Perivascular epithelioid cell tumor outgrowth from the liver

CASE

REPORT

–

OPEN

ACCESS

ContentslistsavailableatScienceDirect

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

Perivascular

epithelioid

cell

tumor

outgrowth

from

the

liver

Mahir

Kirnap

_,

_Gonca

_Ozgun

_,

_Gokhan

_Moray

_,

_Mehmet

_Haberal

a_{DepartmentsofTransplantation,BaskentUniversity,Ankara,Turkey} b_{DepartmentsofPathology,BaskentUniversity,Ankara,Turkey}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received31August2018

Receivedinrevisedform9October2018 Accepted19October2018

Availableonline10November2018

Keywords: Liver PEComa Surgery Mesenchymalneoplasia

a

b

s

t

r

a

c

t

INTRODUCTION:Perivascularepithelioidcelltumor(PEComa)isararemesenchymalneoplasiaandcan befoundinvariousbodysites.Ontheotherhand,hepaticPEComaisveryrare,withonlyafewstudies havingreportedhepaticmalignantPEComa.Thereisnogoldstandardregardingtheuseofdiagnostic imagingstudies.ThediagnosisofhepaticPEComaismadebyapositiveimmunohistochemicalstaining forHMB45andMelanA.Herein,wediscussedthetherapeuticandfollow-upprocessofasymptomatic hepaticPEComacase.

PRESENTATIONOFCASE:A22-year-oldwomanpresentedwithapalpablemassinabdomen.A comput-erizedtomographicexaminationshowedagianthepaticmassofleftlobeorigin,whichwasexcised surgically.ThepathologyresultwasreportedasaPEComa.

DISCUSSION:Thediagnosticapproach,treatmentmodalities,andfollow-upproceduresarenotstandard. ThemaintreatmentmodalityforPEComaissurgicalexcisionwithadequatesurgicalmargin.

CONCLUSION:Alongerfollow-upisrequiredforpatientswithhepaticPEComabecausethenatureofthe diseaseisnotentirelyclear.

©2018TheAuthor(s).PublishedbyElsevierLtdonbehalfofIJSPublishingGroupLtd.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

1. Introduction

Bonetti et al first defined perivascular epithelioid cells in 1992.Thetermperivascularepithelioidcelltumor(PEComa)was registered by Zamboni et al in 1996 [1,2]. The World Health Organization defined PEComaas unusualmesenchymal tumors composedof histologicallyand immunohistochemically distinct perivascular epithelioid cells. PEComa tumorfamily consistsof classicalepithelioidangiomyolipoma(AML), lymphangioleiomy-omatisis,pulmonaryandextrapulmonarytumors[3,4].Thereexist severalhypothesesfortheoriginofPEComa.Thefirstonestates thatPEComadevelopsfromundifferentiatedneuralcrestcellsthat arecapableofsynthesizingthephenotypeofsmoothmuscleand melanocytes.

PEComahasbeenshowntoinvolvemanybodysitesincluding mediastinum,nasopharyngealcavity,buccalmucosa,abdominal wall,skin,spinalcord,duodenum,ileum,jejunum,colon,rectum, ligamentumteresandfalciformligament,bileduct,pancreas, uri-narybladder,prostate,penis,breast,uterus,cervix,vulva,ovaries, heart,lung,kidneys,baseofskull,urinarybladder,andpelvicwall [5].HepaticPEComaisveryrare.Onlyafewstudieshavereported hepaticbenignormalignantPEComa[4].

∗ Corresponding author at: Baskent University, Taskent Caddesi No. 77, Bahcelievler,Ankara,06490,Turkey.

E-mailaddress:rectorate@baskent.edu.tr(M.Haberal).

Nogoldstandard existsfor diagnosticimagingstudies. Hep-aticPEComais diagnosedwithapositive immunohistochemical stainingwithHMB45andMelanA[6].Herein,wediscussedthe therapeuticandfollow-upprocessofa22-year-oldwomanwho presentedwithsymptomatic,gianthepaticPEComathat radiolog-ically outgrewexophyticallyfromtheliver.Thisworkhasbeen reportedinlinewiththeSCAREcriteria[7].

