|Year : 2022 | Volume
| Issue : 1 | Page : 44-50
Ultrasound features and estimated risk of malignancy in thyroid nodules
Aseel O Doubi1, Nouf H Alshammari2, Reenad Hussain Bedaiwi3, Ali Mohammad Alshdokhi4, Dana Aljomah2, Ahmad Albosaily5, Saleh Aldhahri6
1 Department of Otolaryngology Head and Neck Surgery, King Saud Medical City, Riyadh, Kingdom of Saudi Arabia
2 Department of Otolaryngology Head and Neck Surgery, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
3 Department of Otolaryngology Head and Neck Surgery, Taibah University, Medina, Kingdom of Saudi Arabia
4 Department of Otolaryngology Head and Neck Surgery, King Khaled Hospital, Hail, Kingdom of Saudi Arabia
5 Department of Otolaryngology Head and Neck Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Kingdom of Saudi Arabia
6 Department of Otolaryngology Head and Neck Surgery, King Saud University, King Abdulaziz University Hospital, Riyadh, Kingdom of Saudi Arabia
|Date of Submission||30-Jan-2022|
|Date of Decision||21-Feb-2022|
|Date of Acceptance||27-Feb-2022|
|Date of Web Publication||30-Mar-2022|
Dr. Aseel O Doubi
King Saud Medical City, Riyadh, Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
Introduction: A significant uncertainty surrounding the diagnostic accuracy of ultrasound (US) and the risk features in thyroid nodules exist to date which impacts clinical practice and guidelines. Methods: This retrospective descriptive observational study included patients with thyroid nodules with US reports over 10 years and either had a fine-needle aspiration (FNA) cytology result, a pathology report or both. Results: A total of 483 patients were included. Most of the patients were <55 years old (67.3%) and the majority of them were females (91.3%). The FNA cytology results indicated that 311 (64.4%) of the thyroid nodules were benign and 32 (6.6%) were malignant. Overall, only 181 (37.5%) of the patients had a final histopathologic assessment; of these, 80 (44.2%) had malignant thyroid nodules, 78 (43.1%) had benign nodules, and 23 (12.7%) had microcarcinoma. multivariate logistic regression analysis revealed that having US features of hypoechogenicity (adjusted odd ratio 3.37; 95% confidence interval [CI] 1.03–11.00) and a microlobulated or irregular margin (aOR 3.65; 95% [CI] 1.13–11.79) were the only sonographic characteristics that had a statistically significant association with thyroid cancer based on final pathology. Conclusion: Thyroid nodules showing hypoechogenic echogenicity and microlobulated or irregular margin on US need to be closely followed and given the appropriate management based on their risk criteria.
Keywords: Thyroid nodules, thyroid ultrasound, ultrasound risk features
|How to cite this article:|
Doubi AO, Alshammari NH, Bedaiwi RH, Alshdokhi AM, Aljomah D, Albosaily A, Aldhahri S. Ultrasound features and estimated risk of malignancy in thyroid nodules. Saudi J Otorhinolaryngol Head Neck Surg 2022;24:44-50
|How to cite this URL:|
Doubi AO, Alshammari NH, Bedaiwi RH, Alshdokhi AM, Aljomah D, Albosaily A, Aldhahri S. Ultrasound features and estimated risk of malignancy in thyroid nodules. Saudi J Otorhinolaryngol Head Neck Surg [serial online] 2022 [cited 2022 Dec 5];24:44-50. Available from: https://www.sjohns.org/text.asp?2022/24/1/44/341367
| Introduction|| |
The use of ultrasound (US) evaluation for thyroid nodules has become widely accepted as a key diagnostic step in stratifying patients' risk of malignancy. There is, however, a significant uncertainty surrounding the diagnostic accuracy of several of the features analyzed during the sonographic evaluation of thyroid nodules. A better understanding of the US features predictive of malignancy or benign disease may therefore avoid costly confirmatory testing and have a large impact on both guideline recommendations and clinical practice. This study aimed to evaluate the US features most suggestive of a malignant final pathology in thyroid nodules.
| Methods|| |
This retrospective descriptive observational study included patients from 9 to 90 years old who had thyroid nodules on US reports performed over 10 years and either had a fine-needle aspiration (FNA) cytology result, a pathology report, or both. The data were collected from patients' charts and included (age, gender, size of the thyroid nodule, procedure performed if any, FNA results, US report, and the final pathology results). No formal sample size calculation was performed but all available patients in this center were included.
