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Follicular Thyroid Carcinoma

FNMTC

Follicular thyroid cancer is the second most common type of thyroid carcinoma. Although this tumor is well differentiated, it grows invasively and tends to form metastases.


Presentation

Local mass effects are the most frequent complications of FTC, since these tumors generally don't produce thyroid hormones. Consequently, patients present with an asymmetric, palpable mass below the larynx. Due to its close proximity to the latter, patients may be hoarse or dysphonic. They may also claim difficulties while ingesting solid food, less often while swallowing water. Dysphagia may be accompanied by dyspnea. If the tumor exerts pressure on the recurrent laryngeal nerve, the aforementioned symptoms tend to aggravate and the affected person may claim cough. FTC are usually not painful and grow slowly.

Anamnesis and physical examination should address the following issues:

  • A possible familial history of thyroid cancer. As has been stated above, first-degree relatives of people diagnosed with this disease have higher risks of developing such a tumor themselves.
  • Dietary habits. It should be evaluated whether a patient may suffer from iodine deficiency. If indicated, urinary iodine excretion needs to be assessed.
  • Radiation exposure. Patients should be queried for possible radiation exposure at any point in their lifes since latency periods may span decades.
  • Consistency and tenderness of the cervical mass. Thyroid carcinoma are usually firm. Pressure pain is uncommon.
  • Abnormal findings in regional lymph nodes. PTC and MTC tend to spread via lymphatic vessels; FTC rather metastasize hematogenously into internal organs. However, lymph node involvement does not rule out FTC.

FTC patients may present metastases at the time of initial presentation. In some cases, symptoms triggered by functional impairment of lung, liver or bones may dominate the clinical picture. In this context, intolerance to exercise, upper abdominal pain, jaundice and pathologic fractures may be registered.

