Anaplastic Thyroid Carcinoma

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Anaplastic carcinoma of the thyroid (ATC) is the most aggressive thyroid gland malignancy. Although ATC accounts for less than 2% of all thyroid cancers, it causes up to 40% of deaths from thyroid cancer. The aggressive nature of ATC makes treatment studies difficult to perform. The overall 5-year survival rate is reportedly less than 10%, and most patients do not live longer than a few months after diagnosis.

See the figure below.

Patients with ATC typically present with a rapidly growing neck mass. Metastases, particularly in the lung, are likely to be present at diagnosis more than 50% of the time. Treatment is mostly palliative. Surgical resection with adjuvant radiation therapy and chemotherapy may prolong survival somewhat and improve quality of life. 

For patient education resources, see the Endocrine System Center, as well as Thyroid Problems.

Anaplastic carcinoma of the thyroid (ATC) generally occurs in people in iodine-deficient areas and in a setting of previous thyroid pathology (eg, preexisting goiter, follicular thyroid cancer, papillary thyroid cancer). Local invasion of adjacent structures (eg, trachea, esophagus) commonly occurs.

ATC is believed to occur from a terminal dedifferentiation of previously undetected long-standing thyroid carcinoma (eg, papillary, follicular).

ATC has a genetic association with oncogenes C-myc, H-ras, and Nm23. Mutations in genes that code for BRAF, RAS, catenin (cadherin-associated protein), beta 1, PIK3CA, TP53, AXIN1, PTEN, and APC have been found in ATC, and chromosomal abnormalities are common. ^{[1, 2]}

Jonker and collegues performed functional genomic RNA profiling on 25 anaplastic thyroid carcinoma and 80 normal thyroid samples and identified 301 significantly upregulated genes, of which the following were seen as potential therapeutic targets ^[3] :

Anaplastic carcinoma of the thyroid (ATC) constitutes less than 2% of all thyroid malignancies in the United States, whcih equates to slightly more than 1000 new cases annually. ^[4] Fortunately, the incidence appears to be declining. Worldwide frequency likely approximates that in the United States.

The female-to-male ratio is approximately 3:1. Peak incidence occurs during the sixth to seventh decades of life. The age range of affected patients reportedly is 15-90 years.

ATC has a rapidly progressive course and early dissemination. The most common sites of distant spread include, in descending order, the lung, bone, and brain. Metastases, particularly in the lung, are likely to be present at diagnosis in more than 50% of cases. The overall 5-year survival rate is reportedly less than 10%, and most patients do not live longer than a few months after diagnosis. ^[5]

One study has shown that patients younger than 60 years who have ATC confined to the thyroid have a better prognosis than patients who are older and have distant metastases. ^[6]  A retrospective study from Korea found that age less than 60 years, tumor size less than 7 cm, and lesser extent of disease were independent predictors of lower disease-specific mortality. ^[7]

While some studies have suggested that postoperative radiotherapy may be of benefit in terms of survival, definitive prospective trials are lacking.

Akaishi et al conducted a review of 100 patients with ATC in a single hospital (Ito Hospital) from 1993-2009. ^[8]  The 1-year survival rates were as follows:

Multivariate analysis demonstrated worse prognosis with age older than 70 years, white blood cell count of 10,000/μL or more, extrathyroidal invasion, and distant metastases at the time of diagnosis. Survival was significantly better if the patient received complete resection, external radiation at doses of 40 Gy or more, or both. ^[8]

Orita et al developed a prognostic index that can predict prognosis and assist in the early treatment of ATC. ^[9]

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Cabanillas ME, Zafereo M, Gunn GB, Ferrarotto R. Anaplastic Thyroid Carcinoma: Treatment in the Age of Molecular Targeted Therapy. J Oncol Pract. 2016 Jun. 12 (6):511-8. [Medline]. [Full Text].

Jonker PK, van Dam GM, Oosting SF, Kruijff S, Fehrmann RS. Identification of novel therapeutic targets in anaplastic thyroid carcinoma using functional genomic mRNA-profiling: Paving the way for new avenues?. Surgery. 2017 Jan. 161 (1):202-211. [Medline].

Cancer Facts & Figures 2018. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf. Accessed: February 20, 2108.

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Kim TY, Kim KW, Jung TS, Kim JM, Kim SW, Chung KW, et al. Prognostic factors for Korean patients with anaplastic thyroid carcinoma. Head Neck. 2007 Aug. 29(8):765-72. [Medline].

Akaishi J, Sugino K, Kitagawa W, et al. Prognostic factors and treatment outcomes of 100 cases of anaplastic thyroid carcinoma. Thyroid. 2011 Nov. 21(11):1183-9. [Medline].

Orita Y, Sugitani I, Amemiya T, Fujimoto Y. Prospective application of our novel prognostic index in the treatment of anaplastic thyroid carcinoma. Surgery. 2011 Dec. 150(6):1212-9. [Medline].

