History

Fact Explanation
Rapidly growing anterior neck mass. Anaplastic carcinoma grows very rapidly. It accounts for about 1.6% of all thyroid cancers. [1]
Hoarseness [6] This is one of the most common presentation. Hoarseness is due to the involvement of the recurrent laryngeal nerve.
Dysphagia [3] Compression of the esophagus produces dysphagia. This is the second most common symptom of presentation. [6]
Cough [9] Tracheal compression produces cough.
Dyspnea [9] Due to the pulmonary metastases.
Stridor [3,8] Due to tracheal compression.
Cervical pain [6] Invasion of cervical plexus produces neck pain.
Bone pain [7] Metastasis in the bone produce bone pain. Most patients with anaplastic carcinoma of the thyroid will have metastasis at the time of presentation. [4]
Neurologic deficits Due to cerebral metastasis and involvement of the vertebral column. [7]
Symptoms of increased intracranial pressure Anaplastic carcinoma metastasizes to the brain and increase the intra-cranial pressure. [4] Patients have early morning headache and nausea which is relieved by vomiting.
Palpable cervical lymph nodes Cervical lymph nodes enlarge due to local metastasis.
Long history of anterior neck mass with recent rapid enlargement Previously undetected long-standing thyroid carcinoma and goiters (eg, papillary, follicular) are known to progress to anaplastic carcinoma. [2,5]
Anorexia and weight loss [3] Systemic spread of the tumor to the liver produce anorexia and weight loss.
References
  1. SUN M.L., SANG J.S., BYOUNG C.C. Treatment Outcome of Patients with Anaplastic Thyroid Cancer: A Single Center Experience. Yonsei Med J. [online] Mar 1, 2012; 53(2): 352–357. [viewed 6 April 2014] Available from: doi: 10.3349/ymj.2012.53.2.352
  2. HUNDAHL S. A., CADY B., CUNNINGHAM M. P., et al., “Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the united states during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commission on Cancer Patient Care Evaluation study,” Cancer. [online] 2000 89: 202–217,. [viewed 6 April 2014] available at (www.ncbi.nlm.nih.gov/pubmed/10897019)?
  3. NAGAIAH G., HOSSAIN A., MOONEY C. J., PARMENTIER J., REMICK S. C., “Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment,” Journal of Oncology, [online] 2011: 2011 (2011). [viewed 6 April 2014] Available from: http://dx.doi.org/10.1155/2011/542358
  4. B. JEREB, J. STJERNSWARD, AND T. LOWHAGEN, “Anaplastic giant cell carcinoma of the thyroid. A study of treatment and prognosis,” Cancer, [online] 1975. 35 (5), 1293–1295, [viewed 6 April 2014] Available from: http://www.scopus.com/record/display.url?eid=2-s2.0-0016783987&origin=inward&txGid=913BC837E6F75251CA21D16E00A154F8.aqHV0EoE4xlIF3hgVWgA%3a2
  5. SHILLER SM, KONDURI K, HARSHMAN LK, WELCH BJ, O'BRIEN JC. Recurrent thyroid cancer with changing histologic features. Proc (Bayl Univ Med Cent). [online] 2010;23(3):304-310. [viewed 6 April 2014] available at (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900987)?
  6. GIUFFRIDA D, GHARIB H. Anaplastic thyroid carcinoma: Current diagnosis and treatment. Annals of Oncology [online] 2000: 11: 1083-1089. [viewed 6 April 2014] Available from: http://annonc.oxfordjournals.org/content/11/9/1083.full.pdf?origin=publication_detail
  7. SAMAAN NA, ORDONEZ NG. Uncommon types of thyroid cancer. Endocrinol Metab Clin North Am [online] 1990; 19: 637-48[viewed 6 April 2014] available at (http://www.ncbi.nlm.nih.gov/pubmed/2261909)?
  8. AUGUSTO T, FRANCESCA S, MARCO B. Anaplastic Thyroid Carcinoma. Front Endocrinol (Lausanne). [online] 2012; 3: 84. [viewed 6 April 2014] Available from: doi: 10.3389/fendo.2012.00084
  9. ROBERT C. S. Approach to the Patient with Anaplastic Thyroid Carcinoma. J Clin Endocrinol Metab.[online] Aug 2012; 97(8): 2566–2572. [viewed 6 April 2014] Available from: doi: 10.1210/jc.2012-1314
  10. CHUANZHENG S. QIULI LI, ZEDONG HU, JIEHUA HE, CHAO LI, GUOJUN LI, XIAOFENG T., ANKUI YANG. Treatment and Prognosis of Anaplastic Thyroid Carcinoma: Experience from a Single Institution in China. [online] [viewed 8 April 2014] Available from: DOI: 10.1371/journal.pone.0080011