2. Casereport

A22-yearoldwomanpresentedtoourclinicwithapalpable massfor6months.Themasswaspainless.Hermedicalhistory wasnotremarkableforanydisorder.Onphysicalexaminationshe had apalpablemassfilling theleftupperquadrantand epigas-trium.Onlaboratoryexaminationshehadnormallevelsoftotal protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase,blood ureanitrogen,serum creatinine, carbo-hydrate antigen19–9(Ca19-9),carcinoembryonicantigen (CEA) and alpha-fetoprotein(AFP).Shealsohad negativeserologyfor hepatitisBandCviruses.Onultrasonographytherewasa hypoe-choic,solidmasswithsharpcontoursandheterogenouspattern whichhadasizeof16x10cmanddiffusecystic-degenerativeareas andwhichappearshypervascularonDopplerUSG(Fig.1A).The describedmasswasconsideredtoresideexophyticallyintheleft lobeoftheliver.Anurgentabdominaltomographyshowedagiant solidmassthatoriginatedfromtheinferiorpartofthemedial seg-mentoftheleftlobeofliverandthatextendedinferiorly.Itssizewas https://doi.org/10.1016/j.ijscr.2018.10.046

2210-2612/©2018TheAuthor(s).PublishedbyElsevierLtdonbehalfofIJSPublishingGroupLtd.ThisisanopenaccessarticleundertheCCBYlicense(http://creativecommons. org/licenses/by/4.0/).

Downloaded for Anonymous User (n/a) at ULAKBIM Academic Baskent Universitesi from ClinicalKey.com by Elsevier on April 23, 2019. For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

CASE

REPORT

–

OPEN

ACCESS

Fig.1.(A)Dopplerultrasonogramshowinghyperechogenic,cystic,andhypervascularhepaticperivascularepithelioidcelltumor.(B)Computedtomographyscanoftumor.

Fig.2.(A)Intraoperativeviewoftumormass.(B)Viewofsurgicalmargin.(C)Sizeoftumormass.(D)Postoperativecross-sectionalareaoftheliver.

approximately17×15x11cm.Ithadsmoothcontoursandmarked hypervascularity.Itcontaineddiffusecystic-degenerativeareas.A gianthepaticadenomawasprimarilyconsideredinthedifferential diagnosis,whichalsoincludedlivertumorsofmesenchymalorigin orhepatocellularcarcinomaonanon-cirrhoticbasis(Fig.1B).

Thepatient’sabdominalcavitywasexploredwithasubcostal incision. There was a mass with smooth contours, measuring 15x12cmintheleftlobeoftheliver,whichgrewexophytically. Otherpartsoftheliverwerenormal.Themass’sportionoutofthe liverwasofhypervascularappearancethatcompressedadjacent tissuesbutwaseasilyseparablefromthem.Themasswasexcised withlivertissueandgallbladder,withanegativesurgicalmargin, withthehelpofanultrasonicdissectorandcautery.Therewasno additionallesionintheabdominalcavity(Fig.2).

Themacroscopicexamination ofthehepaticresection mate-rialrevealeda tumorallesionwithasizeof14×12x13cm and across-sectional colorof yellow,which containeddiffuse hem-orrhagicandnecroticareas,2cmapartfromthesurgicalmargin.

Sectionspreparedfromthetumorshowedthatitwasseparated fromtheadjacent hepatic parenchyma witha clearborder but showedinfiltrationoftheparenchymainafewfoci(Fig.3A).The tumorwashighlycellular,thecomponentsofwhichwere spin-dleinshapefromplacetoplaceandepithelioidinmostareas,and theyhadround-ovoidnucleiandabundanteosinophiliccytoplasm (Fig.3B).Therewereinterspersedcellsthatshowednuclear coars-ening.Tumor’sbackgroundwashighlyrichinvascularityandthere wereinterspersedfreehemorrhagicfoci.

