Embryology

Embryologically, the median anlage of the thyroid originates from the endodermal segment in the floor of the primitive pharynx at the foramen cecum located in the midline at the junction of the anterior two thirds of the tongue (first branchial arch derivative) and posterior one third (third branchial arch derivative) (see Chapter 2, Applied Embryology of the Thyroid and Parathyroid Glands). Between 5 and 7 weeks of gestation, the gland migrates caudally from the foramen cecum to its normal position below the thyroid cartilage. The path of descent is closely associated with the hyoid bone and is usually anterior to it but can also be posterior to it or within the bone. The lateral thyroid anlage is derived from the ultimobranchial body, a descending diverticulum of the fourth to fifth pharyngeal pouch. The existence of this lateral anlage has been debated, but some believe it becomes incorporated into the median thyroid anlage to contribute morphogenesis of the thyroid parenchyma (see Chapter 2, Applied Embryology of the Thyroid and Parathyroid Glands, Figure 2-3, D).

Thyroglossal Duct Cysts

Between 7 and 10 weeks of gestation, the thyroglossal epithelial tract obliterates. Failure of the thyroglossal duct tract to obliterate can result in formation of thyroglossal duct cysts (TGDC). In autopsy series, thyroglossal tract remnants are found in approximately 7% of the normal population.¹ It represents the most common congenital midline mass. Thyroglossal duct cysts are found mostly in children and adolescents, but they are also found in patients more than 20 years old in one third of cases. Most thyroglossal duct cysts are found between the hyoid and thyroid cartilage (61%,² 67%³), followed by hyoid/suprahyoid (24%,² 33%³), suprasternal (13%³), and in the base of tongue (2%,² 0.1%³).

The standard surgical treatment for thyroglossal duct cyst is the Sistrunk procedure. The procedure involves excising the cyst, removing the thyroglossal duct tract along with the central portion of the hyoid bone, and excising a central core of the base of the tongue at the foramen cecum. This procedure has been shown to be associated with very low (less than 4%) recurrent rates.^2–4

The incidence of malignancy in thyroglossal duct cysts is approximately 1%.^5,6 The majority are papillary thyroid carcinoma, and a small percentage are follicular variant of papillary carcinoma; squamous cell carcinoma is rare.^5,7 Thyroglossal duct malignancies are clinically difficult to distinguish from benign thyroglossal duct cysts and thus are rarely suspected preoperatively. Invasion of local structures, or suspicious metastatic lymphadenopathy on computed tomography (CT) or ultrasound, or the presence of features consistent with papillary thyroid carcinoma, such as microcalcifications, on ultrasound should raise suspicion for malignancy.

The surgical management of thyroglossal duct cyst carcinoma is still controversial. Most authors believe that incidentally discovered thyroglossal duct cyst papillary carcinoma can be adequately resected by the Sistrunk procedure alone,^5,6,8 provided there is no clinical or sonographic suspicion of thyroid lesion or cervical adenopathy. This procedure is associated with a cure rate of 95% in reported series.^5,6,8 Others advocate a more aggressive approach—total thyroidectomy along with the Sistrunk procedure.^9–11 One argument for this aggressive approach is the possibility of papillary carcinoma in thyroglossal duct cysts coexisting with an occult primary carcinoma in the thyroid. The reported incidences of primary thyroid carcinoma concomitant with thyroglossal duct cyst papillary carcinoma is between 11% and 56%.^9,12–14 The tumors in the thyroid are usually small microcarcinomas and are frequently not palpable or detectable by preoperative imaging techniques. Another rationale for concurrent thyroidectomy is to allow postoperative treatment with radioiodine because of a high risk of lymph node metastasis. Hartl et al. reported an overall 75% incidence of lymph node metastases; 40% was in the central neck and 60% in the lateral neck.⁹ Mazaferri suggested that a rational approach might be to treat thyroglossal duct cyst papillary carcinomas similar to well-differentiated thyroid cancers. Thus, low-risk tumors (defined as those existing in a patient under age 45), no prior radiation, ultrasonographically normal thyroid gland, small tumors (i.e., < 1.5 cm) with negative margins, and no cyst wall invasion or metastasis are all conditions that could adequately be treated with the Sistrunk procedure alone.¹⁵ Total thyroidectomy is indicated if there is capsular invasion of the cystic wall or if the TGDC carcinoma is greater than 1 cm, as such tumors may behave more aggressively.¹² Those who advocate total thyroidectomy in addition to the Sistrunk procedure for TGDC carcinomas also recommend postoperative radioactive iodine ablation and thyroxine suppressive therapy.^10,12 In patients with low-risk disease treated with the Sistrunk procedure, there are no data supporting the role of thyroid suppression therapy. The prognosis of papillary carcinoma arising in thyroglossal duct cyst is excellent, with an overall survival rate of 95.6% at 10 years.^5,13 The postsurgical follow-up of patients is limited to an annual clinical and sonographic cervical examination in low-risk patients treated with the Sistrunk procedure. In those who have also undergone total thyroidectomy, serum thyroglobulin levels can also be measured for cancer surveillance, provided the patient does not have antibodies to thyroglobulin.

