Carcinoma of the thyroid professor Ravi kant.ppt

Carcinoma of the thyroid refers to cancer of the thyroid gland. There are several types of thyroid cancer, including:

1. Papillary thyroid carcinoma (PTC): Most common type, often curable.
2. Follicular thyroid carcinoma (FTC): Second most common type, may be more aggressive.
3. Medullary thyroid carcinoma (MTC): Arises from parafollicular cells, associated with genetic syndromes.
4. Anaplastic thyroid carcinoma (ATC): Rare, aggressive, and often fatal.
5. Hurthle cell carcinoma: A variant of follicular carcinoma, may be more aggressive.

Symptoms may include:

- Lump or nodule in the neck
- Hoarseness or voice changes
- Difficulty swallowing
- Pain in the neck or throat
- Swollen lymph nodes

Treatment options depend on the type and stage of cancer and may include:

- Surgery (thyroidectomy)
- Radioactive iodine therapy
- Radiation therapy
- Chemotherapy
- Targeted therapy

Early detection and treatment can improve outcomes.

1. CARCINOMA THYROID:
DIAGNOSIS AND MANAGEMENT
Professor Ravi Kant

2. • Carcinomaofthethyroidglandisanuncommoncancer,but
nonetheless,isthemostcommonmalignancyofthe
endocrinesystem(90%ofallendocrinecancers).
• Constitutelessthan1%ofallhumanmalignanttumors

3. Pathologicalclassificationofmalignantthyroidneoplasms.
A.Carcinoma:
1.Papillaryadenocarcinma
a. Purepapillaryadenocarcinoma
b. Mixedpapillaryandfollicularcarcinoma
c. Papillarymicrocarcinoma
d. Diffusesclerosingcarcinoma
2.Follicularcarcinoma
a. Purefollicularcarcinoma
b. Clearcellcarcinoma
c. Hurthle(Oxyphil)cellcarcinoma

4. 3.Medullarycarcinoma
4.Undifferentiatedcarcinoma
B.OtherMalignanttumors
1. Lymphoma
2. Sarcoma
3. Fibrosarcoma
4. Epidermoidcarcinoma
5. Mucoepidermoidcarcinoma
6. Metastatictumor

5. Clinicalandinvestigativeworkupofapatientwith
suspectedthyroidcancer
Goal:Toidentifythosepatientswhohaveaparticularlyhighrisk
formalignancyandtoeffectivelymanagethosepatientswho
harbormalignantlesions.

6. • MCpresentationsolitarynodule(90%)withorwithout
adenopathy.
• Fixationofmasstotrachea,unusualfirmness,recentgrowth,
symptomsofdysphagia,hoarsenessandpresenceofenlarged
lymphnodesclearlysuggestthepossibilityofthelesion
beingmalignant.

7. • Cancerismorelikelyinanoduleif:
a) Malesexorchildren
b) Historyofpreviousradiationexposure
c) Age>60yrs
d) Coldnodule
e) Inapatientwithgrave’sdisease
f) familyhistoryofMEN

8. 1.Fine needle aspiration cytology
• Gold standard for diagnosis of thyroid carcinoma and nodal
metastasis.
• Fairly accurate except in follicular carcinoma
• Sensitivity ranges from 65-98% and specificity 52-100%.

9. 2.Ultrasonography
• Solidvscystic
• CanhelpinUSGguidedFNAC
• Evaluationofrecurrentthyroidcancerinthethyroidbedand
inregionallymphnodes
featuress/omalignancy.
- Hypoechogenicity
- Microcalcification
- Thick,irregularorabsenthalo
- Irregularmargins
- Invasivegrowth
- regionallymphadenopathy,and
- higherintranodularflow

10. 3.Serum calcitonin
• ThispolypeptideisproducedonlybyCcellsandits
measurementissensitive,accurateandconsistenttoadegree
thatmakesitpossibletodiagnoseMTCassmallas1mm.
• Anelevatedserumcalcitonininthepresenceofthyroidmass
ishighlys/omalignancy;whileanegativetestmakesthe
diagnosisofMTChighlyunlikely.

