Journal of Thyroid Research

Journal of Thyroid Research / 2020 / Article

Research Article | Open Access

Volume 2020 |Article ID 3567658 | https://doi.org/10.1155/2020/3567658

Christos Papaioannou, Demetris Lamnisos, Katerina Kyriacou, Theodoros Lyssiotis, Vasilis Constantinides, Savvas Frangos, Aliki Economides, Panayiotis A. Economides, "Lymph Node Metastasis and Extrathyroidal Extension in Papillary Thyroid Microcarcinoma in Cyprus: Suspicious Subcentimeter Nodules Should Undergo FNA When Multifocality is Suspected", Journal of Thyroid Research, vol. 2020, Article ID 3567658, 7 pages, 2020. https://doi.org/10.1155/2020/3567658

Lymph Node Metastasis and Extrathyroidal Extension in Papillary Thyroid Microcarcinoma in Cyprus: Suspicious Subcentimeter Nodules Should Undergo FNA When Multifocality is Suspected

Academic Editor: Massimo Tonacchera
Received09 Jan 2020
Accepted28 Feb 2020
Published24 Mar 2020

Abstract

Objective. To determine the prevalence of lymph node (LN) metastasis and extrathyroidal extension (ETE) in patients with papillary thyroid microcarcinoma (PTMC) in Cyprus and to evaluate the role of preoperative ultrasound (U/S) examination. Methods. A retrospective study of 102 patients who underwent thyroidectomy for PTMC in a 2-year period. Preoperatively, all patients had a thyroid and neck U/S examination with LN mapping. Tumor size according to the largest diameter, number of foci, LN metastasis, and ETE data was collected from the histopathological report and was compared to the preoperative U/S reports. Results. LN metastasis was present in 23.5% of patients. 15.7% had central, 3.9% had lateral, and 3.9% had both central and lateral LN metastasis. ETE was present in 27.5% of patients. 21.6% had multifocal disease, and in this group, 40.9% had LN metastasis and 36.4% had ETE. Multifocality (), size of tumor (), and ETE () were significantly associated with LN metastasis. The prevalence of LN metastasis in multifocal PTMC ≤5 mm was the same with multifocal PTMC >5 mm. The preoperative U/S sensitivity for the suspicious lateral neck and central LN was 100%, and the specificity was 100%. The preoperative U/S sensitivity for nodules suspicious for ETE was 53.6%, and the specificity was 100%. Conclusion. The presence of LN metastasis and ETE in our PTMC patients in Cyprus is frequent. Neck U/S mapping is a highly reliable and accurate tool in identifying metastatic nodes. LN metastasis is associated with ETE and multifocality. Suspicious subcentimeter nodules should undergo FNA irrespective of size when multifocality is suspected.

1. Introduction

There is a high prevalence of papillary thyroid carcinoma worldwide with an increasing incidence attributed to the increased diagnosis of papillary thyroid microcarcinoma (PTMC) [1, 2]. PTMC are tumors less than or equal to 10 mm along the greatest diameter [3] and are most often incidentally identified during routine thyroid ultrasonography [4, 5] with the major risk factors being a positive family history and exposure to ionising radiation [6]. Their mortality rate is less than 1%, and they have an excellent prognosis [7]. In a 2015 study analysing thyroid nodules of patients in the island of Cyprus, 14.3% of those were found to be malignant [8] with thyroid cancer being the second most common type of cancer in Cypriot female patients [9]. In a cohort of low-intermediate risk papillary thyroid carcinoma patients undergoing radioiodine ablation in a referral oncology center in Cyprus, almost one quarter had cervical LN metastasis [10].

The management of PTMC is controversial and debatable. The American Thyroid Association (ATA), the American Association of Clinical Endocrinologists (AACE), the European Thyroid Association (ETA), and British Thyroid Association (BTA) guidelines advice against ultrasound-guided fine needle aspiration biopsy (USgFNA) in thyroid nodules less or equal to 10 mm provided that there are no metastatic LN or suspicion of ETE [1114]. AACE recommends against FNA in incidental thyroid lesions with a diameter <5 mm as they are considered to have a lower risk of aggressive features, and there is an increased risk of inadequate sampling [13]. In cytologically proven thyroid microcarcinomas, presumed to be low-risk PTMC, active surveillance is currently considered as an alternative to surgery, and close observation may be advised [11, 15].

