What Is Anaplastic Thyroid Cancer?

Overview

Anaplastic thyroid cancer (ATC) is a rare and highly aggressive form of thyroid cancer. While it typically develops from follicular or papillary thyroid cancer, it can also occur on its own. ATC is a difficult disease to treat due to its rapid growth and resistance to standard treatments such as surgery and radiation therapy. In this article, will explore the causes, symptoms, and management of ATC.

Epidemiology of anaplastic thyroid cancer

Anaplastic cancer is a rare disease, with an age-adjusted annual incidence of approximately one to two cases per million individuals. However, it accounts for a significant percentage of all thyroid cancers worldwide, ranging from 0.9 to 9.8 percent. Patients with ATC tend to be older, with a mean age at diagnosis of 65 years. Less than 10 percent of patients diagnosed are younger than 50 years. Additionally, 60 to 70 percent of tumors occur in women.¹

Causes of anaplastic thyroid cancer

The exact cause of Anaplastic Thyroid Cancer (ATC) is unknown, but certain risk factors have been identified. These include exposure to radiation, a family history of thyroid cancer, and certain genetic mutations. Exposure to radiation is the most significant risk factor for ATC, which can occur from environmental exposure, such as nuclear fallout, or medical treatment, such as radiation therapy for other types of cancer.

Signs and symptoms of anaplastic thyroid cancer

Nearly all patients with ATC present with a thyroid mass, but regional or distant spread is apparent at the time of diagnosis in 90% of cases. (Reference 2.)  The signs and symptoms of ATC can vary depending on the size and location of the tumor. Common symptoms include a lump or swelling in the neck, difficulty swallowing or breathing, hoarseness, pain in the neck or throat, fatigue, and unexplained weight loss.

Clinical manifestations:

The primary symptom of ATC is a rapidly enlarging neck mass, occurring in approximately 85% of patients. The enlarging thyroid tumor may cause neck pain and tenderness, compression, or invasion of the upper aerodigestive tract, resulting in dyspnea, dysphagia, hoarseness, and cough. Other symptoms can include chest pain, bone pain, headache, confusion, or abdominal pain from metastases. Constitutional symptoms can occur, including anorexia, weight loss, fatigue, and fever of unknown origin. Rarely, rapid growth of the tumor within the thyroid causes thyroiditis, with symptoms of hyperthyroidism and more severe neck pain and tenderness.

If you are suspected of having anaplastic thyroid cancer (ATC), your doctor will conduct a physical exam and several tests to make a diagnosis. These tests may include blood tests, imaging studies such as CT, MRI, or PET scans, and a biopsy of the tumor. A biopsy is the most definitive way to diagnose ATC, as it involves removing a small piece of tissue from the tumor and examining it under a microscope.

During the physical exam, your doctor will look for signs of thyroid enlargement, typically hard and nodular, with a dominant nodule. Some nodules may be softer and fluctuant, indicating focal tumor necrosis. The goiter may be fixed to the surrounding structures and does not move with swallowing. ATC can also cause other symptoms, such as stridor, tracheal deviation, vocal cord paralysis, venous dilatation, and superior vena cava syndrome. The skin overlying the tumor may be erythematous or even ulcerated, and there may be metastases in the skin of the chest and abdomen.

Lab tests are usually normal, except for a few patients who may have high levels of thyroglobulin. Serum thyroid hormone and thyroid-stimulating hormone (TSH) concentrations are usually normal, except for those few patients with hyperthyroidism. Rare patients have leukocytosis, an increase in the number of white cells in the blood, due to tumor secretion of lymphokines.

Ultrasound findings are not specific for ATC, but detection of extrathyroidal invasion can provide support for the diagnosis of cancer.

