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Verruciform xanthoma of the palatal gingiva: a report of two cases

Da Jung Ryu1, Sang Hoon Lee1, Jong In Yuk2, Hyung Jun Kim3, Joing-Ki Huh1, Kwang-Ho Park1

1Department of Oral and Maxillofacial Surgery, Gangnam Severance Hospital, 2Department of Oral Pathology, Oral Cancer Research Institute, 3Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University, Seoul, Korea

Abstract (J Korean Assoc Oral Maxillofac Surg 2013;39:292-296)

Verruciform xanthoma (VX) is a rare, benign lesion that presents in the oral cavity, skin, or genital organs as a verrucous, papillomatous, or flat papule with varying colors. VX has indistinct clinical features, making histopathological examination necessary for a definitive diagnosis. Histologically, VX is characterized by parakeratosis, rete ridges with uniform depth, and an accumulation of the foam cells, which are also known as the “xanthoma cells”. These foam cells test positive for antibodies, such as CD-68 and vimentin; it is thought that VX foam cells are derived from the monocyte-macrophage lineage, and that VX’s pathogenic mechanism is partly related to an immune mechanism. Nevertheless, the pathogenesis of VX remains unclear. VX can be treated by surgical excision; other medical, chemical, and radiological treatments are not required postoperatively. Recurrence and malignant transformation of VX are rare. Two patients, each with a mass of unknown origin on the palatal gingiva, were presented at our clinic. Excisional biop-sies of the masses were performed for a histological diagnosis after clinical and radiological examinations. Histological examination confirmed a diag-nosis of VX in both cases.

Key words: Verruciform xanthoma, Mouth, Foam cells, Immune mechanism[paper submitted 2013. 8. 12 / revised 2013. 9. 24 / accepted 2013. 9. 26]

ThedevelopmentofVXisthoughttoberelatedtoanon-

specificreaction to localepithelial traumaoran immune

reaction.However,theetiologyandpathogenesisofVXare

notyetfullyunderstood6.VXcanbetreatedwithconserva-

tiveresection.Recurrenceandmalignanttransformationof

VXarerare,andthedisorderusuallyhasagoodprognosis3.

Sofar,onlyafewcasesofVXpresentingintheoralcavity

havebeenreported4.Wereport twocasesofVXthatpre-

sentedonthemaxillarypalatalgingivaofmalepatientsand

reviewtherelevantliteratureonthisdisorder.

II. Cases Report

1. Case 1

A37-year-oldmanvisitedourhospital(GangnamSever-

anceHospitalinSeoul,Korea)becauseofapoorlyhealing

woundonhispalate.Thepatientaccidentallydiscoveredthe

woundoneyearpriortohisfirstvisit.Althoughthepatient

didnotexperienceanypain,hedescribedthelesionasbeing

somewhatuncomfortableorsensitivewhenirritatedbyfood

orpalpation.Thepatientwasadvisedtoundergoabiopsy

eventhoughthelesiondidnotseemtoprogressandchange

I. Introduction

Verruciformxanthoma(VX)isarare,benignlesionthat

presentsintheoralcavity,skin,orgenitalorgans.Itgrows

slowly,usuallywithoutcausingpain,and itsappearance

resembleslocalepithelialhyperplasiasuchasverruciform

papules,papilla,andplaque1.ThecolorofVXcanvarybe-

tweenwhite,pink,andyellow,dependingonthethickness

oftheoverlyingepidermis.VXcontainsfoamcells,which

arelipid-containinghistiocytesfoundwithinthesubmucosal

substrates2,3.Thesefindingsaresimilartothoseobservedin

leukoplakia,papilloma,verrucavulgaris,condylomaacumi-

nata,andcertainmalignantlesions,anditisthusnecessaryto

differentiateVXfromtheselesionswithatissuebiopsy4,5.

CASE REPORThttp://dx.doi.org/10.5125/jkaoms.2013.39.6.292

pISSN 2234-7550·eISSN 2234-5930

Kwang-Ho ParkDepartment of Oral and Maxillofacial Surgery, Gangnam Severance Hospital, College of Dentistry, Yonsei University, 211, Eonju-ro, Gangnam-gu, Seoul 135-720, KoreaTEL: +82-2-2019-4560 FAX: +82-2-3463-4052E-mail: omspark@yuhs.ac

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Copyright Ⓒ 2013 The Korean Association of Oral and Maxillofacial Surgeons. All rights reserved.

