Increasing Diagnosis of Micro-Papillary Thyroid Cancer (

Increasing Diagnosis of Micro-Papillary Thyroid Cancer (<1 cm ) New Trends in Management

Vahab FatourechiVahab Fatourechi MDMD Mayo ClinicMayo Clinic

Tehran EMRI Tehran EMRI

20152015

Learning Objectives

• Recognize different clinical presentations of Recognize different clinical presentations of micropapillary cancer micropapillary cancer

• Be familiar with trends in less aggressive Be familiar with trends in less aggressive management of incidental occult papillary management of incidental occult papillary cancer cancer

• Short reference to 2015 ATA GuidelinesShort reference to 2015 ATA Guidelines

THYROID CANCER FREQUENCY MORTALITY

Papillary 85% 1-2% at 20 years

Follicular 11% 10-20% at 10 years

Medullary 3% 25-50% at 10 years

Anaplastic

1% 90% at 5 years

Surveillance Epidemiology and End Results. http://seer.cancer.gov/statfacts/html/thyro.htmlSurveillance Epidemiology and End Results. http://seer.cancer.gov/statfacts/html/thyro.html

• 1 patient in 1 patient in 100100 with PTC will die due thyroid cancer at 20 years with PTC will die due thyroid cancer at 20 years• 1 patient in 1 patient in 10001000 with low-risk PTC will die at 20 years. with low-risk PTC will die at 20 years.

NOT ALL THYROID CANCERS ARE EQUAL NOT ALL THYROID CANCERS ARE EQUAL

Papillary Cancer Cell Types Associated with Papillary Cancer Cell Types Associated with

Aggressive BehaviorAggressive Behavior

• Columnar cell PTCColumnar cell PTC• Insular cell PTCInsular cell PTC• Tall cell PTCTall cell PTC• Trabecular PTCTrabecular PTC• Higher grades of PTC : Grade 2-4 (majority are grade1)Higher grades of PTC : Grade 2-4 (majority are grade1)• Comment : Most of these present clinically and rarely Comment : Most of these present clinically and rarely

micro-papillarymicro-papillary

Thyroid Thyroid 97.5%97.5%

Low Risk Low Risk 99.9%99.9%

RELATIVE SURVIVAL RATES AT 5 YEARSRELATIVE SURVIVAL RATES AT 5 YEARS

Surveillace Epidemiology and End Results. Surveillace Epidemiology and End Results. http://seer.cancer.gov/statfacts/html/thyro.htmlhttp://seer.cancer.gov/statfacts/html/thyro.html

11 patient in patient in 10001000 affected with affected with low-risk thyroid cancer low-risk thyroid cancer and and treated treated will die due to thyroid will die due to thyroid cancercancer

Slow progression or Slow progression or regressionregression

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Cause-Specific Mortality Rates in FCDCCause-Specific Mortality Rates in FCDCMayo DataMayo Data

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II 1,360 1,360IIII 493 493IIIIII 399 399IVIV 32 32

II 1,360 1,360IIII 493 493IIIIII 399 399IVIV 32 32

n=2,284n=2,2841940-971940-97

P=0.0001P=0.0001

n=2,284n=2,2841940-971940-97

P=0.0001P=0.0001TNM stageTNM stageTNM stageTNM stage

No Change in Mortality over 6 Decades No Change in Mortality over 6 Decades in PTC (Mayo Clinic Data)in PTC (Mayo Clinic Data)

• 2444 2444 cases 1940-1999cases 1940-1999• No change in cause specific mortality No change in cause specific mortality • No change in tumor recurrence rateNo change in tumor recurrence rate• Remnant RA ablation did not change outcomeRemnant RA ablation did not change outcome• For low risk (MACIS <6) CSM 1% and recurrence For low risk (MACIS <6) CSM 1% and recurrence

15%15%

Hay ID, World J Surg 2002: 26;879Hay ID, World J Surg 2002: 26;879Endo Pract 2007 :13 521Endo Pract 2007 :13 521

Thyroid Thyroid CCarcinoma: arcinoma: 1992- 2014 Estimates 1992- 2014 Estimates

• Incidence increased from 20,000 to Incidence increased from 20,000 to 62,80062,800

• 1992 5/100,0001992 5/100,000• 2014 15 /100,000 2014 15 /100,000 • Almost all of increase is papillary thyroid Almost all of increase is papillary thyroid

cancer: over 95% of all thyroid cancerscancer: over 95% of all thyroid cancers• Deaths n=1850 , Not changedDeaths n=1850 , Not changed

Davis L,eta l JAMA Otolaryngol Head Neck Surg 2014;140: 317Davis L,eta l JAMA Otolaryngol Head Neck Surg 2014;140: 317

Increasing Incidence of Increasing Incidence of Thyroid Cancer WorldwideThyroid Cancer Worldwide

• ..

