Differentiating Benign and Malignant Thyroglossal Duct Cysts With Ultrasonography, CT, and PET/CT

Abstract

Background Purpose:

To determine if US, CT, and/or ¹⁸F-FDG PET/CT can differentiate benign and malignant thyroglossal duct cysts (TGDCs).

Methods:

In this retrospective review, we identified 72 patients with cytologically proven benign TGDCs and 11 patients with cytologically proven malignant TGDCs. Patient demographics, US and CT features, and maximum standardized uptake value (SUVmax) on PET/CT were compared. On US, TGDCs were assigned a summary score with one point each for irregular margins, solid-component appearance, vascular flow on Doppler US, and calcifications. Score performance in differentiating benign and malignant TGDCs was analyzed.

Results:

Malignant TGDCs were detected at a younger age (optimal cut-off, 43.5 years) (p = 0.001) and were larger (optimal cut-off, > 1.9 cm) (p = 0.041). Malignant TGDCs more frequently had irregular margins on US (p <0.001), calcifications on US (p <0.001) and CT (p = 0.009), and higher SUVmax on PET/CT (p = 0.001). Summary scores could be calculated for 79 TGDCs. All 54 TGDCs with a score of 0 or 1 were benign, whereas both TGDCs with a score of 4 were malignant. The 23 TGDCs with a score of 2 or 3 could not be differentiated by score.

Conclusion:

Malignant TGDCs are diagnosed at an earlier age, are larger, and have higher uptake on PET/CT than benign TGDCs. On US, cystic TGDCs or those containing only solid tissue with smooth margins may not need an FNA (fine needle aspiration) and may be followed with serial US. TGDCs with solid tissue with irregular margins, increased vascular flow, and calcifications are likely malignant; FNA before excision may be beneficial for documenting malignancy and genetic testing. All other TGDCs require FNA for differentiation. On PET/CT, TGDCs with increased uptake require FNA.

1 |. Introduction

Thyroglossal duct cysts (TGDCs) are the most common congenital neck abnormalities and arise in both children and adults. TGDCs account for approximately 75% of midline neck masses in childhood [1] and have a prevalence of approximately 7% in adults [2]. TGDCs can develop anywhere along the pathway of thyroid descent, but most frequently occur in the midline infrahyoid region of the neck. The majority of TGDCs are painless, but in up to 10% of cases, fistula formation may lead to pain, difficulty swallowing, and/or voice changes [3, 4]. A carcinoma is identified in approximately 1% of TGDC cases, and more than 95% of these carcinomas are of thyroid origin [3, 5, 6]. The majority of thyroid carcinomas arising in TGDCs are papillary [7, 8]; squamous cell carcinoma is a less common pathologic type [9, 10].

TGDCs can be surgically removed using the Sistrunk procedure, which comprises transcervical resection of the TGDC, removal of the hyoid bone, and in some patients, excision of the foramen cecum depending on the location of the TGDC and the thyroglossal tract [5, 11, 12]. Indications for the Sistrunk procedure include repeated infections, fistulous tract formation, patient concern about cosmetic appearance, and malignancy [13–15]. Potential complications of this procedure include bleeding, infection, nerve damage, and airway entry [16].

Suspected TGDCs are usually diagnosed on clinical examination [13] and are often evaluated with ultrasonography (US) of the neck [13–15, 17, 18]. Fine needle aspiration (FNA) can be performed if there is concern about the possibility of a malignant component, and different reports have shown that FNA is performed in 10% to 20% of patients with possible TGDCs [3, 4, 19]. Although complications of FNA are rare, FNA can cause bleeding, infection, and damage to surrounding structures. Another consideration is the cost of an FNA that can be avoided if effective means are determined for following likely benign TGDCs.

Sometimes TGDCs are incidentally discovered on imaging studies other than US, such as computed tomography (CT) and ¹⁸F-fluorodeoxyglucose positron emission tomography (PET)/CT. In patients with TGDCs incidentally discovered on CT or PET/CT, further studies are needed to correctly characterize the TGDC as benign or malignant. Another issue is that TGDCs can develop in patients with a separate primary cancer diagnosis and potentially lead to confusion in staging and treatment options. To the best of our knowledge, no studies have addressed these important issues with US, CT, and PET/CT.

In this study, we sought to determine whether US, CT, and PET/CT can differentiate benign from malignant TGDCs. We report our findings and offer our management recommendations.

2 |. Methods

The Institutional Review Board at our institution approved this study and waived the requirement for informed consent. Data were acquired in compliance with all applicable Health Insurance Portability and Accountability Act regulations.

2.1 |. Study Population

We were aware of the 66 previously reported TGDCs [13]. We searched our cytology and radiology databases for patients with suspected benign and malignant TGDCs who underwent a US-guided FNA at our institution, a tertiary referral center for cancer, during the period from 2000 through 2024, and identified 28 additional cases. Exclusion criteria included the lack of a cytologically proven benign or malignant TGDC and the lack of imaging of the lesion with US or CT. Eleven cases did not meet these criteria and were excluded. A total of 72 patients with benign TGDCs and 11 patients with malignant TGDCs were included in the study.

2.2 |. Review of Imaging Studies

A neuroradiologist (JMD) with over 25 years of experience in interpreting head and neck imaging studies reviewed the patient demographics and the US, CT, and PET/CT examinations.

First, the appearance of the TGDCs on US and CT was described as follows: 1) cystic, 2) cystic with septations, 3) cystic with a solid component (“cystic and solid”), or 4) solid. The presence or absence of calcifications in the TGDC and the presence or absence of adenopathy were also recorded. On PET/CT, the maximum standardized uptake value (SUVmax) of the TGDC and the presence of adenopathy were recorded.

Second, as US is a widely available noninvasive modality that is commonly used in the initial evaluation of the neck [18] and has been reported to be the imaging “modality of choice” for the evaluation of TGDCs, we further evaluated the following US features 1) presence of irregular margins, 2) cystic and solid, 3) vascular flow on Doppler US, and 4) calcifications. Then, the number of components present for each TGDC was recorded. For each TGDC, the total number of components present was considered the “summary score”.

2.3 |. Statistical Analysis

The characteristics of the TGDCs were summarized using descriptive statistics. Continuous variables (age, TGDC size, and PET/CT SUVmax) were summarized using mean, median, interquartile range, and range. Categorical variables (sex, US and CT appearance, and the presence or absence of irregular margins, vascular flow, calcifications, and adenopathy) were summarized using counts and proportions. Univariate logistic regression models were used to evaluate the discriminatory abilities of the variables to differentiate malignant and benign TGDCs. The univariate logistic regression models for age and TGDC size were assessed through receiver operating characteristic (ROC) curve analysis and area under the ROC curve. The optimal cut-off values for age and size were determined by calculating Youden’s index. A p-value less than 0.05 was considered statistically significant. The Benjamini-Hochberg correction for multiple testing was applied. In the multivariable logistic regression analysis, all variables with p < 0.05 in the univariate analysis were initially included. Backward model selection was applied to iteratively remove variables until only those with p < 0.05 remained in the final model. All statistical analyses were performed using R (version 4.2.3).

To compute the diagnostic accuracy of the summary score (sensitivity, specificity, accuracy, positive predictive value, and negative predictive value), for each cut-off value k ( k = 1, 2, 3, or 4), we defined patients with a summary score ≥ k as “cases” and other patients as “controls”. Moreover, the malignant TGDC group was defined as “case” while the benign TGDC group was defined as “control”.

3 |. Results

3.1 |. Study Population

The patient demographics and imaging appearances of the TGDCs are summarized in Table 1. The indications for imaging that revealed the TGDCs were as follows: surveillance imaging for a separate malignancy ( n = 47), palpable neck mass ( n = 20), evaluation of a thyroid nodule ( n = 12), hypercalcemia ( n = 2), evaluation of a parotid mass ( n = 1), and evaluation of thyroiditis ( n = 1).

TABLE 1 |.

