Table of Contents Purpose of This PDQ Summary General Information Cellular Classification Stage Information
Stage I and II Papillary and Follicular Thyroid Cancer Stage III Papillary and Follicular Thyroid Cancer Stage IV Papillary and Follicular Thyroid Cancer Medullary Thyroid Cancer Anaplastic Thyroid Cancer Recurrent Thyroid Cancer Get More Information From NCI Changes to This Summary (02/06/2009) More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of thyroid cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Back to Top General Information
Note: A separate PDQ summary on Genetics of Medullary Thyroid Cancer is also available and information on thyroid cancer in children is available in the PDQ summary on Unusual Cancers of Childhood.
Note: Estimated new cases and deaths from thyroid cancer in the United States in 2008:[1]
- New cases: 37,340.
- Deaths: 1,590.
Carcinoma of the thyroid gland is an uncommon cancer but is the
most common malignancy of the endocrine system.[2] Differentiated tumors
(papillary or follicular) are highly treatable and usually curable. Poorly differentiated tumors (medullary or anaplastic) are much less common, are
aggressive, metastasize early, and have a much poorer prognosis. Thyroid
cancer affects women more often than men and usually occurs in
people between the ages of 25 and 65 years. The incidence of this malignancy has
been increasing over the last decade. Thyroid cancer commonly presents
as a cold nodule. The overall incidence of cancer in a cold nodule is 12% to
15%, but it is higher in people younger than 40 years and in people with calcifications present on preoperative ultrasonography.[3,4]
Risk factors
Patients with a history of radiation administered in infancy and childhood for
benign conditions of the head and neck, such as enlarged thymus, acne, or
tonsillar or adenoidal enlargement, have an increased risk of cancer as well as
other abnormalities of the thyroid gland. In this group of patients,
malignancies of the thyroid gland first appear beginning as early as 5 years
following radiation and may appear 20 or more years later.[5] Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[6-8] Other risk
factors for the development of thyroid cancer include a history of goiter,
family history of thyroid disease, female gender, and Asian race.[9]
Prognostic factors
The prognosis for differentiated
carcinoma is better for patients younger than 40 years without
extracapsular extension or vascular invasion.[10-14] Age appears to be the
single most important prognostic factor.[12] The prognostic significance of lymph node status is controversial. One
retrospective surgical series of 931 previously untreated patients with
differentiated thyroid cancer found that female gender, multifocality, and
regional node involvement are favorable prognostic factors.[15] Adverse factors
included age older than 45 years, follicular histology, primary tumor larger than 4
cm (T2–T3), extrathyroid extension (T4), and distant metastases.[15,16]
Other studies, however, have shown that regional lymph node involvement had no
effect [17,18] or even an adverse effect on survival.[13,14,19] Diffuse, intense
immunostaining for vascular endothelial growth factor in patients with
papillary cancer has been associated with a high rate of local recurrence and
distant metastases.[20] An elevated serum thyroglobulin level correlates
strongly with recurrent tumor when found in patients with differentiated
thyroid cancer during postoperative evaluations.[21,22] Serum thyroglobulin
levels are most sensitive when patients are hypothyroid and have elevated serum
thyroid-stimulating hormone levels.[23] Expression of the tumor suppressor
gene p53 has also been associated with an adverse prognosis for patients with
thyroid cancer.[24]
Patients considered to be low risk by the age, metastases, extent, and size
(AMES) risk criteria include women younger than 50 years and men younger
than 40 years without evidence of distant metastases. Also included in
the low-risk group are older patients with primary tumors smaller than 5
cm and papillary cancer without evidence of gross extrathyroid
invasion or follicular cancer without either major capsular invasion or blood
vessel invasion.[11] Using these criteria, a retrospective study of 1,019
patients showed that the 20-year survival rate is 98% for low-risk patients and
50% for high-risk patients.[11] The 10-year overall relative survival rates for patients in the United States are 93% for papillary cancer, 85% for follicular cancer, 75% for medullary cancer, and 14% for undifferentiated/anaplastic cancer.[2]
The
thyroid gland may occasionally be the site of other primary tumors, including
sarcomas, lymphomas, epidermoid carcinomas, and teratomas and may be the site
of metastasis from other cancers, particularly of the lung, breast, and kidney.
