Abstract
Papillary carcinoma constitutes 80% of thyroglossal duct cyst carcinoma (TGCC). The mainstay of treatment for TGCC is Sistrunk procedure. Due to lack of clear-cut guidelines in managing TGCC, the role of total thyroidectomy, neck dissection and adjuvant radioiodine therapy is still debatable. This was a retrospective study which included cases of TGCC treated in our institution over a period of 11 years. The aim of study was to assess the need for total thyroidectomy in management of TGCC. Patients were divided into two groups based on the surgical treatment they underwent and the treatment outcomes were compared. The histology was papillary carcinoma in all cases of TGCC. Overall, 43.3% of TGCCs had a focus of papillary carcinoma in total thyroidectomy specimen. Lymph node metastasis was noted only in 10% of TGCC and not identified in isolated papillary carcinoma confined to thyroglossal cyst. 7-year overall survival (OS) for TGCC was 83.1%. Prognostic factors like extracapsular extension or lymph node metastasis did not affect OS. Addition of total thyroidectomy and neck dissection to Sistrunk procedure did not offer any survival advantage. In a case of TGCC, FNAC should be done from any clinically suspicious thyroid nodules or lymph nodes. TGCC has a good prognosis following treatment and none of the cases in our series has disease recurrence during follow-up. Sistrunk procedure was an adequate procedure for treatment of TGCC with clinically and radiologically normal thyroid gland.
Keywords: Thyroglossal cyst duct, Papillary carcinoma, Sistrunk procedure
Introduction
Thyroglossal duct cyst is the most common anomaly in the development of the thyroid gland. Seventy percent of thyroglossal duct cysts are diagnosed during childhood and 7% are diagnosed in adulthood [1]. Thyroglossal duct cysts account for 70% of the congenital midline neck swellings in childhood [2]. Only 1% of thyroid carcinoma evolve from thyroglossal duct cysts [3]. Though Sistrunk procedure is gold standard in treatment of thyroglossal cyst carcinoma (TGCC), the role of total thyroidectomy, radioiodine therapy and suppressive thyroxine therapy still remains controversial, besides adding to the economic burden of the patient. Due to rarity of this malignancy and lack of multicentric studies, there is no consensus on the management of TGCC which prompted us to undertake this study in our institution. Our work is unique because it is one of the largest reported series of TGCC in literature and there are very few studies on TGCC from this part of the world.
Materials and Methods
This was a retrospective study conducted in the Department of Head & Neck Surgery, Regional Cancer Centre, Thiruvananthapuram, India. Being the main tertiary cancer centre in the public sector in Kerala, it caters to cancer patients across the state of Kerala, Western and Southern districts of Tamil Nadu. A large number of thyroid malignancies are referred to our centre for treatment. All such cases of thyroglossal cyst carcinoma which were treated between 1 January 2003 and 31 August 2014 in our institution as per institutional protocol were included in the study. The exclusion criteria included cases of papillary carcinoma of thyroglossal cyst operated elsewhere and then referred to our cancer centre for further management. This study was approved by the Institutional Review Board.
Usually, patients come to our centre with ultrasonography and cytology reports done elsewhere. However, in all cases of TGCC, an in-house ultrasonography of the neck was done to confirm the presence of a lesion in thyroglossal cyst and also to rule out any suspicious nodules in the thyroid gland and lymph node metastasis. Fine needle aspiration cytology (FNAC) of the thyroglossal cyst was done to confirm the presence of carcinoma. FNAC was also taken from suspicious nodules in the thyroid gland or significant lymph nodes if any.
Once the diagnosis of carcinoma in thyroglossal cyst was confirmed, the cases were treated as per institutional protocol which included Sistrunk procedure for papillary carcinoma involving the thyroglossal cyst alone. For cases of TGCC with concomitant carcinoma involving thyroid gland, total thyroidectomy was done along with Sistrunk procedure. For cases with metastasis in lymph nodes, neck dissection was also done along with the surgery.
