Thyroid cancer is relatively rare neoplasm worldwide, accounting for approximately 1-5% of all cancers in females and less than 2% in males.¹ Although the incidence of thyroid cancer is relatively rare, it is the most common endocrine malignancy worldwide.¹ Thyroid cancer accounts for 1.2% of all new malignant tumours (excluding skin cancer and in situ carcinomas) diagnosed annually in the United States (0.92% of cancers in men; 2.9% in women).² Approximately 1%-1.5% new cases are diagnosed each year in USA.² Thyroid cancer is the 5^th most common cancer in women ³ and in Italy; it is the 2^nd most common cancer in women below 45 years age.⁴

 Annual mortality of thyroid cancers is low, 5 year survival rate being 97.9%. Thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs. 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population). The risk of malignancy is lower in multinodular goitre than in solitary nodules with a reported rate between 4 and 10%.⁵

Incidence of thyroid malignancies differs in different parts of India. Nationwide relative frequency of thyroid cancer, among all cancer cases is 0.1% to 0.2 %.⁶ Studies in India show papillary carcinomas constituted 60% of thyroid cancers in Bangalore and Chennai, whereas this was around 40% in other registries. Follicular carcinomas accounted for 15% of thyroid cancers in Bangalore and Bhopal; in the other three urban registries this varied from 25-34%. Medullary carcinomas formed 5-6% of the cancers in Bangalore, Delhi and Mumbai, but this was 1% in Chennai and 12% in Bhopal.⁷ Thiruvananthapuram has the highest relative frequency of thyroid cancer.⁶ Hence this study was undertaken to look for pattern of thyroid malignancies in a rural institute of central India by clinical, radiological, cytopathological and histopathological correlation.

Present study was conducted in a rural tertiary care hospital of central India. It was conducted for the duration of 10 years, from September 2007 to September 2017. This was a retrospective and prospective (8 years retrospective and 2 years prospective) time bound non-randomized study.

 Inclusion criteria

• patients who were diagnosed to have thyroid carcinoma as per histopathological report
• patients undergoing thyroidectomy for other indications, who were later diagnosed as thyroid carcinoma as per histopathological report

Exclusion criteria

• patients whose complete data was unavailable
• patients who refused to give consent for prospective study

 The study was undertaken only after due clearance by Institutes ethics committee. Data for the retrospective study was collected from the Population based cancer registry in the hospital and also details about the cases were obtained from hospital information system. The cancer registry in the hospital collects data from more than 10 centers.

For both retrospective and prospective studies, clinical and demographic data was recorded in standard proforma. While collecting clinical data, importance was given to following factors such as clinical history regarding duration of symptoms, size of swelling, symptoms of thyrotoxicosis, hoarseness of voice, dyspnea, dysphagia, local pain, was asked. Family history of thyroid disorders, history of intake goitrogens and antithyroid medications, past history of surgery, radiation exposure and presence of comorbidities was noted. Radiological (USG/CT/MRI) reports and pathological reports (FNAC/Histopathology) were noted.

Statistical analysis of the data recorded was done as per standard applicable methods. The Chi square test was used to find the significance of the results obtained.

The present study was carried out on 188 patients admitted in the rural tertiary care hospital, newly diagnosed to have thyroid carcinoma by FNAC/Histopathology during the period of 10 years (September 2007-sept 2017). Incidence shows increasing trend, from 0.58 to 2.19 till 2016. Mean incidence is 1.15.

Table 1: Incidence of thyroid carcinoma

Maximum number of the patients was in 3^rd and 4^th decades of life (maximum in 4^th decade-26.06%). Mean age was 43 years. 10 cases were present below the age of 20 years. Out of a total of 188 patients, 46 patients were males (24.47%), while 142 patients were females (75.53%) with a female to male ratio of 3.08:1.

Table 2: Age & gender wise distribution of patients

In 84 patients out of 188 (44.68%), patients had symptoms for less than 1 year while only 35 patients(18.62%) had symptoms for more than 5 years. 69 patients (36.72%) had symptoms for a duration of 1 to 5 years.