Patient demographics and discriminatory performance analyzed via univariate logistic regression^a.

			p-valueb	AUCc
Sex	Benign TGDC ( n = 72)a	Malign TGDC (n = 11)a	0.590(0.590)	0.544
Male	39/72 (54.2)	5/11 (45.5)
Female	33/72 (45.8)	6/11 (54.5)
Age, mean (SD), y	57 (16.5)	41.9 (19.3)	0.010(0.016)	0.730
TGDC mean size, cm Range	2 0.6–5.1	2.8 1–4.3	0.041(0.056)	0.723
US appearance			0.007(0.016)	0.834
Cystic	19/72 (26.4)	0/7 (0)
Cystic with septations	12/72 (16.7)	0/7 (0)
Cystic and solid	18/72 (25)	6/7 (85.7)
Solid	23/72 (31.9)	1/7 (14.2)
US features
Irregular margins	2/72 (2.8)	4/7 (57.1)	< 0.001(< 0.001)	0.772
Vascular flow on Doppler imaging	19/71 (26.8)	4/7 (57.1)	0.109(0.137)	0.652
Calcifications	1/72 (1.4)	4/7 (57.1)	< 0.001(< 0.001)	0.779
Adenopathy	6/72 (8.3)	0/6 (0)	0.317(0.366)	0.542
CT appearance			0.015(0.022)	0.729
Cystic	9/41 (21.9)	0/11 (0)
Cystic with septations	8/41 (19.5)	0/11 (0)
Cystic and solid	20/41 (48.8)	10/11 (90.9)
Solid	4/41 (9.8)	1/11 (9.1)
CT features
Calcifications	2/41 (4.9)	4/11 (36.4)	0.009(0.016)	0.657
Adenopathy	5/41 (12.2)	6/11 (54.5)	0.003(0.008)	0.717
PET/CT (mean SUV) Range	0.24 0.24	10.67 (8.2–13.1)	< 0.001(0.002)	1
Adenopathy	3/14 (21.4)	1/2 (50)	0.412(0.441)	0.643

AUC, area under the receiver operating characteristic curve; SUVmax, maximum standardized uptake value.

^aUnless otherwise indicated, values in column are number of patients/number of patients with information available (percentage).

^bBenjamini-Hochberg corrected p-values are shown in parentheses.

^cAUC interpretation: = 0.5, no discrimination; 0.5–0.7, poor discrimination; 0.7–0.8, acceptable discrimination; 0.8–0.9, excellent discrimination; > 0.9, outstanding discrimination.

3.2 |. Differentiation of Benign and Malignant TGDCs

On the univariate logistic regression analysis (Table 1), the groups with benign and malignant TGDCs did not differ with respect to sex. However, patients with malignant TGDCs were younger at detection of TGDCs (p = 0.01) (Figure 1), and malignant TGDCs were larger than benign TGDCs (p = 0.041) (Figure 2).

FIGURE 1 |.

ROC curve for age (years) and cut-off value determined by calculating Youden’s index.

FIGURE 2 |.

ROC curve for TGDC size (cm) and cut-off value determined by calculating Youden’s index.

Both the US appearances (p = 0.007) and the CT appearances (p = 0.015) differed between the patients with benign and malignant TGDCs. On US, calcifications and irregular margins occurred significantly more often in malignant TGDCs (Figures 5 and 6) than in benign TGDCs (Figures 3 and 4), while rates of vascular flow (Figure 6) and adenopathy did not differ between the two groups. On CT, calcifications (Figure 6) and adenopathy occurred significantly more often in malignant TGDCs. On PET/CT, uptake occurred significantly more often in malignant TGDCs (Figure 6), and the rate of adenopathy did not differ between patients with benign and malignant TGDCs.

FIGURE 5 |.

US and CT show a malignant TGDC presenting as a solid lesion in the right of midline anterior neck with irregular margins (score = 2) and increased uptake on PET/CT requiring FNA. A, B Longitudinal and transverse plane US shows irregular margins (arrows) and no Doppler flow or calcifications. C Axial CT with contrast shows cystic and solid components (arrows). D PET/CT shows FDG uptake in the TGDC (arrow).

FIGURE 6 |.

US and CT show a malignant TGDC presenting with a solid component with irregular margins, calcifications, and increased vascular flow (score = 4). A–C Transverse, longitudinal, and transverse US show irregular margins, Doppler flow, and calcifications (arrows). D, E Axial and sagittal CTs with contrast show a solid component of the TGDC and calcifications (arrows).

FIGURE 3 |.

US shows a benign TGDC presenting as a simple cyst (score = 0) that can be followed sonographically. A, B Transverse and longitudinal US shows a hypoechoic cyst (arrows) with increased through transmission.

FIGURE 4 |.

