Multinucleate cell angiohistiocytoma: an uncommon cutaneous tumor,

AnBrasDermatol.2020;95(4):480---483

Anais

Brasileiros

de

Dermatologia

CASE

REPORT

Multinucleate

cell

angiohistiocytoma:

an

uncommon

cutaneous

tumor

夽,夽夽

Anderson

Alves

Costa

_,

_Glaucia

_Ferreira

_Wedy

_,

_Walter

_Belda

_Junior

_,

Paulo

Ricardo

Criado

a_{DepartmentofDermatology,UniversidadedeSãoPaulo,SãoPaulo,SP,Brazil} b_{DepartmentofDermatology,FaculdadedeMedicinadoABC,SantoAndré,SP,Brazil}

Received12May2019;accepted14October2019

Availableonline11May2020

KEYWORDS Casereports; Giantcells; Histiocytoma; Lowerextremity; Neoplasms; Vasculartissue

Abstract Multinucleate cell angiohistiocytoma is a rare, benign vascular proliferation of

unknownetiology.Itoccursmainlyinmiddle-agedwomenandusuallyaffectstheacralregions;

thelesionsappear asdiscrete,grouped,andasymptomaticviolaceouspapules.

Histopathol-ogyshowsproliferationanddilatedsmallvesselsinthepapillarydermis,fibrousstromawith

thickenedcollagenbundles,andmultinucleatedgiantcells.Todate,thereareapproximately

140casesdescribedintheindexedliterature.Thisreportpresentsthecaseofa62-year-old

woman withatypicalclinicalcondition,whochosenotundergotreatment,consideringthe

benigncharacterofherillness. Theclinicaland immunohistologicalaspects ofthisunusual

dermatologicalentityareemphasized.

©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan

openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

Introduction

Multinucleate cell angiohistiocytoma (MCAH) is a rare, benign vascular proliferation of the skin, whose cause was unknown until recently. Currently, approximately 140 cases have been described in indexed literature

夽 _{Howtocitethisarticle:CostaAA,WedyGF,BeldaJrW,Criado}

PR.Multinucleatecellangiohistiocytoma:anuncommoncutaneous

tumor.AnBrasDermatol.2020;95:480---3.

夽夽_{StudyconductedattheDepartmentofDermatology,}

Universi-dadedeSãoPaulo,SãoPaulo,SP,Brazil.

∗_{Correspondingauthor.}

E-mail:anderson.medicinausp@gmail.com(A.A.Costa).

(PubMed/MEDLINE). This report presents another clinical case of MCAH studied underimmunohistologicalbasis and presentsareviewoftherelevantliteraturethatdelineates the prominentclinicopathological features of thisunusual entity,whichisoftenconfusedwithdermatofibromainthe clinicalsetting.

Case

report

A62-year-oldCaucasianwomanwasreferredtothisclinic byhergeneralphysicianduetheonsetofcutaneouslesions on left arm and right forearm eight months ago. The patient’spastmedicalhistorywasunremarkable.An exten-sive panel of routine blood exams revealed nosignificant

https://doi.org/10.1016/j.abd.2019.10.005

0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC

Multinucleatecellangiohistiocytoma:anuncommoncutaneoustumor 481 abnormalities, including negative anti-HIV serology. She

denied previous solid organtransplantor use of immuno-suppressive drugs.The lesions wereasymptomatic. In the lasttwomonths,shenoticedanewgroupoflesionsonher abdomen,rightthigh,andback.Ondermatological exami-nation,asymmetricpainlesserythematoviolaceouspapules wereobserved,with3---10mmindiameter(Fig.1).

Punchbiopsiesoftheskinlesionswereperformed,which showedanormalepidermisandfibrohistiocyticproliferation withsmallvesselsinthereticulardermis,displayinglumen vesselsfilledwithprominentendothelialcells,involvedwith aperivascularinflammatoryresponsecomposedby multin-ucleatedhistiocyticcells (MCs)andafew plasmacells. In thepapillarydermis,fibroblasticproliferationandthickened collagen fibers were found (Figs. 2 and 3) and numer-ousbizarreMCswithscallopedmarginswerefound in the

Figure 1 Cutaneous erythematoviolaceous flatted papules

rangingfrom3to10mmindiameter,arrangedonthedorsum.

Figure 2 Regular acanthosis in the epidermis and overall

increasedcellularitywere present throughoutthedermis, as

well as anincreased number ofdilated blood vessels in the

upperandmiddermis,lymphohistiocyticinfiltrate,andthicker

collagenbundles(Hematoxylin&eosin,×40).

