THYROID GLAND

dr. Humairah Medina Liza Lubis, M. Ked (PA), Sp.PA

DEPARTMENT OF ANATOMICAL PATHOLOGY

FACULTY OF MEDICINE
MUHAMMADIYAH UNIVERSITY OF NORTH SUMATERA
MEDAN 2019
The Endocrine System

Pituitary Gland

Thyroid Gland
Parathyroid Gland

The Endocrine Pancreas

Adrenal Cortex

Adrenal Medulla

Pineal Gland
Thyroid Gland Pathology

Hyperthyroidism

Hypothyroidism

Thyroiditis

Graves disease

Diffuse and
Mutinodular Goiters
Neoplasms of the
Thyroid
Congenital
Anomalies
• Have patient seated on a stool / chair
• Inspect neck before and after
swallowing
• Examine with neck in relaxed position
• Palpate from behind the patient
• Remember the rule of finger tips
• Use the tips of fingers for palpation
• Palpate firmly down to trachea
 Thyroid Evaluation
• Tiitropin Releasing Hormon
• TSH
• Total T3, T4
• Free T3, T4
• Radioactive Iodine Uptake
• Thyroglobulin
• Antibodies: Anti-TPO, Anti-TSHr
Thyroid Evaluation
HYPERTHYROIDISM
Prevalence
Women 2%
Men 0.2%
15% of cases occur in patients older
than 60 years of age
• A hyper metabolic biochemical state
• It is a multi system disease with Elevated
levels of FT4 or FT3 or both
• What is thyrotoxicosis ?
• What is hyperthyroidism ?
• What are the various causes ?
 Causes of Hyperthyroidism

1. Diffuse hyperplasia of the thyroid associated with Graves

disease (accounts for 85% of cases)
2. Hyperfunctional multinodular goiter
3. Hyperfunctional adenoma of the thyroid
4. Plummer’s Disease – Toxic MNG
5. Toxic phase of Sub Acute Thyroiditis - SAT
6. Toxic Single Adenoma – STA
7. Pituitary Tumours
8. Molar pregnancy & Choriocarcinoma (↑↑ βHCG)
9. Metastatic thyroid cancers (functioning)
10. Struma Ovarii (Dermoid and Ovarian tumours)
11. Thyrotoxicosis Factitia
 Clinical Symptoms

Depends on
• Age of patient
• Magnitude of hormonal excess
• Presence of co-morbid condition
• Skin
- Warm
- May be erythematous (due to
increased blood flow)
- Smooth- due to decrease in keratin
- Sweaty and heat intolerance
- Onycholysis –softening of nails and loosening
of nail beds
• Hyperpigmentation
-Due the patient increase ACTH secretion
• Pruritis
-mainly in graves disease
• Thinning of hair
• Vitilago and alopecia areata
-mainly due to autoimmune disease
• Infilterative dermopathy
-Graves disease, most common on shins
 Thyroid Dermopathy

Pink and skin coloured papules, plaques on the shin

Onycholysis
• Eyes

Wide-eyed
Staring gaze
Lid lag
* Due to sympathetic overstimulation of the levator
palpebrae superioris
* Only Graves disease has ophthalmopathy
- Inflammation of extraocular muscles, orbital fat and
connective tissue
- This results in exopthalmos
- More common in smokers
• Impaired eye muscle function (Diplopia)
• Periorbital and conjunctival edema
• Gritty feeling or pain in the eyes
• Corneal ulceration due to lid lag and proptosis
• Optic neuritis and even blindness
 Thyroid Ophthalmopathy

Proptosis

Lid lag
Ophthalmopathy in Graves

Periorbital edema and chemosis

Severe Exophthalmia
Cardiovascular System

• Increased cardiac output (due to increased oxygen

demand and increased cardiac contractibility.
• Tachycardia
• Widened pulse pressure
• High output – heart failure
• Atrial fibrillation, 10-20% of patients. More common in elderly
• Atrial ectopy
• 60% of A-fib will convert to normal sinus rhythm with treatment
(4-months of becoming euthyroid)
• Mitral valve problems
• LVH and cardiomyopathy
Respiratory System

• Dyspnea on rest and with exertion

• Oxygen consumpation and CO2 production increases.
• Hypoxemia and hypercapnea, which stimulates ventilation
• Respiratory muscle weakness
• Decreased exercise capacity
• Tracheal obstruction
• May exacerbate asthma
• Increased pulmonary arterial pressure
GI System

