Thyroid_Cancer - PTabrizian

8/9/2019 Thyroid_Cancer - PTabrizian

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Parissa TabrizianParissa Tabrizian


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55 F referred to endocrine surgery for a palpable55 F referred to endocrine surgery for a palpable

thyroid nodule on physical exam by PMDthyroid nodule on physical exam by PMD

No dysphonia, dysphagia, odynophagia, change inNo dysphonia, dysphagia, odynophagia, change invoice.voice.

No smoking history.No smoking history.

No fevers, chills, weight loss.No fevers, chills, weight loss.

No hx of radiation to neckNo hx of radiation to neck

No PMHx/PSHx, no FHx caNo PMHx/PSHx, no FHx ca

Exam: palpable R thyroid noduleExam: palpable R thyroid nodule


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Labs: TSH, PTH, T4, T3, TBG wnlLabs: TSH, PTH, T4, T3, TBG wnl

Thyroid US: 2 nodules R thyroid (


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Management Guidelines of thyroid nodules?Management Guidelines of thyroid nodules?

Total vs. Hemithyroidectomy?Total vs. Hemithyroidectomy?

Extent of surgery for small papillary ca ?Extent of surgery for small papillary ca ?

Use of radioactive iodine post thyroidectomy?Use of radioactive iodine post thyroidectomy?

Use of thyroxine suppression therapy?Use of thyroxine suppression therapy?

Long Term Follow upLong Term Follow up


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Large population studiesLarge population studies--Framingham study showed clinicallyFramingham study showed clinically

significant nodules in 6.4% F and 1.5% M ages 30significant nodules in 6.4% F and 1.5% M ages 30--59.59.

UltrasoundsUltrasounds-- 20% to 76% F had at least one thyroid nodule20% to 76% F had at least one thyroid nodule

Autopsy surveys show up to 35% clinically silent carcinomaAutopsy surveys show up to 35% clinically silent carcinoma

Nodules: 9 million adults in the USNodules: 9 million adults in the US

New nodules appear at a rate of 0.8%/yrNew nodules appear at a rate of 0.8%/yr

Thyroid cancer is rare 4/100,000 perThyroid cancer is rare 4/100,000 per

1% of all malignancies1% of all malignancies

0.5% of all cancer deaths0.5% of all cancer deaths--mortality rates decreasedmortality rates decreasedOverall 10 year survival rate papillary/follicular ca: 93 vs.Overall 10 year survival rate papillary/follicular ca: 93 vs.

85% (30yrs mortality local:12%, distant:43%)85% (30yrs mortality local:12%, distant:43%)

Recurrence rate 40 yr 35% (2/3 within the first decade afterRecurrence rate 40 yr 35% (2/3 within the first decade after

initial treatment)initial treatment)


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Benign (>90%):Benign (>90%):

Multinodular goiterMultinodular goiter

Hashimotos thyroiditisHashimotos thyroiditis

Simple or Hemorrhagic cystsSimple or Hemorrhagic cystsFollicular adenomasFollicular adenomas

Subacute thyroiditisSubacute thyroiditis

Malignant (6%):Malignant (6%):

Papillary, Follicular cancer ( 93%)Papillary, Follicular cancer ( 93%)

Medullary (5%)Medullary (5%)

Hurthle cellHurthle cell

Anaplastic (1%)Anaplastic (1%)

Lymphoma or metsLymphoma or mets


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History of head and neck radiationHistory of head and neck radiationExposure to radiation, especially in childhood is associatedExposure to radiation, especially in childhood is associated

with increased prevalence of thyroid nodules andwith increased prevalence of thyroid nodules and

malignancy 2%/yr increased risk with peak incidence 15malignancy 2%/yr increased risk with peak incidence 15--2020

yearsyears

Presence of a nodule in a child is 2x as likely to bePresence of a nodule in a child is 2x as likely to becarcinomacarcinoma

