Are you sure the patient has undifferentiated thyroid cancer?


Undifferentiated thyroid carcinoma (UTC) refers to a cancer arising from the follicular thyroid epithelium but lacking the typical differentiation features of the thyroid gland: iodine uptake, thyroglobulin secretion, response to thyroid stimulating hormone (TSH) stimulation. These are the most aggressive types of thyroid malignancy. The female-to-male ratio of UTC is of approximately 2:1. The peak incidence is in the sixth-seventh decades (mean age at diagnosis 55-65 years). In most cases, UTC develops from a pre-existing well differentiated thyroid tumor which has undergone additional mutational events (primarily p53 mutations). Regardless of treatment, mean survival is invariably very poor at approximately 6-8 months from diagnosis.


Patients may complain of a neck mass which appeared a few months or weeks prior to presentation. The mass is rapidly growing and usually accompanied by hoarseness, dysphagia, and dyspnea secondary to compression and/or infiltration of the laryngeal nerves, the esophagus, and the trachea, respectively. Tracheal invasion may require immediate tracheostomy. Local pain may also be present, both with and without palpation. Other symptoms may include weight loss, weakness, and fatigue.


On physical examination, the mass is usually easily visible and palpable. Its consistency is very firm and the mass is fixed. The underlying skin may be inflamed and painful. A venous reticulum may be appreciated on inspection. Multiple enlarged lymph nodes may be palpable on the ipsilateral neck. More rarely, the skin may be ulcerated with protrusion of a necrotic and bleeding tumor.

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Additional findings

Weight loss is common due to dysphagia or the malignancy itself. Distant metastases to the lung, bone, skin, and brain are common at presentation or develop soon after the diagnosis. Lung metastases may be seen on chest X-ray, with computerized tomography (CT) scanning usually demonstrating additional small metastases. These lesions can be associated with respiratory failure and hemoptysis. Bone metastases may be visible on scintigraphy. Brain metastases are less frequent, and as they may be asymptomatic, brain magnetic resonance imaging (MRI) should always be performed. Metastases to the liver and adrenals may occur late in the course of the disease. Death is mainly due to invasion of the respiratory airways.

Key laboratory and imaging tests

Serum thyroid hormone levels are usually in the normal range, but subclinical hypothyroidism may be found when significant portions of the thyroid gland have been affected by the tumor. Serum thyroglobulin levels are usually normal or slightly elevated secondary to thyroid destruction. Sedimentation Rate may be elevated as well as C Reactive Protein. Leukocytosis may be present.

Imaging should include careful neck ultrasonography to assess the presence of regional lymph node metastases. CT scanning of the lungs, mediastinum, and abdomen; brain MRI; and bone scintigraphy are recommended for tumor staging.

Management and treatment of the disease

Currently, there are no effective treatments for anaplastic thyroid cancer. The prognosis is very poor without exception. Whenever possible, radical surgery is the primary treatment. Unfortunately, this is possible in only a few cases. The majority of patients present with massive local invasion which precludes surgery, leaving only tumor debulking or biopsy to confirm the diagnosis as the only remaining options.

Even when radical surgery is performed, local recurrence is very frequent and rapid. For this reason, external beam radiotherapy is indicated in all patients immediately after surgery. Radiotherapy is best performed with a hyperfractionated approach, consisting of 160 rads twice a day, three times a week for 40 days, delivering a total dose of about 6000 rads (60 Gy). Many centers combine radiation therapy with chemotherapy regimens (usually cisplatin or doxorubicin). Such an aggressive treatment regimen should be proposed for patients with high chance of long-term local control. In those with poor general prognosis, aggressive local disease, and distant metastases, palliative supportive measures should be the primary treatment.

In patients with distant metastases, systemic chemotherapy is the only option, although the results have not been promising. The most common single cytotoxic agent used is doxorubicin alone or in combination with cisplatin. Adding bleomycin or other agents does not appear to enhance efficacy. Paclitaxel has been used in limited clinical trials with some improvement in response rates, but not in survival. Novel treatment strategies, including targeted therapy with tyrosine kinase inhibitors, suppressor gene therapy, or drugs able to induce cell cycle arrest are undergoing experimental research trials.

What’s the Evidence?/References

Ain, KB. “Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches”. Thyroid. vol. 8. 1998. pp. 715-26. (Comprehensive review of the natural history and therapeutic strategies for anaplastic thyroid cancer.)

Brierley, JD. “Update on external beam radiation therapy in thyroid cancer”. J Clin Endocrinol Metab. vol. 96. 2011. pp. 2289-95. (This paper describes the current indication of external beam radiotherapy for anaplastic thyroid cancer.)

Haigh, PI, Ituarte, PH, Wu, HS, Treseler, PA, Posner, MD. “Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival”. Cancer. vol. 91. 2001. pp. 2335-42. (In this study evidences are provided that surgery plus adjuvant chemotherapy and radiotherapy can improve survival.)

Sherman, EJ, Lim, SH, Ho, AL, Ghossein, RA, Fury, MG. “Concurrent doxorubicin and radiotherapy for anaplastic thyroid cancer: a critical re-evaluation including uniform pathologic review”. Radiother Oncol. vol. 101. 2011. pp. 425-30. (Effect of combined chemotherapy and radiotherapy is more effective than the two therapies alone.)

Wunderlich, A, Fisher, M, Schlosshauer, T, Ramaswamy, A, Greene, BH. “Evaluation of Aurota kinase inhibitor as a new therapeutic strategy in anaplastic and poorly differentiated follicular thyroid cancer”. Cancer Sci. vol. 102. 2011. pp. 762-8. (This is the first clinical trial with tyrosine kinase inhibitors attempted to treat anaplastic thyroid cancer.)

Smallridge, RC, Marlow, LA, Copland, JA. “Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies”. Endoc Relat Cancer. vol. 16. 2009. pp. 17-44. (Review on the use of tyrosine kinase inhibitor as a new strategy for the treatment of anaplastic thyroid cancer.)