多模态超声对甲状腺微小乳头状癌颈部淋巴结转移的预测价值

doi:10.3877/cma.j.issn.1672-6448.2021.09.004

目的

探讨术前常规超声、超声造影及超微血管成像（SMI）的多模态超声对甲状腺微小乳头状癌（PTMC）颈部淋巴结转移（CLNM）的预测价值。

方法

回顾性分析首都医科大学附属北京天坛医院2018年10月至2021年4月经手术病理证实的99例PTMC患者，术前均行常规超声、超声造影和SMI检查。根据手术病理结果分为颈部淋巴结未转移组60例和转移组39例。观察并记录PTMC常规超声、超声造影、SMI及临床相关特征。应用单因素分析方法（独立样本t检验、χ²检验和Fisher确切概率法）比较2组患者多模态超声和临床特征的差异，将差异有统计学意义的因素纳入多因素Logistic回归分析，分析PTMC颈部淋巴结转移的危险因素。

结果

单因素分析显示，与颈部淋巴结转移组比较，颈部淋巴结未转移组患者年龄大［（47.50±11.48）岁 vs（39.67±9.95）岁］，癌灶最大径小［（0.66±0.02）cm vs（0.77±0.02）cm］，单发癌灶最大径或多发癌灶最大径之和＞1.0 cm占比低（13/60 vs 17/39）、微钙化数量少（无、有且≤5个、＞5个：23、23、14 vs 10、10、19）、超声造影呈等或高增强比例低（9/60 vs 13/39）、增强早期病灶周围被膜连续性中断的比例较低（14/60 vs 17/39），差异具有统计学意义（t=3.491、P=0.001；t=3.376、P=0.001；χ²=5.379、P=0.020；χ²=6.854、P=0.032；χ²=4.596、P=0.032；χ²=4.509、P=0.034）。多因素分析显示患者年龄越小（OR=0.933，P=0.004）、癌灶最大径越大（OR=30.567，P=0.046），颈部淋巴结转移的风险越高；增强早期PTMC临近被膜连续性中断将增加PTMC颈部淋巴结转移的风险（OR=0.296，P=0.032）。

结论

患者年龄较小、PTMC较大及增强早期癌灶周边被膜连续性中断是预测PTMC颈部淋巴结转移的独立危险因素，术前多模态超声检查特征对于PTMC患者是否发生CLNM有一定预测价值。

关键词: 超声检查，多模态, 甲状腺微小乳头状癌, 颈部淋巴结转移

Objective

To investigate the predictive value of multimodal ultrasound consisting of conventional ultrasound, contrast-enhanced ultrasound, and superb microvascular imaging (SMI) in cervical lymph node metastasis (CLNM) of papillary thyroid microcarcinoma (PTMC).

Methods

A retrospective analysis was performed on 99 patients with pathologically confirmed PTMC at Beijing Tiantan Hospital, Capital Medical University from October 2018 to April 2021. Conventional ultrasound, contrast-enhanced ultrasound, and SMI were all performed preoperatively. According to pathologic results, the patients were divided into either a non-metastatic cervical lymph node group (n=60) or a metastatic cervical lymph node group (n=39). Features of multimodal ultrasound and clinical data of PTMC were observed and recorded. Independent-sample t test, Chi-square test, and Fisher exact test were used to compare the differences in all features between the two groups, and the statistically significant factors were included in multivariate Logistic regression analysis to identify the independent risk factors for PTMC with CLNM.

Results

Univariate analysis showed that compared with the patients with CLNM, the patients without CLNM were older [(47.50±11.48) years vs (39.67±9.95) years], had smaller PTMC [(0.66±0.02) cm vs (0.77±0.02) cm], were less likely to have the maximum diameter of single carcinoma or the sum of the maximum diameter of multiple carcinoma＞1.0 cm (13/60 vs 17/39), had less microcalcifications (none, ≤5 but not none, and＞5∶23, 23, and 14 vs 10, 10, and 19, respectively), were less likely to have PTMC with equal or high density enhancement (9/60 vs 13/39), and were less likely to have interruption of capsule continuity in early stage of contrast-enhanced ultrasound (14/60 vs 17/39) (t=3.491, P=0.001; t=3.376, P=0.001; χ²=5.379, P=0.020; χ²=6.854, P=0.032; χ²=4.596, P=0.032; and χ²=4.509, P=0.034, respectively). Multivariate analysis showed that younger age (odds ratio [OR]=0.933, P =0.004), larger PTMC (OR=30.567,P=0.046), and interruption of capsule continuity in early stage of contrast-enhanced ultrasound (OR=0.296, P=0.032) independently increased the risk of CLNM in PTMC.

