Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) develops from the follicular cells of the thyroid gland, a small butterfly-shaped organ located at the base of the neck. The thyroid produces hormones that help regulate metabolism, heart rate, body temperature and many other essential functions. In anaplastic thyroid cancer, follicular cells acquire genetic changes that cause them to grow and divide uncontrollably. Unlike most other types of thyroid cancer, ATC grows rapidly, often extending beyond the thyroid into nearby neck tissues and spreading to distant organs early in the disease course.

Although ATC accounts for only about 1% to 2% of all thyroid cancers, it is one of the most aggressive forms of thyroid cancer and requires prompt evaluation and treatment. It is most frequently diagnosed in adults older than 65, affecting slightly more women than men. Although it remains challenging to treat, ongoing advances in molecular testing, targeted therapies and multispecialty cancer care continue to expand treatment options and improve outcomes for some patients.

Causes and risk factors for anaplastic thyroid cancer

The exact cause of ATC is not fully understood. Most cases develop after follicular cells acquire DNA mutations that allow the cells to grow uncontrollably and invade nearby tissues. Rather than being inherited, these cellular changes occur during a person’s lifetime.

Researchers have identified several factors that may increase the risk of developing anaplastic thyroid cancer. These include age, certain medical conditions and specific genetic alterations. Importantly, having one or more risk factors does not necessarily lead to anaplastic thyroid cancer, and many patients diagnosed with ATC have no known risk factors. Among the most well-recognized are:

• Advanced age – Most patients are diagnosed after age 65.
• Previous differentiated thyroid cancer – ATC can develop from a preexisting papillary or follicular thyroid cancer that acquires additional genetic alterations over time.
• Longstanding thyroid disease – A history of multinodular goiter may increase the risk, although most people with this and other chronic thyroid conditions will never develop ATC.
• Certain genetic alterations – Acquired mutations in genes such as TP53, TERT and BRAF are commonly identified in ATC and are believed to contribute to tumor development and progression.
• Prior radiation exposure – Previous exposure to ionizing radiation involving the head or neck may increase the overall risk of thyroid cancer, although it is more strongly linked to differentiated thyroid cancers.

Signs and symptoms of anaplastic thyroid cancer

The signs and symptoms of anaplastic thyroid cancer depend on the size and location of the tumor and whether it has spread beyond the thyroid. Because ATC is an aggressive cancer, noticeable changes often develop over days or weeks rather than months. The severity of these changes can differ among patients, but progression is typically swift once symptoms appear.

Symptoms of early-stage anaplastic thyroid cancer

A firm, rapidly enlarging lump at the front of the neck is often the first sign of ATC. Other early symptoms may include:

• Neck swelling or tenderness
• Hoarseness or other vocal changes 
• Difficulty swallowing
• Persistent cough not related to an infection

Signs of advanced anaplastic thyroid cancer

As the tumor enlarges or spreads beyond the thyroid, it may begin to invade nearby structures or spread to distant organs. Advanced symptoms of ATC may include:

• Increasing difficulty swallowing
• Shortness of breath or noisy breathing (stridor) caused by pressure on the airway
• Persistent or worsening vocal hoarseness
• Neck pain that may radiate to the ears
• Enlarged lymph nodes in the neck
• Coughing up blood
• Unintended weight loss
• Unexplained fatigue
• Symptoms related to distant spread, such as a persistent cough or bone pain

How anaplastic thyroid cancer is diagnosed

Because ATC can advance quickly, timely evaluation is essential. The diagnostic process typically begins after the patient notices a rapidly enlarging neck mass or other symptoms, such as vocal hoarseness, difficulty swallowing or breathing problems. After reviewing the patient’s medical history and performing a physical examination, the physician may order additional tests to confirm the diagnosis, determine the extent of the cancer and identify its specific type.

