Vicente Sotto Memorial Medical Center Department of Otolaryngology, Head and Neck Surgery

BENIGN THYROID DISEASES

Embryology
Begins its development at the foramen cecum at the base of the tongue Descends through the tissues of the neck and comes to rest overlying the trachea Leaves a tract behind it² could be the source of pathology in later life Descent complete at 7th gestational week.

Embryology
If descent is completely arrested- lingual thyroid results. If the inferiormost portion of the thyroglossal duct tract is maintained- pyramidal lobe is formed. If the remnant of the thyroid tissue is left along the thyroglossal duct tract- it can cystify and enlarge, forming a thyroglossal duct cyst.

Pyramidal Lobe

Lingual Thyroid

Thyroglossal duct Cyst

Anatomy
Composed of 2 lateral lobes connected by an isthmus Rests on the level of 2nd to 4th tracheal cartilages Each lobe measures approximately 4cm high, 1.5 cm wide, 2cm deep. Ventral surface of the gland is covered by the infrahyoid strap muscle musculature.

Anatomy
Capsules: True capsule (thickening of the connecting tissue) False capsule (pretracheal fascia)

Anatomy
Important relations: Anterior: Strap muscles strenohyoid muscle sternothyroid muscle In surgery, retracting these muscles will expose the thyroid gland

Anatomy
Important relations: Posterior: trachea
† enlargement

of thyroid gland can compress trachea and cause difficulty in breathing

esophagus

Anatomy
Important relations: Posterolateral: Carotid artery Internal jugular vein Embedded inside the gland: 2 pairs of parathyroid gland

Anatomy
Nerves: Recurrent laryngeal nerve Runs in the tracheoesophageal groove Passes in between the branches of the inferior thyroid artery
† During 

surgery, inferior thyroid artery will be clamped. RLN can be accidentally damaged as well.
1 side damage: Husky voice  Both side damage: No voice & Stridor

Anatomy
Venous Drainage: Superior thyroid vein
† drains

into internal jugular vein

Middle thyroid vein
† drains

into internal jugular vein

Inferior thyroid vein
† drains

into brachiocephalic vein

Anatomy
Lymphatic drainage Pretracheal lymph node Paratracheal lymph node Deep cervical lymph node

Microscopic Arrangement
Arranged as follicles † lined by cuboidal epithelium † cells secrete thyroxine  binds to globulin & stored as thyroglobulin (colloid) † in between follicles  parafollicular cells (secrete calcitonin)  medullary carcinoma arise from here
†

Physiology
Thyroid Gland produces 2 hormones: T3 and T4 Follicular lumen: used for the storage of hormones and their precursors.

Physiology
Iodide Transport - The thyroid normally concentrates iodide 20-fold to 40-fold over the extracellular space and against an electrical gradient of approx. 40 mV. - Sodium/iodide symporter- protein which is the key to the trapping action of thyroid

Physiology
Iodide Transport - Pendrin: an apical membrane protein which aids in releasing iodide into the follicular lumen - Pendred·s syndrome: associated with mild hypothyroidism, goiter, and hearing loss : mutations in the gene and coding protein of pendrin.

Physiology
Thyroglobulin - a tissue-specific protein that serves as a matrix for the synthesis of hormone and as a vehicle for its storage. - about 10% of its weight is carbohydrate, and about 0.1% and 1% is iodine

Physiology
Iodination and Thyroperoxidase - newly formed thyroglobulin and iodide meet at the apical surface, where hormone synthesis occurs. - process includes: 1. Oxidation of iodide. 2. Subsequent transfer to thyrosyl residues on thyroglobulin, producing MIT and DIT. 3. Coupling of 2 iodotyrosine molecules, either 1 each of MIT and DIT to form T3 or 2 of DIT to form T4.

Physiology
Storage and Release of Hormone - Hormone release is initiated by retrieval of thyroglobulin from follicular lumen. - When released from thyroglobulin, the thyroid hormones and their precursors enter the cytosol; there MIT and DIT are deiodinated by an iodotyrosine-deiodinase, and the released iodotyrosine-enters the iodine pool.

Physiology
Storage and Release of Hormone - Hormone release is initiated by retrieval of thyroglobulin from follicular lumen. - When released from thyroglobulin, the thyroid hormones and their precursors enter the cytosol; there MIT and DIT are deiodinated by an iodotyrosine-deiodinase, and the released iodotyrosine-enters the iodine pool.