Conclusion

Younger age, larger PTMC, and interruption of capsule continuity in early stage of contrast-enhanced ultrasound are independent risk factors for predicting CLNM of PTMC. The features of preoperative multimodal ultrasound have appreciated predictive value for CLNM in patients with PTMC.

Key words: Ultrasonography,multimodal, Papillary thyroid microcarcinoma, Cervical lymph node metastasis

图1 甲状腺微小乳头状癌（PTMC）患者多模态超声部分特征表现。图a为女性患者，41岁，左叶中部PTMC内微钙化数量＞5个；图b为男性患者，31岁，超微血管成像（SMI）显示右叶中部PTMC内部及周边均无明显血流信号，为Rago Ⅰ级；图c为女性患者，29岁，SMI显示左叶中上部PTMC内部有少量血流信号，周边有血流信号，为Rago Ⅱ级；图d为女性患者，32岁，SMI显示右叶中部PTMC内部血流信号丰富，周边有血流信号，为Rago Ⅲ级；图e、f为男性患者，38岁，PTMC位于右叶中下部，图e示增强早期PTMC周围甲状腺被膜连续性中断，图f为图e同步的灰阶超声图像；图g、h为女性患者，33岁，PTMC位于左叶中上部，图g示PTMC造影后呈等增强，图h为图g同步的灰阶超声图像

表1 甲状腺微小乳头状癌患者多模态超声及临床特征的单因素比较分析

组别	例数	男性/女性（例）	年龄（岁， $x ¯$ ±s）	最大径（cm， $x ¯$ ±s）	单发癌灶最大径或多发癌灶最大径之和（例）		病灶数量（例）		病灶分布（例）
组别	例数	男性/女性（例）	年龄（岁， $x ¯$ ±s）	最大径（cm， $x ¯$ ±s）	≤1.0 cm	＞1.0 cm	单灶	多灶	单灶	单叶多灶	双叶多灶
颈部淋巴结未转移组	60	12/48	47.50±11.48	0.66±0.02	47	13	37	23	37	12	11
颈部淋巴结转移组	39	10/29	39.67±9.95	0.77±0.02	22	17	20	19	20	8	11
统计值		χ²=0.043	t=3.491	t=3.376	χ²=5.379		χ²=0.065		χ²=1.482
P值		0.337	0.001	0.001	0.020		0.799		0.477
组别	例数	位置（例）				边缘（例）			形态（例）				实性成分回声（例）				钙化类型（例）
组别	例数	上部	中部	下部		光滑	分叶或不规则		椭圆形	类圆形	不规则		等回声	低回声	极低回声		无钙化	微小钙化	混合钙化
颈部淋巴结未转移组	60	11	25	24		4	56		2	11	47		3	27	30		23	35	2
颈部淋巴结转移组	39	7	20	12		1	38		4	5	30		2	11	26		9	26	4
统计值		χ²=1.037				-			-				-				-
P值		0.596				0.659			0.327				0.281				0.161
组别	例数	微钙化数量（例）				纵横比（例）			桥本甲状腺炎（例）			CDFI Rago分级（例）				SMI Rago分级（例）
组别	例数	无	有且≤5个	＞5个		≤1	＞1		有	无		Ⅰ级	Ⅱ级	Ⅲ级		Ⅰ级	Ⅱ级	Ⅲ级
颈部淋巴结未转移组	60	23	23	14		15	45		16	44		12	40	8		2	37	21
颈部淋巴结转移组	39	10	10	19		11	28		14	25		6	26	7		1	23	15
统计值		χ²=6.854				χ²=0.125			χ²=0.954			χ²=0.609				-
P值		0.032				0.723			0.329			0.737				0.925
组别	例数	造影后病灶边缘（例）			造影剂灌注方向（例）			病灶增强水平（例）			造影强度分布（例）			增强早期被膜连续性（例）			增强早期与腺体比较（例）			增强晚期与腺体比较（例）
组别	例数	清	不清		向心	弥漫		低增强	等或高增强		均匀	不均匀		连续	中断		同步增强	晚于腺体增强		同步消退	早于腺体消退
颈部淋巴结未转移组	60	5	55		40	20		51	9		7	53		46	14		14	46		18	42
颈部淋巴结转移组	39	1	38		28	11		26	13		7	32		22	17		12	27		14	25
统计值		χ²=0.554			χ²=0.289			χ²=4.596			χ²=0.768			χ²=4.509			χ²=0.675			χ²=0.376
P值		0.457			0.591			0.032			0.381			0.034			0.411			0.540

表1 甲状腺微小乳头状癌患者多模态超声及临床特征的单因素比较分析

组别	例数	男性/女性（例）	年龄（岁， $x ¯$ ±s）	最大径（cm， $x ¯$ ±s）	单发癌灶最大径或多发癌灶最大径之和（例）		病灶数量（例）		病灶分布（例）
组别	例数	男性/女性（例）	年龄（岁， $x ¯$ ±s）	最大径（cm， $x ¯$ ±s）	≤1.0 cm	＞1.0 cm	单灶	多灶	单灶	单叶多灶	双叶多灶
颈部淋巴结未转移组	60	12/48	47.50±11.48	0.66±0.02	47	13	37	23	37	12	11
颈部淋巴结转移组	39	10/29	39.67±9.95	0.77±0.02	22	17	20	19	20	8	11
统计值		χ²=0.043	t=3.491	t=3.376	χ²=5.379		χ²=0.065		χ²=1.482
P值		0.337	0.001	0.001	0.020		0.799		0.477
组别	例数	位置（例）				边缘（例）			形态（例）				实性成分回声（例）				钙化类型（例）
组别	例数	上部	中部	下部		光滑	分叶或不规则		椭圆形	类圆形	不规则		等回声	低回声	极低回声		无钙化	微小钙化	混合钙化
颈部淋巴结未转移组	60	11	25	24		4	56		2	11	47		3	27	30		23	35	2
颈部淋巴结转移组	39	7	20	12		1	38		4	5	30		2	11	26		9	26	4
统计值		χ²=1.037				-			-				-				-
P值		0.596				0.659			0.327				0.281				0.161
组别	例数	微钙化数量（例）				纵横比（例）			桥本甲状腺炎（例）			CDFI Rago分级（例）				SMI Rago分级（例）
组别	例数	无	有且≤5个	＞5个		≤1	＞1		有	无		Ⅰ级	Ⅱ级	Ⅲ级		Ⅰ级	Ⅱ级	Ⅲ级
颈部淋巴结未转移组	60	23	23	14		15	45		16	44		12	40	8		2	37	21
颈部淋巴结转移组	39	10	10	19		11	28		14	25		6	26	7		1	23	15
统计值		χ²=6.854				χ²=0.125			χ²=0.954			χ²=0.609				-
P值		0.032				0.723			0.329			0.737				0.925
组别	例数	造影后病灶边缘（例）			造影剂灌注方向（例）			病灶增强水平（例）			造影强度分布（例）			增强早期被膜连续性（例）			增强早期与腺体比较（例）			增强晚期与腺体比较（例）
组别	例数	清	不清		向心	弥漫		低增强	等或高增强		均匀	不均匀		连续	中断		同步增强	晚于腺体增强		同步消退	早于腺体消退
颈部淋巴结未转移组	60	5	55		40	20		51	9		7	53		46	14		14	46		18	42
颈部淋巴结转移组	39	1	38		28	11		26	13		7	32		22	17		12	27		14	25
统计值		χ²=0.554			χ²=0.289			χ²=4.596			χ²=0.768			χ²=4.509			χ²=0.675			χ²=0.376
P值		0.457			0.591			0.032			0.381			0.034			0.411			0.540

