Accepted on 29 Oct 2022
Submitted on 24 Sep 2022
Objective: To retrospectively analyze the clinicopathological characteristics of thyroid cancer patients with respect to age, gender, benign lesions, and lymph node metastasis and to explore the clinicopathological features of multifocal and unifocal papillary thyroid carcinoma with cervical lymph node metastasis.
Methods: The clinicopathological data of 14,431 patients with thyroid cancer who underwent surgical treatment for the first time in the Department of Head and Neck Oncology of our hospital from January 2011 to December 2015 were collected, analyzed, and compared in terms of age, gender, pathological type, benign lesions, and lymph node metastasis.
Results: Among 14431cases, here were 3259 males and 11172 females, with a male-to-female ratio of 1:3.43. Patients aged 30–59 years accounted for 82.15%. The number of thyroid cancer cases showed an increasing trend year by year (P < 0.001), and papillary carcinoma was the most common (98.47%). Among 14,210 patients with papillary thyroid carcinoma, 4736 cases were in the multi-focus group and 9474 cases were in the single-focus group. Comparison of the pathological characteristics between the two groups showed that the multi-focus group had a higher probability of lymph node metastasis (P < 0.001). A single-focus combination of papillary thyroid carcinoma with benign lesions was more common (P < 0.001), and the difference was statistically significant. Among the cases of multifocal papillary thyroid carcinoma, there were 2812 cases in the multifocal papillary thyroid carcinoma group, and 1924 cases in the unilateral and/or isthmus group. The analysis showed that there were more males, younger patients, more patients with benign lesions, and a higher incidence of unilateral microcarcinoma in the unilateral and/or isthmus multifocal thyroid carcinoma group (P = 0.017). p < 0.001, p < 0.001, and p < 0.001, respectively). There were more patients with cervical lymph node metastasis in the bilateral multifocus group (p = 0.016), and the difference was statistically significant.
Conclusion: Multiple lesions are one of the clinical features of papillary thyroid carcinoma, which are more prone to cervical lymph node metastasis and more aggressive than single lesions.
Thyroid carcinoma(TC) is one of the most common cancers in head and neck cancer worldwide, affecting people in both developing and developed countries, with an incidence of 600,000 new cases diagnosed annually [1, 2, 3]. Since the 21st century, the incidence of TC has increased every year, owing to the development of the economy, improvement of medicine, changes in diet structure, ecological environment, and other factors, which have made TC become the fastest growing malignant tumor [4, 5]. Multiple studies have shown that isthmus PTC is more aggressive and is associated with poor prognosis, and its characteristics include multifocal, capsule invasion, extrathyroid extension and lymph node metastasis [6]. Early identification of patients with advanced or high-risk PTC who require more aggressive evaluation may help reduce morbidity and increase life expectancy. In this study, 14431 cases of TC patients diagnosed with TC, the clinical and pathological characteristics were analyzed to provide information for clinical diagnosis and treatment.
We retrospectively analyzed the data of 14431 patients who underwent thyroidectomy between January 2011 and December 2015 from Tianjin Medical University Cancer Institute and Hospital. The exclusion criteria were as follows: 1) non-diagnostic or incomplete data, 2) recurrent cancer, and 3) metastatic thyroid cancer. The final subject population was composed of 3259 men and 11172 women (male to female ratio of 1: 3.43), with a mean age of 45.83 ± 10.83 years(range:6-85 years). Among the 14431 patients, papillary carcinoma accounted for 98.47%(14210 cases), follicular carcinoma accounted for 0.25%(36 cases), medullary carcinoma accounted for 0.73%(106 cases), poorly differentiated carcinoma accounted for 0.14%(21 cases), squamous cell carcinoma accounted for 0.11%(16 cases), malignant lymphoma accounted for 0.17%(25 cases), others accounted for 0.12%(17 cases).
Name of body giving ethical approval:Medical Ethics Committee of Airport Hospital, Tianjin Cancer Hospital; Approval number: LWK-2022-0003.
The clinical and pathological characteristics were compared annually. For data analysis, we used SPSS20.0 for Microsoft Windows Software. Chi-square test or Chi-square trend test was used for comparison of count data, and (x±s) was used for measurement data. T-test or non-parametric test was used for comparison between groups. All statistical results were considered statistically significant with p < 0.05.
The pathological features of the patients are summarized in Table 1. 14431 patients fulfilled the inclusion criteria, including 14210 (98.47%) papillary carcinoma cases, 36 (0.25%) follicular carcinoma cases, 106 (0.73%) medullary carcinoma cases, 21 (0.14%) undifferentiated carcinoma cases, 16 (0.11%) squamous carcinoma cases, 25 (0.17%) malignant lymphomas cases, and 17 (0.12%) other cases. From 2011 to 2015, the number of surgical cases of TC increased annually (2 = 37.183, P < 0.000), the incidence and constituent ratio of papillary carcinoma showed an increased trend (2 = 41.239, P < 0.000). In contrast, the incidence of medullary cancer declined (2 = 11.667, P = 0.001) and that of follicular cancer was relatively stable (P = 0.075).
Table 1
Histological case types and proportion of thyroid cancer patients in total thyroid cancer from 2011 to 2015.
| YEAR | ||||||
|---|---|---|---|---|---|---|
| PATHOLOGICAL TYPES | 2011 | 2012 | 2013 | 2014 | 2015 | TOTAL |
| Papillary carcinoma(%) | 1268(97.09) | 1824(97.70) | 3171(98.42) | 3288(98.59) | 4659(99.11) | 14210(98.47) |
| Follicular carcinoma(%) | 3(0.23) | 10(0.54) | 7(0.22) | 9(0.27) | 7(0.15) | 36(0.25) |
| Medullary carcinoma(%) | 18(1.38) | 18(0.96) | 23(0.71) | 25(0.75) | 22(0.47) | 106(0.73) |
| Undifferentiated carcinoma(%) | 4(0.31) | 0(0) | 7(0.22) | 8(0.24) | 2(0.04) | 21(0.15) |
| Squamous cell carcinoma (%) | 4(0.31) | 3(0.16) | 4(0.12) | 1(0.03) | 4(0.09) | 16(0.11) |
| Malignant lymphoma (%) | 7(0.54) | 7(0.37) | 3(0.09) | 4(0.12) | 5(0.11) | 25(0.17) |
| Other (%) | 6(0.46) | 5(0.27) | 7(0.22) | 0(0) | 2(0.43) | 17(0.12) |
| Total | 1306 | 1867 | 3222 | 3335 | 4701 | 14431 |
The distributions of age and sex are shown in Table 2. The mean age was 45.83 ± 10.83 years (range: 6-85 years), and the sex ratio (Male:Female) was 1:3.43. Patients were divided into seven groups according to age, among which the 30–59 year-old group had the highest incidence of aging, accounting for 82.15%. There were also significant differences in the sex ratio among different groups(non-parametric test, P < 0.001).
Table 2
Incidence and composition ratio of thyroid cancer in different genders in different age groups.
| AGE (YEARS) | MALE | FEMAL | TOTAL | SEX RATIO | |||
|---|---|---|---|---|---|---|---|
| CASES | COMPOSITION RATIO | CASES | COMPOSITION RATIO | CASES | COMPOSITION RATIO | ||
| <20 | 28 | 0.86 | 36 | 0.32 | 64 | 0.44 | 1:1.28 |
| 20–29 | 266 | 8.16 | 743 | 6.65 | 1009 | 6.99 | 1:2.79 |
| 30–39 | 680 | 20.87 | 2181 | 19.52 | 2861 | 19.82 | 1:3.21 |
| 40–49 | 1122 | 34.43 | 3981 | 35.63 | 5103 | 35.36 | 1:3.55 |
| 50–59 | 824 | 25.28 | 3082 | 27.58 | 3906 | 27.07 | 1:3.74 |
| 60–69 | 285 | 8.75 | 1001 | 8.96 | 1286 | 8.91 | 1:3.51 |
| ≥70 | 54 | 1.66 | 148 | 1.32 | 202 | 1.40 | 1:2.74 |
| Total | 3259 | 100 | 11172 | 100 | 14431 | 100 | 1:3.43 |
Among the 14210 patients with papillary thyoid carcinoma, 12792 patients had definite lymph node metastasis, among which 5514 patients had pathological definite lymph node metastasis, accounting for 38.8% of papillary thyoid carcinoma. The lymph node metastasis rate of patients under 20 years old was the highest, and the lymph node metastasis rate of papillary thyroid carcinoma decreased with age (P < 0.001). In addition, we found that age, gender, tumor size, lesion distribution, concurrent Hashimoto’s thyroiditis, and nodular goiter were the influencing factors of lymph node metastasis. Multivariate logistic regression revealed that male sex, tumor size(>1 cm), and bilateral lobe of thyoid were independent risk factors for lymph node metastasis of papillary thyoid carcinoma (P < 0.001), while age was a protective factor for lymph node metastasis of papillary thyoid carcinoma. The older the age, the lower the lymph node metastasis rate (P < 0.001) (Table 3).