Physiology
Circulating Thyroid Hormones - < 1% of circulating thyroid hormones exist as free iodo-amino acids. - The remainder are bound in reversible, noncovalent linkage to 1 of several plasma proteins. - In humans, the most important is TBG, accounting for approximately70% of circulating hormones. - Very high affinity to T4 and low affinity to T3.

Physiology
Metabolism of Thyroid Hormones - Type 2 deiodinase is present primarily in CNS, the pituitary, the placenta, and the skin, and has more recently been found in th thyroid. - Major Role: major production of T3. - May also contribute to circulating T3

Physiology
Metabolism of Thyroid Hormones - Type 2 deiodinase is present primarily in CNS, the pituitary, the placenta, and the skin, and has more recently been found in th thyroid. - Major Role: major production of T3. - May also contribute to circulating T3

Physiology
Control of Thyroid Function
-Circulating levels of TSH are controlled by the opposing influences of thyroid hormones, and TRH from the hypothalamus. -As levels of thyroid hormone increase in response to TSH stimulation, T4 and T3 block the TRH-stimulated release of TSH in the thyrotrope.

Physiology
Control of Thyroid Function

Plasma T4

TSH

Plasma T4

TSH

Physiology
Antithyroid Agents - can inhibit thyroid hormone synthesis and metabolism. Lithium- blocks thyroglobulin endocytosis. Iodinated radiocontrast agentspotent inhibitors of thyroid hormone deiodination

Thank you!

BENIGN THYROID DISEASE
Brenda Jim T. Murga ² SWU MHAM

Differential diagnosis of the thyroid nodule
95%
nodule ² MNG † Adenoma † Cyst † Focal thyroiditis † Carcinoma
† Colloid

Nonthyroid
† Lymph

s/p hemithyroidectomy  Hemiagenesis  Metastasis to thyroid  Nonthyroid 

node † Parathyroid cyst † Cystic hygroma, dermoid, teratoma † Laryngocoele † Thyroglossal duct cyst

Modified from: Castro, MR, Gharib, H. Endocr Pract 2003; 9:128.

Hypothyroidism

Overview of Thyroid Disease States
Hypothyroidism Hyperthyroidism

Hypothyroidism
Hypothyroidism is a disorder with multiple causes in which the thyroid fails to secrete an adequate amount of thyroid hormone
† † †

The most common thyroid disorder Usually caused by primary thyroid gland failure Also may result from diminished stimulation of the thyroid gland by TSH

Hyperthyroidism
Hyperthyroidism refers to excess synthesis and secretion of thyroid hormones by the thyroid gland, which results in accelerated metabolism in peripheral tissues

Typical Thyroid Hormone Levels in Thyroid Disease

Hypothyroidism Hyperthyroidism

TSH High
Low

T4 Low
High

T3 Low
High

Hypothyroidism: Types
Primary hypothyroidism
†

From thyroid destruction From deficient TSH secretion, generally due to sellar lesions such as pituitary tumor or craniopharyngioma Infrequently is congenital From deficient TSH stimulation above level of pituitary³ie, lesions of pituitary stalk or hypothalamus Is much less common than secondary hypothyroidism

Central or secondary hypothyroidism
† †

Central or tertiary hypothyroidism
† †

Bravernan LE, Utiger RE, eds. Werner & Ingbar's The Thyroid. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000. Persani L, et al. J Clin Endocrinol Metab. 2000; 85:3631-3635.

Primary Hypothyroidism: Underlying Causes
Congenital hypothyroidism
† †

Agenesis of thyroid Defective thyroid hormone biosynthesis due to enzymatic defect Chronic autoimmune (Hashimoto) thyroiditis Radiation (usually radioactive iodine treatment for thyrotoxicosis) Thyroidectomy Other infiltrative diseases of thyroid (eg, hemochromatosis)

Thyroid tissue destruction as a result of
† † † †

Drugs with antithyroid actions (eg, lithium, iodine, iodinecontaining drugs, radiographic contrast agents, interferon alpha) In the US, hypothyroidism is usually due to chronic autoimmune (Hashimoto) thyroiditis

Clinical Features of Hypothyroidism
Tiredness Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Inability to Concentrate Thinning Hair/Hair Loss Loss of Body Hair Dry, Patchy Skin Weight Gain Cold Intolerance Elevated Cholesterol Family History of Thyroid Disease or Diabetes Puffy Eyes Enlarged Thyroid (Goiter) Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Difficulty Swallowing Slower Heartbeat Menstrual Irregularities/ Heavy Period Infertility Constipation Muscle Weakness/ Cramps

