Surgical Management of Surgical Management of Differentiated Thyroid CancerDifferentiated Thyroid Cancer

Vanderbilt UniversitySurgical Grand Rounds

Carmen C Solórzano, MD, FACSAssociate Professor

Endocrine and Surgical OncologyVanderbilt University

Nashville, TN

May 7, 2010May 7, 2010

1

4

7

10

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

•• 37,200 Thyroid cancer cases in 2009 37,200 Thyroid cancer cases in 2009

•• 1630 deaths1630 deaths

•• HIGH PREVALENCEHIGH PREVALENCE >300,000 >300,000 individuals with thyroid cancer in the individuals with thyroid cancer in the USAUSA

SEER 2000 Incidence/100,000SEER 2000 Incidence/100,000

Trends in Incidence of Thyroid Cancer (1973-2002) and Papillary Tumours by Size (1988-2002) in the USA (SEER)

Davies, L. et al. JAMA 2006;295:2164-2167

Thyroid cancer has the fastest rising Thyroid cancer has the fastest rising incidence of all major cancers in the USA incidence of all major cancers in the USA

>350% since 1950>350% since 1950

Thyroid Cancer Incidence and Mortality1973-2002

0.45 deaths per 100,000 in 20030.45 deaths per 100,000 in 2003

Increasing Incidence: Why?

• Radiation• Iodine excess/deficient states• Reproductive/hormonal factors• Early detection of subclinical disease

…but the incidence has increased across all tumor sizes

•• Risk factors and molecular Risk factors and molecular mechanisms/markersmechanisms/markers

•• Natural history, patterns of failure and Natural history, patterns of failure and pretreatment staging pretreatment staging

•• Surgical treatmentSurgical treatment

•• Rationale for adjuvant therapyRationale for adjuvant therapy

OutlineOutline

The “Thyroid Nodule”

• Prevalence- 5% of US population (15 million)• 50% if thyroid examined by Ultrasonography

Thyroid carcinoma is uncommon:Lifetime risk of thyroid cancer

0.83% women and 0.33% men

Horner- SEER review 1975-2006

ATA guidelines 2009

Thyroid CancerRisk factors- Environmental

• Exposure to radiation is the only established environmental risk factor

1-Medical sources2-Acute environmental exposure:

nuclear fallout, weapons

1 100 thyroid cancer cases in 1,000,000Nagataki Thyroid 2002

BelarusBelarusII131, 131, KBq/m2KBq/m2

ChernobylChernobyl

Thyroid CancerRisk factors- Genetic:

Familial syndromes -5% of cancers • Unknown gene Isolated familial non-medullary

thyroid cancer• WRN Werner’s• APC familial adenomatosis polyposis (cribiform-

morular PTC)• PTEN PTEN-Hamartoma syndrome

Few patients with these syndromes develop thyroid cancer

Thyroid CancerMolecular mechanisms/markers:•• Activation of Activation of BRAF BRAF --(PTC)(PTC)•• Rearrangements of Rearrangements of RET/PTC RET/PTC --(radiation (radiation

exposure and younger pts)exposure and younger pts)•• Activation of Activation of RASRAS-- (FVPTC)(FVPTC)•• Rearrangement of PAX8/PPARRearrangement of PAX8/PPARˠɣ

--(FTC)(FTC)

•• Others: differential expressed genes, Others: differential expressed genes, epigenetic changesepigenetic changes……

JCEM 94(6): 2092, 2009

470 FNA specimens (328 patients)Panel of mutations: BRAF, RAS, RET/PTC and PAX8/PPARˠ

Only 28% of the indeterminate FNA tested positive

Zeiger, Curr Opinion in Onc 2010

RET-Ras-BRAF-MEKRET-B cateninTRK-PI3K-AKTMDM-p53-PTEN

Epigenetic silencingSingle-nucletide polymorph

Alternative splicingGene expression abnl

•• Risk factors and molecular Risk factors and molecular mechanisms/markersmechanisms/markers

•• Natural history, patterns of failure Natural history, patterns of failure and pretreatment stagingand pretreatment staging

•• Surgical treatmentSurgical treatment

•• Rationale for adjuvant therapyRationale for adjuvant therapy

OutlineOutline

Papillary Thyroid Cancer- has follicular cell differentiation, formation of papillae and/or distinctive nuclear changes

