Thyroglossal duct cysts (TGDCs) are unusual remnants of the thyroid gland that can arise anywhere along the thyroid migration pathway (1). This phenomenon is the most prevalent type of congenital neck mass in children, with a frequency of ~7% in the general population (1). During embryonic development, in the first six weeks of pregnancy, the thyroid gland begins to descend toward its definitive anatomical position, and afterward, the thyroglossal duct normally undergoes complete atrophy by the tenth week (1). However, failure to undergo atrophy can lead to the formation of TGDC, which can be in the form of a cyst, fistula, duct, tract or ectopic thyroid tissue (2). The cyst manifests as a solid, clearly delineated, painless mass that ascends with the protrusion of the tongue and during swallowing, connecting to the foramen caecum through the embryonic duct (3). In the pediatric population, TGDCs have been reported to primarily affect male individuals, while in adults, the prevalence is notably higher among females. The area beneath the hyoid bone emerges as the predominant site of origin for the anomaly. Complications associated with this congenital anomaly may include severe infection, localized inflammation, pain, swelling, malignancy and the development of fistulas (1). According to the literature, cancer rarely develops from TGDCs. The incidence of primary carcinoma within TGDCs among all cases subjected to TGDC removal was documented to vary between 0.7 and 6%. (1,4-7). This rare but significant occurrence presents a diagnostic and management challenge due to its rarity and our limited understanding, as the majority of the available data are from case reports, with some small case series (1,2,4,5,7). The present study aims to showcase the clinical characteristics, diagnosis and management of patients with TGDC carcinoma.

TGDC is one of the most common congenital anomalies, with a wide range of differential diagnoses, that is rarely associated with carcinoma (1,8,9). Although it is uncertain how cancer arises at this location, it is thought to be the result of the neoplastic transformation of normal residual thyroid tissue throughout the thyroglossal cystic tube. The papillary histotype of the condition has two possible origins: Ectopic thyroid tissue formation or metastases from a primary thyroid malignancy, with the latter receiving less attention (4).

TGDC is typically seen in children, yet adults can also be affected. However, it is challenging to pinpoint an exact age distribution for TGDC due to the varied reporting time frames, which may be reported as the age at which the condition was first diagnosed when symptoms began, or some authors may reference the patient's life decade rather than their precise age. Consequently, there is no agreement in the literature concerning the age demographics of patients with TGDC. In previous studies, the age distribution of malignant TGDCs has been reported to be 41-47 years (4,10). In the current study, the mean and median age of the patients were 39.1 and 40 years, respectively.

The usual presentation of TGDC is a moveable, painless midline or, less commonly, a lateral neck mass (11), while malignant TGDC should be suspected in any cysts that are irregular, hard, rapidly increasing in size, fixed to surrounding tissues or present in cervical lymph nodes (12,13). Most of the time, it is impossible to clinically differentiate between a TGC and a benign TGDC. Usually, the diagnosis is made by histopathological examination after excision of the resected tissue (14,15). A study by Kennedy et al (16) showed only three cases of PTC and a single case of squamous cell carcinoma (SCC) in a large review of 115 cases of TGDC, whose presentations were the same as that of benign TGDC. Khalaf et al (17) reported a case of a 44-year-old female with coexisting hyperthyroidism and TGDC. In the current study, all of the cases had anterior neck swelling for a mean and median of 4.2 and 2 months, respectively. Only one case had hypothyroidism, one had hyperthyroidism and the others were euthyroid.

Imaging diagnostic tools for neck masses include US, scintigraphy and computerized tomography (CT), which are less likely to diagnose malignant diseases preoperatively (18,19). The US of TGDC frequently shows a well-defined cystic area with anechoic fluid. Their walls are thin without internal vascularity. On the other hand, the presence of microcalcification and a solid component within the cyst can predict malignancy (7). Branstetter et al (20) reported that carcinoma should be suspected in TGDC when a mural nodule or calcification is seen on CT. Acultae et al (7) reported a case of a 21-year-old female diagnosed with TGC in whom the neck US revealed a predominantly cystic lesion with a central solid component lying between the hyoid bone and thyroid cartilage. In this study, the US revealed a cystic lesion in four cases (50%), a complex nodule in three cases (30%), a cystic lesion with microcalcification and a mural nodule in three cases (30%) (cases 3, 4 and 5).

The role of FNAC in detecting TGC has been well investigated (21). In particular, US-guided FNAC is the main diagnostic investigation of TGC, with a positive accuracy rate of 53% and a false negative rate of 47%. Peripheral locations of swelling in some of the patients, low cellularity of aspirated cytology due to dilution of the cystic region after aspiration and small tumor size make TGC diagnosis by FNAC challenging (6,21). Repeating the FNAC under US guidance and taking a sample from the solid part of the cystic area or soft tissue mass may improve diagnostic accuracy (13). In the current study, only seven of the cases had a preoperative FNAC of TGDC. Of the cases, six were suspected to have PTC and there was just cystic content in the sample of one of the cases.

The first case of PTC in a TGDC was reported by Owen and coworkers in 1927(5). The majority of these malignancies come from the thyroid gland, with 75-85% being PTC, 7% being mixed papillary and follicular carcinoma and ~5% being SCC, which has the poorest prognosis (7). In a previous study, 4% of TGDC cases were found to be carcinomas and all of these were PTC (1). This aligns with prior research that also identified PTC as the most common type of carcinoma associated with TGDC (22). All of the TGCs in this study were PTC.

A common treatment for TGDC is Sistrunk's operation, which consists of the surgical removal of the TGDC and the hyoid bone central segment, along with a portion of tissue surrounding the thyroglossal tract extending towards the oral cavity at the foramen cecum (12). More aggressive management, such as the Sistrunk operation combined with a complete thyroidectomy and neck dissection, followed by treatment with radioactive iodine and thyroxine suppressive dose is beneficial for high-risk patients (older than 45 years, presence of invasion or metastatic lymph nodes in the neck, history of head and neck radiation and patients who present with a malignant thyroid nodule) (13). On the other hand, some authors recommend having a total thyroidectomy when the size of the carcinoma is >10 mm. When the size is <10 mm, a total thyroidectomy should be considered when there is a presence of cyst wall invasion, enlarged cervical lymph nodes clinically or radiologically, or a prior history of radiation (7). Furthermore, total thyroidectomy combined with Sistrunk's procedure for TGC allows for more accurate staging and therapy, as well as long-term follow-up with thyroglobulin level monitoring and a whole-body scan (13). Sistrunk surgery was performed on five patients in this study alone. A total of four of the individuals had malignant thyroid nodules, necessitating both a Sistrunk surgery and a total thyroidectomy. Due to abnormal lymph nodes in the neck, two of them underwent lateral neck dissection. Furthermore, one patient was given radioactive iodine as well as a suppressive dosage of thyroxine. The cited resources in this study have been checked for eligibility (23). The limitations of this study include the availability of only a small number of histopathological images. As some examinations were conducted in external histopathology centers, not all images could be retrieved and the mutation profiles of the patients could not be obtained due to the high cost of the examinations.

In conclusion, carcinomas arising from TGDC remnants are uncommon and may solely present as anterior neck swelling. The use of FNAC in the preoperative assessment of cystic lesions in the neck can be beneficial. If TGC is suspected, both the thyroid gland and different lymph node compartments should be evaluated for malignancy. The Sistrunk operation serves as the gold treatment approach with good outcomes. However, additional management for high-risk TGCs should be considered, such as total or partial thyroidectomy, ablation using radioactive iodine, lateral neck dissection and suppressive therapy with thyroid hormones.