Braz. j. . vol.82 número6

BrazJOtorhinolaryngol.2016;82(6):737---740

www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

CASE

REPORT

Hoarseness:

an

unusual

presentation

of

primary

thyroid

lymphoma

with

laryngeal

infiltration

夽

Rouquidão:

apresentac

¸ão

incomum

de

linfoma

primário

de

tireoide

com

infiltrac

¸ão

da

laringe

Ozan

Gökdo˘

gan

_,

_Ahmet

_Koybasioglu,

_Erkin

_Ismail,

_Timucin

_Erol,

_Gokcen

_Alagoz,

Banu

Yagmurlu,

Seref

Komurcu

AnkaraMemorialHospital,DepartmentofOtorhinolaryngology,Ankara,Turkey

Received11February2015;accepted3May2015 Availableonline7September2015

Introduction

Primary thyroid lymphoma is a relatively rare disease of the thyroid gland. PTL represents approximately 1%---5% of thyroid malignancies and less than 2% of extra nodal lymphomas:theprognosisisgenerallygood.1_Thyroid

lym-phomasaremorecommoninwomenwithapredominance of3---4:1.2

The main clinical manifestation is a rapidly enlarging thyroid mass, commonly in the seventh decade. Approxi-mately30%---50%ofpatientsmanifestcompressionsymptoms of the adjacentstructures, in additiontodysphagia, stri-dor,hoarseness,coughandapressuresensationintheneck. Symptomssuchasfever, nightsweatsand weightlossare less common.Hashimoto’sthyroiditisappears tobearisk factorforthyroidlymphomaalthoughtheassociationisstill debated.1,2

The most common histopathological type of thyroid lymphomas is non-Hodgkin’slymphoma withB cellorigin. Hodgkin’sdiseases andT-cell lymphomas areraretumors.

夽 _{Pleasecitethisarticleas:Gökdo˘ganO,KoybasiogluA,IsmailE,}

ErolT,AlagozG,YagmurluB,etal.Hoarseness:anunusual presen-tationofprimarythyroidlymphomawithlaryngealinfiltration.Braz JOtorhinolaryngol.2016;82:737---40.

∗_{Correspondingauthor.}

E-mail:ozangokdogan@gmail.com(O.Gökdo˘gan).

Patients with pure mucosa associated lymphoid tissue (MALT) lymphomas tend to demonstrate a more indolent courseandabetterprognosiscomparedwithpatientswith diffuse large B-cell types or mixed histological subtypes, whichmayhaveamoreaggressiveclinicalcourse.3

Ageneral 5-yearsurvivalrate for PTLis approximately 90%; therefore a well-planned treatment after rapid and accuratediagnosisgenerallyresultsingoodprognosis.4

Case

report

A52-year-old-womanwasadmittedtothe otorhinolaryngo-logyservicebecauseofatwo-monthhistoryofhoarseness andleftotalgia.Nobreathingorswallowingcomplaintswere present.Priortoadmissiontoourclinic,medicaltreatment hadbeenprovidedforhertwiceforlaryngitis,buther com-plaintsdidnotimprove.

She reported a history of diabetes mellitus, hyperten-sion and hypothyroidism (chronic lymphocytic thyroiditis) andalsocholecystectomy.

On physical examination, theleftvocal cordwasfixed in themidline and fullness onleft false vocal cordcould beobserved.Thethyroidlobesdemonstratednodules bilat-erallyandwereenlarged,withthe leftlobebeingslightly firmer and larger than the right. There were no cervical palpablemassesorlymphadenopathy.

http://dx.doi.org/10.1016/j.bjorl.2015.05.006

738 Gökdo˘ganOetal.

Figure1 Laryngealinfiltrationwithcartilageinvasionof thy-roidmass.

Thyroidfunctiontestswerewithinnormalrangealthough she wasusing thyroid hormones for hypothyroidism. Thy-roidbiopsyhadbeenperformed2yearspreviouslyandthe histopathologicreportrevealedachroniclymphocytic thy-roiditis.

On radiologic evaluation masses in the leftfalse vocal corderodingtheleftthyroidcartilage,continuouswiththe thyroidgland,wereobserved.Therewerenodulesinboth thyroidlobes(Fig.1).

Alaryngealpathologyoriginatingfromtheleftlaryngeal structuresthaterodedthyroidcartilageandextendedtothe thyroid glandwas considered after examination. A direct laryngoscopyandbiopsyprocedurefrombothleftlaryngeal ventriclesandafineneedlethyroidbiopsyfromnodulesof boththyroidlobeswasplanned.