Cervical Lymphadenopathy
  • Common modes of presentation of follicular thyroid carcinoma include a solitary thyroid nodule and cervical lymphadenopathy. We report four patients who presented with axial skeletal metastases rather than the usual neck lumps.[ncbi.nlm.nih.gov]
  • There were no cervical lymphadenopathy or neck masses.[jpmsonline.com]
  • Particularly, the presence of cervical lymphadenopathy is an indirect sign of carcinoma in US diagnosis ( 23 ). Metastasis is often the initial symptom of FC, since patients usually remain asymptomatic in regards to thyroid function ( 1 ).[ncbi.nlm.nih.gov]
  • Palpable cervical lymphadenopathy. Insidious or persistent pain lasting for several weeks. Investigations [ 2 ] TFTs should be performed for any patient with a thyroid nodule.[patient.info]
Stridor
  • 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 may have distant[thyroid.com.au]
  • Any patient with a thyroid lump and associated stridor should be referred for same day review by a secondary care specialist, as this may be due to recurrent laryngeal nerve involvement secondary to a thyroid carcinoma.[patient.info]
Tracheal Deviation
  • He had a tracheal deviation to the left. (a,b) Photographs of the 58-year-old man with metastatic follicular thyroid carcinoma showing multiple scalp and facial masses.[ncbi.nlm.nih.gov]
Malignant Pleural Effusion
  • Malignant pleural effusion (MPE) caused by metastatic differentiated thyroid carcinoma (DTC) is usually associated with a rapid fatal outcome and should be recognized as a grim prognostic indicator.[ncbi.nlm.nih.gov]
Thyroid Nodule
  • Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed.[ncbi.nlm.nih.gov]
  • Few reports have been concerned with the risk of needle track dissemination of tumor cells following fine-needle aspiration biopsy, especially for follicular thyroid nodules.[ncbi.nlm.nih.gov]
  • Although it typically presents as a thyroid nodule, it can spread to distant sites via hematogenous dissemination. Spinal cord compression complicating thyroid carcinoma is rare with only few cases reported in the literature.[ncbi.nlm.nih.gov]
  • There is a large thyroid nodule in the right thyroid gland, which had intense PSMA accumulation. Follicular thyroid lesions can be seen on (68)Ga-PSMA PET/CT imaging.[ncbi.nlm.nih.gov]
  • Although it typically presents as a thyroid nodule, it can spread to distant sites via hematogenous dissemination.[ncbi.nlm.nih.gov]
Goiter
  • Both goiter and thrombus were completely replaced by follicular carcinoma.[ncbi.nlm.nih.gov]
  • A 14.6 year-old girl was diagnosed with nodular goiter, subclinical hypothyroidism and severe iodine deficiency. She had a very high hTG level.[ncbi.nlm.nih.gov]
  • In this report, we describe the case of a 50-year-old Caucasian woman with a normal thyroid-stimulating hormone level who underwent surgery to treat a multi-nodular goiter. The pathology was a clear cell variant of follicular thyroid carcinoma.[ncbi.nlm.nih.gov]
  • We describe a patient with persistent hyperthyroidism after total thyroidectomy for toxic multinodular goiter and without therapy with levothyroxine evaluated with I-131 whole-body scan and with F-18 FDG PET/CT scan.[ncbi.nlm.nih.gov]
  • The patient had undergone partial thyroidectomy for nodular goiter in 1969. Biopsy of skeletal metastases in 1982 confirmed that the primary was follicular thyroid carcinoma.[ncbi.nlm.nih.gov]
Collapse
  • Computerized tomography and bronchoscopy suggested an endobronchial enhancing nodule in the right bronchus intermedius, resulting in right middle lobe (RML) and right lower lobe (RLL) collapse.[ncbi.nlm.nih.gov]
  • Chest computed tomography showed right lung multiple nodules, left pleural effusion, and left lung collapse with left-sided pleural thickening. We treated him with sorafenib. Clinical and radiographic assessments were performed periodically.[ncbi.nlm.nih.gov]
  • Patients with vertebral body metastases and neurologic symptoms from vertebral collapse or tumor compression are candidates for spine stabilization with tumor resection or percutaneous vertebroplasty [ 64 ].[ncbi.nlm.nih.gov]
Arm Pain
  • We report and discuss a unique case of a 70-year-old female patient presenting with arm pain, diagnosed with metastatic well-differentiated follicular carcinoma without a primary tumor in the thyroid.[ncbi.nlm.nih.gov]
Neck Mass
  • There were no cervical lymphadenopathy or neck masses.[jpmsonline.com]
  • Discussion Thyroid cancers account for about 0.5 % of all cancers in men and 1.5 % of all cancers in women. 7 In Pakistan, thyroid cancer is responsible for about 1.2 % cases of all malignant tumours, with patients usually presenting with neck mass. 8,9[jpma.org.pk]
  • Critical Essential Core Tested Community Questions (3) (M1.ON.4754) A 43-year-old female presents to her primary care physician complaining of a gradually enlarging neck mass.[step1.medbullets.com]
  • Before she discovered this oval-shaped tumor on her left scalp, there were no symptomatic signs, such as headache, pain, neck mass or chronic cough. Clinically, the scalp tumor measured about 3.8   1.0 cm with sharp margins and was movable.[edm.bioscientifica.com]
Incontinence
  • This report describes a 53 years old patient with follicular thyroid carcinoma who presented with paraplegia and urinary incontinence. Magnetic resonance imaging (MRI) of neck revealed a mass with destruction of C5 and extension to C6.[ncbi.nlm.nih.gov]
  • This report describes a 35-years-old female patient presenting with paraplegia and urinary incontinence for the last two months. She had no thyroid enlargement; no thyroid related symptoms and her biochemical thyroid profile was normal.[ruralneuropractice.com]

Workup

Workup should aim at tumor staging and grading. Precise localization and size of the primary tumor can be evaluated sonographically. In general, FTC are solitary tumors that don't invade the capsule of thyroid lobes. In order to detect metastases, patients may be submitted to scintigraphic examination. Because this technique is based on enrichment of thyroid-like tissue with radio-labeled iodine, its sensitivity is rather low in case of carcinomas that don't produce thyroid hormones. Here, magnetic resonance imaging or computed tomography scans are indicated [9]. About 10% of FTC patients present metastases at the time of first diagnosis.