Rising Thyroid Cancer IncidenceRising Thyroid Cancer IncidenceOlmsted County Minnesota (Mayo data)Olmsted County Minnesota (Mayo data)

• Comparesd1990-1999 to 2000-2012Comparesd1990-1999 to 2000-2012• 7.1 /100000 7.1 /100000 Increased rate to Increased rate to 13.713.7• 53% asymptomatic incidental finding53% asymptomatic incidental finding• Neck imaging 36%, incidental for thyroid benign Neck imaging 36%, incidental for thyroid benign

disease Surgery 26%, found on routine exam 20%, disease Surgery 26%, found on routine exam 20%, investigation for unrelated symptoms12%investigation for unrelated symptoms12%

• Exclusion of incidental brings rate to Exclusion of incidental brings rate to 6.3%6.3%•

Brio JP et.al, Abstract ATA meeting Oct 2014Brio JP et.al, Abstract ATA meeting Oct 2014

Detection of ReservoirDetection of Reservoir


Widespread use of Widespread use of thyroid ultrasoundthyroid ultrasound Widespread use of Widespread use of thyroid ultrasoundthyroid ultrasound

Fine-needle aspiration Fine-needle aspiration for thyroid nodulefor thyroid nodule

Fine-needle aspiration Fine-needle aspiration for thyroid nodulefor thyroid nodule

Increased in Increased in CT/MRI use CT/MRI use Increased in Increased in CT/MRI use CT/MRI use

US-guided aspiration of US-guided aspiration of thyroid nodulesthyroid nodules

US-guided aspiration of US-guided aspiration of thyroid nodulesthyroid nodules

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Brito JP. Brito JP. BMJ BMJ 2013;347:f47062013;347:f4706


South Korean Experience in n South Korean Experience in n Routine Thyroid Cancer ScreeningRoutine Thyroid Cancer Screening

• In 1999 In south korea national cancer screening In 1999 In south korea national cancer screening program started thyroid was not a part but most program started thyroid was not a part but most provided added US of neck for small feeprovided added US of neck for small fee

• Diagnosis of thyroid cancer increased Diagnosis of thyroid cancer increased 15 fold15 fold

• 40,000 diagnosed in 2011, death rate annually 40,000 diagnosed in 2011, death rate annually 300-400300-400

• Death from thyroid cancer did not changeDeath from thyroid cancer did not change

H.S Ahn et al NEJM Nov 2014 :731:1765H.S Ahn et al NEJM Nov 2014 :731:1765

Thyroid-Cancer Incidence and Related Thyroid-Cancer Incidence and Related Mortality in South Korea, 1993-2011Mortality in South Korea, 1993-2011

Ahn et al: NEJM 371;19, 2004Ahn et al: NEJM 371;19, 2004

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Incidence ofIncidence ofpapillary thyroidpapillary thyroid

cancercancer

Thyroid-cancerThyroid-cancerincidenceincidence

Thyroid-cancer mortalityThyroid-cancer mortality

Thyroid Cancer ReservoirThyroid Cancer Reservoir

Harach HR. Cancer 1985;56:531-8Harach HR. Cancer 1985;56:531-8..

Sectioned thyroids from 101 autopsy specimens, 1-3 mm slices.Sectioned thyroids from 101 autopsy specimens, 1-3 mm slices. Found PTC in 36% of glands, no prior history of thyroid disease.Found PTC in 36% of glands, no prior history of thyroid disease. Speculated that if sectioned carefully enough, many more would Speculated that if sectioned carefully enough, many more would

have been found, perhaps all.have been found, perhaps all.

Incidental Thyroid Micro-cancer In Incidental Thyroid Micro-cancer In AutopsyAutopsy

• Argentina ; n=100,Argentina ; n=100,• 13.6% men , 7.3% women13.6% men , 7.3% women• Spain 5.3%Spain 5.3%• Bellarus 9.3%Bellarus 9.3%

• Greece: Greece: 7.7 %7.7 %

• Sweden: 8.6%Sweden: 8.6%

Cancer ;1989;64;1888Cancer ;1989;64;1888Martinez – Tello Cancer 1003; 71;4022Martinez – Tello Cancer 1003; 71;4022Fufrmanchuck AW Histopathology, 1993,4;319Fufrmanchuck AW Histopathology, 1993,4;319Mitselou, A , Anticancer research 2002 22;427Mitselou, A , Anticancer research 2002 22;427

Incidental Thyroid Micro-cancer In Incidental Thyroid Micro-cancer In AutopsyAutopsy

• Pub Med Search 2011Pub Med Search 2011• 21 countries, 7897 autopsies21 countries, 7897 autopsies• English literatureEnglish literature• 0.14 % MTC0.14 % MTC• 7.6% PTC 7.6% PTC all <0.5 cm no lymph nodes all <0.5 cm no lymph nodes

• ConclusionConclusion : : This should be considered in This should be considered in epidemiologic studies and screening epidemiologic studies and screening recommendationsrecommendations

Valle LE JCEM 2011 96: 109Valle LE JCEM 2011 96: 109

Incidental Micro cancer in Thyroidectomy Incidental Micro cancer in Thyroidectomy for Benign Diseasefor Benign Disease