References
-
American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008.
-
Hundahl SA, Fleming ID, Fremgen AM, et al.: A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments] Cancer 83 (12): 2638-48, 1998.
[PUBMED Abstract]
-
Tennvall J, Biörklund A, Möller T, et al.: Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid carcinoma? Retrospective multivariate analysis of differentiated thyroid carcinoma with long follow-up. Cancer 57 (7): 1405-14, 1986.
[PUBMED Abstract]
-
Khoo ML, Asa SL, Witterick IJ, et al.: Thyroid calcification and its association with thyroid carcinoma. Head Neck 24 (7): 651-5, 2002.
[PUBMED Abstract]
-
Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1502-19.
-
Pacini F, Vorontsova T, Molinaro E, et al.: Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 352 (9130): 763-6, 1998.
[PUBMED Abstract]
-
Cardis E, Kesminiene A, Ivanov V, et al.: Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst 97 (10): 724-32, 2005.
[PUBMED Abstract]
-
Tronko MD, Howe GR, Bogdanova TI, et al.: A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening. J Natl Cancer Inst 98 (13): 897-903, 2006.
[PUBMED Abstract]
-
Iribarren C, Haselkorn T, Tekawa IS, et al.: Cohort study of thyroid cancer in a San Francisco Bay area population. Int J Cancer 93 (5): 745-50, 2001.
[PUBMED Abstract]
-
Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988.
[PUBMED Abstract]
-
Sanders LE, Cady B: Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133 (4): 419-25, 1998.
[PUBMED Abstract]
-
Mazzaferri EL: Treating differentiated thyroid carcinoma: where do we draw the line? Mayo Clin Proc 66 (1): 105-11, 1991.
[PUBMED Abstract]
-
Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994.
[PUBMED Abstract]
-
Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994.
[PUBMED Abstract]
-
Shah JP, Loree TR, Dharker D, et al.: Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164 (6): 658-61, 1992.
[PUBMED Abstract]
-
Andersen PE, Kinsella J, Loree TR, et al.: Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 170 (5): 467-70, 1995.
[PUBMED Abstract]
-
Coburn MC, Wanebo HJ: Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. Am J Surg 164 (6): 671-6, 1992.
[PUBMED Abstract]
-
Voutilainen PE, Multanen MM, Leppäniemi AK, et al.: Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11 (10): 953-7, 2001.
[PUBMED Abstract]
-
Sellers M, Beenken S, Blankenship A, et al.: Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. Am J Surg 164 (6): 578-81, 1992.
[PUBMED Abstract]
-
Lennard CM, Patel A, Wilson J, et al.: Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129 (5): 552-8, 2001.
[PUBMED Abstract]
-
van Herle AJ, van Herle KA: Thyroglobulin in benign and malignant thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 601-618.
-
Ruiz-Garcia J, Ruiz de Almodóvar JM, Olea N, et al.: Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. J Nucl Med 32 (3): 395-8, 1991.
[PUBMED Abstract]
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Duren M, Siperstein AE, Shen W, et al.: Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients. Surgery 126 (1): 13-9, 1999.
[PUBMED Abstract]
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Godballe C, Asschenfeldt P, Jørgensen KE, et al.: Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108 (2): 243-9, 1998.
[PUBMED Abstract]
Back to Top Cellular Classification
Cell type is an important determinant of prognosis in thyroid cancer. There
are four main varieties of thyroid cancer (although, for clinical management of
the patient, thyroid cancer is generally divided into two categories: well differentiated or
poorly differentiated):[1]
- Papillary carcinoma.
- Papillary/follicular carcinoma.
- Follicular carcinoma.
- Hürthle cell carcinoma, a variant of follicular carcinoma with a poorer prognosis.[2]
- Medullary carcinoma.
- Anaplastic carcinoma.
- Small cell carcinoma.
- Giant cell carcinoma.
- Others.
- Lymphoma.
- Sarcoma.
- Carcinosarcoma.
A definition for each major type can be found under stage information.
References
-
LiVolsi VA: Pathology of thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 127-175.
-
Kushchayeva Y, Duh QY, Kebebew E, et al.: Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 195 (4): 457-62, 2008.
[PUBMED Abstract]
Back to Top Stage Information
The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification.[1]
TNM Definitions
Primary tumor (T)
[Note: All categories may be subdivided into (a) solitary tumor or (b)
multifocal tumor (the largest determines the classification).]