Histopathological analysis of tissue samples is required to determine whether a thyroid tumor is benign or malignant, if it is indeed an FTC, and if the latter grows minimally or widely invasive. Although examination of fine needle aspirates may yield important information to this end - nuclear morphology, for instance, may reveal PTC - more extensive tissue samples are often required for a precise diagnosis and prognosis. As has been indicated above, differentiation between minimally or widely invasive growth of FTC may be particularly complicated. Therefore, surgical removal of neoplastic tissue is sometimes applied as a therapeutic and diagnostic measure, since conclusive results can much more easily be provided upon analysis of resected tissue.

Furthermore, serum concentrations of thyroid stimulating hormone (TSH), thyroglobulin, thyroxine (T4) and triiodothyronine (T3) should be measured. Hormone-producing thyroid cancer is associated with increased levels of thyroglobulin, T4 and T3, but concentrations of TSH are reduced due to autonomous activity. The latter may be confirmed by TSH suppression tests, but false-negative results are likely. A significant share of hormone-producing thyroid carcinomas does respond to TSH suppression. It has to be noted that these are not exclusion criteria for FTC, since this type of carcinoma most often does not produce thyroid hormones.

Evaluation of calcitonin and calcium levels is recommended and is particularly useful to differentiate FTC and MTC.

Left Pleural Effusion
  • Chest computed tomography showed right lung multiple nodules, left pleural effusion, and left lung collapse with left-sided pleural thickening. We treated him with sorafenib. Clinical and radiographic assessments were performed periodically.[ncbi.nlm.nih.gov]

Treatment

Surgical resection is the treatment of choice, but recommendations regarding the extent of tissue removal vary.

Some experts advise to limit surgery to lobectomy and isthmusectomy, unless widely invasive FTC has been diagnosed previously [10]. Due to the aforementioned limitations of histopathological analysis of fine needle aspirates, this is rarely the case. Here, determination of the subtype of FTC is realized after surgery and only if a high degree of invasiveness is detected will the remaining part of the thyroid gland be removed. On the other hand, total thyroidectomy may be indicated for all patients diagnosed with FTC [11]. This approach is justified by the fact that the majority of FTC patients do indeed suffer from widely invasive FTC and that this type of thyroid carcinoma is likely to metastasize early.

In any case, total thyroidectomy should be realized if the primary tumor measures more than 1 cm in diameter, if both lobes are affected, if invasive growth has been confirmed, if any metastasis has been detected, and if the patient is older than 40 years. Neck dissection and removal of lymph nodes as well as additional surgical procedures to resect metastases in internal organs may become necessary in such cases, too.

Post-surgical substitution of thyroid hormones is required.

Subsequently, patients should undergo radioactive iodine therapy to destroy possibly remaining tumor cells in the thyroid gland and in metastasis.

Prognosis

Prognosis of FTC is guarded since the disease is related to a mortality of 10-15%. Unfavorable prognostic factors are age over 45 years, size of the primary tumor over 2.5 cm in diameter, widely invasive FTC and histopathological anomalies as well as presence of metastases at the time of diagnosis [8].

Etiology

The etiology of FTC is only partially understood. And although a variety of risk factors for thyroid cancer have been identified, most of them are primarily associated with PTC. Of course, it has to be assumed that both types of differentiated thyroid carcinoma share some causative factors. Little is known about specific triggers of FTC, though.

