J Pathol Transl Med.  2016 Jul;50(4):278-286. 10.4132/jptm.2016.03.29.

Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis

• Pyo JS
• Sohn JH
• Kang G

• KMID: 2345550
• DOI: http://doi.org/10.4132/jptm.2016.03.29

Abstract

BACKGROUND
The clinicopathological characteristics and conclusive treatment modality for multifocal papillary thyroid microcarcinoma (mPTMC) have not been fully established.
METHODS
A retrospective study, systematic review, and meta-analysis were conducted to elucidate the clinicopathological significance of mPTMC. We investigated the multiplicity of 383 classical papillary thyroid microcarcinomas (PTMCs) and the clinicopathological significance of incidental mPTMCs. Correlation between tumor recurrence and multifocality in PTMCs was evaluated through a systematic review and meta-analysis.
RESULTS
Tumor multifocality was identified in 103 of 383 PTMCs (26.9%). On linear regression analysis, primary tumor diameter was significantly correlated with tumor number (R2=0.014, p=.021) and supplemental tumor diameter (R2=0.117, p=.023). Of 103 mPTMCs, 61 (59.2%) were non-incidental, with tumor detected on preoperative ultrasonography, and 42 (40.8%) were diagnosed (incidental mPTMCs) on pathological examination. Lymph node metastasis and higher tumor stage were significantly correlated with tumor multifocality. However, there was no difference in nodal metastasis or tumor stage between incidental and non-incidental mPTMCs. On meta-analysis, tumor multifocality was significantly correlated with tumor recurrence in PTMCs (odds ratio, 2.002; 95% confidence interval, 1.475 to 2.719, p<.001).
CONCLUSIONS
Our results show that tumor multifocality in PTMC, regardless of manner of detection, is significantly correlated with aggressive tumor behavior.

Keyword

Papillary thyroid microcarcinoma; Multifocal; Incidental; Retrospective studies; Meta-analysis

MeSH Terms

Linear Models
Lymph Nodes
Neoplasm Metastasis
Recurrence*
Retrospective Studies*
Thyroid Gland*
Ultrasonography

Figure

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  Fig. 1. Diagnostic flow in 383 patients based on preoperative ultrasonography. mPTMC, multifocal papillary thyroid microcarcinoma; uPTMC, unifocal papillary thyroid microcarcinoma.

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  Fig. 2. Correlation between primary tumor size and multifocality in papillary thyroid microcarcinoma (PTMC). (A) Distribution of tumor multifocality based on primary tumor size in PTMC. (B) Correlation between primary tumor size and number of tumors using linear regression. (C) Correlation between primary and supplemental tumor size by linear regression.

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  Fig. 3. Flow chart of study search and selection.

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  Fig. 4. Forest plot diagram of tumor recurrence difference between multifocal and unifocal papillary thyroid microcarcinomas.15-22 CI, confidence interval.

Reference

1. Mercante G, Frasoldati A, Pedroni C, et al. Prognostic factors affecting neck lymph node recurrence and distant metastasis in papillary microcarcinoma of the thyroid: results of a study in 445 patients. Thyroid. 2009; 19:707–16.

2. Enewold L, Zhu K, Ron E, et al. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol Biomarkers Prev. 2009; 18:784–91.

3. Park YJ, Kim YA, Lee YJ, et al. Papillary microcarcinoma in comparison with larger papillary thyroid carcinoma in BRAFV600E mutation, clinicopathological features, and immunohistochemical findings. Head Neck. 2010; 32:38–45.

4. Ito Y, Miyauchi A, Inoue H, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg. 2010; 34:28–35.

5. Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M, Fujimoto Y. Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg. 2010; 34:1222–31.

6. Mazzaferri EL. Managing small thyroid cancers. JAMA. 2006; 295:2179–82.

7. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009; 19:1167–214.

8. Lee E, Jung W, Woo JS, et al. Tumor sprouting in papillary thyroid carcinoma is correlated with lymph node metastasis and recurrence. Korean J Pathol. 2014; 48:117–25.

9. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York: Springer-Verlag;2009. p. 87–96.

10. Mazeh H, Samet Y, Hochstein D, et al. Multifocality in well-differentiated thyroid carcinomas calls for total thyroidectomy. Am J Surg. 2011; 201:770–5.

11. Dietlein M, Luyken WA, Schicha H, Larena-Avellaneda A. Incidental multifocal papillary microcarcinomas of the thyroid: is subtotal thyroidectomy combined with radioiodine ablation enough? Nucl Med Commun. 2005; 26:3–8.

