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Year : 2018  |  Volume : 14  |  Issue : 9  |  Page : 319-323

Ultrasonography is valuable in evaluation of papillary thyroid microcarcinoma based on 5 mm tumor size

Department of Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China

Date of Web Publication29-Jun-2018

Correspondence Address:
Weiwei Zhan
Department of Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.235347

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 > Abstract 

Introduction: Fine-needle aspiration was once done in suspected malignant thyroid nodules more than 5 mm in diameter. Five millimeter has been applied in many studies as the cut off tumor size in recent years. In this study, we would like to analyze the clinicopathological and ultrasonographic features of papillary thyroid microcarcinoma (PTMC) ≤5 mm and >5 mm with the aim of finding out the diagnostic value of ultrasonography.
Subjects and Methods: A total of 291 patients from January 2012 to October 2014 who underwent an ultrasound examination and were postoperatively diagnosed as PTMC were enrolled in the study. The patients were divided into Group A (≤5 mm) and Group B (>5 mm, ≤10 mm) based on diameter. The clinicopathological and ultrasonographic features of the two groups were statistically analyzed.
Results: In total, 291 thyroid tumors were analyzed in 291 patients. In patients who were identified with multiple tumors, the largest nodule in size was used for analysis. PTMC >5 mm in diameter were found with a higher incidence of lymph node metastasis and advanced tumor-node-metastasis (TNM) Stage (III/IV) with a significant difference, also with a larger part of multiple tumors compared to PTMC <5 mm. Of all the ultrasonographic features studied, calcification and peripheral halo were more significantly correlated with PTMC >5 mm. The presence of vascularity and blood supply were both associated with the tumor size.
Conclusion: Larger tumor size of PTMC is more likely to involve in lymph node metastasis and advanced TNM stage. Correlation of tumor size with calcification, peripheral halo, vascularity, and blood supply do exist in PTMC. Ultrasound is of great value in the evaluation of PTMC.

Keywords: 5 mm, clinicopathological, papillary thyroid microcarcinoma, ultrasonographic

How to cite this article:
Xia S, Dong Y, Kang H, Zhan W. Ultrasonography is valuable in evaluation of papillary thyroid microcarcinoma based on 5 mm tumor size. J Can Res Ther 2018;14, Suppl S2:319-23

How to cite this URL:
Xia S, Dong Y, Kang H, Zhan W. Ultrasonography is valuable in evaluation of papillary thyroid microcarcinoma based on 5 mm tumor size. J Can Res Ther [serial online] 2018 [cited 2020 Oct 30];14:319-23. Available from: https://www.cancerjournal.net/text.asp?2018/14/9/319/235347

 > Introduction Top

The yearly incidence of thyroid carcinoma has tripled these years,[1] among which papillary thyroid microcarcinoma (PTMC) accounted for the most. The revised American Thyroid Association guideline in 2009 recommended 5 mm as the cut-off size for fine-needle aspiration which is the preferential examination in suspicious patients.[2] In recent years, 5 mm has been applied in many studies as the cut off tumor size. The difference of clinicopathological characteristics of PTMC based on 5mm tumor size remains controversial.[3] In this study, we would like to analyze the clinicopathological and ultrasonographic features of PTMC ≤5 mm and >5 mm with the aim of finding out the diagnostic value of ultrasonography.

 > Subjects and Methods Top

Informed consent was waived as there were no potential interests or harm to the patients. The retrospective study was approved by the Institutional Review Board in our hospital. Patient information in our study was anonymized and de-identified prior to analysis.

Clinicopathological features

Patients' data were acquired and retrospectively reviewed in the database of our department. We enrolled 291 patients who were diagnosed as PTMC from January 2012 to October 2014. All of the patients had underwent preoperative thyroid ultrasound examination, and the diagnosis of PTMC was verified by postoperative histopathological examination. All the patients had a lobectomy or total thyroidectomy with prophylactic central compartment neck dissection, and some of them also had lateral compartment neck dissection. These patients were divided into two groups Group A and Group B. Group A included 152 patients with tumor size ≤5 mm while Group B included 139 patients with tumor size >5 mm and ≤10 mm. The classification of the patients was based on the pathological diagnosis. In patients who were identified with multiple tumors, the largest one in size was used for analysis. Tumor-node-metastasis (TNM) stage was classified according to the guideline of American Joint Committee on Cancer (AJCC) TNM staging system (7th edition).

