Skip to main content
Top
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Skip metastasis in papillary thyroid carcinoma is difficult to predict in clinical practice

Authors: Xilin Nie, Zhou Tan, Minghua Ge

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

Cervical lymph node metastases are very common in papillary thyroid cancer (PTC), and typically spread in a predictable stepwise fashion in clinical practice. However, lateral lymph node metastasis (LLNM) without central lymph node metastasis (CLNM) as skip metastasis is not rare in PTC. The aim of this study was to investigate the incidence, risk factors and pattern of skip metastasis in PTC.

Methods

A total of 271 patients with PTC and suspicious LLN diagnosed by pre-operation examinations who underwent total thyroidectomy and central lymph node dissection plus lateral lymph node dissection between January 2008 and December 2011 were enrolled in this study. Clinicopathological features were collected, and the pattern of cervical lymph node metastasis and skip metastasis were analyzed.

Results

The LLNM rate was 74.9% (203/271, diagnosed by postoperative pathology examination) and significantly associated with extrathyroid extension (ETE), primary tumor located at the upper pole, and CLNM (p < 0.05). The skip metastasis rate was 14.8% (30/203) and was more frequently found in microcarcinoma patients, especially when the primary tumor size was ≤0.5 cm (p = 0.001 OR = 12.9). However, skip metastasis was unrelated to the remaining factors examined.