Total thyroidectomy or hemithyroidectomy is the current standard of practice with the latest ATA guidelines favouring towards hemithyroidectomy for PTMC without aggressive features [11, 16]. However, many surgeons suggest total thyroidectomy as the first option as more metastatic LN can be identified during total thyroidectomy with central LN dissection [1618]. In addition, total thyroidectomy improves postoperative follow-up surveillance through the use of serum thyroglobulin and decreases the risk of reoccurrence [16]. Furthermore, when indicated, it facilitates the use of postoperative radioactive iodine ablation [19].

Central LN metastasis can occur in up to 29.3% and lateral lymph node metastasis in 3.7–5.6% of PTMC patients [2022], and this is associated with locoregional re-occurrence and adverse outcomes [23, 24]. ETE is another risk factor that can affect the decision for total vs. hemithyroidectomy [16, 25]. ETE can occur in 28.0–40.3% of PTMC patients [26, 27] and is associated with increased likelihood of central, lateral LN metastasis, and increased tumor size and should be treated more aggressively [28, 29].

Ultrasonography has a major role in preoperatively evaluating the thyroid gland and the central and lateral neck LN [3034]. Ultrasonography assesses tumor extent, the probability of ETE [35], and the location of metastatic nodes. The specificity of US to determine metastatic nodes in PTMC patients ranges from 80 to 95% in both central and lateral compartments of the neck [36]. Ultrasound-guided fine needle aspiration biopsy of the suspicious lymph nodes with thyroglobulin level determination from the aspirate is used to confirm malignancy [11, 12].

Our study is aimed to analyse the prevalence of central, lateral metastatic LN, and ETE in patients with PTMC in Cyprus and to examine the role of thyroid and neck U/S in the preoperative setting.

2. Methods

The records of 102 patients diagnosed with papillary thyroid microcarcinoma between a two-year period (January 2016 to December 2017) at the Thyroid & Endocrinology Center in Nicosia, Cyprus, were retrospectively reviewed. Preoperatively, all patients underwent a clinical evaluation, a thyroid ultrasound examination, U/S-guided FNA, and an U/S of the neck/LN mapping with a detailed diagram [37]. U/S was performed by an endocrinologist experienced in thyroid and neck U/S by a GE Logiq E9 system. LN was defined suspicious based on a rounded shape (ratio of short axis to long axis >0.5), peripheral hypervascularity by color Doppler examination, the presence of calcifications, cystic change, and heterogeneous texture [36]. When the nodule was peripherally located and focally abutting or contacting the thyroid capsule, the suspicion of ETE was noted in the U/S report/diagram [38, 39].

All data including age, gender and family history were recorded. The presence or absence of autoimmune thyroid disease (Hashimoto’s thyroiditis and Graves’ disease) was also recorded and was based on a combination of detailed history taking, clinical and ultrasonographic examination, and the presence of positive thyroid autoantibodies. Tumor size according to the largest diameter, number of foci, ETE, and LN metastasis data was collected from the histopathological report and was compared to the preoperative U/S reports. Minimal ETE was defined as microscopic tumor extension to the extrathyroidal fat, whereas gross ETE was defined as macroscopic extension to the strap muscles. In cases of unifocality, tumor size is the size in mm of the maximum diameter of the tumor. In cases of multifocality (≥2 tumor foci in the same or different lobes including the isthmus), total tumor size was defined as the sum of sizes in mm of the maximum diameter of all tumors.

All 102 patients in this cohort underwent total thyroidectomy by experienced surgeons. Ninety-eight patients had central lymph node dissection (CLND). Eight patients underwent CLND for suspicious central LN on U/S and the other 90 underwent prophylactic CLND. Four patients did not undergo CLND; however, in none of these patients suspicious central LN were seen in the preoperative U/S. Ten patients underwent lateral LN dissection; eight were based on suspicious U/S findings and/or malignant cytology/Tg washout from the LN.

The study protocol was formally submitted for approval to the Cyprus National Bioethics Committee, which advised us that as this was a retrospective record analysis, ethical clearance was not warranted. Patient identities and personal data were not revealed and were kept fully confidential throughout the study analysis.

3. Statistical Analysis

The following factors were examined as possible factors associated with LN metastasis and ETE: gender, age (<55 vs ≥55 years old), family history, multifocality, Hashimoto’s thyroiditis, Grave’s disease, tumor size, and total tumor size. The tumor size was treated as a continuous measurement (in mm) and as binary categorical variable with two categories (≤5 mm vs >5 mm). These factors were analyzed by a series of univariable logistic regression models that consider each factor separately. The association of LN metastasis and ETE with each factor was expressed in OR (odds ratios) and 95% CI (confidence intervals). Statistical analyses were performed using the statistical package SPSS 20, and statistical significance was set at .

4. Results

A total of 102 patients with PTMC were enrolled. Patient and disease characteristics are shown in Table 1. There were 81 females (80.4%) and 21 males (20.6%). 24/102 patients (23.5%) had lateral and/or central LN metastasis; 16/102 (15.7%) had central (level VI) LN metastasis; and 4/102 (3.9%) had lateral LN metastasis (levels II, III and IV). 4/102 (3.9%) patients had both. 9/20 (45.0%) patients with central LN metastasis and 3/8 (37.5%) patients with lateral LN metastasis had micrometastatic disease (metastatic focus <2 mm). No data regarding the size of the metastatic focus were available in 2/8 (25.0%) patients with metastatic lateral LN. The level of LN metastasis is shown in Table 2. Twenty-eight patients (27.5%) had ETE. 19/28 (67.9%) patients with ETE had minimal ETE, whereas 9/28 (32.1%) patients had gross ETE.


CharacteristicsCategoriesFrequency (%)

GenderMale21 (20.6)
Female81 (80.4)
Age<5579 (77.5)
≥5523 (22.5)
Family historyYes15 (14.7)
No87 (85.3)
MultifocalityYes22 (21.6)
No80 (79.4)
Hashimoto’s thyroiditisYes32 (31.4)
No70 (69.6)
Grave’s diseaseYes3 (2.9)
No99 (97.1)
Tumor size (mm)Mean (sd)
5.94 (0.22)
Tumor size≤5 mm47 (46.1)
>5 mm55 (53.9)
ETEYes28 (27.5)
No74 (72.5)
LN metastasisYes24 (23.5)
No78 (77.5)
Level LN metastasisCentral16 (15.7)
Lateral4 (3.9)
Central and lateral4 (3.9)


LevelPrevalence

II2/24 (8.3%)
III4/24 (16.7%)
IV8/24 (33.3%)
V0/24 (0%)
VI20/24 (83.3%)

47/102 (46.1%) patients had tumor size less than or equal to 5 mm; in this group, 4/47 (8.5%) had central lymph node metastasis; 1/47 (2.1%) had lateral lymph node metastasis, and 3/47 6.4%) had both central and lateral lymph node metastasis. 9/47 (19.1%) of these patients had ETE. 55/102 (53.9%) patients had tumor size more than 5 mm; in this group, 12/55 (21.8%) had central lymph node metastasis; 3/55 (5.5%) had lateral lymph node metastasis; and 1/55 (1.8%) had both central and lateral lymph node metastasis. 19/55 (34.5%) of these patients had ETE.

There were 22 patients (21.6%) with multifocal disease, and Table 3 describes the number and size of the foci and the presence or absence of LN metastasis and ETE. Multifocality was suspected on the preoperative U/S in 18 patients (81.8%). 5/22 (22.7%) had central LN metastasis; 1/22 (4.5%) had lateral LN metastasis; and 3/22 (13.6%) had central and lateral LN metastasis. Micrometastatic disease was present in 2/8 (25.0%) patients with central LN metastasis and in 1/4 (25.0%) patient with lateral LN metastasis. No data were available regarding the size of the metastatic foci in 2/4 (50.0%) patients with lateral LN metastasis. 8/22 (36.4%) patients with multifocal disease had ETE. 5/8 (62.5%) had minimal ETE, whereas 3/8 (37.5%) had gross ETE.


Patient numberTumor foci diameter (mm)Total size (mm)Central LNLateral LNCentral and lateral LNETESuspicious foci seen at preop U/S

110, 212+1/2
29, 514+2/2
39, 413++2/2
49, 4132/2
58, 5132/2
68, 4122/2
78, 210++2/2
86, 6, 5, 421+3/4
96, 5112/2
106, 511+2/2
116, 5112/2
126, 4, 313+3/3
136, 410+2/2
145, 49++2/2
155, 492/2
165, 272/2
174, 482/2
184, 48++2/2
194, 48+1/2
204, 26+1/2
214, 2.86.8+2/2
223, 141/2

+: present. −: absent.

80/102 (21.6%) had unifocal disease; in this group, 11/80 (13.8%) had central LN metastasis; 3/80 (3.8%) had lateral LN metastasis; and 1/80 (1.3%) had central and lateral LN metastasis. 20/80 (25.0%) patients had ETE.

