Simultaneous occurrence of follicular and papillary thyroid carcinomas in same thyroid lobe: A case series of six patients from Qatar

ContentslistsavailableatScienceDirect

International

Journal

of

Surgery

Case

Reports

j o u r n al ho m e p a g e :w w w . c a s e r e p o r t s . c o m

Case

Series

Simultaneous

occurrence

of

follicular

and

papillary

thyroid

carcinomas

in

same

thyroid

lobe:

A

case

series

of

six

patients

from

Qatar

Abdelrahman

Abdelaal

_,

_Walid

_El

_Ansari

_,

_Abdelrahman

_Abusabeib

_,

Hanan

Farghaly

_,

_Abdelhakem

_A.M.

_Tabeb

a_{DepartmentofGeneralSurgery,HamadGeneralHospital,HamadMedicalCorporation,Doha,Qatar} b_{DepartmentofSurgery,HamadGeneralHospital,HamadMedicalCorporation,Doha,Qatar} c_{CollegeofMedicine,QatarUniversity,Doha,Qatar}

d_{SchoolofHealthandEducation,UniversityofSk¨ovde,Sk¨ovde,Sweden} e_{DepartmentofLabMedicine&Pathology,HamadGeneralHospital,Doha,Qatar}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received6May2020

Receivedinrevisedform15June2020 Accepted15June2020

Availableonline20June2020

Keywords:

Follicularthyroidcarcinoma Papillarythyroidcarcinoma Differentiated

a

b

s

t

r

a

c

t

BACKGROUND:Papillarythyroidcarcinoma(PTC)andfollicularthyroidcarcinoma(FTC)arethefirstand

secondmostcommonthyroidcancerscomprisingabout85%and10%ofallthyroidcancers.Simultaneous

occurrenceofmedullaryandpapillarythyroidcancerhasbeenreportedwithvariouspresentations,but

simultaneousoccurrenceofFTCinadditiontoPTCasdifferentiatedcancers,isanunusualeventthatis

rarelyreported.

PRESENTATIONOFCASES:WereportourexperienceofsixrarecasesofsynchronouscoexistenceofFTC

andPTCwithuniquefeatures.Case1is31oldEgyptianfemale.Case2isa61yearoldSudanesemale.

Case3isa59yearoldSudanesemale.Case4isa56yearsoldIndianfemale.Case5isa35yearsold

Filipinafemale.Case6isa52yearsoldQatarifemale.Thesixcasesarespecialintheirco-occurrence

oftwothyroidcarcinoma,consistingofhistologicfeaturesoffollicularthyroidcarcinomas,andclassical

papillarythyroidcarcinoma,possiblythefirstcaseseriesofsimultaneousoccurrenceofthesetwotypes

ofthyroidcancerintheMiddleEastandNorthAfricaRegion.

CONCLUSIONS:WepresentrarecasesofconcurrentFTCandPTC.Thesesixcasesaddmoredata

highlight-ingthecoincidentalsimultaneouscoexistenceofFTCandPTC.Endocrinologistsandpathologistsshould

beawareofandvigilanttothisvariety.

©2020TheAuthor(s).PublishedbyElsevierLtdonbehalfofIJSPublishingGroupLtd.Thisisanopen

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

1. Background

Althoughcompositethyroidcarcinomashavebeenreportedin theliterature, thesimultaneous occurrence of multiple thyroid tumors ofdifferenthistopathologicaltypes inthesame thyroid lobeisararepresentationandknownasmixed,hybridtumours orcompositetumours[1].

About71casesofconcurrentpapillarythyroidcancer(PTC)and medullarythyroidcancer(MTC)havebeenreported[2],butcases

∗ Correspondingauthorat:DepartmentofSurgery,HamadGeneralHospital, HamadMedicalCorporation,Doha,Qatar.

E-mailaddresses:aabdelaal1@hamad.qa(A.Abdelaal),welansari9@gmail.com

(W.ElAnsari),aabusabeib@hamad.qa(A.Abusabeib),hfarghaly@hamad.qa

(H.Farghaly),atabeb@hotmail.com(A.A.M.Tabeb).

ofPTCandfollicularthyroidcancer(FTC)presentingsynchronously aremuchrarer[3–5]andsignifythesimultaneousoccurrenceof distinctlydifferent entities.Well-differentiated thyroid carcino-mas(e.g.,PTCandFTC)areusuallysporadicinmostcases[6],and thecoexistenceoftwo independentandsimultaneousfollicular epithelialcellcarcinomas,apapillarycarcinomaandafollicular carcinoma,isextremelyrare[7].