Wong DD, Spagnolo DV, Bisceglia M, et al. Oncocytic adrenocortical neoplasms–a clinicopathologic study of 13 new cases emphasizing the importance of their recognition. Hum Pathol. 2011 Apr. 42(4):489-99. [Medline].

Wagle N, Grabiner BC, Van Allen EM, Amin-Mansour A, Taylor-Weiner A, Rosenberg M, et al. Response and acquired resistance to everolimus in anaplastic thyroid cancer. N Engl J Med. 2014 Oct 9. 371(15):1426-33. [Medline].

Godbert Y, Henriques de Figueiredo B, Bonichon F, Chibon F, Hostein I, Pérot G, et al. Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase-Rearranged Anaplastic Thyroid Carcinoma. J Clin Oncol. 2015 Jul 10. 33 (20):e84-7. [Medline].

Hahn SY, Shin JH. Description and Comparison of the Sonographic Characteristics of Poorly Differentiated Thyroid Carcinoma and Anaplastic Thyroid Carcinoma. J Ultrasound Med. 2016 Sep. 35 (9):1873-9. [Medline]. [Full Text].

Bogsrud TV, Karantanis D, Nathan MA, Mullan BP, Wiseman GA, Kasperbauer JL, et al. 18F-FDG PET in the management of patients with anaplastic thyroid carcinoma. Thyroid. 2008 Jul. 18(7):713-9. [Medline].

Bhatia A, Rao A, Ang KK, Garden AS, Morrison WH, Rosenthal DI, et al. Anaplastic thyroid cancer: Clinical outcomes with conformal radiotherapy. Head Neck. 2009 Nov 2. [Medline].

Noguchi H, Yamashita H, Murakami T, Hirai K, Noguchi Y, Maruta J, et al. Successful treatment of anaplastic thyroid carcinoma with a combination of oral valproic acid, chemotherapy, radiation and surgery. Endocr J. 2009 Apr. 56(2):245-9. [Medline].

Swaak-Kragten AT, de Wilt JH, Schmitz PI, Bontenbal M, Levendag PC. Multimodality treatment for anaplastic thyroid carcinoma–treatment outcome in 75 patients. Radiother Oncol. 2009 Jul. 92(1):100-4. [Medline].

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Mulcahy N. FDA OKs Targeted Therapy Combo for Anaplastic Thyroid Cancer. Medscape Medical News. Available at https://www.medscape.com/viewarticle/896190. May 04, 2018; Accessed: May 08, 2018.

Wiseman SM, Masoudi H, Niblock P, Turbin D, Rajput A, Hay J, et al. Anaplastic thyroid carcinoma: expression profile of targets for therapy offers new insights for disease treatment. Ann Surg Oncol. 2007 Feb. 14(2):719-29. [Medline].

Brignardello E, Palestini N, Felicetti F, Castiglione A, Piovesan A, Gallo M, et al. Early Surgery and Survival of Patients with Anaplastic Thyroid Carcinoma: Analysis of a Case Series Referred to a Single Institution Between 1999 and 2012. Thyroid. 2014 Sep 5. [Medline].

Chiacchio S, Lorenzoni A, Boni G, Rubello D, Elisei R, Mariani G. Anaplastic thyroid cancer: prevalence, diagnosis and treatment. Minerva Endocrinol. 2008 Dec. 33(4):341-57. [Medline].

[Guideline] Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan. 26 (1):1-133. [Medline]. [Full Text].

[Guideline] Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, et al. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2012 Nov. 22 (11):1104-39. [Medline]. [Full Text].

[Guideline] NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma. Version 2.2017. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. May 17, 2017; Accessed: February 9, 2018.

[Guideline] Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. J Endocrinol Invest. 2010. 33 (5 Suppl):51-6. [Medline]. [Full Text].

Anastasios K Konstantakos, MD Clinical Associate Surgeon, Department of Cardiovascular Surgery, Billings Clinic

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Neetu Radhakrishnan, MD Associate Professor (Adjunct) of Medicine, Division of Hematology/Oncology, University of Cincinnati Medical Center; Hematology/Oncology Medical Director, West Chester Outpatient Clinics

Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Lodovico Balducci, MD Professor, Oncology Fellowship Director, Department of Internal Medicine, Division of Adult Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida Morsani College of Medicine

Lodovico Balducci, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American College of Physicians, American Geriatrics Society, American Society of Hematology, New York Academy of Sciences, American Society of Clinical Oncology, Southern Society for Clinical Investigation, International Society for Experimental Hematology, American Federation for Clinical Research, American Society of Breast Disease

Disclosure: Nothing to disclose.

Debra J Graham, MD, is gratefully acknowledged for the contributions made to this topic.

Anaplastic Thyroid Carcinoma

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