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). HRAS and TP53 mutations were detected from UC surgical tissue and postoperative ctDNA. Unexpectedly, the epidermal growth factor receptor (EGFR) 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, EGFR 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.
Keywords: Circulating tumor DNA (ctDNA); case report; epidermal growth factor receptor (EGFR); non-small cell lung cancer (NSCLC); simultaneous cancer; urothelial carcinoma (UC).
2020 Annals of Translational Medicine. All rights reserved.