Stage Information
TNM Definitions
AJCC Stage Groupings
Papillary and Follicular Thyroid Cancer
Medullary Thyroid Cancer
Anaplastic Thyroid Cancer
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
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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]
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Colson YL, Carty SE: Medullary thyroid carcinoma. Am J Otolaryngol 14 (2): 73-81, 1993 Mar-Apr.
[PUBMED Abstract]
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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.
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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]
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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]
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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]
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Neff RL, Farrar WB, Kloos RT, et al.: Anaplastic thyroid cancer. Endocrinol Metab Clin North Am 37 (2): 525-38, xi, 2008.
[PUBMED Abstract]
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