Arch Metab. Endocrinol 2017;61/6 patients undergo, soas to allowanearlydiagnosis of that HT ultrasonographiccontrols frequent more suchasthe could contributetoabetter prognosis, systemic invasion(3,4).Obviously, evenother factors and alessadvancedTNM stage,withoutlocalor a youngerage;itischaracterized bysmallernodules at HT patientstheneoplasiaisgenerallydiscovered of PTC. Infact,in agent against the aggressiveness ofprotective on theotherhandHTcouldbeasort factorformalignancies,but thus becomingagrowth a long-standingHTcouldleadtohighTSHlevels, (2): byliterature (HT) isawell-knowneventreported byHashimoto’sthyroiditis of PTCinpatientsaffected ofsmalltumors(1).Theoccurrence large prevalence inthelastfewdecades,witha has beenincreasing P INTRODUCTION sudden enlargement. addition, PTL should be consideredfor differential diagnosis in elder HTpatients who present with of monitoringHTpatientswithnodularlesions,especiallyiftheyhavelong-standingdisease.In patient hadnoevidenceofrecurrence ofeithermalignancy. This rarecasehighlightstheimportance iodineablationtreatmentforthemicroPTCasperguidelines. radioactive Two after years surgery, the discovered. The patient was then treated withchemotherapy for the PTL, but shedidnot undergo florid HT. Moreover, aunifocalpapillarymicrocarcinoma,classicalvariant(7mm,pT1aNxMx), was performed, andhistologyrevealedadiffuse largeB-celllymphoma(DLBCL)onabackground of growth of a hypoechoic nodule in the right lobe measuring 32 x 20 mm. A total thyroidectomy was enlargement intherightanteriorsideofneck. Thyroid ultrasonography demonstratedincreased woman withlong-standingnodularHTunderreplacementtherapy, whopresentedwithafast,painless inHTpatientsisveryrare.Hereinwereportthe coexistenceofbothtumors thecaseofa66-year-old Despite severalcasesinwhich bothPTCandPTLariseinthesetting ofHashimoto’s thyroiditis (HT), primary thyroid (PTL)isararedisease,accountingfor2%to5% ofallthyroid malignancies. Papillary thyroid carcinoma(PTC)isthemostcommon type ofthyroid . Onthecontrary, SUMMARY Vittorio Cavallari TrovatoMaria by Hashimoto’s thyroiditis carcinoma inapatientaffected thyroidlymphoma andpapillary Coexistence ofdiffuse large B-cell common type of ,common typeofthyroid anditsincidence (PTC)isthemost carcinoma thyroid apillary 1,2 , GiuseppeGiuffrida 2 , MaddalenaRuggeri Rosaria Arch EndocrinolMetab. 2017;61(6):643-6 1 ,Seminara Antonino 1 ,Campennì Alfredo HT under replacement therapy with L-thyroxine (125 therapy with L-thyroxine HT under replacement by cancer, of thyroid affected with no family history wedescribe thecaseofa66-year-oldHerein woman, PATIENT (10). rare PTC isvery 9), whileaDLBCLinthecontextofcoexistingHTand PTC andMALT lymphomashavebeendescribed (7- (5,6). SomecasesofassociationbetweenHTandboth tosystemictreatment cases andhaveabetterresponse tissue (MALT) indolentinmost ,whichare The other 30% comprises mucosa associated lymphoid course andhasaworseoutcome. aggressive a more with lymphoma (DLBCL), which usually presents large B-cell tumors: in70%ofcasesitappearsasdiffuse diseasethataccountsfor5% ofallthyroid (PTL) isarare malignancy. Conversely, lymphoma thyroid primary 3 , SimoneFogliani 5 4 ,

of Messina, Messina, Italy of Messina,Italy Nuclear Medicine,University and Functional Images,Unitof Sciences andMorphological 5 of Milazzo, Messina,Italy 4 Messina, Italy 3 Messina, Italy Pathology, Universityof 2 of Messina,Italy of , University Medicine,Unit Experimental 1 DOI: 10.1590/2359-3997000000313 Accepted onNov/16/2015 Receivedon Aug/11/2015 [email protected] 98125 Messina,Italy Policlinico Universitario “G. Martino” Padiglione H,4piano, UOC diEndocrinologia Clinica eSperimentale, Dipartimento diMedicina Rosaria MaddalenaRuggeri Correspondence to: Provinciale,Azienda Sanitaria Department ofBiomedical Unit ofRadiology, Hospital Department ofHuman Department ofClinicaland case report 643

Copyright© AE&M all rights reserved. Copyright© AE&M all rights reserved. 644 tumor, thyroid lymphocytes. PTC isthemostfrequent cells or thyroid to malignant ones, deriving from noduleswithbenignfeatures variable, rangingfrom (12,13). Thehistologyoftheselesionsiswidely areas in our clinical practice, especially in iodine-deficient nodules is also a common finding of real the presence so-called“pseudo-nodules”;nonetheless, presenting inflammation,often bythechronic usually altered In DISCUSSION ofeithermalignancy.evidence ofrecurrence hospital, twoyearsaftersurgery, thepatienthadno inour PTC asperguidelines(11).Atthelastcontrol for themicro- radioactive iodineablationtreatment chemotherapy forthePTL,whileshedidnotundergo with disease ormetastases.Thepatientwasthentreated biopsy,bone marrow showingnoevidenceofsystemic includingtotal-bodyCTand performed, the PTLwere Staging studiesfor mm, pT1aNxMx),wasdiscovered. classicvariant(7 microcarcinoma, a unifocalpapillary chains, sotheneoplasiawasstagedas1A.Moreover, and anti-BCL6positivity, withmonoclonallambda CD20,anti-BCL2 of theatypicallymphocytesconfirmed 1).Immunohistochemistry cellchanges(Figure Hurtle folliclesofvarioussizeswithdense colloidand thyroid centersand withgerminal by lymphocyticaggregates offloridHT,nucleoli onabackground characterized andsmall nuclei,condensedchromatin irregular large atypicallymphocyteswith DLBCL, revealing thyroidectomy. Histologywascompatiblewitha tototal lesion (THYR3).Thepatientwasreferred lymphocytic infiltration,concludingforindeterminate atypical epithelial cells and examination revealed (FNAB) oftheright-sidednoduleandcytological US-guided fine needle aspiration biopsy before). almost12months control, 18 mmattheprevious measuring 32x20mm(themaximumdiameterwas ofahypoechoicnoduleintherightlobe, growth ultrasonography(US)demonstratedthe Thyroid lesion intherightlobe,movingwithdeglutition. nodular gland withapalpable,firm enlarged thyroid dyspnea, whilephysical examination demonstrated an solid andliquidfoods;shedeniedanyvoicechangeor dysphagiato complaining ofmildandintermittent enlargement intherightanteriorsideofneck, painless toourdivisionforarecent She wasreferred perday)andlong-standingnodulargoiter.micrograms thyroidPapillary carcinoma anddiffuse large B-celllymphomainafemale patientwithHashimoto’s thyroiditis

