Oral phaeohyphomycosis in a patient with squamocellular carcinoma of the lip: second case report

brazilian journal of microbiology48(2017)208–210

h ttp : / / w w w . b j m i c r o b i o l . c o m . b r /

Medical

Microbiology

Oral

phaeohyphomycosis

in

a

patient

with

squamocellular

carcinoma

of

the

lip:

second

case

report

Suanni

Lemos

de

Andrade

_,

_André

_Ferraz

_Goiana

_Leal

_,

Armando

Marsden

Lacerda

Filho

_,

_Danielle

_Patrícia

_Cerqueira

_Macêdo

_,

Maria

do

Carmo

Carvalho

de

Abreu

e

Lima

_,

_Rejane

_Pereira

_Neves

a_{UniversidadeEstadualdoAmazonas,DepartamentodeMicologia,Manaus,Amazonas,Brasil} b_{UniversidadeFederaldePernambuco,DepartamentodeMicologia,Recife,Pernambuco,Brasil} c_{UniversidadeFederaldePernambuco,DepartamentodePatologia,Recife,Pernambuco,Brasil}

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Articlehistory:

Received14April2014 Accepted25February2016 Availableonline22December2016 AssociateEditor:CarlosPelleschi Taborda Keywords: Oralphaeohyphomycosis Squamocellularcarcinoma Lip

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Thiscommunicationreportsthesecondknowncaseoforalphaeohyphomycosisinapatient withsquamocellularcarcinomaofthelip.Thepatient,an82-year-oldblackwoman,aformer smoker(formorethan30years),sufferingfromanulcerousvegetativelesioninthe mid-dlethirdofthelowerlipforapproximately12months.Theresultofthehistopathological analysisindicatedcarcinoma,withwell-differentiatedkeratinizedsquamouscellsandthe presenceofseptatemycelialfilaments.Inthedirectmycologicalexamination,thickand dematiaceousseptatemycelialfilamentswereobserved.Aftertheresectionsurgery,the patientdidnotneedtouseanantifungaldrugtotreatthephaeohyphomycosis,andno follow-upradiotherapywasneededtotreatthesquamocellularcarcinoma.Westressthat thepresenceofthesquamocellularlesionofthelipwasapossiblecontributingfactortothe infection.

©2016SociedadeBrasileiradeMicrobiologia.PublishedbyElsevierEditoraLtda.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Introduction

Phaeohyphomycosis is a term used to denominate a set of cutaneous, subcutaneous and systemic infections caused by pigmented or dematiaceous fungi, producers of melanin. These fungi live in the soiland decomposing

∗ _{Correspondingauthorat:DepartamentodeMicologia/CCB/UFPE,Av.daEngenharia,s/n–CidadeUniversitária,CEP:50740-550,Recife,}

Pernambuco,Brazil.

E-mail:andreferrazleal@yahoo.com.br(A.F.Leal).

plant matter.Theyare the cause ofsporadiccosmopolitan infections that afflictbothhealthyand immunosuppressed individuals. The main genera involved include Alternaria, Bipolaris,Cladophialophora,Cladosporium,Curvularia,Exophiala, Exserohilum,Phaeoacremonium,PhialophoraandWangiella.1,2

Generallythelesionsoriginatefromtheinoculationpoint of fungal structures, through various traumas. They can

http://dx.doi.org/10.1016/j.bjm.2016.02.001

1517-8382/©2016SociedadeBrasileiradeMicrobiologia.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

brazilian journal of microbiology48(2017)208–210

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Fig.1–(A)Ulcerativelesionofthelowerlip.(B)Viewofthelowerlipaftersurgicalresectionofthelesion.

remain local or spread through the adjacent tissues by hematogenicorlymphaticpathways.Whetherornot infec-tionwilloccurbasicallydependsonthreefactors:resistance ofthehost,quantityoftheinoculumandvirulenceofthe fun-gus.Withrespecttovirulence,itisbelievedthatthemelanin producedbythefungusimprovestheintegrityofthecellwalls andincreasesthetotalnegativechargeofthecells,protecting themagainstphagocytosis.Melanincanalsoprotectthe fun-galcellsagainstoxidativestress,extremetemperatures,iron depletionandmicrobialpeptides.1,2

Thediagnosisofphaeohyphomycosisisbasedonclinical observation,directmycological examinationusinga potas-sium hydroxide (KOH) solution, isolation of the fungus in culturemediumandhistopathologicalanalysis.1–3

Thiscommunicationreportsthesecondknowncaseoforal phaeohyphomycosisinapatientwithsquamocellular carci-nomaofthelip.

Case

report

Thepatient

Thepatient, an82-year-oldblackwoman,aformer smoker (formorethan30years),wasattendedbytheheadandneck outpatient service of Pernambuco Cancer Hospital, suffer-ing from anulcerous vegetative lesionin the middle third ofthelower lip.Thelesionmeasuredapproximately 2.5cm (witha “cauliflower” aspect) and had appeared about one year previously (Fig. 1A). For diagnosis of the etiology of thelabiallesion,resectionofthetissuesforevaluationwas indicated.

Diagnosis

Forthehistologicalexamination,atissuefragmentwasstored in10% formalinand sent tothe hospital’s pathology labo-ratory, whereit was imbedded in paraffin and sliced into sections,whichwerestainedwithhematoxylin-eosin(HE)and periodicacidSchiff(PAS).