Examination

Fact Explanation
Anterior neck mass The thyroid gland may contain a single nodule (58%), or multiple nodules (36%), involving a single lobe or both lobes. The gland is firm to hard in consistency and fixed to the surrounding structures. [1]
Cervical lymph nodes Some patients have lymph node enlargement. [3]
Signs of pleural effusions Lungs are the most common site of metastasis. Malinant pleural effusions produce reduced chest expansion, stony dull percussion note, and absent air entry over the affected segment. [1]
Neurologic deficits [2] Due to the cerebral metastasis. [2]
Evidence of bone metastasis Bone metastasis of the spine produces tender points. Vertebral collapse is detected by palpation of the vertebral column. [2]
Laryngoscopic examination of vocal cords This will detect the vocal cord paralysis. [1]
References
  1. GIUFFRIDA D, GHARIB H. Anaplastic thyroid carcinoma: Current diagnosis and treatment. Annals of Oncology [online] 2000: 11: 1083-1089. [viewed 6 April 2014] Available from: http://annonc.oxfordjournals.org/content/11/9/1083.full.pdf?origin=publication_detail
  2. ROBERT E. C., Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity. Clin Cancer Res [online] October 15, 2006 12; 6243s [viewed 6 April 2014] Available from: doi: 10.1158/1078-0432.CCR-06-0931
  3. DAVID F. SCHNEIDER, HERBERT C. New developments in the diagnosis and treatment of thyroid cancer. [online] [viewed 6 April 2014] Available from: DOI: 10.3322/caac.21195

Differential Diagnoses

Fact Explanation
Goiter Diffuse goiter is commoner. Patients may have features of hypo or hyperthyroidism or may be euthyroid. Some patients present with a solitary nodule. [4]
Hyperthyroidism Presence of a a 'cold' nodule in a patient with hyperthyroidism should raise the suspicion of thyroid malignancy. However the occurrence of thyroid cancer in hyperthyroid patients is rare. [5]
Parathyroid Carcinoma Patients present with symptoms of hypercalcemia [6,7](Eg: Nausea, vomiting, loss of appetite, thirst, consthetipation and abdominal pain) or may be asymptomatic.
Thyroid Lymphoma Primary thyroid lymphoma is a rare disease and it is has similar features of anaplastic thyroid carcinoma. The differentiation of the two is made by cytological examination. [8]
Thyroid Nodule A solitary nodule may be incidental or asymptomatic. Exclusion of a malignancy is a major concern. [9]
Follicular adenomas and carcinomas FNAC will help in diagnosing the two but it won’t be able to differentiate the two. [10]
Medullary Carcinoma of the thyroid or papillary Carcinoma of the thyroid Patients present with a palpable neck mass. Fine needle aspiration and cytology (FNAC) will provide the cytological diagnosis. [11]
Thyroiditis [2,3] Diffuse and painful enlargement of the thyroid gland occurs.
Secondary deposits of a malignancy. [12] Thyroid gland is a possible site of tumor metastasis.
References
  1. ROBERT C. S., KENNETH B. A., SYLVIA L. A., KEITH C. B. American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. THYROID. [online] 2012. 22(11) [viewed 6 April 2014] Available from: DOI: 10.1089/thy.2012.0302
  2. MOINUDDIN S, BARAZI H, MOINUDDIN M. Acute blastomycosis thyroiditis. Thyroid [online] 2008 18:659–661. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18578618
  3. WEISS IA, LIMAYE A, TCHERTKOFF V, BRENER JL. Sarcoidosis of the thyroid clinically mimicking malignancy. NY State J Med [online] 1989 89:578–580. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2608217
  4. MARK P. J. V. The epidemiology of thyroid disease. Br Med Bull [online] (2011) 99 (1): 39-51. [viewed 6 April 2014] Available from: doi: 10.1093/bmb/ldr030
  5. GABRIELE R, LETIZIA C, BORGHESE M, DE TOMA G, CELI M, IZZO L, CAVALLARO A. Thyroid cancer in patients with hyperthyroidism. Horm Res. [online] 2003;60(2):79-83. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12876418
  6. KOEA AND J. B., SHAW J. H. F., “Parathyroid cancer: biology and management,” Surgical Oncology, [online] vol. 8, no. 3, pp. 155–165, 1999. [viewed 6 April 2014] Available from: http://www.so-online.net/article/S0960-7404(99)00037-7/abstract
  7. GABRIELE R, MARCO A, MARCO B, GIANLUCA L, LIVIO P, ANGELO S, GIOVANNI T, PIERLUIGI M. Parathyroid Carcinoma: The Importance of High Clinical Suspicion for a Correct Management. International Journal of Surgical Oncology. [online] 2012: (2012), Article ID 649148. [viewed 6 April 2014] Available from: http://dx.doi.org/10.1155/2012/649148
  8. WIDDER S, PASIEKA JL. Primary thyroid lymphomas. Curr Treat Options Oncol. [online] 2004 Aug;5(4):307-13. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15233907
  9. LASZLO H. The Thyroid Nodule. N Engl J Med [online] 2004; 351:1764-1771. [viewed 6 April 2014] Available from: http://blog.utp.edu.co/internaumana/files/2010/10/The-Thyroid-Nodule.pdf
  10. CATHERINE B. B, KATHERINE W. S, BAIXIN Z, GERARDO G, et al. Classification of Follicular Thyroid Tumors by Molecular Signature. Results of Gene Profiling. Clin Cancer Res [online] 2003 9; 1792. [viewed 6 April 2014] Available from: http://clincancerres.aacrjournals.org/content/9/5/1792.long
  11. REBECCA S. S, MUTHUSAMY K., HERBERT C. Current Management of Medullary Thyroid Cancer. The Oncologist [online] May 2008vol. 13 no. 5 539-547 doi:10.1634/theoncologist.2007-0239 The Oncologist May 2008vol. 13 no. 5 539-547 [viewed 6 April 2014] Available from: doi: 10.1634/theoncologist.2007-0239
  12. IRVING B. ROSEN, PAUL G. WALFISH,M, JERALD B., YVAN C. B. Secondary malignancy of the thyroid gland and its management. Annals of Surgical Oncology. [online] May 1995, 2 (3), 252-256. [viewed 6 April 2014] Available from: http://link.springer.com/article/10.1007%2FBF02307032

Investigations - for Diagnosis

Fact Explanation
Fine-needle aspiration and cytology (FNAC) [2] FNAC will provide a cytological diagnosis of anaplastic carcinoma.
Open surgical biopsy [1] When FNAC is inconclusive open surgical biopsy is done to make the definitive diagnosis of anaplastic carcinoma.
References
  1. ROBERT C. S., KENNETH B. A., SYLVIA L. A., KEITH C. B. American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. THYROID. [online] 2012. 22(11) [viewed 6 April 2014] Available from: DOI: 10.1089/thy.2012.0302
  2. US-KRASOVEC M, GOLOUH R, AUERSPERG M, BESIC N, RUPARCIC-O. Anaplastic thyroid carcinoma in fine needle aspirates. Acta Cytol. [online] 1996 Sep-Oct;40(5):953-8. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8842172

