Thyroid: Anaplastic (undifferentiated) carcinoma

Epidemiology	Anaplastic (undifferentiated) carcinoma of the thyroid gland is uncommon, accounting for less than 5% of all cases of thyroid carcinoma. The average age at diagnosis was 66.5 years, with a female to male ratio of 3.1:1 in one study of 70 cases.
Clinics	Most patients are euthyroid with a history of a rapidly enlarging neck mass. Sometimes, the tumor presents as a new-onset thyroid enlargement in a patient with longstanding thyroid nodule(s) or as the recurrence of a well-differentiated thyroid carcinoma. Tumor infiltration of surrounding structures results in secondary symptoms (dyspnea, dysphonia, dysphagia).
Pathology	Tumors are poorly defined, fleshy masses with areas of necrosis and hemorrhage. Microscopically they are composed of anaplastic cells with marked cytologic atypia and high mitotic activity. Tumor necrosis and vascular invasion are common. About one-third of cases of anaplastic thyroid carcinoma (ATC) have coexisting areas of well-differentiated thyroid carcinoma, supporting the hypothesis that ATC arises from well-differentiated thyroid carcinoma. Histologic patterns include spindle, giant and squamoid cell types. Other patterns (e.g. angiomatoid, carcinosarcoma, lymphoepithelioma-like, adenosquamous) have been described. Undifferentiated (anaplastic) carcinoma of the thyroid must be differentiated from other high grade tumors with similar microscopic appearance originating from adjacent structures in the neck (e.g. larynx). Sometimes this distinction is only possible on clinical/anatomical grounds. Immunohistochemically, undifferentiated thyroid carcinoma is generally negative for thyroglobulin and calcitonin. Pankeratin and epithelial membrane antigen (EMA) are positive in about one-half and one-third of cases respectively. Vimentin is positive in about 90%, and epithelial membrane antigen is positive in about 30% of cases. Thyroid transcription factor-1 (TTF-1) staining is present in 0-50% of cases. Although immunostaining is negative for muscle-specific actin, Factor VIII-related antigen, and desmin, these markers can differentiate ATC from some soft tissue sarcomas with which they can be confused.
	Anaplastic (undifferentiated) thyroid carcinoma is a highly malignant tumor composed by undifferentiated malignant cells. The inset in the left lower corner shows a magnified view of a cell in metaphase of mitosis.
Treatment	No effective treatment modalities are currently available. A few patients with resectable disease have been reported to have long-term survival with aggressive multimodal therapy that included surgery, radiation, and chemotherapy. Current clinical practice emphasizes the use of multimodal therapy to achieve local disease control and stabilization of airway patency. Radiotherapy may be hyperfractionated and in combination with chemotherapy. Chemotherapy is usually doxorubicin-based or taxane-based combinations. Preclinical studies using human ATC cell lines show promise that new effective combinations including novel drugs will be found in the future.
Prognosis	Anaplastic (undifferentiated) carcinomas are highly aggressive neoplasms that are usually widely invasive at presentation. Regional and distant metastases are common, and about 75% of patients have distant metastasis in the course of their disease. Most patients die within 1 year of the diagnosis with a median survival of 3 to 6 months. The 5-year survival rate is around 5%, and the surviving cases are typically small tumors confined to the thyroid amenable to local resection.

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