Ultrasonography features of medullary thyroid cancer as predictors of its biological behavior

Abstract

Background

Although there are many well-known prognostic predictors of medullary thyroid carcinoma (MTC), the ultrasonography (US) findings of MTC have not been sufficiently validated in this regard.

Purpose

To investigate the US findings of MTC and their relationship with the biological behavior of MTC.

Material and Methods

The US findings and clinical and pathology records of 123 MTC nodules from 108 patients were retrospectively analyzed at two tertiary referral hospitals. MTCs were classified according to US findings, i.e. MTC with benign (B-MTC) and malignant US findings (M-MTC). We then compared the clinical and pathology findings between the two groups.

Results

Eighty-two M-MTCs (66.7%) and 41 B-MTCs (33.3%) were identified. M-MTCs showed a significantly higher prevalence of lateral lymph node metastases as well as extrathyroidal and extranodal extension (all P < 0.05). M-MTCs larger than 1 cm showed a significantly higher prevalence of multifocality, recurrence, extrathyroidal and extranodal extension than B-MTCs larger than 1 cm in the largest dimension (all P < 0.05). Tumors > 1 cm were more likely to be B-MTC and one-third of all MTCs had benign US features. The common findings of B-MTC included a solid, ovoid to round shape, with a smooth margin, hypoechogenicity, and without calcification.

Conclusion

The biological behavior of M-MTCs results in poorer outcomes than that of B-MTCs.

Keywords

Medullary thyroid cancer ultrasonography biological behavior recurrence prognosis

Introduction

Medullary thyroid cancer (MTC) is rare type of thyroid malignancy arising from parafollicular C cells of the thyroid glands that produces calcitonin. MTC accounts for 3–10% of all thyroid cancers, although it has more aggressive behavior than other types of thyroid cancers and up to 13.4% of all thyroid cancer patient deaths due are related to this type of malignancy (1 –4).

Regarding the most common type of thyroid cancer, papillary thyroid cancer (PTC), it has recently been reported that preoperative ultrasonography (US) findings can also predict its biological behavior (5), i.e. PTC with benign US features had a better prognosis than PTC with malignant US features. Although a variety of clinical and pathologic factors, such as the patient age at the time of the initial diagnosis, extrathyroidal extension, and vascular invasion, are already known prognostic factors for MTC (3,6 –8), only one previous study has reported on US features for predicting the prognosis of MTC (9). However, there was only a small number of patients included in that study. In addition, although calcitonin is known as a useful biomarker for detecting and monitoring macroscopic MTC (10), imaging studies such as US and/or US-guided biopsy are also important for diagnosing MTC. However, to date, only a few studies regarding the US findings of MTC have been performed (11 –13), and the general understanding of the US findings of MTC is still not sufficient.

Therefore, the purpose of our current study was to more fully investigate the US findings for MTC and examine their relationship with the biological behavior of these tumors.

Material and Methods

Patients

Institutional Review Board approval was obtained from Asan Medical Center and Ajou University School of Medicine, which were the two tertiary-care medical institutions involved in this study, and the requirement for informed consent was waived due to the retrospective nature of the analyses. From January 2000 to March 2012, a combined total of 117 patients at both institutions underwent total- or hemi-thyroidectomy with lymph node dissection for detecting MTCs. Nine patients were excluded as they had not undergone preoperative thyroid US. Finally, 123 nodules from 108 patients were included in our present analysis (77 women, 31 men; mean age, 48 ± 15.2 years; age range, 13–81 years). Among these patients, 13 patients had two MTCs (12%) and one patient had three MTCs (0.9%). Eleven patients had MEN type IIa (10.2%), while 97 patients had sporadic MTCs (89.8%).

Among the involved patients, MTCs from 86 patients in our study series were also used in another study conducted by our group, which was recently accepted for publication in another journal. However, that manuscript dealt with the role of core needle biopsy in patients with MTC, an entirely different topic, and there is no association between the two studies.