Image acquisition

Thyroid ultrasound examination was performed with a 5–12 MHz linear array transducer. Philips iU22 (Philips Ultrasound, USA) and ESAOTE My Lab 90 (ESAOTE, Italy) ultrasound diagnostic equipment were used for analysis. Patients were in a supine position, and the anterior thyroid area was exposed. Multi-slice scanning of each tumor was performed by two radiologists with more than 10 years of experience in thyroid ultrasound. The ultrasonographic features of the thyroid tumors were observed. The location, edge (well-/ill-defined), borders (clear/unclear), internal structure (solid/mainly solid/mainly cystic), echo (markedly hypoechoic/hypoechoic/isoechoic/hyperechoic), calcification (without/micro/coarse), peripheral halo (without/hypoechoic/hyperechoic), ultrasound attenuation (without/with/enhance), acoustic shadow (with/without), and degree of capsular abutment were recorded. Color-Doppler ultrasound was also included to analyze the vascularity (without/peripheral/marked intranodular/mixed) and blood supply (without/low/intermediate/high) of the tumors. The location of each tumor was described as left lobe, right lobe, and isthmus. A homogeneous ground-glass appearance was defined as homogeneous echogenicity. Otherwise, heterogeneous echogenicity was recorded. The capsular abutment was recognized as lacking of intervening tissue between the thyroid capsule and thyroid nodule. The degree of the capsular abutment was classified as 0–25 patients, 25–50 patients, 50–75 patients, and 75–100 patients.

Statistical analysis

The statistical analysis was performed with IBM Statistical Product and Service Solutions (version 19.0; SPSS, Chicago, IL, USA). Descriptive statistics were presented as the mean ± standard deviation; categorical variables were presented as proportions and frequencies. Pearson's Chi-square (χ2) test and Fisher's exact test were used to analyze the categorical data. Independent two-sample t-test was performed to compare the descriptive statistics as appropriate. P < 0.05 was considered to indicate a statistically significant difference in all tests.

 > Results Top

Clinicopathological features

Patients' clinical and pathological features were summarized in [Table 1] and [Table 2]. The data indicated that there were no difference in clinicopathological characteristics of the patients except for multifocality, lymph node status, and AJCC TNM stage. Patients with PTMC >5 mm in diameter had a higher incidence of multifocality, lymph node metastasis, and advanced TNM Stage (III/IV) compared with PTMC ≤5 mm.
Table 1: Clinicopathological features of the studied patients

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Table 2: Lymph node metastasis and TNM stage of the two groups

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Ultrasonographic features

Of these thyroid tumors analyzed, there were no significant differences about the location distribution of these tumors in the two groups [Table 3]. The ultrasonographic features under grey-scale ultrasound showed no significant differences except for calcification and peripheral halo [Table 4], [Figure 1]. Furthermore, there was a positive association between larger tumor size and vascularity as well as blood supply under color-Doppler ultrasound [Table 5], [Figure 2]. However, the subtypes of vascularity (peripheral, marked intranodular, and mixed) and blood supply (low, intermediate, and high) did not show any correlation with the tumor size. There was no significant difference as for the edge, boundary, cystic change, echo of solid component, and echogenicity. Moreover, there was no significant difference with regard to the ultrasound attenuation and acoustic shadow between the two groups.
Table 3: Location of the analyzed tumors

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Table 4: Features under grey-scale ultrasound of the two groups

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Figure 1: (a and b) Papillary thyroid microcarcinoma detected in a 57-year-old male with the tumor size of 9.4 mm × 6.7 mm × 6.0 mm. It was a hypoechoic nodule with microcarcification and hypoechoic peripheral halo. Left II/III/VI area were involved with lymph node metastasis

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Table 5: Features under color doppler ultrasound of the two groups

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Figure 2: Vascularity and blood supply of papillary thyroid microcarcinoma. (a) Papillary thyroid microcarcinoma ≤p mm, without vascularity, the absence of blood supply. (b) Papillary thyroid microcarcinoma ≤5 mm, peripheral vascularity, low blood supply. (c) Papillary thyroid microcarcinoma >5 mm, mixed vascularity, high blood supply. (d) Papillary thyroid microcarcinoma >5 mm, intranodular vascularity, intermediate blood supply