  • FTC is generally related to iodine deficiency. In iodine-replete regions, the ratio between PTC and FTC is significantly higher than in iodine-deficient areas. In many countries, FTC incidence could be diminished by introducing iodized salt. Moreover, regional incidence of FTC has been proposed as an indicator of iodine deficiency prevalence [3].
  • In general, exposure to radiation is considered a high risk factor for thyroid cancer. Incidence rates among people who survived the atomic bombings of Hiroshima and Nagasaki in Japan or the nuclear accident of Chernobyl, Ukraine, are very high. However, most tumors diagnosed in these patients correspond to PTC. It has been proposed that the age at exposure plays an important role in development of certain tumor types [4]. Still, radiation of the neck does augment the risk for thyroid carcinoma and most likely, this also applies to FTC.
  • Incidence of thyroid carcinoma is augmented among overweight and obese people [5]. While the former only have a marginally increased risk for this type of cancer, findings regarding obese patients clearly indicate a correlation between body weight and likelihood of thyroid neoplasms.
  • The results of several studies regarding the risk of PTC or FTC in first-degree relatives of patients who have already been diagnosed with these diseases imply a genetic component in thyroid cancer etiology [6].

Epidemiology

In general, thyroid cancer is a rare disease. However, malignancies of the thyroid gland are the most common type of cancer that affects endocrine glands. Its annual incidence doesn't exceed 3 per 100,000 inhabitants, whereby less than 1 per 100,000 people are diagnosed with FTC. Retrospective analyses have shown a reduction of FTC incidence due to less frequent iodine deficiency, followed by a renewed increase of case numbers. The latter is generally ascribed to improved diagnostics.

Women are diagnosed with FTC up to four times more often than men.

FTC may develop at any age.

Sex distribution
Age distribution

Pathophysiology

FTC usually develop as solitary tumors that cause local mass effects but that most often don't produce thyroid hormones. And while the thyroid gland consists of two connected lobes, both of which are surrounded by capsules consisting of taut connective tissue, most FTC are restricted to a single lobe and don't invade the capsule. FTC may be delimited by a pseudocapsule, but may still invade blood or lymphatic vessels. Thus, minimally invasive FTC and widely invasive FTC should be distinguished histopathologically, whereby the latter is more frequently observed. Unfortunately, even though the outcome may depend on invasiveness, clear diagnostic criteria for either type of FTC are not available [7].

Prevention

According to the above described risk factors for FTC, the following measures may diminish the individual risk to develop this disease:

  • Usage of iodized salt to assure an adequate supply with iodine
  • Avoidance of radiation
  • Maintenance of a healthy body weight
  • Regular check-ups in patients who have a first-degree relative that was diagnosed with FTC

Summary

Thyroid cancer is a rather common type of malignant neoplasia, but benign tumors of the thyroid gland are more often observed.

Thyroid neoplasms may originate from distinct cell types, form well-demarcated tumors or grow invasively, and are thus associated with different outcomes. Generally, the following types of thyroid carcinoma are distinguished [1]:

  • Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. About two out of three thyroid malignancies correspond to this type of cancer. Uncontrolled proliferation of thyroid follicular epithelial cells gives rise to this neoplasm, which usually metastasizes into regional lymph nodes.
  • Follicular thyroid carcinoma (FTC) accounts for approximately 20% of thyroid malignancies. Just as PTC, this type of tumor derives from thyroid follicular epithelium and is well differentiated. However, PTC and FTC differ histopathologically as well as clinically. Here, hematogenous metastatic spread is much more common and thus, secondary tumors form in lung, liver or bones instead of lymph nodes. Of note, a mixed follicular-papillary thyroid carcinoma has been described [2].
  • Medullary thyroid carcinoma (MTC) is diagnosed in a minor share of patients suffering from thyroid cancer. Contrary to PTC and FTC, MTC originates from calcitonin-producing thyroid cells (C cells). Tumor cells continue to secrete hormones and this fact is very helpful in diagnosing MTC. Both lymphogenic and hematogenous metastases are observed.
  • Other types of thyroid cancer, e.g., anaplastic thyroid carcinoma or metastases of primary tumors located in other organs, are as rare as MTC.