Table 3
The lymph node metastasis of papillary thyroid carcinoma in different groups.
| GROUP | THE LYMPH NODE METASTASIS | |||
|---|---|---|---|---|
| CASE | COMPOSITION RATIO% | χ2 | P | |
| age | ||||
| ≦45 | 3040 | 44.18 | 126.103 | 0.000 |
| >45 | 2474 | 33.76 | ||
| gender | ||||
| male | 1502 | 52.78 | 139.587 | 0.000 |
| female | 4012 | 40.34 | ||
| Tumor size | ||||
| ≦1 | 2247 | 33.62 | 513.777 | 0.000 |
| >1 | 3267 | 53.49 | ||
| Cancer distribution | ||||
| Unilateral or combined isthmus | 4210 | 41.14 | 70.692 | 0.000 |
| On both sides | 1304 | 50.94 | ||
| concurrent with Hashimoto’s thyroiditis | ||||
| Yes | 292 | 37.34 | 11.287 | 0.001 |
| no | 5222 | 43.48 | ||
| concurrent with nodular goiter | ||||
| Yes | 1176 | 40.55 | 9.969 | 0.002 |
| no | 4338 | 43.85 | ||
Among the 14210 patients with papillary thyroid carcinoma, 4736 patients in the multi-lesion group and 9474 patients in the single-lesion group (Table 4). It was found to have a higher probability of lymph node metastasis in the multi-lesion group (2 = 416.819, P < 0.001) by comparing the pathological characteristics of the two groups (Table 5). There were more cases of single lesion combination with benign lesions in papillary thyroid carcinoma (2 = 416.819, P < 0.001), and the difference was statistically significant (P < 0.001) (Table 6).
Table 4
Papillary carcinoma with benign disease at different time periods.
| BENIGN DISEASE | YEARS | TOTAL | ||||
|---|---|---|---|---|---|---|
| 2011 | 2012 | 2013 | 2014 | 2015 | ||
| Hashimoto thyroiditis | 65 | 54 | 185 | 208 | 309 | 821 |
| Nodular goiter | 420 | 509 | 813 | 789 | 763 | 3294 |
| Thyroid adenoma | 38 | 107 | 154 | 118 | 315 | 732 |
| Lymphocytic thyroiditis | 10 | 30 | 13 | 8 | 9 | 70 |
| Subacute thyroiditis | 1 | 3 | 5 | 3 | 6 | 18 |
| Benigh lesions(>1) | 20 | 22 | 17 | 20 | 29 | 108 |
| Other thyroid nodules | 1 | 2 | 0 | 1 | 3 | 7 |
| Total | 555 | 727 | 1187 | 1147 | 1434 | 5050 |
Table 5
Comparison of papillary thyroid carcinoma with multiple lesions and with single lesion.
| FACTOR | SINGLE LESION GROUP N = 9474 | MULTIFOCAL GROUP N = 4736 | χ2 | P |
|---|---|---|---|---|
| gender | ||||
| Male | 2127 | 1037 | 0.552 | 0.457 |
| Female | 7347 | 3698 | ||
| age | ||||
| ≦45 | 4616 | 2265 | 1.019 | 0.313 |
| >45 | 4858 | 2471 | ||
| With benign lesions | ||||
| Yes | 3916 (40.18%) | 1134 (23.94%) | 416.819 | 0.000 |
| No | 5558 | 3602 | ||
| Cervical lymph node metastasis | ||||
| Yes | 3382 (39.91%) | 2132 (49.42%) | 105.859 | 0.000 |
| No | 5096 | 2182 | ||
Table 6
Comparison of unilateral and bilateral multifocal thyroid papillary carcinoma.
