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Thyroid Cancer

May 10, 2006



Thyroid Cancer

� Accounts for 1.5% of all cancers in the US

� Most common endocrine malignancy (95%)� 22,000 cases per year and estimated 500 ±

1000 patients die annually

� 90% of thyroid cancer cases have favorableprognosis



Classification & Incidence of

Thyroid Cancer Follicular cell origin

� Differentiated

± Papillary 80%± Follicular 10%

± Hurthle cell 3-5%

� Undifferentiated

± Anaplastic 1-2%Parafollicular cell origin

± Medullary 5%



P apillary Carcinoma

� Accounts for 90% radiation induced cancer

� Classified as microcarcinoma, intrathyroidal, and

extrathyroidal

± Histologic variants: tall-cell, clear-cell, columnar , diffuse

sclerosing

� Multicentric in 30-50% of tumors

� Spreads via lymphatics with propensity for mid- andlower-anterior cervical chain (Level VI)

� 20-50% patients have involvement of cervical LN



F ollicular Carcinoma

� Only 10% of thyroid cancers in developed countries, although more prevalent in regions with iodinedeficiency

� Diagnosis depends on demonstration of vascular or capsular invasion

� Classified as minimally or widely invasive

± Vascular invasion tends to have a more aggressive course

than capsular invasion� Uncommon to have multicentric disease

� Hematogenous spread



F ollicular Carcinoma

Where does follicular carcinoma tend to

metastasize?

� Bone

� Lung



H urthle Cell Carcinoma

� High propensity to spread to cervical lymph

nodes and high incidence of distant metastasis

� Less than 10% of Hurthle cell carcinomas takeup radioiodine

� High tumor recurrence rate

� High mortality rate ± 30% mortality at 10 years



Anaplastic Carcinoma

� Increasingly rare

� Arise within differentiated cancers

� Pts > 60 years old with rapidly expanding neck mass

� Local invasion very common at time of dx (FNA)

� Surgery plays limited role given advanced stage at dx

� R adiation and chemotherapy have not demonstrated

any significant improvement in survival

� Median survival ~ 4 - 6 months



M edullary Thyroid Carcinoma

� Originates from the parafollicular C cells

� Elevation in calcitonin and CEA (50%)� 80% have sporadic MTC (unifocal), remainder

have genetic component

� 75% patients have LN metastasis at time of dx, 20% distant mets



M edullary Thyroid Carcinoma

� MEN IIA ± MTC (100%), pheo (40%), hyperparathyroidism (35%)

± AD inheritance

± Missense mutation of extracellular cysteine of RET

± Surgery recommended before 6 years of age

� MEN IIB ± MTC (100%), pheo (50%), mucosal ganglioneuromas (100%),

marfanoid habitus

± AD inheritance

± Missense mutation of tyrosine kinase domain of RET± Surgery recommended in infancy

� Familial MTC



Lymphoma of the Thyroid

� Usually non-Hodgkin¶s B cell type

� Pts with Hashimoto¶s thyroiditis have 70-80

fold increase risk � Typically women > 70yo present with

enlarging neck mass

�F

NA > 80% accuracy� Treatment includes XR T and chemotherapy

� 5 year survival rates 50-70%



45 year old female presents to your office with a

thyroid nodule. What questions will you ask

her?



H istory

1. Characteristics of nodule

2. Is the patient symptomatic?

1. Hyperthyroid/Hypothyroid2. Compressive sxs

3. Family history MEN endocrinopathies

4. R adiation exposure



45 year old female with thyroid nodule

1. Characteristics of nodule found

incidentally by PCP

2. Is the patient symptomatic?

No1. Hyperthyroid/Hypothyroid

2. Compressive sxs

3.F

amily history

None4. R adiation exposure None



P hysical Exam

� Size

� Consistency of nodule, multiple or solitary� Fixed or mobile

� Presence of cervical LAD



P hysical Exam

� Solitary nodule

� Mobile, not obviously adherent to adjacent

structures� No cervical LAD

� Normal voice

� Otherwise well appearing



Evaluating a thyroid nodule

� Thyroid nodules are common, but less than

10% are malignant

� History and PE

� TSH level should be obtained during initial

evaluation± If low, radioisotope study

± If normal or high, then proceed to ultrasound




What is the risk of a ³hot´ nodule on radioiodine

scan being malignant?

� Less than 1%

What about a ³cold´ nodule?

� 15% ± 20%




� R adioisotope studies may also be useful:

± FNA reports ³suspicious for follicular neoplasm´or ³indeterminate´

± Detecting neck metastasis




� What information will an ultrasound provide?

± Number of nodules± Location and size of nodules

± Cystic versus solid




� Which of the following are concerning

findings on ultrasound?

± Halo sign

± Hypoechogenic

± Calcifications

± < 1cm




� FNA is the most reliable and cost efficient wayto determine malignant from benign lesion

� 4 categories:

± Malignant, benign, suspicious, indeterminate

� Limitation of FNA:

± Cannot distinguish benign follicular or Hurthle cell

adenoma from malignancy ± based upon presenceor absence of capsular or vascular invasion

� False negative rate < 5%




� TSH level was normal

� Underwent an ultrasound-guided FNA of the

nodule, pathology revealed papillarycarcinoma in a nodule measuring 2.5cm



M anagement of P apillary Carcinoma

What surgical procedure would you offer her?

� Near-total or total thyroidectomy is recommended if:

± Tumor > 1-1.5cm

± Contralateral nodules± Local or regional metastasis

± + FHx in 1st degree relative

± + history of radiation exposure

± Age >45 yo� Increased extent of surgery lowers recurrence rates

and has improved survival in high-risk patients



M anagement of P apillary Cancer

When is lobectomy an acceptable surgicalprocedure for FNA proven papillary cancer?