Immunohistochemical study showed negative staining with Pan-CK,Hep-Par,CD117.Therewasdiffusecytoplasmicpositivity withHMB-45(Fig.3C)andSMA(Fig.3D).Thebackgroundrich vas-cularnetworkwaspositivelystainedwithCD34,CD31andFactor8 whiletumorcellswerenot.Twomitoticfigureswerenotedunder 50grossmagnification.Morphologicalappearanceand immuno-histochemical study resultssuggested a PEComa. Althoughthe criteriaformalignancyhavenotbeenclearlydefinedforhepatic PEComas,consideringatumorsizegreaterthan5cm,presenceof

Downloaded for Anonymous User (n/a) at ULAKBIM Academic Baskent Universitesi from ClinicalKey.com by Elsevier on April 23, 2019. For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

CASE

REPORT

–

OPEN

ACCESS

M.Kirnapetal./InternationalJournalofSurgeryCaseReports53(2018)295–298 297

Fig.3. (A)Tumorareasinfiltratingthehepaticparenchyma(shownwithyellow arrow).(B)Perivascularepithelioidcellswithroundtoovoidnucleiandabundant eosinophiliccytoplasm,whichareoccasionallyspindle-shapedbutmostly epithe-lioid(shownwithyellowarrow).(C)Diffusepositiveimmunohistochemicalstaining incytoplasmicareaforHMB-45.(D)Diffusepositiveimmunohistochemicalstaining incytoplasmicareaforsmoothmuscleactin.

Fig.4.Computedtomographicfollow-upimage10monthsaftersurgery.

morethan1mitosisunder50GMA,andinfiltrativegrowthpattern, whichhavebeenassociatedwithtumorrecurrenceormetastatic processforsofttissueorgynecologicaltumors,thecasewas con-sideredamalignantPEComa.

The patient was discussed in generalsurgery and oncology councils, which recommend no therapy. The patient recovered uneventfully,and noadditionaltherapywasrecommended.She wasdischarged3daysafterthesurgery.Shewasputunderclose follow-up; her tri-monthly control tomographic examinations revealednopathology.Sheisunderfollow-upwithoutrecurrence 10monthsafterthesurgery(Fig.4).

3. Discussion

HepaticPEComacaseshavebeensporadicallyreported world-wide.Themajorityofcasesareasymptomatic.HepaticPEComas aremostcommonlyseenbetween30and50yearsofagebutthey mayariseatanyage.Somestudieshaveshownthatwomen

sig-nificantly morecommonly develop thedisease.Hormones may play animportantrole inthepathophysiology. However, histo-genesisandpathogenesisoftheperivascularepithelioidcellsare stillunclear[8].HepaticPEComaproducenonspecificclinicalsigns andsymptomsand theyareincidentallydetectedduring physi-calexamination.Theyproducegastrointestinalsymptomssuchas abdominalpain,nausea,adominantpalpablemass,andvomiting; thereasonofthesesymptomsincreasedlesionsizecausing local-izedpressureeffectorhepaticcapsulardistention[9].Ourpatient wasa22-year-oldwomanpresentingwithabdominalswelling,in additiontowhichthereexistednospecificclinicalsymptomsor serologicalabnormalities.

Clinically,apreoperativediagnosisofahepaticlesionis primar-ily dependentonimaging studies.HepaticPEComamayappear asasolitarymassormultiplemasses.AsHepaticPEComashave variablehistologicalappearance,thesetumorslackspecific radi-ological imaging characteristics. HepaticPEComaappears asan echogenityonultrasonography.Amorevascularappearanceofa masscomparedtonormalhepatictissueonDopplerUSGfavorsthe diagnosisofPEComa[10].WhenSulphurhexafluorideis adminis-teredasthecontrastmaterialofadvancedultrasonography,lesions appear hypervascularin thearterialandportal phases[11]. On tomographyandMRIPEComascannotbedistinguishedfromother hepaticmasses.Havingsaidthat,itispossibletointerprettumorsas PEComa,dependingontheirfatdensityandvascularity[12].A com-puterizedtomographyreportedlyrevealedhepaticadenomaand hepatictumorsofmesenchymaloriginprimarilyastheprovisional diagnosisduetoasmoothcontourandmarkedhypervascularityof thehepaticmass.