Table 3: Distribution of patients according to duration of swelling

 98.9% Patients had neck swelling. Rest 1% presented with symptoms of distant metastasis. While most of the patients (67.02%) had no other local symptoms apart from neck swelling, rest showed symptoms of local invasion. The most common local symptom was pain and dysphagia (14.36% each) followed by change of voice (11.70%). Dyspnea was present in 13 patients (6.91%) while 3.72% patients had palpitations/symptoms of thyrotoxicosis.

Table 4: Distribution of patients according to other local symptoms

In 66.49% of the patients only one lobe was involved, while B/L lobes involvement was found in 33.51% of the patients.

Table 5: Distribution of patients according to involvement of lobes

153 patients out of 188(81.38%) were euthyroid, 14.36% were hyperthyroid while 4.26% were hypothyroid.

Table 6: Distribution of patients according to thyroid panel

USG was done in 142 patients of whom 84 results were true positive for thyroid carcinoma (59.15%). Colloid goitre/MNG was present in 29.58% cases while thyroiditis was present in 3.52% cases. CT was done in 51 cases. 82.35% of results were suggestive of thyroid carcinoma while 17.65% of carcinomas were undetected even on CT (goitre in 13.73%).

Table 7: Distribution of patients according to radiological findings

According to FNAC, colloid goitre was present in 27 cases (14.36%) while thyroiditis was present in 2.13% cases. FNAC was true +ve in 78.71% of the cases with most common occurrence of papillary carcinoma (39.89%) followed by follicular carcinoma (25%). Anaplastic carcinoma was present in 5.85% cases while medullary carcinoma was present in 4.25% cases. Hurthle cell neoplasm was present in 2.66% cases. According to FNAC findings, 1.06% cases (2 cases) showed metastasis to thyroid both from squamous cell carcinoma. 1.59% of FNACs were inconclusive. Other FNAC findings like thyroglossal cyst and epithelial malignancy were present in 2.66% cases.

Table 8: Distribution of patients according to FNAC findings

Out of 188 patients, 176 patients were operated for thyroid swelling. Histopathology report is not available in 12 patients who were either inoperable or unwilling for surgery. Papillary carcinoma was the most common type with 119 patients (67.61% cases), followed by follicular carcinoma (21.59%). Medullary carcinoma was 3.98% while hurthle cell neoplasm was present in 2.84% cases. Only 1 case of anaplastic carcinoma was operated (rest being inoperable according to CT findings), making 0.57% of histopathological diagnosis. Lymphoma was detected in only 1 case (0.57%), operated for thyroiditis.

Among papillary carcinoma of thyroid, follicular variant was present in 36 cases while oxyphillic variant was present in 2 cases. Encapsulated variant was present in 3 cases while encysted variant was present in 2 cases, cystic changes were present in 2 cases. Solid, oncocytic, intracystic, micropapillary and insular carcinoma follicular variant was present in 1 case each. Among cases of follicular carcinoma, focal insular variant was present in 1 case while poorly differentiated carcinoma was present in 2 cases. Widely invasive columnar cell variant was present in 2 cases of follicular carcinoma and 1 case of papillary carcinoma. osteoclastic variant was present in 1 case of anaplastic carcinoma.

Table 9: Distribution of patients according to H/P findings

Metastasis (distant or local) was present in 87 cases out of 188. Status of metastasis was present in 10 cases. In the cases of follicular carcinoma metastasis was present in 20 cases, out of which 4 cases had local invasion and 12 patients had distant metastasis. Invasion of surrounding tissue was present mostly in papillary carcinoma while lymph modal involvement was present in anaplastic carcinoma. Among distant metastasis, pulmonary, scalp and bony metastasis was more common. Liver metastasis was present in only 1 case (papillary carcinoma).

Table 10: Correlation of pathological findings with metastasis

Histopathological findings were compared with age of the patients. Cases where histopathology report was unavailable (due to inoperability), cytopathological report was considered. According to pathological distribution, percentage of follicular carcinoma was 20.21%, while papillary carcinoma was 63.29%. Medullary carcinoma was in 3.72%, anaplastic carcinoma in 5.85% while hurthle cell carcinoma was in 2.66%. Most common age group was 31-40 years (26.06%), while most of the cases were present from 21-60 years of age (80.83%). Follicular carcinoma was more common in 31-40 years age group while papillary carcinoma was present in 21-40 years age. Anaplastic carcinoma was more common in 61-70 years age group while medullary carcinoma was more common in 31-50 years age.