11. 4.Serumthyroglobulin
• Reliablemarkerofpersistent,recurrentormetastaticdiseases
• Lowpreoperativethyroglobulinlevelshavebeensuggested
tobeassociatedwithlessdifferentiatedtumorsandhavinga
poorprognosis.
• Afterneartotalortotalthyroidectomy,thyroglobulinlevels
falldownbelow5-10ng/mlbypostopday25(HalfLife65
hrs).

12. 5. Isotopeimaging
- I
131
,I
133
,Tc
99m
pertechnetate
- Thallium201chloride(
201
TL)
99m
Tcmethoxy
isobutylisonitrite(
99m
Tcsestamibi)
-
99m
Tc1,2-bisethane(
99m
TcTetrofosmin)
- Indium111octreotide
- Fluoro-18-deoxyglucose

13. Isotopeimaging(cont.)
• 80-85%ofallthyroidnodulesarehypofunctionalbutonly
10-15%ofhypofunctionalnodulesaremalignantsoscanning
hasalowspecificity.
• Importantmodalitytodetectcancerrecurrenceand
metastasesinthepostoperativeperiod.
• Ablationofanyremnantbyradioiodineandwithdrawalof
supplementarythyroidhormonewillincreasethelevelsof
TSHandhencetheabilityofthemetastasistopickup
radioiodineandconsequentlytheirchancesofbeingpicked
upinthescan.

14. 6.X-rayneck
• Airwaydisplacementandcompression
• Finestippledcalcificationinpapillarycarcinoma
• Densecalcificationandcalcifiednodesinmedullary
carcinoma

15. 7.CTandMRI
• Extrathyroidtumorextensionand/orinvasion
• Destruction,infiltrationordisplacementoflarynx,trachea,
esophagus,carotids
• Retrosternalextension
• Canassesscervicaladenopathy
• Can locate local and distant metastatic deposits.
• CT has a advantage because of its wide availability,
familiarity and lower cost.

16. 8.Geneticmarkersinthyroidcancer
• RET/PTC
• RASmutations
• Inactivatedmutationsofp53
• ThyroglobulinmRNA

17. PRIMARYTREATMENT
Papillarythyroidcarcinoma(PTC)
• MinimalPTCsaredefinedascancerssmallerthan1cm,
whichdonotextendbeyondthethyroidcapsuleandarenot
metastaticorangioinvasive.
• Deathrate0.1%andrecurrencerate5%.
• Unilateraltotallobectomymaybeanappropriate
definitiveprocedure.

18. Papillarythyroidcarcinoma(PTC)(cont.)
• Totalorneartotalthyroidectomyisthepreferredoperation
forhighriskpatientswithPTC.
• OpinionsdifferinlowriskPTC(Hemivstotal)Mostof
thesepatientshaveanexcellentprognosisaslongasgross
tumoriscompletelyresected.Somesurgeonsadvocateless
thanacompletethyroidectomytoavoidhypoparathyroidism
andrecurrentlaryngealnerveinjury.

19. Papillarythyroidcarcinoma(PTC)(cont.)
• Argumentsinfavouroftotalthyroidectomy
- Multifocaldisease
- facilitatespostoperativeuseof
131
Itoablateresidual
thyroidtissueandtoidentifyandtreatresidualor
distanttumor.
- Increasesthyroglobulinsensitivityasaindicatorof
residualdisease.

20. Papillarythyroidcarcinoma(PTC)(cont.)
• Shouldremoveallenlargedlymphnodesincentraland
lateralneckareas.Inthecentralneck,removalisessential
becausereoperationsinthisareadifficult.Prophylactic
lateralneckdissectionnotrecommended;whenlymphnodes
found,modifiedRNDshouldbedone.

