Introduction

Thyroglossal duct cysts (TGDC) develop from the residues of the thyroglossal duct, which usually regress at 6^th to 8^th week of gestational life [1,2]. One of the most common inborn anomaly, its prevalence is reported to be approximately 7% among the general population [3]. These cysts can manifest as a fistula, duct, cyst or ectopic thyroid tissue [3]. The residual thyroid tissue may persist within the duct, and its transformation can result in thyroglossal duct carcinoma [2]. First described in 1911, this condition has a slightly higher incidence in women than men (2.1:1) and typically manifests in middle age [2,3].

Malignancy occurring in TGDC is extremely rare, with a reported incidence of 0.7% to 1%. Papillary thyroid carcinoma is the most common histological type which is most often diagnosed postoperatively through histopathological examination [3-5]. Despite being a rare occurrence, PTC in a TGDC has several challenges with respect to preoperative diagnosis and therapeutic strategies adopted. Clinical symptoms in a TGDC and malignancy arising in TGDC are usually nonspecific. Moreover, FNAC has low accuracy in view of the cystic nature of these lesion, accounting for a false negative diagnosis[5,6]. The therapeutic modalities opted for PTC arising in TGDCs are deduced from the general management guidelines of thyroid PTC, which may not be absolutely pertinent in view of difference in lymphatic drainage, anatomy and embryology [5]. Most of the PTC in TGDCs are diagnosed post surgically. Whether completion total thyroidectomy and or radioiodine therapy is required in these cases is still a matter of debate [7,8].

Rarity of the disease and lack of consensus on management guidelines, makes the case documentation critical in order to add information to the existing literature. Hence we report a case of PTC in TGDC highlighting the pitfalls of the preoperative diagnostic modalities, the importance of harbouring high index of clinical suspicion and the significance of careful pathological examination of excised TGDCs to identify such unexpected findings.

Clinical Presentation

A 60-year-old female patient presented to ENT outpatient department with a persistent swelling in the midline of her neck, which had been present for the past eight to nine years. The swelling had an insidious onset and gradually increased in size over time. Despite the progression, the patient did not experience any associated symptoms such as pain, difficulty in swallowing solids or liquids, or hoarseness of voice. The patient had been otherwise healthy prior to the development of this swelling, with no significant medical history or prior surgeries or any family history. She did not report any known allergies to food or medications.

Despite the long-standing swelling, the patient reported a history of consuming Tab.Thyronorm for only 20 days. On physical examination, a solitary swelling approximately 5 x 5 cm in size was noted at the anterior aspect of the neck, more prominent on the left side. The swelling extended to the sternocleidomastoid muscle bilaterally. The inferior border of the swelling could not be palpated. The swelling was observed to move with deglutition but did not move with protrusion of the tongue. The trachea appeared to be central. The swelling had a smooth, regular surface and was firm in consistency. The skin over the swelling was pinchable, and the swelling was freely mobile in both horizontal and vertical directions.

A thyroid ultrasonography examination (USG) was performed, which revealed a well-defined spongiform nodule in the right lobe of the thyroid, classified as TIRADS I, suggesting benign findings. The isthmus showed a well-defined isoechoic area with circumferential calcification, classified as TIRADS III, likely benign. The left lobe presented a well-defined anechoic cystic lesion, classified as TIRADS 0.

FNAC was performed under ultrasound guidance. FNAC smears from all three lesions, as mentioned in the USG report, showed similar morphology. Smears showed follicular cells in small clusters along with cyst macrophages, singly and in clusters, in a background of thick and thin colloid. A diagnosis of benign nodule possibly colloid goitre was made. (Figure 1)

Figure 1: Smears show only cyst macrophages and think colloid (Haematoxylin and Eosin, x 100)	Figure 2: Firm nodule in the upper pole of isthmus. Cut surface showed solid areas.

Further imaging with a Contrast-Enhanced Computed Tomography (CECT) of the neck revealed a large, well-defined mixed solid-cystic lesion involving the isthmus and left lobe of the thyroid, which was again reported as likely of a benign etiology.

Given the above findings, a left hemi thyroidectomy was performed. On table the surgeon observed the thyroglossal duct which could be traced down to a on the upper margin of the isthmus. On palpation, surgeon observed the nodule to be firm to hard. The firm mass was excised. The excised specimen was sent for histopathological examination (HPE).