Image analysis and nodule classification according to the US features

All patients underwent preoperative, high-resolution, thyroid US examinations using one of two systems, i.e. an iU22 unit (Philips Healthcare, Bothell, WA, USA) or an EUB-7500 unit (Hitachi Medical Systems, Tokyo, Japan), equipped with a linear, high-frequency probe (5–14 MHz). All US images were retrospectively reviewed by two radiologists (CK and EJH).

US findings, including the composition of the solid component, shape, margin, echogenicity, and calcifications, were evaluated (14). The composition of the nodules was defined as solid (more than 90% of the solid component), predominantly solid (more than 50% but less than 90% of the solid component), predominantly cystic (more than 50% but less than 90% of the cystic component), and cystic (more than 90% of the cystic component). The nodule shape was defined as ovoid to round, taller than wide (i.e. the antero-posterior diameter was longer than the transverse diameter), or irregular. The margin was defined as smooth, spiculated, or ill-defined. The echogenicity was defined as marked hypoechoic, hypoechoic, isoechoic, or hyperechoic. The reference echogenicity was that of the thyroid tissue, and the reference echogenicity of “marked hypoechoic” was that of the strap muscle. Calcifications were defined as micro-calcifications (less than 1 mm in largest diameter), macro-calcifications (more than 1 mm in largest diameter), and rim calcifications (11 –13,15).

All lesions were categorized according to their US features, i.e. malignant and probably benign. The malignant US features were defined as taller than wide, a spiculated border, marked hypoechogenicity, or as micro- or macro-calcifications (5,11,12). If a lesion had at least one of these malignant findings, it was regarded as a malignant nodule. Probably benign nodules were classified as nodules with no malignant US features. With respect to the lesion size, the largest diameter measured by US was recorded, and the lesions were classified as 1 cm, less than 1 cm (<1 cm), or greater than 1 cm (>1 cm) at the largest diameter.

Postoperative follow-up and evaluation of recurrence

The calcitonin level, apart from in 12 patients who were not diagnosed preoperatively, was measured prior to surgery; the normal range for the immunoradiometric assay was 10 pg/mL. The postoperative calcitonin was measured in all patients 3 or 6 months after the date of surgery and the lowest calcitonin level was chosen for analysis considering the normalization time after surgery (6,16 –18). We measured calcitonin levels before and after stimulation by calcium gluconate with or without tetragastrin, about 1 week after surgery. A biochemical cure was defined by a basal calcitonin level within the normal range and a peak calcitonin level less than threefold greater than the basal calcitonin level (9,19,20).

Systemic imaging examinations such as thyroid US, CT scans, or PET-CT were performed every 6 months or annually. If findings suggesting recurrence or distant metastases were observed by these imaging studies, with or without pathology confirmation, we regarded this as local tumor recurrence or distant metastasis. We also identified time to progression (TTP). The definition of TTP was from the date of surgery to the date of new local tumor recurrence or distant metastasis. The mean postoperative follow-up period was 63.2 ± 33.9 months (range, 12–134 months).

Histopathology

Histopathology results were based on the pathology reports. Tumor node metastasis (TNM) staging was assessed using the American Joint Committee on Cancer/International Union Against Cancer pathologic TNM classification criteria (21). The multifocality of tumors, the presence of extrathyroidal extension, and extranodal extension of metastatic lymph nodes were also assessed.

Statistical analysis

The clinical characteristics of the study patients were compared statistically between MTCs with benign (B-MTCs) and malignant US findings (M-MTCs). Clinical and pathological characteristics, such as age, genetic type, biochemical cure, multifocality, lymph node metastasis, TNM staging, distant metastasis, and extrathyroidal and extranodal extension in patients with B-MTCs and M-MTCs, were compared according to tumor size. US findings of B-MTCs and M-MTCs were also compared. Comparison of the clinical manifestations between M-MTCs with only one or more than one malignant US feature was also performed.

