Thyroid carcinoma represents an increasingly important public health concern globally, with incidence rates rising from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2002, representing a 2.4-fold increase (1). This dramatic rise has been particularly evident for papillary thyroid carcinoma, which has shown a 2.9-fold increase in incidence over the same period (2). Despite this increasing incidence, thyroid cancer maintains relatively favorable outcomes compared to other malignancies, with five-year survival rates approaching 97% when diagnosed early and treated appropriately (3).

The thyroid gland, the largest endocrine organ in the human body, plays a crucial role in metabolic regulation through the production of thyroid hormones. Malignant transformation within thyroid tissue presents a spectrum of histological entities with diverse clinical behaviors, ranging from well-differentiated papillary and follicular carcinomas with excellent prognosis to poorly differentiated and anaplastic carcinomas with aggressive clinical courses (4). Understanding this heterogeneity is essential for appropriate clinical management and prognostication.

Epidemiological studies have demonstrated significant geographical variations in thyroid cancer incidence and histological distribution. In iodine-sufficient regions, papillary carcinoma accounts for approximately 80% of all thyroid malignancies, while follicular carcinoma shows increased prevalence in iodine-deficient areas (5). These patterns underscore the complex interplay between environmental factors, particularly dietary iodine intake, and thyroid carcinogenesis. Additionally, the widespread implementation of ultrasound screening and improved diagnostic techniques has contributed to increased detection of subclinical thyroid nodules, potentially explaining part of the observed rise in incidence (6).

The etiology of thyroid cancer involves multiple risk factors, with ionizing radiation exposure being the only definitively established environmental carcinogen. The relationship between radiation exposure and thyroid cancer was first recognized by Duffy and Fitzgerald in 1950, with subsequent studies confirming a dose-dependent relationship (7). The Chernobyl nuclear disaster in 1986 provided compelling epidemiological evidence, demonstrating a dramatic increase in pediatric thyroid cancer cases with a shorter latency period than previously reported (8). Other established risk factors include female gender, with a female-to-male ratio ranging from 2:1 to 3:1, age at presentation, family history of thyroid cancer, and pre-existing benign thyroid disease (9).

The clinical evaluation of thyroid nodules remains a common challenge confronting clinicians worldwide. While thyroid nodules are present in approximately 4-7% of the adult population by palpation and up to 50% by ultrasound examination, only 5-10% harbor malignancy (10). This discrepancy necessitates accurate diagnostic strategies to identify malignant lesions while avoiding unnecessary surgical interventions for benign disease. The development and refinement of fine needle aspiration cytology (FNAC) has revolutionized the diagnostic approach to thyroid nodules since its initial description by Martin and Ellis in the 1930s and subsequent popularization in Scandinavia during the 1950s (11).

FNAC has emerged as the cornerstone investigation for thyroid nodule evaluation, offering a minimally invasive, cost-effective, and accurate diagnostic modality. Multiple studies have demonstrated sensitivities ranging from 65-98% and specificities of 72-100% for FNAC in detecting thyroid malignancy (12). The implementation of standardized reporting systems, such as the Bethesda System for Reporting Thyroid Cytopathology, has further improved diagnostic consistency and clinical decision-making. However, limitations persist, particularly in distinguishing follicular adenomas from follicular carcinomas, where histological evaluation of capsular and vascular invasion remains necessary for definitive diagnosis (13).

The surgical management of thyroid cancer has evolved significantly since the pioneering work of Theodore Kocher, who performed over 5,000 thyroidectomies and received the Nobel Prize in Medicine in 1909 for his contributions to thyroid surgery. Contemporary surgical approaches range from lobectomy for small, low-risk tumors to total thyroidectomy with lymph node dissection for more advanced disease (14). The extent of surgical resection remains a subject of ongoing debate, particularly for low-risk differentiated thyroid cancers, where the balance between oncological adequacy and preservation of quality of life must be carefully considered.

Recent advances in molecular diagnostics have provided insights into the pathogenesis of thyroid cancer and identified potential therapeutic targets. The identification of driver mutations, including BRAF V600E in papillary carcinoma and RAS mutations in follicular neoplasms, has improved diagnostic accuracy and prognostication. Furthermore, the recognition of familial thyroid cancer syndromes and the role of germline mutations in RET proto-oncogene for medullary thyroid carcinoma has enabled targeted screening and prophylactic interventions in high-risk individuals (15).