21. FollicularandHurthlecellneoplasms
• Typically,FNAcytologicfindingsarereportedas
“indeterminateorsuspiciousforfollicularor
Hurthlecellneoplasm”.About80%offollicular
andHurthlecellneoplasmarebenign.
• Mostsurgeonsrecommendatotalthyroid
lobectomywithisthmusectomyforfollicularor
Hurthlecellneoplasm.Whenthelesionisbenign,
nofurthertherapyisneeded;whenthetumoris
malignant,completion(total)thyroidectomymay
beindicatedtofacilitatesubsequentradioactive
iodine(RAI)scanningandtherapy.

22. Follicular(cont.)
• SomecliniciansuseRAItoablatetheresiduallobe,in
asmuchasfollicularcarcinomasarerarelybilateral.
• Whenfollicularcarcinomaisminimallyinvasiveand
characterizedonlybylimitedcapsularinvasion,lobectomy
islikelytoprovidedefinitivetherapy.

23. Follicular(cont.)
• Ipsilaterallymphnodemetastaticlesionsoccurinonly
about10%ofpatientswithfollicularthyroidcancer(FTC)
andinabout25%ofpatientswithHurthlecellcancer.
Enlargedlymphnodesinthecentralneckareashouldbe
removed.Afunctionallateralneckdissectionisindicated
forpatientswithclinicallypalpablenodes

24. Stage Papillary or follicular Medullary, any
age
Anaplastic, any
age
Age < 45 yr Age > 45
yr

I M0 T1 T1 -
II M1 T2-3 T2-4 -
III - T4 or N1 N1 -
IV - M1 M1 Any
Staging System for Thyroid Carcinoma
Established by the American Joint Committee on Cancer

25. Riskgroupassignment
EORTC:
Ageinyears:+12ifmale,+10ifmedullary,+10ifpoorly
differentiatedfollicular,+45ifanaplastic,+10ifextending
beyondthyroid,+15ifonedistantmetastasis,+30ifmultiple
distantmetastasis.
AMES:
Highriskiffemaleolderthan50y,maleolderthan40y,male
olderthan40yrs,tumor>5cm(ifolderage),distantmetastases,
substantialextensionbeyondtumorcapsule(follicular)orgland
capsule(papillary).

26. Riskgroupassignment(cont.)
AGES:
0.5xAgeinyrs.(if>40),+1(ifgrade2),+3(ifgrade3or4),+1
(ifextrathyroidal),+3(ifdistantspread),+0.2xmax.tumor
diameter.
MACIS:
3.1(ifage<39yr)or0.08xage(ifage>40yr),+0.3xtumorsize
(incm),+1(ifincompletelyresected),+1(iflocallyinvasive),+3
(ifdistantmetastasespresent).

27. • Lymphnodemetastaticlesionsatthetimeofinitial
examinationdonotincreasetheriskofdeathfromPTCbut
doincreasetheriskoflocalandregionalrecurrence.Initial
nodalmetastaticdiseaseinMTCpredictsahigherriskof
recurrenceanddeath.
• Severalrarethyroidcancerhistologicsubtypesmay
indicateaworseprognosis.TheseincludetheHurthlecell
(oxyphilic)tallcellandcolumnervariantsofPTCand
possible,thediffusesclerosingvariant.

28. • DNAaneuploidydoesnothaveprognosticvalueinPTCor
typicalFTCbutmaypredictsignificantlyincreased
mortalityinoxyphilicFTC.
• Adjuvanttreatmentandclosefollow-upcanthenbe
targetedtohighriskpatients,whereasalessintensive
interventionalapproachcanbeusedinlowriskpatients.

29. Adjuvanttherapy
1.Thyroidhormone:
• GrowthofFCDCcellsisTSHdependentsoadministration
ofsupraphysiologicdosesofthyroidhormonetosuppress
serumTSH.
• Longtermlevothyroxinesuppressivetherapymayhave
adverseeffectonboneandtheheart,includingaccelerated
boneturnover,osteoporosisandAF.