The Student’s t-test or the Mann–Whitney U test was used for the continuous numerical variables. The Chi-square test or Fisher’s exact test was used for categorical variables. Multivariate analysis of the biological behaviors of B-MTC and M-MTC was performed using logistic regression analysis. TTP of both groups were compared using Kaplan–Meier survival analysis with a log-rank test. All statistical analyses were performed using SPSS software (SPSS, Chicago, IL, USA) and a P value < 0.05 was determined to be statistically significant.

Results

The M-MTCs examined in this study comprised 82 tumors (66.7%) in 73 patients, and the B-MTCs comprised 41 tumors (33.3%) in 35 patients. A comparison of the clinical characteristics of patients with B-MTCs or M-MTCs is presented in Table 1. M-MTCs showed a significantly higher prevalence of lateral lymph node metastases as well as extrathyroidal and extranodal extension than B-MTCs (P = 0.014, P = 0.011, and P = 0.015, respectively). Other variables, such as TNM staging, tumor recurrence, and biochemical cure, did not show a significant difference between the two groups. The number of tumors larger than 1 cm at the largest diameter was greater for B-MTCs than for M-MTCs, however, this difference was not significant (P = 0.063). B-MTCs showed a higher mean preoperative calcitonin level and a lower mean postoperative calcitonin level than M-MTCs, although this difference was also not significant (P = 0.979 and P = 0.394). TTP of both groups was not significantly different (Fig. 1).

Fig. 1.

Kaplan–Meier analysis of the time to progression of both groups. (M-MTC, medullary thyroid cancer with malignant US features; B-MTC, medullary thyroid cancer with benign US features).

Table 1.

Clinical characteristics of the study patients with B-MTCs and M-MTCs.

Variable	B-MTCs (n = 41)	M-MTCs (n = 82)	Total (n = 123)	P value
Age (years)	47.5 ± 17.3	48.3 ± 14.1	48 ± 15.2	0.793
Gender (M:F)	13:28	23:59	36:87	0.674
Tumor size (mm)	21.9 ± 14.1	18.8 ± 14.4	19.8 ± 14.4	0.178
≤1.0 cm (%)*	10 (28.6)	34 (46.6)	44 (40.7)	0.063
>1.0 cm (%)*	31 (88.6)	48 (65.7)	79 (73.1)	0.063
Mean preoperative CT level (pg/mL)	2004.8	1250.2	1499.4	0.979
Mean postoperative CT level (pg/mL)	49	142.9	111.6	0.394
Biochemical cure (%)	35 (85.3)	62 (75.6)	97 (78.9)	0.212
Genetic type				0.448
Hereditary type (%)	4 (9.8)	12 (14.6)	16 (13)
Sporadic type (%)	37 (90.2)	70 (85.4)	107 (87)
Multifocality (%)	8 (19.5)	24 (29.3)	32 (26)	0.245
LN metastasis	19 (46.3)	45 (54.9)	64 (52)	0.372
Central (%)	12 (29.2)	13 (15.9)	25 (20.3)	0.081
Lateral (%)	7 (17.1)	32 (39.0)	39 (47.6)	0.014
UICC TNM stage				0.698
Low stage (I, II)	18 (43.9)	33 (40.2)	51 (41.5)
High stage (III, IV)	23 (56.1)	49 (59.8)	72 (58.5)
Distant metastasis at the initial diagnosis	2 (5.7)	3 (4.1)	5 (4.6)	1.0
Lung^†	0	3 (3.7)	3 (2.4)	0.550
Bone^†	1 (2.4)	2 (2.4)	3 (2.4)	1.0
Liver^†	1 (2.4)	1 (1.2)	2 (1.6)	1.0
Recurrence (%)^‡	4 (9.8)	18 (22.0)	22 (17.9)	0.096
Extrathyroidal extension (%)	2 (4.9)	19 (23.2)	21 (17.1)	0.011
Extranodal extension (%)	4 (9.8)	24 (29.3)	28 (22.8)	0.015

Number of sites

†

Number of patients

‡

Defined as the presence of radiologic or pathologic evidence of recurrent disease

B-MTC, medullary thyroid cancer with benign US features; CT, calcitonin; LN, lymph nodes; M-MTC, medullary thyroid cancer with malignant US features.

