Thyroid & Thyroid Cancers
Anatomy & Function of the Thyroid gland:
- Butterfly-shaped gland consisting of two lobes and connected by an isthmus
- Located in front of the neck, along the trachea
- Produces 2 hormones:
- Thyroid hormones - regulates the body’s metabolism, heart rate, blood pressure, body temperature, and weight
- Calcitonin - involved in calcium regulation
- Behind the thyroid gland are the 4 parathyroid glands, which produce parathyroid hormone are involved in calcium regulation
Thyroid Cancer:
- The most common endocrine cancer and can occur in all age groups
- The American Cancer Society estimates that in the US in 2009 there will about 37,200 new cases (27,200 in women and 10,000 in men) and 1,630 deaths
- There are four main types of thyroid cancer and are based on how the cancer cells look under a microscope:
- Papillary
- Follicular
- Medullary
- Anaplastic
- (each described in detail below)
Risk factors:
- Diet low in iodine
- Radiation exposure (ie) history of head or neck radiation treatment in childhood, radioactive fallout (ie nuclear plant accidents, atomic weapons testing)
- Hereditary factors
- Personal history of goiter or benign thyroid nodules
- Gender (females greater than males)
- Age, most commonly in the 20-60 year old age group
Signs & Symptoms:
- In the early stages, symptoms are often absent
- As the cancer grows, signs and symptoms may include:
- Nodule, lump, or swelling in the neck
- Hoarseness/voice changes
- Swollen lymph nodes in the neck
- Difficulty in swallowing or breathing
- Pain in neck or throat that does not go away
- Important to note that many of these signs or symptoms can be caused by other non-cancerous conditions
- Thyroid nodules are common and usually benign
Diagnosis:
- Physical exam: feeling the thyroid for size and nodules, checking the neck for enlarged lymph nodes
Blood tests:
- TSH (thyroid stimulating hormone) levels in the blood: too much or too little TSH means the thyroid is not working properly
- Calcitonin: if MTC is suspected. Also useful to look for recurrence of MTC after treatment
- Thyroglobulin: thyroid hormone precursor protein made by the thyroid gland. Not useful in diagnosing thyroid cancer but can be useful to look for recurrence after treatment. Levels should be low after treatment. If the level is high, it may mean the thyroid cancer is still present or if it is rising, the cancer may be recurring.
Ultrasound: uses sound waves instead of radiation to create images. Useful in determining if a thyroid nodule is solid or fluid-filled. It can also show thyroid nodules too small to be felt.
Radioiodine scan: radioactive iodine is swallowed or injected and absorbed by the thyroid gland. In high doses, it is used as treatment to destroy the thyroid. In smaller does, it can be used as a scan to see where the radioactivity has gone. A camera is used to measure the amount of radiation. Abnormal areas in the gland where there is less radioactivity absorbed than in surrounding areas are called “cold” nodules; where there is more radiation uptake, they are called “hot” nodules. Hot nodules are usually not cancerous. Cold nodules may be benign or cancerous.
Biopsy: the only definitive way of diagnosing thyroid cancer. Tissue samples from the thyroid nodule are sent to a pathologist to look for cancer cells under a microscope
- Fine needle aspiration (FNA): may be done in the doctor’s office. A thin needle is used to take out tissue from the nodule. Ultrasound may be used to help guide needle placement.
- Surgical biopsy: performed in the operating room with the patient under general anesthesia. Done if the FNA result is inconclusive (cannot tell if the nodule is benign or malignant). The whole nodule or lobe may be surgically removed.