Tables 4 and 5 show the results of the analysis of the association between different characteristics of the patients and the LN and ETE. Multifocality (), size of tumor (), total tumor size (), and ETE () were significantly associated with LN metastasis. Tumor size (), total tumor size (), and LN metastasis () were significantly associated with ETE. No association was seen between LN metastasis or ETE and family history, Hashimoto’s thyroiditis, or Graves’ disease.


CharacteristicsCategoriesPercentage of LN metastasis valueOdds ratio (95% confidence interval)

GenderMale23.80.971.02 (0.33, 3.15)
Female23.5Ref
Age<5524.10.821.14 (0.37, 3.48)
≥5521.7Ref
Family historyYes20.00.730.79 (0.20, 3.05)
No24.1Ref
MultifocalityYes40.90.033.00 (1.08, 8.30)
No18.8Ref
Hashimoto’s thyroiditisYes12.50.080.36 (0.11, 1.15)
No28.6Ref
Graves’ diseaseYes33.30.561.65 (0.14, 19.06)
No23.2Ref
Tumor size (mm)0.051.23 (1.00, 1.52)
Tumor size≤5 mm17.00.15Ref
>5 mm29.12.00 (0.77, 5.21)
Total tumor size (mm)0.031.19 (1.02, 1.40)
Total tumor size≤5 mm14.60.07Ref
>5 mm30.02.50 (0.90, 6.98)
ETEYes50.00.006.40 (2.36, 17.33)
No13.5Ref

value for the χ2 test or Fisher’s exact test. value of univariable logistic regression.

CharacteristicsCategoriesPercentage of ETEvalueOdds ratio (95% confidence Interval)

GenderMale23.80.680.79 (0.26, 2.40)
Female28.4Ref
Age<5527.80.871.09 (0.38, 3.14)
≥5526.1Ref
Family historyYes33.30.581.39 (0.43, 4.50)
No26.4Ref
MultifocalityYes36.40.291.71 (0.63, 4.69)
No20.0Ref
Hashimoto’s thyroiditisYes25.00.710.83 (0.32, 2.16)
No28.6Ref
Graves’ diseaseYes66.70.185.62 (0.49, 64.54)
No26.3Ref
Tumor size (mm)0.011.29 (1.05, 1.59)
Tumor size≤5 mm19.10.08Ref
>5 mm34.52.23 (0.89, 5.56)
Total tumor size (mm)0.041.18 (1.01, 1.38)
Total tumor size≤5 mm17.10.05Ref
>5 mm34.42.55 (0.97, 6.73)
LN metastasisYes58.30.00
No17.9

value for the χ2 test or Fisher’s exact test. value of univariable logistic regression.

Stratifying the sample by multifocality (Table 6) indicated that the association of tumor size with LN metastasis was different in unifocal and multifocal patients ( value for interaction of multifocality and tumor size was equal to 0.03). In the multifocal group, 44.4% of patients with a maximum tumor diameter ≤5 mm had LN metastasis, whereas 38.5% of the patients with maximum tumor diameter >5 mm had LN metastasis. In the unifocal group, only 10.5% patients with maximum diameter ≤5 mm had LN metastasis, whereas 38.5% of the patients with maximum tumor diameter >5 mm had LN metastasis. The association of tumor size with ETE was not statistically different in the unifocal and multifocal group ( value for interaction of multifocality, and tumor size was equal to 0.10), although the prevalence of ETE in the multifocal group was 33.3% in a tumor size ≤5 mm and 38.5% in a tumor size >5 mm. In the unifocal group, the prevalence of ETE was 15.8% in patients with maximum diameter ≤5 mm, whereas it was 33.3% in patients with maximum tumor diameter >5 mm.


UnifocalMultifocal
≤5 mm>5 mm≤5 mm>5 mm
PrevalencePrevalenceOdds ratio (95% CI)PrevalencePrevalenceOdds ratio (95% CI) value

LN metastasis10.526.23.02 (0.87, 10.46)44.438.50.78 (0.14, 4.39)0.03
ETE15.833.32.67 (0.90, 7.87)33.338.51.25 (0.21, 7.41)0.10

value for interaction between tumor size and multifocality.