Tothebestofourknowledgethiscouldbethefirstcaseseriesof simultaneousoccurrenceoftwotypesofthyroidcancer(PTCand FTC)reportedfromtheMiddleEastandNorthAfricaregion(MENA). OnecasereportfromtheMiddleEastregionhadthreetypesof thyroidcancer[6].Wereportthesecasesduetotheuniquenessof theirhistopathologicalfindingsandtodebatetheirpossible com-plexhistogenesis.Thiscaseseriesreportisinlinewiththeupdated consensus-basedcaseseries(PROCESS)guidelines[8].

https://doi.org/10.1016/j.ijscr.2020.06.070

2210-2612/©2020TheAuthor(s).PublishedbyElsevierLtdonbehalfofIJSPublishingGroupLtd.ThisisanopenaccessarticleundertheCCBYlicense(http:// creativecommons.org/licenses/by/4.0/).

Fig.1.Papillarythyroidcarcinomawithcharacteristicnuclearfeatures(nuclear crowding,overlapping,clearing,membraneirregularitiesandinclusions).

Fig.2. Thyroidfollicularcarcinomawidelyinvadingthethyroidcapsule.

2. Casepresentations 2.1. Case1

AnEgyptianfemale,31yearsold,presentedtoourthyroidclinic atHamad MedicalCorporation(biggest tertiarycare facility)in Doha,Qatar, withleft neckswelling since a year,increasing in size,associatedwithmild leftneckpain. Shehadnohistory of irradiationtherapyandnofamilyhistoryofcancerthyroid. Exam-inationrevealedaleftneckthyroidnodule(4×3cm)thatmoved withswallowing, and nopalpable lymph nodes. Investigations showednormalthyroidfunctiontests(TFTs).Ultrasound(US)of thethyroidrevealedalargeleft-lobethyroidnodule(5×2.5cm) withsmallthinperipheralhalo,peripheralandcentralvascularity andcoarsecalcifications.Ultrasoundguidedfineneedleaspiration (FNA)showedfollicularcellsofundeterminedsignificance(FLUS). The patient underwent left hemithyroidectomy. Post-operative histopathologyshowedleftpapillarythyroidcarcinoma(PTC)(5× 4cm)(Fig.1)andfollicularthyroidcarcinoma(FTC)(1.3cm)(Fig.2). TheFTChaduninvolvedmargins,thetumorwasveryclosetothe posteriorandanteriormargins(within0.1mm),andAJCCstaging [9]waspT3,N0.ThePTChistologywasoncocytic,withG1, well-differentiatedhistologicgrade,wasadjacenttotheanteriormargin,

andAJCCpathologicstaging[9]waspT1b,N0.Hence,thepatient underwentcompletionrighthemithyroidectomy,and histopathol-ogyrevealedbenignthyroidwithchroniclymphocyticthyroiditis. ShethenreceivedtwofractionateddosesofradioactiveIodine(30 mci).Followupradioactivewholebodyscanshowednoevidenceof radioiodineavidlocalordistantpathology,andfollowupUSofthe neckshowednodefiniteresidualorrecurrenceinthethyroidbed. Laboratoryresultsaftertwoyearsshowedverylowthyroglobulin (<0.1ng/mL)andthyroglobulinantibodies(<0.9IU/mL).