Hypothyroidism
Differential diagnosis Primary gland failure
† † †

Clinical manifestations

† † † †

Hashimoto thyroiditis Iodine deficiency Associated with thyroiditis (lymphocytic/postpartum, subacute) Radiation- induced Postsurgical Drugs (lithium, iodine) Hereditary metabolic defects in hormonogenesi s

Central hypothyroidism

Fatigue, slowed mentation, change in memory, depression, cold intolerance, hoarseness, brittle hair, dry skin, thick tongue, weight gain, constipation/ileus, menstrual disturbance, bradycardia, nonpitting edema, hyporeflexia, psychosis, hyponatremia, psychosis, hyponatremia, hypoglycemia, coma. In infants, mental retardation/ cretinism

Disorders Characterized by Hyperthyroidism

Signs and Symptoms of Hyperthyroidism
Nervousness/Tremor Mental Disturbances/ Irritability Difficulty Sleeping Bulging Eyes/Unblinking Stare/ Vision Changes Enlarged Thyroid (Goiter) Menstrual Irregularities/ Light Period Frequent Bowel Movements Warm, Moist Palms First-Trimester Miscarriage/ Excessive Vomiting in Pregnancy Sudden Paralysis Family History of Thyroid Disease or Diabetes Palpitations/ Tachycardia Impaired Fertility Weight Loss or Gain Heat Intolerance Increased Sweating Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Difficulty Swallowing

Hyperthyroidism
Differential diagnosis Clinical manifestations

Graves disease Toxic nodule/multinodular goiter Thyroiditis Exogenous hyperthyroidism/ struma overii/functional thyroid cancer Thyrotropin, thyrotropin-like secreting tumor (pituitary, trophoblastic, other)

Weight loss, fatigue, nervousness, tremor, palpitations, increased appetite, heat intolerance, muscle weakness, diarrhea, sweating, menstrual disturbance

Hyperthyroidism Underlying Causes
Signs and symptoms can be caused by any disorder that results in an increase in circulation of thyroid hormone
† † † † † †

† †

Toxic diffuse goiter (Graves disease) Toxic uninodular or multinodular goiter Painful subacute thyroiditis Silent thyroiditis Toxic adenoma Iodine and iodine-containing drugs and radiographic contrast agents Trophoblastic disease, including hydatidiform mole Exogenous thyroid hormone ingestion

Graves Disease (Toxic Diffuse Goiter)
The most common cause of hyperthyroidism
Accounts for 60% to 90% of cases † Incidence in the United States estimated at 0.02% to 0.4% of the population † Affects more females than males, especially in the reproductive age range
†

Graves disease is an autoimmune disorder possibly related to a defect in immune tolerance

Thyroid Nodular Disease
Thyroid gland nodules are common in the general population Palpable nodules occur in approximately 5% of the US population, mainly in women Most thyroid nodules are benign
† †

Less than 5% are malignant Only 8% to 10% of patients with thyroid nodules have thyroid cancer

Multinodular Goiter (MNG)
MNG is an enlarged thyroid gland containing multiple nodules
The thyroid gland becomes more nodular with increasing age † In MNG, nodules typically vary in size † Most MNGs are asymptomatic
†

MNG may be toxic or nontoxic
Toxic MNG occurs when multiple sites of autonomous nodule hyperfunction develop, resulting in thyrotoxicosis † Toxic MNG is more common in the elderly
†

Treatment of hyperthyroidism
Treatment is usually initiated with antithyroid drugs in order to render the patient euthyroid Radioiodine ablation represents a more definitive modality which involves oral administration of Iodine 131 .
† Areas

of increased uptake are preferentially injured through beta-radiation

Antithyroid Medication
Propylthiouracil (PTU) and Methimazole
† Thionamides

/ antithyroid drugs introduced in the

1940s † Block iodine organification & TH synthesis. In addition, PTU blocks peripheral conversion of T4 / T3 † PTU is given TID and methimazole OD, both typically require administration over 6-8 weeks before rendering a patient euthyroid

Antithyroid Medication
Iodides
† Potassium

iodide and Lugol solution inhibits organification & prevents TH release † Given preoperatively to decrease thyroid gland vascularity † Antithyroid effect is transient, with escape within 2 weeks, and is termed the Wolff-Chaikoff effect † Prolonged high-dose iodides, especially in the setting of toxic nodular goiter, can result in hyperthyroidism