Preoperative U/S identified all 8 patients with histologically confirmed lateral LN metastasis (sensitivity 100% and specificity 100%). All 8 patients with ultrasonographically suspicious central LN were also histologically confirmed to have central LN metastasis (sensitivity 100% and specificity 100%). The other 12 patients with central LN metastasis did not have ultrasonographically suspicious or enlarged LN, and in these patients, the size of the metastatic foci ranged between 1 and 3 mm in the histopathological examination. In retrospect, these involved small nodes, although not preoperatively characterized as suspicious, were noted and drawn in the U/S diagram. Preoperative U/S was suspicious for ETE in 15 patients with histologically confirmed ETE (sensitivity 53.6% and specificity 100%).

5. Discussion

The goal of this study was to determine the prevalence of LN metastasis and ETE in a cohort of patients with PTMC in Cyprus and to evaluate the role of the preoperative thyroid and neck U/S with LN mapping in assessing these patients.

The prevalence of central LN metastasis in our study is 19.6%. This rate is higher than that of the study by Bradley et al. [40] who showed a 7% prevalence and lower than that of the study by Li et al. who showed a 29.3% prevalence in PTMC patients who underwent prophylactic CLND [20]. CLND alone, without preoperatively examining the lateral neck, may miss “skip metastasis” where metastasis occurs first in the lateral compartment [40, 41]. Skip metastasis was shown in 3.9% of our patients, and this rate is higher compared to Zheng et al. [42] where skip metastasis was observed only in 1.2% of PTMC patients. Our results are similar to a study by Kwak et al. who showed a rate of lateral metastasis of 3.7% in their cohort [21]. However, Luo et al. showed a rate of 5.6% of lateral LN metastasis, and this was associated with multifocality and ETE [22]. Our results confirmed that U/S mapping is a highly reliable and accurate tool in identifying metastatic LN and guiding the surgeon for precise neck dissection. In our study, all lateral metastatic neck LN were identified preoperatively, and our high sensitivity and specificity are in agreement with other published studies [43].

Our ETE prevalence was 27.5%, and this is similar to that of a study by Lee et al. who showed a prevalence of 28% in a series of PTMC patients [26]. Kwak et al., however, showed an ETE prevalence of 40.3% in their PTMC cohort [27], and Zheng et al. showed an even higher prevalence of 65.5% [42]. Our findings showed that the presence of ETE is associated with bigger tumor size and LN metastasis and this was also illustrated by Youngwirth et al. who showed that ETE is strongly associated with metastatic LN [28]. Preoperative neck U/S is also a useful diagnostic tool in evaluating ETE preoperatively. In this regard, our study showed a moderate sensitivity but a high specificity, and this is in agreement with findings from other published studies [27, 44].

Multifocal disease was present in 21.6% of our patients, and this group had a high prevalence of aggressive features with 36.4% of those having ETE and 40.9% of those having lymph node metastasis in either central and/or lateral neck compartments. Our findings agree with those given by Zheng et al. who showed that multifocality is significantly associated with central LN metastasis in PTMC and that this may indicate higher tumor aggressiveness [45]. In our study, the rate of LN metastasis in multifocal tumors with a maximum diameter ≤5 mm was 44.4%, and this was higher to the rate in multifocal patients with a maximum diameter >5 mm. In addition, the high prevalence of ETE even in multifocal PTMC <5 mm suggest that patients with multifocal disease should be managed more aggressively. In the current study, neck ultrasound was highly accurate in the evaluation of multifocality in the preoperative setting.

Our study has some limitations. First, this is a retrospective study of a single institution, which limits the number of cases of patients with PTMC and as our study group is specific our results may not be representative of the entire population of the island. Second, the lateral compartment of the neck was dissected only when there were suspicious or malignant findings. Thus, micrometastatic lateral LN may have been missed. Nonetheless, to the best of our knowledge, this is the first study in Cyprus examining the role of the preoperative U/S examination in patients with PTMC.

In conclusion, the presence of LN metastasis and ETE in our cohort of PTMC patients in Cyprus is frequent. LN metastasis is associated with ETE and multifocality, and this is consistent with previous studies. An unexpectedly high prevalence of aggressive features was observed in multifocal “small” PTMCs less than 5 mm. We propose that multifocality should be considered as a significant risk factor, similar to ETE and LN metastasis, when deciding whether to proceed to USgFNA in subcentimeter nodules and even in <5 mm lesions. As the practice of active surveillance of small “low-risk” lesions gains more acceptance, the careful and detailed U/S examination is becoming even more critical.

Data Availability

The clinical study data used to support the findings of this study are included within the article.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this article.

