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Abstract：
Gene alteration in anaplastic lymphoma kinase (ALK) is rare, and the efficacy of ALK inhibitors in the treatment of carcinoma of unknown primary (CUP) with ALK alteration remains unclear. The patient was a 56-year-old woman who presented with cervical lymph node swelling. Computed tomography revealed paraaortic, perigastric, and cervical lymph node swelling; ascites; a liver lesion; and a left adrenal mass. A cervical lymph node biopsy was performed, and pathological diagnosis of an undifferentiated malignant tumor was conducted. Finally, the patient was diagnosed with CUP and treated with chemotherapy. To evaluate actionable mutations, we performed a multigene analysis, using a next-generation sequencer (FoundationOne® CDx). It revealed that the tumor harbored an echinoderm microtubule-associated protein-like 4 (EML4) and ALK fusion gene. Additionally, immunohistochemistry confirmed ALK protein expression. Alectinib, a potent ALK inhibitor, was recommended for the patient at a molecular oncology conference at our institution. Accordingly, alectinib (600 mg/day) was administered, and the multiple lesions and symptoms rapidly diminished without apparent toxicity. The administration of alectinib continued for a period of 10 months without disease progression. Thus, ALK-tyrosine kinase inhibitors should be considered in patients with CUP harboring the EML4-ALK fusion gene.
摘要：
间变性淋巴瘤激酶（ALK）的基因改变很少见，ALK抑制剂治疗原发灶未知癌（CUP）伴ALK改变的疗效尚不清楚。患者是一名56岁的女性，表现为颈部淋巴结肿大。计算机断层扫描显示主动脉旁,胃周,和颈部淋巴结肿大；腹水；肝脏病变；和左肾上腺肿块。进行了颈淋巴结活检，病理诊断为未分化的恶性肿瘤。最后,患者被诊断为CUP并接受化疗.为了评估可行的突变，我们进行了多基因分析,使用下一代音序器(FoundationOne®CDx)。揭示该肿瘤具有棘皮动物微管相关蛋白样4（EML4）和ALK融合基因。此外,免疫组化证实ALK蛋白表达。阿莱替尼,一种强效的ALK抑制剂,在我们机构的分子肿瘤学会议上推荐给患者。因此，给予阿来替尼（600毫克/天），多发性病变和症状迅速减轻，无明显毒性。阿来替尼的给药持续10个月，无疾病进展。因此，对于携带EML4-ALK融合基因的CUP患者，应考虑使用ALK-酪氨酸激酶抑制剂。
