Skip to main content
Top
Published in: Tumor Biology 7/2016

01-07-2016 | Original Article

Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer

Authors: Ning Qu, Ling Zhang, Wei-li Wu, Qing-hai Ji, Zhong-wu Lu, Yong-xue Zhu, Dao-zhe Lin

Published in: Tumor Biology | Issue 7/2016

Login to get access

Abstract

Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070–7.933), distant metastasis (HR = 3.860, 95 % CI 1.507–9.884), and cancer death (HR = 7.252, 95 % 2.189–24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185–4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300–19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.
Literature
1.
2.
go back to reference Hung W, Sarlis NJ. Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid. 2002;12:683–702.CrossRefPubMed Hung W, Sarlis NJ. Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid. 2002;12:683–702.CrossRefPubMed
4.
go back to reference Eustatia-Rutten CF, Corssmit EP, Biermasz NR, Pereira AM, Romijn JA, Smit JW. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2006;91:313–9.CrossRefPubMed Eustatia-Rutten CF, Corssmit EP, Biermasz NR, Pereira AM, Romijn JA, Smit JW. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2006;91:313–9.CrossRefPubMed
5.
go back to reference Jovanovic L, Delahunt B, McIver B, Eberhardt NL, Bhattacharya A, Lea R, et al. Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma. Pathology. 2010;42:524–33.CrossRefPubMed Jovanovic L, Delahunt B, McIver B, Eberhardt NL, Bhattacharya A, Lea R, et al. Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma. Pathology. 2010;42:524–33.CrossRefPubMed
6.
go back to reference Zhang L, Wei WJ, Ji QH, Zhu YX, Wang ZY, Wang Y, et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. J Clin Endocrinol Metab. 2012;97:1250–7.CrossRefPubMed Zhang L, Wei WJ, Ji QH, Zhu YX, Wang ZY, Wang Y, et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. J Clin Endocrinol Metab. 2012;97:1250–7.CrossRefPubMed
7.
go back to reference Dinse GE, Lagakos SW. Nonparametric estimation of lifetime and disease onset distributions from incomplete observations. Biometrics. 1982;38:921–32.CrossRefPubMed Dinse GE, Lagakos SW. Nonparametric estimation of lifetime and disease onset distributions from incomplete observations. Biometrics. 1982;38:921–32.CrossRefPubMed
9.
go back to reference Koo BS, Lim HS, Lim YC, Yoon YH, Kim YM, Park YH, et al. Occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma. Ann Surg Oncol. 2010;17:1101–5.CrossRefPubMed Koo BS, Lim HS, Lim YC, Yoon YH, Kim YM, Park YH, et al. Occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma. Ann Surg Oncol. 2010;17:1101–5.CrossRefPubMed
10.
go back to reference Lee YS, Lim YS, Lee JC, Wang SG, Kim IJ, Lee BJ. Clinical implication of the number of central lymph node metastasis in papillary thyroid carcinoma: preliminary report. World J Surg. 2010;34:2558–63.CrossRefPubMed Lee YS, Lim YS, Lee JC, Wang SG, Kim IJ, Lee BJ. Clinical implication of the number of central lymph node metastasis in papillary thyroid carcinoma: preliminary report. World J Surg. 2010;34:2558–63.CrossRefPubMed
11.
go back to reference DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990;71:414–24.CrossRefPubMed DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990;71:414–24.CrossRefPubMed
12.
go back to reference Kim HJ, Sohn SY, Jang HW, Kim SW, Chung JH. Multifocality, but not bilaterality, is a predictor of disease recurrence/persistence of papillary thyroid carcinoma. World J Surg. 2013;37:376–84.CrossRefPubMed Kim HJ, Sohn SY, Jang HW, Kim SW, Chung JH. Multifocality, but not bilaterality, is a predictor of disease recurrence/persistence of papillary thyroid carcinoma. World J Surg. 2013;37:376–84.CrossRefPubMed
13.
go back to reference Pasieka JL, Thompson NW, McLeod MK, Burney RE, Macha M. The incidence of bilateral well-differentiated thyroid cancer found at completion thyroidectomy. World J Surg. 1992;16:711–6. discussion 716–717.CrossRefPubMed Pasieka JL, Thompson NW, McLeod MK, Burney RE, Macha M. The incidence of bilateral well-differentiated thyroid cancer found at completion thyroidectomy. World J Surg. 1992;16:711–6. discussion 716–717.CrossRefPubMed