Table 11: Correlation of pathological findings with age in years

Thyroid carcinoma in this study is 3.08 times more common in females than males. Similarly, all the subtypes of thyroid carcinoma were found to be more common in females except medullary carcinoma which was 2.5 times more common in males. Only 1 case of anaplastic carcinoma was present in males, rest other patients being females.

Table 12: Correlation of pathological findings with gender

After correlating FNAC and histopathological diagnosis, it was found that out of 27 cases diagnosed as colloid goitre on FNAC, 2 cases had follicular carcinoma and 25 cases had papillary carcinoma on histopathology. Follicular adenoma proved to be follicular carcinoma on H/P. Out of 47 cases with follicular carcinoma on FNAC, 15 cases had papillary carcinoma on H/P. Out of 4 cases diagnosed as thyroiditis on FNAC, 3 had papillary carcinoma and 1 had lymphoma. 3 Patients whose FNAC was inconclusive had papillary carcinoma in 1 case and other H/P findings of paraganglioma and epithelial malignancy in rest. 1 patient who was diagnosed as thyroglossal cyst on FNAC had papillary carcinoma on H/P. Sensitivity of FNAC was found out to be 67.55 %( 95% CI= 58.88-77.12%).

Table 13: Correlation of FNAC versus histopathological diagnosis

USG was done in 142 patients. Out of 33 patients diagnosed as colloid goitre on USG, 6 patients on histopathology had follicular carcinoma while 25 patients had papillary carcinoma. 1 patient had lymphoma. 8 patients with multinodular goitre had papillary carcinoma. 5 patients with changes of thyroiditis on USG had follicular papillary and hurthle cell carcinoma on H/P. However, the correlation was found to be not significant. Sensitivity of USG was 59.15%.

Table 14: Correlation of USG versus histopathological diagnosis

Thyroid cancer is the most common endocrine malignancy in the world, with approximately 1%-1.5% new cases diagnosed each year in USA. It consists of 0.5-1% of all cancer cases. It is 3 times more common in females.⁵ Annual incidence rates of thyroid malignancies vary according to age, sex, geographic area and ethnicity. Various environmental factors affect the incidence of thyroid carcinoma. Incidence is different in different parts of India. Annual incidence of thyroid malignancies is rapidly increasing in the world, in terms of annual percentage change; it is among the fastest growing cancers.⁷ Reason of this sudden increase in incidence is postulated to be either true rise in incidence or due to over diagnosis. Although annual incidence of thyroid malignancies is increasing over time in both men and women, mortality due to thyroid cancer has decreased over past 50 years.^2,3

In present study, mean incidence of thyroid carcinoma was 1.15 (males-0.43, females-2.58). Increase in incidence was noted from 0.58 to 2.19 till 2016. Incidence of thyroid carcinoma as reported in various studies mentioned below varies significantly. Though incidence in present study is less than most of the studies conducted, this can be compared to the incidence of China as per CI5, volume 11^th(2016)⁸ which was 1.8., and many cancer registries in India like Bangalore(M-1.4, F-3.5), Chennai(M-1.1, F-2.7), Sikkim(M-1.1, F-2.8), Mizoram(M-0.9, F-3.3) and Mumbai(M-0.9, F-2.2).⁸ Female to male ratio in present study was found to be 3.08:1 which are more or less similar to as reported by Rahbhari R et al. (2.9:1).⁹

Occurrence of thyroid carcinoma increases with age. In the present study thyroid carcinoma was more commonly found in 3^rd and 4^th decade of life (45%). In a study by T Pramod et al. (2016), most of the cases of thyroid carcinoma were seen in 21-50 years age group with mean age of occurrence being 36 years.¹⁰ According to Ali Alzahrani et al. (2017), mean age was 39 years and majority of patients were in fourth and fifth decades of life.¹¹

In the present study, 44% patients had symptoms for less than a year, 36.7% for 1 to 5 years and only 18.6% patients had symptoms for more than 5 years. While in a study by T Pramod et al. 53.3% patients had complaints for less than 1 year, 40% for 1 to 5 years and only 6.6% for more than 10 years.¹⁰

