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  • Review Article
  • Published:

Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies

Key Points

  • Anaplastic thyroid carcinoma (ATC) is a rare but almost invariably lethal disease

  • The histological diagnosis of ATC requires an expert pathologist who can distinguish the anaplastic features of ATC from those of poorly differentiated thyroid cancer

  • The molecular and genetic alterations that define ATC have been characterized by next-generation sequencing analysis and have confirmed a major role for TP53 alterations

  • Conventional therapies are unable to prolong the survival of patients with ATC; however, in certain cases, conventional treatments might improve symptoms and quality of life

  • New targeted therapies have been tested in the past 10 years in phase II clinical trials; however, no therapies have yet been officially approved for the treatment of ATC

  • Additional drugs are under evaluation for the treatment of ATC in phase I and phase II clinical trials, with promising results to date

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.

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Figure 1: Axial section of a neck CT scan from a patient with anaplastic thyroid carcinoma.
Figure 2: Haematoxylin and eosin staining of different histological patterns of anaplastic thyroid carcinoma.
Figure 3: Distribution of oncogenic alterations in anaplastic thyroid carcinoma.
Figure 4: Tracheal endoscopy in two patients with anaplastic thyroid carcinoma with tracheal compression or infiltration.
Figure 5: CT scan of the neck of a patient with anaplastic thyroid carcinoma who had a tracheostomy to avoid suffocation.

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E.M., A.B., E.S., L.A., S.M., G.M., S.S-F., A.R., L.T., F.B. and R.E. researched data for the article. E.M. made a substantial contribution to discussions of the content. E.M., C.R. and L.T. wrote the article. E.M., C.R., P.V. and R.E. reviewed and/or edited the article before submission.

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Molinaro, E., Romei, C., Biagini, A. et al. Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol 13, 644–660 (2017). https://doi.org/10.1038/nrendo.2017.76

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