Hence, there were two groups of patients in our case series: 1st group comprised of papillary carcinoma confined to thyroglossal cyst which underwent Sistrunk procedure alone (12/30 cases). The 2nd group comprised of cases of papillary carcinoma involving thyroglossal cyst and thyroid gland with or without metastatic lymph nodes, who underwent Sistrunk procedure with total thyroidectomy with or without neck dissection (18/30 cases). Though there have been several studies on TGCC in literature, none of them have compared treatment outcomes between these two treatment groups. Through our study, we want to address this issue and conclude if Sistrunk procedure is adequate treatment for isolated TGCC confined to thyroglossal cyst.
The 1st group with the presence of papillary carcinoma in thyroglossal cyst without cyst wall invasion in the final histopathology report, in the absence of thyroid nodules or lymph nodes on clinical and radiological evaluation, were kept on thyroid suppression and followed up with annual TSH and ultrasonography. The 2nd group with the presence of papillary carcinoma in thyroglossal cyst and thyroid gland with or without metastatic lymph nodes in the final histopathology report underwent radioiodine whole body scan and radioiodine ablation if indicated. This group was kept on thyroid suppression and followed-up with subsequent radioiodine whole body scans, TSH, thyroglobulin and ultrasonography of the neck.
Clinicopathological details, treatment details and follow-up data of all patients were collected from medical records, Head & Neck Surgical Oncology and Nuclear Medicine clinics. Statistical analysis was done using IBM SPSS software version 24. Survival was calculated using Kaplan–Meier curve and prognostic factors including concomitant involvement of thyroid gland in TGCC, presence of extrathyroidal extension and lymph node metastasis were assessed using Cox’s proportional hazards model. Statistical significance was set at p value < 0.05.
Results
Review of literature revealed that our present study with 30 cases is probably the largest series of TGCC from a single institution. Twenty-one of the 30 patients included in our study were females. The mean age of our case series was 33 years (standard deviation 13.9). The youngest case of TGCC was a 2-year-old girl child who was successfully treated and is presently on regular follow-up. Most of the TGCC cases were less than 40 years of age (70%). The most common presentation was the midline neck swelling. In our study, the most common location of TGCC was the infrahyoid region (Table 1).
Table 1.
Location of thyroid carcinoma of the thyroglossal cyst
| Location | Number | Percentage (%) |
|---|---|---|
| Prehyoid | 7 | 23.3 |
| Infrahyoid | 23 | 76.7 |
There were 30 cases included in our study. FNAC from thyroglossal cyst was diagnostic of papillary carcinoma (Bethesda VI) in 53.3% of cases; the remaining cases had features suspicious of malignancy on FNAC. Cases with clinically or sonologically suspicious nodules in thyroid gland underwent FNAC, and if FNAC was suggestive of malignancy, they underwent total thyroidectomy along with Sistrunk procedure. Similarly suspicious lymph nodes on clinical examination or ultrasonography underwent FNAC; if suspicious of metastasis, neck dissection was done along with the surgery.
Among 18 cases which underwent total thyroidectomy along with Sistrunk procedure, 72.2% (13/18 cases) had malignancy involving the thyroid gland in final histopathology report. Among the 3 cases which underwent neck dissection along with surgery, 100% (3/3 cases) had lymph node metastasis.
The histology of all 30 cases included in our study was papillary carcinoma thyroid. 56.7% of cases had carcinoma confined to thyroglossal cyst alone whereas 33.3% of cases had carcinoma involving the thyroid gland and thyroglossal cyst. Ten percent of cases had metastatic lymph nodes along with carcinoma involving thyroid gland and thyroglossal cyst (Table 2). Overall papillary carcinoma involving the thyroid gland was noted in 43.3% of cases.
Table 2.
Papillary carcinoma identified in histopathology
| Papillary carcinoma identified on histopathology | Number of cases | Percentage (%) |
|---|---|---|
| In thyroglossal cyst only | 17 | 56.7 |
| In thyroglossal cyst and thyroid gland | 10 | 33.3 |
| In thyroglossal cyst, thyroid gland and lymph nodes | 3 | 10 |
Except 2 cases which had extrathyroidal extension (T3), the tumor focus was less than 2 cm and confined to the thyroid gland (T1) in all the remaining 28 cases of TGCCs.
Interesting to note that all cases with lymph node metastasis had tumor involving both the thyroglossal cyst and thyroid gland. None of the 56.7% cases involving the thyroglossal cyst alone had lymph node metastasis.
Only 13.3% patients received radio-iodine ablation as adjuvant treatment for indications such as extrathyroidal extension and lymph node metastasis. The post-ablation follow-up scan done after 6 months in all these cases showed no radioiodine uptake anywhere in the body, suggestive of complete ablation.
All 30 cases were followed-up regularly based on institutional protocol, with a mean follow-up of 10.7 years and maximum follow-up of 18 years. Statistical analysis showed a 7-year overall survival (OS) of 83.1% for TGCC. There was no significant difference in the overall survival when the 1st group of patients who underwent Sistrunk procedure alone (7-year OS 70.1%) was compared to the 2nd group of patients who underwent Sistrunk procedure with total thyroidectomy with or without neck dissection (7-year OS 89.5%) (p value 0.31) (Table 3). None of the patients in either of the two groups developed locoregional recurrence or distant metastases. There were no disease-related deaths in our study.
Table 3.
Comparison of overall survival among patients who underwent Sistrunk procedure alone vs Sistrunk procedure with total thyroidectomy (TT) with or without neck dissection (ND)
| Surgery done | 7-year overall survival | P value |
|---|---|---|
| Sistrunks operation alone | 70.1% | 0.310 |
| Sistrunks operation + TT + ND | 89.5% |
Prognostic factors like the presence of extrathyroidal extension [p value 0.46 with SE(%) 7.4] or lymph node metastasis [p value 0.38 with SE(%) 7.6] did not significantly affect overall survival. Adjuvant treatment with radio-iodine ablation also did not significantly improve overall survival.
Discussion
During embryological development, the thyroid gland develops from an invagination of tissue at the foramen caecum in the base of the tongue which occurs during the 3rd or 4th week of gestation. By 7th week, this tissue descends through or behind the hyoid bone to its midline position in the neck, anterior to the trachea. Usually, this tract gets obliterated later; however if the tract fails to obliterate, a thyroglossal duct cyst may occur at any point along its path of descent [4].
There is a controversy regarding the origin of thyroglossal cyst carcinoma. Rossi et al. [5] suggested that majority of the TGCC develop as primary malignancy from a thyroid remnant, whereas Baglam et al. [6] considered TGCC as a metastatic focus from occult tumour within thyroid gland.
On ultrasonography, thyroglossal cyst appears as an anechoic, hyperechoic or heterogenous complex lesion and cancer within the thyroglossal cyst appears as a mural lesion within the cyst sometimes with microcalcification or as tumour invading cyst wall [7].
FNAC must be done for a thyroglossal cyst prior to surgical treatment since a diagnosis of cancer on FNAC aids the surgeon in planning the optimum surgery needed for the patient [8]. In our study, papillary carcinoma was diagnosed on FNAC in 53% (16/30) of cases. Similarly, the pre-operative diagnostic accuracy of thyroglossal duct cyst carcinoma using FNAC was 53% in the study by Yang et al. [8]. Papillary carcinoma of thyroglossal duct cyst represents more than 80% of TGCC [9]. According to Widstrom et al. [10], to diagnose a primary thyroglossal cyst carcinoma, the carcinoma should be in the thyroglossal cyst wall and carcinoma involving thyroglossal duct cyst should be differentiated from a metastatic cystic lymph node by demonstrating squamous or columnar epithelial lining and normal thyroid follicles in cyst wall.
Since the rate of malignancy in thyroglossal cyst is as low as 1%, the operating surgeon usually does not suspect malignancy in thyroglossal cyst pre-operatively and sometimes even an FNAC is not done [11]. However, chances of malignancy are higher in elderly patients who present with thyroglossal cyst [12].
In our study, the most common location of TGCC was the infrahyoid region which was similar to findings of the study by Patel et al. [13]. Concomitant papillary carcinoma involving thyroglossal cyst and thyroid gland was noted in 43.3% of cases in our study. In the series of 12 cases reported by Heshmati et al. [14], 33% of cases had carcinoma involving both the thyroglossal cyst and the thyroid gland.
