Hürthle Cell Carcinoma Arising in a Thyroglossal Duct Cyst

Abstract

Thyroglossal duct carcinoma is a rare clinical condition, accounting for only 1% of operated cases. It is characterized by ectopic thyroid adenocarcinoma developing within thyroglossal duct cysts (TGDCs). Among these, papillary thyroid carcinoma is the most frequently reported pathological type. The clinical presentation of thyroglossal duct malignancies is often nonspecific, with diagnosis typically confirmed postoperatively via the Sistrunk procedure. Due to the rarity of these cases and their generally favorable prognosis, standardized diagnostic and treatment guidelines have not yet been established. We report a rare case of a 31-year-old patient who underwent surgery for an anterior neck mass that had developed over the years. Histopathological examination revealed a Hürthle cell carcinoma occurring in a thyroglossal duct remnant. Following this diagnosis, the patient underwent a total thyroidectomy. The postoperative management plan included radioactive iodine therapy and thyroid hormone suppressive therapy.

Introduction

Thyroglossal duct cysts (TGDCs) are congenital cervical malformations resulting from the failure of resorption of the canal connecting the base of the tongue to the thyroid isthmus or the pyramidal lobe.[1] This canal typically undergoes progressive degeneration and disappears between the 6^th and 8^th weeks of gestation. In cases of incomplete degeneration of the thyroid canal, a TGDC may form. When regression is incomplete, residual thyroid tissue may persist within the cyst. The transformation of this residual thyroid tissue can lead to the development of thyroglossal duct carcinoma.[2] Neoplastic involvement of TGDCs is rare, with a prevalence ranging from 1% to 1.5%.[3,4,5] Diagnosis is most often established postoperatively, following the histopathological examination of the surgical specimen.[6]

Papillary carcinoma is the most common malignancy arising from ectopic thyroid tissue within a TGDC. However, the Hürthle cell variant is extremely rare and is associated with a poorer prognosis. Compared with classical papillary thyroid carcinoma, these cancers are considered to be more invasive[7] with higher rates of lymph node metastasis and extrathyroidal invasion, an increased likelihood of local recurrence, and lower survival rates.[7]

We report a remarkable case of a 31-year-old patient who underwent surgery for a TGDC, with histopathological analysis confirming a Hürthle cell carcinoma without thyroid involvement.

Case report

This is a 31-year-old patient with no significant pathological history who presented with an anterior cervical swelling that had been progressively increasing in size since childhood. The mass caused no compressive symptoms but was a source of esthetic discomfort.

On clinical examination, the patient was in good general condition. A firm, painless anterior median cervical mass measuring 3 cm × 2 cm was noted. The mass was mobile with swallowing and tongue protraction. Palpation of the thyroid compartment was unremarkable, with no inflammatory signs or cervical adenopathy.

Cervical ultrasound revealed an anterior cervical mass extending from the isthmus of the thyroid, measuring 4 cm × 3 cm. The mass exhibited a hypervascularized tissue structure on Doppler imaging, with some anterior microcalcifications raising suspicion of a TGDC. The thyroid gland appeared normal, and no cervical adenopathy was detected. Fine-needle aspiration cytology (FNAC) was performed, and the results were suspicious of malignancy. The patient underwent surgery using the Sistrunk procedure, which involved excision of the cyst, the tract, the body of the hyoid bone, and a basi-lingual muscle collar.

The excised mass weighed 25 g and measured 5 cm × 3.5 cm × 2.5 cm, with a homogeneous appearance on sectioning. Histopathological examination of the resected specimen revealed a neoplastic proliferation composed of vesicular structures lined by an epithelial border. The nuclei exhibited variable hyperchromasia or clarity with a lacquered appearance and often contained nucleoli of variable size. The cytoplasm was predominantly eosinophilic with oncocytic features. The tumor was encapsulated by a thick fibrous capsule, with focal capsular invasion and minimal vascular emboli (two identified), consistent with Hürthle cell carcinoma with capsular invasion and minimal angioinvasion [Figures 1 and 2]. Preoperative testing for the BRAF V600E mutation was not performed.

Figure 1.

(x10) Stained section of thyroglossal duct cancer

Figure 2.

