Skip to main content
Top
Published in: Endocrine 3/2024

22-09-2023 | Thyroidectomy | Original Article

The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study

Authors: Sayid Shafi Zuhur, Hunkar Aggul, Ugur Avci, Selvinaz Erol, Mazhar Muslum Tuna, Serhat Uysal, Gulhan Akbaba, Faruk Kilinc, Merve Catak, Sakin Tekin, Beyza Olcay Ozturk, Halise Cinar Yavuz, Pinar Kadioglu, Nese Cinar, Taner Bayraktaroglu, Birol Topcu, Yuksel Altuntas, Gulsah Elbuken

Published in: Endocrine | Issue 3/2024

Login to get access

Abstract

Objectives

Despite the presumed overdiagnosis of papillary thyroid microcarcinoma (PTMC) which has resulted in a new trend toward less-extensive surgery and a preference for active surveillance, the impact of microscopic extrathyroidal extension (mETE) on the clinical outcomes of PTMC is still controversial. This study assessed the impact of mETE on the clinical outcomes of patients with classic subtype PTMC.

Methods

The data of consecutive patients who underwent thyroidectomy and were histopathologically diagnosed as classic subtype PTMC were analyzed. Cox’s proportional hazards model was used to assess the impact of contributing variables on persistent/recurrent disease. Disease-free survival was estimated using the Kaplan-Meier method.

Results

This study included 1013 patients (84% females), with a mean follow-up period of 62.5 ± 35.3 months. Patients with mETE had a significantly higher rate of locoregional persistent/recurrent disease than patients without mETE (9.8% vs 2.1%, p < 0.001). The disease-free survival rate was significantly lower in patients with mETE than in those without (90.2% vs 97%, Log-Rank p < 0.001). Furthermore, mETE and neck lymph node involvement were independent predictors of persistent/recurrent disease in multivariate analysis (HR: 2.43, 95% CI:1.02–5.81, p = 0.043; HR: 4.38, 95% CI: 1.7–11.2, p = 0.002, respectively).

