31 December 2024: Articles
A 46-Year-Old Man with an Incidental Finding of a Papillary Thyroid Carcinoma in a Thyroglossal Duct Cyst
Mistake in diagnosis, Unusual or unexpected effect of treatment, Rare coexistence of disease or pathology
Agnieszka Witkowska
DOI: 10.12659/AJCR.945625
Am J Case Rep 2024; 25:e945625
Abstract
BACKGROUND: The thyroglossal duct cyst, which develops from the midline migratory tract between the foramen cecum and the anatomic location of the thyroid, is the most prevalent congenital abnormality of the neck, accounting for about 70% of all cervical neck masses in children and 7% in adults. Only up to 1% of these abnormalities contain malignant thyroid tissue, with 90% of those cases being papillary thyroid carcinoma. Thyroglossal duct cyst is rarely linked to carcinoma. Clinical presentation of thyroglossal duct cyst carcinoma is generally impossible to differentiate from benign tumors before surgery, and most cases are incidentally detected after surgery, due to histopathological evaluation of the resected cyst.
CASE REPORT: A 46-year-old man presented with a painless, progressively enlarging neck lump. Physical examination identified a well-defined, mildly firm mass situated anteroinferior to the hyoid bone. Imaging indicated that a thyroid gland duct cyst was the most likely diagnosis. The patient underwent the Sistrunk procedure. Histopathological analysis revealed papillary thyroid carcinoma within the thyroid gland duct cyst.
CONCLUSIONS: Carcinomas occurring in the thyroglossal cyst are uncommon. The causes of thyroglossal duct carcinoma are unclear, and neither a detailed medical history nor a physical examination can reliably diagnose it before surgery. The management of such cases remains debated, owing to the rarity of reported occurrences. So far, the standard treatment involves the Sistrunk procedure, followed by close patient monitoring. For patients with metastatic disease, a total thyroidectomy is necessary, and if neck metastases are present, neck dissection is required.
Keywords: Thyroglossal Cyst, Thyroid Neoplasms, Thyroidectomy
Introduction
The thyroglossal duct cyst (TGDC) is the most common cervical anomaly, representing 70% of all congenital neck masses seen among children and a prevalence of 7% in adults [1]. Embryologically, the thyroglossal tract is formed because of the thyroid gland descending. The endodermal proliferation starts as an invagination within the tongue, at the location of the foramen cecum, and descends caudally, traversing the hyoid bone and larynx anteriorly, reaching its ultimate location around the cricoid cartilage and upper trachea. If the TGDC fails to disappear, it remains as a cyst tract, duct, or ectopic thyroid within a cyst or duct [1–4]. The likely cause of inappropriate involvement is genetic factors, including mutations in genes responsible for the development of thyroid follicular cells, such as TITF1, TITF2, and PAX8 [5,6]. Typically, 61% of these remnants are located at the level of the hyoid bone, followed by suprahyoid muscle (24%), suprasternal bone (13%), and intralingual muscle (2%) [1]. Mostly, it manifests as a swelling in the midline of the anterior cervical region, being mobilized with deglutition and protrusion of the tongue [7]. Although most midline cervical tumors are diagnosed as benign, up to 0.7% to 1% can contain malignant neoplasms [8]. There are almost no differences in symptoms between TGDC and thyroglossal duct cyst carcinoma (TGDCCa), with both often appearing as a painless mass in the midline of the neck [9]. Only about 3% of patients with TGDCCa report having dysphagia and pain [10]. In 22% to 43% of instances, individuals exhibit swallowing challenges or recurrent throat infections [11]. The most common primary TGDCCa is a papillary carcinoma (80–90%), with the median age of initial diagnosis being in the fourth decade of life [1]. Rarer tumor types, such as mixed papillary-follicular carcinomas (7%), squamous cell carcinoma (5%), follicular carcinoma (1.7%), Hürthle cell carcinoma, anaplastic carcinoma, and adenosquamous carcinoma (0.9%) have all been documented [1,12,13]. Although the discussion has lasted for years, there is no clear consensus on the ideal management of TGDCCa [14]. Several authors believe that well-differentiated thyroid carcinoma in the thyroglossal duct can be effectively treated with the Sistrunk procedure, while others advocate for total thyroidectomy in cases of papillary carcinoma [15]. This study aimed to highlight the clinical features, diagnostic methods, and management of patients with TGDCCa. Currently, there are slightly more than 300 published cases of TGDCCa, with only 2 reported from Poland [16]. This study adheres to the SCARE 2020 criteria [17].