• 15%15% Siassakos Singapore med J 2008Siassakos Singapore med J 2008

• 8.8%8.8% Femando ,Cylone Med J 2009Femando ,Cylone Med J 2009

• 2.2 % in GD 2.2 % in GD Anilam. Rev Med Schir Soc Med Nallasi 2008Anilam. Rev Med Schir Soc Med Nallasi 2008

• 12% 12% Bradley DP, Surgery 146: 2009Bradley DP, Surgery 146: 2009

• 9.3%9.3% Costamagna G , Surg 2013Costamagna G , Surg 2013

• 5.7 %5.7 % Bombil I, S Afr J Surg 2014Bombil I, S Afr J Surg 2014

• 26%26% Ergin AB, Amer J otolaryng, 2014,Ergin AB, Amer J otolaryng, 2014,

• 16.7% 16.7% Fink, Mod path 1996,9;816Fink, Mod path 1996,9;816

• 10%(GD10%(GD)) Karagulle E, Int Surg 2009;94;325 Karagulle E, Int Surg 2009;94;325

Mean 12%Mean 12%

Thyroid Incidental Micro-cancerThyroid Incidental Micro-cancer FDG- PET FDG- PET

• N= 2105N= 2105

• Focal uptake Focal uptake 1.7% 1.7% (35)(35)

• Confirmed PTC 8Confirmed PTC 8

• Malignancy 3 3% on PET PosMalignancy 3 3% on PET Pos

Prichard RS Ir med J ,2011:104;177Prichard RS Ir med J ,2011:104;177

Thyroid Cancer in Ultrasound ScreeningThyroid Cancer in Ultrasound Screening

• N=1140, Hong Kong N=1140, Hong Kong • No thyroid symptoms routine screeningNo thyroid symptoms routine screening• 44% nodules44% nodules• FNA in 258 patientsFNA in 258 patients• 2.3%2.3% FNA suspicious for malignancy FNA suspicious for malignancy• 1.2%1.2% Histologic PTC Histologic PTC• Conclusion: Conclusion: If routine screening is used If routine screening is used 4.24.2 million million

in USAin USA

Yuen AP Head and Neck 2011, 33;453Yuen AP Head and Neck 2011, 33;453


• If we assume only If we assume only 6%6% as prevalence of micro PTC:as prevalence of micro PTC:– Predicts Predicts 1818 million cases in population million cases in population– SEER database reports only SEER database reports only 0.50.5 million prevalence of all million prevalence of all

types and sizes of DTCtypes and sizes of DTC

– We have yet only seen the tip of the icebergWe have yet only seen the tip of the iceberg– In current practice, PTC will be the most rapidly growing In current practice, PTC will be the most rapidly growing

cancer diagnosis for years to come.cancer diagnosis for years to come.

Ross and Tuttle. Thyroid 24:3-6 2013Ross and Tuttle. Thyroid 24:3-6 2013

Likelihood of Death from Histologic Thyroid Likelihood of Death from Histologic Thyroid Cancer Cancer

• Estimated death 1780/year Estimated death 1780/year • with conservative estimate with conservative estimate 7 %7 % of USA population of USA population

(22)(22) million have micro PTCmillion have micro PTC• Thus likelihood of death from all thyroid cancer is Thus likelihood of death from all thyroid cancer is

79 79 per one millionper one million histologic thyroid cancer histologic thyroid cancer ((0.0079%)0.0079%)

• Almost all mortality is from clinical thyroid cancer Almost all mortality is from clinical thyroid cancer not occult. Mortality would be close to zero for not occult. Mortality would be close to zero for occult undiagnosed thyroid canceroccult undiagnosed thyroid cancer

Possible Causes of Increasing Possible Causes of Increasing IncidenceIncidence

• Radiation ExposureRadiation Exposure

• Iodine intakeIodine intake

• Obesity/DiabetesObesity/Diabetes

• Autoimmune DiseaseAutoimmune Disease

• Estrogen/ProgesteroneEstrogen/Progesterone

• Reduced smokingReduced smoking

• But most likely Increasing use of imaging technologiesBut most likely Increasing use of imaging technologies– OverdiagnosisOverdiagnosis

Variable Presentation of Micro PTCVariable Presentation of Micro PTC

• Found on thyroid surgery for benign diseaseFound on thyroid surgery for benign disease

• Occult nodule found on conventional imaging done for Occult nodule found on conventional imaging done for other purposesother purposes

• PET positivity thyroid done for other purposesPET positivity thyroid done for other purposes

• Less than 1 cm nodule palpable on a lean neck , usually Less than 1 cm nodule palpable on a lean neck , usually the isthmus the isthmus

• Evidence of neck node metastases with negative thyroid Evidence of neck node metastases with negative thyroid US or mica noduleUS or mica nodule

• Evidence of distant metastases with benign appearing US Evidence of distant metastases with benign appearing US or micro nodule in thyroidor micro nodule in thyroid

• ..

