Rev. Bras. Hematol. Hemoter. vol.39 número1

rev bras hematol hemoter. 2017;39(1):70–72

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

report

Cutaneous

granulomatous

reaction

as

the

first

manifestation

of

Hodgkin’s

lymphoma

Catarina

Moreira

_,

_Elisabete

_Rios

_,

_Teresa

_Baudrier

_,

_Filomena

_Azevedo

a_{CentroHospitalarSãoJoão,Porto,Portugal}

b_{FaculdadedeMedicinadaUniversidadedoPorto(FMUP),Porto,Portugal}

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Articlehistory:

Received18September2016 Accepted7November2016 Availableonline28December2016

Introduction

Inpatientswithasubjacentmalignancy,thedevelopmentof non-infectiousgranulomasatsiteswherethereisnoevidence ofmalignantinvolvementisawell-recognizedphenomenon buttheparticipationoftheskinisrare.

Case

report

A33-year-old male wasreferred toourdepartment with a three-monthhistoryofweakness,nonproductivecoughand asymptomatic skin lesions of both legs. His medical his-toryincludedasthmathatwasmedicatedwithmontelukast, budesonideandformoterol.Aphysicalexaminationshowed confluent erythematous annular plaques, circumferentially distributedonbothlegsandassociatedwithedema(Figure1). Nohepatomegaly,splenomegalynorlymphadenopathywere palpable.

A biopsy specimen of a cutaneous plaque revealed a lymphohistiocyticinfiltratewithanon-necrotizing granulo-matouspatterninvolvingthedermisandsubcutaneoustissue

∗ _{Correspondingauthorat:DepartmentofDermatologyandVenereology,CentroHospitalarSãoJoão,EPE,AlamedaProf.HernaniMonteiro,}

4200-319Porto,Portugal.

E-mailaddress:[email protected](C.Moreira).

(Figure2).Noatypicalcellsorthepresenceofforeignbodies wasobserved.Testsforbacteria,acid-fastorganismsandfungi were negative.Bacterial,fungal and mycobacterialcultures oftheskinandpolymerasechainreactiontodetect

Mycobac-teriumtuberculosis,CandidaalbicansandAspergillusfumigatusin

cutaneousspecimenswereallnegative.

Laboratory tests showed mild anemia (hemoglobin 12.4g/dL; normal range: 13.0–18.0), relative neutropenia (14.8%;normalrange:53.8–69.8%)andlymphocytosis(71.8%; normal range: 25.3–47.3%) and an increased angiotensin-converting enzyme level (81U/L; normal range: <52U/L). Renaland hepatic profiles,andserum andurinary calcium levels wereallnormal.SerologicaltestsforHIV,hepatitisB andCvirus,syphilisandLymediseasewerenegative.

In order to excludesystemic sarcoidosis, a chest radio-graphy,ophthalmologicexamination,lungfunctiontestsand electrocardiogram wereperformednoneofwhichidentified anyrelevantabnormality.

Thepatient alsounderwent galliumscintigraphy,which revealed increased uptake of the radioactive agent in the rightlowerquadrantoftheabdomen,suggestiveof retroperi-toneal adenopathic conglomerates. Excisional biopsy ofan

http://dx.doi.org/10.1016/j.bjhh.2016.11.004

revbrashematolhemoter.2017;39(1):70–72

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Figure1–Anterior(a)andposterior(b)aspectsoflowerlimbsatpresentation.Confluenterythematousannularplaques circumferentiallydistributedonbothlegsandassociatedwithbilateraledema.

abdominallymphnode was performed. Microscopic exam-ination showed a polymorphous infiltrate of lymphocytes, histiocytes, eosinophils and large atypical cells with the appearanceofReed-Sternbergcellsinill-definednodules sep-aratedbyfibrousbands.Immunohistochemicalstainsshowed thatlargeatypicalcellswerepositiveforCD30andnegativefor CD45,CD20,CD3, CD15and CD68.Small lymphocyteswere mainlyTcells(CD3+_{),althoughsomeBcells(CD20}+_)werealso observed.ImmunostainingofCD68confirmedthepresenceof anabundantpopulationofmacrophagiccells.Thediagnosis ofclassicalHodgkin’slymphoma,nodularsclerosingsubtype, wasestablished.

Afterstaging,thepatientbegananadriamycin,bleomycin, vinblastine,dacarbazine(ABVD)chemotherapyregimen. Par-tialremissionofthehematologicmalignancyandregression ofthe cutaneouslesionswereobservedafterfourcycles of treatment(Figure3).

