|Year : 2017 | Volume
| Issue : 4 | Page : 715-719
Thyroid carcinoma in children and adolescents: Clinical characteristics and follow-up from two centers
Jing-Jing Pan1, Li Zhao2, Rui Cheng2, Yang Yang2, Yu-Hua Hu1
1 Department of Pediatrics and Neonatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210008, Jiangsu Province, China
2 Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu Province, China
|Date of Web Publication||13-Sep-2017|
Department of Neonatology, Children's Hospital of Nanjing Medical University, Guangzhou Road, No. 72, Jiangsu Province
Department of Neonatology, Children's Hospital of Nanjing Medical University, Guangzhou Road, No. 72, Jiangsu Province
Source of Support: None, Conflict of Interest: None
Aim of Study: The aim of this study was to analyze the clinical features and outcomes of thyroid carcinoma (TC) in children and adolescent population treated in our institution.
Materials and Methods: We gathered 43 TC patients 18 years of age or under initial diagnosed between 2009 and 2010 from two hospitals. Patient's clinical characteristics, laboratory tests, and outcomes were collected and analyzed.
Results: (1) The incidence of TC is higher in women (2.4 vs. 1.6). Papillary carcinoma accounted for the major type (67.4%). There was significant difference in tumor number, extra thyroidal invasion, and distant metastasis when compared with the children group (P < 0.05). There were higher proportions of patients with lymph node metastasis (LNM) and radioiodine therapy in adolescent patients. (2) Thyroid peroxidase antibody, thyroglobulin, thyroglobulin antibody, and urine iodine had higher levels as compared to the normal reference range. Moreover, FT3 and urine iodine showed statistical significances in adolescent group (P < 0.05). (3) Papillary carcinoma and medullary TC are more likely to have LNM extrathyroidal invasion. (4) No significant differences were seen in recurrence rate or survival rate. Pulmonary metastasis was the most common way of cancer metastasis.
Conclusion: The initial workup is crucial in determining benign from malignant lesions. Surgery is the most effective therapy even if it is associated with more complications in children. There is an extremely good prognosis for pediatric TC even distant metastasis happens.
Keywords: Adolescents, characteristics, children, thyroid carcinoma
|How to cite this article:|
Pan JJ, Zhao L, Cheng R, Yang Y, Hu YH. Thyroid carcinoma in children and adolescents: Clinical characteristics and follow-up from two centers. J Can Res Ther 2017;13:715-9
|How to cite this URL:|
Pan JJ, Zhao L, Cheng R, Yang Y, Hu YH. Thyroid carcinoma in children and adolescents: Clinical characteristics and follow-up from two centers. J Can Res Ther [serial online] 2017 [cited 2018 Nov 16];13:715-9. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/715/214466
Zhao Li and Pan Jing-Jing contributed equally to this work.
| > Introduction|| |
Thyroid nodules in children are relatively rare in daily clinical work. Compared to a malignancy risk of 5%–15% in adults, the incidence of carcinomas in thyroid nodules in children is 18%–26.7%.,,,, Among them, thyroid carcinoma (TC) is the most common tumor of the endocrine system. It has been reported that the incidence is about 0.5%–3% in malignant tumors in children and adolescents, and increased with age. For example, between 15 and 19 years old, a higher incidence (17.6 per 1 million) is reported for children/young adults. In addition, the risk of recurrence can be as high as 39%. Therefore, thyroid nodules in children and adolescents warrant a higher level of suspicion and more aggressive evaluation than in adults.
Despite the frequency of metastatic disease at presentation, the prognosis of TC is generally very good. Ten-year survival rates of >98% are reported. However, Differ from adult patients, the therapeutic approach including surgical treatment is still full of controversies and study results tend to differ. Several recommendations proposed a less aggressive therapeutic approach (less than total thyroidectomy [TT] and no neck dissection), but some researchers suggested more aggressive therapy. To date, no randomized trials or even prospective studies have ever been performed in the pediatric population, and management has been extrapolated from adult practice and evidence, supported by data from retrospective case series in children.
