Papillary thyroid cancer

Papillary thyroid cancer

Papillary thyroid carcinoma.
Classification and external resources
Specialty oncology
ICD-10 C73
ICD-9-CM 193
ICD-O M8260/3
OMIM 603744
MedlinePlus 000331
eMedicine med/2464
MeSH D013964

Papillary thyroid cancer or papillary thyroid carcinoma[1] is the most common type of thyroid cancer,[2] representing 75 percent to 85 percent of all thyroid cancer cases.[1] It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck.[3] It is often well-differentiated, slow-growing, and localized, although it can metastasize.

Diagnosis

Papillary thyroid carcinoma is usually discovered on routine examination as an asymptomatic thyroid nodule that appears as a neck mass. In some instances, the mass may have produced local symptoms. This mass is normally referred to a fine needle aspiration biopsy (FNA) for investigation. FNA accuracy is very high and it is a process widely used in these cases. Other investigation methods include ultrasound imaging and nuclear scan. The ultrasound is a useful test to distinguish solid from cystic lesions and to identify calcifications.[4] The thyroid ultrasound is also very effective to discover microcarcinomas, which refer to very small carcinomas (<1 cm).

Papillary thyroid carcinomas are also discovered when a hard nodule is found in multinodular goiter, when enlarged cervical lymph nodes are detected, or when there are unidentified metastatic lesions elsewhere in the body.[5] Expanding lesions found in the thyroid gland, especially if they are painful, should be examined as they may indicate the presence of papillary thyroid carcinoma. Other clinical signs that could indicate papillary thyroid are: fixation to the trachea, a firm neck mass, damage to recurrent laryngeal or cervical sympathetic nerves. Fifty percent of the population can have thyroid nodules, and the majority will be benign.[6]

Appropriate workup includes an ultrasound of the neck, followed by lab studies. Patients will usually meet with both an endocrinologist and a surgeon (head and neck surgeon or endocrine surgeon).


Markers

Thyroglobulin can be used as a tumor marker for well-differentiated papillary thyroid cancer.[7][8] HBME-1 staining may be useful for differentiating papillary carcinomas from follicular carcinomas; in papillary lesions it tends to be positive.[9]

Reduced expression of ATP5E is significantly associated with the diagnosis of papillary thyroid cancer and may serve as an early tumor marker of the disease.[10]

Pathology

Papillary thyroid cancer gets its name from the papillae among its cells, visible on microscopy. Features include:

Several variants are recognized, although classical papillary thyroid carcinoma is the most frequent; microscopic, follicular variant, diffuse sclerosing variant, tall cell variant, columnar cell variant, hobnail variant, among others. The encapsulated follicular variant, specifically when noninvasive, has been newly reclassified as the noninvasive follicular thyroid neoplasm with papillary-like nuclear features.[18]

Although papillary carcinoma has a propensity to invade lymphatics, it is less likely to invade blood vessels.[19] These kinds of tumors are most commonly unencapsulated, and they have a high tendency to metastasize locally to lymph nodes, which may produce cystic structures near the thyroid that are difficult to diagnose because of the paucity of malignant tissue.[5][20] Furthermore, papillary tumors may metastasize to the lungs and produce a few nodules or the lung fields may exhibit a snowflake appearance throughout.

Other characteristics of the papillary carcinoma is that E.M. shows increased mitochondria, increased RER, as well as increased apical microvilli. Moreover, papillary carcinomas have an indolent growth, and 40 percent of cases spread out of the capsule.[21]

Associated mutations

Mutations associated with papillary thyroid cancer are mainly two forms of chromosomal translocation and one form of point mutation. These alterations lead to activation of a common carcinogenic pathway—the MAPK/ERK pathway.

Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase receptor that plays essential roles in the development of neuroendocrine cells) located on chromosome 10q11 occur in approximately a fifth of papillary thyroid cancers. The fusion oncoproteins generated are termed RET/PTC proteins (ret/papillary thyroid carcinoma), and constitutively activate RET and the downstream MAPK/ERK pathway.[1] The frequency of ret/PTC translocations is significantly higher in papillary cancers arising in children and after radiation exposure.[1] The gene NTRK1 (encoding the TrkA receptor), located on chromosome 1q, is similarly translocated in approximately 5 percent to 10 percent of papillary thyroid cancers.[1]

Approximately a third to a half of papillary thyroid carcinomas harbor point mutations in the BRAF oncogene, also activating the MAPK/ERK pathway.[1] In those cases the BRAF mutations found were V600E mutation. After performing a multivariate analysis, it was found that the absence of tumor capsule was the only parameter associated (P=0.0005) with BRAF V600E mutation.[5] According to recent studies, papillary cancers carrying the common V600E mutation tend to have a more aggressive long term course. BRAF mutations are frequent in papillary carcinoma and in undifferentiated cancers that have developed from papillary tumors.

