Follicular Thyroid Carcinoma

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Follicular Thyroid Carcinoma

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Follicular thyroid carcinoma (FTC) 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.

FTC and other thyroid neoplasms arising from follicular cells (adenomas, papillary/follicular carcinoma, and noninvasive follicular thyroid neoplasm with papillary-like nuclear features [NIFTP]) show a broad range of overlapping clinical and cytologic features. FTC resembles the normal microscopic pattern of the thyroid, and 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 FTC. Pathological examination showing capsular or vascular invasion may be required for this determination.

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

Despite its well-differentiated characteristics, FTC may be overtly or minimally invasive. In fact, FTC tumors may spread easily to other organs. About 11% of patients with FTC have metastases beyond the cervical or mediastinal area on initial presentation

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]

If all gross disease cannot be resected, or if residual disease is not avid for radioactive iodine, radiation therapy is often employed for locally advanced disease. Similarly, radiation therapy is indicated for unresectable disease extending into adjacent structures. Chemotherapy may be considered in symptomatic patients with recurrent or progressive disease. It could improve quality of life in patients with bone metastases.

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]

United States

The American Cancer Society (ACS) estimates that 53,990 new thyroid cancers will occur in 2018, 13,090 in men and 40,900 in women; the ACS estimates 2060 deaths from thyroid cancer in 2018, 960 in men and 1100 in women. In women, thyroid cancer is the fifth most common cancer, accounting for approximately 5% of all new cases.^[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, the 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.

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.

FTC occurs more frequently in whites than in blacks. The 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]

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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Luigi Santacroce, MD Assistant Professor, Medical School, State University at Bari, Italy