The present study aims to evaluate the clinicopathological characteristics and surgical outcomes of thyroid carcinoma patients treated at a tertiary care center in South India, contributing to the understanding of disease patterns in this population and comparing findings with international literature.

Aims and Objectives

The primary objectives of this study were:

1. To analyze the clinical presentation patterns of thyroid carcinoma patients
2. To determine the relative incidence of various histopathological types of thyroid carcinoma
3. To evaluate the correlation between fine needle aspiration cytology findings and final histopathological diagnosis
4. To assess the surgical management approaches and postoperative outcomes.

Study Design and Setting

This prospective observational study was conducted at K.R. Hospital, Mysore Medical College and Research Institute, Mysore, Karnataka, India, from September 2018 to June 2020. The institution serves as a tertiary care referral center for the region, providing comprehensive surgical and oncological services.

Study Population

The study included all patients diagnosed with thyroid carcinoma who were admitted to various surgical wards during the study period. A total of 49 patients with confirmed thyroid malignancy were enrolled using simple random sampling technique.

Inclusion Criteria

Patients were included if they met the following criteria:

• Age 12 years and above
• Clinical signs and symptoms suggestive of thyroid malignancy
• Cytological or histopathological confirmation of thyroid carcinoma
• Consent for participation in the study and surgical intervention

Exclusion Criteria

The following patients were excluded from the study:

• Age below 12 years
• Benign thyroid disorders
• Patients who refused treatment or withdrew consent
• Recurrent thyroid carcinoma cases
• Patients with previous thyroid surgery

Data Collection

A standardized proforma was developed to collect comprehensive patient information. Data collection included detailed demographic characteristics, clinical history with emphasis on duration and progression of symptoms, physical examination findings, and relevant family history. All patients underwent thorough clinical evaluation including general physical examination and focused thyroid examination assessing gland size, consistency, mobility, and lymph node status.

Diagnostic Evaluation

All patients underwent comprehensive diagnostic workup including:

Laboratory Investigations: Complete blood count, renal function tests, thyroid function tests (serum TSH, free T3, and free T4), and serum calcium levels were obtained for all patients.

Imaging Studies: Chest radiographs in anteroposterior and lateral views were performed to assess tracheal position and detect pulmonary metastases. Neck radiographs were obtained to evaluate for calcifications and tracheal deviation. Ultrasonography of the neck was performed when indicated for further characterization of thyroid nodules and cervical lymph nodes.

Fine Needle Aspiration Cytology: FNAC was performed using standard technique with 23-gauge needles under aseptic precautions. Multiple passes were made to ensure adequate sampling. Smears were prepared and stained with Papanicolaou and May-Grünwald-Giemsa stains. Cytological findings were reported according to the Bethesda System classification.

Indirect Laryngoscopy: Preoperative vocal cord assessment was performed in all patients to document baseline vocal cord function and identify any pre-existing paralysis.

Surgical Management

Surgical procedures were performed by experienced surgeons following standardized techniques. The extent of surgery was determined based on preoperative diagnosis, intraoperative findings, and frozen section results when indicated. Surgical procedures included total thyroidectomy, near-total thyroidectomy, hemithyroidectomy with or without completion thyroidectomy, and functional neck dissection when lymph node metastases were identified.

Histopathological Examination

All surgical specimens were subjected to detailed histopathological examination. Specimens were fixed in 10% formalin, processed routinely, and sections were stained with hematoxylin and eosin. Special stains and immunohistochemistry were performed when necessary for definitive diagnosis.

Postoperative Management and Follow-up

Postoperative monitoring included assessment for complications such as hypocalcemia, recurrent laryngeal nerve injury, hemorrhage, and wound infection. Serum calcium levels were monitored, and clinical signs of hypocalcemia were evaluated. Indirect laryngoscopy was repeated if voice changes occurred postoperatively. All patients with differentiated thyroid carcinoma were referred for radioiodine therapy when indicated. Thyroid hormone replacement was initiated in all patients post-thyroidectomy.

