The thyroid gland is a butterfly-shaped organ that lies in the lower part of the front of the neck below the Adam’s apple. The thyroid gland produces hormones that are involved in the normal functioning of various organs of the body such as the heart, brain, liver, and muscles. These hormones help regulate metabolic functions such as blood pressure, body temperature regulation, Growth, body weight, etc.
Any abnormal and uncontrolled proliferation of cells in the thyroid gland leads to the formation of cancer. Different types of cancer can occur in the gland depending on the type of cell from which they originate, or on the type of cells which are present in the tumor.
Thyroid Cancer Types
Thyroid cancer type is determined after taking a tissue sample from the tumor and is based on the type of cells seen in the tissue. Thyroid cancer encompasses several distinct types, each with unique characteristics and implications for treatment and prognosis
Types of thyroid cancer include:
Differentiated Thyroid cancer
Differentiated thyroid cancers primarily encompass papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), both of which originate from the follicular cells of the thyroid gland. These cancers account for the majority of thyroid cancer cases and generally have better prognoses compared to other types.
- Papillary Thyroid cancer: Papillary thyroid cancer is the most common subtype, representing around 80% of cases. It tends to grow slowly and typically remains localized within the thyroid gland, Papillary thyroid cancer has a propensity to spread to nearby lymph nodes in the neck, particularly in advanced stages and is associated with a low propensity for spreading distant organs such as liver or bones.
- Follicular Thyroid cancer: Follicular thyroid cancer is less common but also arises from follicular cells. Microscopically, follicular thyroid cancer is characterized by the formation of follicular structures resembling normal thyroid tissue. Unlike papillary thyroid cancer, which forms papillary structures, FTC forms follicular patterns. FTC often invades blood vessels within the thyroid gland, allowing cancer cells to spread into the bloodstream and potentially metastasize to distant organs. It may present as either minimally invasive or widely invasive, depending on the extent of tumor invasion into blood vessels and surrounding tissues. Unlike PTC, FTC has a lower tendency to metastasize to lymph nodes in the neck.
- Hurthle cell thyroid cancer accounts for only a small percentage of all thyroid cancers, approximately 3-5%. It is more common in older individuals, typically diagnosed in the sixth or seventh decade of life. Hurthle cell carcinoma tends to be more aggressive than other types of thyroid cancer, with a higher risk of recurrence and metastasis. However, it is still considered a differentiated thyroid cancer, meaning it arises from follicular cells and retains some ability to take up radioactive iodine.
Medullary Thyroid Cancer
Medullary thyroid cancer (MTC) is a type of thyroid cancer that develops from the C cells of the thyroid gland, which produce a hormone called calcitonin unlike other types of thyroid cancer (differentiated variety) that arise from follicular cells. Mutations in RET proto-oncogene play a key role in the development and progression of MTC.
While MTC is relatively rare compared to other types of thyroid cancer, it tends to be more aggressive and has a higher likelihood of spreading to lymph nodes or distant organs.
Anaplastic Thyroid Cancer
Anaplastic thyroid cancer (ATC) is an aggressive and rare form of thyroid cancer that develops rapidly and is often diagnosed at advanced stages. Unlike other types of thyroid cancer, ATC is highly invasive and resistant to standard therapies.
This type of cancer accounts for less than 2% of all thyroid cancer cases but carries a disproportionately high mortality rate due to its aggressive nature.
Anaplastic thyroid cancer arises from the follicular cells of the thyroid gland and can quickly spread to nearby tissues in the neck, such as the trachea and esophagus, leading to compression of vital structures and difficulty breathing or swallowing.
Thyroid Cancer Causes and Risk Factors
Presence of risk factors can increase your propensity for development of thyroid cancer over a period of time. Although the exact cause often remains undetermined. Risk factors are different for different type of thyroid cancer, they include:
Radiation Exposure: Previous exposure to radiation, particularly during childhood or adolescence, increases the risk of developing both papillary and follicular thyroid cancer. This exposure may come from medical treatments (such as radiation therapy for head and neck cancers) or environmental factors (such as nuclear accidents). Although less common, previous radiation exposure may also increase the risk of developing ATC.
Genetic Mutations: About 25% of the Medullary thyroid cancers are hereditary and associated with genetic mutations in the RET proto-oncogene. Multiple endocrine neoplasia type 2 (MEN 2) syndromes, including MEN 2A and MEN 2B, increase the risk of developing MTC.
Specific genetic mutations, such as mutations in the BRAF gene or rearrangements involving the RET or NTRK genes, are commonly associated with papillary thyroid carcinoma.
Some other factors that might play a role include being older (Age), and being a woman (Gender). But even if you have some of these risk factors, it doesn’t mean you’ll definitely get thyroid cancer.