Verruciform xanthoma of the palatal gingiva

293

theprobabilityofmalignancywasquitelow.Anexcisional

biopsy,ratherthananincisionalbiopsy,wasthenplanned

andperformedinordertoresectthetotallesionandobtaina

definitivediagnosis.Histopathologicalexaminationrevealed

apapillaryproliferationofthestratifiedsquamousepithelial

celllayer,whichwascoveredwithahyperkeratoticlayerof

uniformthickness,aboutthatofthestratumspinosum.(Fig.3.

A)Distinctivefoamcells,alsoreferredtoasxanthomacells,

aswellasmacrophageswithvacuolatedcytoplasmcouldbe

seenintheconnectivetissuelayerwhenmagnifiedundera

high-resolutionmicroscope.(Fig.3.B)

Afterthelesionwastotallyresected,thesurgicalsiteun-

derwentnormalsecondaryhealingprocesses.Thepatient

hadnocomplications,andtherewasnoevidenceofrecurrent

diseaseduringthethree-yearfollow-upperiod.(Fig.4)

2. Case 2

A35-year-oldmanwasreferredtoourclinicforevalua-

tionofalesionthatdevelopedonhishardpalate.Thepatient

becameawareofthelesiononemonthpriortohisfirstvisit.

Duringconsultation,hecomplainedthatthelesionbecame

sensitivewhenitcameincontactwithhotandsaltyfoods,but

heexperiencednootherspecificsymptoms.Thepatienthad

ahistoryofanunknownsexuallytransmitteddisease,which

hecontractedoneyearpriortohisfirstvisitandcompletely

recoveredfrombythetimeofconsultation.Inaddition,the

patienthada20-yearhistoryofheavysmoking.Noother

specificgeneraldiseasesorexceptionalmedicalhistorywere

noted.Duringtheclinicalexamination,whichwasconducted

duringhisfirstconsultation,asoftsessilemasswithaverru-

cous,papillarysurfaceresemblingastrawberrywasfoundon

thepalatalgingivaoftheleftmaxillarysecondpremolarand

firstmolar.Thelesionwas2.5×1.0cminsize,welldemar-

cated,andpinkishincolor.Itwasnotpainfulwhenpalpated.

Healsohadanormalresponseinthepercussion,mobility,

insize,shape,orposition.

Thepatientdidnotreportanysignificantpastmedicalhis-

tory,historyoftrauma,orexceptionalmedicalorfamilyhis-

tory.Hereporteda13-yearsmokinghistorybutnootherspe-

cificsocialhabits.Duringtheintraoralexamination,awell-

demarcatedsoftandpedunculatedpapulewithaverruciform

papillarysurfacewasfoundontheleftsideofthehardpalate.

Thelesionwasapproximately1.5cmindiameter,reddishin

color,andclinicallyasymptomatic.(Fig.1)Nootherintraoral

orskinlesionswereidentified.Duringtheradiologicalexam-

ination,completewithperiapicalandpanoramicradiographs,

nospecificfindingswereobserved.(Fig.2)Consideringthe

resultsof theclinicalandradiographicexaminations,we

identifiedmultipleprovisionaldiagnosesofthislesion,in-

cludingleukoplakia,papilloma,condylomaacuminatum,and

malignanciessuchassquamouscellcarcinomaorverrucous

carcinoma.Giventhelesion’ssize,history,well-demarcated

margin,andtheresultsofanecknodeexamination,however,

Fig. 2. Radiological examination of Case 1. A. Periapical view. B. A magni-fied view of orthopantogram. No specif-ing findings on these two radiograph images. Da Jung Ryu et al: Verruciform xanthoma of the palatal gingiva: a report of two cases. J Korean As-soc Oral Maxillofac Surg 2013

Fig. 1. Clinical aspect of the palate lesion in Case 1 on the first visit. A reddish papule with a rough verrucous surface and distinc-tive margin can be observed.Da Jung Ryu et al: Verruciform xanthoma of the palatal gingiva: a report of two cases. J Korean Assoc Oral Maxillofac Surg 2013