Conclusions

In patients with the classic subtype of PTMC, mETE is an independent predictor of persistent/recurrent disease and is associated with a lower DFS rate. However, neck lymph node involvement is the strongest predictor of persistent/recurrent disease. Therefore, PTMCs with mETE and neck lymph node involvement are at a higher risk of persistent/recurrent disease than individuals lacking both characteristics.
Literature
1.
go back to reference M. Pereira, V.L. Williams, J. Hallanger Johnson, P. Valderrabano, Thyroid cancer incidence trends in the United States: Association with changes in professional guideline recommendations. Thyroid 30, 1132–1140 (2020)CrossRefPubMed M. Pereira, V.L. Williams, J. Hallanger Johnson, P. Valderrabano, Thyroid cancer incidence trends in the United States: Association with changes in professional guideline recommendations. Thyroid 30, 1132–1140 (2020)CrossRefPubMed
3.
go back to reference D.T. Hughes, M.R. Haymart, B.S. Miller, P.G. Gauger, G.M. Doherty, The most commonly occurring papillary thyroid cancer in the United States is now a microcarcinoma in a patient older than 45 years. Thyroid 21, 231–236 (2011)CrossRefPubMed D.T. Hughes, M.R. Haymart, B.S. Miller, P.G. Gauger, G.M. Doherty, The most commonly occurring papillary thyroid cancer in the United States is now a microcarcinoma in a patient older than 45 years. Thyroid 21, 231–236 (2011)CrossRefPubMed
5.
go back to reference M. Van Gerwen, N. Alpert, C. Sinclair, M. Kale, E. Genden, E. Taioli, Assessing non-aggressiveness of untreated, local and regional, papillary thyroid cancer. Oral. Oncol. 105, 104674 (2020)CrossRefPubMed M. Van Gerwen, N. Alpert, C. Sinclair, M. Kale, E. Genden, E. Taioli, Assessing non-aggressiveness of untreated, local and regional, papillary thyroid cancer. Oral. Oncol. 105, 104674 (2020)CrossRefPubMed
6.
go back to reference S.S. Zuhur, H. Aggul, U. Avci et al. Do histologically aggressive subtypes of papillary thyroid microcarcinoma have worse clinical outcome than non-aggressive papillary thyroid microcarcinoma subtypes? A multicenter cohort study. Horm. Metab. Res 10, 2032–5810 (2023) S.S. Zuhur, H. Aggul, U. Avci et al. Do histologically aggressive subtypes of papillary thyroid microcarcinoma have worse clinical outcome than non-aggressive papillary thyroid microcarcinoma subtypes? A multicenter cohort study. Horm. Metab. Res 10, 2032–5810 (2023)
7.
go back to reference S. Leboulleux, R.M. Tuttle, F. Pacini, M. Schlumberger, Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance? Lancet Diabetes Endocrinol. 4, 933–942 (2016)CrossRefPubMed S. Leboulleux, R.M. Tuttle, F. Pacini, M. Schlumberger, Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance? Lancet Diabetes Endocrinol. 4, 933–942 (2016)CrossRefPubMed
8.
go back to reference H.J. Moon, E.K. Kim, W.Y. Chung, J.H. Yoon, J.Y. Kwak, Minimal extrathyroidal extension in patients with papillary thyroid microcarcinoma: is it a real prognostic factor? Ann. Surg. Oncol. 18, 1916–1923 (2011)CrossRefPubMed H.J. Moon, E.K. Kim, W.Y. Chung, J.H. Yoon, J.Y. Kwak, Minimal extrathyroidal extension in patients with papillary thyroid microcarcinoma: is it a real prognostic factor? Ann. Surg. Oncol. 18, 1916–1923 (2011)CrossRefPubMed
9.
go back to reference N. Chéreau, C. Buffet, C. Trésallet et al. Does extracapsular extension impact the prognosis of papillary thyroid microcarcinoma? Ann. Surg. Oncol. 21, 1659–1664 (2014)CrossRefPubMed N. Chéreau, C. Buffet, C. Trésallet et al. Does extracapsular extension impact the prognosis of papillary thyroid microcarcinoma? Ann. Surg. Oncol. 21, 1659–1664 (2014)CrossRefPubMed
10.
go back to reference C. Buffet, J.L. Golmard, C. Hoang et al. Scoring system for predicting recurrences in patients with papillary thyroid microcarcinoma. Eur. J. Endocrinol. 167, 267–275 (2012)CrossRefPubMed C. Buffet, J.L. Golmard, C. Hoang et al. Scoring system for predicting recurrences in patients with papillary thyroid microcarcinoma. Eur. J. Endocrinol. 167, 267–275 (2012)CrossRefPubMed
11.