表2 甲状腺微小乳头状癌患者颈部淋巴结转移的多因素Logistic回归分析

因素	β值	SE值	Wals χ²值	P值	OR值	95%CI
年龄	-0.070	0.024	8.295	0.004	0.933	0.890~0.978
癌灶最大径（cm）	3.420	1.711	3.995	0.046	30.567	1.069~874.2
单发癌灶最大径或多发癌灶最大径之和是否＞1.0 cm	-1.131	0.603	3.517	0.061	0.323	0.099~1.052
微钙化数量			2.334	0.311
微钙化数量（1）	-0.960	0.628	2.334	0.127	0.383	0.112~1.312
微钙化数量（2）	-0.440	0.621	0.502	0.479	0.644	0.191~2.175
增强水平	-0.965	0.582	2.755	0.097	0.381	0.122~1.191
增强早期被膜连续性	-1.218	0.568	4.600	0.032	0.296	0.097~0.900
常量	2.974	2.004	2.201	0.138	19.561

表2 甲状腺微小乳头状癌患者颈部淋巴结转移的多因素Logistic回归分析

因素	β值	SE值	Wals χ²值	P值	OR值	95%CI
年龄	-0.070	0.024	8.295	0.004	0.933	0.890~0.978
癌灶最大径（cm）	3.420	1.711	3.995	0.046	30.567	1.069~874.2
单发癌灶最大径或多发癌灶最大径之和是否＞1.0 cm	-1.131	0.603	3.517	0.061	0.323	0.099~1.052
微钙化数量			2.334	0.311
微钙化数量（1）	-0.960	0.628	2.334	0.127	0.383	0.112~1.312
微钙化数量（2）	-0.440	0.621	0.502	0.479	0.644	0.191~2.175
增强水平	-0.965	0.582	2.755	0.097	0.381	0.122~1.191
增强早期被膜连续性	-1.218	0.568	4.600	0.032	0.296	0.097~0.900
常量	2.974	2.004	2.201	0.138	19.561

