Thyroid lesions represent a common clinical concern worldwide.[1] The reported prevalence of thyroid nodules varies widely, with estimates reaching up to 67%, depending on detection methods such as palpation, ultrasonography, or autopsy, and showing significant geographic variation.[2–4] Studies employing ultrasonography or autopsy report prevalence rates ranging from 34% to 66%.[3,5] While palpable nodules are found in approximately 5% of the general population, ultrasonography can detect nodules in 10% to 55% of individuals.[1] Among these nodules, malignancy occurs in roughly 5–15% of cases.[6]

Clinically, nodules larger than 1 cm are generally considered at higher risk for malignancy. However, non-palpable nodules of similar size may carry comparable malignant potential.[7] Fine needle aspiration cytology (FNAC) remains the most sensitive, specific, and cost-effective tool for evaluating thyroid nodules.[8]

Ultrasound imaging frequently reveals thyroid nodules during routine clinical examinations, with incidence reported as high as 68% in certain populations.[9,10] Although the majority of nodules are benign, a significant subset is malignant, underscoring the need for accurate and timely diagnosis.[11,12] FNAC continues to serve as the gold standard for cytological assessment, providing critical information for clinical management.[13] Nevertheless, its limitations include indeterminate results that often necessitate further diagnostic procedures.[14]

Recently, ultrasound elastography has emerged as a valuable adjunct technique. By assessing tissue stiffness, this non-invasive method helps differentiate benign from malignant lesions. [15,16] Malignant nodules typically exhibit increased stiffness compared to benign ones, thereby improving risk stratification and guiding clinical decisions. [13,17]

Given the complementary nature of ultrasonography and FNAC, it is important to evaluate their diagnostic accuracies and combined utility. While ultrasonography identifies nodules warranting FNAC, cytological examination offers definitive histopathological diagnosis. A comparative analysis of these modalities can optimize clinical workflows, minimize unnecessary procedures, and improve patient outcomes.

This study aims to assess and compare the diagnostic performance of high-resolution ultrasonography and FNAC in evaluating thyroid nodules, using histopathology as the reference standard. We will systematically evaluate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy for each method to provide evidence-based guidance on their individual and combined roles in thyroid nodule management.

Study Setting and Design

This retrospective comparative study was conducted at a tertiary care center in India to assess and compare the diagnostic accuracy of ultrasonography (USG) and FNAC in the evaluation of thyroid nodules (TNs). The study involved the analysis of pre-existing medical records of patients diagnosed with TNs during the study period.

Study Participants

A total of 80 patients diagnosed with TNs were included in the study. The sample comprised individuals of both genders, spanning a wide age range from young adults to the elderly.

Inclusion criteria:

• Patients with confirmed thyroid nodules evaluated by both USG and FNAC.

Exclusion criteria:

• Patients with incomplete medical records,
• Prior history of thyroid nodules,
• Missing or inconclusive diagnostic data,
• Non-diagnostic FNAC reports (Bethesda Category I).

Data Collection Methodology

Data were retrieved from patients’ medical files, radiology reports, and pathology records. All collected data were anonymized and encoded to maintain confidentiality. Information included demographic characteristics, USG findings, FNAC results, and histopathological outcomes.

Ultrasonography (USG) Assessment and Categorization

Ultrasound (USG) data of 80 patients were reviewed. Thyroid nodules were categorized based on the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) [18, 19]. TI-RADS categorizes nodules based on composition, echogenicity, shape, margin, and echogenic foci into the following groups:

• TR1 – Benign
• TR2 – Not Suspicious
• TR3 – Mildly Suspicious
• TR4 – Moderately Suspicious
• TR5 – Highly Suspicious

Each nodule was scored and categorized accordingly. These categorizations were then compared with histopathological findings to evaluate diagnostic accuracy.

Fine-Needle Aspiration Cytology (FNAC) Assessment and Categorization

FNAC reports and cytology slides for all 80 patients were reviewed. Adequacy was defined as the presence of at least five groups of follicular cells, each with a minimum of 12 cells. TNs were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) [20, 21]:

• Category I: Non-diagnostic/unsatisfactory (excluded from final analysis)
• Category II: Benign
• Category III: Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS)
• Category IV: Follicular neoplasm or suspicious for follicular neoplasm
• Category V: Suspicious for malignancy
• Category VI: Malignant

FNAC results were correlated with histopathological findings to determine diagnostic performance.