(x10) Microscopy showing the multifocal aspect of Hürthle cell carcinoma

Four weeks later, considering the tumor size (>4 cm), the presence of capsular invasion foci, and to avoid the need for a secondary surgical procedure, a total thyroidectomy with central compartment lymph node dissection was performed. Histopathological analysis revealed thyroid hyperplasia without histological evidence of malignancy, ruling out metastasis from primary thyroid carcinoma. Serum thyroglobulin was measured at 9 ng/mL, and thyroid-stimulating hormone (TSH) was 62 µUI/mL.

Radioactive iodine (RAI) therapy was administered with an ablative intent due to the presence of calcifications, the unfavorable histological type, and the tumor size. This approach also facilitated follow-up, particularly given the patient’s residence in a rural area, which posed an increased risk of loss to follow-up.

A course of RAI therapy with 100 mCi of iodine-131 was delivered under hormonal withdrawal, followed by initiation of LT4-based thyroid hormone suppressive therapy. A post-RAI whole-body iodine-131 scan revealed three iodine-avid parenchymal remnants in the cervical region (median, left paramedian, and right paramedian) without any pathological uptake elsewhere in the body [Figure 3].

Figure 3.

Iodine 131 whole body scan showing three cervical postsurgical thyroid remnants (median, left paramédian and right paramedian), without distant metastases

At the 3-month follow-up under suppressive hormone therapy, the patient remained in good health, with a target TSH value in the lower third of the normal range. A structured active surveillance plan was established for the next 2–5 years, including cervical ultrasound and an efficacy scan at 6 months, followed by annual imaging. In addition, treatment and reassessment during thyroid hormone withdrawal will be conducted over the same period.

Discussion

TGDCs are the most common congenital cervical malformations, accounting for 7% of neck swellings in adults[8] and 75% of cases in children.[9] They result from the abnormal persistence of the thyroglossal duct, an embryonic remnant of the migration of the thyroid gland from the base of the tongue to its definitive anatomical location.[3,10] Most cases are discovered in childhood but can occur at any age, particularly in adults around the fourth decade,[3,4,11] with a slight male predilection. Familial cases of TGDCs have also been reported, with probable autosomal recessive, autosomal dominant, or even multifactorial inheritance patterns.[12] The vast majority of TGDCs are benign. However, neoplastic transformation is rare, with a reported prevalence ranging from 1% to 1.5%.[13] The first documented case of thyroglossal duct carcinoma was reported by Brentano in 1911.[2] Histologically, the most common type is papillary carcinoma,[14] accounting for approximately 83% of cases, followed by mixed papillofollicular carcinomas (8%), squamous cell carcinomas (6%), and, more rarely, Hürthle cell carcinoma, follicular carcinoma, anaplastic carcinoma, and epidermoid carcinoma.[3] Notably, no cases of medullary carcinoma have been reported in the literature.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]

The pathogenesis of thyroglossal duct carcinoma remains debated. Several authors suggest that these carcinomas develop de novo within TGDCs,[12] originating from normal thyroid tissue within the duct wall and along the tract path.[1,16] Others propose that the thyroglossal duct serves as a natural route for carcinoma spread from the thyroid gland.[17] This ongoing debate contributes to variations in therapeutic management, particularly regarding the necessity of thyroidectomy in addition to surgical excision of the TGDC.[8]

The clinical presentation of thyroglossal duct carcinoma is usually nonspecific, with symptoms primarily depending on the location and size of the tumor. This explains why the diagnosis is most often made following the histopathological examination of the surgical specimen.[3,5] In most cases, patients present with cervical swelling without additional symptoms. However, pain, voice changes, rapid tumor progression, weight loss, adenopathy, and respiratory symptoms (such as airway compression) may indicate malignant transformation of the cyst.[4] These symptoms, however, are observed in only a minority of patients[18] and are usually associated with a poor prognosis.

There is considerable controversy regarding the appropriate management of carcinoma discovered on histopathological examination of a resected TGDC, particularly concerning the necessity of thyroidectomy in addition to TGDC excision.[11] Thyroglossal duct carcinoma is relatively rare, and there are limited data on specific diagnostic criteria for this disease. Histopathological examination remains the cornerstone of diagnosis, with key indicators including deeply stained nuclei and intracytoplasmic inclusion bodies.[19]

Currently, the primary clinical diagnostic tools include thyroid ultrasound, cervical CT scan, thyroid function testing, and FNAC, which is often considered the gold standard for diagnosis. However, in the case of TGDCs, the presence of intracystic fluid can limit the diversity of sampled cells, potentially compromising the accuracy of FNAC.[20] Therefore, when ultrasound reveals a TGDC containing a significant amount of fluid, it is recommended to aspirate the fluid before performing the biopsy. Alternatively, a simultaneous biopsy can be performed on any suspicious thyroid nodule to determine the most appropriate surgical approach. Additionally, preoperative testing for the BRAF V600E mutation is frequently conducted, a positive result is strongly associated with malignancy in TGDCs and is often accompanied by lymph node metastases.[21] Morphologically, cervical ultrasound provides valuable information regarding cyst anatomy, extent, presence of parietal nodules, and calcifications. A particularly indicative feature on ultrasound is the “claw sign,” which refers to a median cystic cervical mass embedded in the sublingual muscle band.[22] TGDCs may appear anechoic, hypoechoic, or heterogeneous on ultrasound, but the presence of solid components, wall invasion, and/or calcifications should raise suspicion of malignancy.[23]

Given the rarity of thyroglossal duct carcinoma, no standardized treatment guidelines currently exist for this pathology. Management typically involves a combination of surgery and RAI therapy. Following the initial diagnosis of a thyroglossal cyst, if FNAC indicates a simple cyst, the Sistrunk procedure is performed only if the following conditions are met: An intact tumor envelope, a normal thyroid, patient age <45 years, tumor size <4 cm, and a negative BRAF gene mutation test.[24]

Sistrunk surgery with additional thyroidectomy is recommended in cases where the patient is ≥45 years old, the tumor is ≥4 cm, or the BRAF gene mutation is positive.[24] Furthermore, total thyroidectomy is warranted in cases of cyst wall invasion by carcinoma, histological identification of a vesicular or squamous cell type, or the presence of a clinically or ultrasonographically suspicious thyroid nodule. This approach helps rule out a potential primary thyroid carcinoma and facilitates better follow-up.[25] Some authors also advocate for total thyroidectomy in patients with questionable adherence to regular medical follow-up.[26] Lymph node dissection should be performed when adenopathy is clinically or ultrasonographically suspicious.[3,4]

The role of RAI following thyroglossal duct carcinoma remains controversial. Some retrospective studies suggest that RAI may worsen patient prognosis.[15] Currently, no clear guidelines exist regarding the indications for RAI, and its use is primarily recommended in cases of thyroglossal duct carcinoma associated with thyroid cancer and lymph node metastases.[27] However, thyroid hormone suppressive therapy is always indicated.[3,28] Recurrences may occur several years or even decades later and can be particularly challenging to manage, underscoring the need for lifelong surveillance.[12]

Compared to follicular carcinoma, the Hürthle cell variant is extremely rare and carries a poorer prognosis. It is more invasive[7] with higher rates of lymph node metastasis, an increased likelihood of local recurrence, and lower survival rates.[7]

Prognosis

The prognosis of thyroglossal duct carcinoma appears to be more favorable than that of thyroid carcinoma, primarily due to the rarity of distant metastases.[3,4] The recurrence rate following complete resection of the lesion is <5%.[29] Among all histological types, squamous cell carcinoma of the thyroglossal duct has the poorest prognosis.[30] The presence of significant clinical symptoms at the time of diagnosis may indicate a favorable prognosis and a low probability of recurrence.[31] The 5-year survival rate for Hürthle cell carcinoma is estimated to be between 50% and 60%, according to Rosai,[32] whereas it is reported to be 95.6% for papillary carcinoma, according to Patel.[4,16]

Conclusion

The thyroglossal duct carcinomas are rare, with papillary carcinoma being the most common histological type. However, the Hürthle cell variant is extremely uncommon. These malignancies are typically discovered incidentally through histopathological examination. Their therapeutic management and follow-up remain a subject of debate, particularly in the absence of thyroid involvement. Total thyroidectomy is controversial and is generally recommended for patients over 45 years of age who may benefit from RAI therapy. Lymph node dissection should be performed in patients with confirmed nodal involvement and may also be considered in cases with more aggressive features, such as large tumors or local invasion. The overall prognosis remains poor, with a reported survival rate of 60% and a recurrence rate of 25% among cases documented in the literature.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.