胸部SMARCA4缺失性未分化肿瘤的病理诊断与联合免疫检测点抑制剂治疗  

Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment

作　　者：熊焰[1] 张波[2] 聂立功[3] 吴世凯 赵虎[5] 李东[1] 邸吉廷 XIONG Yan;ZHANG Bo;NIE Li-gong;WU Shi-kai;ZHAO Hu;LI Dong;DI Ji-ting(Department of Pathology,Peking University First Hospital,Beijing 100034,China;Department of Pathology,School of Basic Medical Sciences Peking University/Peking University Third Hospital,Beijing 100191,China;Department of Respiratory and Critical Care Medicine,Peking University First Hospital,Beijing 100034,China;Department of Oncology,Peking University First Hospital,Beijing 100034,China;Department of Thoracic Surgery,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院病理科,北京100034 [2]北京大学基础医学院病理学系/北京大学第三医院病理科,北京100191 [3]北京大学第一医院呼吸与危重症学科,北京100034 [4]北京大学第一医院肿瘤科,北京100034 [5]北京大学第一医院胸外科,北京100034

出　　处：《北京大学学报（医学版）》2023年第2期351-356,共6页Journal of Peking University:Health Sciences

基　　金：中央高水平医院临床科研业务费-北京大学第一医院院内交叉临床研究专项(2022CR35)。

摘　　要：探讨胸部SMARCA4缺失性未分化肿瘤(SMARCA4-deficient undifferentiated tumor,SMARCA4-UT)的临床病理特点和治疗策略。SMARCA4-UT是2021版《世界卫生组织胸部肿瘤分类》中的新类型,各科医生对其诊断、治疗、预后等问题均较为陌生。本次多学科研讨会以北京大学第一医院收治的1例胸部SMARCA4-UT为例,集中研讨了该类肿瘤的病理诊断、分子检测、治疗相关分子靶点、免疫检验点抑制剂治疗以及新辅助治疗反应的病理学评估等问题。患者为老年男性,有长期吸烟史,以右肺下叶实性肿瘤快速进展入院。病理学检测,肿瘤细胞上皮样,组织结构上无任何分化特点;免疫组织化学染色显示,CD34弥漫阳性,SALL4部分细胞阳性,SMARCA4基因编码的蛋白BRG1表达缺失;二代测序证实,肿瘤存在SMARCA4基因突变(c.2196T>G,p.Y732Ter)。综上,病理诊断符合胸部SMARCA4-UT。术前TNM分期为T1N2M0(ⅢA)。程序性细胞死亡1-配体1(programmed cell death 1-ligand 1,PD-L1,克隆号SP263)抗体免疫组化染色显示,阳性肿瘤细胞比例评分(tumor proportion score,TPS)为2%。肿瘤突变负荷(tumor mutation burden,TMB)检测结果为16.3/Mb,微卫星检测结果为微卫星稳定型(microsatellite stability,MSS)。经化疗联合免疫检测点抑制剂新辅助治疗两周后,行胸腔镜下右肺下叶切除术。术后新辅助治疗反应的病理学评估结果为病理学完全缓解(complete pathologic response,CPR),新辅助治疗后病理学分期为ypT0N0M0。术后完成了5周期化疗联合免疫检测点抑制剂辅助治疗。随访截止2022年10月,肿瘤无复发、转移,微小残留病灶(minimal residual disease,MRD)检测阴性。目前认为,只要BRG1免疫组织化学染色阴性,无论是否检测到SMARCA4基因突变,均可归入SMARCA4缺失性肿瘤,SMARCA4缺失性肿瘤包括多种癌和肉瘤。SMARCA4-UT的诊断,除了BRG1表达缺失以外,还必须具备相应的组织形态,并排除其他伴有BRG1表达缺失We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor(SMARCA4-UT).Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors,and doctors are relatively unfamiliar with its diagnosis,treatment,and prognosis.Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example,this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT,including histological features,immu-nohistochemical and molecular phenotype,immune checkpoint inhibitor(ICI)therapy,and pathological assessment of neoadjuvant therapy response.The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung.Histologically,tumor cells were epithelioid,undifferentiated,diffusely positive for CD34,and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells,and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation(c.2196T>G,p.Y732Ter).The pathological diagnosis reached as thoracic SMARCA4-UT,and the preoperative TNM stage was T1N2M0(ⅢA).Tumor proportion score(TPS)detected by immunohistochemistry of programmed cell death 1-ligand 1(PD-L1,clone SP263)was 2%.Tumor mutation burden(TMB)detected by NGS of 1021 genes was 16.3/Mb.Microsatellite detection showed the tumor was microsatellite stable(MSS).Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI.Right lower lobectomy was performed through thoracoscopy after the two weeks’neoadjuvant.The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response(CPR).The post-neoadjuvant tumor TNM stage was ypT0N0M0.Then,five cycles of adjuvant therapy were completed.Until October 2022,neither tumor recurrence nor metastasis was detected,and minimal residual disease(

关 键 词：胸部SMARCA4缺失性未分化肿瘤 程序性细胞死亡1-配体1 肿瘤突变负荷 免疫检验点抑制剂 新辅助治疗 病理学评估 

分 类 号：R365[医药卫生—病理学]