J Korean Assoc Oral Maxillofac Surg 2013;39:292-296

294

Fig. 3. Histopathological examination of Case 1 after excisional biopsy. A. The tissue has a papillary appearance with hyperparakeratosis and uniform rete peg (H&E staining, ×40). B. High magnification (H&E staining, ×200) illustrates large foam cells (xanthoma cells, black arrows) in the connective tissue papillae.Da Jung Ryu et al: Verruciform xanthoma of the palatal gingiva: a report of two cases. J Korean Assoc Oral Maxillofac Surg 2013

Fig. 4. Follow-up clinical photos of Case 1 representing a good secondary healing state. A. Two weeks postoperative. B. Three weeks postoperative. C. Five weeks postoperative. D. Four months postoperative. E. One year postoperative. Da Jung Ryu et al: Verruciform xanthoma of the palatal gingiva: a report of two cases. J Korean Assoc Oral Maxillofac Surg 2013

Fig. 5. Histopathological examination of Case 2 at the diagnostic incisional biopsy. A. Papillary surface with parakeratosis (H&E staining, ×100). B. Xanthoma cells (black arrows) (H&E staining, ×400).Da Jung Ryu et al: Verruciform xanthoma of the palatal gingiva: a report of two cases. J Korean Assoc Oral Maxillofac Surg 2013

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295

(between40and60yearsofage),butitcanalsodevelopin

otheragegroups.Further, ithasnospecificsexpredomi-

nance4,5.Theoralcavityandthegenitalmucosaarethemost

affectedregions,andVXusuallyappearsasasinglelesion.

VXcanariseinanypartoftheoralcavity,althoughthemost

commonlyaffectedsitesare,thegingiva,hardpalate,tongue,

andbuccalmucosa, inorderofcommonality4.Although

multipleVXlesionshavebeenreportedinseveralpatient

groupswithsystemic lipidmetabolicabnormalities, there

has,ingeneral,beennodefinitecorrelationbetweenVXand

systemicdiseases8.Furthermore,VXdoesnotseemtohavea

specificrelationshipwithenvironmentalfactorssuchasahis-

toryofsmokingordrinkingortheuseofprostheticssuchas

dentures5.

Thenameofthediseaseimpliesitsclinicalcharacteristics

aswellasitshistologicaldiagnosis.VXthatdevelopswithin

theoralmucosapresentsclinicallyasasingleindolentlesion

withasurfaceofflatpapillaryorverruciformprotrusions.

Suchlesionsareusuallyabouttwocmindiameterandcan

havevariouscolorsincludinggray,pink,andyellowdepend-

ingonthethicknessandpropertiesoftheoverlyingepider-

mis1-5.Itisessentialtoobtainatissuebiopsyforadefinitive

diagnosisofVXbecauseitisdifficulttoclinicallydifferenti-

atebetweenVXandotherdiseases involvingverruciform

surfaces.Otherconditionswithsimilarclinicalfeaturesthat

shouldbeconsideredareleukoplakia,papilloma,verrucavul-

garis,condylomaacuminata,andmalignantlesionssuchas

squamouscellcarcinomaorverrucouscarcinomawithver-

ruciformsurfaces9,10.