1	Giordano TJ. Genomic hallmarks of thyroid neoplasia [J]. Annu Rev Pathol, 2018, 13: 141-162.
2	Lim H, Devesa S, Sosa J, et al. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013 [J]. JAMA, 2017, 317(13): 1338-1348.
3	Wong R, Farrell S, Grossmann M. Thyroid nodules: diagnosis and management [J]. Med J Aust, 2018, 209(2): 92-98.
4	Haugen B. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: What is new and what has changed? [J]. Cancer, 2017, 123(3): 372-381.
5	Chung S, Choi Y, Lee S, et al. Interobserver reproducibility in sonographic measurement of diameter and volume of papillary thyroid microcarcinoma [J]. Thyroid, 2021, 31(3): 452-458.
6	Nakamura T, Miyauchi A, Ito Y, et al. Quality of life in patients with low-risk papillary thyroid microcarcinoma: active surveillance versus immediate surgery [J]. Endocr Pract, 2020, 26(12): 1451-1457.
7	Wang K, Xu J, Li S, et al. Population-based study evaluating and predicting the probability of death resulting from thyroid cancer among patients with papillary thyroid microcarcinoma [J]. Cancer Med, 2019, 8(16): 6977-6985.
8	Lee K, Cho Y, Kim S, et al. Analysis of the clinicopathologic features of papillary thyroid microcarcinoma based on 7-mm tumor size [J]. World J Surg, 2011, 35(2): 318-323.
9	Zhang L, Wei W, Ji Q, et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients [J]. J Clin Endocrinol Metab, 2012, 97(4): 1250-1257.
10	Bernet V. Approach to the patient with incidental papillary microcarcinoma [J]. J Clin Endocrinol Metab, 2010, 95(8): 3586-3592.
11	Sun J, Jiang Q, Wang X, et al. Nomogram for preoperative estimation of cervical lymph node metastasis risk in papillary thyroid microcarcinoma [J]. Front Endocrinol (Lausanne), 2021, 12: 613974.
12	Hu Y, Cao X, Zhou Y, et al. Management of sonographically suspicious thyroid nodules 1 cm or smaller and candidacy for active surveillance: experience of a tertiary center in China [J]. Endocr Pract, 2021: S1530-891X(21)00048-3. Online ahead of print.
13	Trimboli P, Castellana M, Virili C, et al. Performance of contrast-enhanced ultrasound (CEUS) in assessing thyroid nodules: a systematic review and meta-analysis using histological standard of reference [J]. Radiol Med, 2020, 125(4): 406-415.
14	Li X, Gao F, Li F, et al. Qualitative analysis of contrast-enhanced ultrasound in the diagnosis of small, TR3-5 benign and malignant thyroid nodules measuring ≤1 cm [J]. Br J Radiol, 2020, 93(1111): 20190923.
15	Rago T, Vitti P, Chiovato L, et al. Role of conventional ultrasonography and color flow-doppler sonography in predicting malignancy in 'cold' thyroid nodules [J]. Eur J Endocrinol, 1998, 138(1): 41-46.
16	Siegel R, Miller K, Jemal A. Cancer statistics, 2020 [J]. CA Cancer J Clin, 2020, 70(1): 7-30.
17	Zou Q, Ma S, Zhou X. Association of sonographic features and clinicopathologic factors of papillary thyroid microcarcinoma for prevalence of lymph node metastasis: a retrospective analysis [J]. Arch Endocrinol Metab, 2020: 2359-3997000000297. Online ahead of print.
18	Medas F, Canu G, Cappellacci F, et al. Predictive factors of lymph node metastasis in patients with papillary microcarcinoma of the thyroid: retrospective analysis on 293 cases [J]. Front Endocrinol (Lausanne), 2020, 11: 551.
19	Zhao L, Sun X, Luo Y, et al. Clinical and pathologic predictors of lymph node metastasis in papillary thyroid microcarcinomas [J]. Ann Diagn Pathol, 2020, 49: 151647.
20	Wang Y, Nie F, Wang G, et al. Value of combining clinical factors, conventional ultrasound, and contrast-enhanced ultrasound features in preoperative prediction of central lymph node metastases of different sized papillary thyroid carcinomas [J]. Cancer Manag Res, 2021, 13: 3403-3415.
21	叶添添, 夏宇, 姜玉新, 等. 甲状腺微小乳头状癌原发病变超声特点与颈部大量淋巴结转移的相关性 [J/CD]. 中华医学超声杂志(电子版), 2017, 14(10): 760-765.
22	Dong Y, Wang D, Luo Y, et al. Comprehensive evaluation of risk factors for lymph node metastasis in patients with papillary thyroid carcinoma [J]. Oncol Lett, 2021, 21(3): 188.
23	Zhou B, Wei L, Qin J. Does multifocal papillary thyroid microcarcinoma with a total tumor diameter＞1 cm indicate poor biological behavior? The evidence is insufficient [J]. Endocr Pract, 2021, 27(2): 131-136.
24	Yan T, Qiu W, Song J, et al. Bilateral multifocality, a marker for aggressive disease, is not an independent prognostic factor for papillary thyroid microcarcinoma: a propensity score matching analysis [J]. Clin Endocrinol (Oxf), 2021, 95: 209-216.
25	Hong Y, Yan C, Mo G, et al. Conventional US, elastography, and contrast enhanced US features of papillary thyroid microcarcinoma predict central compartment lymph node metastases [J]. Sci Rep, 2015, 5(1): 7748.
26	章美武, 吕淑懿, 范晓翔, 等. 甲状腺微小乳头状癌颈部淋巴结转移的相关危险因素 [J/OL]. 中华医学超声杂志(电子版), 2021, 18(6): 570-577.
27	Tao L, Zhou W, Zhan W, et al. Preoperative prediction of cervical lymph node metastasis in papillary thyroid carcinoma via conventional and contrast-enhanced ultrasound [J]. J Ultrasound Med, 2020, 39(10): 2071-2080.
28	樊秋兰, 陈霰, 于春洋, 等. 普通超声及超声造影预测甲状腺微小乳头状癌中央区淋巴结转移的价值 [J]. 中国超声医学杂志, 2016, 32(12): 1060-1062.
29	樊金芳, 陶玲玲, 詹维伟, 等. 超声造影和弹性成像对甲状腺微小乳头状癌中央组淋巴结转移的价值 [J]. 医学影像学杂志, 2020, 30(9): 1582-1586.
30	Seifert R, Schäfers M, Heitplatz B, et al. Minimal extrathyroid extension in papillary micro carcinoma of the thyroid is an independent risk factor for relapse through lymph node and distant metastases [J]. J Nucl Med, 2021: jnumed.121.261898. Online ahead of print.

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Predictive value of multimodal ultrasonography in cervical lymph node metastasis of thyroid micropapillary carcinoma

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Predictive value of multimodal ultrasonography in cervical lymph node metastasis of thyroid micropapillary carcinoma