30. Adjuvanttherapy(cont.)
• Consequently,manyexpertsmaintainthatlongterm
completeTSHsuppression(<0.01to<0.1Iu/ml)should
bereservedforhighriskpatients;LessdegreeofTSH
suppressionwillsufficeformostpatientswithPTC
classifiedaslowrisk(0.1-0.4Iu/ml)

31. Adjuvanttherapy(cont.)
2. RadioiodineRemnantablation(RRA)
• Definedas“thedestructionofresidual
macroscopicallynormalthyroidtissueaftersurgical
thyroidectomy”.
• Usedasanadjuncttosurgicaltreatmentwhenthe
primaryFCDChasbeencompletelyresected.

32. Adjuvanttherapy(cont.)
• ThreePotentialadvantages(RRA):
a)
131
Imaydestroymicroscopiccancercells
b)Subsequentdetectionofpersistentorrecurrentdiseaseby
radioiodinescanningisfacilitated.
C) AfterRRA,thesensitivityofserumTgmeasurements
isimprovedduringfollowup
• IssueofRRAinlowriskpatientsremainsunsettled.

33. Longtermfollowup
(I).Thyroglobulin
• Highly specific tumor marker for differentiated thyroid
cancer.
• Level should be <2 ng/ml after surgery and ablation.
• Most useful in patients with high risk FCDC when TSH
level is high after either levothyroxine withdrawal or rh
TSH administration.

34. Longtermfollowup
(II)Diagnostic scanning
• Levothyroxinediscontinuedfor6weeksbeforescan;T3
givenduringfirst4weeks(TSHshouldbe>25Iu/ml)
•
131
IWBSgenerallyperformed48-72hrs.aftergiving
2-5mCiof
131
I

35. Diagnostic scanning (cont.)
• AblativedosesofRAI(30-150mCi)aregivenwhen
functioningremnantsinthethyroidbed;higherdoses
whenmetastaticdisease.
• Posttreatmentscan4-10daysaftertherapeuticdose.
• Problems
- Unpleasant symptoms of hypothyroidism
- Poor patient compliance
- Severe pulmonary or cardiovascular disease
- Intracranial mets

36. Recombinantthyrotropin
• HighlypurifiedrecombinantformofhumanTSH
synthesizedinachinesehamsterovarycellline,longerhalf
life.
•
131
IWBSresultswereconcordantbetweenrhTSH
stimulatedandlevothyroxinewithdrawalphasesinmostof
thepatientsinvariousclinicaltrials.
• rhTSHissafeandeffectivemeansofstimulating
131
I
uptakeandserumTglevelsinpatientsundergoing
assessmentforcancerrecurrence.Nosymptomsof
hypothyroidisminthisgroup.

37. III.Additionalimagingstudies
• HighserumTglevelsbutnegativeWBS
• Pulmonarymetastaticlesions-chestX-rayorCT
Bonemetastasis-conventionalradiographicbonesurveyor
bonescan.
Intracranial,intraabdominalmets-CT/MRI
Alternativescanslikethallium,sestamibi,Tetrofosminor
fluorodeoxyglucosePETscan.
InpatientswithanincreasedserumTglevelandnegative
131
IWBS
someauthoritieshaveadministeredalargetherapeuticdoesof
131
I
withoutanyadditionalimagingprocedures

38. Persistentorrecurrentdisease
(I)Secondarysurgicalintervention
- Localrecurrence
- Bulkymediastinallesions(when
131
Iisineffective)
- Focalpulmonaryorribmetastaticlesion

