Risk factors associated with intrathyroid extension of thyroid microcarcinomas
- 23 Downloads
The aims of this study were to investigate the rate of intrathyroid extension of papillary thyroid microcarcinoma (PTMC) in patients operated for benign thyroid disease and to identify independent risk factors associated with it.
A retrospective study of 301 patients operated for benign thyroid diseases (hyperthyroid diseases, multinodular goitre, Hashimoto thyroiditis and benign thyroid tumours) was performed at a high-volume endocrine surgery unit of a tertiary referral academic hospital, in a 5-year period. These patients had a PTMC incidentally discovered on definite histopathological findings following total or near-total thyroidectomy. Since distinguishing between intrathyroid extension of PTMC as the result of intrathyroid dissemination or as the result of multicentricity is challenging, we observed them together as multifocality. In statistical analysis, we used standard descriptive statistics and univariate and multivariate logistic regression analysis to determine independent risk factors associated with multifocality.
In our study, there were 85.4% females and 14.6% males with a median age of 54 years. A multinodular goitre (32.5%) was the most common indication for an operation. Most patients (68.4%) had a PTMC that was 5 mm or smaller. The most frequent histological variants of PTMC were the follicular variant (52.8%), followed by the papillary variant (22.6%) and the mixed follicular-papillary variant (18.6%). A multifocal PTMC was present in 26.6% of cases. An independent protective factor for multifocality of PTMC was a thyroid gland that weighed more than 38 g (OR 0.55, 95% CI 0.31–0.97, p = 0.039). Size of PTMC greater than 5 mm was an independent risk factor for a multifocal PTMC (OR 3.26, 95% CI 1.85–5.75, p = 0.000). Finally, the mixed follicular-papillary variant of PTMC represents an independent risk factor for a multifocal PTMC (OR 2.42, 95% CI 1.09–5.36, p = 0.030).
Intrathyroid extension is present in more than a quarter of PTMCs found in patients operated for benign thyroid disease. Independent risk factors for intrathyroid extension are size of PTMC greater than 5 mm and the mixed follicular-papillary variant of PTMC, while a large thyroid gland is an independent protective factor.
KeywordsPapillary thyroid microcarcinoma Benign thyroid disease Multifocality Risk factors Tumour size Thyroid weight Mixed follicular-papillary variant
Study conception and design: NS, VZ; Acquisition of data: NS, MJ, BO; Analysis and interpretation of data: NS, VZ; Drafting of manuscript: NS, MJ, BO; Critical revision of manuscript: AD, IP.
Compliance with ethical standards
Conflict of interest
Author Nikola Slijepcevic declares that he has no conflict of interest. Author Vladan Zivaljevic declares that he has no conflict of interest. Author Aleksandar Diklic declares that he has no conflict of interest. Author Milan Jovanovic declares that he has no conflict of interest. Author Branislav Oluic declares that he has no conflict of interest. Author Ivan Paunovic declares that he has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 4.Jung CK, Little MP, Lubin JH, Brenner AV, Wells SA Jr, Sigurdson AJ, Nikiforov YE (2014) The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab 99(2):E276–E285CrossRefPubMedGoogle Scholar
- 5.Baloch ZW, Harrell RM, Brett EM, Randolph G, Garber JR, Committee AESS, Thyroid Scientific C (2017) American Association of Clinical Endocrinologists and American College of Endocrinology Disease state commentary: managing thyroid tumors diagnosed as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Endocr Pract 23(9):1150–1155CrossRefPubMedGoogle Scholar
- 6.Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (2016) 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 : Off J Am Thyroid Assoc 26(1):1–133CrossRefGoogle Scholar
- 8.Slijepcevic N, Zivaljevic V, Marinkovic J, Sipetic S, Diklic A, Paunovic I (2015) Retrospective evaluation of the incidental finding of 403 papillary thyroid microcarcinomas in 2466 patients undergoing thyroid surgery for presumed benign thyroid disease. BMC Cancer 15(1):330CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Kaliszewski K, Strutynska-Karpinska M, Zubkiewicz-Kucharska A, Wojtczak B, Domoslawski P, Balcerzak W, Lukienczuk T, Forkasiewicz Z (2016) Should the prevalence of incidental thyroid cancer determine the extent of surgery in multinodular goiter? PLoS One 11(12):e0168654CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Mimura T, Ito K, Takami H, Takanashi Y (2003) Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg 237(3):399–407PubMedPubMedCentralGoogle Scholar
- 29.Roti E, Rossi R, Trasforini G, Bertelli F, Ambrosio MR, Busutti L, Pearce EN, Braverman LE, Degli Uberti EC (2006) Clinical and histological characteristics of papillary thyroid microcarcinoma: results of a retrospective study in 243 patients. J Clin Endocrinol Metab 91(6):2171–2178CrossRefPubMedGoogle Scholar
- 32.Shi X, Liu R, Basolo F, Giannini R, Shen X, Teng D, Guan H, Shan Z, Teng W, Musholt TJ et al (2015) Differential clinicopathological risk and prognosis of major papillary thyroid cancer variants. J Clin Endocrinol Metab :jc20152917Google Scholar
- 39.Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Sherman SI, Tuttle RM, American Thyroid Association Guidelines Taskforce (2006) Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid : Off J Am Thyroid Assoc 16(2):109–142CrossRefGoogle Scholar
- 40.Wang TS, Goffredo P, Sosa JA, Roman SA: Papillary thyroid microcarcinoma: an over-treated malignancy? World journal of surgery 2014Google Scholar
- 41.American Thyroid Association Guidelines Taskforce on Thyroid N, Differentiated thyroid C, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B et al (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid : Off J Am Thyroid Assoc 19(11):1167–1214CrossRefGoogle Scholar
- 42.DeLellis R, Lloyd R, Heitz P, Eng C (2004) Pathology and genetics of tumors of endocrine organs. IARC Press, LyonGoogle Scholar