Background

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized distinct clinicopathological entity according to the fifth edition of the 2021 World Health Organization Classification (WHO) for thoracic tumors. Thoracic SMARCA4-UTs are diagnostically challenging to diagnose, especially on small biopsies.

Methods

We identified 35 thoracic SMARCA4-UTs from the Department of Pathology of West China Hospital, Sichuan University, between January 2017 and December 2022. In the present study, we summarized the clinicopathological features, prognostic significance and immunotherapy efficacy of thoracic SMARCA4-UTs.

Results

All 35 patients were male, and 88.6 % were smokers. The left upper lobe (25.7 %) and mediastinum (20.0 %) were the most affected sites. 17.1 % of the patients received surgical treatment. 30.4 % of the patients were stage III, and 69.6 % were stage IV. Solid architecture (100 %), rhabdoid morphology (51.4 %) and necrosis (42.9 %) were the common histological features. Immunohistochemical staining revealed CD34 and synaptophysin positivity in most patients (76.9 % and 65.2 %, respectively). Patients had unfavorable outcomes. Patients who received immunotherapy had better OS and PFS than those who did not (p = 0.007 and p = 0.02, respectively). Five patients were evaluated for immunotherapy efficacy, and four of those patients were negative expression of PD-L1. Cases 1–4 presented TIL counts ranging from 20 to 1000/HPF. Case 5 presented TIL counts of 5–10/HPF. Mutations in SMARCA4 were confirmed in cases 4 and 5, and the TMB was 5.98 and 5.03 mutations/Mb, respectively. Case 1 achieved a CR, cases 2–4 achieved a PR, and case 5 had a PD. Five patients who received immunotherapy were all alive, with OS ranging from 10.7 to 33.6 months.

Conclusions

Thoracic SMARCA4-UTs exhibited an aggressive clinical course, presented solid architecture with or without necrosis and/or rhabdoid morphology, and frequently expressed CD34 and synaptophysin. Some thoracic SMARCA4-UTs appear to be associated with responsiveness to immunotherapy, suggesting the need for validation in larger series.

中文翻译：

---

胸部SMARCA4缺陷未分化肿瘤35例临床病理、预后分析及免疫治疗疗效

背景

根据 2021 年第五版世界卫生组织胸部肿瘤分类 (WHO)，胸部 SMARCA4 缺陷型未分化肿瘤 (SMARCA4-UT) 是最近公认的一种独特的临床病理学实体。胸部 SMARCA4-UT 的诊断具有挑战性，尤其是小活检。

方法

我们从2017年1月至2022年12月期间从四川大学华西医院病理科鉴定了35例胸部SMARCA4-UT。在本研究中，我们总结了胸部SMARCA4-UT的临床病理特征、预后意义和免疫治疗疗效。

结果

所有 35 名患者均为男性，其中 88.6% 为吸烟者。左上叶（25.7%）和纵隔（20.0%）是受影响最严重的部位。 17.1%的患者接受了手术治疗。 30.4%的患者为III期，69.6%为IV期。实性结构（100%）、横纹肌样形态（51.4%）和坏死（42.9%）是常见的组织学特征。免疫组织化学染色显示大多数患者 CD34 和突触素阳性（分别为 76.9% 和 65.2%）。患者出现了不利的结果。接受免疫治疗的患者比未接受免疫治疗的患者具有更好的 OS 和 PFS（分别为 p = 0.007 和 p = 0.02）。对 5 名患者进行了免疫治疗疗效评估，其中 4 名患者 PD-L1 表达阴性。病例 1-4 的 TIL 计数范围为 20 至 1000/HPF。病例 5 的 TIL 计数为 5-10/HPF。病例4和病例5证实SMARCA4突变，TMB分别为5.98和5.03个突变/Mb。病例 1 达到 CR，病例 2-4 达到 PR，病例 5 达到 PD。接受免疫治疗的 5 名患者均存活，OS 为 10.7 至 33.6 个月。

结论

胸部 SMARCA4-UT 表现出侵袭性的临床病程，呈现实体结构，有或没有坏死和/或横纹肌样形态，并且频繁表达 CD34 和突触素。一些胸部 SMARCA4-UT 似乎与免疫治疗的反应相关，这表明需要进行更大规模的验证。