Case Report
A 46-year-old man was referred from a family medicine doctor for an asymptomatic midline neck swelling that had been progressively reshaping in size for almost 15 years. For the first time, the patient noticed the swelling during shaving his neck but neglected it. The patient had no history of pain, dysphagia, dyspnea, voice degradation, or loss of weight and appetite. He denied signs of thyroid malfunction, such as tremors, cold or hot intolerance, diarrhea or constipation, tiredness, dry skin, muscle weakness, hair loss, and irregular heartbeats. His familial history of thyroid cancer was negative, but his mother had hypothyroidism and goiter. The patient had a history of gout and hypertension. He worked as a security guard at a military museum. Ten years from the beginning of the lump, the patient was exposed to the isotope of strontium-90, with an activity of 3.6 G Becquerel, with a total radiation dose of 400 μ Sievert, while working on a museum renovation, but it was not directly applied to the neck area. The lump began to grow; however, due to the COVID-19 pandemic, the initial attempt of surgery at another hospital was postponed, and in the meantime, the lump decreased in size. Apart from a lump located anteroinferior to the hyoid bone, the physical examination was unremarkable.
A well-demarcated, round protrusion measured 3×4 cm upon admission to hospital. It was moderately firm yet movable, painless upon palpation, and moved with swallowing motions and tongue protrusion. The rest of the head and neck examination, including flexible fiberoptic upper airway endoscopy, did not reveal any other significant findings. Thyroid gland palpation and functional thyroid tests, including TSH, FT3, and FT4, were also normal. There was no lymphadenopathy or tongue protuberance noted. The skin over the cyst was normal, with no inflammatory signs. All other routine laboratory investigations were within the normal limit.
TGDC was suspected as an initial diagnosis, based on the ultrasonography result. Even though an ultrasonography examination was useful, due to the late onset of TGDC, this hypothesis was verified with contrast-enhanced computed tomography (CT). It revealed a sizeable (3.7×3.2×4.0 cm) homogeneous cyst with a thin capsule with a well-defined and smooth contour located in the middle and slightly left to the level of the laryngeal prominence. However, in the lower part of the cyst, an internal septum with small calcification was visible, with an average of 30 Hounsfield units in the phase before and after contrast administration (Figure 1). The thyroid gland was homogeneous and not enlarged. Lymph nodes in group III were visible on both sides, up to 12 mm in the short axis, but with preserved sinuses. The remaining lymph nodes in the neck were up to 10 mm.
There was no radiologic or clinical evidence of thyroid gland disease or neck lymphadenopathy, apart from microcalcifications inside the TGDC. Based on the imaging findings, the most likely diagnosis was TGDC. The patient underwent surgical removal of the TGDC, using the Sistrunk procedure. The operation was uneventful, and there was no suspicion of malignancy at the time of surgery; therefore, we did not choose to perform a frozen section examination. The recovery was uneventful, without postoperative bleeding, excessive pain, and hematoma. The patient was discharged 2 days later.
The histopathologic findings revealed a fibrous tissue with a TGDC (Figure 2). A papillary thyroid carcinoma measuring 8 mm in width was identified within the TGDC (Figure 3). The cytological features of papillary carcinoma, such as ground glass and intratesticular inclusion, was noted (Figure 4). Furthermore, there was no microscopic vascular, perineural, or adjacent fatty tissue invasion. Overall, the image indicated the development of primary papillary thyroid cancer within the thyroglossal duct, which was positive for cytokeratin 19. The pathologic tumor, node, metastasis staging was determined to be pT1. The hyoid bone was tumor-free. After definitive histopathologic analysis, the blood tests for calcitonin, TPO antibodies, antithyroglobulin antibodies (Ig-M and Ig-G), TSH, FT3, and FT4 were done. All the results were within the reference range, including thyroglobulin levels, which confirmed complete resection of the tumor. An endocrinological consultation recommended to test thyroid hormones and perform ultrasound imaging of the thyroid gland every 6 months. The first check-up ultrasound examination shown typically located bilobed thyroid gland with homogeneous echostructure, not enlarged, without focal changes and increased flow through the gland, with Power Doppler. Visible lymph nodes were normal, with preserved hili.