Figure 3 Characteristic irregular multinucleate cells of

MCAH, typified by angular borders and multiple potentially

hyperchromatic nuclei in the dermis and enlargement of

endothelial nuclei in the capillaries (Hematoxylin & eosin,

×400).

adjacentdermis.Theimmunohistochemical(IHC)panel per-formedfoundthefollowing:S-100protein(negative),FXIIIa (positive)in MCs,CD68 (positive) in MCs, CD34 and CD31 (positive)insmallvessels,andCD4(positive)indermal lym-phocytes(Figs.4and5).Thefinaldiagnosiswasestablished ascompatible with multinucleate cell angiohistiocytoma. Duetothebenign natureof theillness,thepatientchose nottoundergotreatment.

Figure4 Immunohistochemistrystudy.Histiocyticand

multi-nucleatedcellsarepositiveforFactorXIIIa(×400).

Figure 5 Immunohistochemistry study. Positive for CD68

482 CostaAAetal.

Discussion

ThedesignationMCAHwasoriginallyintroducedin1985by SmithandWilson-Jones,1_{representingararefibrohistiocytic}

vascularproliferationofunknownetiologythatisreported three times more frequently in women, and commonly affectsmiddle-aged (> 40 years) or elderly individuals.2,3

To date, there are about 140 cases of MCAH reported in the indexed literature (PubMed/MEDLINE), and its preva-lenceisbelievedtobeunderestimatedduetopoorclinical recognitionofthispathology.

Lesionsareasymptomaticandaremostlylocatedonthe face and in the acral regions, although they have been reportedin other locations, such asthe trunk and, more rarely,themucousmembranes;2 _{theyareusuallyunilateral}

andpresent aspapules rangingfrom2-15mm indiameter. They may appear as reddish, pink, violaceous, or brown papuleswithaslightlyraiseddome-shapedsurface,ormay beflatandsmooth.2,4_{Bilateralinvolvementandeven}

gener-alizedformshavebeendocumentedinafewcases.2_MCAH

lesionsdevelopoverweekstomonths,withnotendencyto spontaneousregression.5

Regarding the differential clinical diagnosis, special attention should be given to Kaposi’s sarcoma, espe-cially when the MCAH is presented as grouped papules.6

Acroangiodermatitis,annulargranuloma,angiofibroma, der-matofibroma, microvenular hemangioma, lichen planus, lymphocytoma,andreaction toinsectbite shouldalsobe included.7

AlthoughtheetiologyandpathogenesisofMCAHarestill unknown,amongthe hypotheses,thepredominant under-standingis that lesionsarise from a reactive ratherthan a neoplasticprocess. This hypothesis is supported by the factthat it is a benignentity withindolentbehavior, the absenceofextracutaneousinvolvementormalignant trans-formation,andthepossibilityofspontaneousregressionis compatiblewithareactiveratherthanneoplastic inflamma-toryprocess.3,8,9

Anothertheory proposesfemalehormonalinfluence on pathogenesis,noting theidentification of estrogen recep-tor(ER)alphaexpressionininterstitialandmultinucleated cells; this factor would explain the higher frequency in women.However,theidentificationofERpositivityhasnot beenconsistentinotherreportedcases.3,8

In2015,Frewpublishedareviewof142casesofMCAH. TheauthorhypothesizedthatalthoughMCAHhasaninitial inflammatoryandvascularorigin, histopathologicalevents associatedwithfibrosis andatrophyplayakeyroleinthe pathogenesisof thedisease,especiallyregarding the pro-gressiontomultiplelesions.10

The main histopathological finding in MCAH is the proliferationofvenulesandcapillariesinthedermis, accom-paniedbylymphocyticinfiltrateandangularmultinucleated cells. These cells may exhibit up to ten hyperchromatic nuclei and have basophilic cytoplasm; the cells express vimentinandfactorXIIIa,andthereisdermal fibrosisand sparselymphohistiocyticinfiltrate.2,7,10

ThehistologicalfindingsofMCAHaresimilartothoseof severalbenignskintumorsandotherfibroangiomatous con-ditions,whichhasledsomeauthorstoquestionthestatusof MCAHasanindependenthistopathologicalentity.6,10 _Some

authorsconsiderMCAHasavariantofdermatofibroma,with

prominent vascular component and peculiar multinucle-atedcells.10_{Otherhistologicaldifferentialdiagnosesinclude}

Kaposi’ssarcoma,angiofibroma,lymphocytomacutis,lichen planusandangiolymphoidhyperplasiawitheosinophilia.

