Zhu Jun, Xun Xin, Liu Jiayun, Su Bin, Li Yi, Chen Hong, Huang Meijin
Department of Oncology, 920th Hospital of Joint Logistics Support Force, People's Liberation Army, Kunming, Yunnan, China.
Front Immunol. 2025 Jun 26;16:1614283. doi: 10.3389/fimmu.2025.1614283. eCollection 2025.
Pulmonary adenosquamous carcinoma (ASC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with poorly defined molecular characteristics and therapeutic strategies. We present a 63-year-old male patient with stage IVa (cT4N3M1b) lung ASC. Next-generation sequencing (NGS) revealed co-occurring mutations in KRAS G12C, BRAF (non-V600E), PIK3CA, and FLT1. Biomarker analysis showed: PD-L1 expression of 18.11% (Tumor Proportion Score, TPS), a tumor mutation burden (TMB) of 3.7 mutations per megabase (mut/Mb), and microsatellite instability (MSI) classified as low (MSI-L) with an instability rate of 35.29%. As first-line treatment, the patient received six cycles of tislelizumab (a PD-1 inhibitor) combined with chemotherapy, followed by tislelizumab maintenance therapy for two years. The patient maintained sustained complete response (CR) with progression-free survival (PFS) reaching 46.5 months, significantly exceeding the typical median PFS of 8-12 months in advanced NSCLC populations. To our knowledge, this presents the first reported case of advanced pulmonary ASC harboring co-occurring driver mutations that demonstrated a remarkable response to immune checkpoint inhibitor (ICI) therapy. Our case highlights the critical role of comprehensive molecular profiling and rational combination strategies in managing rare lung cancer subtypes, establishing a potential treatment paradigm for genomically similar cases.
肺腺鳞癌（ASC）是一种罕见且侵袭性强的非小细胞肺癌（NSCLC）亚型，其分子特征和治疗策略尚不明确。我们报告了一名63岁的男性IVa期（cT4N3M1b）肺ASC患者。二代测序（NGS）显示KRAS G12C、BRAF（非V600E）、PIK3CA和FLT1同时发生突变。生物标志物分析显示：程序性死亡受体配体1（PD-L1）表达为18.11%（肿瘤比例评分，TPS），肿瘤突变负荷（TMB）为每兆碱基3.7个突变（mut/Mb），微卫星不稳定性（MSI）分类为低度（MSI-L），不稳定性率为35.29%。作为一线治疗，该患者接受了六个周期的替雷利珠单抗（一种PD-1抑制剂）联合化疗，随后接受了两年的替雷利珠单抗维持治疗。患者维持持续完全缓解（CR），无进展生存期（PFS）达到46.5个月，显著超过晚期NSCLC人群典型的中位PFS 8至12个月。据我们所知，这是首例报告的晚期肺ASC病例，该病例存在同时发生的驱动基因突变，对免疫检查点抑制剂（ICI）治疗表现出显著反应。我们的病例强调了全面分子谱分析和合理联合策略在管理罕见肺癌亚型中的关键作用，为基因组相似病例建立了潜在的治疗模式。
