The solitary thyroid nodule (STN) has long intrigued clinicians since the seminal observations by Warren H. Cole in 1949, who reported that the incidence of malignancy was significantly higher in solitary nodules than in multinodular goiter [1]. Thyroid nodules are common clinical entities, though their prevalence varies across geographical regions [2]. Globally, the estimated prevalence of thyroid nodules ranges from 4–8% when detected by palpation and up to 19–67% with high-resolution ultrasonography (USG) [3]. In India, recent community-based studies have reported a prevalence of palpable thyroid nodules of approximately 12.2%, with solitary nodules being about four times more common in women than in men [4]. Although the majority of thyroid nodules are benign, malignancy is detected in 5–15% of cases, with several high-risk factors—such as age, sex, radiation exposure, and family history—warranting thorough evaluation [5–7]. Importantly, while nodules are less frequent in men, they often carry a greater risk of aggressive malignancy [8]. Clinically, a solitary thyroid nodule is defined as a localized thyroid enlargement with the rest of the gland appearing normal [9]. Thyroid diseases encompass a broad spectrum, ranging from systemic disorders such as Graves’ disease to localized abnormalities such as goiter or neoplastic growths. Notably, after diabetes mellitus, thyroid disorders represent the second most prevalent endocrine condition worldwide [10]. Given the clinical burden and malignant potential of STN, a structured diagnostic approach combining clinical evaluation, high-resolution ultrasonography with Thyroid Imaging Reporting and Data System (TIRADS) scoring, and cytological assessment through fine-needle aspiration cytology (FNAC) with Bethesda classification has become essential. This study was designed to evaluate the clinico-radiopathological association of solitary thyroid nodules, comparing these diagnostic modalities with histopathological examination (HPE), considered the gold standard.

Place of Study The study was conducted in the Department of General Surgery at Sri Venkateswara Institute of Medical Sciences (SVIMS), where patients presenting with solitary thyroid nodules were prospectively evaluated between February 2023 and May 2024. Study Design and Duration This was a prospective observational study carried out over one year, following approval from the Institutional Thesis Protocol Approval Committee and Institutional Ethics Committee. Sample Size A total of 30 patients clinically diagnosed with solitary thyroid nodules during the study period were included. Inclusion Criteria • Patients with solitary thyroid nodules presenting to the General Surgery Department, SVIMS. • Age between 18 and 60 years. • Patients willing to participate in the study. Exclusion Criteria • Patients younger than 18 years. • Patients with multinodular goiter, diffuse thyroid enlargement, Grave’s disease, or thyroiditis. • Patients in a biochemical state of hypo- or hyperthyroidism. • Patients with a history of previous thyroid surgery. • Pregnant women. • Patients unwilling to participate. Ethical Clearance and Consent The study commenced after approval by the Institutional Thesis Protocol Approval Committee and the Institutional Ethics Committee. Written informed consent was obtained from all participants prior to inclusion. Study Procedure All patients (or legal guardians) were briefed about the study, including investigative and operative procedures, benefits, risks, and possible complications. Only consenting patients were enrolled. The study did not involve additional investigations, significant risks, or financial burden to participants. Patient demographic data (name, age, sex, occupation, socioeconomic status, and residence) were recorded. Detailed history, presenting complaints, chronological progression, nutritional status, and complete physical examination—including systemic evaluation (cardiovascular, respiratory, and neurological systems)—were conducted. Local thyroid examination findings were documented. Laboratory and Imaging Investigations • Routine investigations: Complete hemogram, serum electrolytes, ESR, liver enzymes, coagulation profile, ECG, chest X-ray, and viral markers (HBV, HCV, HIV 1 and 2 per NACO guidelines). • Thyroid-specific investigations: Thyroid function tests (serum free T3, free T4, and TSH). • Cytological evaluation: Fine-needle aspiration cytology (FNAC), classified using the Bethesda system. • Imaging: High-resolution ultrasonography of the neck performed using ESAOTE MY LAB 40 USG machine with a 7–15 MHz linear broadband transducer. Thyroid nodules were evaluated and categorized according to the ACR-TIRADS scoring system. • Additional tests: X-ray of the neck (anteroposterior and lateral views) and indirect laryngoscopy. Patients with hypo- or hyperthyroidism were first managed medically to achieve euthyroid status before further evaluation.