In view of this situation, in this article, we try to analyze and evaluate the detailed treatments of Chinese children and adolescents patients. Moreover, we hope it could offer useful clinical characteristics and information to further surgical work.
| > Materials and Methods|| |
This research was approved by the Ethics Committee of University. The subjects of this study were the 43 TC patients 18 years of age or under who underwent initial surgery in both hospitals between 2009 and 2010. They included 28 females and 15 males. There were 17 (40%) patients 14 years of age or under, and 26 (60%) patients over 14 years of age, and the female–male ratios of the two age groups were 2.4 and 1.6, respectively. All patients were followed up in the outpatient clinic for 5 years.
Their disease was evaluated and diagnosed preoperatively by palpation, chest X-ray, neck ultrasonography, and fine-needle aspiration biopsy. We have routinely used electroconvulsive therapy (ECT) or positron emission tomography (PET) scan for evaluating whether there are systemic metastases. We also use chest X-ray or computed tomography scan to diagnose lung metastasis. Thyroid function, routine blood test, procalcitonin level, thyroid hormone level, and urinary iodine level were routinely detected before surgery.
Extent of surgery
TT is indicated for patients with lymph node metastasis (LNM) or extrathyroidal invasion based on preoperative examinations and clinical findings. Clinical N0 patients undergo prophylactic unilateral central neck dissection alone and therapeutic modified neck dissection is indicated for only clinical N1 patients (LNM stage). TT was performed in 27 patients (62.8%), and neck dissection was performed in 36 patients (83.7%). Tissue samples from all patients were kept for further pathological and immunohistochemical examination.
A postoperative follow-up examination was usually performed at 1, 6, 12 months, and every 6 months thereafter. The serum thyroid hormone level was routinely measured at every hospital visit, and a PET or ECT examination was performed from time to time (interval of 6 months to 1 year). If these examinations resulted in detection of metastasis, completion thyroidectomy was performed and followed by 131 I scintigraphy. All M1 patients underwent TT as the initial surgical procedure and subsequent radioiodine (RI) therapy. Postoperative thyroid-stimulating hormone suppression therapy was performed selectively in patients with distant metastasis, extrathyroidal invasion, and clinical N1.
The data were analyzed with SPSS 13.0 by IBM USA. Quantitative data which obey the normal distribution were analyzed using t- test or one-way ANOVA. Quantitative data which obey the skewed distribution were analyzed using Wilcoxon rank sum test. Qualitative data were analyzed using Chi-square test or Fisher exact test. P = 0.05 was considered statistically significant. This study was performed in accordance with the Declaration of Helsinki.
| > Results|| |
The incidence of TC is higher in women (ratios 2.4 vs.1.6). Papillary carcinoma accounted for the major type of TC (67.4%). There was a significant difference in tumor number, extra thyroidal invasion and distant metastasis when compared with the children group (P < 0.05). Although there weren't statistical significances, more patients with diffuse sclerosing variant (DSV) (11.8%) and Hashimoto's thyroiditis (23.5%) compared to the adolescent group. On the other hand, there were higher proportions of patients with LNM (76.9%) and RI therapy (42.3%) in adolescent patients group. Among them, 15.4% patients (4/26) had hypothyroidism of TC. Because of the uncertain curative effect and side effect of radiotherapy efficacy, higher proportion of children patients gave up RI therapy compared with adolescent patients (14/17 vs. 15/26) shown in [Table 1].
|Table 1: The patient characteristics between children and adolescent patients|
Click here to view
The level of free thyroxine, parathyroid hormone and procalcitonin were all in a normal range and showed no difference between two groups. In contrast, thyroid peroxidase antibody, thyroglobulin (TG), thyroglobulin antibody (TGAB) and urine iodine had higher levels compared to the normal reference range. Moreover, FT3 and urine iodine showed statistical significances in adolescent group (P < 0.05) shown in [Table 2].