� According to the American ThyroidAssociation Guidelines Taskforce, lobectomywith isthmusectomy may be sufficient

treatment for microcarcinoma (e

1cm), low-risk patients, intrathyroidal cancer withoutinvolvement of cervical LN




Will you plan on performing a lymph nodedissection?

� A central compartment (Level VI) neck dissection should be considered

� If nodal disease is evident clinically then a

more extensive cervical lymphadenectomyshould be performed

� LN sampling not recommended



S urgical Anatomy:

Lymphatics

� What are the LNs located superior to the

thryoid gland in the midline called?

� Delphian nodes



45 year old female with

papillary carcinoma

Patient opted to have a total thyroidectomy and

surgical specimen demonstrated unifocaldisease with capsular invasion and negative

LN. Does she have a favorable or unfavorable

prognosis?



P rognostic Risk Classification for P atients with

Well-Differentiated Thyroid Cancer

( AM E S or AGE S)Low Risk High Risk

� Age <40 years >40 years

� Sex Female Male

� Extent No local extension, Capsular invasion, extra-

intrathyroid, no caps thyroidal extension

invasion

� Metastasis None

R egional/distant

� Size <2 cm >4 cm

� Grade Well diff Poorly diff




What further treatment is recommended?

� TSH suppression therapy� R adioiodine ablation therapy



45 year old female with

papillary carcinoma

She wants to know what her long-term survival

is.W

hat will you tell her?

� ~ 90% at 10 years for papillary carcinoma




� TSH level was normal

� Underwent an ultrasound-guided FNA of the

nodule, pathology suspicious for a follicular neoplasm

� What is the risk that this is malignant?

� Approximately 20%

� What surgical procedure will you offer her?



M anagement of FNA suspicious for

follicular neoplasm

� Lobectomy would be a reasonable surgical

procedure, particularly in low-risk patient whoprefers limited surgical intervention

� Near-total or total thyroidectomy still

recommended for high-risk patient and/or

large tumor size



M anagement of FNA suspicious for

follicular neoplasm

� Intra-operative frozen sections can be helpful

in this scenario? True or false

� False




� You performed a lobectomy and the final

pathology reveals Hurthle cell carcinoma

� What further treatment do you recommend?

� Completion thyroidectomy with centralcompartment LN dissection

� TSH suppression therapy



P ost-operative radioiodine

remnant ablation

� To whom should it be offered?

� Stages III and IV disease� Stage II disease in pts under age 45

� Selected pts with Stage I± Multifocal disease

± Nodal metastasis

± Extrathyroidal extension

± Vascular invasion

± Aggressive histology



T MN Classification for differentiated

thyroid cancer

� T1 e 2cm

� T2 2-4cm

� T3 >4cm, limited to thyroid

� T4a Any size, invasion of SQ, trachea, esophagus, R LN

� T4b Any size invasion of prevertebral fascia or encasingcarotid/mediastinal vessels

� N0 no nodes

� N1a Level VI

� N1b All other levels

Stages

� Stage I T1, N0, M0

� Stage II T2, N0, M0

� Stage III T3, N0, M0T1-3, N1a, M0

� Stage IVA T4a, N0, M0

T4a, N1a, M0

T1-3, N1b, M0

� Stage IVB T4b, any N, M0� Stage IVC Any T and N, M1




She asks what her overall 10 year survival will

be with her diagnosis of Hurthle cell

carcinoma?

� ~70%

W

hat if she had follicular carcinoma?� ~70%



Recommendations for follow-up

(differentiated cancers)

� Thyroid cancer recurs in 20-40% patients, most

commonly within the first 2 years

� Thyroglobulin used as tumor marker checked every

6-12 months

� Whole body scan may be useful in intermediate and

high-risk patients 6-12 months after ablation� Ultrasound should be done 6-12 months after surgery,

then annually for the next 3-5 years



M anagement of recurrent and

metastatic disease

� Surgery mainstay of treatment for locoregional

disease

radioiodine

radiation� Metastatic disease treated with radioiodine

± Older patients with bony mets are less likely to

respond to radioiodine and have poor prognosis

± Pulm mets more radio responsive than bone mets



55 year old male presents to your

office with MTC on FNA

� Palpable thyroid nodule and cervical LN

� Diarrhea and flushing

� No FHx of MEN endocrinopathies

� Calcitonin elevated, FNA reveals MTC

Any further tests that you should order?� Genetic testing

� CT scan to see extent of disease





What surgical procedure will you recommend to

him?� Total thyroidectomy with LN dissection in

Level VI and LN sampling in lateral regions

(frozen sectioning intra-operatively)





What do you want to check for before bringing

him into the operating room?

� Presence of a pheochromocytoma





How would you handle the parathyroid glands?

� Some recommend performing a totalparathyroidectomy with autotransplantation in

either the forearm or SCM





� Further treatment remains controversial but

includes radiation therapy and chemotherapy� Surveillance using calcitonin levels



Surgical Anatomy:

Vasculature



Surgical Anatomy:

Vasculature and nerves



S urgical Anatomy

What is the consequence of injurying the

external branch of the superior laryngealnerve?

� Injury results in paralysis of the cricothyroid

muscle



Surgical Anatomy:

Anatomical variations of the

R ight R LN



S urgical Anatomy

What is the result of an injury to the recurrent

laryngeal nerve?

± Ipsilateral paralysis

± Contralateral paralysis



S urgical Anatomy

What would you do if the tumor involved theR LN?

� If vocal cord is paralyzed pre-operatively, thenconsider resecting the R LN along with

specimen� If no vocal cord paralysis, dissect tumor off

nerve



S urgical Anatomy:

The P arathyroids

thyroid disease1

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