14.
go back to reference Pacini F, Elisei R, Capezzone M, Miccoli P, Molinaro E, Basolo F, et al. Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients. Thyroid. 2001;11:877–81.CrossRefPubMed Pacini F, Elisei R, Capezzone M, Miccoli P, Molinaro E, Basolo F, et al. Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients. Thyroid. 2001;11:877–81.CrossRefPubMed
15.
go back to reference Park SY, Park YJ, Lee YJ, Lee HS, Choi SH, Choe G, et al. Analysis of differential braf(v600e) mutational status in multifocal papillary thyroid carcinoma: evidence of independent clonal origin in distinct tumor foci. Cancer. 2006;107:1831–8.CrossRefPubMed Park SY, Park YJ, Lee YJ, Lee HS, Choi SH, Choe G, et al. Analysis of differential braf(v600e) mutational status in multifocal papillary thyroid carcinoma: evidence of independent clonal origin in distinct tumor foci. Cancer. 2006;107:1831–8.CrossRefPubMed
16.
go back to reference Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric papillary thyroid carcinoma. Ann Surg Oncol. 2009;16:2609–16.CrossRefPubMed Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric papillary thyroid carcinoma. Ann Surg Oncol. 2009;16:2609–16.CrossRefPubMed
17.
go back to reference Passler C, Prager G, Scheuba C, Kaserer K, Zettinig G, Niederle B. Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodine substitution. Ann Surg. 2003;237:227–34.PubMedPubMedCentral Passler C, Prager G, Scheuba C, Kaserer K, Zettinig G, Niederle B. Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodine substitution. Ann Surg. 2003;237:227–34.PubMedPubMedCentral
18.
go back to reference Ito Y, Fukushima M, Tomoda C, Inoue H, Kihara M, Higashiyama T, et al. Prognosis of patients with papillary thyroid carcinoma having clinically apparent metastasis to the lateral compartment. Endocr J. 2009;56:759–66.CrossRefPubMed Ito Y, Fukushima M, Tomoda C, Inoue H, Kihara M, Higashiyama T, et al. Prognosis of patients with papillary thyroid carcinoma having clinically apparent metastasis to the lateral compartment. Endocr J. 2009;56:759–66.CrossRefPubMed
19.
go back to reference Ito Y, Miyauchi A, Jikuzono T, Higashiyama T, Takamura Y, Miya A, et al. Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping. World J Surg. 2007;31:838–48.CrossRefPubMed Ito Y, Miyauchi A, Jikuzono T, Higashiyama T, Takamura Y, Miya A, et al. Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping. World J Surg. 2007;31:838–48.CrossRefPubMed
20.
go back to reference Yamashita H, Noguchi S, Murakami N, Toda M, Uchino S, Watanabe S, et al. Extracapsular invasion of lymph node metastasis. A good indicator of disease recurrence and poor prognosis in patients with thyroid microcarcinoma. Cancer. 1999;86:842–9.CrossRefPubMed Yamashita H, Noguchi S, Murakami N, Toda M, Uchino S, Watanabe S, et al. Extracapsular invasion of lymph node metastasis. A good indicator of disease recurrence and poor prognosis in patients with thyroid microcarcinoma. Cancer. 1999;86:842–9.CrossRefPubMed
21.
go back to reference Hotomi M, Sugitani I, Toda K, Kawabata K, Fujimoto Y. A novel definition of extrathyroidal invasion for patients with papillary thyroid carcinoma for predicting prognosis. World J Surg. 2012;36:1231–40.CrossRefPubMed Hotomi M, Sugitani I, Toda K, Kawabata K, Fujimoto Y. A novel definition of extrathyroidal invasion for patients with papillary thyroid carcinoma for predicting prognosis. World J Surg. 2012;36:1231–40.CrossRefPubMed
22.
go back to reference Carcangiu ML. Diagnosis and prognostic factors in papillary carcinoma of the thyroid. Pathologica. 2003;95:271–3.PubMed Carcangiu ML. Diagnosis and prognostic factors in papillary carcinoma of the thyroid. Pathologica. 2003;95:271–3.PubMed
23.
go back to reference Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418–28.CrossRefPubMed Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418–28.CrossRefPubMed
25.