US and CT show a benign TGDC presenting as a solid lesion on CT (score = 1) that can be followed sonographically. A US shows solid tissue with smooth margins along the anterior wall (arrow). B CT with contrast, soft tissue window, shows a solid hyperdense midline neck mass (arrow) that would require US evaluation.

The results of the analysis of the diagnostic accuracy of the summary score are summarized in Table 2, and representative examples of benign and malignant TGDCs are provided in Figures 3–6. Four patients with malignant TGDCs did not have US, so a summary score could not be calculated for these patients, leaving 79 patients with summary scores. All 54 TGDCs with a score of 0 or 1 were benign. Both TGDCs with a score of 4 were malignant. The 23 TGDCs with a score of 2 or 3 could not be differentiated by score.

TABLE 2 |.

Four-feature summary score with diagnostic accuracy^a.

Score	No. of patients (%)			Sensitivity	Specificity	Accuracy	PPV	NPV
	Benign TGDC ( n = 72)	Malignant TGDC ( n = 7)	Total ( n = 79)
0	28 (38.9)	0 (0.0)	28 (35.4)
1	26 (36.1)	0 (0.0)	26 (32.9)	1	0.39	0.44	0.14	1
2	17 (23.6)	4 (57.1)	21 (26.6)	1	0.75	0.77	0.28	1
3	1 (1.4)	1 (14.3)	2 (2.5)	0.43	0.99	0.94	0.75	0.95
4	0 (0.0)	2 (28.6)	2 (2.5)	0.29	1	0.94	1	0.94

NPV, negative predictive value; PPV, positive predictive value.

^aFor accuracy analysis at each cut-off value k ( k = 1, 2, 3, 4), patients with score ≥ k were classified as cases.

4 |. Discussion

Our study provides important information about the patient demographics and the US, CT, and PET/CT appearances of benign and malignant TGDCs. Malignant TGDCs were detected at a younger age than benign TGDCs and were larger than benign TGDCs. In both the US and CT, no malignant TGDC had an appearance of being purely cystic or cystic with septations, and calcifications were significantly more common in malignant TGDCs. Irregular margins on US and FDG-avidity on PET/CT were both significantly associated with malignant TGDCs. In the US, all TGDCs with a summary score of 0 or 1, that is, TGDCs that were cystic with or without septations and/or contained only solid tissue without irregular margins and lacked vascular flow and calcifications, were benign, while both TGDCs with a score of 4, i.e., TGDCs that contained solid tissue with irregular margins, vascular flow, and calcifications, were malignant. A summary score of 2 or 3 could not differentiate benign and malignant TGDCs.

We observed that malignant TGDCs were detected at a younger age than benign TGDCs (optimal cut-off value <43.5 years) and were larger (optimal cut-off value >1.85 cm) than benign TGDCs. These findings echo prior reports that younger age and larger lesion size can signal malignancy in thyroglossal duct anomalies [14, 15]. Salih et al. reported a median age of presentation of malignant TGDCs of 40 years (25–48 years), while Mahajan et al. [15] reported a median age of 47 years (22–48 years). While size has not been universally emphasized as a differentiator, its clinical importance warrants careful attention in younger patients with TGDCs detected during imaging evaluation. Such demographic and morphologic differences reinforce the need for vigilant imaging evaluation to guide management.

Our study underscores the utility of US and CT in differentiating benign and malignant TGDCs. Malignant TGDCs more frequently demonstrated irregular margins, calcifications, and solid appearance, findings consistent with the TGC-Thyroid Imaging Reporting and Data System (TIRADS) classification proposed by Mahajan et al. [15]. While the TGC-TIRADS system emphasizes these features, our four-feature summary score simplifies their integration, offering a more streamlined framework, especially for benign TGDCs, including the elimination of the TGC-TIRADS 1 score for the “absence of remnant tissue along the thyroglossal tract”. Similar to our study, Mahajan et al. [15] recommend that purely cystic TGDCs (TGC-TIRADS 2) or those with internal echos and no mass (TGC-TIRADS 3) do not need an FNA. However, in our study, the TGC-TIRADS 2 and 3 are also eliminated.

