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 favorable prognosis

Classification & Incidence of Thyroid Cancer

Follicular cell origin
Differentiated
Papillary Follicular Hurthle cell 80% 10% 3-5% 1-2% 5%

Undifferentiated
Anaplastic

Parafollicular cell origin

Medullary

Papillary 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- and lower-anterior cervical chain (Level VI) 20-50% patients have involvement of cervical LN

Follicular Carcinoma
Only 10% of thyroid cancers in developed countries, although more prevalent in regions with iodine deficiency 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

Follicular Carcinoma
Where does follicular carcinoma tend to metastasize? Bone Lung

Hurthle Cell Carcinoma

High propensity to spread to cervical lymph nodes and high incidence of distant metastasis Less than 10% of Hurthle cell carcinomas take up 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 Radiation and chemotherapy have not demonstrated any significant improvement in survival Median survival ~ 4 - 6 months

Medullary 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

Medullary 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-Hodgkins B cell type Pts with Hashimotos thyroiditis have 70-80 fold increase risk Typically women > 70yo present with enlarging neck mass FNA > 80% accuracy Treatment includes XRT 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?

History
1. Characteristics of nodule 2. Is the patient symptomatic?
1. Hyperthyroid/Hypothyroid 2. Compressive sxs

3. Family history MEN endocrinopathies 4. Radiation exposure

45 year old female with thyroid nodule

1. Characteristics of nodule found incidentally by PCP 2. Is the patient symptomatic? No
1. Hyperthyroid/Hypothyroid 2. Compressive sxs

3. Family history None 4. Radiation exposure None

Physical Exam
Size Consistency of nodule, multiple or solitary Fixed or mobile Presence of cervical LAD

Physical 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

Evaluating a thyroid nodule

What is the risk of a hot nodule on radioiodine scan being malignant? Less than 1% What about a cold nodule? 15% 20%

Evaluating a thyroid nodule

Radioisotope studies may also be useful:
FNA reports suspicious for follicular neoplasm or indeterminate Detecting neck metastasis

Evaluating a thyroid nodule

What information will an ultrasound provide?
Number of nodules Location and size of nodules Cystic versus solid

Evaluating a thyroid nodule

Which of the following are concerning findings on ultrasound?
Halo sign Hypoechogenic Calcifications < 1cm

Evaluating a thyroid nodule

Which of the following are concerning findings on ultrasound?
Halo sign Hypoechogenic Calcifications < 1cm

Evaluating a thyroid nodule

FNA is the most reliable and cost efficient way to 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 presence or absence of capsular or vascular invasion

False negative rate < 5%

45 year old female with thyroid nodule

TSH level was normal Underwent an ultrasound-guided FNA of the nodule, pathology revealed papillary carcinoma in a nodule measuring 2.5cm

Management of Papillary 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

Management of Papillary Cancer

When is lobectomy an acceptable surgical procedure for FNA proven papillary cancer? According to the American Thyroid Association Guidelines Taskforce, lobectomy with isthmusectomy may be sufficient treatment for microcarcinoma (e 1cm), lowrisk patients, intrathyroidal cancer without involvement of cervical LN

Management of Papillary Cancer

Will you plan on performing a lymph node dissection? A central compartment (Level VI) neck dissection should be considered If nodal disease is evident clinically then a more extensive cervical lymphadenectomy should be performed LN sampling not recommended

Surgical Anatomy: Lymphatics

Surgical 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 unifocal disease with capsular invasion and negative LN. Does she have a favorable or unfavorable prognosis?

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (AMES or AGES)
Age Sex Extent Low Risk <40 years Female
No local extension, intrathyroid, no caps invasion

High Risk >40 years Male

Capsular invasion, extrathyroidal extension

Metastasis Size Grade

None <2 cm Well diff

Regional/distant >4 cm Poorly diff

Management of Papillary Cancer

What further treatment is recommended? TSH suppression therapy Radioiodine ablation therapy

45 year old female with papillary carcinoma

She wants to know what her long-term survival is. What will you tell her? ~ 90% at 10 years for papillary carcinoma

45 year old female with thyroid nodule

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?

Management of FNA suspicious for follicular neoplasm

Lobectomy would be a reasonable surgical procedure, particularly in low-risk patient who prefers limited surgical intervention Near-total or total thyroidectomy still recommended for high-risk patient and/or large tumor size

Management of FNA suspicious for follicular neoplasm

Intra-operative frozen sections can be helpful in this scenario? True or false False

45 year old female with thyroid nodule

You performed a lobectomy and the final pathology reveals Hurthle cell carcinoma

What further treatment do you recommend? Completion thyroidectomy with central compartment LN dissection TSH suppression therapy

Post-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

TMN Classification for differentiated thyroid cancer

Stages T1 e 2cm T2 2-4cm T3 >4cm, limited to thyroid T4a Any size, invasion of SQ, trachea, esophagus, RLN T4b Any size invasion of prevertebral fascia or encasing carotid/mediastinal vessels Stage I Stage II Stage III Stage IVA T1, N0, M0 T2, N0, M0 T3, N0, M0 T1-3, N1a, M0 T4a, N0, M0 T4a, N1a, M0 T1-3, N1b, M0 T4b, any N, M0 Any T and N, M1

N0 no nodes N1a Level VI N1b All other levels

Stage IVB Stage IVC

45 year old female with thyroid nodule

She asks what her overall 10 year survival will be with her diagnosis of Hurthle cell carcinoma? ~70% What 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

Management 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

55 year old male presents to your office with MTC on FNA

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)

55 year old male presents to your office with MTC on FNA

What do you want to check for before bringing him into the operating room? Presence of a pheochromocytoma

55 year old male presents to your office with MTC on FNA

How would you handle the parathyroid glands? Some recommend performing a total parathyroidectomy with autotransplantation in either the forearm or SCM

55 year old male presents to your office with MTC on FNA

Further treatment remains controversial but includes radiation therapy and chemotherapy Surveillance using calcitonin levels

Surgical Anatomy: Vasculature

Surgical Anatomy: Vasculature and nerves

Surgical Anatomy
What is the consequence of injurying the external branch of the superior laryngeal nerve? Injury results in paralysis of the cricothyroid muscle

Surgical Anatomy: Anatomical variations of the Right RLN

Surgical Anatomy
What is the result of an injury to the recurrent laryngeal nerve?
Ipsilateral paralysis Contralateral paralysis

Surgical Anatomy
What is the result of an injury to the recurrent laryngeal nerve?
Ipsilateral paralysis Contralateral paralysis

Surgical Anatomy
What would you do if the tumor involved the RLN? If vocal cord is paralyzed pre-operatively, then consider resecting the RLN along with specimen If no vocal cord paralysis, dissect tumor off nerve

Surgical Anatomy: The Parathyroids

Surgical Anatomy: The Parathyroids

What are your options if the blood supply to the parathyroids has been compromised? Implantation within the sternocleidomastoid muscle or forearm muscle for easy access