Ectopic Thyroid Tissue

Ectopic thyroid tissue, the presence of functioning thyroid tissue in a location other than its normal pretracheal location, can be found anywhere along the course of descent of the thyroid gland (see Chapters 2, Applied Embryology of the Thyroid and Parathyroid Glands, and 10, Reoperation for Benign Disease). According to autopsy studies, the prevalence of ectopic thyroid tissue varies between 7% and 10%. Most cases of ectopic thyroid are diagnosed during the first three decades of life, and they are more common in females.¹⁶ A classification of sites of ectopic thyroid is shown in Table 6-1. Approximately 90% of ectopic thyroid tissue is found in the base of tongue as lingual thyroid.^16–19 Lingual thyroid results from complete arrest of descent of the median thyroid anlage. In 75% of patients with lingual thyroid, it is the only thyroid tissue present and the sole source of thyroid hormone production.¹⁸ Seventy percent of cases present with hypothyroidism.¹⁷ Rarely, lingual thyroid can be present along with normal pretracheal thyroid, but only the lingual thyroid is functional.¹⁹ Hyperthyroidism from hyperfunctioning lingual thyroid has also been reported.²⁰ Most patients with lingual thyroid are asymptomatic; however, some can enlarge sufficiently to cause dysphagia and dyspnea.²¹ Hypertrophy of the lingual thyroid occurs as a response to thyroid-stimulating hormone (TSH) stimulation from normal physiologic demands. Thyroid hormone production from lingual thyroid tissue often cannot meet the normal physiologic needs, which can result in enlargement of gland. Kansal et al. recommended that patients with lingual thyroid, even when small, be placed on lifelong thyroxine replacement to prevent subsequent enlargement.²² Lingual thyroid is typically benign but rarely can harbor malignancy, usually papillary thyroid carcinoma.²³

Table 6-1 Classification of Sites of Ectopic Thyroid

Cervical ectopic thyroid has also been reported to occur in the anterior neck, including the sublingual space,¹⁶ the thyrohyoid region,²⁴ and within the trachea and larynx.^25–27 Unlike lingual thyroid, 75% of intratracheal ectopic thyroids are associated with functioning thyroid gland in its normal location.²⁵ Imaging studies such as CT or magnetic resonance imaging (MRI) typically demonstrate a nonerosive mass in the subglottis or upper trachea that is clearly separate from a normally located thyroid gland. These are often asymptomatic and can be incidental findings on autopsies. The most common presentation is progressive dyspnea, often mistaken for asthma. Stridor and hemoptysis are rare. Primary treatment is endoscopic laser excision. Tracheotomy may be necessary initially for emergent airway control. Radioactive iodine is not recommended for treatment of this rare entity, primarily because of the usual coexistence of normal extratracheal thyroid gland. Malignancy has also been reported in intratracheal ectopic thyroid.^28,29