TheappropriatepreoperativediagnosticmethodforPEComais stillasubjectofdebate.Fineneedleaspirationbiopsy(FNAB)is adiagnosticmethodpracticedinmanypatients.Microscopically, epithelioid, spindle cells and adipocytes canbe defined, which makes pathologistsconsider hepatic PEComainthe differential diagnosis.

They exhibitnormochromatic, small nucleotides withround nucleotides[4].Additionally,theyarepositivelycharacterizedby melanocyticand muscularmarkers.Themostnotable immuno-logical markers include HMB-45, Melan A, and SMA [13]. The microscopicexaminationofourpatientrevealeddiffuselystrong stainingwithHMB45andSMA aswellasaninfiltrativegrowth patternandnuclearatypia.Furthermore,weexcludedother hep-aticmasslesionsbyshowingnegativemarkerslikecytokeratin, CD117,andAFP.

Becauseoftherarenatureofthedisease,there are diagnos-tic challenges and treatment of hepatic PEComa is debated. A greatmajorityofthereportedhepaticPEComacasesshowabenign coursealthoughsomemalignanttumorshavealsobeenreported [14]. There are also some cases that show an invasive growth patternwithdistantmetastasisorrecurrence.Thereisnosingle standardyettoassessthemalignancygradeofahepaticPEComa. Mostofthereportedcasesunderwentsurgicalresectionsoonafter theirdiagnosis.Thisisbecausemosttumorswerepreoperatively misdiagnosedasHCCorhepaticmetastasis.Postoperative compli-cationorrecurrencehasbeenrarelyreported[15].Weperformed opennonanatomic liverresectionupon thesuspicionof a hep-aticadenoma.During surgery,themostimportantpoint topay attentionisthesurgicalmargins.Our patientdidnotsufferany complicationduringoraftertheoperation.

4. Conclusion

HepaticPEComaisararemesenchymalneoplasiaand malig-nanthepaticPEComahasbeenonlyrarelyreported.Thediagnostic approach,treatmentmodalities,andfollow-upproceduresarenot

Downloaded for Anonymous User (n/a) at ULAKBIM Academic Baskent Universitesi from ClinicalKey.com by Elsevier on April 23, 2019. For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

CASE

REPORT

–

OPEN

ACCESS

standard. Theexact diagnosisof PEComaisbased on histologi-calfindings and immunohistochemical properties likeHMB-45, SMA,andmelanA.Althougheveryneoplasiainthelivercannotbe necessarilydetectedbyradiologicalimaging,varioustools includ-ingultrasonography,CT,andMRIcanprovideimportantcluesfor physicians.Themaintreatmentmethodforthediseaseissurgical resectionwithadequatesurgicalmargin.Ifthetumorsizeissmaller than5cm,andifFNABresultisabenignpathology,itmaysufficeto followthepatientclosely.Alongerfollow-upperiodisrequiredto determinetheorigin,differentiation,andnatureofhepaticPEComa.

Conflictsofinterest

None.

Sourcesoffunding

None.

Ethicalapproval

Thisstudywasexemptfromethnicalapprovalbyourinstitution.

Consent

Writtenconsentwasobtainedfrompatientforthepublication ofthiscasereport.

Authorcontribution

MahirKirnap:Datacollection;writingpaper. GoncaOzgun:Studyconcept.

GokhanMoray:Dataanalysis. MehmetHaberal:Dataanalysis.

Registrationofresearchstudies

Notapplicable.

Guarantor

MehmetHaberal,MD.

References

[1]F.Bonetti,M.Pea,G.Martignoni,etal.,PECandsugar,Am.J.Surg.Pathol.16 (1992)307–308.

[2]M.Pea,G.Martignoni,G.Zamboni,F.Bonetti,Perivascularepithelioidcell, Am.J.Surg.Pathol.20(September(9))(1996)1149–11533.