Investigations - Fitness for Management

Fact Explanation
Complete blood count Enables detection of anemia and infection before the surgery. [1,2]
Serum electrolytes and creatinine Renal function should be evaluated prior to the surgery. [1,3]
Chest radiography If there is a history of lung disease. [4] Detection of the anatomical variations of the structures in the neck is also important.
ECG Asses the cardiovascular fitness of the patient. [3]
References
  1. ROBERT C. S., KENNETH B. A., SYLVIA L. A., KEITH C. B. American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. THYROID. [online] 2012. 22(11) [viewed 6 April 2014] Available from: DOI: 10.1089/thy.2012.0302
  2. HAAS V, CELAKOVSKY P, BRTKOVA J, HORNYCHOVA H. Unusual manifestation of anaplastic thyroid cancer. Acta Medica (Hradec Kralove) [online] 2008: 51:233–236. [viewed 6 April 2014]
  3. Practice advisory for preanesthesia evaluation. An updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. [viewed 1 April 2014] Available from: http://www.guideline.gov/content.aspx?id=36197
  4. RUCKER L, FRYE EB, STATEN MA. Usefulness of screening chest roentgenograms in preoperative patients. JAMA [online]250(23):3209-11. [viewed 1 April 2014]

Investigations - Followup

Fact Explanation
Serum calcium levels Permanent hypoparathyroidism is a known complication of radical surgery. [2]
Indirect laryngoscopy [1] Detects post-operative recurrent laryngeal nerve palsy.
References
  1. GIUFFRIDA D, GHARIB H. Anaplastic thyroid carcinoma: Current diagnosis and treatment. Annals of Oncology[online] 2000: 11: 1083-1089. [viewed 6 April 2014] Available from: http://annonc.oxfordjournals.org/content/11/9/1083.full.pdf?origin=publication_detail
  2. ASARI R, PASSLER C, KACZIREK K, SCHEUBA C, NIEDERLE B. Hypoparathyroidism after total thyroidectomy: a prospective study. Arch Surg. [online] 2008 Feb;143(2):132-7. [viewed 6 April 2014] Available from: doi: 10.1001/archsurg.2007.55.

Investigations - Screening/Staging

Fact Explanation
Chest radiography Canon ball appearance is suggestive of lung metastasis. Detects malignant pulmonary effusions.
Ultra sound scan of the neck Detects cervical lymph node metastasis. [4]
CT scan CT scan of the neck detects the local spread of disease (stage IVA). Other than that CT can detect pleural effusions and metastasis in lung, liver, bone, and brain. [2,3,5] If distant metastasis are present the tumor stage is IVC. [4]
MRI Detects similar information like the CT scan. [4]
Bone scanning Detects bone metastasis.
Positron emission tomography (PET) Uses 18F-fluorodeoxyglucose (18F-FDG). This visualizes the primary tumor, and metastases in the lymph nodes, lungs, and other distant sites. [1,3]
Indirect laryngoscopy Detects recurrent vocal cord paralysis. [6]
References
  1. 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. [online] Jul 2008;18(7):713-9. [viewed 6 April 2014]
  2. NGUYEN BD, RAM PC. PET/CT staging and posttherapeutic monitoring of anaplastic thyroid carcinoma. Clin Nucl Med [online] 2007. 32:145–149. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/17242574
  3. POISSON T, DEANDREIS D, LEBOULLEUX S, BIDAULT F, BONNIAUD G, et al. 18F-Fluorodeoxyglucose positron emission tomography and computed tomography in anaplastic thyroid cancer. Eur J Nucl Med Mol Imaging [online] 2010. 37:2277–2285. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20694463
  4. ROBERT C. S. Approach to the Patient with Anaplastic Thyroid Carcinoma. J Clin Endocrinol Metab. [online] Aug 2012; 97(8): 2566–2572. [viewed 6 April 2014] Available from: doi: 10.1210/jc.2012-1314
  5. B. JEREB, J. STJERNSWARD, AND T. LOWHAGEN, “Anaplastic giant cell carcinoma of the thyroid. A study of treatment and prognosis,” Cancer, [online] 1975. 35 (5), 1293–1295, [viewed 6 April 2014] Available from: http://www.scopus.com/record/display.url?eid=2-s2.0-0016783987&origin=inward&txGid=913BC837E6F75251CA21D16E00A154F8.aqHV0EoE4xlIF3hgVWgA%3a2
  6. GIUFFRIDA D, GHARIB H. Anaplastic thyroid carcinoma: Current diagnosis and treatment. Annals of Oncology[online] 2000: 11: 1083-1089. [viewed 6 April 2014] Available from: http://annonc.oxfordjournals.org/content/11/9/1083.full.pdf?origin=publication_detail

