Qian Chengyuan, Dai Nan, Xu Mingfang, Luo Hao, Feng Yan, Zhang Min, Chen Rongrong, Wang Dong
Department of Cancer Center, Daping Hospital & Army Medical Center of the PLA, Chongqing, China.
Geneplus-Beijing, Beijing, China.
Ann Transl Med. 2020 Oct;8(20):1323. doi: 10.21037/atm-20-6552.
The diagnosis and treatment for multiple primary cancers have been a great challenge in clinical practice. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA that circulates in the blood. Herein we report a case that ctDNA facilitated the diagnosis of synchronous urothelial carcinoma (UC) and lung adenocarcinoma. A 58-year-old male patient was diagnosed with UC initially. Computed tomography (CT) revealed multiple metastases without the brain after surgery and adjuvant chemotherapy. However, the patient had a progressively worsened headache symbol during system therapy. We explored the genome variations using next-generation sequencing (NGS). and mutations were detected from UC surgical tissue and postoperative ctDNA. Unexpectedly, the epidermal growth factor receptor () exon 19 deletion (19del) mutation, which is common in non-small cell lung cancer (NSCLC), was also identified in ctDNA. Pathological analysis of a neck lymph node confirmed adenocarcinoma derived from the lung. Meanwhile, 19del was detected in neck lymph node biopsy. The ctDNA contained both UC and lung adenocarcinoma-derived mutations. Thus, the diagnosis was modified into synchronous UC and lung adenocarcinoma. Interestingly, the lung adenocarcinoma-derived lesions responded well to osimertinib (80mg, once daily), while the UC did not. His headache rapidly subsided and disappeared. This case demonstrates that ctDNA analysis may better capture the molecular heterogeneity harbored by multiple primary tumors in a patient and can facilitate the diagnosis and therapy of patients with simultaneous cancers.
多原发性癌症的诊断和治疗一直是临床实践中的巨大挑战。循环肿瘤DNA（ctDNA）是肿瘤来源的片段化DNA，存在于血液中循环。在此，我们报告一例ctDNA有助于同步性尿路上皮癌（UC）和肺腺癌诊断的病例。一名58岁男性患者最初被诊断为UC。计算机断层扫描（CT）显示术后及辅助化疗后出现多处转移，但无脑部转移。然而，该患者在系统治疗期间头痛症状逐渐加重。我们使用下一代测序（NGS）探索基因组变异。在UC手术组织和术后ctDNA中检测到了 和 突变。出乎意料的是，在ctDNA中还发现了非小细胞肺癌（NSCLC）中常见的表皮生长因子受体（）外显子19缺失（19del）突变。颈部淋巴结病理分析证实为肺源性腺癌。同时，在颈部淋巴结活检中检测到19del。ctDNA中同时含有UC和肺腺癌来源的突变。因此，诊断修正为同步性UC和肺腺癌。有趣的是，肺腺癌来源的病灶对奥希替尼（80mg，每日一次）反应良好，而UC则不然。他的头痛迅速缓解并消失。该病例表明，ctDNA分析可能更好地捕捉患者多种原发性肿瘤所具有的分子异质性，并有助于同时患有多种癌症患者的诊断和治疗。