go back to reference R.Y. Song, H.S. Kim, K.H. Kang, Minimal extrathyroidal extension is associated with lymph node metastasis in single papillary thyroid microcarcinoma: a retrospective analysis of 814 patients. World J. Surg. Oncol. 20, 170 (2022)CrossRefPubMedPubMedCentral R.Y. Song, H.S. Kim, K.H. Kang, Minimal extrathyroidal extension is associated with lymph node metastasis in single papillary thyroid microcarcinoma: a retrospective analysis of 814 patients. World J. Surg. Oncol. 20, 170 (2022)CrossRefPubMedPubMedCentral
12.
go back to reference F. Pacini, M. Schlumberger, H. Dralle et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur. J. Endocrinol. 154, 787–803 (2006)CrossRefPubMed F. Pacini, M. Schlumberger, H. Dralle et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur. J. Endocrinol. 154, 787–803 (2006)CrossRefPubMed
13.
go back to reference M.B. Amin, S. Edge, F. Greene, et al. AJCC Cancer Staging Manual. 8th ed. Springer 881–889 (2017). M.B. Amin, S. Edge, F. Greene, et al. AJCC Cancer Staging Manual. 8th ed. Springer 881–889 (2017).
14.
go back to reference D.S. Cooper, G.M. Doherty et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167e1214 (2009)CrossRef D.S. Cooper, G.M. Doherty et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167e1214 (2009)CrossRef
15.
go back to reference B.R. Haugen, E.K. Alexander, K.C. Bible et al. 2015 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. Thyroid 26, 1–133 (2016)CrossRefPubMedPubMedCentral B.R. Haugen, E.K. Alexander, K.C. Bible et al. 2015 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. Thyroid 26, 1–133 (2016)CrossRefPubMedPubMedCentral
16.
go back to reference S.S. Zuhur, H. Aggul, M. Çelik et al. Can age at diagnosis and sex improve the performance of the american thyroid association risk stratification system for prediction of structural persistent and recurrent disease in patients with differentiated thyroid carcinoma? a multicenter study. Endocr. Pr. 28, 30–35 (2022)CrossRef S.S. Zuhur, H. Aggul, M. Çelik et al. Can age at diagnosis and sex improve the performance of the american thyroid association risk stratification system for prediction of structural persistent and recurrent disease in patients with differentiated thyroid carcinoma? a multicenter study. Endocr. Pr. 28, 30–35 (2022)CrossRef
17.
go back to reference D.P. Momesso, R.M. Tuttle, Update on differentiated thyroid cancer staging. Endocrinol. Metab. Clin. North Am. 43, 401–421 (2014)CrossRefPubMed D.P. Momesso, R.M. Tuttle, Update on differentiated thyroid cancer staging. Endocrinol. Metab. Clin. North Am. 43, 401–421 (2014)CrossRefPubMed
18.
go back to reference A. Jang, M. Jin, C.A. Kim et al. Serum thyroglobulin testing after thyroid lobectomy in patients with 1-4 cm papillary thyroid carcinoma. Endocrine 81, 290–297 (2023)CrossRefPubMed A. Jang, M. Jin, C.A. Kim et al. Serum thyroglobulin testing after thyroid lobectomy in patients with 1-4 cm papillary thyroid carcinoma. Endocrine 81, 290–297 (2023)CrossRefPubMed
19.
go back to reference H. Mehanna, T. Al-Maqbili, B. Carter et al. Differences in the recurrence and mortality outcomes rates of incidental and nonincidental papillary thyroid microcarcinoma: a systematic review and meta-analysis of 21 329 person-years of follow-up. J. Clin. Endocrinol. Metab. 99, 2834–2843 (2014)CrossRefPubMed H. Mehanna, T. Al-Maqbili, B. Carter et al. Differences in the recurrence and mortality outcomes rates of incidental and nonincidental papillary thyroid microcarcinoma: a systematic review and meta-analysis of 21 329 person-years of follow-up. J. Clin. Endocrinol. Metab. 99, 2834–2843 (2014)CrossRefPubMed
20.
go back to reference Y. Ito, C. Tomoda, T. Uruno et al. Minimal extrathyroid extension does not affect the relapse-free survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the age of 45 years. Surg. Today 36, 12–18 (2006)CrossRefPubMed Y. Ito, C. Tomoda, T. Uruno et al. Minimal extrathyroid extension does not affect the relapse-free survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the age of 45 years. Surg. Today 36, 12–18 (2006)CrossRefPubMed
21.
go back to reference I.D. Hay, T.R. Johnson, G.B. Thompson, T.J. Sebo, M.S. Reinalda, Minimal extrathyroid extension in papillary thyroid carcinoma does not result in increased rates of either cause-specific mortality or postoperative tumor recurrence. Surgery 159, 11–19 (2016)CrossRefPubMed I.D. Hay, T.R. Johnson, G.B. Thompson, T.J. Sebo, M.S. Reinalda, Minimal extrathyroid extension in papillary thyroid carcinoma does not result in increased rates of either cause-specific mortality or postoperative tumor recurrence. Surgery 159, 11–19 (2016)CrossRefPubMed