The diagnosis of ATC is usually made by examining cells taken from a fine-needle aspiration (FNA) biopsy or tissue taken from a large-needle or surgical biopsy. The biopsy material is examined under a microscope and analyzed with immunohistochemistry to determine the presence of anaplastic cancer. Anaplastic thyroid cancer cells typically have morphological patterns of spindle cell, pleomorphic giant cell, and/or squamoid, and may have a mix of these patterns. The tumors may also have numerous mitotic figures and atypical mitoses and typically have extensive necrosis. ATC cells are less likely to stain positive for certain markers, including thyroid transcription factor 1 (TTF1) or PAX-8, and do not typically stain positive for thyroglobulin in the anaplastic component of the tumor.

Differential Diagnosis

Theree are other types of cancer that can look similar to anaplastic thyroid cancer under the microscope, but have different treatments and prognoses. Some of these other types of cancer include poorly differentiated thyroid cancer, medullary thyroid cancer, lymphoma, melanoma, and sarcoma. It can be difficult to distinguish between anaplastic and poorly differentiated thyroid cancer in some cases, so careful examination of the tumor's appearance and immunohistochemical studies are required.

The differential diagnosis of a neck mass (not necessarily related to thyroid cancer) is also discussed, as there are many possible causes for a neck mass, such as benign thyroid nodules and cysts, differentiated thyroid cancer, primary lymphoma of the thyroid, vascular anomalies, lymph node enlargement, and other neoplastic or inflammatory disorders.

The second part of the text discusses the evaluation and management of anaplastic thyroid cancer. When a patient is diagnosed with anaplastic thyroid cancer based on cytopathology findings (the study of cells under a microscope), further evaluation is necessary. This includes assessing the airway and vocal cords, laboratory evaluation (including thyroid function tests, blood tests, and serum thyroglobulin levels), and imaging studies (such as ultrasound of the neck, PET/CT scans, and brain and skeletal radiographs). Molecular testing is also important, specifically testing for BRAF V600E mutations, as this can help determine treatment options.

Treatment for anaplastic thyroid cancer often involves surgery, radiation therapy, and chemotherapy. However, the prognosis for anaplastic thyroid cancer is typically poor, as it is an aggressive and rapidly growing cancer. Therefore, palliative care is an important part of treatment, which focuses on managing symptoms and improving the patient's quality of life.

Overall, anaplastic thyroid cancer is a rare but very serious type of cancer. Early detection and treatment are important for improving outcomes, but unfortunately, the prognosis is often poor even with aggressive treatment.

Management and treatment for anaplastic thyroid cancer
Staging

Anaplastic thyroid cancer (ATC) is classified using the TNM (tumor, node, metastasis) system, which was updated in 2017. In this system, all anaplastic cancers are considered stage IV cancers. Intrathyroidal anaplastic cancers are designated IVA, whereas anaplastic cancers with gross extrathyroidal extension or cervical lymph node metastases are IVB and with distant metastases IVC.

Treatment Approach: The choice of treatment for ATC depends on the stage of the cancer, the location of the tumor, and the overall health of the patient. The following approach is largely consistent with guidelines from the American Thyroid Association and the National Comprehensive Cancer Network:

BRAF V600E Mutation Identified: For patients with stage IVA ATC who have resectable tumors (there is no technical barrier to surgical excision) and the BRAF V600E mutation, the recommended treatment is complete resection followed by combined chemotherapy and radiation.

Extent of Surgery: For most patients with an intrathyroidal anaplastic cancer, total thyroidectomy is suggested rather than lobectomy. This is because differentiated thyroid cancer and anaplastic thyroid cancer often coexist, and total thyroidectomy offers a greater chance of complete resection, which facilitates subsequent treatment with radioiodine of the accompanying differentiated thyroid cancer.

Chemoradiation: At Memorial Sloan Kettering Cancer Center and other centers, intensity-modulated radiation therapy (IMRT) is given. A randomized phase II study for anaplastic thyroid cancer is also using IMRT with a total dose of 66 Gy in 33 daily fractions. Doxorubicin or paclitaxel is used throughout the radiation course, but there are other reasonable regimens described in the literature.