Conclusion

Small cancers with a pre-operation diagnosis of LLNM are more likely to have skip metastases, especially when the primary tumor size is less than 0.5 cm in diameter; however, this type of metastasis appears to develop in a random fashion. Thus, additional research is needed to identify potential predictive factors, such as a primary tumor located at the upper pole.
Literature
1.
go back to reference Grebe SK, Hay ID. Thyroid cancer nodal metastases: biologic significance and therapeutic considerations. Surg Oncol Clin N Am. 1996;1:43–63. Grebe SK, Hay ID. Thyroid cancer nodal metastases: biologic significance and therapeutic considerations. Surg Oncol Clin N Am. 1996;1:43–63.
2.
go back to reference Kupferman ME, Patterson M, Mandel SJ, LiVolsi V, Weber RS. Patterns of lateral neck metastasis in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2004;7:857–60.CrossRef Kupferman ME, Patterson M, Mandel SJ, LiVolsi V, Weber RS. Patterns of lateral neck metastasis in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2004;7:857–60.CrossRef
3.
go back to reference Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006;3:524–31.CrossRef Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006;3:524–31.CrossRef
4.
go back to reference McConahey WM, Hay ID, Woolner LB, van Heerden JA, Taylor WF. Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc. 1986;12:978–96.CrossRef McConahey WM, Hay ID, Woolner LB, van Heerden JA, Taylor WF. Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc. 1986;12:978–96.CrossRef
5.
go back to reference Hughes CJ, Shaha AR, Shah JP, Loree TR. Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis. Head Neck. 1996;2:127–32.CrossRef Hughes CJ, Shaha AR, Shah JP, Loree TR. Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis. Head Neck. 1996;2:127–32.CrossRef
6.
go back to reference Roh JL, Park JY, Rha KS, Park CII. Central neck dissection necessary for the treatment of lateral cervical nodal recurrence of papillary thyroid carcinoma? Head Neck. 2007;10:901–6.CrossRef Roh JL, Park JY, Rha KS, Park CII. Central neck dissection necessary for the treatment of lateral cervical nodal recurrence of papillary thyroid carcinoma? Head Neck. 2007;10:901–6.CrossRef
7.
go back to reference Machens A, Hinze R, Thomusch O, Dralle H. Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg. 2002;1:22–8.CrossRef Machens A, Hinze R, Thomusch O, Dralle H. Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg. 2002;1:22–8.CrossRef
8.
go back to reference Machens A, Holzhausen HJ, Dralle H. Skip metastases in thyroid cancer leaping the central lymph node compartment. Arch Surg. 2004;1:43–5.CrossRef Machens A, Holzhausen HJ, Dralle H. Skip metastases in thyroid cancer leaping the central lymph node compartment. Arch Surg. 2004;1:43–5.CrossRef
9.
go back to reference Grodski S, Cornford L, Sywak M, Sidhu S, Delbridge L. Routine level VI lymph node dissection for papillary thyroid cancer: surgical technique. ANZ J Surg. 2007;4:203–8.CrossRef Grodski S, Cornford L, Sywak M, Sidhu S, Delbridge L. Routine level VI lymph node dissection for papillary thyroid cancer: surgical technique. ANZ J Surg. 2007;4:203–8.CrossRef
10.
go back to reference Goropoulos A, Karamoshos K, Christodoulou A, Ntitsias T, Paulou K, Samaras A, et al. Value of the cervical compartments in the surgical treatment of papillary thyroid carcinoma. World J Surg. 2004;12:1275–81.CrossRef Goropoulos A, Karamoshos K, Christodoulou A, Ntitsias T, Paulou K, Samaras A, et al. Value of the cervical compartments in the surgical treatment of papillary thyroid carcinoma. World J Surg. 2004;12:1275–81.CrossRef
11.
go back to reference Ducci M, Appetecchia M, Marzetti M. Neck dissection for surgical treatment of lymphnode metastasis in papillary thyroid carcinoma. J Exp Clin Cancer Res. 1997;3:333–5. Ducci M, Appetecchia M, Marzetti M. Neck dissection for surgical treatment of lymphnode metastasis in papillary thyroid carcinoma. J Exp Clin Cancer Res. 1997;3:333–5.
12.
go back to reference Coatesworth AP, MacLennan K. Cervical metastasis in papillary carcinoma of the thyroid: a histopathological study. Int J Clin Pract. 2002;4:241–2. Coatesworth AP, MacLennan K. Cervical metastasis in papillary carcinoma of the thyroid: a histopathological study. Int J Clin Pract. 2002;4:241–2.
13.
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;4:1101–5.CrossRef 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;4:1101–5.CrossRef
14.
go back to reference Lee BJ, Wang SG, Lee JC, Son SM, Kim IJ, Kim YK. Level IIb lymph node metastasis in neck dissection for papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2007;10:1028–30.CrossRef Lee BJ, Wang SG, Lee JC, Son SM, Kim IJ, Kim YK. Level IIb lymph node metastasis in neck dissection for papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2007;10:1028–30.CrossRef
15.