Discussion
DIAGNOSTICS:
The initial test of choice in case of midline neck swelling is ultrasonography. Ultrasound characteristics indicative of malignancy include an enlarged nodule exhibiting a comet tail sign, cystic components, microcalcifications, and poorly defined margins [25]. CT and magnetic resonance imaging play a decisive role in preoperative diagnosis, due to an evaluation of the infiltration of the tumor to the surrounding tissues [26,27]. The most reliable preoperative method for detecting malignancy in midline neck masses is FNAB [28], especially if performed under ultrasound guidance, which reduces the false-negative results [29]. FNAB is a well-tolerated, cost-effective, and safe procedure for diagnosing thyroglossal duct abnormalities [30]. However, there is debate over the utility of FNAB used preoperatively [31], due to its low sensitivity achieved in about 53% to 60% of cases [32–34]. To summarize, even if there are radiologic traits or positive FNAB for suspected lethality, a definitive diagnosis cannot be made until the surgery and histopathological outcome [35]. Immunostaining for cytokeratin 19 is a highly sensitive marker commonly used to verify papillary thyroid carcinoma. It reacts with the smallest human cytokeratin filaments and shows a heterogeneous staining pattern in non-keratinizing squamous epithelia and hair follicles, with strong staining of the basal layer [36]. The patient’s immunochemistry result for cytokeratin 19 was positive.
TREATMENT:
The ultimate treatment for TGDC is the resection of the cyst, along with the central part of the hyoid and the excision of the duct tract. It was first described by Walter Ellis Sistrunk in 1920, and has been considered a criterion standard for the treatment of TGDC to date [21,37]. With reference to TGDCCa, establishing the origin of carcinoma (primary ectopic or metastatic from the thyroid gland proper) has an influence on making treatment decisions. It was believed that normal thyroid tissue in TGDC indicated non-metastatic origin, whereas the absence of orthotopic thyroid tissue suggested an obvious metastatic genesis. This imposed the necessity of thyroidectomy in cases of thyroid gland lack [38]. The comprehensive assembly proposed categorizing risk into low, moderate, and high, based on factors such as patient age, tumor size, presence of thyroid lesions, margin involvement, histological features, multifocality, nodal involvement, and cyst wall participation [39]. Low risk is characterized by age <45 years, no history of radiation exposure, tumor size <1–1.5 cm or 4 cm (based on the series), and the absence of soft tissue invasion, distant or lymphatic metastases, and aggressive tumor histology. For patients at low risk, the modified Sistrunk procedure can be used [39,40]. For individuals with moderate risk, the suggested course involves total thyroidectomy, hormonal suppressing treatment, and radioactive iodine; and for the high-risk category, vertical lymph node dissection is proposed in conjunction with the other specified treatments [41]. Regarding hormone therapy for suppression, there are no data on its benefit in patients with papillary carcinoma with TGDCCa. However, in 2005, Plaza et al proposed an algorithm in which suppression hormone therapy was recommended in patients with low-risk disease [42]. Nevertheless, it is recommended to consider radioactive iodine ablation therapy for patients with sizable tumors and nodal disease or for those with malignancy affecting both the thyroid gland and TGDC [43].