Antithyroid Medication
Beta- adrenergic blockers
† Examples

include propanolol or nadolol † Blocks peripheral TH effects (do not alter TH production) † Useful in symptomatic control while other treatments are initiated and also in transient forms of hyperthyroidism associated with thyroiditis † Contraindicated in patients with asthma, COPD, cardiac failure, insulin-dependent diabetes, bradyarrythmias, and those taking monoamine oxidase inhibitors and tricyclics

Chronic Autoimmune Thyroiditis (Hashimoto Thyroiditis)
Occurs when there is a severe defect in thyroid hormone synthesis
†

Is a chronic inflammatory autoimmune disease characterized by destruction of the thyroid gland by autoantibodies against thyroglobulin, thyroperoxidase, and other thyroid tissue components Patients present with hypothyroidism, painless goiter, and other overt signs

†

Persons with autoimmune thyroid disease may have other concomitant autoimmune disorders
†

Most commonly associated with type 1 diabetes mellitus

Subacute granulomatous thyroiditis
De Quervain thyroiditis, most common cause of painful thyroid Viral in etiology presents with enlarged, painful thyroid, often after upper respiratory tract infection, fever and malaise are common Pain in the perithyroid region typically radiates up the neck to the angle of the jaw. The pain & enlargement may only involve a portion of the gland and later migrate to the opposite lobe.

Lymphocytic thyroiditis
Also termed silent, painless, or postpartum thyroiditis Etiology unknown, but believed to be an autoimmune process Painless with course similar to subacute thyroiditis Occurs sporadically but is common in postpartum females; it may occur in up to 5% of such women Presents as painless, symmetric thyroid enlargement and reversible hyperthyroidism Thyrotoxicosis is self-limiting, no treatment needed.

Acute suppurative thyroiditis
Rare thyroid infection with abscess formation Most often bacterial (commonly due to Staphylococcus, Streptococcus, or Enterobacter) but can be fungal or even parasitic Typically presents in the setting of an upper respiratory tract infection Treatment is with incision and drainage and parenteral antibiotics Children may demonstrate left pyriform sinus fistulae, so after acute treatment, evaluation for this condition is reasonable, including barium swallow, CT, or endoscopy

Reidel struma
Rare inflammatory process of unknown etiology, thyroid equivalent to sclerosing cholangitis or retroperitoneal fibrosis. Large, nontender goiter with a woody consistency fixed to surrounding structures. Clinical course characterized by progressive regional symptoms, include dysphagia, tracheal compression, and possibly RLN paralysis.

Euthyroid goiter
Nontoxic diffuse and multinodular goiter Thyroid enlargement without significant functional derangement may occur with diffuse anodular enlargement (nontoxic diffuse goiter) or through multinodular formation (multinodular goiter). Goiter development can be sporadic or associated with iodine deficiency, inherited metabolic defects or exposure to goitrogenic agents.

Euthyroid goiter
nontoxic diffuse goiter : thyroid function test are normal Multinodular goiter: thyroid function test may show normal T4 and T3, with TSH low normal (subclinical hyperthyroidism) UTZ should be performed even when multiple nodules are present (2 or more nodules measure 1 to 1.5cm; those w/ suspicious sonographic appearance such as microcalcification and intranodular hypervascularity

Degree of clinical concern for carcinoma in a thyroid nodule based on Hx and PE
Less Concern More Concern
Age <20 >60 years Males Rapid growth, pain History of radiation therapy Family history of thyroid carcinoma Hard fixed lesione Lympadenopathy Vocal cord paralysis Size >4cm Aerodigestive tract compromise (Stridor, dysphagia)

Chronic stable examination Evidence of a functional disorder (Hashimoto·s, toxic nodule) Multinodular gland without dominant nodule

WORKUP: LABORATORY EVALUATION

Diagnostic Laboratory
Sensitive TSH assay TPO antibodies Thyroglobulin Calcitonin Radionuclide scanning Ultrasonography FNAB

Laboratory
Sensitive TSH assay
† Excellent

screening test to definitely diagnose euthyroidism, hyperthyroidism , or hypothyroidism and is recommended in the initial evaluation of patients with a thyroid nodule helpful in the diagnosis of Hashimoto thyroiditis