- TX: Primary tumor cannot be assessed
- T0: No evidence of primary tumor
- T1: Tumor 2 cm or less in greatest dimension, limited to the thyroid
- T2: Tumor larger than 2 cm but 4 cm or smaller in greatest dimension,
limited to the thyroid
- T3: Tumor larger than 4 cm in greatest dimension limited to the thyroid
or any tumor with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues)
- T4a: Tumor of any size extending beyond the thyroid capsule
to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve
- T4b: Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumors.
- T4a: Intrathyroidal anaplastic carcinoma—surgically resectable
- T4b: Extrathyroidal anaplastic carcinoma—surgically unresectable
Regional lymph nodes (N)
Regional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes.
- NX: Regional lymph nodes cannot be assessed
- N0: No regional lymph node metastasis
- N1: Regional lymph node metastasis
- N1a: Metastasis to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes)
- N1b: Metastasis to unilateral or bilateral cervical or
superior mediastinal lymph nodes
Distant metastases (M)
- MX: Distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis
AJCC Stage Groupings
Separate stage groupings are recommended for papillary or follicular, medullary, and anaplastic (undifferentiated) carcinoma.
Papillary or follicular thyroid cancer
-
Younger than 45 years
-
Age 45 years and older
- Stage I
- Stage II
- Stage III
- T3, N0, M0
- T1, N1a, M0
- T2, N1a, M0
- T3, N1a, M0
- Stage IVA
- T4a, N0, M0
- T4a, N1a, M0
- T1, N1b, M0
- T2, N1b, M0
- T3, N1b, M0
- T4a, N1b, M0
- Stage IVB
- Stage IVC
Medullary thyroid cancer
- Stage I
- Stage II
- Stage III
- T3, N0, M0
- T1, N1a, M0
- T2, N1a, M0
- T3, N1a, M0
- Stage IVA
- T4a, N0, M0
- T4a, N1a, M0
- T1, N1b, M0
- T2, N1b, M0
- T3, N1b, M0
- T4a, N1b, M0
- Stage IVB
- Stage IVC
Anaplastic thyroid cancer
-
All anaplastic carcinomas are considered stage IV.
Papillary and Follicular Thyroid Cancer
Stage I papillary thyroid cancer
Stage I papillary carcinoma is localized to the thyroid gland. In as many as
50% of cases, there are multifocal sites of papillary adenocarcinomas throughout
the gland. Most papillary cancers have some follicular elements, and these may
sometimes be more numerous than the papillary formations, but this does not
change the prognosis. The 10-year survival rate is slightly better for
patients younger than 40 years than for patients older than 40 years.
Stage II papillary thyroid cancer
Stage II papillary carcinoma is defined as either (1) tumor that has spread
distantly in patients younger than 45 years or (2) tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older
than 45 years. In as many as 50% to 80% of cases there are multifocal
sites of papillary adenocarcinomas throughout the gland. Most papillary
cancers have some follicular elements, and these may sometimes be more numerous
than the papillary formations, but this does not appear to change the
prognosis.
Stage III papillary thyroid cancer
Stage III is papillary carcinoma in patients older than 45 years that is larger than 4 cm and is limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Papillary carcinoma that has
invaded adjacent cervical tissue has a worse prognosis than tumors confined to
the thyroid.
Stage IV papillary thyroid cancer
Stage IV is papillary carcinoma in patients older than 45 years with
extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent distant sites of
spread, though such distant spread is rare in this type of thyroid cancer.
Papillary carcinoma more frequently metastasizes to regional lymph nodes than
to distant sites. The prognosis for patients with distant metastases is poor.
Stage I follicular thyroid cancer
Stage I follicular carcinoma is localized to the thyroid gland. Follicular
thyroid carcinoma must be distinguished from follicular adenomas, which are
characterized by their lack of invasion through the capsule into the
surrounding thyroid tissue. While follicular cancer has a good prognosis, it
is less favorable than that of papillary carcinoma. The 10-year survival is better for
patients with follicular carcinoma without vascular invasion than it is for
patients with vascular invasion.