For each patient, every parameter on the US report was compared to FNA result or their final histopathology and the parameter mostly associated with a malignant final result was studied. Patients with neither FNA cytology nor final pathology were excluded.
The parameters sought in US reports of thyroid nodules are as described in the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer and include:
- Composition: Predominantly cystic, predominantly solid, solid, or spongiform
- Echogenicity: Iso-hyperechogenicity, Hypoechogenicity or marked hypoechogenicity
- Echostructure: Homogeneous or heterogeneous
- Margin: Well circumscribed, microlobulated or irregular margins, infiltrative
- Calcification: None, macrocalcification, microcalcifications, mixed calcifications or hyperechoic spot
- Shape: Wider than tall or taller than wide
- Vascularization: Avascular, hypovascular, hypervascular, or penetrating vessel
- Halo sign: Absent, partly, or complete fine
- Capsule: Absent or present
- Cervical lymph nodes: normal or lymphadenopathy
- Rim calcifications with small extrusive soft tissue component: Absent or present
- Evidence of extrathyroid extension: Absent or present.
The data were coded and analyzed with the statistical software (IBM Corp. Released 2016. IBM SPSS statistics for Macintosh, Version 24.0 Armonk, NY, US). Means and standard deviations (SDs) were obtained for numeric variables, whereas frequencies and percentages were computed for categorical variables. Pearson's Chi-square test was used to assess for the presence of significant differences between categorical variables. To identify potential risk factors for malignancy of the thyroid nodules, univariate and multivariate logistic regression analyses were performed. We included variables with a P < 0.2 in the univariate analysis as well as previously identified risk factors of malignancy of the thyroid nodules in the models using the enter method. The results were presented as odds ratios (ORs) and adjusted ORs (aOR) with their 95% confidence intervals. Multicollinearity between the variables included in the models was assessed using the variance inflation factor. Statistical significance was set at two-sided P < 0.05.
| Results|| |
The present cohort involved 483 patients who had an US report, an FNA cytology report as per the Bethesda System for Reporting Thyroid Cytopathology or a final histopathology. The demographic and histopathologic characteristics of patients who had thyroid nodules are as shown in [Table 1]. Most of the patients n = 325 (67.3%) were <55 years old and majority of them were females n = 441 (91.3%). The FNA cytology results indicated that 311 (64.4%) of the thyroid nodules were benign and 32 (6.6%) were malignant. Overall, only 181 (37.5%) of the patients had a final histopathologic assessment; of these, 80 (44.2%) had malignant thyroid nodules, 78 (43.1%) had benign nodules, and 23 (12.7%) had microcarcinoma.
|Table 1: Demographic and histopathologic characteristics of patients who had thyroid nodules|
Click here to view
[Table 2] summarizes the US features of all patients who had thyroid nodules. The most common nodule size was 1–2.99 cm, n = 238 (49.3%) and the composition of the nodules was mainly solid, n = 420 (87.0%). Most of the thyroid nodules were Iso-hyperechogenic and 166 (34.4%) of them had a heterogeneous echostructure. Furthermore, the margins of the nodules were well-circumscribed in 265 (75.6%), and 182 (37.7%) of them had microcalcifications. Most of the patients 391 (81.0%) had avascular thyroid nodules, but about a third of them, 188 (38.9%) had cervical lymphadenopathy.
|Table 2: Ultrasound features of all patients with thyroid nodules included in the study (n=483)|
Click here to view
Univariate and multivariate logistic regression analysis of factors associated with malignancy of the thyroid nodules based on FNA cytology results are shown in [Table 3]. In the univariate analysis, having a spongiform composition (P = 0.04), a hypoechogenic/marked hypoechogenic echogenicity (P < 0.001), a microlobulated or irregular margin (P < 0.001), a hypervascular or penetrating vessel vascularization (P = 0.01), and extrathyroid extension (P = 0.02) were all significantly associated with malignancy based on FNA cytology findings. However, following multivariate logistic regression analysis having a hypoechogenic/marked hypoechogenic echogenicity (aOR 5.79; 95% [CI] 2.23–15.02), a microlobulated or irregular margin (aOR 5.84; 95% [CI] 2.02–16.85), a hypervascular or penetrating vessel vascularization (aOR 3.33; 95% [CI] 1.11–10.03), and having a positive halo sign (aOR 145.63; 95% [CI] 7.43–2853.75) or complete fine halo sign (aOR 31.30; 95% [CI] 1.35–725.55) were risk factors of malignancy of the thyroid nodules based on FNA cytology findings.