On gross examination the hemi thyroidectomy specimen measured 7.8 x 8.8 x 3.6 cm. The external surface was grey-brown with attached capsule. On cut section, red-brown fluid was expelled. On inspecting the cut surface few grey-white fibrotic areas were noted. On microscopy examination this lesion was reported as Colloid Goitre with Hashimoto’s Thyroiditis.

Also received was another specimen which consisted of a single, irregular, grey-tan soft tissue bit measuring 2.8 x 1.9 x 1 cm. (Figure 2) On cut surface a lumen of duct was identified and the tissue was firm in consistency. At microscopy sections showed a duct made up of fibrous wall with extensive calcific areas. The lumen of the duct showed a tumor comprising of cells in predominantly papillary pattern along with occasional follicle formations. Individual cells lining the papillae and the follicles showed crowding and overlapping. These tumour cells demonstrated moderate eosinophilic cytoplasm, mild nucleomegaly, round to oval with a single nucleus showing nuclear clearing, margination of the chromatin and occasional intra nuclear grooves. Scanty mitosis were also noted. The wall of the duct shows normal thyroid follicles and chronic inflammation. The tumour cells were embedded in the duct walls at places. However, tumour cells were not extending beyond the duct. (Figure 3-6) Hence a final diagnosis of papillary carcinoma of thyroid-classic type (PTC), arising in a thyroglossal duct cyst was made. Patient is doing well one year post surgery. Institutional ethical clearance was obtained from the institutional ethical committee for publication of the as report.

Figure 3: Section shows cyst with tumour within it (Haematoxylin and Eosin, x 40)	Figure 4: Section shows protrusion of tumour cells outside the capsule (Haematoxylin and Eosin, x 100)
Figure 5: Section shows tumour cells trapped within the cyst wall. (Haematoxylin and Eosin, x 100)	Figure 6: Section shows tumoral papillae line by tumour cell showing nuclear crowding, overlapping, nuclear clearing and grooving. (Haematoxylin and Eosin, x 400)

Discussion

The profound rarity of thyroglossal duct cyst carcinoma (TGDCC) is evidenced by reported incidences in literature typically ranging from less than 1% to approximately 1.5% of all TGDC cases, underscoring the importance of early recognition, accurate diagnosis and proper management; especially in the era of personalised oncology care. Among all the histologic types of malignancies, papillary carcinoma is most common, seen in 80 to 94% cases. Rarely squamous cell carcinoma, follicular and anaplastic carcinomas have been reported to occur in TGDC[4,6,9].

Diagnosis of TDCC is most frequently made postoperatively, primarily through careful histopathological evaluation following surgical removal of the cyst. Preoperative evaluations like USG and FNAC frequently suggest a benign lesion, as was observed in the present study. However, the operating surgeon, in the present study observed a firm to hard mass at the end of the thyroglossal duct which was excised[8,9].

The thyroid gland descends from the base of tongue through the thyroglossal duct to its final position in the neck. There may be remnants of thyroid tissue anywhere in its path which is regarded as ectopic thyroid tissue which normally atrophies[1]. But, persistence of it, potentially leads to the formation of cysts. These remnants of ectopic thyroid tissue within the cyst wall are considered the primary site of origin for papillary thyroid carcinoma in TGDCs[3,4]. The presence of thyroid follicles in the cyst wall, as observed histologically, further supports this theory. Few authors have been suggesting that papillary carcinoma in a TGDC could represent metastasis from a primary thyroid tumour, but this phenomenon is rare [1,2]. The frequent co-occurrence of papillary carcinoma in both the TGDC and the normally located thyroid gland is often interpreted as synchronous primary tumours arising independently in ectopic and orthotropic thyroid tissue, rather than a metastatic event. In the present case report, the thyroid gland did not show any evidence of malignancy [2,4]. The exact pathogenesis of PTC occurring in TGDC is not unknown, however the role of molecular alterations BRAF V600E, RET/PTC gene rearrangements akin to that seen in PTC of thyroid gland has been reported [2].

While TGDC are more commonly seen in younger individuals, TGDCC is more likely to be diagnosed in adults, typically in third and fourth decade of life, making the patient's age a relevant factor when considering the possible diagnoses. A midline painless neck swelling is routinely a presenting feature for TGDCCs, but it is not specific for malignancy. While suspicious signs like fixation, firmness, or rapid growth may indicate malignancy but are not definitive. TGDCC are diagnosed late either as intraoperative findings on frozen section or post operatively on histopathological examination. In the present case report, a 60-year-old woman came with a long standing midline swelling in front of neck, slow growing, firm in consistency, freely mobile and was painless. This presentation is nonspecific and does not provide any clue for a PTC arising from a thyroglossal duct cyst. This is similar to the existing literature which points out that that such carcinomas often have an indolent or asymptomatic presentation and are mostly diagnosed post-surgery due to their similarity to benign thyroglossal duct cysts [1,2,5].