go back to reference Roh JL, Kim JM, Park CI. Lateral cervical lymph node metastases from papillary thyroid carcinoma: pattern of nodal metastases and optimal strategy for neck dissection. Ann Surg Oncol. 2008;4:1177–82.CrossRef Roh JL, Kim JM, Park CI. Lateral cervical lymph node metastases from papillary thyroid carcinoma: pattern of nodal metastases and optimal strategy for neck dissection. Ann Surg Oncol. 2008;4:1177–82.CrossRef
16.
go back to reference Wada N, Masudo K, Nakayama H, Suganuma N, Matsuzu K, Hirakawa S, et al. Clinical outcomes in older or younger patients with papillary thyroid carcinoma: impact of lymphadenopathy and patient age. Eur J Surg Oncol. 2008;2:202–7.CrossRef Wada N, Masudo K, Nakayama H, Suganuma N, Matsuzu K, Hirakawa S, et al. Clinical outcomes in older or younger patients with papillary thyroid carcinoma: impact of lymphadenopathy and patient age. Eur J Surg Oncol. 2008;2:202–7.CrossRef
17.
go back to reference Chung YS, Kim JY, Bae JS, Song BJ, Kim JS, Jeon HM, et al. Lateral lymph node metastasis in papillary thyroid carcinoma: results of therapeutic lymph node dissection. Thyroid. 2009;3:241–6.CrossRef Chung YS, Kim JY, Bae JS, Song BJ, Kim JS, Jeon HM, et al. Lateral lymph node metastasis in papillary thyroid carcinoma: results of therapeutic lymph node dissection. Thyroid. 2009;3:241–6.CrossRef
18.
go back to reference Xiao GZ, Gao L. Central lymph node metastasis: is it a reliable indicator of lateral node involvement in papillary thyroid carcinoma? World J Surg. 2010;2:237–41.CrossRef Xiao GZ, Gao L. Central lymph node metastasis: is it a reliable indicator of lateral node involvement in papillary thyroid carcinoma? World J Surg. 2010;2:237–41.CrossRef
19.
go back to reference Kim YS. Patterns and predictive factors of lateral lymph node metastasis in papillary thyroid microcarcinoma. Otolaryngol Head Neck Surg. 2012;1:15–9.CrossRef Kim YS. Patterns and predictive factors of lateral lymph node metastasis in papillary thyroid microcarcinoma. Otolaryngol Head Neck Surg. 2012;1:15–9.CrossRef
20.
go back to reference Kliseska E, Makovac I. Skip metastases in papillary thyroid cancer. Coll Antropol. 2012:59–62. Kliseska E, Makovac I. Skip metastases in papillary thyroid cancer. Coll Antropol. 2012:59–62.
21.
go back to reference Lim YC, Koo BS. Predictive factors of skip metastases to lateral neck compartment leaping central neck compartment in papillary thyroid carcinoma. Oral Oncol. 2012;3:262–5.CrossRef Lim YC, Koo BS. Predictive factors of skip metastases to lateral neck compartment leaping central neck compartment in papillary thyroid carcinoma. Oral Oncol. 2012;3:262–5.CrossRef
22.
go back to reference Park JH, Lee YS, Kim BW, Chang HS, Park CS. Skip lateral neck node metastases in papillary thyroid carcinoma. World J Surg. 2012;4:743–7.CrossRef Park JH, Lee YS, Kim BW, Chang HS, Park CS. Skip lateral neck node metastases in papillary thyroid carcinoma. World J Surg. 2012;4:743–7.CrossRef
23.
go back to reference Lee YS, Shin SC, Lim YS, Lee JC, Wang SG, Son SM, et al. Tumor location-dependent skip lateral cervical lymph node metastasis in papillary thyroid cancer. Head Neck. 2014;6:887–91.CrossRef Lee YS, Shin SC, Lim YS, Lee JC, Wang SG, Son SM, et al. Tumor location-dependent skip lateral cervical lymph node metastasis in papillary thyroid cancer. Head Neck. 2014;6:887–91.CrossRef
24.
go back to reference Xiang D, Xie L, Xu Y, Li Z, Hong Y, Wang P. Papillary thyroid microcarcinomas located at the middle part of the middle third of the thyroid gland correlates with the presence of neck metastasis. Surgery. 2015;3:526–33.CrossRef Xiang D, Xie L, Xu Y, Li Z, Hong Y, Wang P. Papillary thyroid microcarcinomas located at the middle part of the middle third of the thyroid gland correlates with the presence of neck metastasis. Surgery. 2015;3:526–33.CrossRef
25.
go back to reference Rotstein L. The role of lymphadenectomy in the management of papillary carcinoma of the thyroid. J Surg Oncol. 2009;4:186–8.CrossRef Rotstein L. The role of lymphadenectomy in the management of papillary carcinoma of the thyroid. J Surg Oncol. 2009;4:186–8.CrossRef
26.
go back to reference Leboulleux S, Girard E, Rose M, Travagli JP, Sabbah N, Caillou B, et al. Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer. J Clin Endocrinol Metab. 2007;9:3590–4.CrossRef Leboulleux S, Girard E, Rose M, Travagli JP, Sabbah N, Caillou B, et al. Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer. J Clin Endocrinol Metab. 2007;9:3590–4.CrossRef
27.
go back to reference Som PM, Brandwein M, Lidov M, Lawson W, Biller HF. The varied presentations of papillary thyroid carcinoma cervical nodal disease: CT and MR findings. AJNR Am J Neuroradiol. 1994;6:1123–8. Som PM, Brandwein M, Lidov M, Lawson W, Biller HF. The varied presentations of papillary thyroid carcinoma cervical nodal disease: CT and MR findings. AJNR Am J Neuroradiol. 1994;6:1123–8.
28.