Ten percent of TGCC presented with lymph node metastasis in our study. Similarly, Weiss et al. [15] reported lymph node metastasis in 11.3% of primary papillary carcinoma of thyroglossal duct cyst. There is no evidence to perform neck dissection routinely along with surgery for thyroglossal cyst carcinoma [16]. None of the cases in our study had locoregional recurrence or distant metastases. In the case series published by Doshi et al. [17], only one among the 14 cases of TGCC had lung metastasis whereas none of the cases had disease recurrence.
Sistrunk procedure is the gold standard treatment for TGCC. Total thyroidectomy needs to be done in cases with malignancy in the thyroid gland. Neck dissection needs to be considered in cases with lymph node metastasis. Radioiodine ablation therapy should be decided based on final histopathology report and radioiodine scan findings. The indications for more aggressive treatment in cases of TGCC are as follows: age more than 45 years, tumour size more than 4 cm, tumour with soft tissue extension, regional lymph node metastasis or distant metastasis [13].
In our study, among 18 cases which underwent total thyroidectomy along with Sistrunk procedure based on pre-operative evaluation, 72.2% had malignancy involving the thyroid gland in final histopathology report. Hence, pre-operative evaluation including clinical examination, ultrasonography and FNAC guided us in planning adequate surgical treatment which included the addition of total thyroidectomy and neck dissection to Sistrunk procedure wherever indicated.
Literature review shows ours is one among the few studies which compared the treatment outcomes of two groups: the 1st group of patients with carcinoma confined to the thyroglossal cyst and the 2nd group of patients with concomitant carcinoma of thyroglossal cyst and thyroid gland with or without lymph node metastasis. However, the 2nd group of patients had no survival advantage even when total thyroidectomy with or without selective neck dissection was done along with Sistrunk procedure (P value 0.31). Likewise, addition of total thyroidectomy or selective neck dissection to Sistrunk procedure did not have any impact on outcome (P values 0.1 and 0.7) in the univariate analysis of prognostic factors to study overall survival done by Patel et al. [13].
In all cases of thyroglossal cyst carcinoma, total thyroidectomy is not warranted. However, patients who have undergone total thyroidectomy for concomitant malignancy in the thyroid gland can be kept on follow-up with post-operative radioiodine scans and thyroglobulin.
Prognosis of papillary carcinoma of thyroglossal cyst is favourable as compared to prognosis of squamous cell carcinoma of thyroglossal cyst according to Heshmati et al. [14]. Since papillary carcinoma is the most common histologic type of TGCC with a prolonged course, it is mandatory to keep such patients on long-term follow-up [15]. One limitation of our study was that, though our series was amongst the largest reported from a single institution, the sample size is small. Another limitation was that 72.2% of cases which underwent total thyroidectomy along with Sistrunk procedure were followed up with radioiodine scans and thyroglobulin values, whereas such a follow-up was not possible in the remaining 27.8% cases.
Conclusions
In cases of thyroglossal cyst, an ultrasonography of the neck and FNAC from the epithelium lining the thyroglossal cyst should be done pre-operatively. In cases of TGCC, FNAC should be done from any suspicious thyroid nodules or lymph nodes picked up clinically or on ultrasonography as a significant number of TGCCs harbour co-existing malignant lesions in thyroid gland and metastasis in lymph nodes in neck.
In our case series, lymph node metastasis was not seen in isolated papillary carcinoma confined to thyroglossal cyst. None of the cases in either group had disease recurrence on follow-up. This study was done to understand if there was a role for total thyroidectomy in the management of thyroglossal cyst carcinoma, and through our study, we conclude that Sistrunk procedure is an adequate procedure for treatment of thyroglossal cyst carcinoma who have a clinically and radiologically normal thyroid gland. However, more multicentric studies with larger sample size are needed to develop standard guidelines for treatment of TGCC.
Acknowledgements
We take this opportunity to thank the faculty, fellows, post graduates and staff of the Department of Head & Neck Surgery, Nuclear Medicine, Biostatistics & Epidemiology for their whole-hearted cooperation in completion of this study.
Declarations
Ethical Approval
There was adherence to ethical standards in this study. All procedures performed in studies were in accordance with the ethical standards of Regional Cancer Centre, Thiruvananthapuram approved by the Institutional Ethics Committee.
Conflict of Interest
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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