Management - General Measures

Fact Explanation
Tracheostomy The major cause of mortality in patients with anaplastic carcinoma of the thyroid is the airway obstruction. Tracheostomy is a conservative measure to prevent this and prolong the life. [4]
Interventional bronchoscopy Provides access to deliver laser therapy to tracheal metastases. [1] Also enables stenting the narrowed airway. [1]
Patient education Anaplastic carcinoma of the thyroid is a rapidly growing and early metastasizing carcinoma and have median survival of about 4 to 6 months. [2,3] Patient education and psychological support is mandatory.
References
  1. CHIACCHIO S, LORENZONI A, BONI G, RUBELLO D, ELISEI R, MARIANI G. Anaplastic thyroid cancer: prevalence, diagnosis and treatment. Minerva Endocrinol. [online] Dec 2008;33(4):341-57. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18923370
  2. KEBEBEW E, GREENSPAN FS, CLARK OH, WOEBER KA, MCMILLAN A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. [online] 2005;103:1330–1335. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15739211
  3. GILLILAND FD, HUNT WC, MORRIS DM, KEY CR. Prognostic factors for thyroid carcinoma. A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973-1991. Cancer. [online] 1997;79:564–573. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9028369
  4. NOPPEN M, POPPE K, D'HAESE J, MEYSMAN M, VELKENIERS B et al. Interventional bronchoscopy for treatment of tracheal obstruction secondary to benign or malignant thyroid disease. Chest [online] 2004: 125: 723-730. doi:10.1378/chest.125.2.723.