Characteristics between different pathological types
Anaplastic TC were not found in the data we collected, and hence we exclude this type for further statistics. In spite of cancer types, female patients always have a higher incidence of TC. Moreover, papillary carcinoma has a higher proportion of in adolescent compared with follicular carcinoma and medullary TC (MTC). There are no significant difference in tumor size, tumor number, DSV, distant metastasis, and Hashimoto's thyroiditis. It could be seen papillary carcinoma and MTC are more likely to have LNM extra thyroidal invasion. Three types of TC did not show differences in RI therapy and hypothyroidism shown in [Table 3].
After 5-year follow-up, 3 children and 4 teenagers died. Among them, 4 patients died from hypoparathyroidism, 2 died from secondary systemic infection, and 1 died from pulmonary metastases 2 years after the operation. No significant differences were seen in recurrence rate or survival rate. However, the pulmonary metastasis was still the most common way of cancer metastasis shown in [Table 4].
| > Discussion|| |
May be due to a variety of factors, e.g., environmental radiation exposure, genetic predisposition or improved diagnostics, pediatric thyroid cancer has an increasing incidence in these years. By contrast, there have not been many reports or descriptions related to this cancer so far in China. In view of this situation, we performed this retrospective analysis combined with Chinese own characteristics.
The differentiated TC includes papillary TC (PTC), follicular TC (FTC) and MTC. These tumors vary significantly in the biological behavior and prognosis., Where distant metastases do occur in TC, these are usually to the lungs. In our study, distant metastasis was diagnosed in 5 cases (11.6%) of the patients. Moreover, lung metastasis in TC has taken up 87.5% (7/8) already. Distant metastasis rate was 6.9% in PTC, 12.5% in FTC, and 33.3% in MTC. Although in the presence of metastatic disease, the prognosis for these patients in terms of survival is still generally good. However, invasive FTC and MTC have a comparatively poorer prognosis. In our research, the total survival rate of TC was 82.4% in children and 84.6% in adolescents at 5 years on the whole.
Surgical resection seems recommended for pediatric TC patients, but there's still controversy regarding the extent of resection. TT is common favored as the ideal therapy with neck dissection to remove regional lymph nodes. A radical approach to TC with TT as the primary surgery has been advocated. While the rationale behind this method was to minimize the high recurrence rate of this tumor, extensive ablative surgery carries with it the inherent risks of permanent complications, such as hypothyroidism, which are particularly important in children as their growth and development may be affected. In our study, there are also hypothyroidism patients (5/43), but it should be noted that radioactive iodine therapy also could make this happen. In fact, the lack of high-quality randomized controlled trials makes a definitive assessment of one treatment (TT) over another is difficult. Thus, the role of the initial surgery in contributing to clinical outcomes is uncertain, and postsurgical management of these patients may provide a significant contribution to the low mortality rate.
Compared with PTC and FTC, even total resection and lymph node dissection was performed, MTC has a higher infiltration rate (100.0%) and metastasis rate (33.3%). However, pediatric TC still has a high survival rate in spite of the extent of initial surgery. RI therapy is used in the majority of patients with metastasis. The purpose for RI therapy is the ablation of any normal thyroid tissue left following thyroidectomy aimed at facilitating follow-up of the disease with thyroglobulin measurements. Our study also found TG and TGAB significantly higher than normal levels [Table 2], which suggested an effective evaluation indicator of TC. In addition, it is worth mentioning that PET and ECT may be also potential alternatives for cancer disease. As the majority of childhood presentation is locally advanced. Moreover, recurrences are frequent, routine RI ablation has been recommended as an adjuvant therapy following thyroidectomy. However, the routine use in children and adolescents has to be considered against potential adverse side effects, such as the very low risk of extra-thyroidal malignancies, pulmonary fibrosis and gonadal damage. Hence, in daily clinical work, some parents have their concerns. Our research showed that there is no difference between children group and the adolescent group about not using RI therapy [Table 4]. Some retrospective studies have shown the efficacy of RI in children in reducing recurrence rates, but there have been no randomized controlled trials or dose-response studies for the use of RI in pediatric TC.