TPO antibodies
† Are

Laboratory
Thyroglobulin
by both normal and to some degree by malignant thyroid tissue † The assay is interfered with by antithyroglobulin antibodies that occur in approximately 15% to 25% of patients † Extensive overlap in thyroglobulin levels exists between benign thyroid conditions and thyroid carcinoma † Thyroglobulin measures are not useful in the workup of the thyroid nodule and strongly recommended against in management guidelines
† Secreted

Laboratory
Calcitonin
† Is

not thought to be a reasonable routine screening test in patients with a solitary nodule

Radionuclide scanning
† Has

been used routinely in the past for the workup of thyroid nodularity † 95% of all nodules are typically found to be cold, only 10% to 15% of cold nodules are malignant
†

Ultrasonography
Recommended that thyroid sonography should be performed in all patients with one or more suspected thyroid nodules. It can provide an accurate baseline, giving baseline information as to nodule size, identifying other nodules including contralateral nodularity, and identifying cervical adenopathy.

Ultrasonography
Advantages
Most sensitive procedure or identifying lesions in the thyroid (2-3mm) † 90% accuracy in categorizing nodules as solid, cystic, or mixed (Rojeski, 1985) † Best method of determining the volume of a nodule (Rojeski,
†
1985)

Can detect the presence of lymph node enlargement and calcifications † Noninvasive and inexpensive
†

Ultrasonography« when to use«
Long term follow-up for the following:
to evaluate the involution of a multinodular gland or a solitary benign nodule under suppression therapy  monitor for reaccumulation of a benign cystic lesion  follow thyroid nodules enlargement during pregnancy 

Evaluation of a thyroid nodule:
help localize a lesion and direct a needle biopsy when a nodule is difficult to palpate or is deep-seated  Determine if a benign lesion is solid or cystic 

Ultrasonography

Disadvantages
Unable to reliably diagnose true cystic lesions  Cannot accurately distinguish benign from malignant nodules 

Thyroid UTZ
Benign Characteristics Regular border Halo (sonolucent rim) Hyperechoic Egg shell calcification N/A Malignant Characteristics Irregular border No Halo Hypoechoic (more vascular) Microcalcification
Intranodular vascular spots (color doppler)

Evaluation of the Thyroid Nodule
(Radioimaging)

Radioimaging usually not used in initial work-up of a thyroid nodule
Chest radiograph  Computed tomography  Magnetic resonance imaging 

Radioimaging
CXR Ultrasound
† † † †

Solid/cystic Multicentric Lymph node involvement Ultrasound-assisted FNA

CT/MRI of neck
† † †

Mainly for large/recurrent cancers Vascular/lymphatic invasion Cervical/mediastinal metastasis

Evaluation of the Thyroid Nodule
(Radioisotope Scanning)
Prior to FNA, was the initial diagnostic procedure of choice Performed with: technetium 99m pertechnetate or radioactive iodine 

Technetium 99m pertechnetate 
  

cost-effective readily available short half-life trapped but not organified by the thyroid - cannot determine functionality of a nodule

Radioisotope Scanning (continued«) 
Radioactive 

iodine

radioactive iodine (I-131, I-125, I-123)  is trapped and organified  can determine functionality of a thyroid nodule

Radioisotope Scanning (continued...)
Limitations
† Not

as sensitive or specific as fine needle aspiration in distinguishing benign from malignant nodule 


90%-95% of thyroid nodules are hypofunctioning, with 10%-20% being malignant (Geopfert, 1994, Sessions, 1993) Campbell and Pillsbury (1989) performed a meta-analysis of 10 studies correlating the results of radionuclide scans in patients with solitary thyroid nodules with the pathology reports following surgery and found:  17% of cold nodules, 13% of warm or cool nodules, and 4% of hot nodules to be malignant

Radioisotope Scanning (continued«)
Specific uses of thyroid scanning: 
Preoperative 
When

evaluation

patients have benign (by FNA), solid (by U/S)

lesions  When patients have nonoxyphilic follicular neoplasms 
Postoperative 
immediately

evaluation
postop for localization of residual cancer or

thyroid tissue  follow-up for tumor recurrence or metastasis (Geopfert, 1994)

Thyroid Scan
Thyroid nodule: risk of malignancy 6.5% only 5-10% of nodules

Cold nodule

16-20% malignant

´Warmµ Nodule

Hot Nodule

(indeterminant) 5% malignant

Tc-99m < 5% malignant I123 < 1% malignant

FNAB
Fine needle aspiration (FNA) via UTZ guidance is strongly recommended as the diagnostic procedure of choice for the evaluation of thyroid nodules. e

FNAB
Recommendations :
† FNA

is the procedure of choice in evaluation of thyroid nodules † Repeated nondiagnostic aspirate of cystic nodules need close observations or surgical excision. Surgery is highly recommended if the nondiagnostic nodule is solid † Surgery is recommended for all aspirates categorized as malignant † Nodules found to be benign on cytology do not require further diagnostic studies or treatment beyond ff up.