Stage II follicular thyroid cancer
Stage II follicular carcinoma is defined as either tumor that has spread
distantly in patients younger than 45 years, or tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older
than 45 years. The presence of lymph node metastases does not worsen
the prognosis among patients younger than 45 years. Follicular thyroid carcinoma must be distinguished from
follicular adenomas, which are characterized by their lack of invasion through
the capsule into the surrounding thyroid tissue. While follicular cancer has
a good prognosis, it is less favorable than that of papillary carcinoma; the
10-year survival is better for patients with follicular carcinoma without vascular
invasion than for patients with vascular invasion.
Stage III follicular thyroid cancer
Stage III is follicular carcinoma in patients older than 45 years, larger than 4 cm and limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Follicular carcinoma invading
cervical tissue has a worse prognosis than tumors confined to the thyroid
gland. The presence of vascular invasion is an additional poor prognostic
factor. Metastases to lymph nodes do not worsen the prognosis in patients younger than 45 years.
Stage IV follicular thyroid cancer
Stage IV is follicular carcinoma in patients older than 45 years with
extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent sites of spread.
Follicular carcinomas more commonly have blood vessel invasion and tend to
metastasize hematogenously to the lungs and to the bone rather than through the
lymphatic system. The prognosis for patients with distant metastases is poor.
Hürthle cell carcinoma
Hürthle cell carcinoma is a variant of follicular carcinoma with a similar prognosis and should be treated in the same way as equivalent stage non-Hürthle cell follicular carcinoma.[2]
Medullary Thyroid Cancer
Several staging systems have been employed to correlate extent of disease with
long-term survival in medullary thyroid cancer. The clinical staging system of
the AJCC correlates survival to size of the primary tumor, presence or absence
of lymph node metastases, and presence or absence of distance metastasis.
Patients with the best prognosis are those who are diagnosed by provocative
screening, prior to the appearance of palpable disease.[3]
Stage 0 medullary thyroid cancer
Clinically occult disease detected by provocative biochemical screening.
Stage I medullary thyroid cancer
Tumor smaller than 2 cm.
Stage II medullary thyroid cancer
Tumor larger than 2 cm but 4 cm or smaller.
Stage III medullary thyroid cancer
Tumor larger than 4 cm with minimal extrathyroid extension or any primary tumor smaller than 4 cm with metastases limited to the pretracheal, paratracheal, or prelaryngeal/Delphian lymph nodes.
Stage IV medullary thyroid cancer
Stage IV medullary thyroid cancer is divided into:
- Stage IVA (potentially resectable with or without lymph node metastases [for T4a] but without distant metastases).
- Stage IVB (locally unresectable with or without lymph node metastases but no distant metastases).
- Stage IVC (distant metastases).
Medullary carcinoma usually presents as a hard mass and is often accompanied
by blood vessel invasion. Medullary thyroid cancer occurs in two forms,
sporadic and familial. In the sporadic form, the tumor is usually unilateral.
In the familial form, the tumor is almost always bilateral. In addition, the
familial form may be associated with benign or malignant tumors of other
endocrine organs, commonly referred to as the multiple endocrine neoplasia
syndromes (MEN 2A or MEN 2B).
In these syndromes, there is an association with pheochromocytoma of the adrenal
gland and parathyroid hyperplasia. Medullary carcinoma usually secretes
calcitonin, a hormonal marker for the tumor, and may be detectable in blood
even when the tumor is clinically occult. Metastases to regional lymph nodes
are found in about 50% of cases. Prognosis depends on extent of disease at
presentation, presence or absence of regional lymph node metastases, and
completeness of the surgical resection.[4]
Family members should be screened for calcitonin elevation to identify
individuals who are at risk of developing familial medullary thyroid cancer.
MEN 2A gene carrier status can be more accurately determined by analysis of
mutations in the RET gene. Whereas modest elevation of calcitonin may lead to
a false-positive diagnosis of medullary carcinoma, DNA testing for the RET
mutation is the optimal approach in evaluating MEN 2A. All patients with
medullary carcinoma of the thyroid (whether familial or sporadic) should be
tested for RET mutations, and, if they are positive, family members should
also be tested. Family members who are gene carriers should undergo
prophylactic thyroidectomy at an early age.[5-7]
Anaplastic Thyroid Cancer
No generally accepted staging system is available for anaplastic thyroid cancer.