FNAFNAspecimenspecimen

Sub-types Papillary Thyroid Cancer• Follicular variant (most common type)• Tall cell variant (aggressive)• Columnar cell variant (aggressive):

prominent nuclear stratification• Diffuse sclerosing variant

Presenting Features • 30 and 50 yrs of age (mean 45 yrs) • Female predominance: 60% to 80% • Primary tumors: 1 to 4 cm• 28% multi-focal• Extra-thyroidal invasion of adjacent soft

tissues: about 15%• 30-40% may have lymphadenopathy at

presentation• 2% distant metastases

Generally indolent tumor with low metastatic Generally indolent tumor with low metastatic potentialpotential

Recurrence 30%Recurrence 30% (loco(loco--regional or distant regional or distant metsmets) )

Death in approximately 8%: pulmonary Death in approximately 8%: pulmonary metsmets and/or airway obstructionand/or airway obstruction

Overall 10 year survival: Overall 10 year survival: Papillary 93%Papillary 93% Follicular 85% Follicular 85% HurthleHurthle 76%76%

Natural history and patterns of Natural history and patterns of treatment failuretreatment failure

HundahlHundahl Cancer 1998Cancer 1998

Many Staging ClassificationsThe most predictive prognostic factors:

AgeExtent of tumorPresence of distant metastasisHistology- variants

MACIS (Mayo)AJCC/TNM

EORTCAMES, AGES, Munster, Ankara

Clinical Class, OSU, MSKCCNTCTCS, Murcia, Noguchi,

UAB&MDA, CIH Tokyo

6th6th

T= specify solitary/multifocalT1a=<1cm and T1b 1.1-2cm

Cancer-Specific Survival for PTC5 year 10 year 15 year

TNM 6thI 100 100 100II 94.8 94.8 94.8III 90.1 83.6 83.6

IVAIVBIVC

85.766.754.7

67.866.718.2

44.666.718.2

MACISI= <6 99.7 98.9 97.7

II= 6-6.99 90.6 86.8 68.3III= 7-7.99 87.0 64.2 55.1

IV =>8 67.4 42.1 33.7

Case

25 yo female: 2 cm thyroid mass – no symptoms

Firm mass in right lobeFirm mass in right lobeno palpable adenopathyno palpable adenopathy

Palpation is inadequate forevaluation of the thyroid

and/orcervical adenopathy

ULTRASOUND: Evaluates thyroid and lymph nodes BEFORE operative procedure

77--13 MHz13 MHz

Features that mayFeatures that maypredict cancer:predict cancer:

HypoHypo--echoicechoicCalcificationsCalcifications

Irregular bordersIrregular bordersVascularityVascularity

Taller>WiderTaller>Wider

Invasion?Invasion?

Kim EK AJR 2002Papini JCEM 2002

Jabiev, Ann Surg Onc 2009 Mendez, Ann Surg Onc 2008

Ultrasound -Thyroid

Lymph nodesLymph nodes-- UltrasoundUltrasound

Central compartmentCentral compartment

Cystic lymph node = Papillary cancer!Cystic lymph node = Papillary cancer!

Lateral compartmentLateral compartment

• 72 pts with thyroid cancer in one lobe by FNA• Evaluation of the contralateral lobe and lymph

nodes• Non-palpable lymph node mets in 24%• A non-palpable thyroid nodule was found in the

contralateral lobe in 38% 56% were malignant (vs. 14% if no nodule present)

Evaluation of lymph nodes and the contra-lateral Lobe by surgeon-

performed ultrasound (SUS)

Solorzano Am Surg 2004; 70: 576

Ultrasound by the Surgeon or RadiologistUltrasound by the Surgeon or Radiologist

KouvarakiKouvaraki Surgery 2004; 136:1183 and 2003; 134:946Surgery 2004; 136:1183 and 2003; 134:946

Detects lymph node or soft tissueDetects lymph node or soft tissuemetastases in cervical compartmentsmetastases in cervical compartments

believed to be negative on physical exambelieved to be negative on physical examin up to in up to 3030--50%50% of patientsof patients

May prevent persistent May prevent persistent or recurrent diseaseor recurrent disease

Excellent preExcellent pre-- and postand post--op op Diagnostic/Surveillance tool Diagnostic/Surveillance tool

calciumcalcium

VI

II

III

IVV

CentralLateral

Mapping of Lymph NodesMapping of Lymph Nodes

VII

Fine needle aspiration biopsyFine needle aspiration biopsy

What happened to the thyroid scan?What happened to the thyroid scan?