Types of Cancer
Papillary Thyroid Carcinoma (PTC):
- The most common thyroid cancer in the US, representing 75-80%
- Peak onset occurs in those between 30-50 years old
- More common in women than men (3:1)
- Originates from follicular cells, is slow growing, with cells arranged in projections or papillae
- Can be purely papillary or mixed with follicular carcinoma
- Spread to cervical lymph nodes in greater than 50% of cases, causing a higher recurrence rate but not a higher mortality rate
- Distant spread to the lungs or bones is uncommon but can occur in the late stages
- Other variants of PTC include tall-cell and columnar cell, which are more aggressive
Follicular Thyroid Carcinoma (FTC):
- Makes up about 15% of all thyroid cancers (the second most common type)
- Peak onset occurs in those between 40-60 years old
- More common in women than men (3:1)
Originates from follicular cells, is slow growing, with cells arranged in small follicles
- More aggressive than PTC
- Rarely associated with radiation exposure
- Spread to lymph nodes is uncommon, occurring in about 10% of cases
- Commonly invades into the vascular structures within the gland
- Distant spread to the lungs or bones is uncommon
- Variant of FTC is Hürthle cell carcinoma, which has higher risk of metastasis and recurrence
Medullary Thyroid Carcinoma (MTC):
- Represents about 5% of thyroid cancers
- More common in females than males (except in inherited cases)
- Arises from C cells, which produce the hormone calcitonin
- MTC can also secrete histaminase, prostaglandins, serotonin, and other peptides
- Spread to lymph nodes in the neck can occur early
- Distant spread via blood to the liver, lungs, bone, brain, and adrenal medulla can occur late
- More aggressive than PTC and FTC
- Occurs in different clinical settings:
- Sporadic: Accounts for 75-80% of MTCs. Peak onset is 40-60 years old, with females affected more than males (3:2). Typically presents unilaterally as a solitary neck nodule and without other endocrinopathies (has no association with other diseases in other endocrine glands).
- MEN (Multiple Endocrine Neoplasia) 2a Syndrome (Sipple Syndrome): Is a group of endocrine disorders, consisting of MTC, hyperparathyroidism, and bilateral pheochromocytoma. It is inherited in an autosomal dominant fashion and associated with a mutation in the RET proto-oncogene on chromosome 10. Males and females are affected equally with peak incidence in the 30s.
- MEN 2b Syndrome: Is a group of endocrine disorders consisting of MTC, bilateral pheochromocytoma, and multiple mucosal neuromas. Patients also present with a marfanoid habitus. It is the more aggressive form of MTC. It is also inherited in an autosomal dominant fashion involving the RET gene with males and females affected equally. MTC tends to occur at an earlier age, grows and spreads faster than those with MEN 2a.
- Familial: Is inherited without associated endocrinopathies and is the least aggressive of MTCs. Peak onset is 40-50 years old.
Anaplastic (undifferentiated) Thyroid Carcinoma:
- Least common of thyroid cancers (~1%) but is the most aggressive form with a high mortality rate
- Often presents in older patients 65 years and older
- More common in males than females (2:1)
- Can occur in those with a long-standing goiter with sudden growth or those with a history of radiation exposure
- Growth is rapid, which can cause airway obstruction
- Diffuse infiltration into the neck
- Spread to lymph nodes in the neck is common (>90% of cases)
- Distant spread to the lungs and/or bones is also common
- Prognosis is very poor due to its aggressiveness and poor response to treatment
Prognosis of PTC and FTC:
- These are referred to as the well-differentiated thyroid cancers and in general have a very good prognosis with a >90% cure rate if diagnosed at an early stage and is appropriately treated
- Multiple factors determine the prognosis, such as age, sex, and the characteristics of the cancer:
- Favorable factors:
- Age less than 45
- Tumor size ≤ 4 cm
- PTC with well-defined capsule
- FTC with minimal invasion of the capsule
- Absence of local invasion
- Absence of blood vessel invasion
- Absence of lymph node metastasis
- Absence of distant metastasis
- Single thyroid cancer
- Female gender
- Presence of Hashimoto’s thyroiditis
- Less Favorable factors:
- Age 45 or older
- PTC with anaplastic transformation
- Poorly differentiated follicular cancer
- Tall-cell, columnar, or diffuse sclerosing variants of papillary cancer
- Hurthle cell type
- Distant metastasis
- Local invasion
- Blood vessel invasion
- Multiple papillary cancers
- Insufficient surgery
- Delay in therapy
- No levothyroxine therapy
- No radioactive iodine treatment (in some patients)
- Male gender
- Presence of Graves’ disease
5 Year Relative Survival Rate:
| Stage |
Papillary |
Follicular |
Medullary |
Anaplastic |
| I |
100% |
100% |
100% |
- |
| II |
100% |
100% |
97% |
- |
| III |
96% |
79% |
78% |
- |
| IV |
45% |
47% |
24% |
9% |
Anaplastic (undifferentiated) carcinomas are all considered stage IV
Staging:
- Size, metastasis (spread), and if metastasis, to where (most often to LNs, bone, lung)
- US, CT, MRI, CXR, whole body scan to see if the cancer has spread to LNs or other areas of the body
Uses the TNM system:
- T: Tumor size
- N: extent of spread to regional lymph nodes
- M: Metastasis (spread) to other areas of the body
| |
Papillary and Follicular Thyroid Carcinoma |
Medullary Thyroid Carcinoma |
| Patients <45 yrs |
|
|
| Stage I (any T, any N, M0) |
Tumor can be any size
Spread to nearby lymph nodes may or may not be present
No spread to distant sites |
Staging for patient of any age with MTC is the same as for PTC or FTC in people older than age 45 |
| Stage II (any T, any N, M1) |
Tumor can be any size
Spread to nearby lymph nodes may or may not be present
Spread to distant sites present |
|
| Patients ≥ 45 yrs |
|
|
| Stage I (T1, N0, M0) |
Tumor <2 cm across
No spread to nearby lymph nodes or distant sites |
|
| Stage II (T2, N0, M0) |
Tumor 2-4 cm across
No spread to nearby lymph nodes or distant sites |
|
Stage III (T3, N0, M0)
or- (T1-3, N1a, M0) |
Tumor >4 cm or has grown slightly outside the thyroid
No spread to nearby lymph nodes or distant sites
- or -
Tumor is any size
Spread to cervical lymph nodes
No distant spread |
|
Stage IVA (T4a, N0-1a, M0)
- or -
(T1-4, N1b, M0) |
Tumor is any size and has grown beyond the thyroid gland to invade nearby tissues of the neck
Spread to lymph nodes around the thyroid (cervical) may or may not be present
No distant spread
- or -
Tumor is any size and may have grown beyond the thyroid gland to invade nearby tissues of the neck
Has spread to lymph nodes in the side of the neck (lateral)
or upper chest (upper mediastinal)
No distant spread
|
|
| Stage IVB (T4b, any N, M0) |
Tumor is any size and has grown either back to the spine or into nearby large blood vessels
May or may not have spread to nearby lymph nodes
No distant spread |
|
| Stage IVC (any T, any N, M1) |
Tumor is any size and may or may not have grown outside the thyroid
May or may not have spread to nearby lymph nodes
Has spread to distant sites |
|
Anaplastic thyroid cancers are considered stage IV: |
| |
Anaplastic Thyroid Carcinoma |
|
| Stage IVA (T4a, any N, M0) |
Tumor is still within the thyroid and may be respectable
May or may not have spread to nearby lymph nodes
No distant spread |
|
| Stage IVB (T4b, any N, M0) |
Tumor has grown outside the thyroid and is not respectable
May or may not have spread to nearby lymph nodes
No distant spread |
|
| Stage IVC (any T, any N, M1) |
Tumor is any size and may or may not have grown outside the thyroid
May or may not have spread to nearby lymph nodes
Has spread to distant sites |
|
Treatment depends on patient age, the type and stage of the thyroid cancer:
Surgery:
- Lobectomy: lobe containing the cancer is removed, usually along with the isthmus
- Thyroidectomy: total, near-total, or subtotal
- Lymph node removal
Radioactive Iodine Therapy (131I): Thyroid gland normally takes up iodine. When 131I is taken in, it can destroy any thyroid gland not removed by surgery and any thyroid cancer cells remaining. Used for papillary or follicular thyroid cancer.
Thyroid Hormone therapy: used post-surgically to help maintain normal metabolism in the body as well as helps to stop cancer cells from growing by lowering the TSH level
External Radiation Therapy: Using an external beam for a focused delivery of radiation, it helps to destroy cancer cells or slow their rate of growth. More often used as part of the treatment for medullary and anaplastic thyroid carcinomas but also for any type that cannot be treated with surgery or 131I therapy
Chemotherapy: is a systemic therapy to destroy cancer cells
References:
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