All patients are considered to have stage IV disease.
Undifferentiated (anaplastic) carcinomas are highly malignant cancers of
the thyroid. They may be subclassified as small cell or large cell carcinomas.
Both grow rapidly and extend to structures beyond the thyroid. Both small cell
and large cell carcinomas present as hard, ill-defined masses, often with
extension into the structures surrounding the thyroid. Small cell anaplastic
thyroid carcinoma must be carefully distinguished from lymphoma. This tumor
usually occurs in an older age group and is characterized by extensive local
invasion and rapid progression. Five-year survival with this tumor is poor.
Death is usually from uncontrolled local cancer in the neck, usually within
months of diagnosis.[8]
References
-
Thyroid. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 77-87.
-
Haigh PI, Urbach DR: The treatment and prognosis of Hürthle cell follicular thyroid carcinoma compared with its non-Hürthle cell counterpart. Surgery 138 (6): 1152-7; discussion 1157-8, 2005.
[PUBMED Abstract]
-
Colson YL, Carty SE: Medullary thyroid carcinoma. Am J Otolaryngol 14 (2): 73-81, 1993 Mar-Apr.
[PUBMED Abstract]
-
Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1502-19.
-
Lips CJ, Landsvater RM, Höppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331 (13): 828-35, 1994.
[PUBMED Abstract]
-
Decker RA, Peacock ML, Borst MJ, et al.: Progress in genetic screening of multiple endocrine neoplasia type 2A: is calcitonin testing obsolete? Surgery 118 (2): 257-63; discussion 263-4, 1995.
[PUBMED Abstract]
-
Skinner MA, Moley JA, Dilley WG, et al.: Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353 (11): 1105-13, 2005.
[PUBMED Abstract]
-
Neff RL, Farrar WB, Kloos RT, et al.: Anaplastic thyroid cancer. Endocrinol Metab Clin North Am 37 (2): 525-38, xi, 2008.
[PUBMED Abstract]
Back to Top Stage I and II Papillary and Follicular Thyroid Cancer
Surgery is the therapy of choice for all primary lesions. Surgical options
include total thyroidectomy or lobectomy. The choice of procedure is
influenced mainly by the age of the patient and the size of the nodule.
Survival results may be similar; the difference between them lies in the rates
of surgical complications and local recurrences.[1-7]
Standard treatment options:
-
Total thyroidectomy: This procedure is advocated because of the high
incidence of multicentric involvement of both lobes of the gland and the
possibility of dedifferentiation of any residual tumor to the anaplastic cell
type. The procedure is associated with a higher incidence of
hypoparathyroidism, but this complication may be reduced when a small amount of
tissue remains on the contralateral side. This approach facilitates follow-up
thyroid scanning.
I131: Studies have shown that a postoperative course of therapeutic
(ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary
and follicular carcinomas.[4] It may be given in addition to exogenous thyroid
hormone but is not considered routine.[8] Patients presenting with papillary
thyroid microcarcinomas (tumors <10 mm) have an excellent prognosis when
treated surgically, and additional therapy with I131 would not be expected to
improve the prognosis.[9]
-
Lobectomy: This procedure is associated with a lower incidence of
complications, but approximately 5% to 10% of patients will have a recurrence
in the thyroid following lobectomy.[10] Patients younger than 45 years will have the longest follow-up period and the greatest opportunity for
recurrence. Follicular thyroid cancer commonly metastasizes to lungs and bone; with a remnant lobe in place, use of I131 as ablative therapy is compromised. Abnormal regional lymph nodes should be biopsied at the time of
surgery. Recognized nodal involvement should be removed at initial surgery, but
selective node removal can be performed, and radical neck dissection is usually not
required.
This
results in a decreased recurrence rate, but has not been shown to improve
survival.
Following the surgical procedure, patients should receive postoperative
treatment with exogenous thyroid hormone in doses sufficient to suppress
thyroid-stimulating hormone (TSH); studies have shown a decreased incidence of
recurrence when TSH is suppressed.
