壹生资讯-指南精华！一文掌握非小细胞肺癌的诊断问题！

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指南精华！一文掌握非小细胞肺癌的诊断问题！

2020-12-16作者：cmt佳玲资讯

支持护理和治疗的相关问题癌症筛查

非小细胞肺癌(non-small cell lung cancer, NSCLC)占所有最常见肿瘤——肺癌病例的80%~85%。

NSCLC的分期采用根据国际肺癌研究协会(International Association for the Study of Lung Cancer, IASLC) TNM分期系统[1]，并被美国癌症联合委员会(American Joint Committee on Lung Cancer, AJCC)采纳。通常早期病变指无淋巴结转移(T1－2N0)、局部晚期(locally advanced)指淋巴结转移(N＋)的Ⅱ/Ⅲ期病变，而晚期指存在远处转移的Ⅳ期病变。

根据大样本人群数据显示，初诊NSCLC患者中约20%为早期约25%为局部晚期，约55%已发生远处转移[2]。

临床中，非小细胞肺癌的诊断问题一直是医生朋友所需掌握的重点，现小编整理相关内容，希望能够方便各位读者的临床工作！

NSCLC的诊断

▶ 筛查

理想的筛查手段应该在恶性肿瘤发生早期尚可治愈时发现该疾病。目前，低剂量薄层CT扫描已被证明可以发现早期NSCLC，是目前首选最常用的筛查方法。国际肺癌筛查研究显示对于无症状的高危人群进行每年1次的低剂量薄层CT扫描，可以使肺癌(主要是NSCLC)的死亡风险降低20%^[3]。

国际肺癌筛查研究的高危人群指目前吸烟者和有至少30年吸烟史的戒烟者(戒烟至少15年)，年龄55-74岁。中国国家癌症中心推荐的肺癌筛查目标人群为年龄50-74岁人群具备以下任一项危险因素：(1)吸烟30包年(1包/d共30年)，其中包括曾经吸烟至少30包年、但戒烟不足15年者；(2)有慢性阻塞性肺疾病病史；(3)有职业暴露史(至少1年)(石棉、氡、铍、铀、铬、镉、镍、硅等)；(4)不吸烟女性：一起共同生活至少20年的家人或同事吸烟至少30包年。目前缺乏针对不吸烟人群的筛查Ⅰ类证据和目标人群建议。

▶ NSCLC的诊断流程

(1)小结节：低剂量CT是NSCLC首选的筛查方式。为减少过度治疗，NCCN-NSCLC指南将偶发实性肺小结节的阳性cut-off值上调为6 mm。CT发现的肺结节可分为实性和亚实性两种主要类型，后者又分为非实性结节(也称为磨玻璃病变或磨玻璃结节)和部分实性结节(包含磨玻璃和实性成分)。非实性结节若为恶性的主要是原位腺癌或微浸润腺癌，曾被称为细支气管肺泡癌，切除后预后极佳，切除后患者5年无瘤生存率高达90%以上；部分非实性结节病变可自行消失；而持续存在的非实性结节病变也可能不会发展为临床意义上的肺癌。在确诊肺癌和开始治疗之前，需要多学科诊疗团队仔细评估。建议对低剂量CT扫描中发现的高度疑似结节进行活检或手术切除，或根据多学科评估定期随访。

(2)较大肿瘤：诊断策略应根据肿瘤的大小和位置、纵隔是否存在转移病灶、患者的特征(如合并症)和当地具体医疗状况进行个体化选择。活检技术取决于病变部位。活检前行PET-CT检查有助于选择最高分期的部位进行活检。对于怀疑有淋巴结转移的患者，建议采用内镜超声引导下的针吸活检、支气管镜腔内超声引导下的经支气管针吸活检、导航支气管镜检查，或纵隔镜检查等无创或有创分期方法进行纵隔淋巴结的病理评估。支气管镜腔内超声可对2R/2L、4R/4L、7、10R/10L和其他肺门淋巴结进行活检；而内镜超声可检查5区、7区、8区和9区淋巴结。

▶ 病理学评估

(1)术前病理评估：包括以下检查方法：支气管镜刷检、支气管灌洗、痰液、细针穿刺活检、芯针活检、支气管内活检和经支气管活检等。

微创技术可用于晚期不可切除NSCLC患者的标本获取；但当使用小活检和细胞学检查时，可能增加病理诊断的困难。对于适合手术患者，建议手术前尽可能系统地对纵隔淋巴结进行取样，以确定分期和治疗方案。肺叶切除或肺切除标本应在术中进行评估，以确定手术切缘状态，诊断在手术时发现的偶发结节，或评估区域淋巴结。

(2)术后病理评估：术后病理评估是肿瘤类型、分期和预后因素的重要依据。手术病理报告应采用WHO对肺癌的组织学分类，推荐进行免疫组化(immunohistochemistry, IHC)和分子检测明确NSCLC病理类型，尽量不使用非小细胞癌等非特指诊断。

(3)病理亚型分类：根据WHO指南，所有NSCLC应尽量根据形态学和IHC结果进行亚型分类，主要亚型包括腺癌、鳞状细胞癌、腺鳞癌、大细胞癌、类癌和其他少见亚型。

腺癌包括原位腺癌、微浸润腺癌、浸润性腺癌和浸润性腺癌变体。腺鳞癌是由混合的腺癌和鳞状细胞癌组成的肿瘤，每个组成部分至少占肿瘤的10%。大细胞癌是一种缺乏明确的形态学或IHC证据的肿瘤，鳞状细胞癌和腺癌的标志物阴性，诊断需要依靠手术标本，小病检或细胞学标本不要求诊断。

(4) IHC检测：在小病检标本中，需合理分配标本，尽量保存肿瘤组织用于分子检测，这一点对于晚期NSCLC患者尤为重要。细胞学检查可区分腺癌和鳞状细胞癌，如有必要采用IHC协助分型诊断。IHC检测有助于小活检和/或细胞学标本中的低分化NSCLC的分型诊断，TTF-1、NapsinA是肺腺癌的免疫标志物，p40(p63)是鳞癌的IHC标志物。鉴别原发性肺癌和肺转移癌应先检测必要的NSCLC IHC指标，如果结果阴性再检测肺转移癌可能的IHC标志物。TTF-1对鉴别原发性肺腺癌和转移性肺腺癌具有重要意义，70%-90%的非黏液性原发性肺腺癌TTF-1阳性、鳞状细胞癌则阴性、甲状腺癌阳性，而其他器官原发肿瘤阳性少见。

(5)分子检测：目前已有多项研究证实携带某些驱动基因的NSCLC患者，在使用相应的靶向治疗药物后，可显著改善预后、延长总生存。基于这些驱动基因的分子亚型包括：表皮生长因子受体(epidermal growth factor receptor，EGFR)基因敏感性突变、间变性淋巴激酶(anaplasticlymphoma kinase，ALK)融合或c-ros癌基因1(c-ros oncogene 1，ROS1)融合等。鉴于上述分子分型对临床治疗的重要指导价值，目前对于所有含有腺癌成分的NSCLC，无论其临床特征，都建议常规行分子检测。EGFR突变检测应包括第18－21外显子。

▶ 影像学检查

影像学检查的目的是为了准确分期，从而对不同分期的患者进行相应的有针对性治疗。常规的影像学分期检查包括：胸部CT、腹部CT (或超声)、颈部CT (或超声)评价病变大小和侵犯范围；脑MRI检查(推荐，如果存在禁忌证可行脑CT检查)和全身骨扫描了解是否存在远处转移。推荐全身PET-CT检查，可进一步提高NSCLC分期诊断的准确性，文献报道中晚期NSCLC可发现高达37%的隐匿胸外转移，改变14%-26%的NSCLC治疗决策^[4]。

PET-CT发现脑转移的能力低于MRI，所以仍然需要常规行脑MRI检查。全身PET-CT对于指导放疗靶区精确勾画也有重要作用，特别是有肺不张或CT增强禁忌证情况下。因为NSCLC进展速度较快，PET-CT等各项检查4周内开始放疗为佳。

▶ 分期和预后

第8版AJCC/IASLC NSCLC TNM分期系统于2018年1月1日开始应用。具体详见参考文献^[1]。根据IASLC数据库，第8版分期的各临床分期和病理分期患者的生存数据见表1。

表1｜不同临床和病理TNM期别(AJCC第8版)非小细胞肺癌患者的预后

本文作者：中华医学会放射肿瘤治疗学分会中国医师协会放射肿瘤治疗医师分会中国抗癌协会放射治疗专业委员会中国临床肿瘤学会肿瘤放疗专家委员会

本文来源：《中华放射肿瘤学杂志》2020年第8期第29卷，第599-607页.

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