Biopsyof theleftfalsevocal cordwasreportedas dif-fuse large B cell lymphoma. Fine needle aspiration from both thyroid lobes was reported as atypical lymphocytes (Figs.2and 3).The prognosticfactorsof lymphomawere diagnosed as follows: proliferative index of Ki 67 was 80%---90%,LDH (lactatedehydrogenase)andsedimentation wasnormal.Thepatientreportedweightlossof20kginthe

Figure 2 Diffuse lymphoid infiltrations under laryngeal mucosa(with100×magnificationonpathologicexamination).

Figure3 Tumoriscomposedofatypicallymphoidcells,which havealargevesicularnucleolusandsignificantnucleolus.These cellshavepositive membranouspositivity withCD 20marker (with400×magnificationonpathologicexamination).

last4months.Internationalprognosticindex(IPI)scorewas foundas0.

Afludeoxyglucose-positronemissiontomography (FDG-PET) scan for differentiating the lesion between primary thyroidlymphomaorthyroidinvolvementofasystemic dis-ease showedonly diffuse involvementin leftthyroid lobe (Fig.4).

As a result of these diagnostic tests patient was diagnosed as diffuse large B cell primary thyroid lym-phoma, stage 1E. She received 3 courses of R-CHOP (rituximab---cyclophosphamide,doxorubicin,vincristineand prednisolone) treatmentand involved-fieldradiation ther-apy following chemotherapy. Her treatment course was uneventful and her hoarseness improved after treatment (Fig.5).

A team including oncology, radiation oncology, oto-rhinolaryngology, endocrinology departmentsfollowed the patientevery monthafter chemoradiationtreatment. She continues thyroid replacement treatment. Her thyroid is nowgrade3palpableindiffuseandhardpattern.There can-notbeidentifiedanynodularpatterninexamination.Both

Primarythyroidlymphomawithlaryngealinfiltration 739

Figure5 Neckcomputedtomographyaftertreatmentshows onlyminimallylaryngealedema,withoutanymassinboth lar-ynxandthyroidgland(onemonthaftertreatment).

vocal cords aremobile and there is no visible pathologic findinginlaryngealevaluation.

Six monthsafter chemoradiationtherapythepatientis nowinagoodhealthwithoutanycomplaint.Herphysical, laboratory,laryngealandradiologicevaluationiscompletely normalwithoutanyevidenceofrelapse(Fig.6).

Discussion

Extranodal lymphomas are usually seen as non-Hodgkin’s lymphoma (NHL) which constitute 10%---29% of all lym-phomas. Adult NHLs commonly arise from B cells. The main clinical symptom is an enlarging mass in head and neckregion,whichmayalsomanifestadestructiveclinical progress.

ExtranodalmarginalzoneB-celllymphomaofMALTtype mayoccur in thestomach, orbit,intestine, lung, thyroid, salivarygland,skin,softtissues,bladder,kidneyandcentral nervous system. The most common extranodal extralym-phaticsites are theparanasal sinuses,the salivary glands andthethyroidgland.4

Figure6 Neckcomputedtomographysixmonthsafter treat-ment.Laryngealedemahasdecreasedalittlemoreovertime.

The larynx is a rare site for localization of a primary NHL because of relatively low lymphoid content. In the literature,there arefewer than 100 cases of lymphopro-liferative tumors arising from the larynx (including both NHL and immunosuppression-related lymphoproliferative diseases)andfewcasesoflaryngealinfiltrationofPTLhave beenreported.ThereisnoreportedcaseofPTLpresenting with hoarseness and diagnosed through direct laryngo-scopic biopsy, since it typically does not erode thyroid cartilage.

Primaryorsecondarylaryngealpathologiesmaymanifest similarsymptomsincludingdysphonia,hoarseness, dyspha-gia:a cervical mass can be found. A smooth submucosal swellingorpolypoidmasswithout ulcerationaretheusual physical examination findings of primary laryngeal lym-phomas. Primary laryngeal lymphomas usually arise from thesupraglotticregion,specificallyfromtheepiglottisand aryepiglotticfolds.5_{Ourcasealsodemonstratessupraglottic}

infiltrationespecially inleftlaryngeal ventricule. Extrala-ryngealtumorextensionismostfrequentlynotedtoinvolve the hypopharynx, and less commonly the oropharynxand strapmuscles.