In the subgroup analysis according to the tumor size, M-MTCs greater than 1 cm in diameter showed a significantly higher incidence of multifocality, recurrence, extrathyroidal extension, and extranodal extension than B-MTCs greater than 1 cm (Table 2). In the subgroup of patients with tumors ≤ 1 cm, no factor showed a significant difference between B-MTCs and M-MTCs. There were also no patients with distant metastasis in which the tumor diameter was ≤ 1 cm, regardless of the US features.

Table 2.

Univariate analysis of the clinical characteristics of the B-MTC and M-MTC patients according to tumor size.

Variables	≤1.0 cm			>1.0 cm			All
Variables	B-MTCs	M-MTCs	P value	B-MTCs	M-MTCs	P value	B-MTCs	M-MTCs	P value
Number (%)	10 (24.4)*	34 (41.2)^†		31 (75.6)*	48 (58.5)^†		41 (100)	82 (100)
Tumor size (mm)	6.3 ± 2.1	7.0 ± 2.6	0.414	26.9 ± 12.6	27.2 ± 13.5	0.940			0.178
Age (years)	45.4 ± 19.7	50.3 ± 12.8	0.358	48.2 ± 16.8	46.9 ± 15	0.719	47.5 ± 17.3	48.3 ± 14.1	0.793
Genetic type^‡			1.0			0.513			0.448
Hereditary type (%)	1 (10)	4 (11.8)		3 (9.7)	8 (16.7)		4 (9.8)	12 (14.6)
Sporadic type (%)	9 (90)	30 (88.2)		28 (90.3)	40 (83.3)		37 (90.2)	70 (85.4)
Biochemical cure (%)^‡	10 (100.0)	30 (88.2)	0.559	25 (80.6)	32 (66.7)	0.176	35 (85.3)	62 (75.6)	0.212
Multifocality (%)^‡	4 (40)	8 (23.5)	0.422	4 (9.8)	16 (19.5)	0.041	8 (19.5)	24 (29.3)	0.245
LN metastasis (%)^‡	5 (50)	14 (41.2)	0.723	14 (45.2)	31 (33.3)	0.089	19 (46.3)	45 (54.9)	0.372
UICC TNM stage^‡			0.723			0.170			0.698
Low (I or II)	5 (50)	20 (58.8)		13 (41.9)	13 (27.1)		18 (43.9)	33 (40.2)
High (III or IV)	5 (50)	14 (41.2)		18 (52.9)	35 (72.9)		23 (56.1)	49 (60)
Distant metastasis (%)^‡	0	0	N/A	2 (6.5)	3 (3.7)	1.0	2 (4.9)	3 (3.7)	1.0
Recurrence (%)^‡	0	2 (5.9)	1.0	4 (12.9)	16 (33.3)	0.041	4 (9.8)	18 (22.0)	0.096
Extrathyroidal extension (%)^‡	0	3 (8.8)	1.0	2 (6.5)	16 (33.3)	0.005	2 (4.9)	19 (23.2)	0.011
Extranodal extension (%)^‡	0	6 (17.6)	0.310	4 (12.9)	18 (37.5)	0.017	4 (9.8)	24 (29.3)	0.015

B-MTC, medullary thyroid cancer with benign US features; LN, lymph nodes; M-MTC, medullary thyroid cancer with malignant US features; N/A, not applicable.

Values in parentheses are percentages of 41 B-MTCs.

†

Values in parentheses are percentages of 82 M-MTCs.

‡

Values in parentheses are percentages of B-MTCs or M-MTCs which are at the top of the column.