Fine Needle AspirationCancer Rate (histology)

Carcinoma (5-8%) 96-98% CancerBenign (65-75%) up to 4-7% Cancer Non-diagnostic or inadequate (5-10%)

11% cancerIndeterminate (10-20%)

20-40% CaFollicular or Hurthle cell neoplasmSuspicious for carcinoma

Yang Cancer 2007;111:306-315Yassa Cancer 2007;111:508-516

Distribution of FNA results- when the patient visits this surgeon

N=797 patients with FNA’sfrom unpublished data 2010 (1/2003-1/2010)

%

FNA result vs. Histopathology Tertiary Referral Center

# pts

98%49%

#

16% 24%

797 patients with FNA’s who underwent thyroidectomyUnpublished data 1/2003-1/2010

#FN= 37%#HN= 36%

#Susp PTC= 92%

Bethesda System for Reporting Thyroid Cytopathology

• Non-diagnostic• Benign• Atypia of undetermined significance/ Follicular

lesion of undetermined significance (FLUS)• Follicular neoplasm or suspicious for a follicular

neoplasm (specify if Hurthle/Oncocytic)• Suspicious for malignancy• Malignant

NCI- Thyroid FNA State of the Science Conference 2007

Thyroid 2009 vol 19(11), p1159

Papillary Thyroid Cancer Staging

Case 25 yo female: 2 cm R thyroid nodule FNA Suspicious for a Follicular Neoplasm

US: Lateral (II,III,IV,V) lymph nodes not involved, additional small (8mm) thyroid nodule opposite thyroid lobe

Ultrasound (and physical exam findings)

• May be used to alter surgical decision making (total thyroidectomy vs. lobectomy) in patients with indeterminate FNA

• 180 patients with indeterminate FNA• 137 Hurthle/Follicular, 43 suspicious PTC• Adverse nodule features on SUS:

Micro-calcificationsIrregular bordersHypoechoicTaller>Wider

Mendez et al. Ann Surg Onc 15(9):2487, 2008

Adverse thyroid nodule features on SUS in patients with indeterminate FNA

Mendez, Ann of Surg Onc 2008

SUS features

Malignant Benign Total

0 17(29%) 41(71%) 581 18(35%) 33(65%) 512 27(71%) 11(29%) 383 25(89%) 3(11%) 284 5(100%) 0(0%) 5

Total 92(51%) 89(49%) 180

•• Risk factors and molecular mechanisms of Risk factors and molecular mechanisms of tumor developmenttumor development

•• Natural history/patterns of failureNatural history/patterns of failure

•• Pretreatment stagingPretreatment staging

•• Surgical treatmentSurgical treatment

•• Rationale for adjuvant therapyRationale for adjuvant therapy

OutlineOutline

Treating Thyroid CancerStart with the end in mind!!!

Normal postNormal post--op ultrasound op ultrasound and undetectable Tgand undetectable Tg

Goals of Surgical Therapy• Remove the primary tumor, disease extension

beyon thyroid capsule, and affected cervical lymph nodes

• Accurately stage disease• Facilitate radioiodine therapy when appropriate• Permit accurate long-term surveillance for

recurrence• Minimize the risk of recurrence and metastasis• Limit the disease-and treatment-related morbidity

and mortality

Thyroid Cancer Risk stratification for M0 patients

Low risk High Risk

< 40 Age > 40Female Sex Male< 2 cm Size > 2 cmNO Extra-thyroidal invasion YES

? Lymph Nodes Multiple +

AGES, AMES, MACIS, etc

Death from PTC, the most Death from PTC, the most common form of thyroid common form of thyroid cancer, is very rare, and cancer, is very rare, and

therefore, death should not be therefore, death should not be used as a valid endpoint for used as a valid endpoint for

assessment of treatmentassessment of treatment

Cervical recurrence occurs Cervical recurrence occurs 20% low risk20% low risk69% high risk69% high risk

Extent of Surgery Total Thyroidectomy vs. Lobectomy

Total Lobe

Improved in high risk SurvivalLower in high/low RecurrenceAllows delivery Radioactive Iodine Use in follow-up Thyroglobulin

Complications Lower

Mayo clinic 2002 (194Mayo clinic 2002 (194--2000)2000)

Mortality RecurrenceMortality Recurrence

Total Thyroidectomy improves survival Total Thyroidectomy improves survival and recurrence in patients withand recurrence in patients with

