What is Thyroid Cancer?
Thyroid cancer is a disease where abnormal cells start to grow in the thyroid, a gland in the neck. The thyroid gland is made up of two main types of cells: the thyroid follicular cells and the C-cells, also known as parafollicular cells. The follicular cells can lead to a type of thyroid cancer called differentiated thyroid cancer (DTC) while the C-cells can lead to a type termed medullary thyroid carcinoma (MTC). DTC itself has various types including papillary thyroid cancer, follicular thyroid cancer, and Hurthle cell cancer. These types make up about 90-95% of all thyroid cancer cases. On the other hand, MTC is relatively rare, accounting for only about 1 to 2% of cases. Lastly, there’s anaplastic thyroid carcinoma, which is less than 1% of all thyroid cancers.
What Causes Thyroid Cancer?
About 5% of papillary and follicular thyroid cancers, and between 15% to 30% of medullary thyroid cancers are thought to run in families. In recent years, there’s been an increase in the number of people diagnosed with papillary thyroid cancer. This is largely because of improved early detection methods and advances in medical imaging. However, this also increases the chances of diagnosing cancers that may not have caused any issues, which is referred to as overdetection.
Genetic changes, specifically in the genes involved in the MAPK cell signalling pathway, are often associated with most forms of thyroid cancer.
For example, in papillary thyroid cancer, the most common genetic change is a point mutation in the BRAF gene. This mutation is found in 29% to 69% of these cases. There are also cases where rearrangements of certain genes, known as translocations, occur. A common example is the RET/PTC translocation, found in 7% of cases. Additionally, mutations in the RAS gene are found in 10-20% of a subtype of papillary thyroid cancer called follicular variant.
In follicular thyroid cancer, the most common genetic change is in the RAS gene, found in about 40% to 50% of these cases. There’s also a rearrangement in the PAX8 and PPARγ genes identified in 30% to 35%.
In anaplastic thyroid cancers, an inactive mutation of the p53 tumor suppressor gene is common, and early inactivating mutations occur in about 50% to 80% of the cases. Also, about 66% of anaplastic thyroid cancers have mutations in the CTNNB1 gene. The RAS gene mutation is also associated with 20% to 40% of anaplastic thyroid cancers.
In medullary thyroid cancer, inherited forms usually results from mutations in the RET gene and occur in about 25% of cases. Additionally, RAS gene mutations are also found in 25% of cases.
There are also less common gene mutations, like TERT, that are linked to the development of thyroid cancer. These are especially linked to very aggressive forms of papillary thyroid cancer. Some thyroid cancers can be inherited in a way that follows an ‘autosomal dominant inheritance’ pattern, or can be part of certain syndromes that increase a person’s risk of developing tumors.
The main risk factors for developing thyroid cancer include being female, having a family history of thyroid cancer, and having been exposed to radiation in the thyroid area during childhood. While thyroid cancer affects both men and women equally, it’s often detected more in women, potentially due to differences in access to medical care.
Risk Factors and Frequency for Thyroid Cancer
Thyroid cancer accounts for 1% to 4% of all cancer types and is the fifth most frequent cancer in women in the United States. It’s more common in women, with the ratio being around 3:1 (women to men). Over the past three decades, there’s been a steady increase in the number of thyroid cancer cases globally. Particularly, the detection of Papillary Thyroid Cancer (PTC) has gone up by 240%. This rise in thyroid cancer cases has been noted in all genders and races, largely believed to be due to the increased use of diagnostic imaging.
- Thyroid cancer makes up 1% – 4% of all cancers.
- It’s the 5th most common cancer in women in the U.S.
- The female to male ratio of those affected is around 3:1.
- There’s been a steady increase in thyroid cancer cases worldwide, especially PTC, which has risen by 240% over the last 30 years.
- This increase is noticed among all genders and races and is likely due to more diagnostic imaging.
- PTC is the most common type of endocrine cancer, accounting for 96% of all new cases and 66.8% of deaths due to endocrine cancers.
- Most thyroid cancers come from the follicular epithelium, with PTC and Follicular Thyroid Cancer (FTC) being much more common than anaplastic thyroid cancer.
Signs and Symptoms of Thyroid Cancer
Differentiated Thyroid Cancer (DTC) usually shows up as a swelling in the neck, noticed by the patient or a doctor, or as thyroid nodules that appear on neck scans. While thyroid nodules are quite common and generally not cancerous (with only a 5 to 10% chance), the risk is higher for men and people at extreme ages.