Prognosis

Depending on source, the overall 5-year survival rate for papillary thyroid cancer is 96 percent[22] or 97 percent,[23] with a 10-year survival rate of 93 percent.[22]

For a more specific prognosis for individual cases, there are at minimum 13 known scoring systems for prognosis; among the more often used are:

MACIS

The MACIS system of estimating the prognosis of papillary thyroid cancer was developed by Clive S. Grant at the Mayo Clinic, and was based on careful evaluation of a large group of patients. It is probably the most reliable staging method available.[25]

It assigns scores to the main factors involved, and uses the sum of this score to calculate the prognosis:

Factors[25] Score[25]
Distant Metastasis: spread of the cancer to areas outside the neck Yes 3
No 0
Age at the time the tumor was discovered Less than 39 years 3.1
Over 40 years 0.08 x age
Invasion into surrounding areas of the neck as seen by the naked eye Yes 1
No 0
Completeness of surgical resection (or removal) of the tumor Incomplete 1
Complete 0
Size of the tumor 0.3 x size in cm
Sum of MACIS score[25] 20 yr Survival[25]
< 6.0 99%
6.0 - 6.99 89%
7.0 - 7.99 56%
> 8.0 24%

Most patients fall into the low risk category (MACIS score less than 6.0) and are cured of the cancer at the time of surgery.[25]

Children with multiple lung metastases and/or a miliary aspect still have an excellent long-term prognosis if given adequate treatment.[26]

Stage

Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.[27]

Treatment

Surgery remains the mainstay of treatment for papillary thyroid cancer. The Revised 2009 American Thyroid Association guidelines for papillary thyroid cancer state that the initial procedure should be near-total or total thyroidectomy. Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastasis.[28]

Arguments for total thyroidectomy are:[29]

Arguments for hemithyroidectomy:

Thyroid total body scans are less reliable at finding recurrence than TG and ultrasound.

Papillary tumors tend to be more aggressive in patients over age 45. In such cases it might be required to perform a more extensive resection including portions of the trachea. Also, the sternocleidomastoid muscle, jugular vein, and accessory nerve are to be removed if such procedure allows apparently complete tumor resection. If a significant amount of residual tumor is left in the neck, external radiotherapy has been indicated and has proven useful especially in those cases when residual tumor does not take up radioiodine.

After surgical thyroid removal, the patient waits around 4–6 weeks to then have radioiodine therapy. This therapy is intended to both detect and destroy any metastasis and residual tissue in the thyroid. The treatment may be repeated 6–12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.[30]

Patients are administered hormone replacement levothyroxine for life after surgery, especially after total thyroidectomy. Chemotherapy with cisplatin or doxorubicin has proven limited efficacy, however, it could be helpful for patients with bone metastases to improve their quality of life. Patients are also prescribed levothyroxine and radioiodine after surgery. Levothyroxine influences growth and maturation of tissues and it is involved in normal growth, metabolism, and development. In case of metastases, patients are prescribed antineoplastic agents which inhibit cell growth and proliferation and help in palliating symptoms in progressive disease.

After successful treatment, 35 percent of the patients may experience recurrence within a 40-year span. Also, patients may experience a high incidence of nodule metastasis, with 35 percent cases of cervical node metastases. Approximately 20 percent of patients will develop multiple tumors within the thyroid gland.[31]

There is ongoing discussion regarding the best management regarding the optimal surgical procedure for papillary thyroid cancer. Prognosis of patients with papillary thyroid cancer is found to be dependent on the patient's age, size of the tumor, presence of metastatic disease, and presence of tumor invasion into adjacent tissues near the thyroid gland. Recent studies have examined a more conservative approach to surgery and have demonstrated that hemithyroidectomy may be acceptable for patients with low-risk papillary thyroid cancer with tumor size 1 cm to 4 cm with no presence of invasion to tissues surrounding the thyroid or metastasis. Studies examining large databases of patients with papillary thyroid cancer have concluded that there is no survival advantage for patients with stage I papillary thyroid cancer size 1–4 cm receiving total thyroidectomy versus hemithyroidectomy.[32] In light of this data, choosing the optimal course of surgical and medical management of papillary thyroid cancer should involve shared decision making from patient, endocrinologists, and surgeons.

References

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Endocrine gland

External links

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