eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Thyroid, Follicular Carcinoma

Author: Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Coauthor(s): Silvia Gagliardi, MD, Consulting Staff, Department of Surgery, Medical Center Vita, Italy; Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Contributor Information and Disclosures

Updated: Apr 9, 2009

Introduction

Background

Cancer of the thyroid is the most common endocrine malignancy. Some 5-10% of patients with thyroid cancer will die of their disease. 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, 2-3% of patients with papillary thyroid cancer and 11% of patients with follicular thyroid cancer. 

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. Patents with follicular thyroid cancer are more likely to develop lung and bone metastases than are patients with papillary thyroid cancer. The bone metastases in follicular thyroid cancer are osteolytic. Older patients have an increased risk of developing bone and lung metastases. 

Pathophysiology

Activating point mutations in the ras oncogene are well known in patients with follicular adenoma
and carcinoma,1,2,3 especially in poorly differentiated (55%) and anaplastic carcinoma (52%).

Such mutations determine lock of p21-RAS in the active form leading to the constitutive activation of the protein and tumor development4 by biochemical pathways that may be therapeutic targets for FTC.

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

Frequency

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. During the last few 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. 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 spreading. 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. Sexual predilection of the disease is related to 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.

A useful and updated source for information about the epidemiology of the Follicular Carcinoma of the Thyroid is the American Cancer Society (ACS) website. 

Estimated New  Thyroid Carcinoma Cases and Deaths by Sex, US, 2008 according to the ACS Cancer Facts and Figures 2008

Open table in new window

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Table

 Cases and Deaths

  Total 

  Males

Females

Estimated New Cases


37,340


8,930


28,410

Estimated Deaths  


1,590


680


  910

 Cases and Deaths

  Total 

  Males

Females

Estimated New Cases


37,340


8,930


28,410

Estimated Deaths  


1,590


680


  910

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.

Clinical

History

  • Many cases of FTC are subclinical.
  • The most common presentation of thyroid cancer is an asymptomatic thyroid mass, or a nodule, that can be felt in the neck.
  • Record a thorough medical history to identify any risk factors or symptoms.
    • For any patient with a lump in the thyroid that has appeared recently, focus on obtaining history regarding every prior exposure to ionizing radiation as well as the lifetime and duration of the radiation.
    • Consider family history of thyroid cancer.
  • Some patients have persistent cough, difficulty breathing, or difficulty swallowing.
  • Pain seldom is an early warning sign of thyroid cancer.
  • Other symptoms (eg, pain, stridor, vocal cord paralysis, hemoptysis, rapid enlargement) are rare. These symptoms can be caused by less serious problems.
  • At diagnosis, 10-15% of patients have distant metastases to bone and lung and initially are evaluated for pulmonary or osteoarticular symptoms (eg, pathologic fracture, spontaneous fracture).

Physical

  • Feel the patient's neck to evaluate the size and firmness of the thyroid and to check for any thyroid nodules. The principal sign of thyroid carcinoma is a palpable, firm, and nontender nodule in the thyroid area. This mass is painless.
  • Some patients have a tight or full feeling in the neck, hoarseness, or signs of tracheal or esophageal compression.
  • With thyroid palpation, a usually solitary nodule that has a hard consistency, an average size of less than 5 cm, and ill-defined borders can be felt. This nodule is fixed in respect to surrounding tissues and moves with the trachea at swallowing.
  • Usually, signs of hyperthyroidism or hypothyroidism are not observed.

Causes

  • The thyroid is particularly sensitive to the effects of ionizing radiation. Exposure to ionizing radiation results in a 30% risk for thyroid cancer.
    • A history of exposure of the head and neck to x-ray beams, especially during childhood, has been recognized as an important contributing factor to the development of thyroid cancer.
    • Seven percent of the individuals exposed to the atomic bomb in Japan developed thyroid cancers.
    • Therapeutic irradiation of body areas was used to treat tumors and benign conditions, such as acne, excessive facial hair, tuberculosis in the neck, fungal diseases of the scalp, sore throats, chronic coughs, and enlargement of the thymus, tonsils, and adenoids, from the 1920s to the 1960s. About 10% of these individuals who were treated with irradiation developed thyroid cancer after a latency period of 30 years.
    • Patients who need radiotherapy for certain types of cancer of the head and neck area also may have an increased risk of developing thyroid cancer.
    • Exposure to diagnostic x-rays does not increase the risk of developing thyroid cancer.
  • Although follicular cancer is frequently present in goitrous thyroids, the relationship between prolonged elevation of thyroid-stimulating hormone (TSH) and follicular carcinoma is not known.
  • Several reports have shown a relationship between iodine deficiency and the incidence of thyroid carcinoma.
  • Incidence of FTC has decreased in geographic areas of endemic goiter where the iodination of salt was instituted.
  • Some studies demonstrate that mutations of the ras oncogene could be implicated in the neoplastic transformation of thyrocytes in FTC. n-ras and h-ras mutations (in codon 61) should be the first events in the pathogenesis of FTC, followed by several further mutations (ie, deletions on chromosomes 3q, 11, and 13q).
  • Some molecules that physiologically regulate the growth of the thyrocytes, as interleukins (IL-1 and IL-8) or other cytokines (IGF1, TGF-beta, EGF) could play a role in the pathogenesis of the FTC.
  • More recently, a histochemical study has shown that delta Np73 plays a role predominantly in the early phase of thyroid carcinoma progression. As a consequence, this seems to be a new effective marker to differentiate follicular adenomas and carcinomas of the thyroid.

More on Thyroid, Follicular Carcinoma

Overview: Thyroid, Follicular Carcinoma
Differential Diagnoses & Workup: Thyroid, Follicular Carcinoma
Treatment & Medication: Thyroid, Follicular Carcinoma
Follow-up: Thyroid, Follicular Carcinoma
Multimedia: Thyroid, Follicular Carcinoma
References
Further Reading
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Further Reading

The progress of the knowledge in molecular bases of thyroid cancers offers new therapeutic targets for FTC treatment and, in the future, prevention. A recent, interesting paper on this subject is Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis from MN Nikiforova and YE Nikiforov (Expert Review of Molecular Diagnostics, January 2008, Vol. 8, No. 1, Pages 83-95).

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Keywords

follicular thyroid carcinoma, FTC, thyroid cancer, thyroid cancer treatment, thyroid cancer medications, thyroid cancer diagnosis, thyroid cancer symptoms, thyroid cancer pictures, Hürthle cell carcinoma, Hurthle cell carcinoma, papillary carcinoma, tumor

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Contributor Information and Disclosures

Author

Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Disclosure: Nothing to disclose.

Coauthor(s)

Silvia Gagliardi, MD, Consulting Staff, Department of Surgery, Medical Center Vita, Italy
Disclosure: Nothing to disclose.

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Medical Editor

Philip Schulman, MD, Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Clinical Professor, Department of Medicine, New York University School of Medicine
Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, and Medical Society of the State of New York
Disclosure: celgene Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; genetech/idec Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting

 
 
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