The US findings of both B-MTCs and M-MTCs are presented in Table 3. The common findings in B-MTCs included solidity, an ovoid to round shape, a smooth margin, hypoechoic echogenicity, and no calcification (Figs. 2 –4). Ovoid to round-shaped, smooth-margined, and hypoechoic lesions were also significantly more common for B-MTCs than for M-MTCs (all P < 0.001). Solid, ovoid to round-shaped lesions with a spiculated/microlobulated margin, marked hypoechogenicity, and micro-calcification were common US findings for M-MTCs (Figs. 5 –7). Only five (6.1%) M-MTC nodules in our study series showed a taller than wide shape, and there were no cystic masses in any of the B-MTCs or M-MTCs.

Fig. 2.

US image of medullary thyroid cancer with benign US features from a 34-year-old man. The tumor was solid, ovoid to round in shape, and had hypoechoic echogenicity compared with the normal thyroid parenchyma.

Fig. 3.

US image of medullary thyroid cancer with benign US features from a 64-year-old man. The size of the tumor was 2.5 cm, and showed solid, ovoid shape, isoechoic echogenicity, and well-defined margin.

Fig. 4.

US image of medullary thyroid cancer with benign US features from a 54-year-old woman. The tumor size was 3 cm, and showed predominantly solid, ovoid shape, iso- to hypoechoic echogenicity, and well-defined margin.

Fig. 5.

US image of medullary thyroid cancer with malignant features from a 37-year-old man. The tumor was solid and had a spiculated margin, marked hypoechogenicity, and micro-calcification (arrowhead).

Table 3.

Comparison of the US findings for B-MTC and M-MTC.

US findings	B-MTCs (n = 41)	M-MTCs (n = 82)	Total (n = 123)	P value
Composition				0.115
Solid (%)	36 (87.8)	79 (96.3)	115 (93.5)
Predominantly solid (%)	5 (12.2)	3 (3.6)	8 (6.5)
Shape				0.004
Ovoid to round (%)	38 (92.7)	54 (65.9)	92 (74.8)
Taller than wide (%)	0	5 (6.1)	5 (4.1)
Irregular (%)	3 (7.3)	23 (28)	26 (21.1)
Margin				<0.001
Smooth (%)	29 (70.7)	19 (23.2)	48 (39)
Spiculated/microlobulated (%)	0	43 (52.4)	43 (35)
Ill-defined (%)	12 (29.3)	20 (24.4)	32 (26)
Echogenicity				<0.001
Isoechoic (%)	9 (22)	2 (2.4)	11 (8.9)
Hypoechoic (%)	32 (78)	35 (42.7)	67 (54.5)
Marked hypoechoic (%)	0	45 (54.9)	45 (36.6)
Calcification				<0.001
No calcification (%)	41 (100)	28 (34.1)	69 (56.1)
Microcalcification (%)	0	30 (36.6)	30 (24.4)
Macrocalcification (%)	0	23 (28)	23 (18.7)
Rim calcification (%)	0	1 (1.2)	1 (0.8)

B-MTC, medullary thyroid cancer with benign US features; M-MTC, medullary thyroid cancer with malignant US features.

Table 4 presents the results of univariate analysis for the clinical manifestations of M-MTCSs, according to the number of malignancy features seen on US. M-MTCs with more than two malignancy features on US showed a significantly lower prevalence of biochemical cure than M-MTCs with only one US malignancy feature, and extrathyroidal and extranodal extensions were more common in the patients with two or more US malignancy features than in those with only one US malignancy feature. No distant metastasis was evident on the initial diagnosis in any patient with an M-MTC and one US malignancy feature.

Table 4.

Univariate analysis of the clinical manifestations of M-MTC according to the number of malignancy features seen on US.