|Table 3: Ultrasound features and risk of malignancy of thyroid nodules based on fine needle aspiration cytology|
Click here to view
Univariate and multivariate logistic regression analysis of factors associated with malignancy of the thyroid nodules based on final histopathology assessment is shown in [Table 4]. In the univariate analysis, having a hypoechogenic echogenicity (P = 0.004), a microlobulated or irregular margin (P = 0.004) or infiltrative margin (P = 0.001), were all significantly associated with malignancy of thyroid nodules based on final histopathology assessment. However, following multivariate logistic regression analysis, only having a hypoechogenic echogenicity (aOR 3.37; 95% [CI] 1.03–11.00) and a microlobulated or irregular margin (aOR 3.65; 95% [CI] 1.13–11.79) were risk factors of malignancy of the thyroid nodules based on final histopathology assessment.
|Table 4: Ultrasound features and risk of malignancy of thyroid nodules based of final histopathology|
Click here to view
| Discussion|| |
The current thyroid guideline recommendations call for US in all patients with a suspected thyroid nodule. However, significant uncertainty remains surrounding the diagnostic accuracy of sonographic features used to predict the malignant potential of thyroid nodules. Low-to-moderate quality evidence suggests that individual US features are not accurate predictors of thyroid cancer. Two features, cystic content and spongiform appearance, however, might predict benign nodules, but this has limited applicability to clinical practice due to their infrequent occurrence. One meta-analysis showed that US features in isolation did not provide reliable information to select nodules that should have an FNA performed. Hence, a combination of US characteristics with higher likelihood ratios and consequently with higher posttest probabilities of malignancy would probably identify nodules with an increased risk for malignancy. This is seen in this study where the univariate analysis showed that having a spongiform composition was significantly associated with malignancy based on FNA cytology findings (P = 0.04). However, following multivariate logistic regression anlysis, that conclusion was untrue.
In this study, the multivariate logistic regression analysis showed that having a hypoechogenic/marked hypoechogenic echogenicity, a microlobulated or irregular margin, a hypervascular or penetrating vessel vascularization, and a positive halo sign or complete fine halo sign were risk factors of malignancy of the thyroid nodules based on FNA cytology findings. This is similar to a study done by Li et al. who also looked at the FNA cytology findings and concluded that the sonographic characteristics that had a statistically significant association with thyroid cancer were: nodule composition (solid portion ≥50%, P = 0.000), eccentric solid portion (P = 0.001), irregular nodule shape (P = 0.000), microcalcification (P = 0.000), and intranodular vascularity (P = 0.001). Other studies were conducted examining the ultrasonographic and pathological data, some of which found that malignant nodules more commonly presented with an anteroposterior and transversal diameters ≥1, solid structure, infiltrative margins, hypoechoic appearance, and microcalcifications (P < 0.01). For others, the US features which showed a significant association with malignancy were: solid component, hypoechogenicity, marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. Batawil and Alkordy, similarly found that malignancy was significantly associated with solid nodules and an irregular border. In this study, however, the multivariate logistic regression analysis showed that only having hypoechogenicity and a microlobulated or irregular margin were risk factors of malignancy of the thyroid nodules based on final histopathology.