Common diagnostic tests for anaplastic thyroid cancer include:

• Physical examination – The physician will manually examine the neck for evidence of a thyroid mass, enlarged lymph nodes or compression of the airway or other nearby structures.
• Blood work – Thyroid function tests can help evaluate overall thyroid health, although thyroid hormone levels are often normal in patients with ATC.
• Neck ultrasound – Using high-frequency sound waves, this noninvasive test can capture real-time images of the thyroid gland and nearby lymph nodes, helping identify suspicious thyroid nodules or enlarged lymph nodes and guiding biopsy procedures.
• Fine-needle aspiration biopsy or core needle biopsy – A sample of suspicious tissue is obtained and examined under a microscope to confirm the diagnosis, distinguish ATC from other thyroid cancers and provide tissue for molecular testing when appropriate.
• Molecular testing – A specialized laboratory analysis can identify genetic alterations, such as BRAF mutations, that may help guide targeted treatment decisions.
• Computed tomography (CT) or magnetic resonance imaging (MRI) scan – Cross-sectional images can help evaluate whether the tumor has invaded nearby structures, such as the trachea, esophagus or major blood vessels.
• Positron emission tomography (PET)/CT scan – PET imaging may detect cancer that has spread beyond the neck and provide additional staging information.
• Laryngoscopy – A thin, flexible tube with a miniature camera attached may be used to examine the vocal cords if voice changes suggest involvement of the recurrent laryngeal nerve.

How anaplastic thyroid cancer is staged

The cancer staging process provides important information that helps physicians assess the extent of the tumor, create an optimal treatment plan and estimate the prognosis. Like many other cancers, ATC is staged using the American Joint Committee on Cancer (AJCC) TNM staging system, which evaluates the primary tumor (T), nearby lymph nodes (N) and distant metastasis (M).

Because anaplastic thyroid cancer is exceptionally aggressive, it is always classified as stage 4 under the AJCC staging system. Stage 4 is divided into three substages based on how far the cancer has spread:

• Stage 4A – The cancer remains confined to the thyroid.
• Stage 4B – The cancer has grown beyond the thyroid into nearby tissues in the neck.
• Stage 4C – The cancer has spread to distant organs, such as the lungs, bones or brain.

How anaplastic thyroid cancer is treated

Treatment for ATC is highly individualized based on the tumor’s size, stage, genetic profile and resectability (whether it can be completely removed surgically), as well as the patient’s overall health. Due to the aggressive nature of the cancer, treatment often begins soon after diagnosis. Care is usually provided by a multispecialty team, which may include head and neck surgeons, medical oncologists, radiation oncologists, endocrinologists, radiologists, pathologists and supportive care specialists.

Treatment options for anaplastic thyroid cancer may include:

• Surgery – If the tumor can be removed safely, surgery may involve a total thyroidectomy along with removal of affected lymph nodes or nearby structures when necessary. In some cases, targeted therapy, chemotherapy or radiation therapy may be used before surgery to shrink the tumor and improve the likelihood of complete removal.
• Chemotherapy – Cancer-fighting drugs may be used alone or in combination with radiation therapy or other systemic treatments to help control rapidly growing cancer cells or manage advanced disease.
• Targeted therapy – Molecular testing may identify certain gene alterations, such as a BRAF V600E mutation, that make the tumor eligible for targeted medications designed to block cancer growth.
• Immunotherapy – Immune checkpoint inhibitors may be recommended for select patients, either alone or in combination with other systemic therapies, depending on the tumor’s molecular characteristics and the current treatment guidelines.
• Radiation therapy – External beam radiation therapy (EBRT), including intensity-modulated radiation therapy (IMRT), may be used after surgery or alongside systemic therapy to improve local tumor control and relieve symptoms.
• Supportive care – Symptom management, nutritional support, airway management, speech and swallowing therapy and other supportive services can help maintain quality of life throughout treatment.
• Clinical trials – Eligible patients may have access to investigational therapies through clinical research studies evaluating new targeted therapies, immunotherapies and combination treatment approaches.

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The Moffitt Cancer Center difference for anaplastic thyroid cancer

Effective treatment of ATC requires a prompt clinical assessment followed by specialized, highly coordinated care. At Moffitt, patients can benefit from the expertise of a multispecialty team with extensive experience managing anaplastic thyroid cancer and other rare and complex thyroid tumors. Using advanced diagnostic techniques, comprehensive molecular profiling and the latest evidence-based therapies, our team develops individualized treatment plans designed to address each patient's specific tumor characteristics, overall health and treatment goals.

As a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, Moffitt also offers access to a robust portfolio of clinical trials. These important research studies are designed to evaluate innovative therapies for anaplastic thyroid cancer, providing eligible patients with promising new treatment options that may not be available elsewhere.

To learn more about anaplastic thyroid cancer, you can request an appointment with a specialist in Moffitt’s Thyroid Clinic by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals and virtual visits are also available for patients in Florida.