Thyroid carcinomaDr. Zahoor Ahmad

PGR, SU-ISZMC/H. RYK, Pakisatan

Anatomy of Thyroid gland

includes 2 lobes. Isthmus: conical or pyramidal shape.

Embryology• 4th week: thyroid gland appears.• 5th week: break down of the thyroglossal duct, thyroid gland continue descending• 7th week: thyroid gland migrates to its position, anterior to the trachea• 10th week: thyroglossal duct disappears

Anatomy Locate deep to the sternohyoid muscle, from level C5 to T1 vertebrae or

anterior to the 2nd and 3rd tracheal rings.

Thyroid gland is attached to the trachea by the lateral suspensory (Berry) ligaments.

Blood supply

Blood supply: sup. & inf. thyroid arteries

thyroid ima artery (1.5% to 12%)

Lymph vessels:

drain to prelaryngeal, pretracheal paratracheal nodes.

Innervation: superior, middle, inferior sympathetic ganglia

Venous drainage

Superior thyroid v (to IJV) middle thyroid v. (to IJV) Inferior thyroid v. (to

brachiocephalic trunk)

Rec. laryngeal nerve location

Sim’s triangle1. Carotid artery2. Trachea3. Inferior pole of thyroid

LRLN runs parallel with the TEG

RRLN runs diagonal with the TEG

Histology of thyroid gland

Lobule: 20-30 follicles Follicle: functional unit Follicular cells Contains colloid Parafollicular cell or C-cell

Thyroid physiology

5 steps of thyroid hormone formation

1. Iodide absorption in gut2. Peroxidation of iodide3. Binding with tyrosine4. Formation of MIT & DIT5. Coupling and formation of T3 & T4 Negative feed back mechanism

Frequency

17,000 cases diagnosed annually.

Women 3 times more than men. Peak incidence 30-40s. Papillary 80%, follicular 10%,

medullary 5-10%, anaplastic 1-2%.

Etiology/Risk factors

RADIATION (most important) Family history of Goiter (ret oncogene) Family history of familial polyposis Personal history of Autoimmune

thyroiditis Inheritance of oncogenes (ret/PTC1,

ret/PTC3) Female sex Age > 45 years

Chernobyl (26-04-1986, 1:23 a.m.)

History Chief complaints Rapidly growing, Painless, palpable,

irregular, solitary nodule. Cervical lymph node enlargement Associated symptomsNeck pain, hoarseness, dysphagia, dyspnea, stridor, hemoptysis

Physical Examination

Thyroid gland Soft tissues of neck Solid, soft, mobile, or fixed? Tenderness? Laryngoscopy if hoarse preop!

Labs & investigations

Baseline labs S. calcium & S. phosphate Tumor markers (S. thyroglobulin,

S. calcitonin) CXR TFTs

Labs & investigations (cont.....)

FNAC Trucut biopsy Incisional biopsy USG neck CT scan neck & thorax MRI Thyroid scan

Classification of

CA thyroid

According to origin of cellTumors of Follicular Cell OriginDifferentiated Papillary 75%� � Follicular 10%� � Hurthle Cell 5%� � Undifferentiated Anaplastic 5%� �Tumors of Parafollicular Medullary 5%� �Other� Lymphoma <1%� �

Types Primary

1. Follicular cells (papillary, follicular, and anaplastic)

2. Para-follicular cells (medullary)3. Lymphocytes (lymphoma)

Secondary1. Metastases2. Local infiltration

STAGING FOR DIFFERENTIATED STAGING FOR DIFFERENTIATED THYROID CANCER THYROID CANCER

TNM system� AMES system AGES System GAMES system MACIS system University of Chicago system Ohio State University system National Thyroid Cancer Treatment Cooperative

Study (NTCTCS)

TNM Classification Tx- size of primary tumor unknown T1- tumor size < 2 cm T2- tumor size 2-4 cm T3- tumor size >4 cm with minimal extra-

thyroidal extension T4a- tumor of any size with extra-

thyroidal involvement up to trachea, esophagus, larynx, RLN

T4b- tumor invades paravertebral fascia, carotid artery, mediastinal lymph nodes

Nx- nodes not assesed N0- no nodes involved N1- node involvement up to level

1(pretracheal. Paratracheal, prelaryngeal)

N2- cervical or superior mediastinal l/node involvement

Mx- extent of mets can not be assesed M0- no metastases M1- presence of distant mets

University of Chicago system

An easy An easy- to-remember staging system for papillary carcinoma Class I— disease limited to the thyroid glandClass II— lymph node involvementClass III— extrathyroidal invasionClass IV — distant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

The NTCTCS created a staging approach that wasapplied prospectively to a registry of patients drawnfrom 14 cooperating institutions . pathologic staging was based upon: patient age at diagnosis� � tumor histology� � tumor size� � intrathyroidal multifocality� � extraglandular invasion� � metastases� � tumor differentiation� �

MAICS Scoring MAICS Scoring

Developed by the Mayo Clinic for staging� � It is known to be the most accurate predictor of a � �

patient's outcome patient's outcome with papillary thyroid cancer

(M = Metastasis, A = Age, I = Invasion, C = Completeness of (M = Metastasis, A = Age, I = Invasion, C = Completeness of

Resection, S = Size) Resection, S = Size) MAICS Score MAICS Score 20 year Survival 20 year

Survival <6 <6 = = 99% 99% 6 6- -7 7 = = 89% 89% 7 7- -8 8 = = 56% 56% >8 >8 = = 24% 24%P

Papillary Carcinoma

Most common (80%) Women 3 times more common 30-40 years of age Familial also Radiation exposure as a child Patients with Hashimoto’s thyroiditis Slow growing, TSH sensitive, take up

iodine, TSH stimulation produces thryroglobulin response.

