Anaplastic Thyroid Cancer
Anaplastic thyroid cancer is one of the most aggressive forms of cancer affecting the thyroid gland, growing rapidly and often spreading to other parts of the body before diagnosis, yet recent advances in targeted treatments offer new hope for some patients.
Table of contents
- What is anaplastic thyroid cancer?
- Signs and symptoms
- Causes and risk factors
- How doctors diagnose this cancer
- Staging of the disease
- Treatment approaches
- Outlook and survival
What is anaplastic thyroid cancer?
anaplastic thyroid carcinoma, undifferentiated thyroid cancer, ATC
Anaplastic thyroid cancer, also known as anaplastic thyroid carcinoma or undifferentiated thyroid cancer, is a rare and extremely aggressive form of cancer that develops in the thyroid gland. The thyroid is a butterfly-shaped gland located at the front of your neck that produces hormones regulating your body’s metabolism[1].
- thyroid gland
- neck
- lymph nodes
- trachea (windpipe)
- esophagus (food pipe)
- vocal cords
This type of cancer is called “undifferentiated” because the cancer cells don’t look or behave like normal thyroid cells. They have lost the typical characteristics of thyroid tissue and grow in a disorganized, chaotic way[1].
Anaplastic thyroid cancer is extremely rare, accounting for less than 2% of all thyroid cancer cases. However, despite its rarity, it is responsible for 20% to 50% of all deaths from thyroid cancer due to its aggressive nature[2][6].
This cancer is known for growing very quickly and spreading rapidly to nearby structures in the neck and to distant parts of the body. Because it grows so fast, all cases of anaplastic thyroid cancer are classified as stage IV cancer at the time of diagnosis, regardless of the tumor size[1][3].
Signs and symptoms
Unlike other types of thyroid cancer that may not cause symptoms, anaplastic thyroid cancer typically causes noticeable problems because it grows so quickly. Most commonly, it starts as a lump or nodule (a small mass) on the front of your neck. This lump is usually hard, painful, and can be both seen and felt. The lump often appears suddenly and grows rapidly, sometimes over just a few weeks[1][4].
As the tumor grows larger, it can press against and invade other structures in your neck, causing a range of symptoms. These include difficulty swallowing, as the tumor presses on the esophagus (the tube that carries food from your mouth to your stomach). You may also experience difficulty breathing or feel pressure or shortness of breath, especially when lying flat, because the tumor is pressing on your trachea (windpipe)[1][4].
Changes to your voice are common. Your voice may become hoarse or change in other ways if the tumor affects the nerves that control your vocal cords. Some people experience vocal cord paralysis, where the vocal cords cannot move properly. You might also notice loud breathing sounds or develop a persistent cough[1][5].
When anaplastic thyroid cancer has spread to other parts of the body, additional symptoms may appear. These can include bone pain if the cancer has spread to your bones, swollen lymph nodes in your neck, general weakness, and neurological problems if the cancer has reached the brain[1].
Causes and risk factors
Scientists do not know the exact cause of anaplastic thyroid cancer. They believe that in many cases, it develops from other, less aggressive types of thyroid cancer that already exist. Nearly half of all cases occur in people who previously had differentiated thyroid cancer, such as papillary thyroid cancer or follicular thyroid cancer. This suggests that the cancer cells from these slower-growing cancers can change and become more aggressive over time[2][6].
Several factors can increase your risk of developing this type of cancer. Age is an important factor—anaplastic thyroid cancer most commonly occurs in people over the age of 60, with an average age of diagnosis around 60 to 67 years[1][5].
This cancer is more common in women than in men. Having a history of other thyroid cancers, particularly papillary or follicular thyroid cancer, increases your risk. A long-standing goiter (an enlarged thyroid gland) or a history of other thyroid diseases also raises your risk[1][4].
Past radiation exposure to the chest or neck area is another risk factor. This includes radiation therapy treatments that may have been given for other medical conditions[4].
How doctors diagnose this cancer
If you have symptoms suggesting anaplastic thyroid cancer, especially a rapidly growing neck mass, your doctor will need to perform several tests to confirm the diagnosis and determine the extent of the disease.
The main diagnostic procedure is a needle biopsy. During this procedure, your doctor uses a very thin needle to remove a small tissue sample from the mass in your thyroid. A specialist called a pathologist then examines this tissue under a microscope to look for cancer cells and determine what type of thyroid cancer is present[1][3].
Sometimes a fine needle biopsy may not provide enough tissue for a clear diagnosis. In these cases, your doctor may recommend a core needle biopsy, which uses a larger needle to obtain more tissue. This type of biopsy is more sensitive and specific for diagnosing anaplastic thyroid cancer. Occasionally, a surgical biopsy may be necessary[3][4].
Once anaplastic thyroid cancer is diagnosed, your doctor will order imaging tests to see if the cancer has spread. These tests typically include blood tests, a CT scan (a special type of X-ray that creates detailed pictures of the inside of your body), an MRI (which uses magnets and radio waves to create images), and a type of PET scan called F-fluorodeoxyglucose positron emission tomography[1].
Your doctor may also perform a flexible laryngoscopy, where a thin tube with a camera is inserted down your throat to check if the cancer has affected your vocal cords[4].