Unlike the multiparameter approach of TIRADS in thyroid nodules, our system focuses exclusively on TGDC-specific characteristics. Consistent with recommendations from Mahajan et al. [15], our findings suggest that lesions with solid tissue on CT should be referred for detailed US evaluation. Furthermore, our findings suggest that the combination of solid tissue with one or more additional suspicious features on US (irregular margins, vascular flow, or calcifications) requires an FNA to rule out malignancy. This is similar to Mahajan et al. [15], who recommend an FNA for the presence of calcifications, internal vascularity, and irregular margins. However, their study differs in that a TGDC, which is “solid cystic in composition”, would require an FNA, whereas our findings suggest that a solid mass with smooth margins can be followed sonographically.

Since most malignant TGDCs in our study were in the intermediate category (score 2 or 3), the scoring system remains exploratory, and further assessment with more malignant TGDCs is needed before it can be implemented. An advantage of our four-feature summary score is that it can aid in discussions with cytologists and may help determine whether additional passes are necessary to obtain more tissue. This could be explored in future studies.

The role of PET/CT in TGDC evaluation remains understudied, with most insights derived from case reports [20–22]. Our findings demonstrate that malignant TGDCs exhibit significantly higher SUVmax than benign TGDCs do, akin to the pattern observed in FDG-avid thyroid nodules. Felder et al. [23] highlighted the high malignancy risk of FDG-avid thyroid nodules, particularly those categorized as TR4 or TR5 by TIRADS. Ren et al. [24] found that thyroid nodules that were FDG-avid and categorized as TIRADS 1 or TIRADS 2 or had no suspicious sonographic features had “a 0% incidence of malignancy and thus may not require further assessment with fine needle aspirate cytology (FNA) when detected incidentally”. Furthermore, Ren et al. wrote that FDG-avid nodules that were classified as TIRADS 3 or higher required FNA independent of size “due to the high risk of malignancy and poor sensitivity of the TIRADS classification system”. Our current recommendation is that FDG-avid TGDCs should be evaluated sonographically with FNA; such TGDCs could be the topic of further study.

Lymphadenopathy has been reported in patients with malignant TGDC, particularly those with concurrent thyroid malignancies [15]. Our study found that lymphadenopathy did not differentiate benign versus malignant TGDCs, especially in a cancer-heavy cohort (more than half of the patients in our cohort had the TGDC detected on surveillance imaging for a separate malignancy). Despite this, lymph node evaluation remains essential on all imaging modalities. CT offers the most comprehensive assessment, detecting smaller nodes that may be missed on US or PET/CT. It is routine practice at our center to assess the lateral region of the neck sonographically in all patients to ensure a thorough assessment for cervical lymphadenopathy.

Limitations of our study include its retrospective, single-center study design, with a single reviewer and small malignant TGDC cohort size. As malignant TGDCs are rare, the case-control study design is inherently susceptible to sampling bias. The small number of malignant TGDCs ( n = 11) limits statistical power. Additionally, the components retrospectively characterized as “solid” in the US images could represent debris, which may be better distinguished in prospective real-time US evaluations. On PET/CT, potential for false positive findings exist. One issue is that a thyroglossal duct cyst may be inappropriately diagnosed as a pyramidal lobe nodule, and care should be taken to avoid misdiagnosis. Another area of interest is intraoral TGDCs, which were not included in this study but represent a unique subgroup requiring further research. Future studies should aim to evaluate these groups and refine imaging-based scoring systems to guide management. The evaluation of confounding factors, including coexisting thyroid disease, may also be of interest, as well as the potential for false-positive findings on PET/CT.

5 |. Conclusion

Our findings suggest that compared with benign TGDCs, malignant TGDCs are more likely to occur in patients younger than 44 years old, have a size greater than 1.85 cm, contain calcifications on US and CT, demonstrate irregular margins on US, and have increased uptake on PET/CT. In our four-point grading system (solid tissue, irregular margins, increased vascular flow, and calcifications), TGDCs that are cystic with or without septation or contain only solid tissue without irregular margins (score 0 or 1) may not need an FNA and may be followed with serial US imaging. TGDCs that contain solid tissue with irregular margins, increased vascular flow, and calcifications (score 4) will likely be malignant and ultimately require surgical excision; FNA before excision may be beneficial for documentation of malignancy and genetic testing. All other TGDCs (score of 2 or 3) require an FNA to determine if they are benign or malignant. On CT, TGDCs with solid tissue and/or calcifications require US evaluation and possibly FNA. On PET/CT, TGDCs with increased uptake require FNA.