References

  1. B. James, J. Mitchell, H. Jeon, N. Vasilottos, R. Grogan, and B. Aschebrook-Kilfoy, “An update in international trends in incidence rates of thyroid cancer, 1973–2007,” Cancer Causes & Control, vol. 29, no. 4-5, pp. 465–473, 2018. View at: Publisher Site | Google Scholar
  2. M. Alevizaki, G. Papageorgiou, G. Rentziou et al., “Increasing prevalence of papillary thyroid carcinoma in recent years in Greece: the majority are incidental,” Thyroid, vol. 19, no. 7, pp. 749–754, 2009. View at: Publisher Site | Google Scholar
  3. World Health Organisation, Classification of Tumours: Pathology and Genetics of Tumours of the Endocrine Organs, IARC Press, Lyon, France, 3rd edition, 2004.
  4. S. Gorostis, T. Raguin, O. Schneegans, C. Takeda, C. Debry, and A. Dupret-Bories, “Incidental thyroid papillary microcarcinoma: survival and follow-up,” The Laryngoscope, vol. 129, no. 7, pp. 1722–1726, 2019. View at: Publisher Site | Google Scholar
  5. P. Miccoli, M. N. Minuto, D. Galleri et al., “Incidental thyroid carcinoma in a large series of consecutive patients operated on for benign thyroid disease,” ANZ Journal of Surgery, vol. 76, no. 3, pp. 123–126, 2006. View at: Publisher Site | Google Scholar
  6. J. E. Sandler, H. Huang, N. Zhao et al., “Germline variants in DNA repair genes, diagnostic radiation, and risk of thyroid cancer,” Cancer Epidemiology Biomarkers & Prevention, vol. 27, no. 3, pp. 285–294, 2017. View at: Publisher Site | Google Scholar
  7. V. Vlassopoulou, A. Vryonidou, S. Paschou et al., “No considerable changes in papillary thyroid microcarcinoma characteristics over a 30-year time period,” BMC Research Notes, vol. 9, no. 1, 2016. View at: Publisher Site | Google Scholar
  8. I. S. Hadjisavva, R. Dina, M. A. Talias, and P. A. Economides, “Prevalence of cancer in patients with thyroid nodules in the island of Cyprus: predictive value of ultrasound features and thyroid autoimmune status,” European Thyroid Journal, vol. 4, no. 2, pp. 123–128, 2015. View at: Publisher Site | Google Scholar
  9. P. A. Farazi, “Cancer trends and risk factors in Cyprus,” Ecancermedicalscience, vol. 8, no. 8, p. 389, 2014. View at: Publisher Site | Google Scholar
  10. S. Frangos, I. P. Iakovou, R. J. Marlowe et al., “Difficulties in deciding whether to ablate patients with putatively “low-intermediate-risk” differentiated thyroid carcinoma: do guidelines mainly apply in the centres that produce them? results of a retrospective, two-centre quality assurance study,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 42, no. 13, pp. 2045–2055, 2015. View at: Publisher Site | Google Scholar
  11. B. Haugen, E. Alexander, K. 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, vol. 26, no. 1, pp. 1–133, 2016. View at: Publisher Site | Google Scholar
  12. G. Russ, S. J. Bonnema, M. F. Erdogan, C. Durante, R. Ngu, and L. Leenhardt, “European thyroid association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS,” European Thyroid Journal, vol. 6, no. 5, pp. 225–237, 2017. View at: Publisher Site | Google Scholar
  13. A. Nodules, “American association of clinical endocrinologists, american college of endocrinology, and associazione medici endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules,” Endocrine Practice, vol. 12, no. 1, pp. 63–102, 2016. View at: Google Scholar
  14. P. Perros, S. Colley, K. Boelaert et al., Guidelines for the Management of Thyroid Cancer, British Thyroid Association, London, UK, 2014.
  15. F. Freni, B. Galletti, F. Galletti, and G. Dionigi, “Improved outcomes for papillary thyroid microcarcinoma care: active surveillance and case volume,” Therapeutic Advances in Endocrinology and Metabolism, vol. 9, no. 7, pp. 185-186, 2018. View at: Publisher Site | Google Scholar
  16. S. Xue, P. Wang, J. Liu, and G. Chen, “Total thyroidectomy may be more reasonable as initial surgery in unilateral multifocal papillary thyroid microcarcinoma: a single-center experience,” World Journal of Surgical Oncology, vol. 15, no. 1, 2017. View at: Publisher Site | Google Scholar