Family History of MCT or MEN 2Family History of MCT or MEN 2

Age < 20 or > 70 yearsAge < 20 or > 70 years

MaleMale

Growing noduleGrowing nodule

Firm or hard consistencyFirm or hard consistency

Cervical adenopathyCervical adenopathy

Fixed noduleFixed nodule

Persistent hoarseness, dysphonia, dysphagia, or dyspneaPersistent hoarseness, dysphonia, dysphagia, or dyspnea


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SignificantSignificant selectionselection biasbias inin surgicalsurgical seriesseries

NorthNorth CarolinaCarolina studystudy inin aa communitycommunity hospitalhospital ptsptswithwith nodulesnodules werewere referredreferred toto surgerysurgery withoutwithout

biopsybiopsy andand 66..55%% ofof excisedexcised nodulesnodules werewere

carcinomascarcinomas

Catania,Catania, ItalyItaly 23272327 ptspts withwith nodulesnodules werewere

evaluatedevaluated byby FNAFNA andand ofof thosethose 391391 werewere selectedselected

forfor surgerysurgery.. CarcinomasCarcinomas werewere foundfound inin 2828 whichwhich

waswas 55%% ofof totaltotal


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Complete history and physical examComplete history and physical exam

Thyroglobulin levels are nonThyroglobulin levels are non--specific/nonspecific/non--sensitivesensitive

USUS: Is it truly a nodule that corresponds to the exam?: Is it truly a nodule that corresponds to the exam?

Is the nodule > 50% cysticIs the nodule > 50% cystic

Is it located posteriorly in the thyroid gland?Is it located posteriorly in the thyroid gland?

Other nodules?Other nodules?

Position/shape/size/margins/content/echogenic/vascuPosition/shape/size/margins/content/echogenic/vascular pattern/risk of malignancylar pattern/risk of malignancy

1919--67% of nodules detected in randomly selected67% of nodules detected in randomly selected

individualsindividuals


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FNAFNA::

Sensitivity/SpecificitySensitivity/Specificity:: 8383%%//9292%%

Simple,Simple, safesafe officeoffice procedureprocedure

TissueTissue samplesample obtainedobtained byby 2525 gaugegauge needleneedle

WithWith experienceexperience adequateadequate samplesample maymay bebe obtainedobtained inin

9090 --9797%% ofof aspiratesaspirates ofof solidsolid nodulesnodules

FalseFalse negativenegative raterate (FNA(FNA benignbenign butbut nodulenodule turnturn outout

malignant)malignant) isis 00--55%% usuallyusually duedue toto samplingsampling errorerrorFalseFalse positivepositive ratesrates (malignant(malignant butbut turnsturns outout benign)benign)


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MostMost commoncommon thyroidthyroid cancercancerAfterAfter radiationradiation exposure,exposure, RETRET protoproto--oncogeneoncogeneOverexpressionOverexpression ofof TRK,TRK, MAPK,MAPK, DNADNA hypermethylation,hypermethylation, andand activatingactivating

mutationsmutations ofof RASRAS

BestBest prognosisprognosis:: 55%% mortalitymortality atat 2020 yearsyears ifif nono locallocal invasioninvasionLateralLateral aberrantaberrant thyroidthyroid cervicalcervical lymphlymph nodenode infiltratedinfiltrated withwith

metastaticmetastatic thyroidthyroid cancercancer

2020--5050%% cervicalcervical lymphlymph nodenode involvementinvolvement (( USUS identificationidentification 2020--3131 %%))

MicrometastasisMicrometastasis upup toto 9090 %%CanCan spreadspread toto lunglung (also(also bone,bone, liver,liver, brain)brain)VeryVery rarerare conversionconversion toto anaplasticanaplastic typetype


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PsammomaPsammoma bodiesbodies:: laminatedlaminated calcifiedcalcified spheres,spheres, diagnosticdiagnostic ofof

papillarypapillary cancercancerCertainCertain histologicalhistological variantsvariants havehave higherhigher riskrisk ofof recurrencerecurrence::TallTall cell,cell, columnarcolumnar cell,cell, diffusediffuse sclerosingsclerosing cellcell