39. (II)Radioactive iodine
- Nodal metastatic lesions not large enough to excise
- Locally recurrent invasive FCDC after surgical
resection.
- Diffuse lung metastatic growths
S/E:Nausea,Vomiting
Salivaryglanddamage
Bonemarrowdepression(anaemia,leukopenia,thrombo
cytopenia)
Smallincreaseinbladderandbreastcancer
Transientreductioninspermcount

40. (III)Externalirradiation
- Anaplasticthyroidcancers
- Lymphomaofthethyroid
- PostoperativepatientswithFCDCwhohavegross
evidenceoflocalinvasion

41. MedullaryThyroidcarcinoma
• Representsmalignanttransformationofneuroectodermally
derivedparafollicularCcells.
• 75%aresporadicand25%arehereditary.

42. Sporadic
Surgicaltreatmentshouldincludetotalthyroidectomy,central
compartmentlymphnodedissectionandipsilateralmodified
radicalneckdissection.
Riskfactorsforrecurrenceanddeathincludetumorsize,
preoperativecalcitoninlevel,advancedage,extrathyroidtumor
extension,progressionofcervicalnodaldiseasetothe
mediastinum,extranodaltumorextensionandincompletetumor
excision.

43. Sporadic(cont.)
• Serumcalctoninlevelsshouldbemeasured8-12wks.
Postoperativelytoassessthepresenceofresidualdisease.
Forresiduallocaldisease-USGofneck
Formetastaticlesions-
CTandMRI
Scanningwithsestamibi,radioiodinatedMIBG,Octreotide
and
131
IantiCEAantibody
Laparoscopicliverbiopsy

44. Hereditarymedullarycarcinoma:
• MENtypeIIA,MENIIBandisolatedfamilialMTC;
MENIIAismostcommon.
• MENIIAincludesMTC(in100%ofpatients),
pheochromocytomaoradrenalmedullaryhyperplasia(in
50%)andhyperparathyroidism(in35%).

45. Hereditarymedullarycarcinoma:
• MENIIBincludesMTC(morevirulentandatearlyage),
pheochromocytoma,Marfanoidhabitus,mucosalneuromas,
ganglioneuromatosisofGIT.
• FamilyMTCisdefinedbypresenceof4ormorecasesina
familywithoutotherassociatedendocrinopathy.

46. Hereditary(cont.)
• SpecificgermlinemutationsofRETproto-oncogenewhich
codesfortyrosinekinasereceptor.
• Genetictestingshouldbeginbynolaterthanage6yrsin
MENIIAandshortlyafterbirthinMENIIBfamilies.

47. Hereditary(cont.)
• Currentstandardofcareistorecommendsurgical
treatmentforMTCfamilymembersdiagnosedwith
appropriateRET mutations.
• Thistreatmentmaybeaccomplishedasearlyasage2
years; allshouldbescreenedpreoperativelyfor
pheochromocytoma.
• Prophylactictotalthyroidectomyandcentral
compartment lymphnodedissection.

48. Anaplasticthyroidcarcinoma
• Highlyaggressivetumor
• 5
th
-6
th
decadesoflife
• Rapidlyexpandingthyroidmasswithhoarseness,
dyspnea, dysphagia,cervicalpain,tracheal
obstructionand metastasis.
• Maybemultipleandbilateral;shortdurationof
symptoms.
• Histologically3predominantfeatures:spindlecell,
giant cellandsquamoidcell.

49. • Treatmentcontroversial.Surgicalbiopsymaybe
necessary forconfirmationofthediagnosisand
protectionofairway althoughsomesurgeonsattempt
primaryresection.Valueof prophylactictracheostomy
isuncertain,mayleadtolocal wound healing
complicationsthatcouldpreventordelay useof
postoperativeexternalbeamradiotherapy.

50. • Theuseofcombinationtherapiestoinclude
preoperative irradiationand chemotherapy
(doxorubicin,cisplatin, bleomycin,vincristinand5-
FUinvariouscombinations) followed by
aggressivelocaltumorresectionmayyieldan
increaseddurationofsurvival.