate for HRBCCs through SEPMC, with a mean of 2.63 stages of excision over 48 monthsoffollow-up.

Patientswithatumorsizemorethan20mm,nasalBCCs, recurrentBCCs,andthosewithmorethantworiskfactors requiredmoresurgicalexcisions.

TheresultsofthisstudyshowedthatfailureofSEPMCwas more possible in thehigh-risk pathologic types, recurrent BCCs,multipleriskfactors,andlong-standingdiseases.

Inthe present study,patients withrecurrentBCCs and more riskfactors requiredmore surgical excision andhad more possibilityof treatment failure.Therefore, patients withthementionedvariablesrequiremoreattentionfora completecure.

Several studies have indicated 95% cure rate for BCCs throughSEPMC.6---9

The present studyalso showedanearly 90%successful treatmentrateforHRBCCsbySEPMC.

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Itisbelievedthatthisdiscrepancyisduetothepresence and multiplicity of therisk factors, particularly recurrent BCCs.Inaddition,insomepreviousstudies,SEPMChasbeen performedineitherlow-andhigh-riskBCCsorspeciﬁcareas suchasthenoseorperiorbitalarea.7---9

ThefactorsthatcausetreatmentfailurethroughSEPMC includemaintumorswithskipareas,perineuralinvasionof some high-risk BCCs, and inconsistency between the sur-geonandthepathologistinmarkingthetissuesamplesfor pathologicassessment.11,12

Itappears thatrecurrentBCCsleadtoirregulargrowth andexpansionoftumorislandsfromtheprimarytumor loca-tion,makingthemdifﬁcult tocureby SEPMCandevenby MMS.10_Many_studies_have_reported_the_successful_treatment ofrecurrentBCCsislessprobablethanthatoftheprimary BCCs,eventhroughMMS,andrequires moresurgical exci-sions,whichisconsistentwiththecurrentﬁndings.13---15

Obviously, in cases of the disease with delayed treat-ment, the lesion is associated with an increased size, deeperpenetration,andmorepossibilityofskipareasand metastasis.1,16,17_Therefore,_treatment_failure_is_more_likely incaseswithalongevolution,andespeciallyafterordinary surgicalexcisions.

Inthepresent study,nasallesionshadahighernumber ofsurgicalexcisions,whichisconsistentwiththeresultsof manypreviousstudies.NasalBCCsaremorelikelytodevelop fan-like dissemination and perineural invasion. There are also more pathologic and clinically high-risk cases that increasethenumberofsurgicalprocedures.5,18,19

BCCswithhigh-riskpathologicfeatures---including mor-phoeic, inﬁltrative, and micronodular types --- are more likely to develop skip area dissemination and perineu-ral invasion; therefore, recurrence is possible even with MMS.2,11---13,16,17

In the current study,patients withhigh-risk pathologic lesionsshoweda signiﬁcantly higherrecurrencerate than thosewithlow-riskpathologiclesionsdespitestagedsurgical excisions.

Conclusion

TreatmentofHRBCCsthroughSEPMCresultedinahighcure rate.Patientswithmorethantworiskfactorsandrecurrent lesionsrequireda highernumberofsurgical excisionsand hadahigherpossibilityoftreatmentfailure.

PatientswithBCCslargerthan20mm andnasallesions requiredagreaternumberofsurgicalexcisions.BCCswith high-risk pathologic type and duration of more than 48 monthswereassociatedwithmorepossibilityoftreatment failure.The authorssuggestnewstudiesfor better assess-mentoftheﬁndingsofthepresentstudy.

Financial

support

Nonedeclared.

Authors’

contributions

RezaKavoussi:Draftingandeditingofthemanuscript; col-lection,analysis,andinterpretationofdata.

Hossein Kavoussi: Approval of ﬁnal version of the manuscript;conceptionand planningof thestudy; partic-ipationinthestudydesign.

AliEbrahimi:Participationinthestudydesign; intellec-tualparticipationin the propaedeutic and/or therapeutic conductof thestudiedcases;criticalreviewof the litera-ture;criticalreviewofthemanuscript.

NaderSalari:Statistical analysis;critical reviewof the manuscript.

Seyed Hamid Madani: Conception and planning of the study;collection,analysis,andinterpretationofdata.

Conﬂicts

of

interest

Nonedeclared.

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