2.2. Case2

ASudanesemale,61 yearold,wasbeingfollowedupatthe urologydepartmentforarecentradicalprostatectomyforprostatic cancerthatwasfollowedbyradiationtherapy.Duringfollowup,CT scanofthechestshowedanincidentalfindingofanenlargedright thyroidlobethathada centralareaofhypodensity.Thepatient wasreferredtoourthyroid clinic.Onexamination,we founda rightthyroid mass. Therewasnofamily history of cancer thy-roid.InvestigationsshowednormalTFTs.Ultrasoundofthethyroid glandshowedenlargedrightthyroidlobe(3.1cmanterio-posterior dimension)thatcontainedalarge,mainlyisoechoic,heterogenous noduleoccupyingalmostalloftherightthyroidlobe,withslightly increasedperipheralvascularity.Theleftthyroidlobemeasured 1.5 cm (anterio-posterior dimension), showed normal echotex-tureandnormalflowoncolourDoppler,andcontainedmultiple smallnodules,thelargestofwhichappearedcysticinthelower polemeasuring1×0.7cm. UltrasoundguidedFNAoftheright thyroidraisedsuspicionforfollicularneoplasm.Thepatient under-wentrighthemithyroidctomy.Histopathologyindicatedunifocal FTC(6×3×2.7cm),encapsulated,uninvolvedmargins, angio-invasive(focal<4vessels),nolymphaticorperineuralinvasion and no extrathyroidalextension. Pathologic stage (pTNM,AJCC eighthedition)[9]waspT3aNx.Thespecimenwasalsosentfor reviewattheMayoClinicwhichindicatedawell-differentiated fol-licularneoplasmwithangioinvasionandcapsularinvasion,most consistentwithfollicularcarcinoma,withaseparatefocusof pap-illarythyroidmicrocarcinoma(3mm),pathologicstagepT1aNx [9].Thepatient underwentcompletion lefthemithyroidectomy. Histopathologyindicatednodularhyperplasiawithpredominant noduleona backgroundofchronicnon-specificthyroiditis.The patientreceivedhighdose(100mci)radioactiveIodineablation (RAI).Followupwholebodyscan3monthslatershowedno evi-denceofeitherresidualthyroidtissueormetastatictumor;and followupUS pftheneck1yearlatershowednothyroid tissue residual,orfocallesionatthethyroidbed.Laboratoryresultsafter 15monthsshowedverylowthyroglobulin(<0.2ng/mL)and thy-roglobulinantibodies(<0.9IU/mL).

2.3. Case3

ASudanesemale,59yearold,presentedtoourthyroidclinic withrecurrentmultinodulargoiterinvolvingmainlytheisthmus andleftlobe.Hehadhistoryofthyroidsurgery20yearsbackin Sudan,nohistoryofirradiationtherapyandnofamilyhistoryof cancerthyroid.Onexamination,thepatientwasclinically euthy-roid,withahugefrontalneckswelling(15×7cm).Investigations showednormalTFTs.USofthethyroidshowedabsenceofright thyroidlobe, andtheleftlobeandisthmus wereenlarged with multiplenodules,showingsolidcomplex echotexturewith par-tiallyill-definedmarginsandcentralareasofanechoiccomponents suggestiveofcysticdegeneration,thelargestofwhichmeasured 4.1×2.8cm.UltrasoundguidedFNAshowedfollicularlesionof FLUSonabackgroundoflymphocyticthyroiditis.Completionleft thyroidectomywasdone.HistopathologyshowedFTC,widely inva-sive(5cm),abuttingtheinkedanteriormarginand0.1mmfrom

inkedposteriorresectionmargins,withlymphovascularinvasion butnoperineuralorangioinvasion,noextrathyroidalextension,of stagepT3apNx[9].TherewasalsoaseparatefocusofPTC (great-estdimension=1.5cm)ofstagepT1bpNx[9],abuttingtheinked anteriormargin,withnolymphovascular,perineuralor angioin-vasion,noextrathyroidalextension.Thepatientwasdiscussedat ourthyroidmulti-disciplinarymeeting(MDT)andwascategorized ashighriskstratification(ATA2015). HereceivedRAI100mci, thenfollowupUSshowedresidualthyroidtissue,sothepatient receivedanother30mciRAI.Follow-upUS oftheneck after22 monthsshowednoresidualthyroidtissue,andboththyroidbeds werenormal.Finallaboratoryfindingsshowedthyroglobulin3.6 ng/mL,andthyroglobulinantibodies1.2IU/mL.

