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Year : 2019  |  Volume : 5  |  Issue : 2  |  Page : 57-62

Ectopic Thyroid Tissue in Submandibular Region

1 MBBS student, Maulana Azad Medical College & Lok Nayak Hospital, New Delhi, India
2 Department of Radiodiagnosis, Maulana Azad Medical College & Lok Nayak Hospital, New Delhi, India
3 Department of Ear, Nose and Throat Surgery, Maulana Azad Medical College & Lok Nayak Hospital, New Delhi, India

Date of Web Publication20-Aug-2019

Correspondence Address:
MD, Professor Jyoti Kumar
Department of Radiodiagnosis, Lok Nayak Hospital, Maulana Azad Medical College, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mamcjms.mamcjms_18_19

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Ectopic thyroid is the presence of gland at any location except for its normal position in the anterior neck in front of the trachea. It may result from an early arrest of migration or migration along an abnormal path. Ectopic thyroid in the submandibular region is relatively unusual and may or may not be accompanied with the orthotopically located thyroid gland. Pathological changes reported in the literature in the ectopic gland include goitrous change, hyperplasia, malignancy, and, rarely, inflammation. Patients usually present as a palpable, mobile, and painless mass below the lateral jaw. The important differentials include salivary gland tumor, lymphoma, inflammatory lymphadenopathy, lipoma, and cysts. Ultrasonography, radionuclide scan, computed tomography, and magnetic resonance imaging are the diagnostic modalities for documenting the presence of ectopia. Evaluation of functional status with thyroid profile and histopathological examination after fine-needle aspiration cytology directs further management. Surgical removal is the preferred treatment for ectopic thyroid. Thyroidectomy predisposes the patient to iatrogenic hypothyroidism if eutopic thyroid is absent or hypofunctioning. Such patients require lifelong thyroid replacement. However, asymptomatic cases may be managed conservatively. Ectopic thyroid in the submandibular region has important clinical implications and hence, even though rare, should be considered as one of the differentials in the patient presenting with swelling below the lateral jaw.

Keywords: Ectopic thyroid, goitrous change, iatrogenic hypothyroidism, submandibular, thyroid dysgenesis, thyroid imaging

How to cite this article:
Karna R, Kumar J, Srividya B, Prakash A, Singh I, Garg A. Ectopic Thyroid Tissue in Submandibular Region. MAMC J Med Sci 2019;5:57-62

How to cite this URL:
Karna R, Kumar J, Srividya B, Prakash A, Singh I, Garg A. Ectopic Thyroid Tissue in Submandibular Region. MAMC J Med Sci [serial online] 2019 [cited 2022 Jan 28];5:57-62. Available from: https://www.mamcjms.in/text.asp?2019/5/2/57/264776

  Background Top

Thyroid is an endocrine organ located in the anterior neck between second and fourth tracheal cartilages. Embryologically, the gland descends anterior to the hyoid bone and laryngeal cartilages to lie in front of the trachea, which is its final location.[1] Ectopic thyroid is defined as any location of thyroid gland except for the normal usual position in the anterior neck. It is the most common type of thyroid dysgenesis comprising 48% to 61% of the cases.[1] This condition is uncommon with a prevalence of one per 100,000 to 300,000 people.[2] Postmortem studies reveal higher incidence of asymptomatic ectopic thyroid along the path of thyroglossal duct in 7% to 10% of adult population.[3] There are several circumstances when normal or abnormal thyroid tissue may be found within the neck but outside the thyroid gland. Rosai and Ackerman’s classification[4] distinguishes such tissue as follows:
  1. Ectopic thyroid tissue resulting from faulty embryogenesis.
  2. Hyperplastic thyroid tissue outside the gland in patients with Graves’ disease.
  3. Mechanical implantation of thyroid tissue in the neck secondary to surgical intervention or accidental trauma.
  4. A sequestered thyroid nodule, also known as a parasitic or accessory nodule, that is, the occurrence of a peripherally located thyroid nodule in which the anatomic connection with the main gland is either lost or missed by the surgeon.
  5. Thyroid tissue within cervical lymph nodes, which may develop by two unrelated processes: metastases of clinically undetected thyroid carcinomas, always of papillary variety (most cases), or the development of normal follicles within lymph nodes.
  6. Thyroid tissue as a component of a teratoma, particularly in the ovary.