Statistical Analysis

Data were entered in Microsoft Excel and analyzed using SPSS version 23.0. Descriptive statistics were presented as frequencies and percentages for categorical variables and means with standard deviations for continuous variables. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of FNAC were calculated using histopathology as the gold standard. The AMES (Age, Metastases, Extent, Size) risk stratification system was applied to categorize patients with differentiated thyroid carcinoma into low-risk and high-risk groups.

Ethical Considerations

The study protocol was approved by the Institutional Ethics Committee of Mysore Medical College and Research Institute. Written informed consent was obtained from all participants before enrollment. Patient confidentiality was maintained throughout the study period.

Demographic Characteristics

Among the 49 patients with confirmed thyroid carcinoma, the mean age at presentation was 42.3 ± 14.8 years, with a range of 19 to 79 years. The peak incidence occurred in the fourth decade of life (30-39 years), accounting for 30.6% of cases. Female patients predominated with 35 cases (71.4%), resulting in a female-to-male ratio of 2.5:1.

Table 1: Age and Gender Distribution of Thyroid Carcinoma Patients

Clinical Presentation

The most common presenting symptom was anterior neck swelling, observed in 47 patients (95.9%). The median duration of symptoms before presentation was 6 months, with a range from 1 month to 7 years. Among patients with thyroid swelling, 29.7% presented within 3 months of symptom onset, while 76.6% sought medical attention within one year. Associated symptoms included hoarseness of voice in 3 patients (6.1%), dysphagia in 3 patients (6.1%), and dyspnea in 3 patients (6.1%). Cervical lymphadenopathy was clinically evident in 3 patients (6.1%) at presentation. One patient (2.0%) presented with distant metastasis to bone.

Table 2: Clinical Features and Duration of Symptoms

Diagnostic Findings

Preoperative indirect laryngoscopy revealed vocal cord palsy in 4 patients (8.2%), with 3 cases involving the right vocal cord and 1 involving the left. Radiological evaluation showed tracheal deviation in 7 patients (14.3%) and calcification within the thyroid gland in 3 patients (6.1%).

Fine needle aspiration cytology was performed in all 49 patients. The cytological diagnoses included papillary carcinoma in 39 cases (79.6%), follicular neoplasm in 8 cases (16.3%), anaplastic carcinoma in 1 case (2.0%), and lymphoma in 1 case (2.0%). When compared with final histopathology from 903 thyroid specimens during the study period, FNAC demonstrated a sensitivity of 73.5%, specificity of 98.7%, positive predictive value of 81.2%, negative predictive value of 98.1%, and overall diagnostic accuracy of 97.05%.

Table 3: Correlation of FNAC with Histopathological Diagnosis

Histopathological Distribution

Final histopathological examination revealed papillary carcinoma as the predominant malignancy in 35 cases (71.4%), with 4 cases showing follicular variant morphology. Follicular carcinoma was diagnosed in 8 cases (16.3%), follicular variant of papillary carcinoma in 4 cases (8.2%), anaplastic carcinoma in 1 case (2.0%), and primary thyroid lymphoma in 1 case (2.0%). No cases of medullary carcinoma or Hürthle cell carcinoma were identified during the study period.

Disease Staging and Risk Stratification

According to the American Joint Committee on Cancer (AJCC) 2017 staging system, 30 patients (61.2%) presented with stage I disease, 5 patients (10.2%) with stage II, 4 patients (8.2%) with stage III, and 10 patients (20.4%) with stage IVA disease. No patients presented with stage IVB disease.

Application of the AMES risk stratification system to the 47 patients with differentiated thyroid carcinoma revealed 30 patients (63.8%) in the low-risk category and 17 patients (36.2%) in the high-risk category. Among papillary carcinoma patients specifically, 25 (64.1%) were classified as low-risk and 14 (35.9%) as high-risk.

Table 4: AJCC Staging and AMES Risk Stratification

Surgical Management

Total thyroidectomy was the most commonly performed procedure, undertaken in 41 patients (83.7%). Near-total thyroidectomy was performed in 3 patients (6.1%) where complete resection would risk injury to the recurrent laryngeal nerve. Three patients (6.1%) initially underwent hemithyroidectomy for follicular neoplasm on FNAC, followed by completion thyroidectomy after histopathological confirmation of malignancy. Functional neck dissection was performed in 2 patients (4.1%) with clinically evident lymph node metastases.