FNAB
Reading suspicious for papillary carcinoma or Hurthle cell neoplasm should be treated with either lobectomy or total thyroidectomy. There is no need for radionuclie scanning.

Fine-Needle Aspiration (continued«)
FNA halved the number of patients requiring thyroidectomy (Mazzaferri, 1993) FNA has double the yield of cancer in those who do undergo thyroidectomy (Mazzaferri, 1993)

Fine-Needle Aspiration (continued«)
Pathologic results are categorized as:
positive,  negative, or  indeterminate 

Hossein and Goellner (1993) use four categories. They pooled data from seven series and came up with the following rates:
benign - 69%  suspicious -10%  malignant - 4%  nondiagnostic - 17% 

Fine-Needle Aspiration (continued«)
Limitations 

skill of the aspirator  

Sampling error in lesions <1cm, >4cm, multinodular lesions, and hemorrhagic lesions Error can be diminished using ultrasound guidance

expertise of the cytologist  difficulty in distinguishing some benign cellular adenomas from their malignant counterparts (follicular and Hurthle cell) 

False negative results = 1%-6% (Mazzeferri, 1993) False positive results = 3%-6% (Rojeski, 1985, Mazzeferri,
1993, Hall, 1989)

Evaluation of the Thyroid Nodule
(Fine-Needle Aspiration) Currently considered to be the best first-line diagnostic procedure in the evaluation of the thyroid nodule: Advantages:
Safe  Cost-effective  Minimally invasive  Leads to better selection of patients for surgery than any other test (Rojeski, 1985) 

Modified from: Castro, MR, Gharib, H. Endocr Pract 2003; 9:128.

Solitary Thyroid Nodule
FNAC Result
Benign Malignant Indeterminate Observe and repeat FNAC 1 year Surgery serum TSH normal Serum TSH low InadequateRepeat FNA Surgery Scintiscan

Fine-Needle Aspiration
Best tool for determining pathology other than surgical excision. Can be as high as 80 % sensitive and 95% specific. Operator dependent in obtaining adequate amount of tissue. 25 gauge needle is optimal. Should not be relied on if negative in patient with previous neck irradiation.
† Multifocal

tumors common.

Interpreting the Biopsy Report
What you get:
benign † indeterminate † suspicious † inadequate specimen
†

What it means:
benign - 90-95% likelihood it is benign † indeterminate- who knows? † suspicious- it·s malignant. † inadequate specimen - do it again (and again)
†

Benign Lesions

Papillary Carcinoma
Surgical Specimen FNA

Follicular Lesions on FNA: Can·t Distinguish!

RED flags for Thyroid cancer
Male gender Extremes in age (younger than 20 years old and older than 65 years) Rapid growth of nodule Symptoms of local invasion (dysphagia, neck pain, hoarseness) History of radiation to the head or neck Family history of thyroid cancer or polyposis (Gardner·s syndrome)

THANK YOU
Brenda Murga

MALIGNANT THYROID DISEASE
Clent Banaay

Classification of Malignant Thyroid Neoplasms
Papillary carcinoma
Follicular variant  Tall cell  Diffuse sclerosing  Encapsulated 

Medullary Carcinoma Miscellaneous
Sarcoma  Lymphoma  Squamous cell carcinoma  Mucoepidermoid carcinoma  Clear cell tumors  Pasma cell tumors  Metastatic  

  

Follicular carcinoma
Overtly invasive  Minimally invasive 

Hurthle cell carcinoma Anaplastic carcinoma
Giant cell  Small cell 

Direct extention Kidney Colon Melanoma

Papillary Carcinoma
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accounts for 80 % of all thyroid malignancies in iodine-sufficient areas and is the predominant thyroid cancer in children and individuals exposed to external radiation. More common in women (2:1 ratio) Mean age: 30-40 yrs old Most patients are euthyroid and present with a slow-growing painless mass in the neck

Histologic subtypes
Follicular variant  Tall cell  Columnar cell  Diffuse sclerosing  Encapsulated 

Prognosis is 80% survival at 10 years Females > Males Mean age of 35 years

Lymph node involvement is common 
Major

route of metastasis is lymphatic 46%-90% of patients have lymph node involvement Clinically undetectable lymph node involvement does not worsen prognosis

Lymph node metastases are common, especially in children and young adults, and may be the presenting complaint. Diagnosis is established by FNA biopsy of the thyroid mass or lymph node. Distant metastases are uncommon at initial presentation, but may ultimately develop in up to 20 percent of patients. The most common sites are the lungs, followed by bone, liver, and brain.