Papillary Carcinoma

Pathology:Unencapsulated, arborizing papillae. Well differentiated, rare mitoses.

50% have psammoma bodies (calcific concretions, circular laminations.

Multicentric with tumor present in contralateral lobe as well.

Papillary Carcinoma

Local invasion through capsule, invading trachea, nerve, causing dyspnea, hoarseness.

Propensity to spread to the cervical lymph nodes. Clinically evident in 1/3 patients. Most commonly central compartment, located medial to carotids, from hyoid to sternal notch.

Distant spread to bone, lungs.

Follicular Carcinoma

Second most common (10%) Iodine deficient areas 3 times more in women Present more advanced in stage than

papillary Late 40’s Also TSH sensitive, takes up iodine,

produces thryroglobulin.

Follicular Carcinoma

Pathology: round, encapsulated, cystic changes, fibrosis, hemorrhages. Microscopically, neoplastic follicular cells.

Differentiated from follicular adenomas by the presence of capsule invasion, vascular invasion.

Cannot reliably diagnose based on FNA.

Follicular Carcinoma

Local invasion is similar to papillary cancer with the same presentation.

Cervical metastases are uncommon. Distant metastases is significantly

higher (20%), with lung and bone most common sites.

Treatment and Prognosis

Controversy regarding extent of therapy continues.

Surgical excision whenever possible. Total thyroidectomy has been

mainstay (all apparent thyroid tissue removed). Complications include nerve damage bilaterally, parathyroid injury bilaterally.

After, get radioiodine scan, ablation if residual disease or recurrence.

Treatment and Prognosis

Over the years, modification to procedure to reduce the above complications.

Subtotal thyroidectomy( small portion of thyroid tissue opposite the side of malignancy is left in place) and postop ablation.

Thyroid lobectomy and isthmectomy also a viable option with small tumors

Neck

Examine the neck prior to surgery to detect lymph node spread.

Gross cervical mets should be removed en bloc with a dissection in the compartment in which they reside.

Excision of single nodes is not adequate.

Elective lymph node dissection is not done, as radioactive iodine takes care of this.

Postoperative Radioiodine and Ablation

Radioiodine targets residual thyroid tissue and tumor after thyroidectomy.

Given in diagnostic doses and therapeutic doses to ablate tissue.

Thyroid Suppression Therapy

Maintained on thyroxine after surgery and ablation. Low TSH levels reduce tumor growth rates and reduce recurrence rates.

Most recommend TSH levels of 0.1 mU/l.

Follow-up q 6 months with thyroglobulin levels and repeat scans.

Thyroglobulin is good because well differentiated tumors produce it.

Prognosis

Age: at diagnosis. Cancer relate death more common if patient is older than 40 years.

Recurrences common in patients diagnosed when they were less than 20 years or older than 60 years.

Men are twice more likely as women to die.

Tumors greater than 4 cm have higher recurrence, death.

Prognosis

Histology:papillary has 30 year cancer related death rate of 6%. Follicular has a 30 year cancer related death rate of 15%.

Local invasion portends poorer prognosis. After surgery, thyroxine is given. Do I scanning

after stopping it for 6 weeks, TSH high now. Do scan, if some tissue remains on diagnostic dose, ablate it. Do it again if needed.

LN metastases not important for prognosis. Distant metastases associated with a 68.1-fold

increase in the rate of disease specific death.

Hurthle Cell

A variant of follicular, also known as oncocytic carcinoma. 5 year survival 50%.

More common in women than men, presents in 5th decade of life.

Same clinical presentation. Cannot diagnose on FNA Does not take up iodine, so treat

aggressively. Thyroid suppression and radioiodine don’t

work.

Medullary Carcinoma

5%, female preponderance 75% sporadically, 25% familial. Familial

cases are usually all over the gland, sporadic usually not multifocal.

MEN 2A, MEN2B and FMTC syndromes.

Men 2a, 2b, FMTC

MEN 2a is Sipple syndrome,MTC, pheochromocytoma, hyperparathyroidism.

MEN 2b is MTC, pheo, ganglionomas, marfan habitus.

FMTC is just MTC Medullary cancer in these are most

aggressive, younger age, rapid growth and metastases.

In sporadic you get painless nodule, symptoms of invasion.

Biochemical Testing

Stimulating calcitonin release with IV pentagastrin increases sensitivity of test.

First measure baseline calcitonin, then give pentagastrin. Measure calcitonin serially 1.5 and 5 min later.

Used as tumor marker postop rather than screening now.

Use genetic testing for screening. Histologically test for calcitonin and

CEA.

Treatment

Total thyroidectomy Lymph node dissection of level VI. Parathyroid reimplantation if necessary. Lymph node mets are very common. Prophylactic thyroidectomy in children

with MEN 2a,b. Surveillance with CEA, calcitonin. Does not take up iodine, so no

radioiodine. Prognosis 10 y is 65%.

Anaplastic Thyroid Carcinoma

Bad.

Indications for Thyroid Lobectomy

Suspicion for malignancy Compressive symptoms Cosmetic issues Patient wishes Well-differentiated thyroid carcinoma in

low risk patient (controversial)

Indications for Total Thyroidectomy

Well-differentiated thyroid cancer Medullary thyroid cancer Sarcoma of thyroid Lymphoma of thyroid Obstructive goiter