Follicular Thyroid Carcinoma

Updated: Jul 15, 2016
  • Author: Luigi Santacroce, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Overview

Background

Cancer of the thyroid is the most common endocrine malignancy. Thyroid neoplasms arising from follicular cells (adenoma, carcinoma, and follicular/papillary carcinoma) show a broad range of overlapping clinical and cytologic features. A clear distinction between benign and malignant disease based solely on cytological examination of a needle biopsy specimen may be difficult. For this reason, a surgical procedure to remove all or a large portion of the thyroid gland may be necessary to obtain sufficient tissue for a definitive diagnosis of follicular thyroid cancer. Pathological examination showing capsular or vascular invasion may be required for this determination.

Follicular thyroid carcinoma (FTC) is a well-differentiated tumor. In fact, FTC resembles the normal microscopic pattern of the thyroid. FTC originates in follicular cells and is the second most common cancer of the thyroid, after papillary carcinoma. Follicular and papillary thyroid cancers are considered to be differentiated thyroid cancers; together they make up 95% of thyroid cancer cases.

Papillary/follicular carcinoma must be considered a variant of papillary thyroid carcinoma (mixed form), and Hurthle cell carcinoma should be considered a variant of FTC.

Thyroid cancers are found more often in patients with a history of low-dose or high-dose external irradiation to the cervical or thyroid area. The most common thyroid tumor to develop after exposure to radiation is papillary thyroid cancer. Patients whose thyroid cancer has developed following radiation to the head and neck area may present with more extensive disease. Overall, about 5% of patients with thyroid cancer have metastases beyond the cervical or mediastinal area on initial presentation, as do 2-3% of patients with papillary thyroid cancer and 11% of patients with follicular thyroid cancer. Some 5-10% of patients with thyroid cancer will die of their disease.

Despite its well-differentiated characteristics, follicular carcinoma may be overtly or minimally invasive. In fact, FTC tumors may spread easily to other organs. Life expectancy of affected patients is related to their age; the prognosis is better for younger patients than for patients who are older than 45 years. Patients with FTC are more likely to develop lung and bone metastases than are patients with papillary thyroid cancer. The bone metastases in FTC are osteolytic. Older patients have an increased risk of developing bone and lung metastases.

Current National Comprehensive Cancer Network (NCCN) guidelines recommend lobectomy plus isthmusectomy as the initial surgery for patients with follicular neoplasms, with prompt completion of thyroidectomy if invasive FTC is found on the final histologic section. The NCCN recommends total thyroidectomy as the initial procedure only if invasive cancer or metastatic disease is apparent at the time of surgery, or if the patient wishes to avoid a second, completion thyroidectomy should the pathologic review reveal cancer. [1]

In a study by Asari et al of 207 patients with FTC, the 127 patients with minimally invasive growth had no lymph node metastases. According to the authors, total thyroidectomy is recommended for all patients with FTC, but patients with widely invasive FTC need more aggressive surgery because of a higher tendency toward lymph node metastases. Patients with minimally invasive disease have an excellent prognosis with a limited need for nodal surgery, according to this study. [2]

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Pathophysiology

Activating point mutations in the ras oncogene are well known in patients with follicular adenoma and carcinoma, [3, 4, 5] especially in poorly differentiated (55%) and anaplastic carcinoma (52%).

As a result of such mutations, p21-RAS becomes locked in its active conformation, leading to the constitutive activation of the protein and tumor development. [6] The biochemical pathways that this process follows may be therapeutic targets for FTC. [7]

Accidental (not diagnostic) x-ray exposure may influence both occurrence and pattern of ras mutation.

A study of differential gene expression profiling of aggressive and nonaggressive follicular carcinomas identified 94 genes that distinguish follicular carcinomas from follicular adenomas (including PBP and CKS2) and 4 genes that distinguish aggressive follicular carcinomas from nonaggressive follicular carcinomas (NID2, TM7SF2, TRIM2, and GLTSCR2). [8]

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Epidemiology

Frequency

United States

The American Cancer Society (ACS) estimates that 64,300 new thyroid cancers will occur in 2016, 14,950 in men and 49,350 in women; the ACS estimates 1980 deaths from thyroid cancer in 2016, 910 in men and 1070 in women. [9] In the United States, about 10-15% of all thyroid cancers are follicular.

International

Thyroid cancers are quite rare, accounting for only 1.5% of all cancers in adults and 3% in children. The highest incidence of thyroid carcinomas in the world is among female Chinese residents of Hawaii. In Hawaii, incidence of FTC ranges from 10-30 new cases a year per million inhabitants. In recent years, the frequency of FTC has appeared to increase; however, this increase is related to improvement in diagnostic techniques and a successful campaign of information about this carcinoma.

Of all thyroid cancers, 17-20% are follicular. According to world epidemiologic data, follicular carcinoma is the second most common thyroid neoplasm; in some geographic areas, however, FTC is the most common thyroid tumor. The relative incidence of follicular carcinoma is higher in areas of endemic goiter.

Mortality/Morbidity

In contrast to other cancers, thyroid cancer is almost always curable. In fact, most FTCs are slow growing and are associated with a very favorable prognosis. Mean mortality rates are 1.5% in females and 1.4% in males.

Mean survival rate after 10 years is 60%. Metastases are still rare and are due to angioinvasion and hematogenous spread. Lymphatic involvement is even more rare, occurring in fewer than 10% of cases. In some patients, metastases are found at diagnosis.

Autopsy reviews show a high incidence of microscopic foci of thyroid carcinoma worldwide.

Unlike medullary thyroid carcinoma, FTC is not part of a multiple endocrine neoplasia (MEN) syndrome.

Race

FTC occurs more frequently in whites than in blacks.

Sex

Incidence is higher in women than men by a factor of 2-3 or more. The ratio varies by patient age:

  • In patients younger than 19 years, the female-to-male ratio is 4:1
  • In patients aged 20-45 years, the female-to-male ratio is 3:1
  • In patients older than 45 years, the female-to-male ratio is 4:1

In postmenopausal women, a weak positive association (relative risk < 1.20) has been found between increased body mass index and thyroid cancer. [10]

Age

Thyroid carcinoma is common in all age groups, with an age range of 15-84 years (mean age, 49 years). In older adults, FTC tends to occur more frequently than papillary carcinoma.

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