MACIS high risk PTCMACIS high risk PTC

Mayo experience low-risk AMESAMES low-riskM0 Men < 41, woman < 51Older patients with: T < 5 cm intrathyroidal, M0

Hay, Surgery 1998;124:958N = 1,656, 1940-1991

0

5

10

15

20

25

any site local regional

UL

BL

8

19

14

2

22

6

Recurrence Site

% R

ecur

renc

e

UL

UL

BL

BL

UL=unilateral lobectomyUL=unilateral lobectomyBL=bilateral lobectomyBL=bilateral lobectomy

Ann Ann SurgSurg 20072007

52,173 patients; 83% total thyroidectomyFor all tumors >1cm, and for tumors 1-2 cm, total thyroidectomy associated with improved survivalReinforces the current common practice

Follicular variant PTC multifocal (2.2 cm)Follicular variant PTC multifocal (2.2 cm)

25 yo with FNA indeterminate25 yo with FNA indeterminate

Lymph nodes in the central neck appearedLymph nodes in the central neck appearednormalnormal-- should they be should they be

removed removed prophylacticlyprophylacticly??

Pattern of LN metastasis (micro-metastases, H+E negative)

• 80 patients total thyroid and central and ipsilateral lateral neck dissection

• 53% had lymph node micro-metastases by Immunohistochemistry

• Upper 1/3 tumors upward lymphatic flow• Lower 1/3/isthmus tumors downward flow• Early thyroid cancer micromets do not cross

the midline and remain in the ipsilateral side of the tumor Qubain, Surgery 2002:131:249-56

PrePre--trachealtrachealParaPara--trachealtracheal

level II,IIIlevel II,IIIlaterallateral

<1cm tumors- 26% micro-mets>1.1cm-66% micro-mets

Pattern of LN metastasis (H+E positive)

• 134 patients total thyroid, central and lateral neck dissection

• The ipsilateral lateral compartment involved as often as the central (lat 29% vs. central 32%); re-ops (lat 21% vs. central 37%)

• The ipsilateral central compartment most common site for LN mets

• Patients who have central lymph node mets have at least a 70% chance of ipsilateral lateral LN involvement Marchens, Surgery 2009; 145;175-81

Marchens WJS 2002;26:22-8

Lymph Node Metastases in PTCLymph Node Metastases in PTC

• Cervical LN metastases are quite common 20-50%

• Micro-metastases -present in 90%• Lymph node metastases in PTC

significantly correlate with persistence and recurrence of PTC

• Lymph node metastases and their effect on mortality remains controversial

Lymph Node Metastases in PTCLymph Node Metastases in PTC

• Making evidence based recommendations for the treatment of LN metastases is challenging– Studies are retrospective– Indolent disease– Heterogeneity of literature (use of

ultrasound, terminology, prophylactic vs. therapeutic… etc)

The argument against prophylactic (elective) LN dissection

of the central compartment• Lymph node metastases have no

impact on cause specific mortality or recurrence

• More radical surgery greater morbidity (hypoparathyroidism and permanent nerve injury)…

Roh Ann Surg 2007;245:604Bardet Eur J endo 2008

Palestini Langenbeck’s Arch 2008Henry Langenbeck’s Arch 1998

The argument in favor of prophylactic (elective) LN dissection

of the central compartment• Even experienced surgeons can not tell

if lymph nodes are affected• May reduce recurrence/persistence• May improve survival • Re-operations in the central neck are

morbidNoguchi Arch Surg 1998;133:276

White W J Surg 2007; 31:895Sywak, Surgery 2006

Tisell et al. WJS 20:854-859, 1996Zaydfudim et al. Surgery 144: 1070, 2008

Historical Perspective• 1950’s –Frazell, Foote Jr, Crile Jr- ? the need

for radical and then prophylactic neck dissections

• 1970’s- Shiro Noguchi- 90% of PTC patients already have lymph node micromets- ? the need for routine dissections- unless gross disease, >40 yo or >1.5 cm

• 1977- Ernest Mazzaferri- neck dissections do not influence recurrence or survival- extent of thyroidectomy and RAI treatment does

Historical Perspective Cont…• 1980-90’s-The great debates

Hay/Cady/Shaha about Total thyroid vs. lesser…no mention of neck dissections

• 2000’s-Ultrasound and Thyroglobulin- The goal posts have changed position!