The most common location for ectopic thyroid is lingual whereas, sometimes, it can also be found in suprahyoid, hyoid, and subhyoid regions and has been reported in trachea, submandibular and lateral cervical regions, axilla, palatine tonsils, carotid bifurcation, iris of the eye and pituitary gland.[5],[6],[7] Ectopic thyroid tissue can occur with or without the presence of orthotopically located gland, both situations reported with equal frequency in the literature.[3]

However, rarely ectopic thyroid in the submandibular region has been described in the literature.[1] This review focuses on ectopic thyroid tissue in the submandibular region and various pathologic changes in it underscoring clinical approach, imaging considerations, and treatment options. Here, we demonstrate a case example of submandibular ectopic thyroid tissue on ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI). This article will help radiologists and treating physicians hone their approach toward a submandibular mass and optimize their knowledge about ectopic thyroid.

Here, we present a representative case accompanying the article demonstrating the clinical and radiological features. Appropriate consent from the patient has been taken.

A 16-year-old female presented with a history of swelling in the anterior aspect of the neck since birth. The swelling gradually increased in size and eventually caused mild difficulty in swallowing food at the time of presentation.

The patient’s birth and developmental history were insignificant. No other significant family history was present.

On clinical examination, a 4 × 4 cm well-defined mass lesion was noted in the anterior upper neck in the midline. On laboratory investigations, she was found to be hypothyroid with a borderline decrease in her T3 levels − 1.6 nmol/L (reference range 1.3–3.1 nmol/L) and T4 levels − 72 nmol/L (reference range 66–181 nmol/L) and markedly elevated thyroid stimulating hormone (TSH) level − 112.7 μIU/mL (reference range 0.27–4.2 μIU/mL), respectively.

On USG, there was a well-defined heterogeneous, predominantly hypoechoic mass seen in the submandibular space and normal thyroid gland was not seen in its anterior pretracheal location [[Figure 1]A and B].
Figure 1 (A) USG of the neck depicts a well-defined heterogeneous hypoechoic mass in the submandibular space in the midline with an echogenic nodule within (arrow). (B) USG of the neck does not show thyroid gland in its normal pretracheal location with empty thyroid bed (arrow). USG, ultrasonography.

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On CT, a well-defined heterogeneous lesion (measuring 3.6 × 2.5 cm) was seen in the submandibular space in the midline. The lesion had nonenhancing cystic areas within. We confirmed absent eutopic thyroid gland on lower CT images [[Figure 2]A and B].
Figure 2 Axial (A) and mid-sagittal (B) contrast enhanced computed tomography (CECT) images depict a well-defined, predominantly cystic lesion in the submandibular space in the midline with an enhancing well-defined nodule within (yellow arrow), representing goitrous thyroid gland. Also note the absence of normal thyroid gland in its expected location in inferior neck in image (B) (white arrow).

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On MRI, the lesion was heterogeneously hyperintense on T1 weighted (T1W)/T2 Weighted (T2W) imaging with no signal suppression on short TI inversion recovery (STIR) [[Figure 3]A and B]. There was minimal postcontrast enhancement [[Figure 4]A and B].
Figure 3 Coronal T1W (A) and axial T2W MR (B) images depict a heterogeneously hyperintense lesion in the midline in submandibular space, just below mylohyoid muscle (thin arrow in A) with an isointense to hypointense nodule within (thick arrow). This was the ectopic thyroid gland with colloid goitrous change. MR, magnetic resonance.

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Figure 4 (A) Axial postcontrast MRI image depicts subtle enhancement of the isointense nodule (arrow). MRI, magnetic resonance imaging.

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On fine-needle aspiration cytology, the lesion was proven to be a cystic colloid goiter.

She was treated with ELTROXIN 75 μg/day for 4 months, following which her thyroid profile was found to be within normal limits with the T3, T4, and TSH levels of 117.0 ng/mL, 10.2 ng/dL, and 4.5 μIU/mL, respectively (reference value − T3: 61.0–181 ng/dL; T4: 4.5–12.6 ng/dL; and TSH: 0.27–4.2 μIU/mL).