-Weight loss due to increased calorigenesis

-Hyperdefecation
-Malabsorption
-Steatorrhea
-Celiac Disease (in Grave’s Disease)
-Hyperphagia (weight gain in younger patient)
-Anorexia- weight loss in elderly
-Dysphagia
-Abnormal LFT especially phosphate
Hematological System

• Normochromic normocytic anemia

• Serum ferritin may be high
• Graves disease
– ITP
– Pernicious anemia
– Anti-neutrophiliac antibody
GU System

• Urinary frequency and nocturia

• Enuresis is common in children
Skeletal System
• Bone resorption
• Increased porosity of cortical bone
• Reduced volume of trabecular bone
• Serum alkaline phosphate is increased
• Increased osteoblasts
• Inhibit PTH secretions
• Decreased calcium absorption and increased
excretion
• Osteoporosis, Fractures
Skeletal System
Grave’s disease is associated with thyroid acropathy
-Clubbing of nails
-Periosteal bone formation in metacarpal bone or
phalanges
 Graves with Acropathy

Graves Goiter Acropathy

 Thyroid Acropathy

Clubbing and
Osteoarthropathy
Neuromuscular System

• Tremors-outstretched hand and tongue

• Hyperactive tendon reflexes
Psychiatric
• Hyperactivity
• Emotional lability
• Anxiety
• Decreased concentration
• Insomnia
Muscle Weakness

• Proximal muscle weakness in 50% pts.

• Decreased muscle mass and strength
• May take up to six months after euthyroid state to
gain strength
• Hypokelemic periodic paralysis especially in Asian
men (cause is not known)
• Myesthenia Gravis, especially in Grave’s disease
 Diagnosis

1. Typical clinical presentation

2. Markedly suppressed TSH (<0.05 µIU/mL)
3. Elevated FT4 and FT3 (Markedly in Graves)
4. Thyroid antibodies – by Elisa – anti-TPO, TSI
5. ECG to demonstrate cardiac manifestations
6. Nuclear Scintigraphy to differentiate the causes
HYPOTHYROIDISM
• Hypothyroidism  any structural or
functional derangement that interferes
with the production of adequate levels of
thyroid hormone
• From a defect anywhere in the
hypothalamic-pituitary-thyroid axis
• Epidemiology
– Most common endocrine disease
– Females > Males – 8 : 1
• Presentation
– Often unsuspected and grossly under diagnosed
– 90 % of the cases are Primary Hypothyroidism
– Menstrual irregularities, miscarriages, growth retard.
– Vague pains, anaemia, lethargy, gain in weight
– In clear cut cases - typical signs and symptoms
– Low free T4 and High TSH
– Easily treatable with oral Levo-thyroxine
 Classification of Hypothyroidism

A. Primary Primary contd..

1. Enlarged Thyroid 3. Post Ablative
- Hashimoto’s (65%) - Permanent
- Iodine Deficiency (25%) - Transient
- Drug-induced (Lithium) - Sub-clinical
- Dysharmonogenesis 4. Congenital
2. Normal Thyroid B. Secondary / Central
- Spontaneous Atrophic Pituitary/ hypothalamic

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Primary
Developmental (thyroid dysgenesis: PAX-8, TTF-
2, TSH-receptor mutations)
Thyroid hormone resistance syndrome (TRβ
mutations)
Postablative
Surgery, radioiodine therapy, or external
radiation
Autoimmune hypothyroidism
Hashimoto thyroiditis *
Iodine deficiency *
Drugs (lithium, iodides, p-aminosalicylic acid) *
Congenital biosynthetic defect
(dyshormonogenetic goiter) *
Secondary
Pituitary failure
Tertiary
 Thyroid Failure - Organ Systems

Cardiovascular
• Decreased ventricular contractility
• Increased diastolic blood pressure
• Decreased heart rate
Central Nervous
• Decreased concentration
• General lack of interest
• Depression
Gastro-instestinal
• Decreased GI motility
• Constipation
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 Thyroid Failure - Organ Systems

Musculoskeletal
 Muscle stiffness, cramps, pain,
weakness, myalgia
 Slow muscle-stretch reflexes,
muscle enlargement, atrophy
Renal
 Fluid retention and oedema
 Decreased glomerular filtration
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 Thyroid Failure - Organ Systems

Reproductive
• Arrest of pubertal development
• Reduced growth velocity
• Menorrhagia, Amenorrhea
• Anovulation, Infertility
Hepatic
• Increased LDL / TC
• Elevated LDL + triglycerides
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 Thyroid Failure - Organ Systems

Skin and Hair

 Thickening and dryness of skin
 Dry, coarse hair, Alopecia
 Loss of scalp hair and / or
lateral eyebrow hair

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 Congenital Hypothyroidism

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Urine Iodine Conc. < 50 µg/L

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 Myxedema

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Myxedema

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 Macroglossia

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Xanthomata

Tuberous Xanthoma

Xanthelasma

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 Solid Oedema Xanthomata
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THYROIDITIS
• Thyroiditis, or inflammation of
the thyroid gland, encompasses a
diverse group of disorders characterized
by some form of thyroid inflammation
• These diseases include conditions that
result in acute illness with severe thyroid
pain (e.g., infectious thyroiditis, subacute
granulomatous thyroiditis) and disorders
in which there is relatively little
inflammation and the illness is
manifested primarily by thyroid
dysfunction (subacute lymphocytic
thyroiditis and fibrous [Reidel] thyroiditis)
 Hashimoto’s Thyroiditis
• Most common cause of goiter and hypothyroidism in
the U.S.
• Physical
– Painless diffuse goiter
• Lab studies
– HypothyroidisM
– Anti Thyroglobulin antibodies (20-50%)
– Acute Hyperthyroidism (5%)
• Treatment
– Levothyroxine if hypothyroid
– Triiodothyronine (for myxedema coma)
– Thyroid suppression (levothyroxine) to decrease
goiter size
• Contraindications
• Stop therapy if no resolution noted
– Surgery for compression or pain.
Morphology

• The thyroid is often diffusely enlarged

• The capsule is intact, and the gland is well
demarcated from adjacent structures
• The cut surface is pale, yellow-tan, firm, and
somewhat nodular
Gross and Microscopic Pathology of
Chronic Thyroiditis
• Microscopic examination reveals extensive
infiltration of the parenchyma by a mononuclear
inflammatory infiltrate containing small
lymphocytes, plasma cells, and well-developed
germinal centers
• The thyroid follicles are atrophic and are lined in
many areas by epithelial cells distinguished by
the presence of abundant eosinophilic, granular
cytoplasm, termed Hürthle cells
• In "classic" Hashimoto thyroiditis, interstitial
connective tissue is increased and may be
abundant
Silent Thyroiditis
Post-partum Thyroiditis

• Silent thyroiditis is termed post-partum thyroiditis

if it occurs within one year of delivery.
• Clinical
– Hyperthyroid symptoms at presentation
– Progression to euthyroidism followed by
hypothyroidism for up to 1 year.
– Hypothyroidism generally resolves
• Diagnosis
– May be confused with post-partum Graves’ relapse
• Treatment
– Beta blockers during toxic phase
– No anti-thyroid medication indicated
– Iopanoic acid (Telopaque) for severe
hyperthyroidism
– Thyroid hormone during hypothyroid phase. Must
withdraw in 6 months to check for resolution.
Subacute Thyroiditis
DeQuervain’s, Granulomatous

• Most common between the ages of 30 and 50

• Affects women considerably more often than
men (3:1 to 5:1)
• Caused by a viral infection or a postviral
inflammatory process
Morphology

• The gland may be unilaterally or bilaterally enlarged and firm, with

an intact capsule
• It may be slightly adherent to surrounding structures
• On cut section, the involved areas are firm and yellow-white and
stand out from the more rubbery, normal brown thyroid substance.
• Histologically, the changes are patchy and depend on the
stage of the disease
• Early in the active inflammatory phase, scattered follicles
may be entirely disrupted and replaced by neutrophils
forming microabscesses
• Later, the more characteristic features appear in the form
of aggregations of lymphocytes, histiocytes, and plasma
cells about collapsed and damaged thyroid follicles
• Multinucleate giant cells enclose naked pools or
fragments of colloid  granulomatous thyroiditis
Acute Thyroiditis

• Causes
– 68% Bacterial (S. aureus, S. pyogenes)
– 15% Fungal
– 9% Mycobacterial

• May occur secondary to

– Pyriform sinus fistulae
– Pharyngeal space infections
– Persistent Thyroglossal remnants
– Thyroid surgery wound infections (rare)