To determine whether a nodule is likely to be cancerous, doctors will look at the patient’s medical history and carry out a physical examination. These might not always give definitive answers, but certain signs can flag a higher risk. For instance, a nodule that has grown quickly and causes symptoms such as a hoarse voice, difficulty swallowing or breathing, or Horner’s Syndrome (a condition affecting the eyes and facial muscles), could be a sign of cancer. Other risk factors include a family history of thyroid cancer, exposure to radiation in the head or neck area during childhood, and systemic effects such as weight loss and fatigue. During a physical examination, hard, immovable nodules or the presence of lymph nodes in the neck can also point towards cancer.
Anaplastic thyroid cancer, on the other hand, can show up as a neck mass that grows very quickly and causes symptoms affecting the breathing and digestive tracts. Some patients might also experience general symptoms such as fever, weight loss, and loss of appetite.
Testing for Thyroid Cancer
If you have a thyroid nodule, the first step your doctor usually takes is to perform a thyroid function test. If the results indicate an overactive thyroid, the chances of the nodule being cancerous are lower. In this case, your doctor might order a radionuclide uptake scan, which checks how well your thyroid is functioning. If your thyroid is overactive, a fine-needle aspiration biopsy (FNAB) – a procedure where a tiny needle is used to remove a sample of cells from your thyroid – is typically avoided because the results might not be accurate and these nodules are rarely cancerous.
However, if your thyroid function is normal or underactive, your doctor will start with a detailed thyroid ultrasound. This can help your doctor assess the nodule for any high-risk factors, detect any additional nodules that were not found during a physical exam, check for any neck lymph nodes, and guide a FNAB if necessary. Some of these high-risk factors include growth from previous imaging, a dark appearance on ultrasound, irregular edges, size wider than tall, small calcifications, a solid internal structure, extension outside the thyroid, and blood vessels in the center. Features that suggest a lower risk of cancer include a purely liquid-filled nodule, a porous appearance, comet tail shadowing, and blood vessels around the edge. Whether a nodule needs a FNAB or not is based on these features and guidelines from the Thyroid Imaging Reporting and Data System (TIRADS) or the American Thyroid Association (ATA).
It’s important to note that the accuracy of the FNAB depends on the skills of both the person performing the procedure and the one examining the results. This test is great for diagnosing papillary thyroid carcinoma (PTC) but can’t detect capsular or vascular invasions by follicular thyroid carcinoma (FTC). It can only classify certain findings as suspicious for FTC and a diagnosis can only be made after a surgical resection.
The results of FNAB are usually reported using the Bethesda Criteria for Reporting Thyroid Cytology. This system categorizes biopsy results based on the cell type and advises next steps. For instance, Bethesda Category 1 denotes a non-diagnostic FNAB, where re-aspiration is necessary. Bethesda Category 2 suggests that the nodule is benign, and can be monitored with periodic thyroid ultrasound. Categories 3 and 4 imply that it’s unclear whether or not there’s thyroid cancer, hence a repeat FNAB, molecular testing, or a partial thyroid removal may be warranted. Bethesda Categories 5 and 6 generally require surgery.
Molecular testing is used when the FNAB results are unclear. Traditionally, tests for single mutations like BRAF V600E or RET/PTC translocations were performed. While these tests are quite specific, they lack sensitivity. Recently, broader gene panel testing has been introduced, improving test sensitivity and specificity.
Computed tomography (CT) and magnetic resonance imaging (MRI) scans aren’t routinely used to evaluate thyroid nodules for cancers. However, they might be useful in assessing the local spread in more advanced diseases or in cases where the cervical nodes are enlarged with a suspicious mass. A CT scan might be recommended for patients with a thyroid mass that is extending into the substernal region, as confirmed by ultrasound or standard X-rays.
Treatment Options for Thyroid Cancer
Papillary and follicular thyroid cancers represent some of the most common types of thyroid cancer. The primary method of treatment for both of these cancers is a surgical procedure known as surgical resection, followed by radioiodine ablation (a procedure where iodine is used to destroy remaining cancer cells) and hormone therapy with thyroid hormone. The use of radiation and chemotherapy is limited and is typically reserved for advanced cases that are not responding to other treatments.
Before surgery, an experienced thyroid specialist would typically perform a comprehensive ultrasound of your neck. This procedure helps to determine the type of surgery needed, which can range from the removal of half the thyroid (hemithyroidectomy) to the removal of the entire thyroid (total thyroidectomy), with or without the removal of lymph nodes. The decision of which surgery to undergo depends on several factors including the size of the tumor, the presence of any lymph node metastasis (spread of cancer), extension of the cancer beyond the thyroid, the patient’s age, and any other conditions the patient might have.