| FACTOR | BILATERAL MULTIFOCAL GROUP N = 2812 | UNILATERAL LOBE N = 1924 | χ2 | P |
|---|---|---|---|---|
| gender | ||||
| Male | 584 (20.77%) | 454 (23.60%) | 5.672 | 0.017 |
| Female | 2228 | 1470 | ||
| age | ||||
| ≦45 | 1384 (49.22%) | 1046 (54.37%) | 12.120 | 0.000 |
| >45 | 1428 | 878 | ||
| With benign lesions | ||||
| Yes | 311 (11.06%) | 823 (42.78%) | 630.993 | 0.000 |
| No | 2501 | 1101 | ||
| Cervical lymph node metastasis | ||||
| Yes | 1305 (50.94%) | 827 (47.20%) | 5.802 | 0.016 |
| No | 1257 | 925 | ||
| Simple small | ||||
| Yes | 1271 (45.20%) | 1153 (59.93%) | 99.175 | 0.000 |
| No | 1541 | 771 | ||
In the multifocal cases of papillary thyroid carcinoma, the bilateral multifocal group was compared with the unilateral and/or isthmus multifocal group (Table 6). In the multifocal cases of papillary thyroid carcinoma, 2812 cases were bilateral and 1924 cases were unilateral and/or isthmus. The analysis and comparison showed that the unilateral and/or isthmus multi-lesion group had more males, younger age, more benign lesions, and higher incidence of unilateral microcarcinoma (P = 0.017, P < 0.001, P < 0.001, P < 0.001), and the differences were statistically significant. There were more patients with cervical lymph node metastasis in bilateral multi-lesion group (2 = 5.802, P = 0.016).
Thyroid cancer(TC) is the most common endocrine tumor among head and neck malignant tumors [8]. Studies have shown that since 2004, thyroid cancer patients in the United States have been increasing at an annual rate of 6.6% for females and 5.5% for males, becoming the fastest growing malignant tumor in the United States [9, 10]. In a study on the incidence of head and neck cancer inpatients in China from 1993 to 2011, it was found that thyroid cancer increased at an average annual rate of 25.3%, which was the tumor with the fastest increase in incidence. This study analyzed the clinicopathological data of 11431 patients with thyroid cancer who underwent surgical resection for the first time in Tianjin Medical University Cancer Institute and Hospital in the past 5 years. It showed that the number of patients undergoing surgical treatment showed an increasing trend year by year (P < 0.001), and papillary cancer showed an increasing trend similar to the overall trend (P < 0.001). The incidence of other pathological types was relatively stable or decreased. At the same time, we found that the incidence of follicular carcinoma and Tianjin Medical University Cancer Institute and Hospital were much lower than the data frequently cited in many literatures [11]. This may be due to the significant increase in the incidence of papillary thyroid cancer in the past 20 years, resulting in a decrease in the proportion of follicular cancer and medullary cancer in the overall thyroid cancer. In addition, we also found that the incidence of medullary carcinoma was higher than that of follicular carcinoma (P < 0.05), which was different from the results of most studies [12, 13], which may be related to RET proto-oncogene mutation caused by severe environmental pollution and ionizing radiation, or due to regional differences. The specific mechanism needs to be further studied.
Papillary thyroid cancer is the most common pathology of TC, and multicentricity is one of its clinical features [14, 15]. We found that 33.33% of patients were multifocal with bilateral lobe, which is nearly 1.5 times that of unilateral lobe involvement, which was similar to domestic and foreign reports [16, 17]. Multifocal patients were more likely to have cervical lymph node metastasis, especially those with bilateral lobes. Papillary thyroid cancer often develops along with benign thyroid diseases, especially nodular goiter and Hashimoto thyroiditis [18]. Hashimoto thyroiditis is a common autoimmune thyroid disease [19, 20]. Although the immediate relationship between papillary thyroid carcinoma and Hashimoto’s thyroiditis is unclear, many scholars have hypothesized that the occurrence of Hashimoto’s thyroiditis could stimulate hyperplasia of the thyroid follicular epithelium due to the loss of autoimmune mechanisms, which may lead to disorder and cancerous cell growth [21, 22, 23]. Here, we found that papillary carcinoma combined with Hashimoto’s thyroiditis increased annually, which may contribute to the increase in papillary thyroid cancer. However, this mechanism requires further investigation.
In our study, we found that papillary thyroid carcinoma in younger patients tended to have lymph node metastasis (P < 0.001). This may be related to hormone secretion and rapid metabolism [24]. In addition, male sex, tumor size (>1 cm), and tumor presence in the contralateral lobe were independent risk factors for lymph node metastasis. Therefore, more caution should be exercised in these patients during the evaluation of the lymph nodes.
Currently, the etiology of this increase in TC is unclear. Many scholars believe that the improvement of inspection technology, popularization of color Doppler ultrasound, application of high-resolution high-frequency probes, and improvement of health consciousness are improving the detection rate of asymptomatic and subclinical tumor [25, 26]. Some studies have shown that ionizing radiation is also a risk factor for an increase in thyroid cancer [27, 28]. Similarly, some studies have suggested that it may also be related to diet structure, lifestyle, environmental pollution, and autoimmunity [29]. However, these findings still lack mechanistic research, and the causes of the rising incidence remain controversial [30].