I131: Studies have shown that a postoperative course of therapeutic
(ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary
and follicular carcinomas.[4] It may be given in addition to exogenous thyroid
hormone but is not considered routine.[8] Patients presenting with papillary
thyroid microcarcinomas (tumors <10 mm) have an excellent prognosis when
treated surgically, and additional therapy with I131 would not be expected to
improve the prognosis.[9]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I papillary thyroid cancer, stage I follicular thyroid cancer, stage II papillary thyroid cancer and stage II follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1502-19.
-
Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988.
[PUBMED Abstract]
-
Cady B, Rossi R: An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 104 (6): 947-53, 1988.
[PUBMED Abstract]
-
Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994.
[PUBMED Abstract]
-
Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994.
[PUBMED Abstract]
-
Tollefsen HR, Shah JP, Huvos AG: Follicular carcinoma of the thyroid. Am J Surg 126 (4): 523-8, 1973.
[PUBMED Abstract]
-
Edis AJ: Surgical treatment for thyroid cancer. Surg Clin North Am 57 (3): 533-42, 1977.
[PUBMED Abstract]
-
Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984.
[PUBMED Abstract]
-
Hay ID, Grant CS, van Heerden JA, et al.: Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 112 (6): 1139-46; discussion 1146-7, 1992.
[PUBMED Abstract]
-
Hay ID, Grant CS, Bergstralh EJ, et al.: Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124 (6): 958-64; discussion 964-6, 1998.
[PUBMED Abstract]
Back to Top Stage III Papillary and Follicular Thyroid Cancer
Standard treatment options:
- Total thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease.
- I131 ablation following total thyroidectomy if the tumor demonstrates
uptake of this isotope.[1]
- External-beam radiation therapy if I131 uptake is minimal.[2]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III papillary thyroid cancer and stage III follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984.
[PUBMED Abstract]
-
Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978.
[PUBMED Abstract]
Back to Top Stage IV Papillary and Follicular Thyroid Cancer
The most common sites of metastases are lymph nodes, lung, and bone. Treatment
of lymph node metastases alone is often curative. Treatment of distant
metastases is usually not curative but may produce significant palliation.
Standard treatment options:
- I131: Metastases that demonstrate uptake of this isotope may be ablated
by therapeutic doses of I131.
- External-beam radiation therapy for patients with localized lesions that are
unresponsive to I131.[1]
- Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of I131.
- Thyroid-stimulating hormone suppression with thyroxine is also effective in many
lesions not sensitive to I131.
Patients unresponsive to I131 should also be considered candidates for
clinical trials testing new approaches to this disease.
Treatment options under clinical evaluation:
- Clinical trials evaluating new treatment approaches to this disease should also
be considered for these patients. Chemotherapy has been reported to produce
occasional complete responses of long duration.[2-4]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV papillary thyroid cancer and stage IV follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978.
[PUBMED Abstract]
-
Gottlieb JA, Hill CS Jr, Ibanez ML, et al.: Chemotherapy of thyroid cancer. An evaluation of experience with 37 patients. Cancer 30 (3): 848-53, 1972.
[PUBMED Abstract]
-
Harada T, Nishikawa Y, Suzuki T, et al.: Bleomycin treatment for cancer of the thyroid. Am J Surg 122 (1): 53-7, 1971.
[PUBMED Abstract]
-
Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.
[PUBMED Abstract]
Back to Top Medullary Thyroid Cancer
Medullary thyroid cancer (MTC) comprises 3% to 4% of all thyroid cancers.
These tumors usually present as a mass in the neck or thyroid, often associated
with lymphadenopathy,[1] or they may be diagnosed through screening family
members. MTC can also be diagnosed by fine-needle aspiration biopsy. Cytology
typically reveals hypercellular tumors with spindle-shaped cells and poor
adhesion.[2]
The overall survival of patients with MTC is 86% at 5 years and 65% at 10 years. Poor prognostic
factors include advanced age, advanced stage, prior neck surgery, and
associated multiple endocrine neoplasia (MEN) 2B.[2-4]
Approximately 25% of reported cases of MTC are familial.
Familial MTC syndromes include MEN 2A, which is
the most common; MEN 2B; and familial non-MEN syndromes. (Refer to the PDQ summary on Genetics of Medullary Thyroid Cancer for more information.) Any patient with a
familial variant should be screened for other associated endocrine tumors,
particularly parathyroid hyperplasia and pheochromocytoma. MTC can secrete
calcitonin and other peptide substances. Determining the level of calcitonin
is useful for diagnostic purposes and for following the results of treatment.