Incidental PTC and benign thyroid Incidental PTC and benign thyroid nodulenodule

Case 1Case 1

AA BB

FNA shows:FNA shows:A, PTCA, PTCB, Follicular neoplasmB, Follicular neoplasm

Lt LongitudinalLt Longitudinal

Case-2Case-2

• ..66 year old lady a palpable 66 year old lady a palpable level IIb Rt FNA positive level IIb Rt FNA positive for PTCfor PTC US 4 mm hypoechoic noduleUS 4 mm hypoechoic nodule Rt lobe no suspicious Rt lobe no suspicious features. 2.3 cm nodulefeatures. 2.3 cm nodule Rt upper neck with proven Rt upper neck with proven FNA shows PTCFNA shows PTC

Case-2Case-2

RT lobe transverseRT lobe transverse Rt lobe longitudinalRt lobe longitudinal

Rt upper neck PTC MetsRt upper neck PTC Mets

Case-2Case-2

• Surgery: bilateral thyroidectomy 3 mm PTC Surgery: bilateral thyroidectomy 3 mm PTC Rt upper pole and 2 mm left lower pole. Other Rt upper pole and 2 mm left lower pole. Other than palpable 2.3 cm nodule 35 nodes IIa , than palpable 2.3 cm nodule 35 nodes IIa , II,II and IV, VI were negativeII,II and IV, VI were negative

• RAI therapyRAI therapy

• No recurrence , Tg undetectable at one year No recurrence , Tg undetectable at one year F/UF/U

Case-3Case-3

• A female in A female in 20002000 at age 59 presented with at age 59 presented with multiple lung nodules biopsy was PTCmultiple lung nodules biopsy was PTC

• US of thyroid showed benign appearing less US of thyroid showed benign appearing less than 6 mm nodules, no lymphadenopathythan 6 mm nodules, no lymphadenopathy

• Bilateral thyroidectomy, only 5 mm Occult Bilateral thyroidectomy, only 5 mm Occult PTC Rt lobe PTC Rt lobe

• One central node compartment positive One central node compartment positive

Case -3Case -3

• Remnant ablation, 2 doses of 200 mCi I-131Remnant ablation, 2 doses of 200 mCi I-131

• Good uptake in lung metastases in 2001 and Good uptake in lung metastases in 2001 and 20022002

• Last WBS negative in Last WBS negative in 20052005

• Lung nodules stable less than 6 mm 2004-Lung nodules stable less than 6 mm 2004-20142014

• Excellent quality of life at last visit in Excellent quality of life at last visit in Nov 2014Nov 2014

Outcome of 900 Micro PTCOutcome of 900 Micro PTC1994-2004 (Mayo Data)1994-2004 (Mayo Data)

• Median size 7 mmMedian size 7 mm• 85% bilateral lobectomy, RAI in 17%85% bilateral lobectomy, RAI in 17%• 30% neck node positive30% neck node positive• 0.3% distant mets, 0.6% incomplete excision0.3% distant mets, 0.6% incomplete excision• 0.3% died of PTC, Recurrence rate in 40Yrs 6%0.3% died of PTC, Recurrence rate in 40Yrs 6%• Higher recurrence in multifocal tumors, and node Higher recurrence in multifocal tumors, and node

positivespositives• 99% not at risk of distant spread or mortality99% not at risk of distant spread or mortality• RAI or bilateral lobectomy did not change outcome RAI or bilateral lobectomy did not change outcome

Hay ID, surgery; 2008;144:980Hay ID, surgery; 2008;144:980

14045 Micro Papillary Cancer in Korea 14045 Micro Papillary Cancer in Korea Single Institution 1986-2013Single Institution 1986-2013

• Total thyroidectomy 47%, less than total 53%Total thyroidectomy 47%, less than total 53%• Central compartment node 27% lateral neck 4.9%Central compartment node 27% lateral neck 4.9%• 10-20 yrs. survivals 98% and 94%10-20 yrs. survivals 98% and 94%• 10-20 yrs. disease free survivals, 97% and 94%10-20 yrs. disease free survivals, 97% and 94%• No difference between thyroidectomy total and less No difference between thyroidectomy total and less

than totalthan total

Lee c et.al. Presented in OCT 2014, ATA MeetingLee c et.al. Presented in OCT 2014, ATA Meeting

%%

Brito JP, et. al.. BMJ 2014 in press. Brito JP, et. al.. BMJ 2014 in press.

Surgery 140:1000-1005, 2006Surgery 140:1000-1005, 2006Arch Surg 383:167-169, 1998Arch Surg 383:167-169, 1998Ann Surg 245:604-610, 2007Ann Surg 245:604-610, 2007Cancer 115:251-258, 2009Cancer 115:251-258, 2009

Reported Complications of Thyroid SurgeryReported Complications of Thyroid Surgery

Less-aggressive treatment options for Micro-papillary Less-aggressive treatment options for Micro-papillary Thyroid CancerThyroid Cancer

• Lobectomy vs. bilateral surgeryLobectomy vs. bilateral surgery

• Targeted ablative proceduresTargeted ablative procedures

– Percutaneous ethanol ablationPercutaneous ethanol ablation

– Radiofrequency ablation (RFA)Radiofrequency ablation (RFA)