2.4. Case4

AnIndian female,56 yearold,withHodgkin’s lymphomain remission since 2001.Presenting at ourthyroid clinic,she had noticedaleftsideneckswellingsinceoneyearandstarted feel-ingpressure symptomssince onemonth.Examinationrevealed a bilateralneckswellingthat moved withswallowing.Shehad nohistoryofirradiationtherapyandnofamilyhistoryofthyroid cancer.InvestigationsshowednormalTFTs.Followupwholebody fluorodeoxyglucosepositronemissiontomographyintegratedwith computedtomography(FDGPETCT)showednosignsoflymphoma relapseorlymph nodeordistantorganmetastasis,butshowed incidentalhighlyFDGpositivebilateralthyroidnodules.USofthe thyroidshowedleftthyroidnodule(4.5cm)withasmallernodule withinitwithheavyrimcalcificationandsolidcomponentwith microcalcificationat thebottom.US of theneckalsoshowed2 hypoechoicnodulesintherightlobe,thelargestwasill-defined withcoarsecalcificationmeasuring(7×7×10mm).Nosuspicious lymphnodeswereseen.UltrasoundguidedFNAshowedatypical follicularlesionofundeterminedsignificance (AUS).Thepatient underwenttotalthyroidectomy,andhistopathologyshowedFTC, minimallyinvasiveandmultifocalclassicalvariantPTC.TheFTC intheleftlobewasunifocal(4.5×3.5×2.5cm),minimally inva-sive,<0.1mmfromtheposteriormargin,noperineuralinvasion orangioinvasion,butpresentlymphaticinvasion,andno extrathy-roidalextension.PathologicstagewaspT3apNx[9].ThePTCwas multifocalwithnodularhyperplasia,presentinboth lobes(first focusinrightlobe1×0.8×0.7cm,0.1mmfromtheanterior mar-gin;secondfocusinrightlobe0.5cminmaximumdimension;third focusinleftlobe0.6cminmaximumdimension).Nolymphatic, perineuralorangioinvasionorextrathyroidalextension.Pathologic stagewasmpT1apNx[9].Thepatientwasdiscussedinour thy-roidMDTmeetingandcategorizedashighriskstratification(ATA 2015)eligibleforhighdoseradioactiveiodineablation.Thepatient travelledoutofthecountryandwaslosttofollowup.

2.5. Case5

A Filipinafemale, 35 years old, was referred toour thyroid clinicwithmultinodulargoiterandadominantnoduleintheright lobe.Shecomplainedofmildhoarsenessofvoice,butnopressure symptoms.Therewasnofamilyhistoryofthyroidcancerandno historyorirradiation.Onexamination,therewasrightthyroidlobe enlargement.Shewasclinicallyeuthyroid,withnormalTFTs.USof theneckshowedheterogeneousechopatternwithmildincreased vascularityandmultiplenoduleswithcalcificationinbothlobes. Therewereatleastthreenodulesintherightlobe,thelargest com-plexnodulewasinthelowerpole(2.1× 1.9 cm),andanother solidnodulewithcalcificationintheupperpole(1.8×1cm).The leftlobealsoshowedmultiplenodules,where thelargest com-plexnodulemeasured4.8×2.5cm.Therewerenosignificantly enlargedcervicallymphnodes.FNA(ultrasoundguided)showed

rightthyroidnodulescomprisingmalignantcellsconsistentwith PTC.Thepatientunderwenttotalthyroidectomy.Histopathology showedrightmicroPTC,multifocal(twofoci),largestwasatleast 0.8cm,withuninvolvedmargins,nolymphovascular,perineural, orangioinvasionandnoextrathyroidalextension,andpathologic staging waspT1aN0 [9]. Histopathologyalsoshowed rightFTC, unifocal,atleast1.3cm,withuninvolvedmargins,no lymphovas-cular,perineuralorangioinvasionandnoextrathyroidalextension, andpathologicstagingpT1bN0[9].Thepatientwasdiscussedat ourthyroidMDTmeetingandcategorizedashighrisk stratifica-tion(ATA2015)eligibleforhighdoseradioactiveiodineablation. Thepatient travelledoutof thecountryand waslosttofollow up.