Management - Specific Treatments

Fact Explanation
Total thyroidectomy About one third of the patients with anaplastic carcinoma have small, resectable carcinoma at the time of diagnosis (stage IVA). [8] These patients are suitable candidates for the total thyroidectomy. [5,6] The patients are given radiotherapy after the surgical resection for better outcome. [12,19] Often multimodal approach with surgery, radiotherapy, and chemotherapy is used. [13,15]
Doxorubicin Doxorubicin is an antineoplastic agent which inhibits topoisomerase II and produces free radicals. These free radicals damage the DNA of the rapidly growing cells. This is the most effective therapy in metastatic disease. Mono-therapy with doxorubicin is inferior than the combined therapy with doxorubicin and cisplatin.[7] Doxorubicin is often combined with external beam radiotherapy for more effective tumor suppression. [10,11]
Cisplatin Cisplatin is a chemotherapeutic agent which forms DNA crosslinks and denature the DNA double helix. These actions will inhibit the cell proliferation.
Valproic acid Valporic acid induces apoptosis of the cancer cells. It enhances the action of doxorubicin by increasing the sensitivity of anaplastic cancer cell lines to doxorubicin. [2]
External beam radiotherapy Radiotherapy with larger doses will improve the survival. [1,3] It is a very effective method of limiting the loco regional spread of the tumor. [13] For patients who are less than or 70 years old with tumor size of 5 cm or less with no distant disease benefit from post-operative radiotherapy. [9] Often larges doses are used in the treatment. [15,16]
BRAF and EGFR inhibitors BRAF mutations and EGFR overexpression are known associated genetic changes in anaplastic thyroid carcinoma. Inhibition of the activity of these two genes will inhibit the proliferation of malignant cells. [14] Erlotinib is an EGFR inhibitor. [18]
Imatinib This is an inhibitor of C-kit, platelet-derived growth factor receptor. [17]
References
  1. BHATIA A, RAO A, ANG KK, GARDEN AS, MORRISON WH, ROSENTHAL DI, et al. Anaplastic thyroid cancer: Clinical outcomes with conformal radiotherapy. Head Neck. [online] Nov 2 2009 [viewed 6 April 2014] Available from: doi: 10.1002/hed.21257.
  2. 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. [online] Apr 2009;56(2):245-9. [viewed 6 April 2014] Available from: https://www.jstage.jst.go.jp/article/endocrj/56/2/56_K08E-016/_article
  3. 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. [online] Jul 2009;92(1):100-4. [viewed 6 April 2014] Available from: doi: 10.1016/j.radonc.2009.02.016. Epub 2009 Mar 26.
  4. 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. [online] Feb 2007;14(2):719-29. [viewed 6 April 2014] Available from: 10.1245/s10434-006-9178-6
  5. GOLDMAN JM, GOREN EN, COHEN MH, et al.: Anaplastic thyroid carcinoma: long-term survival after radical surgery. J Surg Oncol [online] 14 (4): 389-94, 1980. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7442263?dopt=Abstract
  6. DE CREVOISIER R, BAUDIN E, BACHELOT A, et al.: Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys [online] 60 (4): 1137-43, 2004. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15519785?dopt=Abstract
  7. SHIMAOKA K, SCHOENFELD DA, DEWYS WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer [online] 56 (9): 2155-60, 1985. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3902203?dopt=Abstract
  8. MCIVER B, HAY ID, GIUFFRIDA DF, DVORAK CE, GRANT CS, THOMPSON GB, et al. Anaplastic thyroid carcinoma: a 50-year experience at a single institution. Surgery. [online] 2001;130:1028–1034. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11742333
  9. PIERIE JP, Muzikansky A, Gaz RD, Faquin WC, Ott MJ. The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma. Ann Surg Oncol. [online] 2002;9:57–64. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11833496
  10. KIM JH, LEEPER RD. Treatment of anaplastic giant and spindle cell carcinoma of the thyroid gland with combination Adriamycin and radiation therapy. A new approach. Cancer. [online] 1983;52:954–957. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/6883279
  11. KIM JH, LEEPER RD. Treatment of locally advanced thyroid carcinoma with combination doxorubicin and radiation therapy. Cancer. [online] 1987;60:2372–2375. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3664425
  12. KEBEBEW E, GREENSPAN FS, CLARK OH, WOEBER KA, MCMILLAN A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. [online] 2005 Apr 1;103(7):1330-5. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15739211
  13. ROBERT C. S. Approach to the Patient with Anaplastic Thyroid Carcinoma. J Clin Endocrinol Metab. [online] Aug 2012; 97(8): 2566–2572. [viewed 6 April 2014] Available from: doi: 10.1210/jc.2012-1314
  14. PRAHALLAD A, SUN C, HUANG S, DI NICOLANTONIO F, SALAZAR R, et al. 2012. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature[online] 483:100–103. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22281684
  15. TENNVALL J, LUNDELL G, WAHLBERG P, BERGENFELZ A, GRIMELIUS L, AKERMAN M, HJELM SKOG AL, WALLIN G. 2002. Anaplastic thyroid carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery. Br J Cancer [online] 86:1848–1853. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12085174
  16. 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 [online] 2009. 92:100–104. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19328572
  17. HA HT, LEE JS, URBA S, KOENIG RJ, SISSON J, GIORDANO T, WORDEN FP. A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid [online] 2010. 20:975–980. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20718683
  18. HOGAN T, JING JIE YU, WILLIAMS HJ, ALTAHA R, XIAOBING LIANG, QI HE. Oncocytic, focally anaplastic, thyroid cancer responding to erlotinib. J Oncol Pharm Pract [online] 2009. 15:111–117. [viewed 6 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19276143
  19. CHUANZHENG SUN, QIULI LI, ZEDONG HU, JIEHUA HE, CHAO LI, GUOJUN LI, XIAOFENG TAO, ANKUI YANG. Treatment and Prognosis of Anaplastic Thyroid Carcinoma: Experience from a Single Institution in China. PLoS ONE [online] 8(11): e80011. [viewed 6 April 2014] Available from: doi:10.1371/journal.pone.0080011