– CryoablationCryoablation

• Active surveillanceActive surveillance

Observation for Micro PTCObservation for Micro PTC

Better Better Active surveillance Active surveillance

AWARENESS ABOUT THE EXISTENCE OF AWARENESS ABOUT THE EXISTENCE OF TREATMENT OPTIONSTREATMENT OPTIONS

Ito Y, Ito Y, World J Surg World J Surg 2010;34:28-352010;34:28-35

Active Surveillance for Micro-PTCActive Surveillance for Micro-PTCAge of PatientAge of Patient

• 1235 patient chose observation 1993-20111235 patient chose observation 1993-2011• Progression lowest in over age 60Progression lowest in over age 60• Highest in the younger <age 40Highest in the younger <age 40• Young age independent predictor of progressionYoung age independent predictor of progression• None of 1235 had distant mets or died from PTCNone of 1235 had distant mets or died from PTC• 4% had TSH suppression, except one all clinically stable191 had 4% had TSH suppression, except one all clinically stable191 had

surgery surgery

• ConclusionConclusion: : Older patients with Micro PTC best candidates for Older patients with Micro PTC best candidates for obserrvation,obserrvation,

• For younger under observation, it is not too late to surgery if For younger under observation, it is not too late to surgery if progressionprogression

Ito Y et al thyroid 2014: 25:27Ito Y et al thyroid 2014: 25:27

Ito Y, Ito Y, Thyroid Thyroid 20142014Active Surveillance of Micro-PTCActive Surveillance of Micro-PTC

>3 mm growth>3 mm growth Lymph node mets Lymph node mets

Age effectAge effectAge effectAge effect

20 years 20 years F/uF/u

Distinct Types of Micro PTCDistinct Types of Micro PTC Under Observation Under Observation

• I- Incidental finding – observed and no change in sizeI- Incidental finding – observed and no change in size• II- Increase in size during observation – Lobectomy is II- Increase in size during observation – Lobectomy is

suggestedsuggested• III- Clinically symptomatic, needs more aggressive III- Clinically symptomatic, needs more aggressive

management management • 230 out of 244 accepted observation\300 lesions: 5 year 230 out of 244 accepted observation\300 lesions: 5 year

observation: 7% increase in size, 90% unchanged 3% observation: 7% increase in size, 90% unchanged 3% decreased: decreased: Conclusion:Conclusion: Observation 95% are type I and Observation 95% are type I and can be observed can be observed

Sugitani I etal World I surg 2010 ;34:1222Sugitani I etal World I surg 2010 ;34:1222

Tumors not Candidate for Active Tumors not Candidate for Active SurveillanceSurveillance

• Peripheral and bulging Peripheral and bulging • Close to trachea with angle over 90 degreesClose to trachea with angle over 90 degrees• Evidence of node or distance mets Evidence of node or distance mets • Multifocal?Multifocal?• Family history of non medullary thyroid cancer Family history of non medullary thyroid cancer • History of radiation exposure History of radiation exposure • PET positive tumors?PET positive tumors?• Patient preference Patient preference

Minimally Invasive Intervention Minimally Invasive Intervention

• Ethanol ablationEthanol ablation

• Radio-frequency ablationRadio-frequency ablation

• CryoablationCryoablation

Ethanol Ablation for Micro-papillary Thyroid Cancer –Mayo pilot study

13 patients, 9 F, 4 M, 5 with co-morbidity, ages 36-8613 patients, 9 F, 4 M, 5 with co-morbidity, ages 36-86

Tumor sized 4-13 mm, injection of 95% alcohol, 2 injections in subsequent days, Ethanol 0.45-Tumor sized 4-13 mm, injection of 95% alcohol, 2 injections in subsequent days, Ethanol 0.45-1.25 1.25

F/u 0.3-4.4 yrs. Medium 1.6 yrs.F/u 0.3-4.4 yrs. Medium 1.6 yrs.

Median volium reduction 76 % all shrunk 4 disappeared Median volium reduction 76 % all shrunk 4 disappeared

Conclusion: Conclusion: For micropapilalry thyroid cancer, patients not comfortable with surgery or active For micropapilalry thyroid cancer, patients not comfortable with surgery or active survellance ethanol ablation may be a n attractive minimally invasive optionsurvellance ethanol ablation may be a n attractive minimally invasive option

Hay, ID et al , ITC 2015Hay, ID et al , ITC 2015

2015 ATA GuidelinesChanging Diagnostic and Treatment Recommendation

• Less aggressive detectionLess aggressive detection• Less aggressive surgery for low risk PTCLess aggressive surgery for low risk PTC• Less RAI therapy for remnant ablationLess RAI therapy for remnant ablation• Lower dose RAI for remnant ablationLower dose RAI for remnant ablation• Central compartment Node excision optional for Low risk Central compartment Node excision optional for Low risk

PTCPTC

Haugen et al Thyroid 2015Haugen et al Thyroid 2015

2015 ATA Guidelines for Thyroid Nodule

Nodule TSH Nodule TSH normal or highnormal or highNodule TSH Nodule TSH normal or highnormal or high