In general, patients with papillary carcinoma have an excellent prognosis with a greater than 95 % 10year survival rate. Pathologic feature:
Gross - vary considerably in size - often multi-focal - unencapsulated but often have a pseudocapsule  Histology - closely packed papillae with little colloid - psammoma bodies - nuclei are oval or elongated, pale staining with ground glass appearanc - Orphan Annie cells  

Microcarcinomas - a manifestation of papillary carcinoma
‚ ‚ ‚ ‚ ‚

‚

Definition - papillary carcinoms smaller than 1.0 cm Most are found incidentally at autopsy Autopsy reports indicate that these may be present in up to 35% of the population Usually clinically silent Most agree that the morbidity and mortality from microcarcinoma is minimal and near that of the normal population One study showed a 1.3% mortality rate

Papillary Carcinoma - Surgical treatment
€

Proponents of total thyroidectomy argue that the procedure
y y y y y y

(1) enables one to use RAI to effectively detect and treat residual thyroid tissue or metastatic disease; (2) makes the serum Tg level a more sensitive marker of recurrent or persistent disease; (3) eliminates the contralateral occult cancers as sites of recurrence; (4) reduces the risk of recurrence and improves survival; (5) decreases the 1% risk of progression to undifferentiated or anaplastic thyroid cancer; (6) reduces the need for reoperative surgery with its attendant risk of increased complication rates.

Investigators that favor lobectomy argue that (1) total thyroidectomy is associated with a higher complication rate than lobectomy; (2) recurrence in the remaining thyroid tissue is unusual (5 %) and most are curable by surgery; (3) tumor multicentricity seems to have little prognostic significance; and (4) patients who have undergone lesser procedures, such as lobectomy, still have an excellent prognosis

During thyroidectomy, enlarged ipsilateral central neck nodes should be removed. Lymph node metastases in the lateral neck in patients with papillary carcinoma are usually managed with modified radical or functional neck dissection Prophylactic neck node dissection is not necessary in patients with papillary thyroid cancer, because these cancers do not appear to metastasize systemically from lymph nodes and micrometastases appear to be ablated with RAI therapy.

Follicular Carcinoma
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account for 20 percent of thyroid cancers and occur more commonly in iodine-deficient areas. Female:male = 3:1 50 yrs old = mean age FNA biopsy is unable to distinguish benign follicular lesions from follicular carcinomas. Large follicular tumors (>4 cm) in older men are more likely to be malignant.

Pathology
- encapsulated, solitary  Histology - very well-differentiated (distinction between follicular adenoma and carcinoma is difficult) - Definitive diagnosis - evidence of vascular and capsular invasion  FNA and frozen section cannot accurately distinquish between benign and malignant lesions 
Gross

Surgical treatment and prognosis ² follicular carcinoma   

Patients diagnosed by FNA biopsy as having a follicular lesion should undergo thyroid lobectomy because at least 80% of these patients will have benign adenomas. Total thyroidectomy should be performed when thyroid cancer is diagnosed. The cumulative mortality rate from follicular thyroid cancer is approximately 15 % at 10 years and 30 % at 20 years.

H¨urthle Cell Carcinoma
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3 % of all thyroid malignancies considered to be a subtype of follicular thyroid cancer characterized by vascular or capsular invasion, and therefore cannot be diagnosed by FNA biopsy. Tumors contain sheets of eosinophilic cells packed with mitochondria, which are derived from the oxyphilic cells of the thyroid gland.