Discussion

Itiswellknownthatpatientswithmalignanttumorsdevelop non-infectiousgranulomasinnon-involvedorgans.1,2_Lymph

nodes,theliverand spleenare theorgans mostfrequently affectedwithskininvolvementbeingararephenomenon.

In 1986, Brincker described the occurrence of sarcoid reactions in 4.4%ofcarcinomas, in 13.8% ofpatients with Hodgkin’s disease, and in 7.3% of cases of non-Hodgkin lymphomas.3_{Heclaimedanassociationbetweensarcoidosis}

andmalignantlymphoproliferativediseaseandproposedthe existenceofasarcoidosis-lymphomasyndrome.3 _Theterm

“sarcoidosis-lymphoma”however, isnotalwaysappropriate as many patients onlyexhibit sarcoid-like tissue reactions withclinicalorlaboratoryevidenceinsufficientfordiagnosing sarcoidosis.4,5_{Infact,inthecasewepresent,despitethe}

pres-enceofcutaneoussarcoid-typegranulomasandanelevated angiotensin-convertingenzyme,noothersystemic manifes-tationsofsarcoidosisweredetected.

Althoughthefewreportedcutaneoushistologicfeatures aremostlythoseofsarcoid-typenon-caseatinggranulomas, otherfeatures,suchastuberculoidandpalisadedgranulomas, havebeendescribed.6

Theexactcause ofgranulomatousreactionsinsystemic lymphomas needs to be clarified. Some authors consider thatthesereactionsarecausedbyantigenicfactorsderived from the tumor cells.1,7 _{Others suggest mechanisms that}

include reactions to foreign bodies or against unidentified

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Figure3–Anterior(a)andposterior(b)aspectsoflowerlimbsafterfourcyclesofchemotherapy.Regressionofcutaneous lesions.

opportunisticmicroorganisms,orreactionstochemotherapy or to the contrast media used in tumor staging.4,8 _{In our}

patient,neitherthepresenceofforeignbodiesnor opportunis-ticinfectionswereidentified,and,inthelackofatemporal correlationbetweentheonsetofskinlesionsand chemother-apyorimagingtests,thereisnosupportastoatriggeringrole ofthesefactors.

Mainlyduetothepaucityofpublishedcases,theprognostic implicationsofcutaneousgranulomasinthesettingof sys-temicmalignanciesremainunclear.Ithasbeenhypothesized that,astheyserveasahost-protectiveresponseagainstthe tumor,thegranulomaswouldbeagoodprognosticindicator, although,somecasesdescribinganaggressivecourseofthe disease,contradictthisclaim.4,9

We describe a patient who presented with a non-necrotizing granulomatous skinreaction, without evidence of malignancy, and, in whom the complementary study diagnosedHodgkin’slymphoma.Othercausesofcutaneous granulomas were excluded. Chemotherapy led to partial remissionofthetumorandresolutionofcutaneouslesions, suggestinganarrowrelationshipbetweentheskinreaction and systemic malignancy.Westress that the possibility of systemic lymphomashould be considered in patients pre-sentingwithnon-infectiousgranulomatousskinreactionsin theabsenceofabetterexplanation.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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2.LeathamEW,EelesR,SheppardM,MoskovicE,WilliamsMP, HorwichA,etal.Theassociationofgermcelltumoursofthe testiswithsarcoid-likeprocesses.ClinOncol(RCollRadiol). 1992;4(2):89–95.

3.BrinckerH.Sarcoidreactionsinmalignanttumours.Cancer TreatRev.1986;13(3):147–56.

4.FarrellAM,HenryK,WoodrowD,FrancisN,NewlandsES, MitchellDN,etal.Cutaneousgranulomasassociatedwith high-gradeT-cellnon-Hodgkin’slymphoma.BrJDermatol. 1999;140(1):145–9.

5.YukawaM,SatohT,TakayamaK,YokozekiH.Cutaneous sarcoidreactioninapatientwithbladdercancer.EurJ Dermatol.2010;20(2):235.

6.RongiolettiF,CerroniL,MassoneC,BassoM,CiambellottiA, ReboraA.Differenthistologicpatternsofcutaneous granulomasinsystemiclymphoma.JAmAcadDermatol. 2004;51(4):600–5.

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Inflammatorycellsintheformationoftumor-relatedsarcoid reactions.HumPathol.2005;36(5):546–54.

8.CantwellARJr.Variablyacid-fastbacteriainararecaseof coexistentmalignantlymphomaandcutaneoussarcoid-like granulomas.IntJDermatol.1982;21(2):99–106.