Radiological modalities like USG and CECT play a key role in the preliminary evaluation of TGDCs [2,4,5,7,11]. While these imaging techniques can highlight characteristics that suggest a possible malignancy within the cyst (TGDCC), they typically lack definitive diagnostic value on their own [2,8]. While USG can identify features such as calcification, lymphadenopathy, and solid components within a cyst, CECT can give a clear picture of the extent of the lesion and its relationship with adjacent structures. In the present case, the thyroid USG showed calcification in the isthmus which was interpreted as TIRADS III, and the CECT scan showed a large mixed solid-cystic lesion involving the isthmus and left lobe of the thyroid, which was likely benign. This is concordant with the findings of Mahajan et al., Kirmani et al., and Bu et al. who suggested that the presence of calcification within a thyroglossal duct cyst should increase suspicion for carcinoma [2,6,12]. Additionally, Kirmani et al., Mahajan et al., and Srivanitchapoom et al. pointed out that USG showing a central solid component is a predictor of malignancy in suspected TGDCs [6,12,13]. Despite the presence of calcification and a mixed lesion in this case, which can be associated with malignancy, the initial radiological assessment favoured a benign aetiology, underscoring the inherent limitations of imaging in definitively diagnosing TGDCC.

Though FNAC is a highly sensitive tool in triaging patients with thyroid lesions, its role in TGDCC is often limited by scanty cellularity and cystic nature of the lesion [5,13]. Few of the TGDCCs find place in the indeterminate category, especially when the cells show degenerative atypia due to their presence in cystic fluid further adding to the diagnostic dilemma[5,7]. However, recent progress in molecular cytology allows application of mutational and gene expression analysis for risk stratification of such indeterminate cases [1,2].

Following surgical excision of a suspected thyroglossal duct cyst, HPE is crucial for definitive diagnosis, especially with long standing TGDCs. Histopathology report confirmed the unexpected finding of papillary carcinoma in the thyroglossal duct cyst. However, the left lobe and isthmus of thyroid gland revealed the presence of colloid goitre with Hashimoto's thyroiditis.

HPE of PTC in TGDC shows classical features of PTC like true papillae, distinctive nuclear features consistent with papillary carcinoma like nuclear enlargement, nuclear grooves, and pseudo inclusions along with psammoma bodies. However differentiating this from a metastatic PTC is important in terms of difference in prognostic and therapeutic implications. Joseph and Komorowski et al proposed following criteria for distinguishing PTC in TGDC from metastatic PTC: i) presence of thyroglossal duct remnant, ii) presence of ectopic thyroid tissue in the cyst wall and iii) absence of PTC in the thyroid gland. In the present case report all three criteria were met [14].

Extent of the surgery in TGDCCs is controversial. Similar to TGDC, the standard surgical treatment for low risk TGDCC is Sistrunk procedure. Here the cyst, the central part of the hyoid bone, and a channel extending towards the base of the tongue are removed [4]. However in the presence of high risk features like coexistent malignancy in thyroid gland, lymph node metastasis, aggressive histologic subtype, capsular invasion, total thyroidectomy with radical neck dissection in advocated[6,12]. Nevertheless, the decision to over treat should not outweigh the risk of surgical morbidity.

Radioiodine therapy is indicated in TGDCCs cases who had undergone total thyroidectomy. Regular follow-up usually involves ultrasound examination and serum thyroglobulin assay to monitor for any signs of recurrence[1,8]. The prognosis of TGDCC is excellent following total surgical excision[1,4].

Comprehensive review of existing literature on TDCC is depicted in table. [Table 1]

Conclusion

This case report highlights the importance of considering malignancy, however infrequent, in the differential diagnosis of TGDC masses, even in the absence of overt suspicious features. The case underscores the need for thorough pathological examination of excised TGDCs to identify such unexpected findings. Recent advances in radiological, molecular and cytological approaches can pave way for accurate preoperative diagnosis, ensuring personalized therapeutics. Further literature on individual case reports, or series or multi-institutional studies are required which could serve as data base for formulation management guidelines for this uncommon malignancy.

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