Family members should be screened for calcitonin elevation and/or for the RET
proto-oncogene mutation to identify other individuals at risk for developing
familial MTC. All patients with MTC (whether familial or sporadic) should be
tested for RET mutations, and if they are positive, family members should
also be tested. Whereas modest elevation of calcitonin may lead to a false-positive diagnosis of medullary carcinoma, DNA testing for the RET mutation is
the optimal approach. Family members who are gene carriers should undergo
prophylactic thyroidectomy at an early age.[5,6]
Treatment options:
-
Thyroidectomy: Patients with medullary thyroid cancer should be treated with a total
thyroidectomy, unless there is evidence of distant metastasis. In patients
with clinically palpable medullary carcinoma of the thyroid, the incidence of
microscopically positive nodes is more than 75%; routine central and bilateral
modified neck dissections have been recommended.[7] When cancer is confined to
the thyroid gland, the prognosis is excellent.
-
External radiation therapy: External radiation therapy has been used for palliation of locally recurrent
tumors, without evidence that it provides any survival advantage.[8] Radioactive iodine has no place in the treatment of patients with MTC.
-
Palliative chemotherapy: Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease.[9-12] No single drug regimen can be
considered standard. Some patients with distant metastases will experience
prolonged survival and can be managed expectantly until they become
symptomatic.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with thyroid gland medullary carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Soh EY, Clark OH: Surgical considerations and approach to thyroid cancer. Endocrinol Metab Clin North Am 25 (1): 115-39, 1996.
[PUBMED Abstract]
-
Giuffrida D, Gharib H: Current diagnosis and management of medullary thyroid carcinoma. Ann Oncol 9 (7): 695-701, 1998.
[PUBMED Abstract]
-
Saad MF, Ordonez NG, Rashid RK, et al.: Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 63 (6): 319-42, 1984.
[PUBMED Abstract]
-
Bergholm U, Bergström R, Ekbom A: Long-term follow-up of patients with medullary carcinoma of the thyroid. Cancer 79 (1): 132-8, 1997.
[PUBMED Abstract]
-
Lips CJ, Landsvater RM, Höppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331 (13): 828-35, 1994.
[PUBMED Abstract]
-
Decker RA, Peacock ML, Borst MJ, et al.: Progress in genetic screening of multiple endocrine neoplasia type 2A: is calcitonin testing obsolete? Surgery 118 (2): 257-63; discussion 263-4, 1995.
[PUBMED Abstract]
-
Moley JF, DeBenedetti MK: Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229 (6): 880-7; discussion 887-8, 1999.
[PUBMED Abstract]
-
Brierley JD, Tsang RW: External radiation therapy in the treatment of thyroid malignancy. Endocrinol Metab Clin North Am 25 (1): 141-57, 1996.
[PUBMED Abstract]
-
Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.
[PUBMED Abstract]
-
De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Invest 14 (6): 475-80, 1991.
[PUBMED Abstract]
-
Wu LT, Averbuch SD, Ball DW, et al.: Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine. Cancer 73 (2): 432-6, 1994.
[PUBMED Abstract]
-
Orlandi F, Caraci P, Berruti A, et al.: Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol 5 (8): 763-5, 1994.
[PUBMED Abstract]
Back to Top Anaplastic Thyroid Cancer
Standard treatment options:
-
Surgery: Tracheostomy is frequently necessary. If the disease is confined to the local area, which is rare, total thyroidectomy is warranted to
reduce symptoms caused by the tumor mass.[1,2]
-
Radiation therapy: External-beam radiation therapy may be used in patients who are not surgical candidates or whose tumor cannot be surgically
excised.
-
Chemotherapy: Anaplastic thyroid cancer is not responsive to I131 therapy;
treatment with individual anticancer drugs has been reported to produce partial
remissions in some patients. Approximately 30% of patients achieve a partial
remission with doxorubicin.[3] The combination of doxorubicin plus cisplatin
appears to be more active than doxorubicin alone and has been reported to
produce more complete responses.[4]
Treatment options under clinical evaluation:
- The combination of chemotherapy plus radiation therapy in patients following complete
resection may provide prolonged survival but has not been compared to any one
modality alone.[5,6]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with anaplastic thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Goldman JM, Goren EN, Cohen MH, et al.: Anaplastic thyroid carcinoma: long-term survival after radical surgery. J Surg Oncol 14 (4): 389-94, 1980.