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 > Discussion Top

The retrospective study was performed, and the clinicopathological, and ultrasonographic features of the PTMCs were analyzed. Larger tumor size has been previously recognized to be related to aggressive features such as lymph node metastasis, extrathyroid extention, capsule invasion and distant metastasis.[4] Similarly, in our study, we found that PTMC >5 mm had a higher incidence of lymph node metastasis, which was consistent with the previous study,[3] which indicates that there is a positive association between larger tumor size and lymph node metastasis. However, there was no significant difference as for extrathyroid extention, and the incidence of extrathyroid extention was very low. Cervical lymph node metastasis is related to the higher possibility of recurrence.[5] Even though several previous studies have shown no significant differences in recurrence between PTMC ≤5 mm and PTMC >5 mm,[6] the examination of lymph node metastasis in PTMC should be carefully carried out by the sonographer.

Multifocality is another independent risk factor that could predict lymph node metastasis and recurrence.[7] According to our data, multiple tumors were more likely to be found in patients with larger tumor size regardless of bilaterality or unilaterality, which was not consistent with the previous study.[7] The largest tumor in the size of the patient was considered as the criteria of grouping even though there were coexistent tumors ≤5 mm in diameter. Disregard of the small coexistent tumors may lead to bias in our study.

Since AJCC published the first edition of TNM staging system in 1977, persistent challenges have always been existed that TNM staging system of thyroid cancer does not meet needs of clinicians and patients; TNM stage is largely limited to anatomic information and TNM must maintain the anatomic base. In our study, patients were classified based on AJCC guideline. Finally, the patients were classified into three Stages (I, III, IV) with the absence of Stage II. Advanced Stage (III/IV) accounted for a larger incidence in PTMC >5mm while early stage were more likely to be related with PTMC ≤5 mm. The study showed that Stage II was absent in TNM stage in terms of PTMC. The definition of Stage II was TxNxM1 (any T stage, any N stage and M1) under the age of 45 years old or T2N0M0 (tumor size 2~4 cm without lymph node involvement and distant metastasis) no <45 years old, and also the incidence of M1 (distant metastasis) is actually low; therefore, Stage II in PTMC seldom exists.

Calcification is a common feature in thyroid diseases, which can be detected both in benign and malignant tumors with different performances. Microcalcification in thyroid tumors, which is pathologically diagnosed as psammoma bodies containing 10–200 μm rough, smooth and bright calcific aggregations under a light microscope, has a very high suspicion for thyroid carcinoma,[8] while coarse calcification has been found to be a less valuable indicator for malignancy.[9] It was reported that microcalcification forms as a result of autocrine tumor cells growth while coarse calcification may occur secondary to dystrophic calcification with the process of rapid growth of tumor cells, degeneration, and the subsequent calcium deposition.[10] Thus, tumors with microcalcifications would be considered as an indicator of malignancy. In the current study, the presence of microcalcification accounted for a larger part in PTMC >5 mm. This was the same case referring to coarse calcification. Statistically significant difference in calcification was identified between the two groups.

Peripheral halo is a kind of echogenic rim surrounding the tumors.[11] Halos around benign tumors are commonly regarded as a small vessel, edema or mucoid degeneration under ultrasonographic imaging. Irregular hypogenic halo which is pathologically diagnosed as fibrous capsule without blood vessel usually predicts malignancy, folicular adenoma or Hurthle cell adenoma.[12] Previous findings indicated that the capsule tends to be thicker and more irregular in follicular carcinomas than adenomas.[13] In our study, a small part of the tumors were found with peripheral halo, including hypoechoic halo and hyperechoic halo. The study showed a positive correlation of peripheral halo and tumor size. A possible explanation is that the formation of the halo is resulted by a progressing desmoplastic reaction or fibrosis around a slowly growing malignancy.[14]

Hypoxia in tumors induces angiogenesis which restores a supply of nutrients and further facilitates rapid tumor growth. Thus neovascularization is regarded as a common phenomenon in malignant tumors. Under color-Doppler ultrasound, abundant blood flow in malignant tumors is the result of neovascularization. Several studies demonstrated that high degree of blood flow in thyroid nodules was associated with poor prognosis.[15] Our data revealed that tumors with larger diameter were more likely to be involved with abundant blood supply, which was rare in smaller tumors. The study also showed significant difference with regard to the vascularity between the two groups. The reason why smaller tumors are found with sparse blood supply may be because the low-velocity blood signals could not be shown due to the smaller size of the tumors.

