Anaplastic Thyroid Cancer: A Rare but Urgent Diagnosis – What Referring Providers Need to Know

Anaplastic thyroid cancer (ATC) is one of the rarest yet most aggressive forms of thyroid cancer, accounting for only 1–2% of all thyroid malignancies. Despite its low incidence, ATC contributes to a disproportionate number of thyroid cancer-related deaths due to its rapid progression, high metastatic potential and resistance to conventional therapies. Rapid, comprehensive evaluation by an expert multidisciplinary team can impact patient outcomes.  

Recognizing, diagnosing and directing patients with suspected ATC to multidisciplinary teams for timely and effective management is imperative for the best patient outcomes.

Recognizing the Signs and Symptoms

ATC typically presents with rapidly progressing symptoms due to local invasion and distant metastasis. Providers should watch for:

• Rapidly enlarging neck mass
• Hoarseness or vocal cord paralysis
• Dysphagia or dyspnea
• Neck pain or pressure
• Cervical lymphadenopathy
• History of goiter or differentiated thyroid cancer with sudden changes

Because of its clinical overlap with benign or indolent thyroid disease, ATC may be under-recognized in early stages—prompt evaluation is essential.

Diagnosis and Challenges in Management

Diagnosis involves:

• Imaging (ultrasound, CT, MRI for structural invasion)
• Biopsy (fine-needle aspiration, though core biopsy is preferred and often required to facilitate comprehensive molecular testing)
• Histology: ATC is characterized by undifferentiated giant cells, spindle cells, or squamoid morphology, often mixed with areas of poorly differentiated carcinoma or residual differentiated thyroid cancer. The pathologic diagnosis can be challenging and may require expert input.
• Molecular profiling: Mutations in TP53, TERT promoter, BRAF V600E, PIK3CA, and NRAS are common. Testing for these genetic alterations is critical for therapeutic targeting and prognosis stratification. Rapid testing for BRAF V600E is crucial to facilitate therapy with BRAF and MEK inhibitors for appropriate candidates.

Challenges include:

• High rate of unresectable disease at diagnosis
• Poor response to traditional chemotherapy or radiation when used alone
• Median survival of just three–five months in advanced cases

Why Multidisciplinary Cancer Care Matters

Due to the aggressive behavior of ATC, care should be initiated at specialized centers rapidly. At Moffitt Cancer Center, the experts in the Head and Neck and Endocrine Oncology Program offer:

• Head and neck surgery for curative resection or airway stabilization
• Endocrine oncology and medical oncology care for chemotherapy, targeted therapies and immunotherapy, including consideration for neoadjuvant approaches
• Molecular diagnostics for mutation-driven treatment selection
• Radiation oncology using advanced IMRT techniques
• Access to clinical trials and novel Immunotherapeutics

Our multidisciplinary team of experts, including multidisciplinary appointments, allows patients to obtain both a surgical and oncology perspective in one visit. Close collaboration across specialties allows for rapid development of personalized treatment plans. Also, referring patients to an NCI-designated Comprehensive Cancer Center, such as Moffitt, isn’t just a choice. It is an opportunity for the highest standard of cancer care, backed by measurable improvements in survival and quality of life.

"The era of precision-targeted therapies and immunotherapy has provided a promising landscape of treatment for a rare aggressive disease, resulting in better outcomes in terms of overall survival, potential improved surgical outcomes with neoadjuvant approaches, and better quality of life given the tolerability of newer therapies," says Dr. Sarimar Agosto Salgado. 

"Caring for patients with anaplastic thyroid cancer and seeing firsthand, how in the best scenarios, newer therapies can allow patients to live longer provides hope of a cure in the future and certainly highlights the importance of patient-centered care by an expert multidisciplinary team working together to delineate the best course of action for each affected individual."

Latest Treatment Advancements

Fortunately, the implementation of molecular marker testing and targeted therapies has changed how ATC is treated for the better. Groundbreaking studies and FDA approvals have revolutionized ATC care:

Targeted Therapy and Immunotherapy

• The combination of BRAF and MEK inhibitors plus) immune checkpoint inhibitors have extended survival to over 43 months in some BRAF V600E+ cases. Immunotherapy may augment responses based on recent preliminary reports, and the triple therapy with dabrafenib, trametinib, and pembrolizumab in BRAF V600E-driven tumors has improved survival and facilitation of surgery in select candidates.

Neoadjuvant Systemic Therapy

• Preoperative use of combination therapy has enabled successful surgery in cases with certain molecular markers previously deemed inoperable, with two-year survival rates reaching 69%.

Genetic Profiling–Driven Treatments

• Patients with RET fusions or NTRK fusions may benefit from selpercatinib or larotrectinib, respectively.
• Molecular stratification enables the selection of targeted agents for otherwise ineligible patients, particularly those with advanced or metastatic disease.

Advanced Radiation Therapy

• IMRT and hypofractionated approaches help reduce toxicity while improving local control—a critical advantage in tumors involving the airway or mediastinum.

Role of the Referring Provider

Referring physicians are key to early detection and timely referral. Those most likely to encounter early symptoms include:

• Endocrinologists
• Otolaryngologists (ENTs)
• Primary care physicians
• Medical and radiation oncologists

When imaging or clinical suspicion suggests aggressive thyroid malignancy, providers should expedite referral to a high-volume cancer center such as Moffitt with expertise in thyroid and head and neck oncology. Delays can lead to airway compromise, unresectable disease and a worse prognosis. Newly diagnosed patients can be seen by our experts within one week. 

To refer a patient for anaplastic thyroid cancer treatment, please complete the online referral form or contact our physician liaisons at Physician.Relations@Moffitt.org.

Sources:
journals.sagepub.com/doi/full/10.1177/20420188211054692
ASCO 2025