Case for diagnosis. Diffuse ulcerated nodular lesions

AnBrasDermatol.2019;94(5):615---617

Anais

Brasileiros

de

Dermatologia

WHAT

IS

YOUR

DIAGNOSIS?

Case

for

diagnosis.

Diffuse

ulcerated

nodular

lesions

夽,夽夽

Paulo

Henrique

Teixeira

Martins

_,

_Gabriela

_Dallagnese

_,

_Laura

_Luzzatto

_,

Manuela

Lima

Dantas

a_{DepartmentofDermatology,SantaCasadeMisericórdiadePortoAlegre,PortoAlegre,RS,Brazil}

b_{DepartmentofDermatology,UniversidadeFederaldeCiênciasdaSaúdedePortoAlegre,PortoAlegre,RS,Brazil}

Received21August2018;accepted15November2018

KEYWORDS

Histiocytosis; Inflammation; Neoplasms

Abstract Langerhans cellhistiocytosis isa rare clonal proliferative disease, characterized by theinfiltrationofoneormultipleorgansbyhistiocytes. Duetothediversityofsignsand symptoms,thediagnosisofthisdiseaseisoftenlate.Theestimatedincidenceinadultsisone totwocasespermillion,butthediseaseisprobablyunderdiagnosedinthispopulation.This reportpresentsacaseofdisseminatedLangerhanscellhistiocytosis.Theauthorshighlightthe mostcharacteristicaspectsofthisrareandheterogeneousdisease,whichusuallypresentsas achallengingclinicaldiagnosis.

©2019SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

Case

report

Afemalepatient,63yearsold,hadpruriticanddiffused red-dishspotsonherbodywithaboutsixmonthsofevolution. Her external laboratory tests showed thrombocytopenia andanemia,andtheanatomopathologicalexamsuggested pharmacodermy.Thephysicalexaminationshowedmultiple

夽 _{Howtocitethisarticle:MartinsPH,DantasML,DallagneseG,} LuzzattoL.Casefordiagnosis.Diffuseulceratednodularlesions.An BrasDermatol.2019;94:615---7.

夽夽_{StudyconductedattheHospitalSantaCasadeMisericórdia,} PortoAlegre,RS,Brazil.

∗_{Correspondingauthor.}

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

violaceous papules and nodules, sometimes with ulcera-tionandcrusting atboth endsandlace-likeerythematous spotsintheabdomen(Figs.1and2).Skinbiopsywas per-formed.Theanatomopathologicalexamshowedhistiocytic infiltrateinthepapillaryandreticulardermis,formingcell aggregatesof intermediatesize, withclear and abundant cytoplasm,nucleisometimescleaved,andwithpseudoclefts (Fig. 3). Immunohistochemistry showed immunoreactivity for S100, CD1a (Fig. 4), and langerin, suggesting, along with the anatomopathological exam and clinical history, Langerhans cell histiocytosis (LCH). The patient initiated systemic chemotherapy with vinblastine associated with prednisone.Due tolittleresponse after threecycles,the treatmentwasreplacedwithcytarabine.Thepatientdied

https://doi.org/10.1016/j.abd.2019.09.021

0365-0596/©2019SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).

616 MartinsPHetal.

Figure1 Ulcerwithcrustcentersontheleftlowerlimb.

Figure2 Nodularlesionontherightlowerlimb.

due to acuterespiratory failure, likely due to pulmonary sepsis.

Discussion

LCHisarare andheterogeneousdisease.Withtherecent discoveryoftheBRAF-V600Emutationinahighprevalence of LCH cases (50%---60%), the disease was recognized as cancer with marked inflammation.1,2 _{Recent studies} sug-gest a clinical correlation between the presence of the

Figure3 HistopathologywithHematoxylin&eosinstaining, ×40.