Statistical Analysis

All statistical analyses were performed using SPSS version 28. Descriptive statistics were calculated for patient demographics and diagnostic outcomes. The diagnostic accuracy of USG and FNAC was evaluated by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) using histopathology as the gold standard. Comparisons between diagnostic modalities were conducted using the Chi-square test for categorical variables and independent t-test for continuous variables, where appropriate. A p-value < 0.05 was considered statistically significant.

Table 1: Characteristics of Nodules (n = 80)

Note: MNG – Multiple nodules in the gland.

Table 1 summarizes the characteristics of thyroid nodules in 80 patients. The majority of nodules were firm in consistency (65.0%), with fewer being solid (16.3%) or soft (18.7%). Regarding size, most nodules measured between 1 and 4 cm (55.0%), followed by those larger than 4 cm (42.5%), while small nodules under 1 cm were rare (2.5%). In terms of shape, multiple nodules within the gland (MNG) were most common (56.3%), compared to solitary nodules (36.2%) and diffuse nodules (7.5%).

Table 2: Association between USG and FNAC (n = 80)

Table 2 shows the association between ultrasound (USG) findings and fine-needle aspiration cytology (FNAC) results in 80 cases. Among nodules identified as benign by ultrasound, 88.9% were confirmed benign by FNAC, while 26.3% of nodules labeled malignant by FNAC were incorrectly classified as benign by USG. Conversely, 73.7% of nodules identified as malignant by ultrasound were confirmed malignant by FNAC, with 11.1% misclassified as benign. The chi-square test revealed a significant association between USG and FNAC results (χ² = 28.76, p < 0.001), indicating that ultrasound is a reliable tool for differentiating between benign and malignant thyroid nodules.

Table 3: Association between US and FNAC Findings According to Nodule Size

FNAC: Fine-needle aspiration cytology. US: Ultrasound.

The association between ultrasound (US) findings and fine-needle aspiration cytology (FNAC) results was analysed according to the size of thyroid nodules. For nodules smaller than 1 cm, all benign FNAC results corresponded with benign US findings, while malignant nodules were also correctly identified, although the association was not statistically significant (p = 0.275, chi square= 0.333). In the 1–4 cm group, a significant association was observed (p = 0.002, chi square= 0.426), with 88.9% of benign FNAC cases showing benign US results and 72.7% of malignant FNAC cases matching malignant US findings. Similarly, for nodules larger than 4 cm, a strong and statistically significant correlation was noted (p = 0.001, chi square= 0.442), indicating that US findings reliably corresponded with FNAC results in distinguishing benign from malignant nodules in this size category.

Table 4: Validity of Ultrasound in the Diagnosis of Thyroid Carcinoma (n = 80)

                   *PPV: Positive predictive value, NPV: Negative predictive value, CI: Confidence interval.

                   P < 0.05 is considered statistically significant.

Table 4 presents the diagnostic validity of ultrasound in detecting thyroid carcinoma among 80 patients. The sensitivity of ultrasound was 87.5% (95% CI: 73.2–95.8%), indicating its strong ability to correctly identify malignant nodules. Specificity was 76.47% (95% CI: 61.2–87.4%), showing its effectiveness in correctly recognizing benign nodules. The positive predictive value (PPV) was 77.78%, and the negative predictive value (NPV) was 86.11%, reflecting the test’s reliability in predicting true positive and true negative cases, respectively. Overall accuracy of ultrasound in this diagnosis was 81.25% (95% CI: 70.5–89.5%) The results are                           statistically significant with a p-value less than 0.05

This study evaluated the diagnostic accuracy of USG compared to FNAC in assessing thyroid nodules among 80 patients. The majority of nodules were firm in consistency (65.0%) and ranged between 1 and 4 cm in size (55.0%), consistent with previous reports describing common characteristics of thyroid nodules.[22]

Multinodular goiter (MNG) was the predominant

Presentation (56.3%), followed by solitary nodules

(36.2%), reflecting regional epidemiological patterns. The predominance of MNG poses unique

Diagnostic and therapeutic challenges compared to solitary nodules, requiring careful and nuanced clinical management.