22.
go back to reference Y. Ito, C. Tomoda, T. Uruno et al. Prognostic significance of extrathyroid extension of papillary thyroid carcinoma: massive but not minimal extension affects the relapse-free survival. World J. Surg. 30, 780–786 (2006)CrossRefPubMed Y. Ito, C. Tomoda, T. Uruno et al. Prognostic significance of extrathyroid extension of papillary thyroid carcinoma: massive but not minimal extension affects the relapse-free survival. World J. Surg. 30, 780–786 (2006)CrossRefPubMed
23.
go back to reference Z. Al-Qurayshi, N. Nilubol, R.P. Tufano, E. Kandil, Wolf in sheep’s clothing: Papillary thyroid microcarcinoma in the US. J. Am. Coll. Surg. 230, 484–491 (2020)CrossRefPubMedPubMedCentral Z. Al-Qurayshi, N. Nilubol, R.P. Tufano, E. Kandil, Wolf in sheep’s clothing: Papillary thyroid microcarcinoma in the US. J. Am. Coll. Surg. 230, 484–491 (2020)CrossRefPubMedPubMedCentral
24.
go back to reference T. Diker-Cohen, D. Hirsch, I. Shimon et al. Impact of minimal extra-thyroid extension in differentiated thyroid cancer: Systematic review and meta-. J. Clin. Endocrinol. Metab. 103, 2100–2106 (2018)CrossRef T. Diker-Cohen, D. Hirsch, I. Shimon et al. Impact of minimal extra-thyroid extension in differentiated thyroid cancer: Systematic review and meta-. J. Clin. Endocrinol. Metab. 103, 2100–2106 (2018)CrossRef
25.
go back to reference R. Seifert, M.A. Schäfers, B. Heitplatz, L. Kerschke, B. Riemann, B. Noto, Minimal extrathyroid extension in papillary micro carcinoma of the thyroid is an independent risk factor for relapse through lymph node and distant metastases. J. Nucl. Med. 62, 1702–1709 (2021)CrossRefPubMedPubMedCentral R. Seifert, M.A. Schäfers, B. Heitplatz, L. Kerschke, B. Riemann, B. Noto, Minimal extrathyroid extension in papillary micro carcinoma of the thyroid is an independent risk factor for relapse through lymph node and distant metastases. J. Nucl. Med. 62, 1702–1709 (2021)CrossRefPubMedPubMedCentral
26.
go back to reference Z.W. Baloch, S.L. Asa, J.A. Barletta et al. Overview of the 2022 WHO classification of thyroid neoplasms. Endocr. Pathol. 33, 27–63 (2022)CrossRefPubMed Z.W. Baloch, S.L. Asa, J.A. Barletta et al. Overview of the 2022 WHO classification of thyroid neoplasms. Endocr. Pathol. 33, 27–63 (2022)CrossRefPubMed
27.
go back to reference J.S. Park, J.W. Chang, L. Liu, S.N. Jung, B.S. Koo, Clinical implications of microscopic extrathyroidal extension in patients with papillary thyroid carcinoma. Oral. Oncol. 72, 183–187 (2017)CrossRefPubMed J.S. Park, J.W. Chang, L. Liu, S.N. Jung, B.S. Koo, Clinical implications of microscopic extrathyroidal extension in patients with papillary thyroid carcinoma. Oral. Oncol. 72, 183–187 (2017)CrossRefPubMed
28.
go back to reference R.M. Tuttle, B. Haugen, N.D. Perrier, Updated american joint committee on cancer/ tumor-node-metastasis staging system for differentiated and anaplastic thyroid cancer (eighth ed.): what changed and why? Thyroid 27, 751–756 (2017)CrossRefPubMedPubMedCentral R.M. Tuttle, B. Haugen, N.D. Perrier, Updated american joint committee on cancer/ tumor-node-metastasis staging system for differentiated and anaplastic thyroid cancer (eighth ed.): what changed and why? Thyroid 27, 751–756 (2017)CrossRefPubMedPubMedCentral
29.
go back to reference X.M. Yu, Y. Wan, R.S. Sippel, H. Chen, Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18,445 cases. Ann. Surg. 254, 653–660 (2011)CrossRefPubMed X.M. Yu, Y. Wan, R.S. Sippel, H. Chen, Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18,445 cases. Ann. Surg. 254, 653–660 (2011)CrossRefPubMed
30.
go back to reference K.W. Schmid, S. Synoracki, H. Dralle et al. Proposal for an extended pTNM classification of thyroid carcinoma. Pathologe 40(Suppl 1), 18–24 (2019)CrossRefPubMed K.W. Schmid, S. Synoracki, H. Dralle et al. Proposal for an extended pTNM classification of thyroid carcinoma. Pathologe 40(Suppl 1), 18–24 (2019)CrossRefPubMed
31.
go back to reference M.B. Amin, F.L. Greene, S.B. Edge et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J. Clin. 67, 93–99 (2017)CrossRefPubMed M.B. Amin, F.L. Greene, S.B. Edge et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J. Clin. 67, 93–99 (2017)CrossRefPubMed