Another part of the clinical sample was sent for anal-ysis atthe medical mycology laboratory of the Center for BiologicalSciencesofPernambucoFederalUniversity,where

directmycologicalexaminationandcultureanalysiswere car-ried out. A 20% aqueous solution of potassium hydroxide was usedinthedirectmycologicalexaminationfor visual-izationofthefungalstructuresunderanopticalmicroscope. Forculturing,theclinicalsamplewasfragmentedand inoc-ulated inPetridishescontainingSabouraudagar andbrain heart infusion agar plus 50mg/L of chloramphenicol. The dishes were then maintained at 30◦C and 37◦C for over 30days.

Theresultofthehistopathologicalanalysisindicated car-cinoma,withwell-differentiatedkeratinizedsquamouscells andthepresenceofseptatemycelialfilaments.

Inthedirectmycologicalexamination,thickand dematia-ceousseptatemycelialfilamentswereobserved(Fig.2).There wasnofungalgrowthintheculturemedia.

Aftertheresectionsurgery,thepatientdidnotneedtouse anantifungaldrugtotreatthephaeohyphomycosis,andno follow-upradiotherapywasneededtotreatthe squamocellu-larcarcinoma(Fig.1B).

Fig.2–Directmycologicalexamination:clinicalsample clarifiedwith20%KOH,exhibitingthickanddematiaceous septatemycelialfilaments.

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Discussion

Thefirstcasereportoforalphaeohyphomycosisinthelipwas publishedin2007byCardosoandcollaborators,4_inwhicha

57-year-oldfemalepatientpresentedanodularlesiononthe lowerlipmeasuring0.5cmindiameter.Thepatientreported she did not recall having suffered any type of injury, but statedshehadusedaherbalinfusiontotreatarenal infec-tion.Besidesdrinkingtheherbaltea,shealsohadchewedthe infusedleaves.Aftertheinitialclinicalevaluation,theteam believeditwasacaseofpleomorphicadenoma,andsurgical excisionwasproposedastreatment.However,the histopatho-logicalexaminationrevealedthepresenceofseptatehyphae anddematiaceousyeast-likestructures,characterizingacase oforalphaeohyphomycosis.Throughpolymerasechain reac-tion(PCR),theauthorsconfirmedthecauseasbeingafungus ofthegenusAlternaria.Despitethisfinding,treatmentwith antifungalswasnotnecessary.Theauthorsstressedthatthe typeofclinicallesionafflictingthepatientisverycommonand forthisreasonitisimportanttoperformdifferentialdiagnosis. Amongtheclinicalmanifestationsofphaeohyphomycosis, superficialand subcutaneousinfectionsare mostcommon. Clinicalcases ofonychomycosis,tineanigra, subcutaneous lesions, chromoblastomycosis, eumycetoma and keratitis havebeenreportedinthemedicalliterature.Besides super-ficialandsubcutaneousinfections,thesefungicanalsocause allergicreactionssuchasallergicfungalsinusitisandallergic bronchopulmonarymycosis.Amongthemostserious infec-tions,dematiaceousfungihavebeenconfirmedasetiological agentsofpneumonia,brainabscessanddisseminateddisease. Inthesecasesofhighlethalityand morbidity,thepatients havepresentedsometypeofimmunosuppression.1,2,5

Histopathalogical examination can help diagnose the ailment,byidentifyinginflammatoryalterationsand dema-tiaceous fungal elements.3 _{We found fungal structures}

in the histopathological examination. However, the direct mycological analysis produced more specific results (bet-ter visualization of the dematiaceous fungal structures). AccordingtoCunha-Filhoetal.,3 _{thediagnosis of}

phaeohy-phomycosis should mainly bebased on directmycological examination,sincetheclinicalappearancecanbevaried,the histopathologyresultsunspecificandtheculturenegative(no fungalgrowth).Inthiscase,itwasnotpossibletoisolateand identifythefungusbecausetherewasnogrowthinthe cul-turemedium.However,whenanalyzingthe logofsamples testedattheMedicalMycologyLaboratoryofUFPE,wefound thatthefungiinvolvedinthephaeohyphomycosiscaseswere

Cladosporiumspp.and Curvulariaspp.asagentsofsystemic infections,and Exophialaspp. and Phaeoacremonium spp. as agentsofsubcutaneousinfections(datanotshown).

Thereis nostandard treatment forphaeohyphomycosis at present. In certain cases, complete surgical excision is

sufficient for cure, with no need to administer antifungal drugs. Incaseswhereantifungaltherapy isnecessary, itra-conazole, voriconazole and posaconazole are the drugs of choice,throughoraladministration.6

Basedonthefindingsintheliterature,webelievethisis thesecondreportofacaseoforalphaeohyphomycosisinthe lip.Thereareonlytwootherpublishedreports,oneofwhich describes afungal infection ofthe palate and theother of thejaw,withoutanyinvolvementofthelip.6,7_Westressthat

thepresenceofthelesion,withwell-differentiated keratini-zedsquamouscellswasapossiblecontributingfactortothe infection.Somedematiaceousfilamentousfungiareknown tohavetheabilitytodegradekeratin.2_{Inlightofthiscase}

report,itcanbeinferredthatmorecarefulinvestigationis nec-essary regardingtheassociationbetweencancerouslesions oftheoralcavityandfungalinfections.Recentstudieshave indicated that microbes,including fungi, can contributeto carcinogenesisintheoralmucosaaswellasatother body sites.5,8,9

Conflicts

of

interest

None.Theauthorsaloneareresponsibleforthecontentand writingofthemanuscript.

Acknowledgment

ThisworkwassupportedbytheConselhoNacionalde Desen-volvimentoCientíficoeTecnológico(CNPq).

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