The rationale for why the Sistrunk operation alone is sufficient for low-risk patients stems from multiple studies examining the frequency of coexisting primary thyroid carcinoma and TGDCCa, which ranges from 0% to 40% [44–47]. As a result, total thyroidectomy, coupled with removal of TGDC, is not endorsed for patients at low risk [48]. Sistrunk surgery alone is sufficient when the cyst wall is well circumscribed, there is no tumor invasion beyond the cyst wall and no lymph node metastasis, and the tumor originates primarily from the cyst floor [2,45,49]. Authors who discern no benefit in thyroidectomy for the patient use arguments such as increased morbidity arising from repeated interventions, the potential for effective follow-up with reintervention at a later stage if thyroid cancer is detected, and ultimately, the optimistic prognosis, such as low recurrence rate (1.8%) [1,49]. Yet, selecting a subset of patients who are free from the risk of concurrent thyroid cancer or do not require radioactive iodine ablation therapy is a challenging task [44]. The European Society for Medical Oncology recommends total thyroidectomy solely for cases classified as T1a, T1b, and T2, with a history of radiation exposure during childhood or adolescence, a family history of thyroid cancer, aggressive features on cytology (if conducted), multifocality, or suspected minimal extrathyroidal extension [50]. Conversely, Balallaa et al [8] argue that total thyroidectomy is indicated regardless of clinical or radiological evidence of thyroid involvement. They argue that it aids in staging, enhances the detection of metastases, and emphasizes that the risk of recurrent laryngeal nerve or parathyroid gland injury is exceedingly rare in skilled hands, with the highest risk observed in redo surgery. It is essential to weigh the potential risks of recurrent laryngeal nerve injury and hypocalcemia against the benefits of radioactive iodine ablation therapy in the aftermath of total thyroidectomy [47].
Our patient was exposed to a radioactive isotope of strontium-90 at work. It is one of the most dangerous products of nuclear explosions. The radioactive isotope strontium-90 is characterized by beta radiation (energy 0.54 MeV), a very long half-life T (1/2)=28 years, and a long biological decay period of 10 years. It can be inhaled along with dust in the air, but it mainly enters the body through the food we eat. Strontium-90 is taken by the body similarly to calcium and can be incorporated into the bone structure. Most of the absorbed strontium is quickly excreted, 20% to 30% is retained in the skeletal system, and approximately 1% is retained in the blood [51]. It can increase the risk of bone cancer and leukemia. Due to its breakdown and beta radiation, it can damage thyroid cells.
Even though this exposure could have influenced TGDC neogenesis, we decided not to perform thyroidectomy, due the context of our practice, where long-term follow-up is generally accessible.
PROGNOSIS:
The prognosis of papillary carcinoma originating in the TGDC duct is excellent [19,52]. Recent reports show a favorable prognosis, with reported survival rates of 99.4% to 100% and 95.6% at 5 and 10 years, respectively [5,32]. Long-term monitoring of these individuals is essential, as delayed metachronous occurrences of papillary thyroid cancer can arise several years after the primary surgery in fewer than 2% of cases [1,19]. Follow-up involves reviewing medical history, conducting physical examinations, performing neck sonography, and conducting whole-body scintigraphy [52]. Additionally, all papillary thyroid cancers should be tested for the BRAFV600E gene mutation, as it is linked to more aggressive cancer growth and a higher mortality rate. Patients who test positive may benefit from more aggressive treatment [53]. Our patient tested negative.
Based on the available literature, we decided against performing a total thyroidectomy and opted to carefully monitor the patient’s condition, despite his history of radiation exposure during adolescence. The total radiation dose did not exceed that of a standard mammography examination. The walls of TGDC were free from carcinoma infiltration, and a CT scan showed no pathological findings in the thyroid gland or lymph nodes. The decision was primarily based on the recommendations of the Polish Society of Endocrinology, which advises against surgery for papillary carcinoma when it presents as a single focal lesion measuring ≤1 cm [54].
Conclusions
The primary challenge with cancer arising from a TGDC is that it is typically diagnosed either during surgery or through detailed histopathological analysis afterward. Suspicion of malignancy should be heightened in elderly patients with a TGDC, due to the rarity of this condition in that age group. Additionally, consideration of malignancy is warranted when the cyst displays hardness, fixation, or irregularities. High-resolution ultrasonography or CT is recommended for all cases suspected of being malignant. FNAB conducted under ultrasound guidance can aid in sampling the mural nodule associated with cystic lesions. The Sistrunk procedure is generally sufficient for most patients, with total thyroidectomy or cervical lymph node dissection reserved for specific, carefully selected cases. Follow-up of these cases is crucial. The prognosis for individuals with papillary cancer associated with TGDC is exceptionally favorable. While surgical removal of the malignancy is considered the standard of care, treatment for TGDCCa should always be personalized and guided by a multidisciplinary team.
Figures
References:
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