• More common in HIV

• Diagnosis
– Warm, tender, enlarged thyroid
– FNA to drain abscess, obtain culture

• Treatment
– High mortality without prompt treatment
– IV Antibiotics
• Nafcillin / Gentamycin or Rocephin for empiric
therapy
– Search for pyriform fistulae (BA swallow,
endoscopy)
– Recovery is usually complete
Riedel’s Thyroiditis

• Rare disease involving fibrosis of the

thyroid gland

• Diagnosis
– Thyroid antibodies are present in 2/3
– Painless goiter “woody”
– Open biopsy often needed to diagnose
– Associated with focal sclerosis syndromes
(retroperitoneal, mediastinal, retroorbital, and
sclerosing cholangitis)

• Treatment
– Resection for compressive symptoms
– Chemotherapy with Tamoxifen, Methotrexate,
or steroids may be effective
– Thyroid hormone only for symptoms of
hypothyroidism
Histopathology of
Riedel’s Thyroiditis
GRAVES DISEASE
• 60 to 80% of hyperthyroidism
• Autoimmune disorder
• Common between 30 and 40 years
• Woman, 0.5 per 1000
• Family history
Clinical
Presentation

• Manifestations of hyperthyroidism:
hypermetabolic state
• Manifestations of Graves’ disease:
 Ophthalmopathy
 Localized dermopathy
 Thyroid acropachy
Diagnostic Modality

• Decreased TSH
• Increased free T4 and
increased T3
• TSHR-Ab
• Thyroid radioactive iodine
uptake and scan
 Morfologi

• Membesar simetris karena hipertrofi dan hiperplasia difus dari epitel

sel folikel tiroid
• Halus dan lembut, dan kapsulnya tetap utuh
• Pada pemotongan, parenkim memiliki tampilan yang lembut, meaty,
menyerupai otot normal
• Secara histologi, gambaran dominan adalah banyak sel  sel epitel
folikular terlihat lebih tinggi ddan crowded. Koloid dalam lumen folikel
pucat, dengan margin berbentuk scalloping. Infiltrat limfoid, terutama
mengandung sel T dengan beberapa sel B dengan sel plasma
matang, yang dijumpai pada interstitium dan germinal centre
 Graves’ Gross and
Microscopic Pathology
Treatment

• Anti-thyroid drugs
• Radioactive iodine therapy
(RAI)
• Surgery
Anti-thyroid drugs

• Propylthiouracil
• Carbimazole → Methimazole
• Both inhibit thyroid peroxidase
• PTU also inhibits T4 to T3
conversion
• Immunomodulatory action?
Adverse effects

• Rash
• Arthralgias
• Urticaria
• GI symptoms
• Agranulocytosis
Surgery

• Young age
• Male sex
• Pregnancy/lactation
• Patient preference
• Large or nodular goiter
• Inability to tolerate ATDs
Complications

• Thyroid storm or thyrotoxic

crisis
• Hypothyroidism
• Recurrent hyperthyroidsim
• Recurrent laryngeal nerve
injury
• Hypoparathyroidism
GOITER
 Benign Thyroid Disease

• Benign Nontoxic Conditions

– Diffuse and Nodular Goiter
• Benign Toxic Conditions
– Toxic Multinodular Goiter
– Graves’ Disease
– Toxic Adenoma
• Inflammatory Conditions
– Chronic (Hashimoto’s) Thyroiditis
– Subacute (De Quervain’s) Thyroiditis
– Riedel’s Thyroiditis
 Goiter
• Goiter: Chronic enlargement of the
thyroid gland not due to neoplasm
• Endemic goiter
– Areas where > 5% of children 6-12 years of
age have goiter
– Common in China and central Africa
• Sporadic goiter
– Areas where < 5% of children 6-12 years of
age have goiter
– Multinodular goiter in sporatic areas often
denotes the presence of multiple nodules
rather than gross gland enlargement
• Familial
 Goiter
• Etiology
– Hashimoto’s thyroiditis
• Early stages only, late stages show atrophic changes
• May present with hypo, hyper, or euthyroid states
– Graves’ disease
• Due to chronic stimulation of TSH receptor
– Diet
• Brassica (cabbage, turnips, cauliflower, broccoli)
• Cassava
– Chronic Iodine excess
• Iodine excess leads to increased colloid formation and
can prevent hormone release
• If a patient does not develop iodine leak, excess iodine
can lead to goiter
– Medications
• Lithium prevents release of hormone, causes goiter in
6% of chronic users
– Neoplasm
 Goiter
• Pathogenesis
– Iodine deficient areas
• Heterogeneous response to TSH
• Chronic stimulation leads to multiple nodules
– Iodine replete areas
• Thyroid follicles are heterogeneous in their
growth and activity potential
• Autopsy series show MNG >30%.