Figure4 Immunohistochemistry---CD1a.

mutationandtherecurrenceandseverityofthedisease.3 Thereisacurrentdivisionbetweenlocalanddisseminated LCH. The clinical manifestations vary widely due to dif-ferencesbetween theage ofonset,theproliferation rate of Langerhans cells, and the tissues andorgans involved. Bone involvement is the most common formof presenta-tion,bothinadultsandchildren.Skinrashesofthisdisease in adultscan simulateother commondermatoses,suchas seborrheic dermatitis and atopic eczema.4,5 _{In this case,} diffusederythematouslesionsgenerated aclinical diagno-sisofpharmacodermy.Cutaneouslesionsarepresentin40% ofcasesassociatedwiththemultisystemdisease,thustheir presence must motivate the investigation of other organs involved.6 _{Thediagnosis requiresahighindexofsuspicion} and depends on clinical and radiology findings associated withhistopathology andimmunohistochemistry.4 _{The gold} standardtestverifiesthepresenceofBirbeckbodies, gran-ules inthe cytoplasmof Langerhanscells,in theelectron microscopy.The main immunohistochemical manifestation is the presence of the proteins S100 and CD1a(+).6,7 _The treatment must be individualized, considering the organs infected,thediseaseextent,andtheagegroupaffected.7 Surgery,intralesionalcorticotherapy,andlocalradiotherapy aresomeofthetherapeuticoptionsforthelocaldisease.In case of multisystemdisease or involvementof risk organs (spleen, liver, bone marrow, and lung), chemotherapy is indicated(vinblastineandprednisolone,cytarabine,among others).2,6_{BRAFinhibitorssuchasvemurafenibarenew} ther-apeuticoptions.2_{Althoughthetherapyimprovesthesurvival}

Casefordiagnosis.Diffuseulceratednodulelesions 617 rate,morbidity remainshigh for patientswithLangerhans

cellshistiocytosis,andpermanentsequelaeareobservedin 20%---30%ofpatients.8_{Thetreatmentofthisconditionneeds} to beprovided in specialized centers in order toprovide multidisciplinarycare.3,7

Financial

Support

Nonedeclared.

Author’s

contribution

Paulo Henrique Teixeira Martins: Statistical analysis;

approval of the final version of the manuscript; concep-tionandplanningof thestudy;elaboration andwritingof the manuscript;obtaining, analyzing andinterpreting the data;intellectualparticipationinpropaedeuticand/or ther-apeuticconductofthecasesstudied;criticalreviewofthe literature;criticalreviewofthemanuscript.

Gabriela Dallagnese: Elaboration and writing of the

manuscript;criticalreviewoftheliterature;criticalreview ofthemanuscript.

Laura Luzzatto:Effective participationinresearch

ori-entation.

Manuela Lima Dantas: Elaboration and writing of the

manuscript;criticalreviewoftheliterature;criticalreview ofthemanuscript.

Conflicts

of

interest

Nonedeclared.

Acknowledgements

Tothepreceptorsoftheservice,thepatientandtheir fam-ilies.

References

1.AllenCE,MeradM,McClainKL.Langerhans-cellhistiocytosis.N EnglJMed.2018;379:856---68.

2.HegemannMV,SchremlS.MultisystemicLangerhanscell histio-cytosisinanadult.JAADCaseRep.2017;3:162---4.

3.Ng-Cheng-Hin B, O’Hanlon-Brown C, Alifrangis C, Waxman J. Langerhanscellhistiocytosis:olddiseasenewtreatment.QJM. 2011;104:89---96.

4.HarocheJ,Cohen-AubartF,RollinsBJ,DonadieuJ,CharlotteF, IdbaihA,etal.Histiocytoses:emergingneoplasiabehind inflam-mation.BRAFmutationcorrelateswithhigh-riskLangerhanscell histiocytosisandincreasedresistancetofirst-linetherapy.Lancet Oncol.2017;18:e113---25.

5.HéritierS,EmileJF,BarkaouiMA,ThomasC,FraitagS, Boudje-maaS,etal.BRAFmutationcorrelateswithhigh-riskLangerhans cellhistiocytosisandincreasedresistancetofirst-linetherapy.J ClinOncol.2016;34:3023---30.

6.deBritoMD,MartinsÉ,AndradeJ,GuimarãesJ,MarizJ. Adult-hoodLangerhanscellhistiocytosis:experienceoftwoPortuguese Hospitals.ActaMedPort.2014;27:726---30.

7.Lian C, Lu Y, Shen S. Langerhans cell histiocytosis in adults: a case report and review of the literature. Oncotarget. 2016;7:18678---83.

8.RigaudC,Barkaoui MA,ThomasC,BertrandY,Lambilliotte A, MironJ,etal.Langerhanscellhistiocytosis:therapeuticstrategy and outcome ina 30-yearnationwide cohortof1478patients under18yearsofage.BrJHaematol.2016;174:887---98.