High High suspicionsuspicionHigh High suspicionsuspicion

Low Low suspicionsuspicionLow Low suspicionsuspicion

IntermediateIntermediate patternpatternIntermediateIntermediate patternpattern

Very lowVery low suspicionsuspicionVery lowVery low suspicionsuspicion

FNAFNA>1 cm>1 cm

FNAFNA>1.5 cm>1.5 cm

FNAFNA>2 cm>2 cm

USUS

Pure cyst or Pure cyst or benign patternbenign patternNo FNANo FNA

Haugen et al, Thyroid, 2015Haugen et al, Thyroid, 2015

2009 ATA Guidelines2009 ATA GuidelinesRecommendationRecommendation

• For >1 cm initial surgery bilateral near -or total For >1 cm initial surgery bilateral near -or total unless contraindicationsunless contraindications

• Lobectomy for <1cm, uni-focal intra-thyroidal low Lobectomy for <1cm, uni-focal intra-thyroidal low risk PTC unless prior head and neck radiation risk PTC unless prior head and neck radiation or lymph node involvement (or lymph node involvement (recommendation Arecommendation A) ) Thyroid ; Nov 2009Thyroid ; Nov 2009

2015 ATA Guidelines for Micro-papillary Thyroid cancer

• Less than Less than 1 cm 1 cm suspect nodule no FNA and observe particularly suspect nodule no FNA and observe particularly in olderin older

• When diagnosed R/O metastasis , if unifocal , no radiation When diagnosed R/O metastasis , if unifocal , no radiation history or syndromal PTC: history or syndromal PTC: lobectomy and no lymph node lobectomy and no lymph node sampling sampling

• May consider active surveillance, in certain situationsMay consider active surveillance, in certain situations• 1-4 cm no other risks lobectomy a consideration1-4 cm no other risks lobectomy a consideration

Haugen et al. Thyroid 2015Haugen et al. Thyroid 2015

Evaluate and Consider Less-aggressive Evaluate and Consider Less-aggressive Treatment OptionsTreatment Options

• Lobectomy vs. bilateral surgeryLobectomy vs. bilateral surgery

• Emerging targeted ablative proceduresEmerging targeted ablative procedures

– Percutaneous ethanol ablationPercutaneous ethanol ablation

– Radiofrequency ablationRadiofrequency ablation

– CryoablationCryoablation

• Active surveillanceActive surveillance

Management of Occult Papillary Thyroid Management of Occult Papillary Thyroid CancerCancer

• For unilateral incidental For unilateral incidental ::

Lobectomy if unifocal or multifocalLobectomy if unifocal or multifocal

Observation may be an optionObservation may be an option

• For incidental found on surgery less than 1 cmFor incidental found on surgery less than 1 cm

Lobectomy and no radioactive iodine, No data if T4 therapy is neededLobectomy and no radioactive iodine, No data if T4 therapy is needed

• With lymph node metastasis or distant metastases at presentationWith lymph node metastasis or distant metastases at presentation

Near total thyroidectomy and RAI remnant ablation for stages II (younger Near total thyroidectomy and RAI remnant ablation for stages II (younger than 45) and Stages III and IV (older than age 45)than 45) and Stages III and IV (older than age 45)

• For PET positive incidental PTCFor PET positive incidental PTC

Perhaps more aggressive, but data is neededPerhaps more aggressive, but data is needed

Management of Occult Papillary Thyroid Management of Occult Papillary Thyroid CancerCancer

Special situations when more aggressive bilateral near Special situations when more aggressive bilateral near total or total thyroidectomy may be neededtotal or total thyroidectomy may be needed

•History of head and neck radiationHistory of head and neck radiation

•Non- medullary hereditary differentiated thyroid cancer or Non- medullary hereditary differentiated thyroid cancer or family history in first degree relativesfamily history in first degree relatives

•PTC larger >1.5 cm or extra thyroidal extensionPTC larger >1.5 cm or extra thyroidal extension

•Syndromic FCDTCSyndromic FCDTC

•PTC found on PET? (data needed)PTC found on PET? (data needed)

Issues Needing More DataIssues Needing More Data

• If observation is chosen should T4 therapy given?If observation is chosen should T4 therapy given?• If lobectomy is done should therapy with T4 given?If lobectomy is done should therapy with T4 given?• Should multifocal PTC be treated differently? Should multifocal PTC be treated differently? • Should non- invasive ehanol or RFA ablation be a standard Should non- invasive ehanol or RFA ablation be a standard

option for diagnosed occult PTCoption for diagnosed occult PTC• Should we be less aggressive in performing FNA for less Should we be less aggressive in performing FNA for less

than 1 cm suspect incidental PTCs specially in elderly ?than 1 cm suspect incidental PTCs specially in elderly ?• Need confirmation that older asymptomatic patients with Need confirmation that older asymptomatic patients with

Micro PTC are not subject to higher age related risk Micro PTC are not subject to higher age related risk

Micropapillary Thyroid Cancer Found Micropapillary Thyroid Cancer Found on PET scans on PET scans