Pathohistologically,VXpresentswithrelativelyspecific

characteristics.Ingeneral,hematoxylin-eosinstainingshows

aparakeratotic layer thatextendsto thepapillarysurface,

whiletheepithelialretepeghasagenerallyeventhickness

withaprominentextension into theunderlyingconnec-

tivetissue.Amarkedincreaseinepithelialcelldivisionor

pseudo-epithelialhyperplasiaisnotobserved.Infiltrationof

chronicinflammatorycellsthatcontainfewneutrophilsand

cellgroupsconsistingofseveralsmallandlargecellswith

vacuolatedcytoplasmaredominant inthedermalconnec-

tivetissuelayerbetweentheextendedretepegs.Theseare

specificfoamcellscalledxanthomacells,whichcouldbethe

pathologicalandhistologicalcharacteristicsofadefinitive

diagnosisforVX2.Whenstainedbyscharlachred,xanthoma

cellspresentwithanorange-redcolortypicaloflipids,and

severalsmalland large lipidgranulescanbeseen in the

cytoplasmwhenhistologyslidesareviewedunderahigh-

resolutionmicroscope.OtherfeaturesofVXsuchasswell-

andvitalitytestsofhisteeth,however;thepalatalaspectof

his leftmaxillaryfirstmolarshowedmildgingivalreces-

sion.Theradiologicalexamination,includingperiapicaland

panoramicradiographs,didnotyieldspecificresults.Further,

therewasnoenlargementorindurationofhisbilateralneck

lymphnodesonpalpation.Thoughwecouldnotobtainmore

informationabouthismedicalhistoryinregardtohissexual-

lytransmitteddisease,wesuspectedarelationship.Wediag-

nosedthelesionwithdifferentialsthatincludedsyphilisand

malignanciessuchassquamouscellcarcinomaorverrucous

carcinoma.Anincisionalbiopsyforadefinitivediagnosis

wasperformedoneweekaftertheinitialexamination.During

histopathologicexamination,histologyslidesobtainedfrom

thebiopsyshowedapapillarysquamousepithelialcelllayer

coveredwithparakeratoticsurface(Fig.5.A)andxanthoma

cellsinthesubepithelialconnectivetissuelayer(Fig.5.B),

distinctivefeaturesofVX.Conservativesurgicalresection

wasperformedaftertheresultsofthebiopsywereconfirmed.

Postoperativefollow-upexaminationshowedawell-healed

surgicalsite,andthepatienthadnocomplaints.

Fouryearsafterthisresection,thepatientreturnedtoour

clinicfortherecurrentappearanceofthelesionatthesame

site.Thelesionappearedtohavegrowntoasimilarsize,and

itsshapewasalsosimilartotheoneresectedpreviously.Fur-

ther,therecurringmassaffectedthesamepartofthebuccal

gingivaaroundhisleftmaxillarysecondpremolarandfirst

molar.Onceaclinicaldiagnosisofarecurrentlesionofthe

pre-existingVXwasmade,awidesurgicalresection,which

includedseeminglynormaltissuessurroundingthelesion,

wasperformed.Theresultsofthehistopathologicexamina-

tionoftherecurrentlesionwerethesameasthatoftheinitial

lesion.Thepatienthasbeenfollowed-upatregularintervals

offewerthansixmonthsforthepasttenyears,andtherehas

beennoevidenceofVXrecurrence.

III. Discussion

VXisarelativelyrarebenignlesionthatwasfirststudied

anddefinedbyShafer1in1971.Sincethen,thepresenceof

VXintheoralcavityhasbeenreportedinabout300cases4,

whileonlyfivecasesofVX-relatedskinlesionshavebeen

reportedinSouthKorea6,7.Althoughtherehavebeennodefi-

nitestudiesontheincidenceofthisdisease,aprevalenceof

approximately0.025%to0.094%hasbeenreported4,5.To

date,onlyabouttencasesofVXhavebeenreportedinAsian

andAfrican-Americanstudies,withthemajorityofpatients

beingCaucasian1-5.VXcommonlyoccursduringmiddleage

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nologicallycompromisedstatus,systemicdiseases,andVX,

wedeemitnecessarytoimprovetheknowledgeofVXand

havethereforereportedtwocasesofVXtreatedatourclinic.

References

1. ShaferWG.Verruciformxanthoma.OralSurgOralMedOralPathol1971;31:784-9.

2. ZegarelliDJ,Zegarelli-SchmidtEC,ZegarelliEV.Verruciformxanthoma.Furtherlightandelectronmicroscopicstudies,withtheadditionofathirdcase.OralSurgOralMedOralPathol1975;40:246-56.

3. vanderWaalI,KerstensHC,HensCJ.Verruciformxanthomaoftheoralmucosa.JOralMaxillofacSurg1985;43:623-6.

4. PhilipsenHP,ReichartPA,TakataT,OgawaI.Verruciformxan-thoma--biologicalprofileof282orallesionsbasedonaliteraturesurveywithninenewcasesfromJapan.OralOncol2003;39:325-36.

5. YuCH,TsaiTC,WangJT,LiuBY,WangYP,SunA,etal.Oralverruciformxanthoma:aclinicopathologicstudyof15cases.JFormosMedAssoc2007;106:141-7.