Patient Information

The thyroid gland is located in the neck, below the larynx. It consists of two lobes that are connected by an isthmus. Thyroid tumors usually manifest in form of a palpable, firm, painless mass. Most of these tumors are benign, but malignant degeneration of thyroid cells may also occur. Dependent on the precise origin of such a malignant tumor, several types of thyroid cancer are distinguished. Follicular thyroid carcinoma (FTC) is the second most common one, with papillary thyroid carcinoma being the only type of thyroid cancer that is more frequently diagnosed.

Although FTC are generally well differentiated, they may grow invasively and form metastases in distant organs, namely in lung, liver and bones. An early diagnosis facilitates treatment and reduces the likelihood of metastatic spread. Thus, any mass suspicious of thyroid cancer should be thoroughly examined. Patients who suffer from thyroid cancer like FTC often claim difficulties while swallowing and breathing. Hoarseness and persistent cough may also be noted.

Diagnostic imaging techniques such as sonography and scintigraphy, in some cases also magnetic resonance imaging or computed tomography should be applied to assess localization and size of the primary tumor and to revise the whole body for possible metastases.

According to the results of these test, therapy will be planned: Thyroid cancer requires surgical removal of degenerated tissue. In order to avoid recurrence, the whole thyroid gland is removed in many cases. If metastases have been detected, further surgical interventions may become necessary.

Patients who underwent thyroidectomy need to replace thyroid hormones by medication.

References

Article

  1. Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin. 2013; 63(6):374-394.
  2. Hanna AN, Michael CW, Jing X. Mixed medullary-follicular carcinoma of the thyroid: diagnostic dilemmas in fine-needle aspiration cytology. Diagn Cytopathol. 2011; 39(11):862-865.
  3. Kalk WJ, Sitas F, Patterson AC. Thyroid cancer in South Africa--an indicator of regional iodine deficiency. S Afr Med J. 1997; 87(6):735-738.
  4. Williams ED, Abrosimov A, Bogdanova T, et al. Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness. Br J Cancer. 2004; 90(11):2219-2224.
  5. Schmid D, Ricci C, Behrens G, Leitzmann MF. Adiposity and risk of thyroid cancer: a systematic review and meta-analysis. Obes Rev. 2015; 16(12):1042-1054.
  6. Handkiewcz-Junak D, Banasik T, Kolosza Z, et al. Risk of malignant tumors in first-degree relatives of patients with differentiated thyroid cancer -- a hospital based study. Neoplasma. 2006; 53(1):67-72.
  7. Ban EJ, Andrabi A, Grodski S, Yeung M, McLean C, Serpell J. Follicular thyroid cancer: minimally invasive tumours can give rise to metastases. ANZ J Surg. 2012; 82(3):136-139.
  8. DeGroot LJ, Kaplan EL, Shukla MS, Salti G, Straus FH. Morbidity and mortality in follicular thyroid cancer. J Clin Endocrinol Metab. 1995; 80(10):2946-2953.
  9. Summaria V, Rufini V, Mirk P, Costantini AM, Reale F, Maresca G. Diagnostic imaging of differentiated thyroid carcinoma. Rays. 2000; 25(2):177-190.
  10. Goffredo P, Cheung K, Roman SA, Sosa JA. Can minimally invasive follicular thyroid cancer be approached as a benign lesion?: a population-level analysis of survival among 1,200 patients. Ann Surg Oncol. 2013; 20(3):767-772.
  11. Asari R, Koperek O, Scheuba C, et al. Follicular thyroid carcinoma in an iodine-replete endemic goiter region: a prospectively collected, retrospectively analyzed clinical trial. Ann Surg. 2009; 249(6):1023-1031.

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Last updated: 2018-06-21 20:11