Table 1 & Figure 1: Demographic and Clinical Characteristics The study included 30 patients with solitary thyroid nodules. The mean age was 37.7 ± 9.3 years, with the largest proportion (43.3%) belonging to the 31–40 year age group, followed by 26.7% in the 41–50 year group. A strong female predominance was noted (80%), compared to 20% males. On clinical examination, firm nodules were the most common (46.7%), followed by soft (33.3%) and hard (20%) nodules (Figure 1). Table 2 & Figure 2: Ultrasonographic Evaluation (ACR-TIRADS Classification) Ultrasonography categorized 50% of nodules as TIRADS II, suggestive of benign nature, followed by 43.3% as TIRADS III (mildly suspicious). Only one case each fell under TIRADS I and IV (3.3% each). Importantly, no nodules were categorized as TIRADS V, the highly suspicious category. Histopathological confirmation (Figure 2) revealed benign lesions in 76.7% and malignant lesions in 23.3%, correlating with the imaging impression of low overall malignancy risk. Table 3: Cytological (Bethesda) vs. Histopathological Correlation FNAC revealed that Bethesda II (benign) nodules accounted for 76.7%, while Bethesda III and IV represented 13.3% and 10%, respectively. No nodules were reported as Bethesda V or VI. On correlation with HPE, all Bethesda II nodules were benign, while Bethesda III and IV showed mixed outcomes. Specifically, 50% of Bethesda III and all Bethesda IV nodules were malignant. Table 4: Clinical Presentation The most common presenting symptom was neck swelling, observed in all patients (100%). Other symptoms included pain in swelling (13.3%), dysphagia (6.7%), hoarseness of voice (3.3%), and pressure symptoms (3.3%). No patients were asymptomatic. These findings emphasize that cosmetic and local compressive complaints dominate the clinical spectrum of solitary thyroid nodules. Table 5: Histopathological Spectrum Histopathological examination demonstrated that colloid nodules (40%) were the most frequent benign lesion, followed by nodular hyperplasia (23.3%) and follicular adenoma (13.3%). Among malignant lesions, papillary carcinoma was the most common (16.7%), followed by follicular carcinoma (3.3%) and medullary carcinoma (3.3%). This pattern underscores the predominance of papillary carcinoma among malignant solitary nodules. Table 1. Age and gender distribution of patients with solitary thyroid nodule (n=30) Variable Frequency (n) Percentage (%) Age group (years) 21–30 6 20.0 31–40 13 43.3 41–50 8 26.7 51–60 3 10.0 Mean ± SD 37.7 ± 9.3 — Gender Male 6 20.0 Female 24 80.0 Table 2. Distribution of solitary thyroid nodules according to ACR-TIRADS classification (n=30) TIRADS Category Number of Cases (n) Percentage (%) TIRADS I 1 3.3 TIRADS II 15 50.0 TIRADS III 13 43.3 TIRADS IV 1 3.3 TIRADS V 0 0.0 Total 30 100.0 Table 3. FNAC results (Bethesda classification) and correlation with histopathological examination (HPE) FNAC (Bethesda Category) Number of Cases (n) Percentage (%) HPE Benign (n) HPE Malignant (n) Bethesda II (Benign) 23 76.7 23 0 Bethesda III (AUS/FLUS) 4 13.3 2 2 Bethesda IV (Suspicious) 3 10.0 0 3 Bethesda V (Susp. Malig.) 0 0.0 0 0 Bethesda VI (Malignant) 0 0.0 0 0 Total 30 100.0 25 (83.3%) 5 (16.7%) Table 4. Clinical presentation of patients with solitary thyroid nodule (n=30) Presenting Symptom Number of Cases (n) Percentage (%) Neck swelling 30 100.0 Pain in swelling 4 13.3 Dysphagia (difficulty swallowing) 2 6.7 Hoarseness of voice 1 3.3 Pressure symptoms 1 3.3 Others / asymptomatic 0 0.0 Table 5. Histopathological spectrum of solitary thyroid nodules (n=30) Histopathological Diagnosis Number of Cases (n) Percentage (%) Benign lesions Colloid nodule 12 40.0 Nodular hyperplasia 7 23.3 Follicular adenoma 4 13.3 Malignant lesions Papillary carcinoma 5 16.7 Follicular carcinoma 1 3.3 Medullary carcinoma 1 3.3 Total 30 100.0