Staging of the disease
Because anaplastic thyroid cancer is so aggressive, all cases are classified as stage IV cancer when diagnosed. This is different from most other cancers, where staging depends on tumor size and spread. The aggressive nature of this cancer means it has usually already begun to spread by the time it is discovered[1].
However, stage IV is divided into three substages based on where the cancer is located. Stage IVA means the cancer is only in your thyroid gland. This occurs in about 10% of cases[1].
Stage IVB means the cancer has spread beyond the thyroid to nearby areas in your neck, typically to lymph nodes, but has not spread to distant parts of your body. This happens in about 40% of cases[1].
Stage IVC means the cancer has spread to distant organs in your body, such as your lungs, bones, or brain. This is found in about 50% of cases at the time of diagnosis[1].
Treatment approaches
Treatment for anaplastic thyroid cancer needs to begin as soon as possible due to the rapid growth of the tumor. The treatment approach typically involves a combination of different therapies, including surgery, radiation therapy, chemotherapy, targeted therapy, and palliative care (care focused on relieving symptoms and improving quality of life)[1][3].
Surgery
If medically possible, your healthcare team will likely recommend surgery to remove the tumor. However, in many cases, surgery is not possible because the tumor is too large, has grown into critical structures, or the patient has other medical conditions that make surgery too risky[1].
The most common surgical procedure is called debulking surgery. This involves removing as much of the tumor as possible, especially any part that is threatening your airway. Even when complete removal is not possible, surgery can help relieve symptoms and improve breathing[1][4].
In some cases where the tumor is compressing the airway, a tracheostomy may be necessary. This procedure creates an opening in your windpipe and places a plastic tube below the tumor to help you breathe[5].
Radiation therapy
Radiation therapy uses high-energy rays or particles to destroy cancer cells. It is commonly used for anaplastic thyroid cancer and is usually given to both the thyroid and neck area to help slow down and control the growth of the cancer[14].
Sometimes radiation therapy is given at the same time as chemotherapy, which is called chemoradiation. A standard radiation schedule gives treatment once a day. Alternatively, smaller doses may be given twice a day, which is called hyperfractionation. This approach may allow doctors to deliver higher total doses with potentially less toxicity[12][14].
Chemotherapy
Chemotherapy uses anticancer drugs to destroy cancer cells. For anaplastic thyroid cancer, the chemotherapy drugs most commonly used are doxorubicin and cisplatin. Sometimes doxorubicin is used alone. Other drugs that may be used include paclitaxel or docetaxel[12][14].
Chemotherapy may be given alone or in combination with radiation therapy as part of chemoradiation treatment.
Targeted therapy
Targeted therapy is a newer type of treatment that uses drugs to target specific molecules or proteins in cancer cells. For anaplastic thyroid cancer, several targeted therapy drugs are available and may be very effective, especially if your tumor has certain genetic changes[14].
The combination of dabrafenib and trametinib is used for patients whose tumors have a specific genetic change called a BRAF V600E mutation. In 2018, the Food and Drug Administration approved this combination specifically for anaplastic thyroid cancer with this mutation. This treatment has shown promising results, with more than half of patients achieving a partial response[12].
Other targeted therapy drugs include sorafenib and lenvatinib, which are multitarget drugs that can be used regardless of the tumor’s genetic makeup. Lenvatinib was approved in Japan for treating unresectable anaplastic thyroid cancer[15].
Additional targeted drugs may be used if specific genetic changes are found in your tumor. For example, selpercatinib is used for tumors with RET gene changes, and larotrectinib or entrectinib are used for tumors with NTRK gene changes[14].
Because different genetic changes require different treatments, your doctor should test your tumor for these mutations to determine the best treatment approach for you[15].
Immunotherapy
Immunotherapy is a treatment that helps your body’s own immune system fight cancer. Some anaplastic thyroid cancer tumors may respond to immunotherapy drugs called checkpoint inhibitors, such as spartalizumab and pembrolizumab, which work against proteins called PD-1 and PD-L1[15].
Palliative care
Palliative care focuses on relieving symptoms and improving quality of life rather than treating the cancer itself. This type of care is important for all patients with anaplastic thyroid cancer and should be included from the beginning of treatment. A palliative care team can help manage pain, control symptoms, and address emotional, psychological, and spiritual needs[25].
Outlook and survival
Anaplastic thyroid cancer has a very poor prognosis overall. The average survival time after diagnosis is about six months, and most patients do not survive longer than a few months. The five-year survival rate is less than 5% to 10%[2][4][8].
However, outcomes vary depending on the stage of the disease at diagnosis and the treatments available. Patients with stage IVA disease (cancer confined to the thyroid) have a median survival of about 15.8 months. Those with stage IVB disease (cancer spread to the neck but not distant organs) have a median survival of 6.1 months. Patients with stage IVC disease (cancer spread to distant organs) have the poorest outlook, with a median survival of only 2.8 months[15].
Despite these discouraging statistics, some people with anaplastic thyroid cancer have lived for years after treatment. Recent advances in targeted therapies and improved treatment approaches offer hope for better outcomes in the future. It is important to remember that survival statistics reflect averages for groups of people and cannot predict what will happen to any individual person[1][5].
Early discussions about goals of care, including end-of-life planning, are important for patients with this diagnosis. These discussions should include naming a person who can make medical decisions if you are unable to do so, and establishing your wishes regarding resuscitation and end-of-life care[25].