Symptomatically, most of the tumours in this study presented without any other symptom than neck swelling. M Sepuri et al.,¹² a neck swelling in 71.42% cases, hoarseness of voice in 10.61% cases and dysphagia in 9.29% cases. Neck swelling was present in all the patients in a study by T Pramod et al.,¹⁰ hoarseness of voice in 10% cases dysphagia in 3.3% cases and changes of thyrotoxicosis and 6% cases. In the present study 98.9% patients presented with neck swelling, 67.02% patients had no other symptom than a neck swelling. The most common local symptom was pain and dysphagia followed by change of voice. 14.36% patients had pain; 11.7% patients experienced change in voice. 21% patients had dysphagia and dyspnea while 3.72% patients experienced palpitations.

Biochemically 81.38% patients in the study were euthyroid, hyperthyroidism was found in only 14.36% patients while 4.26% patients were hypothyroid. Association between hyperthyroidism and thyroid carcinoma was found 1.2% by C Lin et al.,¹³ and 13.3% by TC Chao et al.,¹⁴

According to the literature available, papillary carcinoma is the most common pathological variety of thyroid cancer. In the present study, papillary carcinoma was the most common type, followed by follicular carcinoma. In the present study papillary carcinoma consisted of 63.2% of cases, percentage of follicular carcinoma was 20% while that of medullary and anaplastic carcinoma was 3.7% and 5.8% respectively. This result was consistent with most of the studies except for the percentages which may differ. H. Katoh et al.,¹⁵ found percentage of PCT 85-90%, FCT 5-10 %. Madhuri Sepuri et al.,¹² found the percentage of PCT 79%, FCT 19%, anaplastic and medullary carcinomas comprised 2 %.

 USG neck was done in 142 patients. 59.15% patients were diagnosed of having malignancy on USG. 23.34% patients had colloid goitre on ultrasound, 6% multinodular goitre, 5.6% a thyroid nodule, 3.52% thyroiditis. CT/MRI was done in only 51 patients. 82.35% patients were diagnosed to have thyroid carcinoma correctly, while 13.73% patients had goitre on CT/MRI. Table 9 shows comparison of sensitivity of USG. Winson JH et al.,¹⁶ found it to be 41%, while L R Remonti et al.,¹⁷ found it to be 87.9%. In the present study, it was 59.15%.

FNAC was done all the patients. FNAC diagnosed papillary carcinoma in 39.89% patients, medullary carcinoma in 4.25% patients. Colloid/nodular goitre in 14.36% cases. Percentage of medullary and anaplastic carcinoma was 4.25% and 5.85% respectively. 2.13% Patients had thyroiditis. Sensitivity in a study by P. Pandey et al.,¹⁸ was 57.12%, while it was 91.66% in a study by N R et al.,¹⁹ Sensitivity of FNAC was found out to be 67.55 % (95% CI=58.88-77.12%) which is more or similar to the study by Afroze et al.,²⁰

Incidence of thyroid carcinoma is increasing worldwide and India is not an exception. In the present study, it has been observed that incidence of thyroid carcinoma increased from 0.58 (2007) to 2.19 (2016). However, it was only 1.14 in 2017. The cause of this decreased incidence may be due to underreporting or patients going elsewhere. More increasing incidence could be due to better investigative facilities where early detection by USG & FNAC is possible. However, this increase could be attributed to the reflections in the increased detection of subclinical disease and this may not be actually the true occurrence of thyroid carcinoma. More studies with involvement of multiple centers are needed to know true incidence of thyroid carcinoma and thus planning better management. 

It was found that incidence of thyroid carcinoma is increasing. Papillary carcinoma is the most common variety. Also, female preponderance can be seen. More increasing incidence could be due to increased use of USG & FNAC for the diagnosis of thyroid swellings, thereby increasing the diagnosis of small thyroid swellings (microadenomas).

However, this increase could be attributed to the reflections in the increased detection of subclinical disease and this may not be actually the true occurrence of thyroid carcinoma. So, either ‘overdiagnosis’ or true rise in incidence can be the reason. More studies with involvement of multiple centers are needed to know the true incidence of thyroid carcinoma and thus planning better management.

