AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

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.

Pathophysiology

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 has a rapid course and early dissemination. The most common sites of distant spread include (in descending order) lung, bone, and brain. Metastases (particularly in the lung) are likely to be present at diagnosis more than 50% of the time.

Frequency

United States

ATC comprises less than 2% of all thyroid malignancies. Fortunately, the incidence appears to be declining.

International

Worldwide frequency likely approximates that in the United States.

Mortality/Morbidity

ATC typically has a rapidly progressive course. The overall 5-year survival rate is reportedly less than 10%, and most patients do not live longer than a few months after diagnosis.

Sex

The female-to-male ratio is approximately 3:1.

Age

Peak incidence occurs during the sixth to seventh decades of life. The age range of affected patients reportedly is 15-90 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients with anaplastic thyroid carcinoma (ATC) typically present with a rapidly growing neck mass. Patients with metastases may also note bone pain, weakness, and cough. Neurologic deficits may be observed with brain metastases. The rapidly growing neck mass may produce the following symptoms:

• Dysphagia
• Cough
• Neck pain
• Dyspnea

Physical

Physical examination typically reveals a dominant neck mass. More than 40% of affected patients have lymph node enlargement, indicating local metastases. Pleural effusions may lead to decreased breath sounds on auscultation. With metastases, the physician may note bone pain and neurologic deficits.

Causes

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Thyroid, adenoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Anaplastic thyroid carcinoma (ATC) cannot be definitively diagnosed with laboratory examinations of the blood or urine.
• Obtain serum calcium levels to rule out medullary thyroid carcinoma or parathyroid neoplasms.

Imaging Studies

• Chest radiography may be used to determine the presence of lung metastases.
• Preoperative cervical ultrasonography can detect lymph node metastases.
• Cervical CT scanning can be used to define the local spread of disease. Detection of distant metastases to the mediastinum, liver, lung, bone, and brain is also possible via CT scanning or MRI.
• Bone scanning can be used to determine the presence of bone metastases.

Procedures

• Fine-needle aspiration often yields enough cytologic information to allow diagnosis; however, if fine-needle aspiration is inadequate, patients may require an open surgical biopsy.

Histologic Findings

Grossly, ATC is described as a large, fleshy, off-white tumor. Infiltration of adjacent structures can be observed grossly and microscopically. Histologically, observation of regions of spontaneous necrosis and hemorrhage may be observed. Typically, angioinvasion is detectable.

The main histologic variants include spindle cell, giant cell (osteoclastlike), squamoid, and paucicellular. The giant cell subtype typically exhibits local calcification with significant osteoid formation. The paucicellular subtype demonstrates rapid growth, intense fibrosis, focal infarction, diffuse calcification, and encroachment of adjacent vascular tissue by atypical spindle cells.

Thyroid lymphoma is the only curable condition that may be confused with ATC. Rule out lymphoma in the presence of a poorly differentiated large cell thyroid tumor. This investigation involves lymphoid tissue markers (eg, cytoplasmic immunoglobulin, immunoglobulin receptors, gene rearrangement studies).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Treatment is mostly palliative.
• Phase I studies are as follows:
• • Consider patients with unresectable tumors who are in good general condition for phase I studies.
  • These studies are available in any major cancer center, are generally financed by the industry, and may help individual patients.
  • Phase I trials represent the only opportunity to recognize drugs of some activity in this unusual disease.

Surgical Care

• Perform surgery in conjunction with radiation and chemotherapy.
• Use surgery to obtain a definitive diagnosis when fine-needle aspiration is unsuccessful.
• Protect the airway when performing surgery; thus, performing an early prophylactic tracheostomy may be required.
• Despite the typically large size of these tumors, the extent of resection is limited when the diagnosis is made.
• Rather than performing complete thyroidectomy, resect as much thyroid tissue as possible without attempting resection of all adjacent structures because of the high incidence of postoperative morbidity (eg, vocal cord paralysis, esophageal fistula). Although a greater extent of resection may be associated with slightly longer survival, this hypothesis is not confirmed.