12. Rodríguez-Cuevas S, Labastida-Almendaro S, Cortés-Arroyo H, López-Garza J, Barroso-Bravo S. Multifactorial analysis of survival and recurrences in differentiated thyroid cancer: comparative evaluation of usefulness of AGES, MACIS, and risk group scores in Mexican population. J Exp Clin Cancer Res. 2002; 21:79–86.

13. Voutilainen PE, Siironen P, Franssila KO, Sivula A, Haapiainen RK, Haglund CH. AMES, MACIS and TNM prognostic classifications in papillary thyroid carcinoma. Anticancer Res. 2003; 23:4283–8.

14. Pyo JS, Sohn JH, Kang G, Kim DH, Yun J. Total surface area is useful for differentiating between aggressive and favorable multifocal papillary thyroid carcinomas. Yonsei Med J. 2015; 56:355–61.

15. Baudin E, Travagli JP, Ropers J, et al. Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience. Cancer. 1998; 83:553–9.

16. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH. Papillary microcarcinoma of the thyroid-Prognostic significance of lymph node metastasis and multifocality. Cancer. 2003; 98:31–40.

17. Hay ID, Hutchinson ME, Gonzalez-Losada T, et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery. 2008; 144:980–7.

18. Kim KJ, Kim SM, Lee YS, Chung WY, Chang HS, Park CS. Prognostic significance of tumor multifocality in papillary thyroid carcinoma and its relationship with primary tumor size: a retrospective study of 2,309 consecutive patients. Ann Surg Oncol. 2015; 22:125–31.

19. Lombardi CP, Bellantone R, De Crea C, et al. Papillary thyroid microcarcinoma: extrathyroidal extension, lymph node metastases, and risk factors for recurrence in a high prevalence of goiter area. World J Surg. 2010; 34:1214–21.

20. Neuhold N, Schultheis A, Hermann M, Krotla G, Koperek O, Birner P. Incidental papillary microcarcinoma of the thyroid: further evidence of a very low malignant potential: a retrospective clinicopathological study with up to 30 years of follow-up. Ann Surg Oncol. 2011; 18:3430–6.

21. Ross DS, Litofsky D, Ain KB, et al. Recurrence after treatment of micropapillary thyroid cancer. Thyroid. 2009; 19:1043–8.

22. Zheng X, Wei S, Han Y, et al. Papillary microcarcinoma of the thyroid: clinical characteristics and BRAFV600E mutational status of 977 cases. Ann Surg Oncol. 2013; 20:2266–73.

23. Haymart MR, Cayo M, Chen H. Papillary thyroid microcarcinomas: big decisions for a small tumor. Ann Surg Oncol. 2009; 16:3132–9.

24. Noguchi S, Yamashita H, Uchino S, Watanabe S. Papillary microcarcinoma. World J Surg. 2008; 32:747–53.

25. Mazzaferri EL. Managing thyroid microcarcinomas. Yonsei Med J. 2012; 53:1–14.

26. Papini E, Guglielmi R, Bianchini A, et al. Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab. 2002; 87:1941–6.

27. Strate SM, Lee EL, Childers JH. Occult papillary carcinoma of the thyroid with distant metastases. Cancer. 1984; 54:1093–100.

28. Roh JL, Kim JM, Park CI. Central cervical nodal metastasis from papillary thyroid microcarcinoma: pattern and factors predictive of nodal metastasis. Ann Surg Oncol. 2008; 15:2482–6.

29. Cheema Y, Olson S, Elson D, Chen H. What is the biology and optimal treatment for papillary microcarcinoma of the thyroid? J Surg Res. 2006; 134:160–2.

30. Macedo FI, Mittal VK. Total thyroidectomy versus lobectomy as initial operation for small unilateral papillary thyroid carcinoma: a meta-analysis. Surg Oncol. 2015; 24:117–22.

31. Kuo SF, Lin SF, Chao TC, Hsueh C, Lin KJ, Lin JD. Prognosis of multifocal papillary thyroid carcinoma. Int J Endocrinol. 2013; 2013:809382.

32. Ito Y, Miyauchi A. Appropriate treatment for asymptomatic papillary microcarcinoma of the thyroid. Expert Opin Pharmacother. 2007; 8:3205–15.

33. Yu XM, Lloyd R, Chen H. Current treatment of papillary thyroid microcarcinoma. Adv Surg. 2012; 46:191–203.

34. Renshaw AA. Sensitivity of fine-needle aspiration for papillary carcinoma of the thyroid correlates with tumor size. Diagn Cytopathol. 2011; 39:471–4.