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RAS mutations, chromosomal rearrangements (PAX8RAS mutations, chromosomal rearrangements (PAX8

fused to PPARfused to PPAR--gammagamma--1)1)

Older population, advanced tumor stageOlder population, advanced tumor stage

Hurthle cell variant of FCCHurthle cell variant of FCC


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Neck imagingNeck imaging::

preop neck USpreop neck US

routine use of other imaging studiesroutine use of other imaging studies( CT/MRI/PET) not recommended( CT/MRI/PET) not recommended

Serum thyroglobulinSerum thyroglobulin::

routine preop measurement not indicatedroutine preop measurement not indicated


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Total thyroidectomyTotal thyroidectomy:: ++

Papillary foci are b/l in 60Papillary foci are b/l in 60--85% of patients85% of patients

55--10% recurrence rates for papillary ca after10% recurrence rates for papillary ca after

unilateral surgery for microcarcinomaunilateral surgery for microcarcinoma

Effectiveness of treatment with 131I and f/uEffectiveness of treatment with 131I and f/u

with serum Tg are highest with maximalwith serum Tg are highest with maximal

resectionresection


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Total thyroidectomy:Total thyroidectomy: --

Minimal benefit for more extensive surgeryMinimal benefit for more extensive surgery

Higher risk of hypoparathyroidismHigher risk of hypoparathyroidism

Higher risk of injury to recurrent laryngealHigher risk of injury to recurrent laryngeal

nervenerve

Tumor multicentricity seems to have littleTumor multicentricity seems to have littleprognostic significanceprognostic significance

If recurrence, usually those lesions are treatableIf recurrence, usually those lesions are treatable


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MostMost concensusconcensus guidelinesguidelines statestate::

ForFor papillarypapillary caca::

IfIf >> 11 cm,cm, oror mets,mets, oror extendsextends beyondbeyond

thyroid,thyroid, contralateralcontralateral disease,disease, oror hxhx ofof

irradiationirradiation totaltotal thyroidectomythyroidectomy

IfIf


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RegionalRegional lymphlymph nodenode metsmets atat timetime ofof

diagnosisdiagnosis::2020--9090%%

ConsiderationConsideration ofof routineroutine centralcentral--compartmentcompartment(level(level VI)VI) neckneck dissectiondissection inin papillarypapillary

ca/suspectedca/suspected HurtleHurtle caca

LateralLateral neckneck (( IIII--IV)IV) andand posteriorposterior triangletriangle (( V)V)LNLN dissectiondissection forfor nodalnodal diseasedisease reducesreduces

recurrencerecurrence andand mortalitymortality ratesrates..


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National Cancer Data Base (19851998)

52,173 patients with surgery for PTCSurvival estimated by Kaplan-Meier method, compared using log-rank tests

Cox Proportional Hazards modeling stratified by tumor size used to assessimpact of surgical extent on outcomes

Results: 43,227 (82.9%) underwent total thyroidectomy, 8946 (17.1%)

underwent lobectomy. For PTC1 cm, lobectomy resulted in higher risk of recurrence and

death (P = 0.04, P = 0.009)

1 to 2 cm lesions were examined separately: lobectomy again resulted

in a higher risk of recurrence and death (P = 0.04, P = 0.04).


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299299 casescases (( 19751975--20012001))

MultivariateMultivariate analysisanalysisRecurrentRecurrent local/distantlocal/distant metsmets associatedassociated

lymphlymph nodenode metsmets

bilateralbilateral tumortumor

sclerosantsclerosant variantvariant

TumorTumor sizesize (


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SpecificSpecific uptakeuptake intointo follicularfollicular cellscells

UndergoesUndergoes --decay,decay, releasingreleasing highhigh energyenergy

electronselectronsradiationradiation cytotoxicitycytotoxicity

GOALGOAL::

DestroysDestroys residualresidual thyroidthyroid tissue/decreasetissue/decrease

recurrence/mortalityrecurrence/mortality

IncreasesIncreases specificityspecificity ofof futurefuture scansscans forfor residualresidualcaca