Consultations

Involve a surgeon with experience in thyroid operations in the operative care of affected patients.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antineoplastics

Chemotherapeutic agents that may be used in advanced disease include doxorubicin and cisplatin.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Role of adjuvant therapy
• • Radiotherapy: Despite the fact that anaplastic thyroid carcinoma (ATC) is largely radioresistant, use external beam radiotherapy for local control. Some evidence shows that hyperfractionation may lead to better success at local control by permitting delivery of higher doses of total radiation with less toxicity.
  • Chemotherapy: Currently, no available chemotherapeutic agent or combination of chemotherapeutic agents shows sufficient antineoplastic activity to prevent death; yet in rare instances, chemotherapy may prolong life by a few weeks or perhaps months. Doxorubicin and cisplatin are the 2 most common agents used; however, resistance from cellular extrusion of the drugs occurs.
• Since ATC is a relatively uncommon disease, large phase III clinical trials of systemic therapies are not possible to perform. For that reason, the value of newer therapies, such as taxanes, gemcitabine, and irinotecan, and targeted therapies, such as receptor tyrosine kinase inhibitors, is unknown.

Complications

• Risk of complications from a thyroid disease operation (eg, permanent hypoparathyroidism, recurrent laryngeal nerve palsy) may be increased with ATC if an aggressive surgical attempt is made.
• With limited thyroid resection, incidence of these local complications should not be significantly greater.

Prognosis

• ATC typically has a rapidly progressive course. The overall 5-year survival rate is reportedly less than 10%, and most patients do not live longer than a few months after diagnosis.
• A recent study has shown that patients younger than 60 years who have intrathyroidal ATC have a better prognosis compared with patients who are older and have distant metastases.
• While some studies have suggested that postoperative radiotherapy may be of benefit in terms of survival, definitive prospective trials are lacking.

Patient Education

• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose anaplastic thyroid carcinoma (ATC) at an early stage before it spreads both locally and distantly, which underscores the importance of meticulous history and physical examination assessment
• Failure to perform fine-needle aspiration for any suspicious thyroid mass; an equivocal or indeterminate mass should be re-aspirated or surgically excised if any question remains as to the histology of the lesion
• Failure to assess airway patency, which is foremost in the physician's treatment plan
• Failure to seriously consider intubation and/or tracheostomy if cancer is producing local airway compromise

Special Concerns

• Because ATC tends to occur in areas of previous thyroid pathology, consider the diagnosis in patients with a medical history of thyroid disease who present with a recently enlarging neck mass.
• If metastases are found, aggressive surgical therapy is not warranted.
• While recent trials of immunotherapy and gene therapy have been postulated, no definitive evidence suggests any benefit from these modalities; they should be considered experimental at best.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Ain KB. Anaplastic thyroid carcinoma: a therapeutic challenge. Semin Surg Oncol. 1999;16:64-69. [Medline].
• Austin JR, el-Naggar AK, Goepfert H. Thyroid cancers. II. Medullary, anaplastic, lymphoma, sarcoma, squamous cell. Otolaryngol Clin North Am. 1996;29:611-27. [Medline].
• Goutsouliak V, Hay JH. Anaplastic thyroid cancer in British Columbia 1985-1999: a population-based study. Clin Oncol (R Coll Radiol). Apr 2005;17(2):75-8. [Medline].
• Kapp DS, LiVolsi VA, Sanders MM. Anaplastic carcinoma following well-differentiated thyroid cancer: etiological considerations. Yale J Biol Med. 1982;55:521-8.
• Kebebew E, Greenspan FS, Clark OH, et al. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. Apr 1 2005;103(7):1330-5. [Medline].
• Schott M, Scherbaum WA. Immunotherapy and gene therapy of thyroid cancer. Minerva Endocrinol. Dec 2004;29(4):175-87. [Medline].
• Udelsman R, Lakatos E, Ladenson P. Optimal surgery for papillary thyroid carcinoma. World J Surg. 1996;20:88-93. [Medline].
• Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. Jun 2005;12(2):245-62. [Medline].

Article Last Updated: Apr 18, 2006