If you have concerns any concerns related to your risk for thyroid cancer, consult your healthcare physician for evaluation.
Thyroid cancer Symptoms
lets discuss about the ways in which thyroid cancer may present.
Thyroid cancer often doesn’t cause noticeable symptoms in its early stages. However, as the cancer grows, it may produce signs and symptoms that vary depending on the type of thyroid cancer and the extent of the disease.
Here are some common signs and symptoms of thyroid cancer:
- Neck Lump or Nodule: One of the most common signs of thyroid cancer is a lump or nodule in the front of the neck, just below the Adam’s apple. This lump may be painless and can sometimes be felt by gently palpating the neck.
- Changes in Voice: Thyroid cancer can affect the nerves that control the vocal cords, leading to changes in voice quality, such as hoarseness or persistent voice changes.
- Difficulty Swallowing (Dysphagia): As thyroid tumors grow, they may compress the nearby structures in the neck, including the esophagus, leading to difficulty swallowing or the sensation of a lump in the throat.
- Neck Pain or Pressure: Some people with thyroid cancer may experience neck pain or discomfort, especially if the tumor is pressing on nearby tissues or nerves.
- Swollen Lymph Nodes: Thyroid cancer can spread to nearby lymph nodes in the neck, causing them to become enlarged or palpable.
- Changes in Breathing: In advanced cases of thyroid cancer, tumors may grow large enough to obstruct the airway, leading to difficulty breathing, shortness of breath, or wheezing.
- Persistent Cough: Some individuals with thyroid cancer may develop a persistent cough that doesn’t go away, particularly if the tumor is pressing on the trachea (windpipe).
- Difficulty Swallowing or Breathing: In rare cases where thyroid cancer has spread extensively or metastasized to distant organs, individuals may experience symptoms related to the affected organs, such as difficulty breathing (if the cancer has spread to the lungs) or bone pain (if the cancer has spread to the bones).
Occurrence of these symptoms should warn you about the abnormality present in your body which may be due to various other diseases also (not necessarily thyroid cancer). However, if you experience any persistent or concerning symptoms, it’s essential to see a healthcare provider for a thorough evaluation and appropriate testing.
Thyroid Cancer Diagnosis
At the suspicion of Thyroid cancer, your doctor may ask for further tests along with physical examination to better understand about the type, stage of cancer and thus make plan for further treatment.
During a physical exam, your doctor will feel your neck to check for any lumps, swelling, or enlargement of the thyroid gland. They may also look for other signs, such as changes in your voice or difficulty swallowing.
Imaging
- Ultrasound (Sonography): Ultrasound imaging uses high-frequency sound waves to produce real-time images of the thyroid gland and surrounding tissues. Ultrasound is often the first-line imaging modality for evaluating thyroid nodules, as it can provide detailed information about the size, shape, texture, and characteristics of the nodules. It helps determine if a nodule is solid or cystic and can identify features suggestive of thyroid cancer, such as irregular borders, microcalcifications, or increased vascularity.
- Computed Tomography (CT) Scan: CT scans use X-rays and computer technology to create cross-sectional images of the thyroid gland, neck, and chest. CT scans can provide more detailed information about the size and extent of thyroid nodules, as well as detect any spread of cancer to nearby lymph nodes or other structures in the neck or chest. CT scans are particularly useful for evaluating the extent of disease in cases of advanced or aggressive thyroid cancer.
- Magnetic Resonance Imaging (MRI): MRI uses powerful magnets and radio waves to create detailed images of the thyroid gland and surrounding structures. MRI provides excellent soft tissue contrast and can help identify the spread of cancer to nearby tissues, such as the trachea, esophagus, or blood vessels. MRI is often used in conjunction with other imaging modalities, particularly in cases where CT or ultrasound findings are inconclusive or when there is concern about invasion of nearby structures.
- Positron Emission Tomography-Computed Tomography (PET-CT): PET-CT combines PET and CT imaging to provide both metabolic and anatomical information about the thyroid gland and distant sites in the body. PET-CT is particularly useful for detecting distant metastases of thyroid cancer to organs such as the lungs, bones, or lymph nodes outside the neck. It helps assess the overall extent of the disease and guide treatment planning, especially in cases of advanced or metastatic thyroid cancer.
- Radioactive Iodine (RAI) Scan: Radioactive iodine scans involve administering a small amount of radioactive iodine orally or intravenously, which is taken up by thyroid cells. The distribution of radioactive iodine in the thyroid gland is then visualized using a gamma camera. RAI scans are primarily used in cases of well-differentiated thyroid cancer (such as papillary or follicular thyroid cancer) to assess the presence of residual or metastatic thyroid tissue after surgery and to detect any remaining cancer cells.