| > Conclusion|| |
Although most pediatric thyroid nodules are benign, the initial workup is crucial in determining benign from malignant lesions. Surgery is the most effective therapy even if it is associated with more complications in children. There is an extremely good prognosis for PTC even distant metastasis happens. Therapeutic procedures for pediatrics are currently debated with controversy, so further research including multicenter studies is necessary.
We thank for the understanding of patients and their parents.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Hung W. Solitary thyroid nodules in 93 children and adolescents. A 35-years experience. Horm Res 1999;52:15-8.
Raab SS, Silverman JF, Elsheikh TM, Thomas PA, Wakely PE. Pediatric thyroid nodules: Disease demographics and clinical management as determined by fine needle aspiration biopsy. Pediatrics 1995;95:46-9.
Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric papillary thyroid carcinoma. Ann Surg Oncol 2009;16:2609-16.
Niedziela M. Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer 2006;13:427-53.
Gupta A, Ly S, Castroneves LA, Frates MC, Benson CB, Feldman HA, et al.
A standardized assessment of thyroid nodules in children confirms higher cancer prevalence than in adults. J Clin Endocrinol Metab 2013;98:3238-45.
Yu GP, Li JC, Branovan D, McCormick S, Schantz SP. Thyroid cancer incidence and survival in the national cancer institute surveillance, epidemiology, and end results race/ethnicity groups. Thyroid 2010;20:465-73.
Welch Dinauer CA, Tuttle RM, Robie DK, McClellan DR, Svec RL, Adair C, et al.
Clinical features associated with metastasis and recurrence of differentiated thyroid cancer in children, adolescents and young adults. Clin Endocrinol (Oxf) 1998;49:619-28.
Rivkees SA, Mazzaferri EL, Verburg FA, Reiners C, Luster M, Breuer CK, et al.
The treatment of differentiated thyroid cancer in children: Emphasis on surgical approach and radioactive iodine therapy. Endocr Rev 2011;32:798-826.
Stiller C. National Registry of Childhood Tumours Progress Report 2012, National Cancer Intelligence Network (NCIN); 2012.
Rosai J, DeLellis CM. Atlas of Tumour Pathology. 4th
ed.. Washington, DC: AFIP; 1992.
Padhi S, Sahoo JP, Kamalanathan S, Sarangi R. Papillary thyroid carcinoma and subclinical thyrotoxicosis: Brief insight into the thyroid regulators other than thyroid stimulating hormone. J Cancer Res Ther 2015;11:1037.
Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, et al.
Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid 2015;25:716-59.
Welch Dinauer CA, Tuttle RM, Robie DK, McClellan DR, Francis GL. Extensive surgery improves recurrence-free survival for children and young patients with class I papillary thyroid carcinoma. J Pediatr Surg 1999;34:1799-804.
Jin X, Masterson L, Patel A, Hook L, Nicholson J, Jefferies S, et al.
Conservative or radical surgery for pediatric papillary thyroid carcinoma: A systematic review of the literature. Int J Pediatr Otorhinolaryngol 2015;79:1620-4.
Hay ID, Gonzalez-Losada T, Reinalda MS, Honetschlager JA, Richards ML, Thompson GB. Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008. World J Surg 2010;34:1192-202.
Sugino K, Nagahama M, Kitagawa W, Shibuya H, Ohkuwa K, Uruno T, et al.
Papillary thyroid carcinoma in children and adolescents: Long-term follow-up and clinical characteristics. World J Surg 2015;39:2259-65.
[Table 1], [Table 2], [Table 3], [Table 4]