Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies

Abstract

Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1-2% of all thyroid cancers. Although rare, ATC accounts for the majority of deaths from thyroid carcinoma. ATC often originates in a pre-existing thyroid cancer lesion, as suggested by the simultaneous presence of areas of differentiated or poorly differentiated thyroid carcinoma. ATC is characterized by the accumulation of several oncogenic alterations, and studies have shown that an increased number of oncogenic alterations equates to an increased level of dedifferentiation and aggressiveness. The clinical management of ATC requires a multidisciplinary approach; according to recent American Thyroid Association guidelines, surgery, radiotherapy and/or chemotherapy should be considered. In addition to conventional therapies, novel molecular targeted therapies are the most promising emerging treatment modalities. These drugs are often multiple receptor tyrosine kinase inhibitors, several of which have been tested in clinical trials with encouraging results so far. Accordingly, clinical trials are ongoing to evaluate the safety, efficacy and effectiveness of these new agents. This Review describes the updated clinical and pathological features of ATC and provides insight into the molecular biology of this disease. The most recent literature regarding conventional, newly available and future therapies for ATC is also discussed.

Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

“…21 Currently, there aren't any effective therapies for this disease. 22,23 Indeed, the median overall survival has not changed in the last decades. 24,25 It is well recognized that EMT represents a major mechanism of tumor progression and, in particular, in thyroid carcinogenesis.…”

“…While the prognosis of PTC is generally favorable, ATC represents one of the most aggressive human cancers and is characterized by a high proliferation rate and aneuploidy . Currently, there aren't any effective therapies for this disease . Indeed, the median overall survival has not changed in the last decades …”

Anaplastic thyroid carcinoma: review of treatment protocols

“…In immunohistochemistry, ATC is characterized by negative staining for typical thyroid markers e.g. thyroglobulin (Molinaro et al 2017). ATC is per se classified as stage IV disease by the American Joint Committee on Cancer (AJCC) and is further divided in stage IVA (T4a: intrathyroidal ATC and M0); stage IVB (T4b: extrathyroidal ATC and M0) and stage IVC disease (any T and M1) .…”

Comparison of sonographic characteristics of primary thyroid lymphoma and anaplastic thyroid carcinoma

“…Most ATC lesions are composed of undifferentiated tumor cells and well-differentiated thyroid carcinoma which may have a dense and compact cellular structure (39)(40)(41). Meanwhile, the microcalcifications are the other reason leading to acoustic attenuation behind the lesions of ATC.…”