Women > Men Lymphatic spread seen in 30% of patients (Goldman,
1996)

Distant metastases to bone and lung is seen in 15% at the time of presentation

Prognosis
Based on age, sex, and findings at the time of surgery
(Geopfert, 1998)

Several prognostic schemes represented by acronyms have been developed by different groups:
AMES (Lahey Clinic, Burlington, MA)  GAMES (Memorial Sloan-Kettering Cancer Center, New York, NT)  AGES (Mayo Clinic, Rochester, MN) 

Prognosis 

Depending on variables, patients are categorized in to one of the following three groups:
1) Low risk group - men younger than 40 years and women younger than 50 years regardless of histologic type - recurrence rate -11% - death rate - 4%

Prognosis 

1) Intermediate risk group - Men older than 40 years and women older than 50 years who have papillary carcinoma

- recurrence rate - 29% - death rate - 21%  2) High risk group - Men older than 40 years and women older than 50 years who have follicular carcinoma - recurrence rate - 40% - death rate - 36%

Management is similar to that of follicular neoplasms, with lobectomy and isthmusectomy being sufficient surgical treatment for unilateral H¨urthle cell adenomas. When H¨urthle cell neoplasms are found to be invasive on intraoperative, frozen-section, or definitive paraffin-section histology, then total thyroidectomy should be performed.

Medullary Thyroid Carcinoma
10% of all thyroid malignancies 1000 new cases in the U.S. each year Arises from the parafollicular cell or C-cells of the thyroid gland
derivatives of neural crest cells of the branchial arches  secrete calcitonin which plays a role in calcium metabolism 

Medullary Thyroid Carcinoma
Developes in 4 clinical settings:  Sporadic MTC (SMTC)  Familial MTC (FMTC)  Multiple endocrine neoplasia IIa (MEN IIa)  Multiple endocrine neoplasia IIb (MEN IIb)

Medullary Thyroid Carcinoma 

Sporadic MTC:
‚ ‚ ‚ ‚ ‚ ‚

70%-80% of all MTCs (Colson, 1993, Marzano, 1995) Mean age of 50 years (Russell, 1983) 75% 15 year survival (Alexander, 1991) Unilateral and Unifocal (70%) Slightly more aggressive than FMTC and MEN IIa 74% have extrathyroid involvement at presentation
(Russell, 1983)

Medullary Thyroid Carcinoma
Familial MTC: 


Autosomal dominant transmission

Not associated with any other endocrinopathies  Mean age of 43  Multifocal and bilateral  Has the best prognosis of all types of MTC  100% 15 year survival

Medullary Thyroid Carcinoma
Multiple endocrine neoplasia IIa (Sipple·s Syndrome):
MTC, Pheochromocytoma, parathyroid hyperplasia  Autosomal dominant transmission  Mean age of 27  100% develop MTC (Cance, 1985)  85%-90% survival at 15 years (Alexander, 1991, Brunt, 1987) 

Medullary Thyroid Carcinoma 

Multiple endocrine neoplasia IIb (Wermer·s Syndrome, MEN III, mucosal syndrome):
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Pheochromocytoma, multiple mucosal neuromas, marfanoid body habitus 90% develop MTC by the age of 20 Most aggressive type of MTC 15 year survival is <40%-50%

Medullary Thyroid Carcinoma 

Diagnosis
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Labs: 1) basal and pentagastrin stimulated serum calcitonin levels (>300 pg/ml) 2) serum calcium 3) 24 hour urinary catecholamines (metanephrines, VMA, normetanephrines) 4) carcinoembryonic antigen (CEA) Fine-needle aspiration Genetic testing of all first degree relatives
x

RET proto-oncogene

Morphologic feature  

These tumors typically show a solid pattern of growth and do not have connective tissue capsules Histology demonstrates abundant deposition of amyloid, visible here as homogeneous extracellular material, derived from calcitonin molecules secreted by the neoplastic cells

Anaplastic Carcinoma of the Thyroid
Highly lethal form of thyroid cancer Median survival <8 months 1%-10% of all thyroid cancers Affects the elderly (30% of thyroid cancers in patients >70 years) Mean age of 60 years 53% have previous benign thyroid disease 47% have previous history of WDTC

Anaplastic Carcinoma of the Thyroid
Pathology
Classified as large cell or small cell  Large cell is more common and has a worse prognosis  Histology - sheets of very poorly differentiated cells little cytoplasm numerous mitoses necrosis extrathyroidal invasion 

Management  

Surgery is the definitive management of thyroid cancer, excluding most cases of ATC and lymphoma Types of operations:
lobectomy with isthmusectomy - minimal operation required for a potentially malignant thyroid nodule total thyroidectomy - removal of all thyroid tissue - preservation of the contralateral parathyroid glands subtotal thyroidectomy - anything less than a total thyroidectomy

References
Robin·s Pathologic basis of Diseases 9th edition MHAM third year notes Website: www.medscape.com

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