PTL is a lymphamatous process which develops in the thyroid without involvement of primary lymphoid organs or distant metastasis at the time of diagnosis. PTL com-prises2%---8% of thyroidmalignancies. It ismostly seen in a middle-aged elderly women with a median age of 56 years. Patients usually have a history of hypothyroidism orthyroiditisand massin thyroidglandwhich canrapidly grow.Dyspnea,stridor,dysphagia,andhoarsenessare com-monsymptoms in patients with thyroid lymphoma, while mainfindingmayonlybeanenlargingcervicalmasswhich presentsinover87%ofpatients.HoweverPTLmaysuddenly growandcompromisetheairway.

Themajorityof PTLsarehighgradewhile only30%are low-grade.Earlydiagnosisandappropriatetreatmentof thy-roidlymphomascanprovidelongtimesurvival.3

Anaplastic thyroid cancers (ATC) also present with a rapidlygrowing large mass in elderly patients. Anaplastic thyroidcancers,whichcompromise1%---2%ofthyroid malig-nancies,havesimilarclinicalprogressandmustbeincluded in the differential diagnosis of thyroid lymphomas. ATC’s mayrapidlyprogress andcompromisetheairwaywithan averagemeansurvivalof6---7months.Onradiologic evalu-ationATCispresentsasalarge,solidmassaccompaniedby necrosis, hemorrhage, dense calcification, directinvasion ofadjacentstructuresandcervicallymphnodemetastasis. Tumornecrosishasbeenknowntobeoneofthemost valu-ableparametersin differentiatingATC fromother thyroid masses, and low attenuation value on post contrast scan (attenuationvalue<100HU)isanotherpredictorof anaplas-ticcarninoma.6

740 Gökdo˘ganOetal.

Fineneedleaspirationwithor without ultrasonography isthefirststepindiagnosticstrategyforathyroidnodule, butaccuracyisquitelowinthyroidlymphomaoranaplastic cancer. The diagnostic approaches for an enlarging thy-roidmassareFNA,core needlebiopsy(CNB),openbiopsy, and/orsurgical intervention.Thediagnostic effectof FNA identifies30%---80%ofthyroidlymphomapatients;therefore furtherdiagnostic approaches maybe useful when FNAis inconclusive.8_{Coreneedlebiopsy(CNB)generallyprovides}

enoughtissueneededforthecertaindiagnosisofaggressive thyroidcancerslikelymphomaorATC.ThereforeCNBmay bethefirstdiagnosticstepwhenalargeaggressivethyroid massisencounteredonradiologicevaluation.

Histological and phenotypic analyses such as flow cytologyorimmunohistochemistryareveryhelpfulin patho-logicalevaluation.MostthyroidlymphomasareB-cellorigin withdiffuselarge-celltype.

Mostpatientspresent withearlystagesIE(30%---66%)or stageIIE(25%---66%)disease.9_{Forstaging,CTscansofhead,}

neck,chest,abdomenandpelvisorFDG-PETscanshouldbe performed.

Treatmentoptionsconsistofchemotherapyalone, radia-tiontherapyaloneandcombinedchemo-radiationtherapy. Although there are some articles that advise thyroidec-tomy followed by radiation therapy, the series reported aretoosmalltoacceptaswidespreaduse asatreatment option.

The overall relapse rates are 7.7%, 37.1% and 43% for chemoradiation therapy, radiation therapy alone, and chemotherapy alone respectively. Local relapse rates are 2.6%,12.6%and23%forchemoradiationtherapy,radiation therapyalone,andchemotherapyalonerespectively.1

The most common chemotherapy regimen is R-CHOP (rituximab---cyclophosphamide,doxorubicin,vincristineand prednisolone).Thebiologicagentrituximab,amonoclonal antibody directed against B-cell-specific antigen CD 20 is generallyusedwithCHOP chemotherapyin thetreatment ofthyroidlymphoma.

Radiotherapyisgenerallychosenafter3---6CHOPcourses intheformofmodifiedmantleirradiation,includingthyroid, bilateralneck,supraclavicularareaandmediastinum.

Age(>60years),elevatedlevelsofserumlactate dehy-drogenase (LDH), and ␤2 macroglobulin, extra nodal site

involvementandstageIII---IVclassificationarepoor progno-sticfactors.10

Ourpatientreceived R-CHOP basedchemotherapy and radiotherapyandisalivewithoutanysignofdisease.

Conclusion

The present reportdetails the firstknowncase diagnosed with thyroid lymphoma through direct laryngoscopy and biopsy.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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