ImprovesImproves sensitivitysensitivity ofof futurefuture TgTg screenscreen


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RestrictedRestricted toto patientspatientsstagestage IIIIII andand IVIV diseasedisease

stagestage IIII andand


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ForFor maximummaximum radioiodineradioiodine uptakeuptake afterafter

thyroidectomy,thyroidectomy, wantwant TSHTSH >>3030--5050 mU/LmU/L (no(no

controlledcontrolled study)study)

StopStop thyroxinethyroxine forfor 44--66 weeksweeks iatrogeniciatrogenic

hypothyroidismhypothyroidism

BecauseBecause liothyronineliothyronine hashas aa shortershorter tt11//22,, cancan givegiveuntiluntil 22 weeksweeks priorprior toto treatmenttreatment

AvoidAvoid iodinatediodinated contrastcontrast forfor CTCT forfor 11--33 monthsmonths priorprior

toto treatmenttreatment

LowLow idodineidodine dietdiet forfor 11--22 weeksweeks priorprior RIARIA

TheseThese samesame principlesprinciples applyapply toto radioiodineradioiodine

scanningscanning forfor f/uf/u


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Persistent disease and tumor stage cannot bePersistent disease and tumor stage cannot beidentified shortly after surgery when there is aidentified shortly after surgery when there is alarge thyroid remnantlarge thyroid remnant

Without RA, half of lung metastases in childrenWithout RA, half of lung metastases in childrencannot be identifiedcannot be identified

But:But: Transient loss of tasteTransient loss of taste

Acute and chronic radiationAcute and chronic radiation--induced parotitisinduced parotitis Sialadenitis with possible xerostomiaSialadenitis with possible xerostomia Transient testicular damageTransient testicular damage Side effects tend to be doseSide effects tend to be dose--relatedrelated


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11--33 months/months/66--1212 monthsmonths afterafter initialinitial ablationablation

IfIf negativenegative 9090%% 1010 yearyear relapserelapse--freefree survivalsurvival

IfIf consecutivelyconsecutively negativenegative xx22 >>9595%% 1010 yearyear

relapserelapse--freefree survivalsurvival

ConsensusConsensus guidelinesguidelines:: surveillancesurveillance scanningscanningbeyondbeyond thisthis periodperiod onlyonly indicatedindicated if if

clinical/diagnosticclinical/diagnostic findingsfindings occuroccur

WBSWBS


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ProducedProduced exclusivelyexclusively byby thyroidthyroid follicularfollicular cellscells

UsedUsed toto detectdetect residual,residual, recurrent,recurrent, oror metastaticmetastaticdiseasedisease (( levelslevels >> 22ng/mL)ng/mL)

MeasurementMeasurement everyevery 66--1212 monthsmonths inin totaltotalthyroidectomy,thyroidectomy, periodicperiodic inin hemythyroidectomyhemythyroidectomyandand totaltotal w/ow/o RIARIA

SensitivitySensitivity ofof 8585--9595%% forfor detectiondetection ofof diseasediseaseduringduring thyroidthyroid hormonehormone withdrawalwithdrawal

SensitivitySensitivity ofof 5050%% withwith TSHTSH suppressionsuppression oror

dedifferentiateddedifferentiated tumorstumors


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ReportedReported TgTg concentrationsconcentrations cancan bebe falselyfalselyloweredlowered byby autoAbsautoAbs thatthat bindbind TgTg andandpreventprevent detectiondetection byby immunoassaysimmunoassays

TheseThese antithyroglobulinantithyroglobulin AbsAbs areare presentpresent ininasas manymany asas 2525%% ofof ptspts withwith thyroidthyroid cancer,cancer,andand 1010%% ofof generalgeneral populationpopulation

MethodsMethods toto detectdetect TgTg mRNAmRNA areare inindevelopmentdevelopment thoughthough theirtheir utilityutility hashas beenbeenquestionedquestioned


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MetaMeta--analysisanalysis:: constantconstant suppressionsuppression ofof TSHTSH

(


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Thyroid_Cancer - PTabrizian