Conducting a thorough risk assessment after surgery is vital, it helps determine the need for additional treatment, like radioiodine ablation. Two systems commonly used for this purpose are the TNM (Tumour, Node, Metastasis) system and the American Thyroid Association risk stratification system. These systems consider various factors such as the size of the tumor, the presence and extent of the disease, number of nodal metastases, and age, among others.
Following surgery, some patients may need additional treatment such as radioiodine (RAI) ablation therapy or thyroid hormone suppression therapy. RAI therapy works by destroying any residual thyroid tissue or microscopic areas of thyroid cancer that couldn’t be removed during surgery. Hormone suppression therapy, on the other hand, minimizes the stimulation of potential thyroid cancer growth by suppressing the thyroid-stimulating hormone (TSH).
In some rare cases, thyroid cancers may not respond to the initial treatment or could recur. In such situations, there are several potential treatment options. One of these is the percutaneous ethanol injection, a procedure used for treating cervical lymph node metastasis, which is the spread of cancer to the lymph nodes in the neck. Another is radiofrequency ablation, used to treat small distant metastases in bones or lungs. Other treatment options include external beam radiation and systemic chemotherapy.
Systemic chemotherapy, a treatment option that uses drugs to kill cancer cells, is usually only considered in patients with a significant spread of the disease or rapidly progressing disease. The drugs used for this type of treatment are chosen based on the patient’s genetic profile.
In addition to initial treatments, continuous monitoring and reassessment are crucial. It helps track the progress of the disease, the effectiveness of the treatment, and decide on future treatment strategies. The frequency of this monitoring depends on how the disease initially responded to the treatment.
Unlike other types of thyroid cancer, medullary thyroid cancer is treated differently. It is typically managed by total removal of the thyroid and any metastases. Radioiodine ablation or thyroid hormone suppression are not effective treatments for this type of cancer. However, if the medullary thyroid cancer becomes resistant to treatment, taking certain types of chemotherapy drugs known as kinase inhibitors can be beneficial.
Anaplastic thyroid cancer, a rare and aggressive form of thyroid cancer, requires a combination of surgery, radiation, and chemotherapy. Certain genetic factors can guide treatment decisions. Unfortunately, this type of cancer often spreads quickly, making it challenging to treat.
What else can Thyroid Cancer be?
When discussing medical conditions related to the thyroid, a few possibilities could include:
- Benign thyroid nodule
- Toxic nodular goiter
- Primary thyroid lymphoma
- Cervical lymphadenopathy
What to expect with Thyroid Cancer
The outlook for patients with thyroid cancer can greatly vary and it depends on several factors. These factors might include, what type of thyroid cancer it is, the size of the tumor, whether or not it’s spread to other parts of the body, the patient’s age, and whether surgery is an option. On a positive note, the prognosis is typically quite good. In fact, up to 95% of patients of all ages and ethnicities survive for at least 5 years after their diagnosis.
Unfortunately, not all cases are easy to treat. Certain factors can make the outlook less favorable, including the presence of larger tumors, cancers that have spread beyond the thyroid to other parts of the body, being older in age, or having particular types of aggressive thyroid cancer such as undifferentiated cancer.
Possible Complications When Diagnosed with Thyroid Cancer
If thyroid cancer isn’t treated, it can begin to spread and affect nearby areas such as the airway, esophagus, or nearby nerves and blood vessels. It can also potentially spread to distant areas such as the lung, bone, and other soft tissues.
Both thyroid lobectomy (removal of part of the thyroid gland) and total thyroidectomy (removal of the entire thyroid gland) carry risks. The most common risk is damage to the recurrent laryngeal nerve, which can lead to a change in voice and potentially difficulty breathing if both sides are affected.
Pregnant women who receive treatment for thyroid cancer, usually through thyroidectomy, do not seem to have any significant increase in pregnancy complications.
Key Points:
- Untreated thyroid cancer can negatively affect nearby areas and spread to distant areas like the lung and bone.
- Surgery to treat thyroid cancer carries the risk of nerve damage, which can affect voice and breathing.
- Treatment of thyroid cancer in pregnant women doesn’t seem to increase pregnancy complications.
Preventing Thyroid Cancer
As we’ve mentioned before, people who have been exposed to radiation treatments in the head and neck area, or have a family history of thyroid cancer, should be regularly checked for thyroid cancer. This is particularly important if these individuals discover lumps, known as thyroid nodules, in the neck area – either with or without feelings of pressure or discomfort.
