Anaplastic thyroid cancer (ATC) is an undifferentiated tumour of the follicular epithelium. It is rare but extremely aggressive, with a median survival of 5– 7 months after diagnosis and a 20% 1- year survival rate. It tends to develop in older individuals (mean age 65 years) and can be associated with DTC. Genetically, anaplastic cancer presents with activating BRAF and RAS mutations (similar to DTC), but also new mutations involving p53 tumour suppressor protein, TERT, or PIK3CA. It is thus believed that anaplastic cancer develops from more differentiated tumours after a dedifferentiation event, which is probably the acquisition of a new mutation.
ATC generally presents as a rapidly growing, fixed cervical tumour mass. It can extend into the perithyroidal fat to the strap muscles, trachea, oesophagus, blood vessels, and laryngeal recur rent nerves which leads to pain, dysphonia, dysphagia, dyspnoea, and cough. Distant metastases are present in up to 50% of patients at diagnosis (often in the lungs, bone, brain, skin, adrenal glands) and can manifest as systemic symptoms: fatigue, anorexia, weight loss or focal signs of compression: bone pain, neurological symptoms.
The initial evaluation should include a full blood count, bio chemistry, thyroid function tests and neck ultrasound. Marked leukocytosis is sometimes present due to tumour secretion of lymphokines. Some patients present with hypocalcaemia due to invasion of the parathyroid glands or humoral hypercalcaemia of malignancy. Thyroid function is usually normal, but hypothyroidism can occur in extensive disease destroying the normal parenchyma. Ultrasound reveals a hypoechoic, infiltrative mass, often with areas of extensive necrosis and lymph node metastasis. Diagnosis re quires FNAB or core needle biopsy and immunohistochemistry is needed to distinguish ATC from poorly differentiated and medullary thyroid carcinomas, thyroid lymphoma, melanoma, and sarcoma.
Cross- sectional CT or MRI studies should be performed for staging purposes and to define local extension and the potential for surgical resection. 18FDG- PET/ CT is helpful to identify distant metastases. According to the TNM staging system, all ATCs are considered stage IV: intrathyroidal tumours are stage IVA, gross extrathyroidal extension means stage IVB and distant metastases— IVC.
Due to their aggressive nature, prompt management of ATC is essential. Surgery should be performed for all intrathyroidal tumours as complete resection increases survival. In invasive tumours surgical resection should be followed by radiotherapy and chemo therapy. Combination therapy decreases the risk or recurrence but doesn’t influence survival. In patients with distant metastases no therapy was proven effective and median survival is 4 months. External beam radiation therapy (EBRT) can provide pain relief in patients with bone metastases. Cytotoxic chemotherapy with doxorubicin, doxorubicin + cisplatin, or paclitaxel usually provides only short- term responses. If available, patients should be enrolled in clinical trials with new therapies based on the molecular profile of the tumour. Radioiodine therapy and TSH suppression have no role in ATC, because the undifferentiated cells are not capable of 131I uptake, but can be useful in patients with associated DTC. Palliative treatment should focus on securing the airway and maintaining access for nutritional support (tracheostomy and gastrostomy), as death usually occurs due to aerodigestive obstruction. Adequate management of pain should be provided as well as emotional and spiritual support.
