Langenbeck's Archives of Surgery

, Volume 403, Issue 5, pp 615–622 | Cite as

Risk factors associated with intrathyroid extension of thyroid microcarcinomas

  • Nikola Slijepcevic
  • Vladan Zivaljevic
  • Aleksandar Diklic
  • Milan Jovanovic
  • Branislav Oluic
  • Ivan Paunovic



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.


Papillary thyroid microcarcinoma Benign thyroid disease Multifocality Risk factors Tumour size Thyroid weight Mixed follicular-papillary variant 


Authors’ contributions

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.

Ethical approval

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

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Endocrine SurgeryClinical Centre of SerbiaBelgradeSerbia
  2. 2.Faculty of MedicineUniversity of BelgradeBelgradeSerbia
  3. 3.Emergency CentreClinical Centre of SerbiaBelgradeSerbia

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