Variable	Number of malignancy features
Variable	Low (1)	High (2 or 3 or 4)	P value
Biochemical cure (%)	33 (89.2)	29 (64.4)	0.009
Genetic type			0.129
Hereditary type (%)	3 (8.1)	9 (20)
Sporadic type (%)	34 (91.9)	36 (80)
Multifocality (%)	11 (29.7)	13 (28.9)	0.934
LN metastasis (%)	19 (51.4)	26 (57.8)	0.561
Distant metastasis on the initial diagnosis (%)	0 (0)	3 (6.7)	0.248
Recurrence (%)	5 (13.5)	13 (28.9)	0.094
Extrathyroidal extension (%)	4 (10.8)	15 (34.1)	0.014
Extranodal extension (%)	6 (16.2)	18 (40)	0.018
Total	37 (100)	45 (100)

LN, lymph nodes; M-MTC, medullary thyroid cancer with malignant US features.

In multivariate analysis of biological behavior, M-MTCS showed a significantly more extrathyroidal extensions and lateral lymph node metastases, i.e. the odds ratio (OR) for extrathyroidal extension was 5.7 (95% confidence interval [CI], 1.2–27.9; P = 0.031) and that for lateral lymph node metastasis was 3.1 (95% CI, 1.1–8.3; P = 0.029). When the tumor size was greater than 1 cm at the largest diameter, it was 3.4 times more likely to be demonstrate benign features, although it is an MTC (P = 0.006). In the patient subgroup with a tumor size greater than 1 cm, the M-MTCs showed significantly higher ORs for multifocality (OR = 5.3; 95% CI, 1.5–18.6; P = 0.01) and extrathyroidal extensions (OR = 10.8; 95% CI, 2.2–52.5; P = 0.003).

Discussion

Our present large cohort study demonstrated that the biological behavior of M-MTCs is more clinically serious than that of B-MTC. In particular, M-MTCs larger than 1 cm at the largest diameter and having more than two malignant US features showed the poorest outcomes. We thus determined that US findings can predict the biological behavior of medullary thyroid cancer. Meanwhile, tumors larger than 1 cm were more likely to be B-MTCs and one-third of all the tumors we analyzed had benign US features. Among the benign features of thyroid nodules, common features of B-MTCs were found to be solidity, an ovoid to round shape, a smooth margin, hypoechogenicity, and no calcification. Therefore, even in a clinical setting where a nodule has benign features, it should be specifically targeted for biopsy or treatment if it has any of the features mentioned above.

Two previous studies have suggested that malignant US findings are related to the biological behavior and prognosis of thyroid cancers. Nam et al. (5) reported that the biological behavior of PTC could be predicted with US findings, and that lesions with benign US features (B-PTC) had a better prognosis than those with malignant US features (M-PTC). Another study on MTC (9) reported that B-MTC showed a better prognosis than M-MTC. However, there were several limitations to that study including the use of US criteria which differed from the current standards (22), a poor description of the US findings, and a small study population. We here enrolled a much larger study patient population and used the same malignant US criteria as previous studies (23,24).

There have been many reports regarding the prognostic factors of MTC. The extent of primary surgical resection, capsule invasion, distant metastasis, extrathyroidal invasion, and vascular invasion were the significant prognostic factors in the previous studies (6,7,25). In our current study, M-MTC showed a significantly higher prevalence of extrathyroidal extension, extranodal extension, and lateral lymph node metastases (P = 0.011, P = 0.015, and P = 0.014, respectively) than B-MTC. In our subgroup analysis, M-MTCs greater than 1 cm at the largest diameter showed a higher prevalence of multifocality, recurrence, extrathyroidal extension, and extranodal extension than B-MTC greater than 1 cm (P = 0.041, P = 0.041, P = 0.005, and P = 0.017, respectively). We also found that M-MTCs with more than two US malignancy features showed a significantly lower chance of biochemical cure, and higher prevalence of extrathyroidal and extranodal extension, than M-MTCs with only one US malignancy feature (P = 0.009, P = 0.014, and P = 0.018, respectively).