Tissue Diagnosis
During a biopsy, a small sample of tissue is collected from the thyroid gland or a thyroid nodule for examination under a microscope. There are different biopsy techniques, but the most common method for thyroid nodules is called fine needle aspiration (FNA) biopsy. In an FNA biopsy, a thin needle is inserted into the nodule, and cells are gently suctioned out for analysis.
The collected cells are examined under a microscope by a pathologist, who specializes in diagnosing diseases by studying tissues and cells. The pathologist evaluates the cellular morphology, architecture, and other characteristics to determine if the cells are benign (non-cancerous), malignant (cancerous), or indeterminate (uncertain). In cases where cancer is suspected, the pathologist may further classify the cancer subtype based on specific features observed in the cells.
Blood investigation in regard to Thyroid cancer
Underlying blood investigations are usually performed in a patient with thyroid cancer after diagnosis to assess the thyroid function along with specific tumor markers to assess the spread of disease.
- Thyroid Stimulating Hormone (TSH): TSH is a hormone produced by the pituitary gland that stimulates the thyroid gland to produce thyroid hormones (T3 and T4). In cases of thyroid cancer, TSH levels may be within the normal range or slightly elevated, depending on the specific subtype of thyroid cancer and the function of the remaining thyroid tissue. Abnormal TSH levels may indicate thyroid dysfunction or inadequate suppression of TSH production by thyroid cancer cells.
- Thyroglobulin (Tg): Thyroglobulin is a protein produced by normal thyroid cells and thyroid cancer cells. After thyroidectomy (surgical removal of the thyroid gland), thyroglobulin levels in the blood should ideally be undetectable or very low. Persistent or elevated thyroglobulin levels following thyroidectomy may indicate residual thyroid tissue, recurrence of thyroid cancer, or metastatic spread of cancer to other parts of the body. Thyroglobulin blood tests are commonly used as tumor markers to monitor response to treatment and detect recurrent or metastatic thyroid cancer.
- Calcitonin: Calcitonin is a hormone produced by the C cells of the thyroid gland, which are involved in regulating calcium levels in the body. Elevated levels of calcitonin in the blood may indicate the presence of medullary thyroid cancer (MTC), a less common subtype of thyroid cancer that originates from the C cells. Calcitonin blood tests are used to screen for and monitor MTC, particularly in individuals with a family history of MTC or certain genetic mutations associated with the disease.
- Thyroid Peroxidase Antibodies (TPOAb) and Thyroglobulin Antibodies (TgAb): Thyroid peroxidase antibodies and thyroglobulin antibodies are markers of autoimmune thyroid diseases, such as Hashimoto’s thyroiditis and Graves’ disease. While not specific to thyroid cancer, the presence of these antibodies in the blood may indicate underlying autoimmune thyroid dysfunction, which can affect thyroid function and complicate the interpretation of thyroid function tests and thyroglobulin measurements in patients with thyroid cancer.
These blood tests are valuable tools in the diagnosis, staging, and monitoring of thyroid cancer. They provide important information about thyroid function, tumor markers, and response to treatment, helping healthcare providers tailor individualized treatment plans and optimize outcomes for patients with thyroid cancer.
Genetic Testing
In some cases, genetic testing may be performed to identify specific genetic mutations associated with thyroid cancer, particularly in cases of medullary thyroid cancer or hereditary forms of thyroid cancer.
Here’s an overview of genetic testing for thyroid cancer:
RET Proto-Oncogene Testing: Mutations in the RET proto-oncogene are commonly associated with medullary thyroid carcinoma (MTC). Genetic testing for RET mutations can help diagnose hereditary forms of MTC, such as multiple endocrine neoplasia type 2 (MEN2) syndromes (MEN2A and MEN2B), familial MTC, and sporadic MTC. Identifying RET mutations can guide clinical management decisions, including surveillance strategies and prophylactic thyroidectomy in at-risk individuals.
BRAF V600E Mutation Testing: The BRAF V600E mutation is one of the most common genetic alterations found in papillary thyroid carcinoma (PTC). The presence of this specific mutation is associated with aggressive tumor behavior, increased risk of recurrence, and resistance to certain therapies. Identifying BRAF mutations can help stratify patients into risk categories and guide treatment decisions, including the selection of targeted therapies and clinical trial eligibility.
RAS Gene Mutation Testing: RAS gene mutations, including mutations in HRAS, KRAS, and NRAS, are found in a subset of thyroid cancers, including follicular thyroid carcinoma (FTC) and poorly differentiated thyroid carcinoma (PDTC). While RAS mutations are less common than BRAF mutations in PTC, they are associated with a poorer prognosis and may influence treatment decisions.