In conclusion, the findings of this retrospective analysis indicate that the number of thyroid carcinomas treated in our hospital has increased annually, with a prominent increase in PTC. The incidence in women was significantly higher than that in men and occurred mostly in patients aged 30–59 years. Thyroid malignancies often coexist with benign diseases. Male age, tumor size >1 cm, and bilateral tumors are risk factors for PTC lymph node metastasis. Our subsequent study will collect the sequencing data of the samples to further investigate the indicators affecting the prognosis of thyroid cancer. In our next study, it is worthwhile to further explore and study the clinical and pathological characteristics of thyroid cancer, so as to provide information for clinical diagnosis and treatment, and indicate the prognosis.
The patient provided informed consent for the publication of this case. Data are available on request from the authors.
The authors have no competing interests to declare.
The respective role of each author:
Xiaomeng Wang: Collect the data and write the initial draft, Na Pan, Jie Cao and Weijiao Du visualization/data presentation. Weihong Zhang: Data curation. Shui Cao:critical review, commentary or revision–including pre-or post publication stages.
First author: Xiaomeng Wang, MS, E-mail: wxmdream1@163.com.
Co-First author: Na Pan.
Provenance and peer review. Not commissioned, externally peer-reviewed.
Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet[J]. 2016 Dec 3; 388(10061): 2783–2795. DOI: https://doi.org/10.1016/S0140-6736(16)30172-6
Pringle DR, Vasko VV, Ya L, et al. Follicular thyroid cancers demonstrate dual activation of PKA and mTOR as modeled by thyroid-spicific deletion of Prkarla and Pten in mice[J]. J Clin Endocrinol Metab. 2014; 99(5): E804–E812. DOI: https://doi.org/10.1210/jc.2013-3101
Udayanga V, Jayarajah U,Colonne SD, et al. Quality of the patient-oriented information on thyroid cancer in the internet[J]. Health Policy and Technology. 2020; 9(3): 302–307.3. DOI: https://doi.org/10.1016/j.hlpt.2020.03.007
Wei Z, Yan M, Yirong F. Detection rate and its time trend analysis on thyroid cancer from 2009 to 2013 in Shaoxing, Zhejiang Province[J]. Chin J Endocrinol Metab. 2015; 30(1): 4–9.
Kitahara CM, Platz EA, Freeman LE, et al. Obesity and thyroid cancer risk among U.S. men and women:a pooled analysis of five prospective studies[J]. Cancer Epidemiol Biomarkers Prev. 2011; 20(3): 464–472. DOI: https://doi.org/10.1158/1055-9965.EPI-10-1220
Chang YW, Lee HY, Kim HS, et al. Extent of central lymph node dissection for papillary thyroid carcinoma in the isthmus[J]. Ann Surg Treat Res. 2018 May; 94(5): 229–234. DOI: https://doi.org/10.4174/astr.2018.94.5.229
Mathew G, Agha R, for the STROCSS Group. STROCSS 2021: Strengthening the Reporting of cohort, cross-sectional and case-control studies in Surgery. International Journal of Surgery. 2021; 96: 106165. DOI: https://doi.org/10.1016/j.ijsu.2021.106165
Siegel RL, Miller KD, Jemal A. Cancer statistics[J], 2020. CA Cancer J Clin. Epub 2019 Jan 8.
Yujie W. Thyroid cancer has become a problem that gravely impacts public health[J]. Chin J Endocrinol Metab. 2015; 31(1): 1–3.
Chiofalo MG, Signoriello S, Fulciniti F, et al. Predictivity of clinical, laboratory and imaging findings in diagnostic definition of palpable thyroid nodules. A multicenter prospective study[J]. Endocrine. 2018 Jul; 61(1): 43–50. DOI: https://doi.org/10.1007/s12020-018-1577-5
Biyun Q, Kexin C, Min H, et al. The Survey on Thyroid Carcinoma Incidence in Urban District of Tianjin[J]. Chin J Clin Oncol. 2005; 21(5): 432–434.
Yao Y, Yuan Z, Lei X. Analysis of the clinicopathological features and therapy of 667 cases of thyroid cancer[J]. Chin J Surg Onco. 2013; 2: 76–78.