go back to reference Grigsby PW, Reddy RM, Moley JF, Hall BL. Contralateral papillary thyroid cancer at completion thyroidectomy has no impact on recurrence or survival after radioiodine treatment. Surgery. 2006;140:1043–7. discussion 1047–1049.CrossRefPubMed Grigsby PW, Reddy RM, Moley JF, Hall BL. Contralateral papillary thyroid cancer at completion thyroidectomy has no impact on recurrence or survival after radioiodine treatment. Surgery. 2006;140:1043–7. discussion 1047–1049.CrossRefPubMed
26.
go back to reference Zhao Q, Ming J, Liu C, Shi L, Xu X, Nie X, et al. Multifocality and total tumor diameter predict central neck lymph node metastases in papillary thyroid microcarcinoma. Ann Surg Oncol. 2013;20:746–52.CrossRefPubMed Zhao Q, Ming J, Liu C, Shi L, Xu X, Nie X, et al. Multifocality and total tumor diameter predict central neck lymph node metastases in papillary thyroid microcarcinoma. Ann Surg Oncol. 2013;20:746–52.CrossRefPubMed
27.
go back to reference Zhou YL, Gao EL, Zhang W, Yang H, Guo GL, Zhang XH, et al. Factors predictive of papillary thyroid micro-carcinoma with bilateral involvement and central lymph node metastasis: a retrospective study. World J Surg Oncol. 2012;10:67.CrossRefPubMedPubMedCentral Zhou YL, Gao EL, Zhang W, Yang H, Guo GL, Zhang XH, et al. Factors predictive of papillary thyroid micro-carcinoma with bilateral involvement and central lymph node metastasis: a retrospective study. World J Surg Oncol. 2012;10:67.CrossRefPubMedPubMedCentral
28.
go back to reference Kim HJ, Park HK, Byun DW, Suh K, Yoo MH, Min YK, Kim SW, Chung JH: Number of tumor foci as predictor of lateral lymph node metastasis in papillary thyroid carcinoma. Head Neck 2014. Kim HJ, Park HK, Byun DW, Suh K, Yoo MH, Min YK, Kim SW, Chung JH: Number of tumor foci as predictor of lateral lymph node metastasis in papillary thyroid carcinoma. Head Neck 2014.
29.
go back to reference Shepet K, Alhefdhi A, Lai N, Mazeh H, Sippel R, Chen H. Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol. 2013;20:1451–5.CrossRefPubMed Shepet K, Alhefdhi A, Lai N, Mazeh H, Sippel R, Chen H. Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol. 2013;20:1451–5.CrossRefPubMed
30.
go back to reference Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL. Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab. 1998;83:4116–22.PubMed Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL. Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab. 1998;83:4116–22.PubMed
31.
go back to reference Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, et al. Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab. 2004;89:5583–91.CrossRefPubMed Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, et al. Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab. 2004;89:5583–91.CrossRefPubMed
32.
go back to reference Lee SH, Lee SS, Jin SM, Kim JH, Rho YS. Predictive factors for central compartment lymph node metastasis in thyroid papillary microcarcinoma. Laryngoscope. 2008;118:659–62.CrossRefPubMed Lee SH, Lee SS, Jin SM, Kim JH, Rho YS. Predictive factors for central compartment lymph node metastasis in thyroid papillary microcarcinoma. Laryngoscope. 2008;118:659–62.CrossRefPubMed
33.
go back to reference Moo TA, Umunna B, Kato M, Butriago D, Kundel A, Lee JA, et al. Ipsilateral versus bilateral central neck lymph node dissection in papillary thyroid carcinoma. Ann Surg. 2009;250:403–8.PubMed Moo TA, Umunna B, Kato M, Butriago D, Kundel A, Lee JA, et al. Ipsilateral versus bilateral central neck lymph node dissection in papillary thyroid carcinoma. Ann Surg. 2009;250:403–8.PubMed
34.
go back to reference Koo BS, Choi EC, Yoon YH, Kim DH, Kim EH, Lim YC. Predictive factors for ipsilateral or contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma. Ann Surg. 2009;249:840–4.CrossRefPubMed Koo BS, Choi EC, Yoon YH, Kim DH, Kim EH, Lim YC. Predictive factors for ipsilateral or contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma. Ann Surg. 2009;249:840–4.CrossRefPubMed
Metadata
Title
Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer
Authors
Ning Qu
Ling Zhang
Wei-li Wu
Qing-hai Ji
Zhong-wu Lu
Yong-xue Zhu
Dao-zhe Lin
Publication date
01-07-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4533-5

Other articles of this Issue 7/2016

Tumor Biology 7/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine