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Journal of Clinical Otorhinolaryngology Head and Neck Surgery logoLink to Journal of Clinical Otorhinolaryngology Head and Neck Surgery
. 2020 Jul 5;34(7):615–617. [Article in Chinese] doi: 10.13201/j.issn.2096-7993.2020.07.009

cN0声门上型喉癌的颈淋巴结隐匿性转移及处理

Analysis and management of occult cervical lymph node metastasis of cN0 supraglottic laryngeal carcinoma

Chen HU 1, Ming ZHANG 1,*, Jiyao XUE 1, Hongli GONG 1, Lei TAO 1, Liang ZHOU 1
PMCID: PMC10133113  PMID: 32791636

Abstract

Objective

To explore the rule of occult cervical lymph nodes metastasis in clinically node negative(cN0) supraglottic laryngeal carcinoma.

Method

The clinical data of 185 patients with cN0 supraglottic laryngeal carcinoma were analyzed retrospectively. All patients received surgical resection of the primary lesions and lateral neck dissection. The survival curve was analyzed by Kaplan-Meier method, and the survival rate was compared by chi-square test and log rank test.

Result

The total incidence of occult cervical lymph nodes metastasis in cN0 supraglottic laryngeal carcinoma was 38.9%(72/185), the unilateral and bilateral neck occult metastases were determined in 51 cases(27.6%) and 21 cases(11.4%) respectively. A total of 266 positive nodes were collected, and the distributions of the 266 positive nodes were as follows: 220(82.7%) in level Ⅱ, 42(15.8%) in level Ⅲ, and 4(1.5%) in level Ⅳ. The occult metastasis rates of bilateral cervical lymph nodes with different degrees of differentiation were 37.5%(12/32) for poorly differentiated squamous cell carcinoma, 7.4%(6/81) for moderately differentiated squamous cell carcinoma, and 4.2%(3/72) for high differentiated squamous cell carcinoma; the occult metastasis rates of bilateral cervical lymph nodes at T1, T2, T3, T4 were 0, 2.7%(2/73), 8.1%(6/74), 46.4%(13/28), respectively, and the difference was statistically significant(P < 0.01).

Conclusion

cN0 supraglottic laryngeal carcinoma has a high rate of occult cervical lymph nodes metastasis, and its metastatic area is mainly located in level Ⅱ-Ⅲ, so the primary tumor of the laryngeal carcinoma and the neck lymph node of level Ⅱ-Ⅲ should be managed at the same time. For the cN0 patients with poorly differentiated squamous cell carcinoma or T4 staging should be treated with bilateral neck dissection.

Keywords: laryngeal neoplasms, occult lymph node metastasis, neck dissection, prognosis

喉癌是头颈部常见的恶性肿瘤之一，声门上区局部淋巴组织丰富，故声门上型喉癌颈部淋巴结有较高的隐匿性转移率〔1〕，发生淋巴结隐匿性转移的患者生存率明显下降〔2-4〕，但是针对cN0声门上型喉癌的隐匿性淋巴结转移风险该采取何种治疗方式仍存在争议〔5-6〕。本研究回顾性分析我院诊治的185例cN0声门上型喉癌患者的临床资料，分析其隐匿性颈淋巴结转移率及转移区域，以及与肿瘤T分期、病理分化程度的关系，从而指导cN0声门上型喉癌患者的颈部处理。

1. 资料与方法

1.1. 临床资料

收集2006-01-2017-11我院收治的185例(248侧)cN0声门上型喉癌患者的临床资料。入选标准：①cN0诊断标准为临床医师颈部触诊无肿大淋巴结，增强CT/MRI检查颈淋巴结直径≤1.0 cm，且形态正常，无液化坏死、不规则强化等异常表现；②喉部原发灶病理确诊为鳞状细胞癌；③术前均接受颈部增强CT和(或)MRI检查；④手术作为首次治疗，术前未行放疗、化疗；⑤无远处转移。喉部原发灶病理分别为：低分化鳞状细胞癌32例，中分化鳞状细胞癌81例，高分化鳞状细胞癌72例。肿瘤分期根据AJCC(第8版)的TNM分类标准：T1 10例，T2 73例，T3 74例，T4 28例。

1.2. 治疗方法

185例患者行喉部手术的同时行颈淋巴结清扫术，其中行全喉切除术116例，喉环状软骨上部分切除术17例，喉水平部分切除术49例，喉垂直部分切除术3例。原发病灶位于喉内一侧，未达喉中线者行同侧颈侧清扫术，共122例，其中Ⅱ~Ⅲ区清扫33例，Ⅱ~Ⅳ区清扫89例；原发病灶位于喉中线者，或位于喉内一侧但侵及或超越喉中线者行双侧颈侧清扫术，共63例(126侧)，其中Ⅱ~Ⅲ区清扫26例，Ⅱ~Ⅳ区清扫37例。术中以缝线对淋巴结进行分区标记后送病理检查。

1.3. 随访

随访时间起始于行颈清扫术的时间，截止时间为2019年9月15日。随访方式为门诊复诊及电话联系。总生存时间(overall survival)定义为从颈清扫手术开始至死亡时间或最后1次随访时间；无病生存时间(disease-free survival)定义为自颈清扫术开始至复发或最后1次随访时间。

1.4. 统计学方法

采用SPSS 22.0统计学软件对数据进行分析。生存曲线绘制采用Kaplan-Meier法，生存率的比较采用卡方检验、log rank检验。

2. 结果

2.1. 颈淋巴结隐匿性转移及分布情况

185例(248侧)中行单侧颈清扫122例，行双侧颈清扫63例(126侧)。颈清扫术后淋巴结阳性(pN+)72例，颈淋巴结隐匿性转移率为38.9%(72/185)，其中单侧颈淋巴结隐匿性转移率为27.6%(51/185)，双侧颈淋巴结隐匿性转移率为11.4%(21/185)。本组185例(248侧)颈清扫标本共获淋巴结4686枚，平均每侧18.9枚，其中病理阳性淋巴结266枚，位于Ⅱ区220枚(82.7%)，Ⅲ区42枚(15.8%)，Ⅳ区4枚(1.5%)。所有淋巴结阳性患者均为Ⅱ区转移或Ⅱ区伴其他分区转移，无单独其他颈部分区(Ⅲ、Ⅳ)转移。不同分化程度鳞状细胞癌的单侧颈淋巴结隐匿性转移率分别为低分化12.5%(4/32)，中分化34.6%(28/81)，高分化26.4%(19/72)，差异无统计学意义(P=0.058)；不同分化程度鳞状细胞癌的双侧颈淋巴结隐匿性转移率分别为低分化37.5%(12/32)，中分化7.4%(6/81)，高分化4.2%(3/72)，差异有统计学意义(P < 0.01)。随着T分期的进展，双侧颈淋巴结隐匿性转移率也随之上升，不同肿瘤T分期的双侧颈淋巴结隐匿性转移率分别为T1 0，T2 2.7%(2/73)，T3 8.1%(6/74)，T4 46.4%(13/28)，差异有统计学意义(P < 0.01)。

2.2. pN+患者与pN0患者预后比较

185例声门上型喉癌患者中，pN+与pN0 5年总生存率分别为50.0%和63.7%，差异有统计学意义(P < 0.05)，见图 1。

图 1.

图 1

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pN+患者与pN0患者总生存率比较

2.3. 随访及生存情况

本组185例患者无住院期间死亡；随访期间死亡42例，其中喉复发8例，颈部复发9例，肺转移7例，肝转移和骨转移各1例，第2原发癌7例，死因不明1例，失访8例(按死亡计)。

3. 讨论

声门上型喉癌易发生颈部淋巴结转移〔1〕，研究显示cN0声门上型喉癌隐匿性转移率为30.2%~38.0%〔7〕，而pN+的cN0患者5年总生存率下降约50%〔8-9〕。有学者认为早期喉癌的择区性颈清扫术相比于随访观察无明显优势，为避免切除正常颈部组织，主张早期的cN0声门上型喉癌可先行原发灶切除，颈部淋巴结采取随访观察，若随访中发现确有转移再行挽救性颈清扫术〔10-11〕。然而，隐匿性淋巴结转移会不可避免地发展成为明确的临床转移，并且部分隐匿性转移患者会因为没有定期随访而延误最佳手术时机。一般认为，当患者颈淋巴结隐匿性转移风险>15%时即可考虑行择区性颈清扫术〔5〕。目前，任何术前评估检查都有隐匿性转移遗漏的可能：CT、MRI检查对颈部隐匿性转移的敏感度为38%~78%〔12〕，PET-CT检查有较高的假阴性(76%)〔9, 13〕。因此，探讨cN0声门上型喉癌颈部淋巴结隐匿性转移规律对指导临床医师处理颈部淋巴结的方式和时机至关重要。

本研究185例cN0声门上型喉癌患者行喉部手术的同时行颈侧清扫术：同侧颈侧清扫术者122例，其中Ⅱ~Ⅲ区清扫33例，Ⅱ~Ⅳ区清扫89例；双侧颈侧清扫术者63例(126侧)，其中Ⅱ~Ⅲ区清扫26例，Ⅱ~Ⅳ区清扫37例。185例患者颈淋巴结隐匿性转移率为38.9%，pN+与pN0患者相比患者5年生存率下降了13.7%，差异有统计学意义(P < 0.05)。共获病理阳性淋巴结266枚，位于Ⅱ、Ⅲ区262枚(98.5%)，其余4枚为Ⅳ区转移，所有淋巴结阳性病例均为Ⅱ区转移或Ⅱ区伴其他分区转移，无单独其他颈部分区(Ⅲ、Ⅳ)转移。根据喉声门上区的解剖特点及淋巴引流规律，淋巴结转移应首先到达颈Ⅱ区及Ⅲ区，再扩展至Ⅳ区，本研究结果与之一致，因此对于原发灶局限于喉内的cN0声门上型喉癌，应将颈Ⅱ、Ⅲ区作为重点清扫区域，Ⅰ、Ⅳ区可不作常规清扫。cN0喉癌颈淋巴结隐匿性转移与肿瘤分型、T分期以及病理分化程度有关〔4, 8, 14〕。本研究中，随着肿瘤T分期的增加、病理分化程度的降低，颈部淋巴结隐匿性转移风险均逐步上升；并且T4期及低分化鳞状细胞癌患者发生双侧颈淋巴结隐匿性转移的风险显著提升(P < 0.05)。针对此类患者，在处理原发灶的同时应行双侧颈侧清扫术(Ⅱ~Ⅲ区)。

综上，cN0声门上型喉癌具有较高的隐匿性转移率，且pN+患者的生存率显著下降，对T4期或低分化鳞状细胞癌的cN0患者应行双侧Ⅱ~Ⅲ区颈清扫术。

Funding Statement

上海市自然科学基金(No：17ZR1404700)；上海市浦东新区卫计委联合攻关项目(No：PW2016D-11)

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