Objective: To investigate the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumors, and the diagnostic value of the cells in serous effusion. Methods: Eleven cases of SMARCA4-deficient tumor were collected from the Affiliated Hospital of Hebei University, China from January 2018 to July 2023, which were diagnosed using cell block of serous effusion. The clinical, histopathological, immunohistochemical and molecular genetic features were reviewed, along with related literature. Results: All the 11 patients were males with ages ranging from 54 to 77 years (median 64 years). Nine patients were smokers and two had an unknown smoking history. Most of them complained of cough and dyspnea with pleural effusion. The primary tumor sites included lung (9 cases), thoracic wall (1 case), and mediastinum (1 case), while 3 patients had a history of lung surgery. Histologically, tumor cells were large and pleomorphic, with increased nuclear-cytoplasmic ratio. They also showed round nuclei, conspicuous nucleoli, and basophilic cytoplasm in serous effusion. Immunohistochemically, tumor cells in all cases were negative for SMARCA4/BRG1, CKpan and CK7, but positive for SMARCB1/INI1. Some of the cases were positive for CD34 (7/11), synaptophysin (4/11) and SALL4 (2/11). Histologically, monotonous tumor cells formed solid sheets or anastomosing islands with poor cell adhesion and rhabdoid morphology. Brisk mitotic figures were accompanied by large areas of necrosis. Some cases focally exhibited syncytia, and some had bright cytoplasm and vesicular chromatin. The immunohistochemical profiles in the tumor tissues were consistent with those of cytology. Six cases were negative for PD-L1 (22c3). Among the 6 cases analyzed by targeted next generation sequencing, concurrent SMARCA4 and TP53 mutations were detected in all 6 cases. Some of the 6 tumors showed mutations of STK11, CDKN2A, and MET, and amplification of ERBB2, exon deletion of BRCA2, etc. Follow-up information was available in all cases and ranged from 2 to 24 months. The patients showed metastases to various sites, including lymph node, liver, kidney, adrenal gland, brain, bone and other sites. Four patients died of the tumor. The survival time of 4 patients who underwent radical resection or radiofrequency ablation was more than 13 months. Conclusions: SMARCA4-deficient thoracic sarcoma is a rare but highly aggressive tumor with dismal prognosis and rhabdomyoid features. It is difficult to diagnose this disease using only serous effusion samples. This tumor thus warrants careful consideration. Accurate diagnosis can greatly improve early diagnosis and treatment of these tumors.
目的： 探讨浆膜腔积液中SMARCA4缺失胸部未分化肿瘤的细胞病理学特点，及浆膜腔积液细胞学结合免疫组织化学在该肿瘤的诊断价值。 方法： 收集河北大学附属医院2018年1月至2023年7月以浆膜腔积液细胞学为首次诊断依据的SMARCA4缺失胸部未分化肿瘤11例的临床及病理学资料，分析浆膜腔积液细胞形态、免疫组织化学特征，并分析患者相应的原发或转移病灶的组织学标本病理特征，对部分病例进行二代测序基因检测。 结果： 患者均为男性，年龄54~77岁，中位年龄64岁，9例有长期吸烟史。多伴咳嗽、发憋、胸痛症状，均伴胸腔或心包积液。影像学提示原发部位肺部9例，纵隔1例，肺及胸壁均累及1例。其中3例有外院肺肿瘤手术史，1例有对侧肺腺癌手术史。浆膜腔积液肿瘤细胞大且异型性明显，核质比增大，核大圆形，核仁明显，部分核形不规则，胞质嗜酸性。免疫组织化学SMARCA4/BRG1均失表达，广谱细胞角蛋白、细胞角蛋白7均阴性，SMARCB1/INI1均阳性；7例CD34阳性，4例突触素弱阳性，2例SALL4弱阳性。组织学标本瘤细胞黏附性差，不规则片状或巢状排列，横纹肌样，核分裂象多见，伴肿瘤性坏死。部分肿瘤细胞呈合体细胞样，部分细胞胞质空亮。免疫组织化学表达与浆膜腔积液细胞一致，6例行PD-L1（22C3）检测均阴性。二代测序6例均有SMARCA4移码突变及TP53突变，部分病例检测到STK11、CDKN2A、MET突变及ERBB2扩增，BRCA2部分外显子缺失。随访时间2~24个月，患者均发生不同程度区域淋巴结转移，或肝、肾、肾上腺、颅脑、骨转移，4例死亡，4例经手术根治性切除或射频消融的病例生存时间均超过13个月。 结论： SMARCA4缺失胸部未分化肿瘤恶性程度高，患者预后差，形态有横纹肌样特征。浆膜腔积液细胞诊断困难，选取针对性的免疫组织化学指标可协助诊断。工作中应提高对此病的警惕性，避免漏诊及误诊，以达到早诊断、合理治疗的目的。.