go back to reference Robbins KT, Clayman G, Levine PA, Medina J, Sessions R, Shaha A, et al. Neck dissection classification update: revisions proposed by the American head and neck society and the American Academy of Otolaryngology-Head and Neck Surgery. Arch Otolaryngol Head Neck Surg. 2002;7:751–8.CrossRef Robbins KT, Clayman G, Levine PA, Medina J, Sessions R, Shaha A, et al. Neck dissection classification update: revisions proposed by the American head and neck society and the American Academy of Otolaryngology-Head and Neck Surgery. Arch Otolaryngol Head Neck Surg. 2002;7:751–8.CrossRef
29.
go back to reference Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;6:1471–4.CrossRef Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;6:1471–4.CrossRef
30.
go back to reference Sivanandan R, Soo KC. Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid. Br J Surg. 2001;9:1241–4.CrossRef Sivanandan R, Soo KC. Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid. Br J Surg. 2001;9:1241–4.CrossRef
31.
go back to reference Machens A, Hofmann C, Hauptmann S, Dralle H. Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results. Eur J Endocrinol. 2007;1:85–93.CrossRef Machens A, Hofmann C, Hauptmann S, Dralle H. Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results. Eur J Endocrinol. 2007;1:85–93.CrossRef
32.
go back to reference Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Mimura T, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg. 2003;3:399–407. Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Mimura T, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg. 2003;3:399–407.
33.
go back to reference Shaha AR. Complications of neck dissection for thyroid cancer. Ann Surg Oncol. 2008;2:397–9.CrossRef Shaha AR. Complications of neck dissection for thyroid cancer. Ann Surg Oncol. 2008;2:397–9.CrossRef
34.
go back to reference Patron V, Bedfert C, Le Clech G, Aubry K, Jegoux F. Pattern of lateral neck metastases in N0 papillary thyroid carcinoma. BMC Cancer. 2011;8 Patron V, Bedfert C, Le Clech G, Aubry K, Jegoux F. Pattern of lateral neck metastases in N0 papillary thyroid carcinoma. BMC Cancer. 2011;8
35.
go back to reference Ali S, Tiwari RM, Snow GB. False-positive and false-negative neck nodes. Head Neck Surg. 1985;2:78–82.CrossRef Ali S, Tiwari RM, Snow GB. False-positive and false-negative neck nodes. Head Neck Surg. 1985;2:78–82.CrossRef
36.
go back to reference Kim E, Park JS, Son KR, Kim JH, Jeon SJ, Na DG. Preoperative diagnosis of cervical metastatic lymph nodes in papillary thyroid carcinoma: comparison of ultrasound, computed tomography, and combined ultrasound with computed tomography. Thyroid. 2008;4:411–8.CrossRef Kim E, Park JS, Son KR, Kim JH, Jeon SJ, Na DG. Preoperative diagnosis of cervical metastatic lymph nodes in papillary thyroid carcinoma: comparison of ultrasound, computed tomography, and combined ultrasound with computed tomography. Thyroid. 2008;4:411–8.CrossRef
37.
go back to reference Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, et al. Papillary microcarcinoma of the thyroid: how should it be treated? World J Surg. 2004;11:1115–21.CrossRef Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, et al. Papillary microcarcinoma of the thyroid: how should it be treated? World J Surg. 2004;11:1115–21.CrossRef
38.
go back to reference Noguchi S, Noguchi A, Murakami N. Papillary carcinoma of the thyroid. I. Developing pattern of metastasis. Cancer. 1970;5:1053–60.CrossRef Noguchi S, Noguchi A, Murakami N. Papillary carcinoma of the thyroid. I. Developing pattern of metastasis. Cancer. 1970;5:1053–60.CrossRef
39.
go back to reference Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid2016. 2015;1:1–133. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid2016. 2015;1:1–133.
40.
go back to reference Lin KL, Wang OC, Zhang XH, Dai XX, Hu XQ, Qu JM. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma. Ann Surg Oncol. 2010;12:3294–300.CrossRef Lin KL, Wang OC, Zhang XH, Dai XX, Hu XQ, Qu JM. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma. Ann Surg Oncol. 2010;12:3294–300.CrossRef
41.
go back to reference Jovanovic L, Delahunt B, McIver B, Eberhardt NL, Grebe SK. Most multifocal papillary thyroid carcinomas acquire genetic and morphotype diversity through subclonal evolution following the intra-glandular spread of the initial neoplastic clone. J Pathol. 2008;2:145–54.CrossRef Jovanovic L, Delahunt B, McIver B, Eberhardt NL, Grebe SK. Most multifocal papillary thyroid carcinomas acquire genetic and morphotype diversity through subclonal evolution following the intra-glandular spread of the initial neoplastic clone. J Pathol. 2008;2:145–54.CrossRef
42.
go back to reference Jung CK, Kang YG, Bae JS, Lim DJ, Choi YJ, Lee KY. Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma. Mod Pathol. 2010;9:1201–8.CrossRef Jung CK, Kang YG, Bae JS, Lim DJ, Choi YJ, Lee KY. Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma. Mod Pathol. 2010;9:1201–8.CrossRef
Metadata
Title
Skip metastasis in papillary thyroid carcinoma is difficult to predict in clinical practice
Authors
Xilin Nie
Zhou Tan
Minghua Ge
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3698-2

Other articles of this Issue 1/2017

BMC Cancer 1/2017 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