2.6. Case6

AQatarifemale,52yearsold,presentingwithaneckswelling a yearago, associatedwithsomepain onswallowing,no com-pressionsymptoms,underwentanFNAinThailandthatshowed suspiciousfollicularlesionandwashencereferedtoourthyroid clinic.Onexamination,therewasanodularswellingofthethyroid gland,butitwasnottender.USofthethyroidshowedmultiple rightlobesolid thyroidnodules,largestwascomplex, predomi-nantlysolid(15×26mm),showingrimcalcification,cysticchange, andintranodularvascularity.Theleftlobemeasured21mm,and hadanisoechoicthyroidnodule,(17×20mm)showing hypoe-choichaloandintranodularvascularity.Therewereafewcervical lymphnodeswithpreservedechogenichilum.Ultrasoundguided FNAwasrepeatedatourinstitution,therightthyroidnodulewas FLUS,andtheleftthyroidnodulewasalsoFLUS.Thepatientwas discussedatourthyroidMDTandplannedfortotalthyroidectomy whichwasundertaken.Histopathologyrevealedrightlobesingle focusFTC(2.7× 1.5× 1.5cm)withcapsularinvasion, margins werefreeofcarcinoma,<0.5mmfrombothanteriorand poste-riormargins,nolymphovascular,perineural,orangioinvasionno extrathyroidalextension,andpathologicstagingwaspT2NX[9]. Therewasalsoasinglefocuspapillarythyroidmicrocarcinoma, fol-licularvariant(0.8×0.6×0.4cm),non-capsulated,marginswere uninvolvedbythecarcinoma,closestmarginsweretheanterior andposteriormarginswith<0.5mmclearance,no lymphovascu-lar,perineural,orangioinvasion,noextrathyroidalextension,and pathologicstagingwaspT1aNX[9].Inaddition,thehistopathology showedanadenomatoidnoduleintheleftlobe(thirdlesion), clas-sifiedaspT1a[9].ThepatientwasdiscussedatourthyroidMDT meeting,andshewasstraifiedasintermediaterisk (ATA guide-line).ShewasplannedforlowdoseRAIablationandthyroidcancer surveillancewithneckUSandthyroglobulintumormarkers,and suppressivetherapywithLevothyroxine.USoftheneckposttotal thyroidectomyandRAIablationshowedsofttissuestructuresin boththyroidbedsbilaterallythatcouldrepresentresidualor recur-rentthyroidtissue,althoughthenonstimulatedthyroglobulinwas verylow(0.2ng/ml)andthyroglobulinantibodieswerenegative. Table1depictsasummaryofthesixcases.

3. Discussion

PTCandFTCarebothderivedfromthyroidfollicularcells,where PTCisthemostcommonandFTCthesecondmostcommonofall thyroidcarcinomas[10].BothPTCandFTCaredifferentiated thy-roidcarcinomathatcomprises90%ofallcasesofthyroidcancer (incidenceabout0.5–10newcasesper100,000population glob-ally) [11–13]. Thyroidcarcinomas account forabout 4%of new cancercasesintheUnitedStates[14].InQatar,thyroidcanceris thesixthmostcommoncanceracrossallnationalitiesandgenders; thesecondmostcommonmalignantcanceramongfemalesofall

Table 1 Summary of characteristics of six patients with concurrent follicular thyroid carcinoma and papillary thyroid carcinoma. Case Age Sex Country Path Side Focus Size (cm) AJCC stage Margins Invasion EE Rx Follow up L PN AI Scan Lab 1 31 F Egypt FTC L U 5 × 4 pT3 N0 UI N N N N L hemi T; completion R hemi T; 2 fractionated doses RI (30 mci) No evidence of RI avid local/distant path; No residual /recurrence in TY Very low TG (<0.1 ng/mL) and TGA (<0.9 IU/mL) PTC L U 1.3 pT1b N0 N N N N 2 61 M Sudan FTC R U 6 × 3 × 2.7 pT3a Nx UI N N Y N R hemi T; completion L hemi T; high dose RI (100 mci) No evidence of residual TY tissue / metastatic tumor / focal lesion in TY bed Very low TG (<0.2 ng/mL) and TGA (<0.9 IU/mL) PTC R U 0.3 pT1a Nx UI * — — — — 3 59 M Sudan FTC L U 5 pT3a Nx I Y N N N Completion L T; RI ablation 100 mci Residual TY tissue; received another 30 mci RAI. US Neck follow up showed no residual TY tissue TG 3.6 ng/ mL, TGA 1.2 IU/mL PTC L U 1.5 pT1bp Nx I N N N N 4 56 F India FTC L U 4.5 × 3.5 × 2.5 pT3a Nx I Y N N N Total T, then post T high dose RI ablation Patient travelled out of the country, lost to follow up PTC L M 0.6 MD pT1a Nx UI * — — — — R M 1 × 0.8 × 0.7 pT1a Nx UI * N N N N R M 0.5 MD pT1a Nx UI * — — — — 5 35 F Philippines FTC R U 1.3 pT1b N0 UI N N N N Total T Patient travelled out of the country, lost to follow up PTC R M 0.8 pT1a N0 UI * N N N N 6 52 F Qatari FTC R U 2.7 × 1.5 × 1.5 pT2 Nx UI N N N N Total T, then post T low dose RI ablation Residual TY tissue; US Neck follow up showed residual TY tissue TG 0.2 ng/ mL, TGA 9.1 IU/mL PTC R U 0.8 × 0.6 × 0.4 pT1a Nx UI * N N N N *Micro papillary carcinoma; AI Angio-invasion; AJCC American Joint Commission pTNM [ 8 ]; EE Extrathyroid extension; F female; FTC; follicular thyroid carcinoma; I involved; L left; L lymphatic; Lab laboratory; M male; M multifocal; MD maximum dimension; N no; Path Pathology; PN Peri-neural; PTC papillary thyroid carcinoma; R right; RI radioactive iodine; Rx treatment; Rx treatment; T thyroidectomy; TG thyroglobulin; TGA thyroglobulin antibodies; TY thyroid; U unifocus; UI uninvolved; Y yes.

nationalities;andthesecondandfourthmostcommonmalignant canceramongnon-QatariandQatarifemalesrespectively[15].

Despitetherelativelyhighprevalenceofthyroidcancer,the syn-chronousco-occurrenceofmultiple,distinctsub-typesofprimary thyroidcarcinomasisuncommon.Intheliterature,upto2017,very fewcasesofsynchronousPTCandFTChavebeenreported, includ-ingthreewithadditionalmedullarycarcinoma,onewithadditional undifferentiatedcarcinoma[3–6,16,17], andin one patient, fol-licularcarcinoma,anoccultpapillarycarcinomaandamedullary carcinoma[7].

Table1depictsthesummaryofcharacteristicsofoursixpatients withconcurrentFTCandPTC.Intermsofage,threeofourpatients agreewiththeagerangeofthepublishedliterature;however,one patientwas31yearsold,youngerthanthemeanage.Asfor inva-siveness,amongthesixcasesweobserved,thePTCdidnotexhibit lymphatic,peri-neuralorangio-invasiveness;however,theFTCin twooutofthesixpatients(Cases3and4)hadlymphatic invasive-ness,andinonepatient,itshowedangioinvasion(Case2).

Intermsoforigin,differentiatedthyroidcarcinomas,e.g.,PTC and FTC originate from follicular epithelial cells derived from medianendodermalanalogues[18].Whilstthesynchronous coex-istence of more than one type of thyroid cancer could be a coincidence,several theorieshave beenpostulated aspotential explanations for such synchronous coexistence. These include propositions that theymight be linkedto thepresence of RET protooncogenemutationinbothpapillaryandmedullarythyroid cells[19];‘commonstemcelltheory’[20];orcommontumorigenic stimulussuchasradiationexposurethatpromotesthemalignant transformationofbothendodermalandneuralcrest-derivedcell lines[21].Reportsalsopostulatethatthepathogeneticmechanisms ofhybridtumorsincludecollisiontheorythatproposes simultane-ousmultifocaloriginfromdifferentcellclones[22],suggestingthat twoindependenttumoursarelocatedinthesamelesionbysimple coincidence[18];orhostagetheorythatproposesthat adenoma-tousareasaresequestratedbyanothertumourtype,thoughthe exactetiologyiselusive[1].Wherecomponentswereseparated bynormalthyroidtissue,otherssuggestedthattheoccurrenceof e.g.,concurrentMTC/PTCismostlyasimplereflectionofincidental papillarymicrocarcinoma,andthatconcurrentMTCandPTCinthe samethyroidshouldbeconsideredascoincidental[18].Interms oflaterality,fiveofourcaseshadboththeFTCandPTCinthesame lobe.Inaddition,Case4hadPTCinbothlobes.Likewise,threeof ourpatients(Cases2,4and5)hadanFTCandamicroPTCinthe samelobe(PTCmeasuringfrom0.3–1cm)suggestingthatthePTC inthesecaseswasincidental.

Asforthepathologicalassessment,allthepatientspresented inthiscaseserieswereexaminedbythesamepathologistatthe samelaboratoryinthesameinstitution,inagreementthat cau-tiousandvigilantpathologicalassessmentiscriticalindisclosing suchpatternsofpathology.Suchvigilanceisreflectedinour pathol-ogyassessmentofthiscaseseriesthatinvolvedundertakingmany ultra-thinsectionsthatenabledthedetectionofmicroPTC.

Asregardstostagingandriskprediction,inlinewithothers,we undertookAJCCstagingsystemandATAstratificationprediction systemastheyarethebestpredictorsofmortalityandrecurrence respectively[23].WealsoemployedtheAJCC8theditionthatbetter differentiatesdifferentiatedthyroid carcinoma(DTC)risk recur-rencefor earlystages ofdiseasecomparedwiththe7th edition [24].

In termsof treatment, prognosisand survival, weinstigated prompttreatment,andfourofsixpatientswerecuredfromthe disease,inagreementwiththatDTCisusuallycurablewhen discov-eredatanearlystage[25],andthatthyroidmalignancieshavegood long-term prognosis,as earlyand appropriate treatmentyields goodresults[26].Likewise,withfullpreoperativeevaluationand stringentfollow-upaftersurgeryatourtertiarycareinstitution,for

fourpatientsinthisseries,weobservednorecurrenceandgood survival,insupportthattheprognosisforDTCisexcellentafter appropriatesurgicaltreatment,thoroughpreoperativeassessment andstrictpostoperativefollow-up[27].Twoofourpatients trav-elledoutofthecountryandwerelosttofollowup.InQatar,the 3-yearsurvivalfrommalignantthyroidcancerduringtheperiod 2013–2015was90.0%(47.3–98.5%)[15].Ourfindingssupportthat theprognosisofdifferentiatedthyroidcarcinomaisfavorable,with a10-yearsurvivalrateof80–95%[28],andthatearlierdetection ofsmalldifferentiatedthyroidcancerwithlessextensivedisease andstandardizationoftreatmentmaycontributetothedecreased disease-specificmortalityofsuchpatients[29].

4. Conclusions

Thepatientspresentedinthiscaseserieshaddifferent ethnici-ties,andallhadconcurrentFTCandPTCinthesamethyroidlobe.No apparentcausewasfound.Fourofthesixpatientswerecured,with norecurrenceandgoodsurvival,whilsttheremainingtwopatients travelledoutofthecountryandwerelosttofollowup. Endocrinolo-gistsandpathologistsshouldbevigilant,awareofandsuspiciousto thepossiblesimultaneousoccurrenceofthesetypes.Giventhevery fewcasesreportedintheliterature,furthersearchfortheunusual simultaneousoccurrenceofFTCandPTCiswarranted.

DeclarationofCompetingInterest Nothingtodeclare.

Sourcesoffunding Nothingtodeclare. Ethicalapproval

Approvedbymedicalresearchcenter,HamadMedical Corpora-tionreferencenumber(MRC17256/17).

Consent

Writteninformedconsentwasobtainedfromfourpatientsfor publicationofthiscasereportandaccompanyingimages.Acopyof thewrittenconsentsisavailableforreviewbytheEditor-in-Chief ofthisjournalonrequest.

Twopatientstravelledoutofthecountryaftersurgery.Written informedconsentwasnotobtainedfromthesepatients.Theheadof ourmedicalteamhastakenresponsibilitythatexhaustiveattempts havebeenmadetocontactthefamilyandthatthepaperhasbeen sufficientlyanonymisednottocauseharmtothepatientsortheir families.Acopyofasigneddocumentstatingthisisavailablefor reviewbytheEditor-in-Chiefofthisjournalonrequest.

Authorcontribution

Abdelrahman Abdelaal: Conceptualization, Data curation, Investigation, Methodology, Project administration, Writing -review&editing.WalidElAnsari:Conceptualization,Data cura-tion,Investigation,Methodology,Projectadministration,Writing -originaldraft,Writing-review&editing.Abdelrahman Abus-abeib:Datacuration,Writing-review&editing.HananFarghaly: Datacuration,Validation,Writing-review&editing.Abdelhakem A.M.Tabeb:Datacuration,Writing-review&editing.Allauthors readandapprovedthefinalmanuscript.

Registrationofresearchstudies

NotfirstinMan,henceUINnotrequired. Guarantor

WalidElAnsari:welansari9@gmail.com. Provenanceandpeerreview

Notcommissioned,externallypeer-reviewed Acknowledgements

Theauthorswishtoacknowledgethepatientsincludedinthis report.TheauthorsalsoacknowledgeDrsMSAl-HassanandM Ziriefortheconstructivecommentsonthepaperthathelpedto improveitscontent.

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