• 12 patients with incidental PET positive PTC12 patients with incidental PET positive PTC• 25% multifocal25% multifocal• 66% extra thyroidal extension66% extra thyroidal extension• 41% angioinvasion41% angioinvasion• 16% lung mets 16% lung mets

Conclusion: 92% had intermediate or high risk Conclusion: 92% had intermediate or high risk per ATA criteria. Thyroid carcinomas per ATA criteria. Thyroid carcinomas detected by18-F-FDG PPET have aggressive detected by18-F-FDG PPET have aggressive histology and likely worse prognosis histology and likely worse prognosis

Pedro Marques et. al. Endo Practice 2014; 20: 1129Pedro Marques et. al. Endo Practice 2014; 20: 1129

CHOOSING THE “RIGHT” TREATMENT CHOOSING THE “RIGHT” TREATMENT

A 44-year-old executive A 44-year-old executive concerned about future concerned about future metastatic disease might opt metastatic disease might opt for thyroid surgeryfor thyroid surgery

A singer, or a public A singer, or a public speaker, concerned about the speaker, concerned about the possible perioperative possible perioperative damage to voice may opt for damage to voice may opt for active surveillanceactive surveillance

Conclusion-1Conclusion-1

• Worldwide increase in papillary thyroid cancer is Worldwide increase in papillary thyroid cancer is mostly related to increased imaging and finding of mostly related to increased imaging and finding of non–significant micro -PTCnon–significant micro -PTC

• Incidentally discovered micro PTC in thyroidectomy Incidentally discovered micro PTC in thyroidectomy for benign disease can be considered not clinically for benign disease can be considered not clinically significant and no further action is neededsignificant and no further action is needed

• For PTC less than 1.0 cm active surveillance may For PTC less than 1.0 cm active surveillance may be offered in future if acceptable to the patientbe offered in future if acceptable to the patient


• Decision for FNA of a <1.5 m nodule if incidentally Decision for FNA of a <1.5 m nodule if incidentally discovered should be more conservative following discovered should be more conservative following 2015 ATA guidelines2015 ATA guidelines

• Controlled studies of active surveillance vs. surgery or Controlled studies of active surveillance vs. surgery or minimally invasive procedure such as alcohol ablation minimally invasive procedure such as alcohol ablation are underwayare underway

• If surgery is chosen for incidental micro PTC If surgery is chosen for incidental micro PTC Lobectomy should be adequate and central Lobectomy should be adequate and central compartment node sampling may not be needed compartment node sampling may not be needed


• Rare cases of Micro PTC with significant neck Rare cases of Micro PTC with significant neck node mets or distant mets exist. But they are node mets or distant mets exist. But they are usually diagnosed by clinical metastasis and usually diagnosed by clinical metastasis and primary source may be occult and their primary source may be occult and their management is according to the staging of the management is according to the staging of the cancercancer

That is it!That is it!

q2stins q2stins

Thank YOUThank YOU

200

22

002

19851985 Brito JP. Brito JP. BMJ BMJ 2013;347:f47062013;347:f4706

Incidence of thyroid Incidence of thyroid cancer in multiple cancer in multiple countries, 1985 vs. countries, 1985 vs. 20022002

19851985

2002

2002

Clinically “silent” diseaseClinically “silent” disease

PTCPTCCC

LOW LOW RISKRISKPTCPTC

IDENTIFICATION OF PATIENTS AT IDENTIFICATION OF PATIENTS AT LOW RISK LOW RISK

LOOKING AHEADLOOKING AHEAD

• The term microPLIC should also be tested to ensure that it The term microPLIC should also be tested to ensure that it promotes careful deliberation and patient-centered treatment.promotes careful deliberation and patient-centered treatment.

• RCT of active surveillance vs. thyroid surgery and other potential RCT of active surveillance vs. thyroid surgery and other potential treatment options for PLICstreatment options for PLICs

• Role of decision aids to avoid overtreatment for PLICsRole of decision aids to avoid overtreatment for PLICs• Interventions to prevent overdiagnosis and overtreatment of Interventions to prevent overdiagnosis and overtreatment of

PLICsPLICs– Molecular or other markers of aggressionMolecular or other markers of aggression– Less invasive treatment options – PEI, RFA, Laser, etcLess invasive treatment options – PEI, RFA, Laser, etc

• Role of guidelines and recommendations to overcome Role of guidelines and recommendations to overcome overdiagnosis and overtreatmentoverdiagnosis and overtreatment

Recent rise in thyroid cancer incidence is related to discovery of a reservoir of Recent rise in thyroid cancer incidence is related to discovery of a reservoir of previously unrecognized subclinical disease: a population-based study in previously unrecognized subclinical disease: a population-based study in

Olmsted County, Minnesota during 2000 through 2012Olmsted County, Minnesota during 2000 through 2012

Thyroid Incidental Micro-cancer In Thyroid Incidental Micro-cancer In AutopsyAutopsy

• FinlanFinlandd:: n=101 n=101

• 35% thyroid cancer35% thyroid cancer

• ( 2-3 mm cuts) (range 0.1 mm-( 2-3 mm cuts) (range 0.1 mm-15mm) 67% under 1 mm15mm) 67% under 1 mm