There are some limitations in the study. Since we only included the largest tumor in size in patients with multiple tumors, selection bias may exist in the study. Moreover, nodules that are too small would probably be hardly detected or precisely evaluated even by high-resolution ultrasound. This might result in information bias in the analyzed materials.

 > Conclusion Top

Larger tumor size of PTMC is more likely to be involved in lymph node metastasis and advanced TNM stage. Calcification, peripheral halo, vascularity and blood supply in ultrasonography are positively correlated with larger tumor size in PTMC. Ultrasound is of great value in the evaluation of PTMC.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 2014;140:317-22.  Back to cited text no. 1
American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214.  Back to cited text no. 2
Kim E, Choi JY, Koo do H, Lee KE, Youn YK. Differences in the characteristics of papillary thyroid microcarcinoma ≤5 mm and >5 mm in diameter. Head Neck 2015;37:694-7.  Back to cited text no. 3
Lim YS, Lee JC, Lee YS, Lee BJ, Wang SG, Son SM, et al. Lateral cervical lymph node metastases from papillary thyroid carcinoma: Predictive factors of nodal metastasis. Surgery 2011;150:116-21.  Back to cited text no. 4
Ross DS, Litofsky D, Ain KB, Bigos T, Brierley JD, Cooper DS, et al. Recurrence after treatment of micropapillary thyroid cancer. Thyroid 2009;19:1043-8.  Back to cited text no. 5
Mercante G, Frasoldati A, Pedroni C, Formisano D, Renna L, Piana S, 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.  Back to cited text no. 6
Mantinan B, Rego-Iraeta A, Larrañaga A, Fluiters E, Sánchez-Sobrino P, Garcia-Mayor RV. Factors influencing the outcome of patients with incidental papillary thyroid microcarcinoma. J Thyroid Res 2012;2012:469397.  Back to cited text no. 7
Chammas MC, de Araujo Filho VJ, Moysés RA, Brescia MD, Mulatti GC, Brandão LG, et al. Predictive value for malignancy in the finding of microcalcifications on ultrasonography of thyroid nodules. Head Neck 2008;30:1206-10.  Back to cited text no. 8
Kim BK, Choi YS, Kwon HJ, Lee JS, Heo JJ, Han YJ, et al. Relationship between patterns of calcification in thyroid nodules and histopathologic findings. Endocr J 2013;60:155-60.  Back to cited text no. 9
Das DK. Psammoma body: A product of dystrophic calcification or of a biologically active process that aims at limiting the growth and spread of tumor? Diagn Cytopathol 2009;37:534-41.  Back to cited text no. 10
Sillery JC, Reading CC, Charboneau JW, Henrichsen TL, Hay ID, Mandrekar JN. Thyroid follicular carcinoma: Sonographic features of 50 cases. AJR Am J Roentgenol 2010;194:44-54.  Back to cited text no. 11
Propper RA, Skolnick ML, Weinstein BJ, Dekker A. The nonspecificity of the thyroid halo sign. J Clin Ultrasound 1980;8:129-32.  Back to cited text no. 12
Sobrinho-Simões M, Eloy C, Magalhães J, Lobo C, Amaro T. Follicular thyroid carcinoma. Mod Pathol 2011;24 Suppl 2:S10-8.  Back to cited text no. 13
Zhang JZ, Hu B. Sonographic features of thyroid follicular carcinoma in comparison with thyroid follicular adenoma. J Ultrasound Med 2014;33:221-7.  Back to cited text no. 14
Zhan WW, Zhou P, Zhou JQ, Xu SY, Chen KM. Differences in sonographic features of papillary thyroid carcinoma between neck lymph node metastatic and nonmetastatic groups. J Ultrasound Med 2012;31:915-20.  Back to cited text no. 15


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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