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Thyroid Cancer Treatment (PDQ®)

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Stage Information for Thyroid Cancer

Definitions of TNM
Papillary and Follicular Thyroid Cancer
Medullary Thyroid Cancer
Anaplastic Thyroid Cancer



Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define thyroid cancer.[1]

Table 1. Primary Tumor (T)a,b
TXPrimary tumor cannot be assessed.
T0No evidence of primary tumor.
T1Tumor ≤2 cm in greatest dimension limited to the thyroid.
T1aTumor ≤1 cm, limited to the thyroid.
T1bTumor >1 cm but ≤2 cm in greatest dimension, limited to the thyroid.
T2Tumor >2 cm but ≤4 cm in greatest dimension, limited to the thyroid.
T3Tumor >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).
T4aModerately advanced disease.
Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve.
T4bVery advanced disease.
Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels.
cT4aIntrathyroidal anaplastic carcinoma.
cT4bAnaplastic carcinoma with gross extrathyroid extension.

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.
bAll categories may be subdivided: (s) solitary tumor and (m) multifocal tumor (the largest determines the classification).
cAll anaplastic carcinomas are considered T4 tumors.

Table 2. Regional Lymph Nodes (N)a,b
NXRegional lymph nodes cannot be assessed.
N0No regional lymph node metastasis.
N1Regional lymph node metastasis.
N1aMetastases to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes).
N1bMetastases to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII).

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.
bRegional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes.

Table 3. Distant Metastasis (M)a
aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.
M0No distant metastasis.
M1Distant metastasis.

Table 4. Anatomic Stage/Prognostic Groupsa,b
Stage T N M 
Papillary or follicular (differentiated)
YOUNGER THAN 45 YEARS
IAny TAny NM0
IIAny TAny NM1
45 YEARS AND OLDER
IT1N0M0
IIT2N0M0
IIIT3N0M0
T1N1aM0
T2N1aM0
T3N1aM0
IVAT4aN0M0
T4aN1aM0
T1N1bM0
T2N1bM0
T3N1bM0
T4aN1bM0
IVBT4bAny NM0
Stage IVCAny TAny NM1
Medullary carcinoma (all age groups)
IT1N0M0
IIT2N0M0
T3N0M0
IIIT1N1aM0
T1N1aM0
T2N1aM0
T3N1aM0
IVAT4aN0M0
T4aN1aM0
T1N1bM0
T2N1bM0
T3N1bM0
T4aN1bM0
Stage IVBT4bAny N
IVBT4bAny NM0
IVCAny TAny NM1
Anaplastic carcinoma c
IVAT4aAny NM0
IVBT4bAny NM0
IVCAny TAny NM1

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.
bSeparate stage groupings are recommended for papillary or follicular (differentiated), medullary, and anaplastic (undifferentiated) carcinoma.
cAll 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 45 years than for patients older than 45 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 with no metastases or larger than 4 cm with minimal extrathyroid extension.

Stage III medullary thyroid cancer

Tumor of any size 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 the following categories:

  • Stage IVA (moderately advanced with or without lymph node metastases [for T4a] but without distant metastases).

  • Stage IVB (very advanced 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
  1. Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96. 

  2. 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]

  3. Colson YL, Carty SE: Medullary thyroid carcinoma. Am J Otolaryngol 14 (2): 73-81, 1993 Mar-Apr.  [PUBMED Abstract]

  4. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72. 

  5. 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]

  6. 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]

  7. 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]

  8. Neff RL, Farrar WB, Kloos RT, et al.: Anaplastic thyroid cancer. Endocrinol Metab Clin North Am 37 (2): 525-38, xi, 2008.  [PUBMED Abstract]