• Thyroid function evaluation

– TSH, T4, T3
– Overt hyperthyroidism (TSH low, T3/T4 high)
– Subclinical hyperthyroidism (TSH low, T3/T4
normal)

• Determination of thyroid state is key in

determining treatment
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
 Non-Toxic Goiter

• Cancer screening in non-toxic MNG

– Longstanding MNG has a risk of malignancy identical to
solitary nodules (<5%)
– MNG with nodules < 1.5 cm may be followed clinically
– MNG with non-functioning nodules > 4cm should be excised
• No FNA needed due to poor sensitivity
• Incidence of cancer (up to 40%)
– FNA in MNG
• Sensitivity 85% - 95%
• Specificity 95%
• Negative FNA can be followed with annual US
• Insufficient FNA’s should be repeated
• Incoclusive FNA or papillary cytology warrants excision
– Hyperfunctioning nodules may mimic follicular neoplasm on
FNA
 Non-Toxic Goiter
• Treatment options (no compressive symptoms)
– US follow-up to monitor for progression

– Thyroid suppression therapy

• May be used for progressive growth
• May reduce gland volume up to 50%
• Goiter regrowth occurs rapidly following therapy cessation

– Surgery
• Suspicious neck lymphadenopathy
• History of radiation to the cervical region
• Rapid enlargement of nodules
• Papillary histology
• Microfollicular histology (?)
 Non-Toxic Goiter
• Treatment options (compressive
symptoms)

– RAI ablation
• Volume reduction 33% - 66% in 80% of
patients
• Improvement of dysphagia or dyspnea in
70% - 90%
• Post RAI hypothyroidism 60% in 8 years
• Post RAI Graves’ disease 10%
• Post RAI lifetime cancer risk 1.6%

– Surgery
• Most commonly recommended treatment
for healthy individuals
 Toxic Goiter
• Evaluate for
– Graves’ disease
• Clinical findings (Pretibial myxedema,
Opthalmopathy)
• Anti-TSH receptor Ab
• High RAUI
– Thyroiditis
• Clinical findings (painful thyroid in Subacute
thyroiditis)
• Low RAUI
– Recent Iodine administration
• Amiodarone
• IV contrast
• Change in diet

• FNA evaluation
– Not indicated in hyperthyroid nodules due to low
incidence of malignancy
– FNA of hyperthyroid nodules can mimic follicular
neoplasms
 Toxic Goiter
• Risks of hyperthyroidism
– Atrial fibrillation
– Congestive Heart Failure
– Loss of bone mineral density
– Risks exist for both clinical or subclinical
disease

• Toxic Goiter
– Toxicity is usually longstanding
– Acute toxicity may occur in hyperthyroid
states (Jod Basedow effect) with
• Relocation to iodine replete area
• Contrast administration
• Amiodarone (37% iodine)
 Toxic Goiter
• Treatment for Toxic MNG
– Thionamide medications
• Not indicated for long-term use due to
complications
• May be used for symptomatic individuals until
definitive treatment.
– Radioiodine
• Primary treatment for toxic MNG
• Large I131 dose required due to gland size
• Goiter size reduction by 40% within 1 year
• Risk of hypothyroidism 11% - 24%
• May require second dose
– Surgery
• Used for compressive symptoms
• Hypothyroidism occurs in up to 70% of subtotal
thyroidectomy patients
• Pre-surgical stabilization with thionamide
medications
• Avoid SSKI due to risk for acute toxic symptoms
 Endemic Goiter
• No longer a problem
in the US and the
developed world
• Still a serious health
concern in parts of
the world with iodine
deficiency including
mountainous areas
or areas with high
rainfall/flooding
NEOPLASMS
 Thyroid Carcinoma
• Incidence
– Thyroid carcinoma occurs relatively infrequently compared to the
common occurrence of benign thyroid disease
– Thyroid cancers account for only 0.74% of cancers among men, and
2.3% of cancers in women in the US
– The annual rate has increased nearly 50% since 1973 to
approximately 18 000 cases
• Thyroid carcinomas (percentage of all US cases)
– Papillary (80%)
– Follicular (about 10%)
– Medullary thyroid (5%-10%)
– Anaplastic carcinoma (1%-2%)
– Primary thyroid lymphomas (rare)
– Metastatic from other primary sites (rare)
Risk factors for
Malignancy
• Solitary thyroid nodules in patients >60 or <30 years
of age
• Irradiation of the neck or face during infancy or
teenage years
• Symptoms of pain or pressure (especially a change
in voice)
• Male sex
• Large Nodules (>3 or 4 cm)
• Growth of nodule
 Evaluating Thyroid Nodules

• TSH measurement
• Ultrasound of the thyroid
• Fine needle aspiration
• Radioactive iodine imaging
Thyroid Ultrasonography
Thyroid Ultrasonography

• Excellent for
characterizing size and
other features of nodule
• Useful in localizing
nodule for FNA
• Cannot distinguish
between benign vs.
malignant
 Thyroid Ultrasonography

• Certain features may suggest greater risk of cancer:

– Irregular or poorly defined borders of nodule
– Lack of a "halo“
– Hypo-echogenicity
– Evidence of microcalcifications
– Increased blood flow
– Growth and interval change on serial ultrasounds
 RAI imaging

• Formerly had been used extensively in the initial

work up of nodular thyroid disease
FNA is now considered the gold standard
RAI imaging

• The problem:
– Although “hot” nodules are usually never
cancer, only 5% of all nodules are
hyperfunctioning
– The remaining 90-95% that are warm or
cold could be cancer and thus require FNA
Thyroid FNA

• Now considered the

most cost effective and
sensitive/specific
diagnostic test of thyroid
nodules
• The use of US has
expanded the role of
FNA in evaluating
nodules and improved
the validity of the results
Thyroid FNA

Possible FNA Results

– Benign: 70 -75 %
– Malignant: Up to 5%
– Suspicious: About 10%
– Nondiagnostic: About 10 - 20%
Thyroid FNA

Limitations
• False negatives: (< 5% of FNA) more likely in large (>4cm)
or small (<1cm) nodules
• Suspicious FNA (Follicular and Hurhtle cell neoplasm):
cannot distinguish benign vs malignant of hypercellular
nodules by FNA alone, ALWAYS require surgical
pathology for dx (up to 10 – 30% of these will be CA)
• Non-diagnostic results: NEVER consider equivalent to
benign, up to 10% of ND FNA will contain CA on resection
 Typical Presentation of
Thyroid Cancer

• Painless lump
• Normal thyroid function tests
• Found on routine examination or by the patient
• Slow growth or no growth over several months
 Types of Thyroid
Cancer

• Papillary (80%-85%): develops from thyroid follicle cells in

1 or both lobes; grows slowly but can spread
• Follicular (5%-10%): common in countries with insufficient
iodine consumption; lymph node metastases are
uncommon
• Medullary: develops from C-cells, can spread quickly;
sporadic and familial types
• Anaplastic: develops from existing papillary or follicular
cancers; aggressive, usually fatal
• Lymphoma: develops from lymphocytes; uncommon
 Papillary Thyroid Cancer

• Most common type

• Makes up about 80% of all
thyroid carcinomas in the United
States
• Females outnumber males 3:1
– Highest incidence in women in
midlife
Papillary Thyroid Cancer
Characteristics

• Unencapsulated tumor nodule with ill-defined

margins
• Tumor typically firm and solid
• May present as nodal enlargement
• Commonly metastasizes to neck and mediastinal
lymph nodes
– 40% to 60% in adults and 90% in children
• <5% of patients have distant metastases at time of
diagnosis
– Lung is most common site
Follicular Thyroid Cancer

• Second most common type

of thyroid cancer
• Solid invasive tumors,
usually solitary and
encapsulated
• Usually stays in the thyroid
gland, but can spread to the
bones, lungs, and central
nervous system
• Usually does not spread to
the lymph nodes
Follicular Thyroid Cancer
Diagnosis and Prognosis

• Most FTCs present as an asymptomatic neck mass

• If caught early, this type of thyroid cancer is often
curable
– Tumors >3 cm have a much higher mortality rate
Hürthle Cell Cancer

• A variant of follicular
cancer that tends to be
aggressive Hürthle Cell Tumor
• Represents about 3% to
5% of all types of thyroid
cancer
High power magnification
Hürthle Cell Cancer
Prognosis

• May be benign or malignant, based on

demonstration of vascular or capsular
invasion
• Malignancies tend to have a worse
prognosis than other follicular tumors
and rarely respond to 131I therapy
• Tend to be locally invasive
Anaplastic Thyroid Cancer

• Extremely aggressive
and exceptionally
virulent
• Composed wholly or in
part of undifferentiated
cells
Anaplastic Thyroid Cancer
(Continued)

• Tumor is typically hard, poorly circumscribed,

and fixed to surrounding structures
• Often occurs in the elderly population (mean
age: 65 years)
• 3-fold greater risk in iodine-deficient areas
Medullary Thyroid Cancer

• Tumor arising from the

calcitonin-secreting C-cells
of the thyroid gland
• Mortality rate of 10% to
20% at 10 years
Medullary Thyroid Cancer
Types

• 70% to 80% of cases are

sporadic disease
(median age=51 years)
• 20% to 30% are part of 3
familial autosomal
dominant syndromes
(MEN-2A, MEN-2B, or
familial non-MEN medullary
thyroid cancer [median
age=21 years])
Medullary Thyroid Cancer
Metastases

• Cervical lymph node metastases occur early

• Tumors >1.5 cm are likely to metastasize,
often to bone, lungs, liver, and the central
nervous system
• Metastases usually contain calcitonin and
stain for amyloid
Primary Thyroid
Lymphoma

• A rare type of thyroid

cancer
– Affects fewer than 1 in
2 million people
• Constitutes 5% of thyroid
malignancies
Primary Thyroid Lymphoma
Characteristics and Diagnosis

• Develops in the setting of pre-existing

lymphocytic thyroiditis
• Often diagnosed because of airway
obstruction symptoms
• Tumors are firm, fleshy, and usually pale
 Etiology of Thyroid Cancers

• Usually unknown
• Radiation exposure
– Medical uses during childhood in the 1950s
– Current medical uses in cancer therapy
– Nuclear accidents
Management and Follow up of Thyroid
Carcinoma
 Thyroid Cancer Risk Stratification
Low Risk Intermediate Risk High Risk

Age <45 years >45 years

Gender Female Male

Size <2 cm >4 cm

Mixture of
Extent Intraglandular Extraglandular
Features
Grade Low High
Distant
Absent Present
Metastases

Treated, % 39 39 22
Death Rate, % <1 13 53
 Thyroid Cancer
Initial Treatment Strategy
Diagnosis of Thyroid Cancer

Surgery
Low Risk Intermediate
and High Risk

Lobectomy Total
Isthmusectomy Thyroidectomy

Shaha AR. Cancer Control. 2000;7:240-245.

Kinder BK. Curr Opin Oncol. 2003;15:71-77.
 Thyroid Cancer
Initial Treatment Strategy
Diagnosis of Thyroid Cancer

Surgery Intermediate
Low Risk
and High Risk

Lobectomy Total
Isthmusectomy Thyroidectomy

Physical Exam RAI Ablation

Ultrasound Kinder BK. Curr Opin Oncol. 2003;15):71-77.
Sherman SI. Lancet. 2003;361:501-511.
Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.
 Treatment of Thyroid Cancer With
Radioactive Iodine
• Destroys remnants of normal thyroid tissue
• Destroys thyroid cancer cells
• Identifies distant metastases
• Maximizes sensitivity and specificity of
serum thyroglobulin
 Standard Treatment of
Thyroid Cancer

Total
Thyroidectomy

RAI
Ablation

Suppression
Therapy

1 Year
Whole Body Scan
Tg Assay
 Treatment of Thyroid Cancer Summary
• Papillary and follicular thyroid cancer
– Generally excellent prognosis
– Risk for recurrence for as long as 30 years
• Initial management
– Surgery and radioactive iodine
– LT4 suppressive therapy
• Follow-up
– Physical examination
– Radioactive iodine scans
– Serum Tg
– TSH and T4
CONGENITAL ANOMALIES
• Thyroglossal duct or cyst
• A persistent sinus tract may remain as a vestigial remnant of the
tubular development of the thyroid gland. Parts of this tube may be
obliterated, leaving small segments to form cysts.
• These occur at any age and might not become evident until adult
life
• Mucinous, clear secretions may collect within these cysts to form
either spherical masses or fusiform swellings, rarely over 2 to 3 cm
in diameter
• Present in the midline of the neck anterior to the trachea.