Results

Demographic and functional profile

The mean age was 44.88 ± 15.34 years (median, 44.0; range, 16-75 years), with the highest concentration of patients in the fourth and fifth decades. Of the 178 enrolled patients, 108 (60.67%) were female and 70 (39.33%) were male (F:M = 1.54:1). Hypothyroidism was the most common functional state, observed in 103 (57.87%) patients, followed by euthyroidism in 70 (39.33%) patients and hyperthyroidism in 5 (2.81%) patients. The mean TSH level was 4.95 ± 2.71 mIU/L and did not differ significantly between HPE-malignant cases (5.11 ± 2.85 mIU/L) and HPE-benign cases (4.53 ± 2.35 mIU/L; p = 0.36). Demographic and functional data are summarized in Table 1.

Parameter | Category | n (%)
Age group (years) | ≤40 | 76 (42.69)
 | 41-60 | 71 (39.89)
 | > 60 | 31 (17.42)
Sex | Female | 108 (60.67)
 | Male | 70 (39.33)
Thyroid status | Euthyroid | 70 (39.33)
 | Hypothyroid | 103 (57.87)
 | Hyperthyroid | 5 (2.81)

Sonographic and cytological distribution

TI-RADS 2 was the most prevalent sonographic category, observed in 87 (48.88%) patients, while TI-RADS 4/5 categories were present in 52 (29.21%) patients. Bethesda II predominated on cytology and was observed in 143 (80.34%) patients, whereas Bethesda V/VI categories comprised 21 (11.79%) patients. The four Bethesda III and 10 Bethesda IV cases represented the diagnostically indeterminate subset in whom sonographic correlation was most valuable. The full distribution is presented in Table 2.

TI-RADS | n (%) | Bethesda | n (%)
TR1 | 1 (0.56) | II | 143 (80.34)
TR2 | 87 (48.88) | III | 4 (2.25)
TR3 | 38 (21.35) | IV | 10 (5.62)
TR4 | 23 (12.92) | V | 19 (10.67)
TR5 | 29 (16.29) | VI | 2 (1.12)

Histopathological spectrum

Of the 178 enrolled patients, 68 (38.20%) underwent surgery and had histopathological confirmation, while the remaining 110 (61.80%) did not undergo surgery during the study period because they were managed conservatively or monitored with clinical and ultrasonographic surveillance according to routine clinical decision-making. Among the 68 operated patients, malignant/borderline histopathology was identified in 36 (52.94%) patients, including 8 (11.76%) patients with NIFTP, whereas benign disease was identified in 32 (47.06%) patients. The malignant/borderline histopathology prevalence of 36 out of 68 (52.94%) reflects the surgically verified subgroup and should not be interpreted as the prevalence among all 178 enrolled patients, because surgical referral was based on clinical decision-making and likely selected patients with higher-risk findings. FTC was the most frequent malignant diagnosis, observed in 10 (14.71%) patients, followed by classical papillary thyroid carcinoma (PTC) in 8 (11.76%) patients, NIFTP in 8 (11.76%) patients, and follicular-variant PTC in 6 (8.82%) patients. Colloid goiter was the most frequent benign diagnosis, observed in 11 (16.18%) patients. The full breakdown is shown in Figure 2.

Figure 2: Distribution of histopathological diagnoses among surgically verified patients (n = 68)FTC, follicular thyroid carcinoma; PTC, papillary thyroid carcinoma; FV-PTC, follicular-variant papillary thyroid carcinoma; NIFTP, non-invasive follicular thyroid neoplasm with papillary-like nuclear features; TFND, thyroid follicular nodular disease; MNG, multinodular goiter

Correlation with histopathology

Bethesda category was strongly associated with HPE (χ² = 50.43, P < 0.0001), with concordance strongest at both extremes: all Bethesda V/VI cases had malignant/borderline histopathology, while most Bethesda II cases were correctly benign, except for three unexpected malignancies (predominantly FTC and NIFTP). TI-RADS also correlated significantly with malignancy (χ² = 19.45, P = 0.0002), increasing stepwise from TR2 to TR5; malignant/borderline histopathology was identified in 9 of 34 (26.47%) patients with combined TI-RADS 2/3 nodules. Thyroid functional status showed no such association (χ² = 2.35, P = 0.309). Category-wise malignant/borderline histopathology rates are illustrated in Figure 3.

Figure 3: Malignant/borderline histopathology rates according to Bethesda cytology category and ACR TI-RADS category in surgically verified patients (n = 68).(A) Proportion of malignant/borderline histopathology across Bethesda categories II to VI.(B) Proportion of malignant/borderline histopathology across ACR TI-RADS categories TR2 to TR5.HPE, histopathological examination; TI-RADS, Thyroid Imaging Reporting and Data System

Diagnostic performance

FNAC showed high specificity and PPV, with no false-positive results at the Bethesda V/VI positivity threshold. However, 15 malignant/borderline lesions were classified below this threshold, resulting in limited sensitivity. The 15 false-negative FNAC results occurred predominantly in follicular-patterned lesions, including FTC, NIFTP, and follicular-variant PTC; three were classified as Bethesda II. USG achieved higher sensitivity than FNAC, reflecting its ability to flag structural atypia even when FNAC is cytologically reassuring or indeterminate, at the cost of lower specificity: its seven false positives reflected recognized sonographic mimics of malignancy. Both modalities showed similar, moderate kappa agreement with HPE, but the differing pattern of error each makes is the practical rationale for combining them. Because PPV, NPV, and overall accuracy are influenced by disease prevalence and were calculated only in the surgically verified subgroup, these estimates may not be directly generalizable to unselected patients with thyroid nodules. The observed diagnostic performance should therefore be interpreted in the context of partial reference-standard verification. Full diagnostic performance metrics with 95% CIs are presented in Table 3.

Parameter | FNAC (Bethesda) | USG (TI-RADS)
Sensitivity | 58.33% (42.20-72.86) | 75.00% (58.93-86.25)
Specificity | 100.00% (89.28-100.00) | 78.12% (61.24-88.98)
PPV | 100.00% (84.54-100.00) | 79.41% (63.20-89.65)
NPV | 68.09% (53.83-79.60) | 73.53% (56.88-85.40)
Accuracy | 77.94% (66.74-86.15) | 76.47% (65.14-84.97)
Cohen's kappa | 0.57 (moderate) | 0.53 (moderate)