32.
go back to reference R. Forleo, G. Grani, M. Alfò et al. (2021). Minimal extrathyroidal extension in predicting 1-year outcomes: A longitudinal multicenter study of low-to-intermediate-risk papillary thyroid carcinoma (ITCO#4). Thyroid 31(12), 1814–1821 (2021)CrossRefPubMed R. Forleo, G. Grani, M. Alfò et al. (2021). Minimal extrathyroidal extension in predicting 1-year outcomes: A longitudinal multicenter study of low-to-intermediate-risk papillary thyroid carcinoma (ITCO#4). Thyroid 31(12), 1814–1821 (2021)CrossRefPubMed
33.
go back to reference J. Lee, J.H. Park, C.R. Lee, W.Y. Chung, C.S. Park, Long-term outcomes of total thyroidectomy versus thyroid lobectomy for papillary thyroid microcarcinoma: comparative analysis after propensity score matching. Thyroid 23, 1408–1415 (2013)CrossRefPubMed J. Lee, J.H. Park, C.R. Lee, W.Y. Chung, C.S. Park, Long-term outcomes of total thyroidectomy versus thyroid lobectomy for papillary thyroid microcarcinoma: comparative analysis after propensity score matching. Thyroid 23, 1408–1415 (2013)CrossRefPubMed
34.
go back to reference S. Leboulleux, C. Bournaud, C.N. Chougnet et al. Thyroidectomy without radioiodine in patients with low-risk thyroid cancer. N. Engl. J. Med 386(10), 923–932 (2022)CrossRefPubMed S. Leboulleux, C. Bournaud, C.N. Chougnet et al. Thyroidectomy without radioiodine in patients with low-risk thyroid cancer. N. Engl. J. Med 386(10), 923–932 (2022)CrossRefPubMed
35.
go back to reference F. Pacini, D. Fuhrer, R. Elisei et al. 2022 ETA Consensus Statement: What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer? Eur. Thyroid J. 11(1), e210046 (2022)CrossRefPubMed F. Pacini, D. Fuhrer, R. Elisei et al. 2022 ETA Consensus Statement: What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer? Eur. Thyroid J. 11(1), e210046 (2022)CrossRefPubMed
37.
go back to reference J. Pachucki, L.A. Burmeister, Evaluation and treatment of persistent thyroglobulinemia in patients with well-differentiated thyroid cancer. Eur. J. Endocrinol. 137, 254e26 (1997) J. Pachucki, L.A. Burmeister, Evaluation and treatment of persistent thyroglobulinemia in patients with well-differentiated thyroid cancer. Eur. J. Endocrinol. 137, 254e26 (1997)
38.
go back to reference M.F. Bates, M.R. Lamas, R.W. Randle et al. Back so soon? Is early recurrence of papillary thyroid cancer really just persistent disease? Surgery 163, 118–123 (2018)CrossRefPubMed M.F. Bates, M.R. Lamas, R.W. Randle et al. Back so soon? Is early recurrence of papillary thyroid cancer really just persistent disease? Surgery 163, 118–123 (2018)CrossRefPubMed
39.
go back to reference G. Sapuppo, M. Tavarelli, A. Belfiore, R. Vigneri, G. Pellegriti, Time to separate persistent from recurrent differentiated thyroid cancer: Different conditions with different outcomes. J. Clin. Endocrinol. Metab. 104, 258–265 (2019)CrossRefPubMed G. Sapuppo, M. Tavarelli, A. Belfiore, R. Vigneri, G. Pellegriti, Time to separate persistent from recurrent differentiated thyroid cancer: Different conditions with different outcomes. J. Clin. Endocrinol. Metab. 104, 258–265 (2019)CrossRefPubMed
Metadata
Title
The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study
Authors
Sayid Shafi Zuhur
Hunkar Aggul
Ugur Avci
Selvinaz Erol
Mazhar Muslum Tuna
Serhat Uysal
Gulhan Akbaba
Faruk Kilinc
Merve Catak
Sakin Tekin
Beyza Olcay Ozturk
Halise Cinar Yavuz
Pinar Kadioglu
Nese Cinar
Taner Bayraktaroglu
Birol Topcu
Yuksel Altuntas
Gulsah Elbuken
Publication date
22-09-2023
Publisher
Springer US
Published in
Endocrine / Issue 3/2024
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-023-03533-1

Other articles of this Issue 3/2024

Endocrine 3/2024 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Webinar | 06-02-2024 | 20:00 (CET)

Mastering chronic pancreatitis pain: A multidisciplinary approach and practical solutions

Severe pain is the most common symptom of chronic pancreatitis. In this webinar, experts share the latest insights in pain management for chronic pancreatitis patients. Experts from a range of disciplines discuss pertinent cases and provide practical suggestions for use within clinical practice.

Sponsored by: Viatris

Developed by: Springer Healthcare