Other Genetic Alterations: In addition to RET, BRAF, and RAS mutations, other genetic alterations and rearrangements may occur in thyroid cancer, including mutations in the PIK3CA, PTEN, and TP53 genes, and gene fusions involving the RET, NTRK, and ALK genes.
Genetic testing for thyroid cancer plays a critical role in personalized medicine by guiding treatment decisions, prognostication, and risk assessment. Identifying specific genetic mutations can help tailor treatment strategies, such as the use of targeted therapies or immunotherapies.
Thyroid Cancer Treatment
After diagnosing the Thyroid cancer, and after evaluation of type and stage of cancer, your doctor may advise further treatment which may be appropriate for your disease. In the following session, we’ll discuss about various treatment modalities used for thyroid cancers
Surgery
Surgery is the primary treatment for most types of thyroid cancer and involves the removal of part or all of the thyroid gland. The extent of surgery depends on factors such as the size and location of the tumor, the type of thyroid cancer, and whether the cancer has spread to nearby lymph nodes or tissues. Common surgical procedures for thyroid cancer include:
- Thyroidectomy: This involves the removal of the entire thyroid gland. Total thyroidectomy is typically recommended for most cases of thyroid cancer to ensure complete removal of the tumor and reduce the risk of recurrence.
- Lobectomy: In some cases, only one lobe of the thyroid gland containing the tumor may be removed, preserving the function of the remaining thyroid tissue.
- Neck Dissection: If thyroid cancer has spread to nearby lymph nodes, a neck dissection may be performed to remove affected lymph nodes.
Surgery is performed traditionally performed by open technique in which a cut is make over the skin directly over the thyroid gland in front of neck. Nowadays, minimally invasive surgery is gaining popularity as it offer several benefits, including smaller incisions, reduced postoperative pain, shorter hospital stays, and quicker recovery times compared to traditional open surgery.
Various minimally invasive techniques for thyroid cancer surgery include Endoscopic thyroid surgery, Robotic surgery using Da Vinci system, Transoral thyroidectomy via vestibular approach, Alcohol or Radiofrequency ablation of small nodules.
Radioactive Iodine (RAI) Therapy
Radioactive iodine therapy is often used after surgery to destroy any remaining thyroid tissue and cancer cells. It involves the administration of radioactive iodine, which is taken up by thyroid cells, including cancer cells, and destroys them. RAI therapy is particularly effective for well-differentiated thyroid cancers, such as papillary and follicular thyroid carcinoma. Patients may need to follow a low-iodine diet and temporarily discontinue thyroid hormone replacement therapy before RAI treatment to enhance the uptake of radioactive iodine by thyroid cells.
Hormone Replacement Therapy
After thyroidectomy or RAI therapy, patients may need to take synthetic thyroid hormone medication (levothyroxine) to replace the hormones normally produced by the thyroid gland. This hormone replacement therapy helps maintain normal thyroid hormone levels in the body, prevents hypothyroidism, and suppresses the production of TSH (thyroid-stimulating hormone), which can stimulate the growth of any remaining thyroid cancer cells.
External Beam Radiation Therapy (EBRT)
External beam radiation therapy involves the use of high-energy X-ray beams directed at the thyroid gland and surrounding tissues to kill cancer cells and shrink tumors. EBRT may be used as an adjuvant therapy after surgery to reduce the risk of recurrence or as palliative therapy to relieve symptoms in advanced cases of thyroid cancer. It is less commonly used than RAI therapy but may be recommended in certain situations, such as when RAI therapy is not effective or feasible.
Targeted Therapy and Immunotherapy
For advanced or metastatic thyroid cancer that does not respond to traditional treatments, targeted therapy drugs or immunotherapy drugs may be used. These drugs target specific molecular pathways or immune checkpoints involved in cancer growth and spread, helping to slow down tumor growth and improve survival. Targeted therapy drugs, such as tyrosine kinase inhibitors (TKIs), may be used to treat certain types of thyroid cancer with specific genetic mutations, such as BRAF or RET mutations.
Thyroid Cancer Survival
Thyroid cancer generally has a favorable prognosis compared to many other types of cancer, with high overall survival rates.
However, depending on factors such as the subtype and stage of your thyroid cancer, your age at diagnosis, treatment received, and other individual characteristics specific to you, Your doctor may estimate the 5 year survival in your case. Although these survival rates are based on the data based on studies on similar patients, it may not predict the individual outcome.
Therefore, it’s essential for you to work closely with their healthcare team to develop a personalized treatment plan and receive ongoing support and surveillance to optimize your outcomes and quality of life.