HAVE WE EVOLVED OR, HAVE WE MERELY COME FULL CIRCLE?

Zeiger JSO 2010

Extent of Central LN Dissection The New Paradigm!

R27R27……Prophylactic central compartment Prophylactic central compartment neck dissection (ipsilateral or bilateral) may neck dissection (ipsilateral or bilateral) may be performed in patients with PTC with be performed in patients with PTC with clinically uninvolved central neck lymph clinically uninvolved central neck lymph nodes, especially for advanced primary nodes, especially for advanced primary tumors (T3 or T4)tumors (T3 or T4)……

American Thyroid Association: American Thyroid Association: Thyroid Cancer GuidelinesThyroid Cancer Guidelines--R27 R27 Thyroid Thyroid 20092009

Recommendation R27 should be interpreted in light of available expertise

““Prophylactic central neck dissection can be Prophylactic central neck dissection can be considered but is not required in all casesconsidered but is not required in all cases””

National Cancer Center Network-Guidelines 2010

Extent of Central LN Dissection The New Paradigm!

Extent of LN Dissection The punch line!

• Obvious gross lymph node disease in the central compartment should be removed with a therapeutic central LN dissection

• Level VI central neck dissection can be achieved with low morbidity**

• Prophylactic (elective) central dissection? controversial

Gemsenjager JACS 197:182-190, 2003Tisell et al. WJS 20:854-859, 1996** in experienced hands** in experienced hands

Extent of LN Dissection The punch line continued!

• Lateral LN disease when evident clinically, on ultrasound or at the time of surgery should be treated with a functional compartment directed dissection (levels II-V)

• The level VI (central) lymph nodes should also be dissected

• NO BERRY PICKING Tisell et al. WJS 20:854-859, 1996

Musacchio Am Surg. 2003;69(3):191-196

Central and lateral neck dissectionCentral and lateral neck dissection

•• Risk factors and molecular mechanisms Risk factors and molecular mechanisms of tumor developmentof tumor development

•• Natural history/patterns of failure Natural history/patterns of failure

•• Pretreatment staging Pretreatment staging

•• Surgical treatmentSurgical treatment

•• Rationale for adjuvant therapyRationale for adjuvant therapy

OutlineOutline

• Extent of the initial surgical procedureThyroid remnantAdequate lymph node removal

• Radioactive Iodine (RAI)

• TSH suppression (oral LT4)

Loco-regional recurrence

Can be decreased by:Can be decreased by:

--Eradicates residual, notEradicates residual, not--resected microscopic resected microscopic or gross tumoror gross tumor

--Ablates any thyroid tissue to facilitate:Ablates any thyroid tissue to facilitate:

Tg measurements Tg measurements

RAI whole body scans (WBS)RAI whole body scans (WBS)

--May detect subMay detect sub--clinical lung metastasesclinical lung metastases

--Improves survival in high risk patientsImproves survival in high risk patients

Rationale for RAI ablationRationale for RAI ablation

Recurrence following RAI

0

5

10

15

20

25

30

35

40

5 10 15 20 25 30 35

RAI no RAI

Mazzaferri, Am J Med 1994;97:418

N = 138

N = 802

years

% R

ecur

renc

e

Stage 2 and 3 Mazzaferri (T>1.5cm)

Also TSH suppressionAlso TSH suppression

-- No consensus on ablation dose of INo consensus on ablation dose of I131131

-- Does it improve survival?Does it improve survival?

-- RAI ablation in low risk patients?RAI ablation in low risk patients?

May not be necessary!May not be necessary!

RAI ongoing controversiesRAI ongoing controversies

TSH is a growth factor for thyroid cancerTSH is a growth factor for thyroid cancer

Keeping TSH at a low level (<0.1mU/l) can Keeping TSH at a low level (<0.1mU/l) can decrease recurrencedecrease recurrence

Rationale for TSH suppressionRationale for TSH suppression

National Thyroid Cancer Treatment Cooperative Registry n=617 PTC Thyroid 1998;8:737-744

Degree of TSH suppression in patients with high-risk papillary cancer correlated with time to progression

No correlation in low risk patients

TSH suppression not for all?TSH suppression not for all?