First author, year Country Method WomenN (%)

Men N (%)

Mortensen 1955 (& Woolner)

USA (Mayo Clinic)

All nodules 318/821 (38%)

191/538 (34%)

Harach 1985 Finland All of gland 13/48 (27%)

23/53 (43%)

Lang 1988 Germany ‘Suspicious areas’ only

24/421(6%)

39/599(7%)

Ottino 1989 Argentina not clearly defined 3/41(7%)

8/59(14%)

Martinez-Tello 1993 Spain All of gland 6/34(18%)

16/66(24%)

Solares 2005 Guatemala ‘Suspicious areas’ only

1/34(3%)

2/116(2%)

Thyroid Cancer ReservoirThyroid Cancer Reservoir

Rat

e p

er 1

00 0

00R

ate

per

100

000

<1 cm<1 cm<1 cm<1 cm

1-2.51-2.5 cm cm1-2.51-2.5 cm cm

>3 cm>3 cm>3 cm>3 cm

IDENTIFICATION OF PATIENTS AT IDENTIFICATION OF PATIENTS AT LOW RISK LOW RISK


Case-1Case-1

What should be management?What should be management?

•1- Radioactive iodine remnant ablation1- Radioactive iodine remnant ablation•2-Suppressive thyroxine therapy to TSH< 0.12-Suppressive thyroxine therapy to TSH< 0.1•3-Annual thyroid US for 5 years3-Annual thyroid US for 5 years•4-No follow up neck US is needed4-No follow up neck US is needed

Case-2Case-2

1.1. Patient needs completion thyroidectomyPatient needs completion thyroidectomy

2.2. Patient needs central compartment node Patient needs central compartment node samplingsampling

3.3. If FNA of the larger nodule was benign If FNA of the larger nodule was benign observation might have been an optionobservation might have been an option

4. None of the above4. None of the above

Study Points to Overdiagnosis of Thyroid CancerStudy Points to Overdiagnosis of Thyroid CancerNew York Times, November 6, 2014New York Times, November 6, 2014

Korea's Thyroid-Cancer “Epidemic” Korea's Thyroid-Cancer “Epidemic” — Screening and Overdiagnosis— Screening and OverdiagnosisN Engl J Med 2014; 371:1765-1767 November 6, 2014N Engl J Med 2014; 371:1765-1767 November 6, 2014

Thyroid cancer (PTC) is now the Thyroid cancer (PTC) is now the most most Prevalent cancer in Korea.Prevalent cancer in Korea.

New Thyroid Cancer Cases per year - USA - 1974-2012

0

10000

20000

30000

40000

50000

60000

1970 1974 1978 1982 1986 1990 1994 1998 2002 2006 2010

Year

Ne

w C

as

es

(N

)

Total (N)

Male (N)

Female (N)

Rat

e p

er 1

00 0

00R

ate

per

100

000

Incidence Rates for Thyroid CancerIncidence Rates for Thyroid Cancer

Surveillance Epidemiology and End Results. http://seer.cancer.gov/statfacts/html/tSurveillance Epidemiology and End Results. http://seer.cancer.gov/statfacts/html/thyro.htmlhyro.html

4.84.8

14.314.3

Differentiated Thyroid CarcinomaDifferentiated Thyroid Carcinoma

• Follicular cell derived Follicular cell derived thyroid carcinomas thyroid carcinomas (PTC and FTC) (PTC and FTC) comprise up to 95% of comprise up to 95% of all thyroid carcinomasall thyroid carcinomas

• The vast majority of The vast majority of these tumors are well these tumors are well differentiateddifferentiated

2%3%10%

85%

Papillary Follicular

Medullary Other

Grebe & Hay 1995

Case-1Case-1

• 32 year old lady seen in 2012 with hyperthyroidism,32 year old lady seen in 2012 with hyperthyroidism,• Thyroid US: Heterogenous pattern and tiny Thyroid US: Heterogenous pattern and tiny

nodularity not suspicious. Isotopic scan diffuse nodularity not suspicious. Isotopic scan diffuse enlargement, serology consistent with Gravesenlargement, serology consistent with Graves

• Treated for 2 years with antithyroid medications Treated for 2 years with antithyroid medications poor response poor response

• Surgery in 2014 bilateral diffuse hyperplasia. Surgery in 2014 bilateral diffuse hyperplasia. Left Left lobe had 1.3 cm follicular variant of PTClobe had 1.3 cm follicular variant of PTC

• What should be management?What should be management?

Case -2Case -2

68 year old with a palpable68 year old with a palpable

newly found 2.5 cm nodule in the leftnewly found 2.5 cm nodule in the left

Case-2Case-2

• Lobectomy doneLobectomy done

• The 2.5 cm lesion was follicular benign The 2.5 cm lesion was follicular benign adenomaadenoma

• 5 mm PTC in the left lobe and also 2 other 5 mm PTC in the left lobe and also 2 other foci of 2 and 3 mm PTCfoci of 2 and 3 mm PTC

Increasing Diagnosis of Micro-papillary Thyroid Cancer New Trends in Management

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