In conclusion, understanding the TNM system and the recommended treatment approach for ATC can help patients make informed decisions about their care. If you have been diagnosed with ATC, talk to your doctor about your options and what course of treatment may be best for you.

Treatment options

Anaplastic thyroid cancer (ATC) is a rare and aggressive form of thyroid cancer that is challenging to treat. The optimal management of ATC is not clear, as randomized controlled trials are not available to definitively prove the benefit of combined modality therapy. However, some treatments have shown possible survival advantages. Here are the management strategies for the four stages of ATC:

Stage IVA - For patients with resectable disease, surgery is followed by chemoradiation therapy with weekly doxorubicin (10 mg/m2) concurrently with radiation therapy. Some patients have prolonged survival (>2 years) with surgery combined with postoperative adjuvant chemoradiation. For patients with unresectable disease, options include chemoradiation, clinical trials, or best supportive care.

Stage IVB - If a BRAF V600E mutation is present, neoadjuvant dabrafenib (150 mg twice daily) plus trametinib (2 mg daily) should be initiated to improve the chance of complete tumor resection. In patients with resectable disease, surgery is followed with chemoradiation as described for stage IVA. For patients with unresectable disease, dabrafenib plus trametinib can be continued if associated with disease stability or improvement. If the response is not favorable, alternative management options include chemoradiation, clinical trials, or best supportive care.

Stage IVC - There is no curative therapy for metastatic ATC, and the disease is uniformly fatal. For patients who present with metastatic disease who desire active therapy, enrollment in clinical trials of BRAF-targeted therapy (based on molecular testing) is strongly encouraged . If clinical trials are not available, dabrafenib plus trametinib is suggested. Surgical resection for residual tumor can be considered if the disease is responsive. If resectable, surgery should then be followed by re-initiation of dabrafenib plus trametinib if the distant metastases are stable or improved during prior therapy. If not resectable, dabrafenib plus trametinib can be continued if the response to therapy is favorable. If not, options include chemoradiation, clinical trials, or best supportive care.

FAQs

How is anaplastic thyroid cancer diagnosed?

How can I prevent anaplastic thyroid cancer?

Unfortunately, there is no known way to prevent ATC. However, avoiding exposure to radiation and maintaining a healthy lifestyle may help reduce your risk of developing thyroid cancer.

Who are at risks of anaplastic thyroid cancer?

People who have a history of exposure to radiation, a family history of thyroid cancer, a personal history of goiter or other thyroid conditions, or certain genetic mutations may be at higher risk for developing ATC.

How common is anaplastic thyroid cancer?

ATC is a rare type of cancer, accounting for less than 2% of all thyroid cancers. However, it is one of the most aggressive and difficult to treat forms of thyroid cancer.

When should I see a doctor?

If you experience any of the symptoms associated with ATC, such as a lump or swelling in the neck, difficulty swallowing or breathing, hoarseness or voice changes, pain in the neck or throat, fatigue, or unexplained weight loss, you should see a doctor as soon as possible. While these symptoms can be caused by a variety of conditions, they may also be signs of thyroid cancer or another serious medical condition.

Summary

• Anaplastic thyroid cancer is a rare and aggressive form of thyroid cancer that is difficult to treat
• It typically arises from follicular or papillary thyroid cancer but can also develop on its own
• Exposure to radiation, a family history of thyroid cancer, and certain genetic mutations are risk factors for ATC
• Symptoms of ATC include a lump or swelling in the neck, difficulty swallowing or breathing, hoarseness or voice changes, pain in the neck or throat, fatigue, and unexplained weight loss
• A biopsy of the tumor is the most definitive way to make a diagnosis of ATC
• Treatment for ATC depends on the stage of the cancer, the location of the tumor, and the overall health of the patient
• Surgery, radiation therapy, chemotherapy, and targeted therapy are all options for treating ATC.
• The prognosis for ATC is poor, with a five-year survival rate of less than 5%