Differential diagnosis with Kaposi’s sarcoma (KS) is important, because there is great clinical similarity betweentheentities,buttherearesomehistopathological differences.6,8,10 _{Microscopically, KS consists of}

irregu-lar anastomotic vascular channels and sieve-like chinks, extravasation of red blood cells, hemosiderin deposits, and spindle-shaped endothelial cells.3 _{KS cells express}

podoplanin,amarkerofthelymphaticendothelium,which isnotexpressedbyMCAHendothelialcells.Confirmationof humanherpesvirus8(HHV8)positivity(demonstratedwith IHCorinsituhybridization)allowsthedistinctionofKSfrom MCAH.3,10

InmostreportedcasesofMCAH,theIHCpanelperformed included staining for factor VIII,factor XIIIa, CD31,CD34, CD68, andvimentinin both thevascular endotheliumand MCs.InFrew’sreviewarticle,IHCshowed60%CD68-stained vascularendothelialcells.10 _{Asexpected,endothelialcells}

alsoexpressedfactorVIIIstaining,CD31,andCD34,andin the present case, CD31 andCD34 markers werealso pos-itive in these cells. Frew noted that MCs were negative in stainingfor endothelial markers, factor VIII,andCD34, with approximately half of the cases positively staining macrophages/histiocyteswithfactorXIIIaandCD68.10

Fac-torXIIIaandCD68werealsonotedintheMCsofthepresent case.

MCAHtreatmentisgenerallynotrequiredbecauseofthe benignnatureofthecondition,exceptforestheticreasons. Lesions can be treated with intralesional corticosteroids, surgical excision, cryotherapy, argonlaser, intense pulsed light, andCO2 laser.Recently, a case treated withpulsed

dyelaserwasreported,withgoodresult.3,5

The present report adds another case of MCAH to the literature, highlighting the difficulty of diagnosing this condition in dermatological practice. It is important to establish the correct diagnosis for this clinical condition and, especially, to excludemore serious diseases suchas KS, mainly in the scenario of patientswith AIDS or organ transplantation.

Financial

support

Nonedeclared.

Authors’

contributions

Anderson Alves Costa: Drafting and editing of the manuscript.

GlauciaFerreiraWedy: Conceptionandplanningof the study.

Walter Belda Junior: Intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases.

Paulo Ricardo Criado: Drafting and editing of the manuscript; intellectual participationin the propaedeutic and/or therapeutic conduct of the studied cases; critical reviewoftheliterature;criticalreviewofthemanuscript.

Multinucleatecellangiohistiocytoma:anuncommoncutaneoustumor 483

Conflicts

of

interest

Nonedeclared.

References

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2.WangM,Abdul-FattahB,WangC,ZhaoY,QuX,Al-MurieshM. Generalizedmultinucleatecellangiohistiocytoma:casereport andliteraturereview.JCutanPathol.2017;44:125---34.

3.GrgurichE,QuinnK,OramC,McClainR,LountzisN. Multinucle-atecellangiohistiocytoma:casereportandliteraturereview.J CutanPathol.2019;46:59---61.

4.ApplebaumDS,Shuja F,HicksL,CockerellC,HsuS. Multinu-cleatecellangiohistiocytoma:acasereportandreviewofthe literature.DermatolOnlineJ.2014;20:22610.

5.RicherV, LuiH. Facialmultinucleatecell angiohistiocytoma: long-termremissionwith585nmpulseddyelaser.ClinExp Der-matol.2016;41:312---3.

6.JonesWE,CerioR,SmithNP.Multinucleatecell angiohistiocys-toma:anacquiredvascularanomalytobedistinguishedfrom Kaposi’ssarcoma.BrJDermatol.1990;122:651---3.

7.DoaneJA,PurdyK,PasternakS.Generalizedmultinucleatecell angiohistiocytoma.JCutanMedSurg.2015;19:323---5.

8.CesinaroAM,RoncatiL,MaioranaA. Estrogenreceptoralpha overexpression in Multinucleate cell angiohistiocytoma: new insightsintothepathogenesisofareactiveprocess.AmJ Der-matopathol.2010;32:655---9.

9.Calderaro J, Rethers L, Ortonne N. Multinucleated cells angiohistiocytoma: a reactive lesion? Am J Dermatopathol. 2010;32:415---7.

10.Frew JW.Multinucleate cell angiohistiocytoma: clinicopatho-logicalcorrelationof142caseswithinsightsintoetiologyand pathogenesis.AmJDermatopathol.2015;37:222---8.