There have been several studies which emphasized the early diagnosis of MTC for surgical cure and improving the survival rates (8,26). In our present study, no distant metastases were found in patients with either M-MTCs or B-MTCs of less than 1 cm at the largest diameter, and no patient with a B-MTC of less than 1 cm showed recurrence or any extrathyroidal or extranodal extensions. On multivariate analysis, the prevalence of extrathyroidal extension was higher in M-MTCs greater than 1 cm than in B-MTCs greater than 1 cm (P = 0.003; OR = 10.8; 95% CI, 2.2–52.5). Our study findings also demonstrated that the early detection of MTC has an important influence on the patient prognosis.

Fig. 6.

US image of medullary thyroid cancer with malignant features from a 45-year-old woman. The tumor showed taller than wide, marked hypoechogenicity, and lobulated or spiculated margin. The size was 1.6 cm.

Fig. 7.

US image of medullary thyroid cancer with malignant features from a 49-year-old man. The tumor size was 0.7 cm, and showed taller than wide, spiculated margin, and marked hypoechoic echogenicity.

It was a notable finding that larger than 1 cm-sized tumors were 3.4 times more likely to demonstrate benign features, although it is an MTC. In a previous study (9), B-MTCs were also reported to be significantly larger than M-MTCs (B-MTC, 3.2 ± 1.3 cm; M-MTC, 2.2 ± 1.4 cm; P = 0.0007). This suggested that B-MTCs might be detected and treated at a later stage than M-MTCs due to their typically benign morphology seen on US. We thus contend that for patients with a clinically suspected MTC, lesions with benign US features should be assessed as early as possible even if no malignant features are evident.

In our present study, TNM staging, tumor recurrence, biochemical cure, and TTP did not differ significantly between the M-MTC and B-MTC groups. Previously, B-PTCs had a lower TNM stage and lower tumor recurrence rate than M-PTCs (5). However, B-PTCs greater than 1 cm comprised only 29 of the 79 B-PTCs (39.2%) detected in that study, whereas 31 B-MTCs greater than 1 cm of a total of 41 B-MTCs (75.6%) were included in our present study. As the tumor size plays an important role in T-staging in the present TNM system, this will affect the TNM staging regardless of the US features. From this perspective, we speculated that tumor size might also have a significant role in tumor recurrence or a biochemical cure.

In our current study, the B-MTCs were most commonly solid, ovoid to round-shaped lesions with a smooth margin, hypoechogenicity, and no calcification. We also found that one-third of the total number of MTCs in our series had benign US features. In a previous study (9), a similar finding was reported and approximately 30% of the total number of MTCs had benign US features (23 B-MTCs and 54 M-MTCs). Another study reported that MTCs tended to have an oval shape and a circumscribed margin, although without statistical significance (13). Choi et al. also reported that MTCs are solid, round to oval in shape, and with a smooth margin and hypoechogenicity compared to PTCs (12). No cystic lesion was found in the MTCs in their study and a taller than wide shape was a rare finding in the MTCs analyzed (6/36, 16.7%). We re-emphasize from the evidence to date that a greater understanding of the benign US features of MTCs is very important for determining the target lesion for biopsy in patients suspected of having this cancer, as B-MTCs account for a relatively large portion of MTCs.

Our study had several noteworthy limitations, including its retrospective nature. Moreover, as our analysis was performed with an awareness of the final diagnosis, this may have influenced our results. Another limitation was that we included familial MTCs as well as sporadic MTCs, with familial MTCs constituting 13% (16/123) of the total number of MTCs. However, as the purpose of our present analysis was to investigate the overall biological trends for MTCs, we included consecutive patients during limited time period. Therefore, a strength of our current study is that our results could be applied to actual clinical practice.

In conclusion, US findings can predict the biological behavior of MTCs which is more medically serious in the case of M-MTCs. The common findings for B-MTCs were their solid, ovoid to round shape, smooth margin, hypoechogenicity, and lack of calcification. B-MTCs represented one-third of the total number of MTCs analyzed and were larger than M-MTCs. An understanding of the common US findings for B-MTCs is important in cases of a suspicious MTC without malignant US findings.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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