  Developmental Aspects of Thyroid Top

Thyroid gland is located in the anterior neck region between the cricoid cartilage and suprasternal notch. Embryologically, there is a migration of developing thyroid from the thyroid anlage region in the midline to its final location in front of the trachea.[1] Lateral anlages formed from the fourth pharyngeal pouch, which are earlier infiltrated by C-cells precursors, form the lateral thyroid contributing 1% to 30% of total gland weight.[8]

Any premature arrest of migration or migration along aberrant paths leads to the ectopic location of the thyroid gland. Defective migration of median thyroid anlage leads to ectopic submandibular thyroid tissue formation.[1] However, some authors argue that ectopic thyroid in the submandibular region derives from lateral thyroid anlage, which fails to migrate and fuse to the median thyroid anlage.[1]

Transcription factors seem to play an indispensable role in the formation of the thyroid gland. Experiments in animal models have elucidated the role of forkhead box E1 (FOXE1) in thyroid migration; homozygosity for FOXE1 mutations in mice is associated with ectopic thyroid.[1] Mutations in transcription factor thyroid transcription factor 2 (TTF-2), which is required for migration of thyroid, have been postulated to cause ectopic thyroid.[9],[10] However, human ectopic thyroid has not been associated with any mutation in known genes till now and the cause remains unknown.

  Pathology and Clinical Implications Top

Helidonis et al.[11] described ectopic thyroid in the submandibular region for the first time in 1980. Ectopic thyroid in this region is more common in women and generally presents as a right-sided submandibular swelling.[12] Ectopic thyroid tissue may or may not be accompanied by orthotopic thyroid gland.[12],[13] In cases of dual thyroid with ectopic described in submandibular region, pathological changes have been described either in ectopic thyroid or eutopic thyroid or both.[13] Ectopic thyroid may undergo pathological changes similar to an orthotopic gland like adenoma, hyperplasia, inflammation, and malignancy, and when located in the submandibular region may mimic submandibular gland anomaly.[14] Majority of the patients with the thyroid in the submandibular region are asymptomatic. A patient may present at any age as a palpable, mobile, and painless mass that may begin to grow rapidly or grow insidiously for long.[14] Some patients also complain of occasional pain and dysphagia.[14] Patients may have associated clinical features of hypothyroidism or hyperthyroidism reflecting the functional status of the gland. Ectopic submandibular thyroid swelling may mimic a number of other clinical conditions including inflammatory or malignant lymphadenopathy, thyroglossal duct cyst, salivary gland tumor, lipoma, branchial cleft cyst, and sebaceous and dermoid cyst. Thyroid cancer metastasis is, probably, the most important differential and must be excluded in all cases. Although rare, ectopic thyroid should be considered among differentials of submandibular swelling.

Ectopic thyroid tissue in the submandibular region may also undergo goitrous changes.[14],[15] The submandibular ectopic thyroid gland in literature has mostly been described as euthyroid but may be associated with hypothyroidism or hyperthyroidism.[12],[16],[17] Although ectopic thyroid secretes structurally normal hormone, the quantity may be insufficient to meet metabolic demands especially during periods of stress including puberty, menstruation, pregnancy, infection, trauma, and surgery, consequently increasing TSH production and secondary hypertrophy of the gland.[16],[18]Ectopic thyroid tissue may, rarely, undergo malignant change. The rate of malignant transformation in ectopic thyroid tissue is similar to orthotopic thyroid gland.[18]

Tumor formation in the gland is usually diagnosed after histopathological examination of the excised gland. However, transformation to papillary carcinoma is relatively uncommon as compared to eutopic thyroid neoplasms, of which papillary carcinoma is the most common type.[19] Very few cases of malignant transformation of submandibular thyroid have been described in the literature. Histologic subtypes include signet ring cell follicular adenoma, clear cell follicular adenoma, papillary carcinoma, and follicular carcinoma.[19],[20],[21],[22] It is, however, very difficult to differentiate carcinoma arising from ectopic thyroid tissue from metastatic carcinoma. There are several pointers toward carcinoma arising from ectopic submandibular thyroid like separate blood supply of ectopic gland from extracervical vessels, no previous history of malignancy or surgery, and normal or absent eutopic thyroid gland.[23]

  Investigations Top

Thyroid function tests should be carried out in all patients with submandibular ectopic thyroid and the test results may indicate hypothyroidism, euthyroidism, or hyperthyroidism. USG is a useful initial assessment for evaluation of submandibular swelling and it can concurrently identify normal eutopic thyroid gland, if present. The sensitivity of USG is increased by combining it with color Doppler technique. It may preclude the need for thyroid scintigraphy before excision of the ectopic thyroid gland if eutopic thyroid is found to be normal. USG is cheap and does not expose patients to radiation; it is, therefore, a useful modality for initial assessment of submandibular swelling.