[3]L.Xie,J.Jessurun,J.C.Manivel,S.E.Pambuccian,Hepaticepithelioid angiomyolipomawithtrabeculargrowthpattern:Amimicofhepatocellular carcinomaonfineneedleaspirationcytology,Diagn.Cytopathol.40(2012) 639650.

[4]C.D.Fletcher,K.K.Unni,F.Mertens,WorldHealthOrganizationClassification ofTumorsofPathologyandGeneticsofTumoursofSoftTissueandBone,IARC Press,Lyon,2002,pp.221–222.

[5]J.P.Zeng,J.H.Dong,W.Z.Zhang,J.Wang,X.P.Pang,Hepaticangiomyolipoma: aclinicalexperienceindiagnosisandtreatment,Dig.Dis.Sci.55(2010) 32353240.

[6]WenyingChen,YeqingLiu,YanyanZhuang,JuanfeiPeng,FengtingHuang, ShinengZhang,Hepaticperivascularepithelioidcellneoplasm:aclinicaland pathologicalexperienceindiagnosisandtreatment,Clin.Oncol.6(April(4)) (2017)487–493,Publishedonline2017Feb16.

[7]R.A.Agha,A.J.Fowler,A.Saetta,I.Barai,S.Rajmohan,D.P.Orgill,fortheSCARE Group,TheSCAREstatement:consensus-basedsurgicalcasereport guidelines,Int.J.Surg.34(2016)180–186.

[8]B.Abhirup,K.Kaushal,M.Sanket,etal.,Malignanthepaticperivascular epithelioidcelltumor(PEComa):casereportandabriefreview,J.EgyptNatl. CancerInst.27(2015)239–242.

[9]A.Zimmermann,C.vonderBrelie,B.Berger,A.Kappeler,D.Candinas,Primary perivascularepithelioidcelltumorofthelivernotrelatedtohepatic ligaments:hepaticPEComaasanemergingentity,Histol.Histopathol.23 (2008),11851193.

[10]R.Akitake,H.Kimura,S.Sekoguchi,H.Nakamura,H.Seno,T.Chiba,S. Fujimoto,Perivascularepithelioidcelltumor(PEComa)oftheliverdiagnosed bycontrastenhancedultrasonography,Intern.Med.48(2009)20832086. [11]P.DellaVigna,L.Preda,L.Monfardini,etal.,Growingperivascularepithelioid

celltumoroftheliverstudiedwithcontrast-enhancedultrasonographyand magneticresonanceimaging,J.UltrasMed.27(2008)1781–1785. [12]S.R.Prasad,H.Wang,H.Rosas,C.O.Menias,V.R.Narra,W.D.Middleton,J.P.

Heiken,Fatcontaininglesionsoftheliver:radiologicpathologiccorrelation, Radiographics25(2005)321331.

[13]A.L.Folpe,D.J.Kwiatkowski,Perivascularepithelioidcellneoplasms: pathologyandpathogenesis,Hum.Pathol.41(2010)115.

[14]H.Shi,Y.Bai,A.Guo,Fourcasesofprimarymalignantperivascularepithelioid celltumouroftheliver,Pathology45(2013)614–616.

[15]K.Kamimura,A.Oosaki,S.Sugahara,S.Mori,T.Moroda,O.Satoh,T.Morita,K. Kimura,T.Kamura,M.Nomoto,Y.Aoyagi,Malignantpotentialofhepatic angiomyolipoma:casereportandliteraturereview,Clin.J.Gastroenterol.3 (2010)104110.

OpenAccess

ThisarticleispublishedOpenAccessatsciencedirect.com.ItisdistributedundertheIJSCRSupplementaltermsandconditions,which permitsunrestrictednoncommercialuse,distribution,andreproductioninanymedium,providedtheoriginalauthorsandsourceare credited.

Downloaded for Anonymous User (n/a) at ULAKBIM Academic Baskent Universitesi from ClinicalKey.com by Elsevier on April 23, 2019. For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.