100%100%

90%90%

80%80%

50%50%

10% 10%

Overall survival in high risk Overall survival in high risk differentiated thyroid cancer according differentiated thyroid cancer according

to TSH scoreto TSH score

TSH=Undetectable/subnormalTSH=Undetectable/subnormal

TSH=Normal or elevatedTSH=Normal or elevated

0 2 4 6 8 10 140 2 4 6 8 10 14YearsYears

JonklaasJonklaas Thyroid 2006Thyroid 2006Outcomes of patients with DTC following therapyOutcomes of patients with DTC following therapy

TSH suppression

• For high risk patients- YES <0.1 mIU/L• For low risk patients- NO• Moderate suppression for intermediate

risk• Duration?

ConclusionsConclusions

Surgeons play a key role in the Surgeons play a key role in the management of thyroid cancermanagement of thyroid cancer

•• Staging, performing or completing Staging, performing or completing adequate thyroid cancer removaladequate thyroid cancer removal

•• Member of the multidisciplinary team Member of the multidisciplinary team –– Help with surveillance and removal of Help with surveillance and removal of recurrent diseaserecurrent disease

THANK YOUTHANK YOU

Ann Ann SurgSurg 2007200752,173 patients in NCDB52,173 patients in NCDB

For his work on the physiology, pathology, For his work on the physiology, pathology, and surgery of the thyroid glandand surgery of the thyroid gland

Emile Theodor KocherEmile Theodor Kocher

Nobel Prize 1909Nobel Prize 1909

Resident performing endocrine surgeryResident performing endocrine surgery

Medical studentMedical student

Nerve monitorNerve monitorHarmonic scalpelHarmonic scalpel

Parathyroid AutotransplantParathyroid Autotransplant

High incidence of cervical LN High incidence of cervical LN metsmets at diagnosisat diagnosis

ACS ACS CoCCoC patient care evaluation study patient care evaluation study 55835583 cases of cases of thyroid cancerthyroid cancer--

Extent of lymph node dissectionExtent of lymph node dissectionA current controversy!A current controversy!

Type % No LN evaluated

% <1cm

Papillary 54 27Follicular 77 6Hurthle 71 3

Medullary 40 11

HundahlHundahl, Cancer 2000; 89:202, Cancer 2000; 89:202--217217

DFS following RAI: U of Chicago

0

20

40

60

80

100

120

5 10 15 20 25 30 35

RAI no RAI

DeGroot, JCEM 1990;71:414N = approx. 200

Surgeryalone

RAI

U of C stage I and II (intrathyroidal or N1) with T > 1cm

% D

isea

se F

ree

(DFS

)

years

DFS following TSH suppression

0

20

40

60

80

100

120

0 5 10 15

TSH <0.1 TSH>1.0

Pujol, JCEM 1996;81:4318.Stage of disease variable

years

% D

isea

se F

ree

TSH suppression as a determinant of recurrence: 70% papillary

TSH < 0.1 (N=18)

TSH > 1.0 (N=15)

Treating Thyroid Cancer…Start with the end in mind!!!

Non-palpable contra-lateral nodule found by SUS

N=27(38%)

Non-palpable contra-lateral nodule found by SUS

N=27(38%)

No contra-lateral nodule found by SUSN=32

No contra-lateral nodule found by SUSN=32

Total thyroidectomy

N=25

Total thyroidectomy

N=25

Thyroid lobectomy

N=2

Thyroid lobectomy

N=2

14/25 (56%)cancer in

contralaterallobe nodule

14/25 (56%)cancer in

contralaterallobe nodule

Total thyroidectomy

N=28

Total thyroidectomy

N=28

Thyroid lobectomy

N=4

Thyroid lobectomy

N=4

4/28 (14%)cancer in

contralateral lobe

4/28 (14%)cancer in

contralateral lobe

72 patients with thyroid cancer SUS evaluation of contra-lateral lobe72 patients with thyroid cancer SUS evaluation of contra-lateral lobe

SUS identified nonSUS identified non--palpable lymph node metastasis in 24%palpable lymph node metastasis in 24%

Evaluation of Lymph Nodes and the Contralateral Lobe by SUS

Historical Perspective

…“The general lack of a great body of material for prolonged follow-up studies emphasizes the need for extreme caution in making all-inclusive pronouncements of a prognostic nature about a form of cancer in which the most noteworthy attribute is extreme chronicity”…

FrazellFrazell and and FooteFoote Cancer 1958;11:895Cancer 1958;11:895Memorial Center for Cancer and Allied Memorial Center for Cancer and Allied DzDz--NYNY