Postoperative Complications

The overall complication rate was 16.3%. Transient hypoparathyroidism, manifesting as symptomatic hypocalcemia, occurred in 10 patients (20.4%) and resolved with calcium supplementation within 2-4 weeks. Permanent recurrent laryngeal nerve injury was documented in 2 patients (4.1%), both of whom had extensive local disease with nerve involvement. No cases of postoperative hemorrhage, wound infection, or perioperative mortality were observed.

Table 5: Surgical Procedures and Postoperative Complications

Postoperative Management

All patients with differentiated thyroid carcinoma were referred for radioiodine ablation therapy at specialized oncology centers. The single patient with anaplastic carcinoma was referred for external beam radiotherapy, while the lymphoma patient received combination chemotherapy with radiotherapy. All patients were initiated on levothyroxine replacement therapy postoperatively with dose adjustment based on TSH suppression goals according to risk stratification.

This prospective study provides valuable insights into the clinicopathological patterns and surgical outcomes of thyroid carcinoma in a South Indian population. Our findings demonstrate several important trends that both align with and diverge from international literature, offering opportunities for comparative analysis and identification of population-specific characteristics.

The age distribution in our cohort showed peak incidence in the fourth decade of life (30-39 years), accounting for 30.6% of cases, with a mean age of 42.3 years. This finding contrasts with studies from Western populations where peak incidence typically occurs in the fifth and sixth decades. Dave et al. reported the commonest affected age group as the fifth decade, while Bhansali et al. found predominance in the sixth decade (1,2). The younger age at presentation in our population may reflect increased awareness and earlier healthcare seeking behavior in recent years, though genetic and environmental factors cannot be excluded. Similar patterns of younger age at diagnosis have been reported from other developing nations, suggesting possible common underlying factors.

The female predominance observed in our study (71.4%) with a female-to-male ratio of 2.5:1 aligns with global epidemiological data. Dos Santos Silva and Swerdlow reported a female-to-male ratio of 3:1 in their comprehensive analysis of hormone-dependent cancers in England and Wales (3). The slightly lower ratio in our population may reflect cultural factors affecting healthcare access or biological differences in susceptibility. Interestingly, while females showed higher absolute numbers, the proportion of high-risk cases was similar between genders, suggesting that male gender alone may not confer worse prognosis when other risk factors are considered.

Clinical presentation patterns in our study revealed thyroid swelling as the predominant symptom (95.9%), higher than the 77% reported by Simon et al. and 84% by Kannan et al. (4,5). This difference may reflect delayed presentation until visible swelling develops, as suggested by the median symptom duration of 6 months in our cohort. The relatively low incidence of presenting cervical lymphadenopathy (6.1%) compared to Kannan's series (42%) suggests that most patients sought medical attention before extensive nodal spread occurred, though subclinical nodal disease may have been underestimated without routine prophylactic neck dissection.

The diagnostic performance of FNAC in our study demonstrated a sensitivity of 73.5% and specificity of 98.7%, with an overall accuracy of 97.05%. While our specificity exceeded that reported by Silverman et al. (96.5%) and Harsoulis et al. (95.4%), the sensitivity was lower than their reported values of 93% and 89.2%, respectively (6,7). This discrepancy likely reflects sampling limitations and the challenge of distinguishing follicular neoplasms, which accounted for a significant proportion of false-negative results. The high specificity confirms FNAC's value in ruling in malignancy when positive, supporting its role as the primary diagnostic modality for thyroid nodule evaluation.

The histopathological distribution in our series showed papillary carcinoma predominance (79.5%), consistent with global trends but higher than the 66.4% reported by Simon et al. and comparable to the 81% reported by Scott et al. (8,9). The proportion of follicular carcinoma (16.3%) falls between these two series (27.2% and 13.6%, respectively), possibly reflecting regional iodine sufficiency status. The absence of medullary carcinoma in our cohort, despite representing 3-5% of thyroid malignancies globally, may be due to the relatively small sample size or referral bias, as these cases might be managed at specialized oncology centers.

Disease staging revealed a predominance of early-stage disease, with 61.2% presenting as stage I according to AJCC 2017 criteria. This favorable stage distribution likely reflects the high proportion of papillary carcinoma and younger patient age, both favorable prognostic factors in the staging system. However, the 20.4% of patients presenting with stage IVA disease indicates that a significant minority still present with locally advanced disease, emphasizing the need for improved early detection strategies.