Rong ge X, Xiao ling Z, Wei wei Z. Clinical pathological analysis of 1318 cases of thyroid carcinoma in Cangzhou area[J]. Modern Oncology. 2016; 24(11): 1722–1724.
Sipos JA, Mazzaferri EI. Thyroid cancer epidemiology and prognostic variables[J]. Clin Oncol(R Coll Rsdiol). 2010; 22(6): 395–404. DOI: https://doi.org/10.1016/j.clon.2010.05.004
Zhiddong S. The change of constituent ratio and clinical analysis of multifocal papillary thyroid carcinoma[D]. Dalian Medical University; 2012.
Shattuck TM, Westra WH, Ladenson PW, et al. Independent clonal origins of distinct tumor foci in multifocal papillary thuroid carcinoma. N Engl J Med. 2005; 352(23): 2406–2412. DOI: https://doi.org/10.1056/NEJMoa044190
Yi kai L, Jian ming S, Wen he Z, et al. Multifocal papillary thyroid carcinoma: clinical analysis of 168 cases. Chin J Surg. 2009: 47(6): 451–453.
Wang H, Cao Z, Shao Y, Xu J. Thytoid nodules: Retrospectively analysis 1238 cases and literature review. Modern Oncology. 2015; 23(07): 0921–0925.
Dong S, Xie Xj, Xia Q, et al. Indicators of multifocality in papillary thyroid carcinoma concurrent with Hashimoto’s thyroiditis. Am J Cancer Res[J]. 2019; 9(8): 1786–1795
Boi F, Pani F, Calò PG, et al. High prevalence of papillary thyroid carcinoma in nodular Hashimoto’s thyroiditis at the first diagnosis and during the follow-up. J Endocrinol Invest[J]. 2018 Apr; 41(4): 395–402). DOI: https://doi.org/10.1007/s40618-017-0757-0
Graceffa G, Patrone R, Vieni S, et al. Association between Hashimoto’s thyroiditis and papillary thyroid carcinoma: a retrospective analysis of 305 patients. BMC Endocr Disord[J]. 2019 May 29; 19(Suppl 1): 26. DOI: https://doi.org/10.1186/s12902-019-0351-x
Uhliarova B, Hajtman A. Hashimoto’s thyroiditis – an independent risk factor for papillary carcinoma. Braz J Otorhinolaryngol[J]. 2018 Nov–Dec; 84(6): 729–735. DOI: https://doi.org/10.1016/j.bjorl.2017.08.012
Osorio C, Ibarra S, Arrieta J, et al. Association between chronic lymphocytic thyroiditis and papillary thyroid carcinoma: A retrospective study in surgical specimens. Rev Esp Patol[J]. 2020 Jul–Sep; 53(3): 149–157. DOI: https://doi.org/10.1016/j.patol.2019.07.004
Ma F, Wang H, et al. The relationship between thyroid papillary carcinoma and serum thyroid stimulating hormone[J]. Chin J Oper Proc Gen Surg (Electronic Edition). 2015; 6: 59–60.
Dedhia PH, Rubio GA, Cohen MS, et al. Potential effects of molecular testing of indeteminalte thyroid nodule fine needle aspiration biopsy on thyroidectomy volume[J]. World J Surg, 2014; 38(3): 634–638. DOI: https://doi.org/10.1007/s00268-013-2430-x
Sippel RS, Caron NR, Clark OH. An Evidence-based approach to familial nonmedullary thytoid cancer:screening, clinical management, and follow-up. World J Srug. 2007; 31: 924–933. DOI: https://doi.org/10.1007/s00268-006-0847-1
Morris LG, Sikora AG, Tosteson TD, et al. The increasing incidence of thyroid cancer: the influence of access to care [J]. Thytoid. 2013; 23(7): 885–891. DOI: https://doi.org/10.1089/thy.2013.0045
Cramer JD, Fu P, Harth KC, et al. Analysis of the rising incidence of thytoid cancer using the Surveillance, Epidemiology and End Results national cancer data registry[J]. Surgery. 2010; 148(6): 1147–1152. DOI: https://doi.org/10.1016/j.surg.2010.10.016
Yu Qin L, Shu Quan Z, Wan Qing C, et al. Trend of incidence and mortality on thyroid cancer in China during 2003–2007[J]. Chin J Epidemiol. 2012; 33(10): 1044–1048.
Wang Y, Wang W. Increasing incidence of thytoid cancer in Shanghai, China, 1983–2007[J]. Asia Pac J Public Health. 2012; 27(2): NP223–NP229. DOI: https://doi.org/10.1177/1010539512436874