Similar to the results seen here, a study using different US Thyroid Imaging Reporting and Data Systems (TI-RADS) concluded that marked hypoechogenicity was the most significant independent predictor for malignancy (P < 0.05). Others reported a significant correlation between the central echogenic area finding and papillary carcinoma with a P < 0.01. on the other hand, Ycaza et al., found that the presence of nodular calcifications was the strongest predictor of thyroid malignancy while Woo et al. reported that the only statistically significant factor on US was hypoechogenicity. Because of all of these findings, Rosário and Purisch suggested that US characteristics rather than nodule growth should be selected as a criterion for repeat FNA in cases where the nodule reveals initial benign cytology. This is important because it was found that in nodules with inadequate cytology, the rate of Malignancy of nodules having suspicious US feature was significantly higher than those of nodules without any suspicious US feature (P < 0.001). More studies are therefore needed to establish the US features that are more likely to predict malignancy.
| Conclusion|| |
Since US has become an indispensable tool in the evaluation and risk assessment of thyroid nodules, certain high-risk features merit more workup than others. In this analysis, it was found that having a hypoechogenic nodule and a microlobulated or irregular margin were the most suggestive of a malignant final pathology. We believe more studies are needed to standardize high-risk US features and enable clinicians to use these parameters in evaluating their patients.
Acknowledgment to Dr. Samer El-Kaissi, MD, consultant endocrinologist, Cleveland clinic Abu Dhabi. For record keeping and technical data sharing.
Financial support and sponsorship
None to disclose.
Conflicts of interest
There are no conflicts of interest
| References|| |
Brito JP, Gionfriddo MR, Al Nofal A, Boehmer KR, Leppin AL, Reading C, et al.
The accuracy of thyroid nodule ultrasound to predict thyroid cancer: Systematic review and meta-analysis. J Clin Endocrinol Metab 2014;99:1253-63.
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al.
2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-133.
Cibas ES, Ali SZ. The 2017 Bethesda system for reporting thyroid cytopathology. Thyroid 2017;27:1341-6.
Remonti LR, Kramer CK, Leitão CB, Pinto LC, Gross JL. Thyroid ultrasound features and risk of carcinoma: A systematic review and meta-analysis of observational studies. Thyroid 2015;25:538-50.
Li W, Zhu Q, Jiang Y, Zhang Q, Meng Z, Sun J, et al.
Partially cystic thyroid nodules in ultrasound-guided fine needle aspiration: Prevalence of thyroid carcinoma and ultrasound features. Medicine (Baltimore) 2017;96:e8689.
Gu WJ, Yan HX, Luo YK, Wang FL, Yang GQ, Guo QH, et al.
Characterization of papillary thyroid microcarcinomas using sonographic features in malignant papillary thyroid cancer: A retrospective analysis. Medicine (Baltimore) 2015;94:e841.
Kwak JY, Han KH, Yoon JH, Moon HJ, Son EJ, Park SH, et al.
Thyroid imaging reporting and data system for US features of nodules: A step in establishing better stratification of cancer risk. Radiology 2011;260:892-9.
Batawil N, Alkordy T. Ultrasonographic features associated with malignancy in cytologically indeterminate thyroid nodules. Eur J Surg Oncol 2014;40:182-6.
Wang Y, Lei KR, He YP, Li XL, Ren WW, Zhao CK, et al.
Malignancy risk stratification of thyroid nodules: Comparisons of four ultrasound Thyroid Imaging Reporting and Data Systems in surgically resected nodules. Sci Rep 2017;7:11560.
Siebert SM, Jeffrey RB, Gomez AJ, Kamaya A. Central echogenic areas in thyroid nodules: Diagnostic performance in prediction of papillary cancer. Eur J Radiol 2018;101:45-9.
Espinosa De Ycaza AE, Lowe KM, Dean DS, Castro MR, Fatourechi V, Ryder M, et al.
Risk of malignancy in thyroid nodules with non-diagnostic fine-needle aspiration: A retrospective cohort study. Thyroid 2016;26:1598-604.
Woo SH, Kim KH, Kim RB. Thyroid nodules with repeat nondiagnostic cytologic results: The role of clinical and ultrasonographic findings. World J Surg 2015;39:1721-7.
Rosário PW, Purisch S. Ultrasonographic characteristics as a criterion for repeat cytology in benign thyroid nodules. Arq Bras Endocrinol Metabol 2010;54:52-5.
Yoon JH, Moon HJ, Kim EK, Kwak JY. Inadequate cytology in thyroid nodules: Should we repeat aspiration or follow-up? Ann Surg Oncol 2011;18:1282-9.
[Table 1], [Table 2], [Table 3], [Table 4]