Risk stratification using the AMES criteria classified 63.8% of differentiated thyroid carcinomas as low-risk, similar to international series where low-risk patients typically comprise 60-70% of cases. The prognostic implications are significant, as low-risk patients have reported 20-year cause-specific mortality rates of less than 2%, while high-risk patients face mortality rates of 40-50% (10). This stratification guides decisions regarding extent of surgery, radioiodine therapy, and follow-up intensity.

Surgical management in our series showed a strong preference for total thyroidectomy (83.7%), reflecting current guidelines favoring complete thyroid removal for most differentiated thyroid carcinomas larger than 1 cm. This approach aligns with the 81% total thyroidectomy rate reported by Gullamondegui et al. (11). The rationale for total thyroidectomy includes facilitation of radioiodine ablation, improved sensitivity of thyroglobulin monitoring, and reduced recurrence risk. The 6.1% of patients undergoing initial hemithyroidectomy followed by completion thyroidectomy highlights the diagnostic limitations of FNAC for follicular neoplasms, where definitive diagnosis requires histological assessment of capsular and vascular invasion.

The complication profile in our study compares favorably with published literature. Transient hypoparathyroidism occurred in 20.4% of patients, within the reported range of 10-30% for total thyroidectomy (12). All cases resolved with calcium supplementation, suggesting careful parathyroid preservation during surgery. The permanent recurrent laryngeal nerve injury rate of 4.1% is slightly higher than the 1-2% typically reported in high-volume centers, likely reflecting the inclusion of locally advanced cases requiring more extensive dissection (13).

The universal referral for radioiodine therapy in our differentiated thyroid carcinoma patients reflects international guidelines recommending ablation for intermediate and high-risk patients. Recent evidence suggests more selective use of radioiodine, particularly for low-risk patients where the absolute benefit may be minimal (14). However, in settings with limited follow-up resources, upfront ablation may facilitate surveillance through stimulated thyroglobulin measurement and whole-body scanning.

Our study's strengths include prospective design, standardized diagnostic and treatment protocols, and comprehensive clinicopathological correlation. The inclusion of all consecutive cases minimizes selection bias, while the correlation of FNAC with histopathology in over 900 specimens provides robust diagnostic accuracy data. Limitations include the relatively small sample size, which may explain the absence of rare histological variants, and the short follow-up period, precluding survival analysis.

The implications of our findings for clinical practice are several. First, the high proportion of patients presenting with prolonged symptom duration suggests opportunities for earlier detection through public awareness campaigns. Second, the younger age at presentation in our population may warrant age-adjusted screening recommendations. Third, the excellent specificity but moderate sensitivity of FNAC emphasizes the need for clinical judgment in managing cytologically benign but clinically suspicious nodules. Fourth, the acceptable complication rates support the feasibility of thyroid cancer surgery in resource-limited settings with appropriate training and protocols.

Future research directions include long-term follow-up to assess recurrence patterns and survival outcomes, molecular profiling to identify population-specific genetic alterations, and cost-effectiveness analyses of different management strategies in the Indian healthcare context. The integration of molecular markers into diagnostic algorithms may improve the preoperative distinction of benign and malignant follicular neoplasms, potentially reducing unnecessary surgery (15).

This comprehensive analysis of 49 thyroid carcinoma cases provides important insights into disease patterns in a South Indian tertiary care setting. Papillary carcinoma remains the predominant histological type, accounting for 79.5% of cases, with most patients presenting with early-stage disease amenable to surgical cure. The younger age at presentation compared to Western populations and the female predominance align with regional epidemiological patterns.

FNAC proves to be a valuable diagnostic tool with high specificity (98.7%) and acceptable sensitivity (73.5%), supporting its continued use as the primary investigative modality for thyroid nodules. Total thyroidectomy remains the preferred surgical approach, with complication rates comparable to international standards. The predominance of low-risk disease by AMES criteria suggests favorable long-term outcomes for the majority of patients.

These findings emphasize the importance of early detection, accurate preoperative diagnosis, and appropriate surgical management in optimizing outcomes for thyroid carcinoma patients. The successful management of thyroid cancer in resource-limited settings is feasible with adherence to evidence-based protocols and multidisciplinary care coordination.

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