  17. S.-M. Chow, S. C. K. Law, J. K. C. Chan, S.-K. Au, S. Yau, and W.-H. Lau, “Papillary microcarcinoma of the thyroid?Prognostic significance of lymph node metastasis and multifocality,” Cancer, vol. 98, no. 1, pp. 31–40, 2003. View at: Publisher Site | Google Scholar
  18. L. Shirley, N. Jones, and J. Phay, “The role of central neck lymph node dissection in the management of papillary thyroid cancer,” Frontiers in Oncology, vol. 7, 2017. View at: Publisher Site | Google Scholar
  19. S. Frangos, I. P. Iakovou, R. J. Marlowe et al., “Acknowledging gray areas: 2015 vs. 2009 American Thyroid Association differentiated thyroid cancer guidelines on ablating putatively low-intermediate-risk patients,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 44, no. 2, pp. 185–189, 2016. View at: Publisher Site | Google Scholar
  20. M. Li, X. Y. Zhu, J. Lv et al., “Risk factors for predicting central lymph node metastasis in papillary thyroid microcarcinoma (CN0): a study of 273 resections,” European Review for Medical and Pharmacological Sciences, vol. 21, no. 17, pp. 3801–3807, 2017. View at: Google Scholar
  21. J. Y. Kwak, E.-K. Kim, M. J. Kim et al., “Papillary microcarcinoma of the thyroid: predicting factors of lateral neck node metastasis,” Annals of Surgical Oncology, vol. 16, no. 5, pp. 1348–1355, 2009. View at: Publisher Site | Google Scholar
  22. Y. Luo, Y. Zhao, K. Chen et al., “Clinical analysis of cervical lymph node metastasis risk factors in patients with papillary thyroid microcarcinoma,” Journal of Endocrinological Investigation, vol. 42, no. 2, pp. 227–236, 2019. View at: Publisher Site | Google Scholar
  23. L. Yang, W. Shen, and N. Sakamoto, “Population-based study evaluating and predicting the probability of death resulting from thyroid cancer and other causes among patients with thyroid cancer,” Journal of Clinical Oncology, vol. 31, no. 4, pp. 468–474, 2013. View at: Publisher Site | Google Scholar
  24. S. Y. Choi, J.-K. Cho, J. H. Moon, and Y.-I. Son, “Metastatic lymph node ratio of central neck compartment has predictive values for locoregional recurrence in papillary thyroid microcarcinoma,” Clinical and Experimental Otorhinolaryngology, vol. 9, no. 1, pp. 75–79, 2016. View at: Publisher Site | Google Scholar
  25. H. Yamashita, S. Noguchi, N. Murakami, H. Kawamoto, and S. Watanabe, “Extracapsular invasion of lymph node metastasis is an indicator of distant metastasis and poor prognosis in patients with thyroid papillary carcinoma,” Cancer, vol. 80, no. 12, pp. 2268–2272, 1997. View at: Publisher Site | Google Scholar
  26. J. Lee, Y. Rhee, S. Lee et al., “Frequent, aggressive behaviors of thyroid microcarcinomas in Korean patients,” Endocrine Journal, vol. 53, no. 5, pp. 627–632, 2006. View at: Publisher Site | Google Scholar
  27. J. Y. Kwak, E.-K. Kim, J. H. Youk et al., “Extrathyroid extension of well-differentiated papillary thyroid microcarcinoma on US,” Thyroid, vol. 18, no. 6, pp. 609–614, 2008. View at: Publisher Site | Google Scholar
  28. L. M. Youngwirth, M. A. Adam, R. P. Scheri, S. A. Roman, and J. A. Sosa, “Extrathyroidal extension is associated with compromised survival in patients with thyroid cancer,” Thyroid, vol. 27, no. 5, pp. 626–631, 2017. View at: Publisher Site | Google Scholar
  29. N. Chereau, E. Dauzier, G. Godiris–Petit et al., “Risk of recurrence in a homogeneously managed pT3-differentiated thyroid carcinoma population,” Langenbeck’s Archives of Surgery, vol. 403, no. 3, pp. 325–332, 2018. View at: Publisher Site | Google Scholar
  30. C. Zhao, W. Jiang, Y. Gao, W. Niu, X. Zhang, and L. Xin, “Risk factors for lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC): role of preoperative ultrasound,” Journal of International Medical Research, vol. 45, no. 3, pp. 1221–1230, 2017. View at: Publisher Site | Google Scholar