[PUBMED Abstract]
-
Aldinger KA, Samaan NA, Ibanez M, et al.: Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 41 (6): 2267-75, 1978.
[PUBMED Abstract]
-
Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1502-19.
-
Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.
[PUBMED Abstract]
-
Haigh PI, Ituarte PH, Wu HS, et al.: Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival. Cancer 91 (12): 2335-42, 2001.
[PUBMED Abstract]
-
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 60 (4): 1137-43, 2004.
[PUBMED Abstract]
Back to Top Recurrent Thyroid Cancer
Patients treated for differentiated thyroid cancer should be followed carefully
with physical examinations, serum quantitative thyroglobulin levels, and radiologic studies based
on individual risk for recurrent disease.[1] Approximately 10% to 30% of
patients thought to be disease-free after initial treatment will develop
recurrence and/or metastases. Of these patients, approximately 80% develop recurrence
with disease in the neck alone, and 20% develop recurrence with distant metastases. The most
common site of distant metastasis is the lung. In a single series of 289
patients who developed recurrences after initial surgery, 16% died of cancer at
a median time of 5 years following recurrence.[2]
The prognosis for patients
with clinically detectable recurrences is generally poor, regardless of cell
type.[3] Those patients who recur with local or regional tumor
detected only by I131 scan, however, have a better prognosis.[4] The selection of
further treatment depends on many factors, including cell type, uptake of
I131, prior treatment, site of recurrence, and individual patient
considerations. Surgery with or without I131 ablation can be useful in
controlling local recurrences, regional node metastases, or, occasionally,
metastases at other localized sites.[5] Approximately 50% of the patients
operated on for recurrent tumors can be rendered free of disease with a second
operation.[3] Local and regional recurrences detected by I131 scan and not
clinically apparent can be treated with I131 ablation and have an excellent
prognosis.[6]
Up to 25% of recurrences and metastases from well-differentiated thyroid cancer
may not show I131 uptake. For these patients, other imaging techniques shown
to be of value include imaging with thallium-201, magnetic resonance imaging,
and pentavalent dimercaptosuccinic acid.[7] When recurrent disease does not
concentrate I131, external-beam or intraoperative radiation therapy can be
useful in controlling symptoms related to local tumor recurrences.[8] Systemic
chemotherapy can be considered. Chemotherapy has been reported to produce
occasional objective responses, usually of short duration.[4,9]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Ross DS: Long-term management of differentiated thyroid cancer. Endocrinol Metab Clin North Am 19 (3): 719-39, 1990.
[PUBMED Abstract]
-
Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994.
[PUBMED Abstract]
-
Goretzki PE, Simon D, Frilling A, et al.: Surgical reintervention for differentiated thyroid cancer. Br J Surg 80 (8): 1009-12, 1993.
[PUBMED Abstract]
-
De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Invest 14 (6): 475-80, 1991.
[PUBMED Abstract]
-
Pak H, Gourgiotis L, Chang WI, et al.: Role of metastasectomy in the management of thyroid carcinoma: the NIH experience. J Surg Oncol 82 (1): 10-8, 2003.
[PUBMED Abstract]
-
Coburn M, Teates D, Wanebo HJ: Recurrent thyroid cancer. Role of surgery versus radioactive iodine (I131) Ann Surg 219 (6): 587-93; discussion 593-5, 1994.
[PUBMED Abstract]
-
Mallin WH, Elgazzar AH, Maxon HR 3rd: Imaging modalities in the follow-up of non-iodine avid thyroid carcinoma. Am J Otolaryngol 15 (6): 417-22, 1994 Nov-Dec.
[PUBMED Abstract]
-
Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985.
[PUBMED Abstract]
-
Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.
[PUBMED Abstract]
Back to Top Get More Information From NCI
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Back to Top Changes to This Summary (02/06/2009)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Cellular Classification
Added text about the poorer prognosis assoicated with Hürthle cell carcinoma, a variant of follicular carcinoma (cited Kushchayeva et al. as reference 2).
Stage Information
Added Neff et al. as reference 8.
Back to Top More Information
About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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