OBJECTIVES In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement identifies a subgroup of patients who are sensitive to ALK tyrosine kinase inhibitors (TKIs). ALK fusion is extremely rare in small-cell lung cancer (SCLC). To the best of our knowledge, only two cases of SCLC harboring ALK fusion mutation has been reported previously, both of whom carrying EML4-ALK fusion. There are no standard treatment options for SCLC patients with ALK fusion mutations. Herein, we described a rare case of ALK-rearranged SCLC responding to ALK inhibitors. MATERIALS AND METHODS Immunohistochemistry (IHC) assay and next-generation sequencing (NGS) were performed on the biopsied tumor tissue. RESULTS NGS detected a novel pleckstrin homology and RUN domain containing M2 (PLEKHM2)-ALK fusion, while the IHC analysis revealed an ALK-positive tumor. For extensive SCLC patients, median OS was about 8-13 months. The patient in this case had durable clinical benefit upon the treatment with ALK inhibitors, achieving an overall survival (OS) of more than 27 months. CONCLUSION This case provides a meaningful reference for the treatment of SCLC patients with ALK fusion mutations. This case also provides valuable information on the response to ALK inhibitors of patients with PLEKHM2-ALK fusion and better understanding of ALK-TKI applications in the future. NGS may be used as a routine test to explore more treatment opportunities for tumor SCLC patients.

中文翻译：

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PLEKHM2-ALK：小细胞肺癌中的新型融合药物，对ALK抑制剂具有持久反应。

目的在非小细胞肺癌（NSCLC）中，间变性淋巴瘤激酶（ALK）重排可识别对ALK酪氨酸激酶抑制剂（TKIs）敏感的患者亚组。ALK融合在小细胞肺癌（SCLC）中极为罕见。据我们所知，以前仅报道了两例带有ALK融合突变的SCLC病例，两例均携带EML4-ALK融合。对于ALK融合突变的SCLC患者，没有标准的治疗选择。在这里，我们描述了一种罕见的ALK重组SCLC对ALK抑制剂反应的案例。材料与方法在活检的肿瘤组织上进行了免疫组织化学（IHC）分析和下一代测序（NGS）。结果NGS检测到一种新的pleckstrin同源性和RUN域，其中包含M2（PLEKHM2）-ALK融合蛋白，IHC分析显示ALK阳性肿瘤。对于广泛的SCLC患者，中位OS​​约为8-13个月。在这种情况下，患者接受ALK抑制剂治疗后具有持久的临床益处，实现了超过27个月的总生存期（OS）。结论本病例为ALK融合突变的SCLC患者的治疗提供了有意义的参考。该案例还提供了有关PLEKHM2-ALK融合患者对ALK抑制剂反应的有价值信息，并为以后更好地了解ALK-TKI应用提供了信息。NGS可用作常规测试，以探索肿瘤SCLC患者更多的治疗机会。达到27个月以上的总生存期（OS）。结论本病例为ALK融合突变的SCLC患者的治疗提供了有意义的参考。该案例还提供了有关PLEKHM2-ALK融合患者对ALK抑制剂反应的有价值信息，并为以后更好地了解ALK-TKI应用提供了信息。NGS可用作常规测试，以探索肿瘤SCLC患者更多的治疗机会。达到27个月以上的总生存期（OS）。结论本病例为ALK融合突变的SCLC患者的治疗提供了有意义的参考。该案例还提供了有关PLEKHM2-ALK融合患者对ALK抑制剂反应的有价值信息，并为以后更好地了解ALK-TKI应用提供了信息。NGS可用作常规测试，以探索肿瘤SCLC患者更多的治疗机会。