Approximately 10% of ectopic thyroid is found in the lateral neck. Lateral aberrant thyroid tissue is defined as thyroid tissue found lateral to the internal jugular vein. Most of these thyroid nests are found in cervical nodes. It has long been believed that if thyroid tissue is found in a cervical node, even if it appears benign histologically, it represents metastatic papillary thyroid carcinoma, and one simply needs to look thoroughly for a primary in the thyroid.³⁰ However, others have challenged this belief and argue that a small amount of normal-appearing thyroid tissue found in medially located cervical lymph nodes in a subcapsular location within the node may represent an embryologic rest within the capsules of the nodes.^31–34 Kozol et al. reported eight cases of thyroid tissue found in cervical nodes without any identifiable malignancy in the thyroid.³²

Other locations in the lateral neck where ectopic thyroid can be found are the submandibular region^35–39 and the parapharyngeal space.^40–43 In the submandibular region, it has been reported as the only functioning thyroid tissue or in conjunction with a normal thyroid.^35,38 There are some theories on how of ectopic thyroid tissue occurs in the lateral neck. One theory is that nodular growths on the surface of the thyroid gland progressively enlarge and ultimately lose connection to the thyroid, termed exophytic thyroid nodules. Persistence of the lateral thyroid anlage may also be another explanation for occurrence of nonmidline ectopic thyroid tissue in the neck.⁴⁴

Ectopic thyroid can also be found in the anterior mediastinum (see Chapter 7, Surgery of Cervical and Substernal Goiter). In contrast to substernal goiters, which are extensions of neck goiters into the mediastinum, true primary ectopic mediastinal goiters are rare and occur in less than 1% of all goiters. Ectopic thyroid in the mediastinum is usually located near the thymus. Heterotopic thyroid in the mediastinum probably developed from rudiments of developing thyroid being drawn into the chest during descent of the heart and great vessels during embryogenesis (i.e., thyroid rests; see Chapters 2, Applied Embryology of the Thyroid and Parathyroid Glands [Figure 2-3, B] and 10, Reoperation for Benign Disease). This could explain its aberrant locations in the pericardium, heart, and aortic wall.^45–48

Ectopic thyroid has also been reported in the abdomen, such as in the liver, gallbladder, pancreas, and adrenal gland.^49–52 In addition, heterotopic thyroid tissue can occur in the pelvis as struma ovarii, which is a germ cell tumor in the ovary with thyroid tissue comprising more than 50% of the tissue.^53,54 Approximately 5% of struma ovarii are malignant.^53–56 The most common histopathologic subtype of malignant struma ovarii is papillary carcinoma, followed by follicular carcinoma, and a follicular variant of papillary carcinoma.⁵⁷ Diagnosis of malignant struma ovarii is usually made from primary biopsy of the ovary or oophorectomy. Rarely, the diagnosis may be suspected on radioactive iodine whole-body scanning for thyroid malignancy after total thyroidectomy. In such cases oophorectomy establishes the diagnosis. Because the thyroid tissue in struma ovarii is iodine avid and produces thyroglobulin, oophorectomy in such cases facilitates subsequent radioiodine treatment and ease of cancer surveillance.

Rarely, ectopic cervical thyroid can be present at two different sites simultaneously. Lingual/sublingual thyroid was the most common ectopic location. Subhyoid was the most common site of a second ectopic thyroid. In approximately 75% of the patients, ectopic thyroid tissue is the only functioning thyroid tissue.^58–61

Treatment of ectopic thyroid in the neck and chest depends on its location and size and whether or not the patient has symptoms or complications from it. Thyroid function tests, neck ultrasound, and thyroid uptake scan may be useful in diagnosis and in clinical management. Small and asymptomatic ectopic thyroid can be observed, as it may be the only functioning thyroid in the patient. Patients with compressive symptoms, suspected bleeding, malignancy, and ulceration need to be treated, either with surgery or radioiodine. Patients with relatively small ectopic mediastinal goiters are usually without symptoms and present with an abnormal incidental chest radiograph. Blood supply is typically from thoracic vessels, and a surgical approach by median sternotomy may be necessary for surgical removal if the ectopic tissue extends quite inferiorly (see Chapter 7, Surgery of Cervical and Substernal Goiter).