A statistically significant association was observed between USG and FNAC diagnoses (χ² = 28.76, p < 0.001). USG demonstrated a high diagnostic yield, correctly identifying 88.9% of benign nodules and 73.7% of malignant nodules confirmed by FNAC. However, the misclassification of 26.3% of malignant nodules as benign highlights limitations of USG, particularly its reduced sensitivity in ruling out malignancy. These findings align with studies by Dev B. et al. (2024) [23] and Kumar EP et al. (2021), [24] who similarly reported substantial concordance between USG and FNAC but emphasized the risk of false-negative USG results. Salman MT et al. (2023) [25] also underscored the utility of USG as an initial screening tool while affirming FNAC’s essential role in definitive diagnosis.

Subgroup analysis by nodule size revealed no significant concordance between USG and FNAC for nodules smaller than 1 cm (p = 0.275), likely due to limited sample size and inherent technical challenges in detecting subcentimetric features via USG. In contrast, nodules measuring 1–4 cm (p = 0.002) and those larger than 4 cm (p = 0.001) showed significant diagnostic agreement, with moderate to strong effect sizes (Cramér’s V), indicating improved USG reliability with increasing nodule size. These observations are supported by prior work from Tamhane S and Gharib H (2016) [2] and Ebrahim H et al. (2023), [26] which also reported enhanced USG performance for larger nodules.

The diagnostic performance metrics of USG in this study included a sensitivity of 87.5%, specificity of 76.47%, positive predictive value (PPV) of 77.78%, and negative predictive value (NPV) of 86.11%, yielding an overall diagnostic accuracy of 81.25%. These results reaffirm USG as a reliable initial imaging modality, particularly in settings where FNAC may not be readily available. Similar performance metrics have been reported by Salman MT et al. (2023) [25] and Alshoabi SA et al. (2019). [27] However, the moderate specificity and relatively high false-negative rate caution against relying solely on USG to exclude malignancy. Operator dependency and limitations in sonographic resolution, particularly for small or complex lesions, may contribute to these false negatives.

Given its high sensitivity and wide accessibility, USG serves as a valuable first-line diagnostic tool, especially when suspicious sonographic features such as microcalcifications, irregular margins, and marked hypoechogenicity are present. In cases with indeterminate or suspicious USG findings, FNAC should be promptly performed to confirm malignancy and guide clinical decision-making. This combined diagnostic approach optimizes accuracy, minimizes unnecessary surgical interventions for benign nodules, and ensures timely management of malignant lesions.

This study is limited by its relatively small sample size, particularly within the subgroup of nodules smaller than 1 cm, which may affect the generalizability of these findings. Additionally, the operator-dependent nature of USG may have introduced variability in diagnostic accuracy. The single-center design may further limit the broader applicability of the results. Future multicenter studies with larger, more diverse populations and standardized imaging protocols are warranted to validate and extend these findings.

Ultrasonography demonstrates strong diagnostic potential for thyroid nodules larger than 1 cm, with high sensitivity and acceptable specificity, making it a reliable initial screening modality. However, due to its limitations in confidently excluding malignancy especially in smaller nodules FNAC remains essential for definitive diagnosis. Employing a combined diagnostic strategy incorporating both USG and FNAC enhances diagnostic precision, improves patient care, and supports informed clinical decision-making.

This study evaluated the characteristics of thyroid nodules and compared the diagnostic accuracy of US with FNAC. Most nodules were firm and ranged predominantly from 1 to 4 cm, with MNG being more common than solitary or diffuse nodules. A significant correlation between US and FNAC findings (χ² = 28.76, p < 0.001) supports the reliability of US as a non-invasive initial diagnostic tool to differentiate benign from malignant nodules.

Subgroup analysis showed strong concordance for nodules sized 1–4 cm (p = 0.002) and >4 cm (p = 0.001), while correlation for nodules <1 cm was not statistically significant, likely due to a small sample size.

Diagnostic performance metrics revealed that US had a sensitivity of 87.5%, specificity of 76.5%, positive predictive value of 77.8%, negative predictive value of 86.1%, and overall accuracy of 81.3% for detecting thyroid carcinoma. These results affirm the clinical utility of ultrasound as a highly sensitive and moderately specific modality for initial thyroid nodule assessment, particularly for nodules larger than 1 cm, guiding the judicious use of FNAC and optimizing patient management.

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