6. NamYH,OhCW.Acaseofverruciformxanthomapresentingasleukoplakiaonthelowerlip.KoreanJDermatol2006;44:508-11.

7. ChoiYH,MoonYJ,LeeYW,WonJY,SongES.Acaseofmul-tipleverruciformxanthomaoforalcavityandgastrointestinaltract.KoreanJDermatol2002;40:162-5.

8. TravisWD,DavisGE,TsokosM,LebovicsR,MerrickHF,MillerSP,etal.Multifocalverruciformxanthomaoftheupperaerodiges-tivetractinachildwithasystemiclipidstoragedisease.AmJSurgPathol1989;13:309-16.

9. MeteO,KurkluE,BilgicB,BekaH,UnurM.Flat-typeverruci-formxanthomaofthetongueanditsdifferentialdiagnosis.Derma-tolOnlineJ2009;15:5.

10. NevilleBW,DammDD,AllenCM,BouquotJE.Oral&maxillo-facialpathology.2nded.Philadelphia:WBSaunders;2002.

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13. HuJA,LiY,LiS.Verruciformxanthomaof theoralcavity:clinicopathologicalstudyrelatingtopathogenesis.Reportofthreecases.APMIS2005;113:629-34.

14. MostafaKA,TakataT,OgawaI,IjuhinN,NikaiH.Verruciformxanthomaoftheoralmucosa:aclinicopathologicalstudywithim-munohistochemicalfindingsrelatingtopathogenesis.VirchowsArchAPatholAnatHistopathol1993;423:243-8.

15. VisintiniE,RizzardiC,ChiandussiS,BiasottoM,MelatoM,DiLenardaR.Verruciformxanthomaoftheoralmucosa.Reportofacase.MinervaStomatol2006;55:639-45.

ingofthemitochondria,extensionoftheGolgiapparatus,

expansionoftheendoplasmicreticulum,anddestructionof

thejunctionalcomplexescanalsobeobservedunderahigh-

resolutionmicroscope.HistologicalfeaturesofVX,includ-

inghyperkeratosis,infiltrationofneutrophils,andfoamcells,

areregularlyseeninotherinjuredcells,andit istherefore

thoughtthatVXstartswithepitheliumatrophyanddestruc-

tionandthenproceedstothegenerationoffoamcells11.This

premiseissupportedbyreportsthatshowthatVXisassoci-

atedwithdiseasessuchaslichenplanus,lupuserythemato-

sus,vesicularepidermolysisbullosa,pemphigusvulgaris,and

graft-versus-hostdisease8,11,12.

In2005,Huetal.13conductedimmunohistochemicaltests

usingvariousmonoclonalantibodiesinanefforttoidentify

thepathogenesisofVX.Theauthorsconcludedthatfoam

cellsinVXtestedpositiveforspecificantibodiesofCD68

andvimentin,andthatmacrophagesandimmunecellsinthe

monocytesystemfulfilledaroleintheimmunemechanism.

However,Huetal.13couldnotidentifyaclearpathogenesis

forVX.Thusfar,variousstudieshavepresentedpossible

factorsthatcouldcauseVX,includingmicrobialcommunity,

humanpapillomavirus,lymphedema,genetictendency,and

dermaltraumawithaninflammatoryresponse11,13,14.Never-

theless,toourknowledge,nopublishedstudyhasidentified

significantcorrelationsbetweenthesefactorsandtheoccur-

renceofVX.Thus,itisnecessarytoinvestigatesuchcorrela-

tionsinthefuture.

VXcanbetreatedwithconservativeresection,anditdoes

notrequiremedical,chemical,orradiologicaltreatmentafter

surgery.RecurrentVXandmalignant transformationsare

rare.Inthiscasepresentation,wereportonecaseofrecur-

rencefouryearsafterconservativesurgicalresection.After

thesecondsurgicalprocedure,VXdidnotrecurinafollow-

upperiodlongerthantenyears.Thereportedcasesalsoshow

thattheprognosisofVXisrelativelygood1-5,9,10,15.

AsVXisararebenigntumor,generalpractitionersand

evenspecialistssuchasoralandmaxillofacialsurgeonsare

rarelyawareofthisdisease.Thusfar,therehavebeenvery

fewreportsofVX.Consideringthattherearealimitednum-

berofstudiesinvestigatingtherelationshipamonganimmu-