patients affected byHT, is architecture patients affected thyroid

magnification x200; G, H, andI, totalmagnification x400). lambda monoclonal chains, BCL2 and BCL6, respectively (F and G, total x200). thyroiditis associatedwithparenchimatous goiter(H&E, totalmagnification (DLBLC), Stage1A(H&E, total magnificationx200). H&E; totalmagnificationx200). in size, pT1aNxMx) with no aggressive histology (hematoxylin and eosin, magnification x400). presents also asmall intranuclear inclusion (black arrow) (MGG, total inaclusterof follicularcells;onecell of areasmoderateanisokaryosis magnification x100). by polygonalfollicularcells(May-GrünwaldGiemsa, MGG; total lymphocytes, filamentouscelldebris, andacellularformationcomposed diffuse large B-cell lymphoma (panels FJ). occurring inthecontextofHT. Immunohistochemicalcharacterizationof thyroidmicrocarcinomaanddiffuse large B-celllymphoma papillary Figure 1. Panels F, G, H, I, andJ: Cytological(panels AB) andhistological (panels CE) featuresof Panel C: Panel B: High magnificationhighlights thepresence Unifocal papillary microcarcinoma(7mm Unifocal papillary Panel D: Immunoreactionsforcytokeratin, CD20, Arch Metab. Endocrinol 2017;61/6 DiffuselargeB-celllymphoma Panel A: Panel E: Moderate amount of Hashimoto’s Arch Metab. Endocrinol 2017;61/6 In the case we describe, we detected two distinct and thus explainingthechances ofabetteroutcome(21). thelysisof neoplasticcells, HT patients,couldprevent activation ofthecomplement system,usuallyhigherin tumor. Inparticular,asinYamakawa andcols.,the withthe factorscouldinterfere time, someprotective epithelialneoplasmsandHT(20).Atthesame thyroid e.g., cyclooxygenase-2,whichhasbeendetectedin tumorigeniccompounds, inflammation couldproduce DLBCL;second, toward heavy chainswithprogression lymphocytes couldgradually gain monoclonality for antigenicstimulation ways: first,becauseofthechronic tumorigenicactionsintwo autoimmunity mayexert a unifyingpathogenetichypothesis,insuchpatients average 18monthsafterthediagnosisofHT(19).In on somecasesofPTLdiscovered and cols.reported many years after the diagnosis of HT, but Watanabe HT patients(18).TheonsetofPTLgenerallyhappens in lymphomas, of clonalBcells,generallypresent evolve tomalignancy, asdemonstratedbythefinding antigenicstimulation could changes duetochronic HT, however, isalsoariskfactorfor PTL,ascellular againsttheinflammation(2-4,14). a cytotoxicresponse drive antibodies (TPOAb) could probably peroxidase ofneoplasia:thyroid againsttheaggressiveness role with HT, whichsomehowcouldplayaprotective for PTC ifit co-occurs abetterprognosis papers report of PTCwithHT(16,17).Ontheotherhand,several intheassociation perse,mayplayamajorrole thyroiditis TSHinHTpatients,ratherthanautoimmune of serum increase also hasbeenhypothesizedthattheprogressive betweenthetwoconditions,andit causal relationship donotclearlydemonstrate a theliterature data from disease(15).However,clinically expressive mostofthe and thushighlightingtheirhigherriskofdevelopinga molecular geneticevidenceofcancerinthispopulation a large numberofHTpatientswithoutPTC,showing PTC 1andRET/PTC3oncogeneswasfoundevenin fortheRET/ andcols.,mRNAexpression Wirtschafter response (14).Inaddition, inastudyby inflammatory the authors suggest a possible, specific tumorigenic isactuallyunknown: antibodies (TgAb),whoserole cancer togetherwith antithyroglobulin of thyroid study, TSH≥1 publishedprospective nodules.Inarecently thyroid factorfor infact,TSHisaknowngrowth thyroiditis; rise in TSHlevelscaused by long-standing progressive with HT(2),whichcouldbeexplainedthe and severalstudieshaveshownasignificantassociation µIU /ml was an independent predictor /ml wasanindependentpredictor Papillary thyroidPapillary carcinoma anddiffuse large B-celllymphomainafemale patientwithHashimoto’s thyroiditis Thus, whenPTCandPTLcoexistinthesamepatient, bytheonehavingworsestage(7-9). likely affected the coexistenceoftwodiseases,butratherismore too,doesnotseemtobeworsenedby the prognosis, themanagementofotherneoplasm(7); not affect tosurgery. referred are The management ofonedoes symptoms, e.g.,hoarsenessordyspnea,andthepatients mass oftenassociated with compressive thyroid-related however, ofa thediagnosisis made afterarapidgrowth InmostcasesofPTL, scantyintheliterature. diseases are management ofsuchanassociationneoplastic to MALT theoptimal lymphomas.Dataconcerning compared courseandaworseprognosis aggressive more association withPTC(10).Ofnote,aDLBCLhas in in the contextof Hashimoto’s thyroiditis reported this isthesecondpatientinwhichaDLBCLhadbeen cells andlymphocytes.To thebestofourknowledge, as DLBCL),originating,respectively, follicular from sim 6. 5. 4. 3. 2. 1. REFERENCES was reported. relevant tothisarticle nopotentialconflictofinterest Disclosure: byanygrant. Funding: thisworkwasnotsupported diagnosis. PTL inthedifferential patients withHTshouldleadphysicianstoconsider enlargement inelder in particular,asuddenthyroid anearlydiagnosis: to reach follow-upinorder regular of nodular lesions,ourcasehighlightstheimportance neoplasia inHTpatientswithlong-standingdiseaseand and/ortheworsestageatdiagnosis. prognosis hasto prioritize the tumorwithworse treatment stagingofbothdiseasesismandatory,a careful and

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