Conflict of Interest: None to declare

Source of funding: Nil.

1. Louise Davies, H. Gilbert Welch. Increasing Incidence of Thyroid Cancer in the United States, 1973-2002. JAMA. 2006;295(18):2164–2167. doi:10.1001/jama.295.18.2164
2. Kilfoy BA, Zheng T, Holford TR, et al. International patterns and trends in thyroid cancer incidence, 1973–2002. Cancer causes & control : CCC. 2009;20(5):525-531.
3. Jemal A, Murray T, Ward E, et al. American Cancer Society. Cancer Statistics, 2005. CA Cancer J Clin 2005; 55:10–30
4. dal Maso, M. Lise, P. Zambon et al., “Incidence of thyroid cancer in Italy, 1991–2005: time trends and age-period-cohort effects,” Annals of Oncology, vol. 22, no. 4, pp. 957–963, 2011.
5. Shepperd MC. Thyroid cancer. Oxford textbook of Medicine, edited by Weatherall DJ, Ledingham JGG, Warrel DA, Oxford University press, New York, 1996, 3^rd edition, vol 2, 1618.
6. Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological perspective. Indian Journal of Endocrinology and Metabolism. 2011;15(Suppl2):S78-S81.
7. National Cancer Registry Programme- Population based and Hospital based cancer Registry.
8. P. Curado, B. Edwards, H. R. Shin et al., Cancer Incidence in Five Continents, vol. 11 of IARC Scientific Publications, tables, IARC, 2016.
9. Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future oncology (London, England). 2010;6(11):1771-1779.
10. T Pramod, B S Shivaswamy, G Ananth, G Rajashekara Babu, K Latha, K Jagadeesh, Clinical Study of Carcinoma Thyroid and its Management. International Journal of Scientific Study, Jan 2016, Vol 3, Issue 10
11. Ali S. Alzahrani, Haneen Alomar, and Nada Alzahrani, “Thyroid Cancer in Saudi Arabia: A Histopathological and Outcome Study,” International Journal of Endocrinology, vol. 2017, Article ID 8423147, 7 pages, 2017.
12. Sepuri M, Das B. Spectrum of thyroid carcinomas in coastal Andhra Pradesh: A retrospective study. J. Evid. Based Med. Healthc. 2016; 3(71), 3840-3844.
13. Chih-HsinLin, Feng-YuChiang, Ling-FengWang Prevalence of Thyroid Cancer in Hyperthyroidism Treated by Surgery The Kaohsiung Journal of Medical Sciences Volume 19, Issue 8, August 2003, Pages 379-383
14. Tzu-Chieh Chao, Jen-Der Lin, Long-Bin Jeng, Miin-Fu Chen. Thyroid Cancer With Concurrent Hyperthyroidism. Arch Surg. 1999;134(2):130–134.
15. Katoh H, Yamashita K, Enomoto T, Watanabe M (2015) Classification and General Considerations of Thyroid Cancer. Ann Clin Pathol 3(1):1045
16. Winson JH Tan, Kaushal Sanghvi, Kui Hin Liau, Cheng Hock Low, An Audit Study of the Sensitivity and Specifi city of Ultrasound, Fine Needle Aspiration Cytology and Frozen Section in the Evaluation of Thyroid Malignancies in a Tertiary Institution; Ann Acad Med Singapore 2010;39:359-62.
17. Remonti LR, Kramer CK, Leitão CB, Pinto LCF, Gross JL. Thyroid Ultrasound Features and Risk of Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies. Thyroid. 2015;25(5):538-550.
18. Pandey P, Dixit A, Mahajan NC. FNA of thyroid, A Cytopathological correlation with critical evaluation of discordant cases, Thyroid Res Pract 2012;9:32-9.
19. N R, B V, T G. Comparative Study of FNAC And histopathology in the diagnosis of thyroid Swelling. The Internet Journal of Head and Neck Surgery. 2012 Volume 5 number 2.
20. Afroze N, Kalyani N, Hassan SH, Role of FNAC in the diagnosis of palpable thyroid lesions, Indian J Pathology Microbiology, 2002 Jul;45(3):241-6.