Undifferentiated (Anaplastic) Thyroid Carcinoma

Abstract

Undifferentiated (anaplastic) thyroid carcinoma (UTC), previously also called “giant and spindle cell carcinoma,” is an extremely aggressive thyroid malignancy. In line with the latest 5th edition of the WHO classification of thyroid neoplasms, squamous cell carcinoma of the thyroid is now considered as a subtype of UTC. UTC accounts for less than 5% of thyroid cancers and carries the worst prognosis. Most patients succumb to their disease within 6 months to 1 year of the initial diagnosis. Patients with UTC show characteristic clinical features: these tumors are rarely seen in individuals below the age of 50, and patients often present with a hard, rapidly growing mass. Half of patients report significant neck compression that results in symptoms such as dyspnea, dysphagia, hoarseness, and/or pain. One-quarter to one-half of patients present with lymphadenopathy and/or distant metastases, most commonly to the lungs. Aspirates show variable cellularity but are usually moderately to markedly cellular. Neoplastic cells are arranged as isolated cells and/or in variably sized groups and are epithelioid (round to polygonal) and/or spindle-shaped, ranging in size from small to giant cells. “Plasmacytoid” and “rhabdoid” cell shapes are seen. Necrosis, extensive inflammation (predominantly neutrophils, “abscess-like”), and/or fibrous connective tissue may be present. Osteoclast-like giant cells (non-neoplastic) are conspicuous in some cases. Immunocytochemical stains often show focal immunostaining for pan-keratins and PAX8; TTF-1 and thyroglobulin are usually nonreactive. Molecular alterations include the early thyroid carcinogenesis mutations of RAS and BRAF and the late carcinogenesis mutations of TP53 and CTNNB1 (β-catenin).