  31. E. J. Kuo, P. Goffredo, J. A. Sosa, and S. A. Roman, “Aggressive variants of papillary thyroid microcarcinoma are associated with extrathyroidal spread and lymph-node metastases: a population-level analysis,” Thyroid, vol. 23, no. 10, pp. 1305–1311, 2013. View at: Publisher Site | Google Scholar
  32. R. Ghossein, I. Ganly, A. Biagini, E. Robenshtok, M. Rivera, and R. M. Tuttle, “Prognostic factors in papillary microcarcinoma with emphasis on histologic subtyping: a clinicopathologic study of 148 cases,” Thyroid, vol. 24, no. 2, pp. 245–253, 2014. View at: Publisher Site | Google Scholar
  33. G. Ardito, L. Revelli, E. Giustozzi et al., “Aggressive papillary thyroid microcarcinoma,” Clinical Nuclear Medicine, vol. 38, no. 1, pp. 25–28, 2013. View at: Publisher Site | Google Scholar
  34. X.-M. Yu, Y. Wan, R. S. Sippel, and H. Chen, “Should all papillary thyroid microcarcinomas Be aggressively treated?” Annals of Surgery, vol. 254, no. 4, pp. 653–660, 2011. View at: Publisher Site | Google Scholar
  35. M. R. M. Machado, M. R. Tavares, C. A. Buchpiguel, and M. C. Chammas, “Ultrasonographic evaluation of cervical lymph nodes in thyroid cancer,” Otolaryngology-Head and Neck Surgery, vol. 156, no. 2, pp. 263–271, 2016. View at: Publisher Site | Google Scholar
  36. M. W. Yeh, A. J. Bauer, V. A. Bernet et al., “American thyroid association statement on preoperative imaging for thyroid cancer surgery,” Thyroid, vol. 25, no. 1, pp. 3–14, 2015. View at: Publisher Site | Google Scholar
  37. E. J. Chisholm, P. Economides, B. Elmiyeh, C. Pepper, R. Dwivedi, and P. H. Rhys-Evans, “Pictorial ultrasound reports combined with fine needle washout thyroglobulin assay to aid thyroid surgery,” The Laryngoscope, vol. 121, no. 6, pp. 1231-1232, 2011. View at: Publisher Site | Google Scholar
  38. H. Kim, J.-A. Kim, E. J. Son et al., “Preoperative prediction of the extrathyroidal extension of papillary thyroid carcinoma with ultrasonography versus MRI: a retrospective cohort study,” International Journal of Surgery, vol. 12, no. 5, pp. 544–548, 2014. View at: Publisher Site | Google Scholar
  39. J. S. Choi, J. Kim, J. Y. Kwak, M. J. Kim, H. S. Chang, and E.-K. Kim, “Preoperative staging of papillary thyroid carcinoma: comparison of ultrasound imaging and CT,” American Journal of Roentgenology, vol. 193, no. 3, pp. 871–878, 2009. View at: Publisher Site | Google Scholar
  40. N. Bradley and S. Wiseman, “Papillary thyroid microcarcinoma: the significance of high risk features,” BMC Cancer, vol. 17, no. 1, 2017. View at: Publisher Site | Google Scholar
  41. Y. S. Lee, S.-C. Shin, Y.-S. Lim et al., “Tumor location-dependent skip lateral cervical lymph node metastasis in papillary thyroid cancer,” Head & Neck, vol. 36, no. 6, pp. 887–891, 2014. View at: Publisher Site | Google Scholar
  42. X. Zheng, P. Chen, G. Ming et al., “Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: a study of 1,587 patients,” Cancer Biology & Medicine, vol. 16, no. 1, p. 121, 2019. View at: Publisher Site | Google Scholar
  43. D. Kocharyan, F. Schwenter, M. Bélair, and E. Nassif, “The relevance of preoperative ultrasound cervical mapping in patients with thyroid cancer,” Canadian Journal of Surgery, vol. 59, no. 2, pp. 113–117, 2016. View at: Publisher Site | Google Scholar
  44. K. Shimamoto, H. Satake, A. Sawaki, T. Ishigaki, H. Funahashi, and T. Imai, “Preoperative staging of thyroid papillary carcinoma with ultrasonography,” European Journal of Radiology, vol. 29, no. 1, pp. 4–10, 1998. View at: Publisher Site | Google Scholar
  45. W. Zheng, K. Wang, J. Wu, W. Wang, and J. Shang, “Multifocality is associated with central neck lymph node metastases in papillary thyroid microcarcinoma,” Cancer Management and Research, vol. 10, pp. 1527–1533, 2018. View at: Publisher Site | Google Scholar

Copyright © 2020 Christos Papaioannou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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