Radionuclide thyroid imaging using Tc-99, I-131, or I-123 is considered as the investigation of choice for detection of the ectopic thyroid gland and is useful for identifying ectopic and normotopic functional thyroid tissue. It is more sensitive and specific than USG and CT in detecting ectopic thyroid. It can also unmask other unidentified sites of thyroid tissue. However, it may be difficult to detect smaller submandibular ectopic tissues as uptake may occur in the salivary glands, nasal mucosa, sinusitis, and dental disease.[24],[25] Some clinicians advocate the use of scans only in the presence of clinical hypothyroidism or failure of ultrasonogram to detect normotopic thyroid. Facilities of thyroid scintigraphy may not be available at all centers across the country. One limiting factor of scintigraphy is the formation of a single planar image.

CT and MRI are other useful imaging modalities in the investigation of patients with ectopic submandibular thyroid. Ectopic thyroid has higher attenuation coefficient than surrounding muscle on CT because of the high iodine content of the colloid and is helpful to delineate the exact anatomy and spatial relationship of ectopic thyroid to other cervical organs and absence of lymph nodes. However, routine use of CT in these patients is not recommended due to high radiation dose and lower specificity than radionuclide scan. Contrast-enhanced multidetector CT provides multiplanar and three-dimensional imaging with high spatial and temporal resolution and is more reliable than non-contrast CT.[26] Single-photon emission tomography–CT can be used to obtain anatomical and functional status together.[27] Fine-needle aspiration cytology is one of the most accurate diagnostic modality and can identify undergoing pathologic changes in the ectopic thyroid. It is the modality of choice when a malignant lesion is suspected.

  Treatment Top

The treatment offered to patients with ectopic thyroid depends upon a number of factors including the size of the mass, local symptoms, age, functional status of the gland, and associated complications. Asymptomatic or incidentally discovered euthyroid patients can be managed with regular follow-up and observation. Functional status of both eutopic and ectopic thyroid should be determined. In hypothyroid patients, with high TSH levels and continuously increasing submandibular mass, levothyroxine treatment can be initially administered. It helps manage thyroid levels as well as compressive symptoms by reducing the size of ectopic thyroid gland while TSH levels return to normal values. Antithyroid drugs may be tried for clinically hyperthyroid patients. Removal of ectopic thyroid surgically is the recommended treatment and should be followed by histopathologic evaluation of the tissue to differentiate benign ectopic thyroid tissue from follicular carcinoma. However, resection should be carried out with caution because ectopic thyroid in the submandibular region may be the only thyroid tissue in the body. Resection should be performed when a malignant transformation is suspected with the fast growth of tumors or when USG shows microcalcifications.[19] Hypothyroidism not controlled with hormonal therapy, bleeding, and obstructive features in patients are also indications of surgical removal.[28] The presence of thyroid tissue at the normal anatomical location and its functional status should be confirmed preoperatively to prevent iatrogenic hypothyroidism. Lifelong exogenous thyroid supplementation would be needed after surgery in most cases. Radioactive I-131 therapy has also been recommended as an alternative or adjunct to surgical excision and has a beneficial role in managing compressive symptoms in hyperthyroid, euthyroid, and hypothyroid individuals. It can be performed in cases when surgery carries a higher risk. Some authors recommend I-131 ablation in patients who are unlikely to respond to levothyroxine supplementation except in cases in which malignancy is suspected.[29],[30]

The requirement of high doses (20 mCI or higher) to induce regression especially in euthyroid and hypothyroid cases is a limiting factor. I-131 therapy is generally avoided in young ages considering its long-term effects.[31],[32]

  Conclusion Top

Ectopic thyroid located in the submandibular region is an extremely rare anomaly. The cause is not fully known; however, mutations in transcription factors responsible for migration of the gland have been postulated. Pathological changes similar to orthotopic thyroid occur in submandibular ectopic thyroid including adenoma, hyperplasia, inflammation, and malignancy. It is mostly asymptomatic and usually presents as enlarging submandibular swelling in periods of stress. Conservative management should be performed for asymptomatic cases. Surgery is the modality of choice with lifelong levothyroxine supplementation for malignancy and when submandibular thyroid could not be managed conservatively or undergoes complications. Although rare, this entity should be considered in patients with a mass in the submandibular region.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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