The solitary thyroid nodule (STN) remains a frequent clinical problem and an important diagnostic challenge. In our study, the mean age of presentation was 37.7 years, with the majority between 31 and 40 years. This age profile is consistent with global reports, where STNs are most commonly observed in the third and fourth decades of life [11,12]. A clear female predominance (80%) was noted, which is well documented in literature and attributed to hormonal and autoimmune factors influencing thyroid disease [13]. Neck swelling was the most common presenting complaint, observed in all patients, followed by local compressive symptoms such as dysphagia and hoarseness. These findings mirror prior studies, which reported that cosmetic and local mass effects remain the usual clinical manifestations [14]. Importantly, hard nodules on examination correlated more frequently with malignancy, although clinical consistency alone was not sufficient to rule in or rule out cancer. Ultrasonography is a cornerstone in the initial evaluation of STN. In our cohort, the majority of nodules were TIRADS II and III, with only one case each of TIRADS I and IV, and none in TIRADS V. This distribution aligns with prior findings that most solitary nodules are benign and that malignancies cluster in TIRADS IV and V categories [15]. The histopathological confirmation of benign lesions in 76.7% and malignancies in 23.3% reinforces the diagnostic value of the ACR-TIRADS system in risk stratification. Histopathology revealed colloid nodules as the most common benign diagnosis, followed by nodular hyperplasia and follicular adenoma. Among malignant cases, papillary carcinoma was the most frequent subtype, a finding consistent across multiple series worldwide [16,17]. Follicular and medullary carcinoma were less common, but their presence highlights the spectrum of pathology possible in solitary nodules. FNAC remains the gold standard preoperative investigation. In our study, Bethesda II nodules strongly correlated with benign outcomes on histology, supporting its reliability in excluding malignancy. However, Bethesda III (AUS/FLUS) and Bethesda IV (suspicious for follicular neoplasm) demonstrated diagnostic uncertainty, with a substantial proportion proving malignant on histology. This confirms the limitations of FNAC in indeterminate categories and justifies the need for surgical excision in such cases [18,19]. Overall, our study emphasizes the importance of a multimodal diagnostic approach — integrating clinical findings, ultrasonography with TIRADS, and FNAC with Bethesda classification — to improve accuracy in distinguishing benign from malignant STNs. Histopathological examination remains the definitive diagnostic tool and the benchmark for evaluating other modalities [20].

The evaluation of solitary thyroid nodules requires a structured, stepwise approach. In our study, the majority of patients were young females presenting with neck swelling, with most nodules proving benign. Ultrasonography using ACR-TIRADS and cytological assessment with the Bethesda system provided valuable risk stratification, though indeterminate cytology continued to pose challenges. Histopathology confirmed that benign lesions were predominant (76.7%), while 23.3% were malignant, with papillary carcinoma being the most common subtype. FNAC showed strong correlation with HPE in benign nodules but limited predictive value in indeterminate categories. We conclude that clinical evaluation, ultrasonography, and FNAC are complementary tools, but histopathology remains the gold standard for final diagnosis. An integrated approach not only optimizes preoperative evaluation but also helps in timely surgical intervention and improved patient outcomes.

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