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Introduction Lung cancer remains the most common cause of cancer-related deaths worldwide, with Non-Small Cell Lung Cancer (NSCLC) the predominant histologic subtype. Increasingly, molecular mutations are identified and used as therapeutic targets. We describe the case of a woman diagnosed with locally metastatic NSCLC, and distinct pulmonary masses, later identified as two independent primary lung tumors based on molecular profiling. Case Report A 58-year-old-female presented with cough and hemoptysis. Chest Computed Tomography (CT) revealed a 4.3cm mass in the right lung apex, 2.0 cm nodule in the right lower lobe (RLL), and right paratracheal/hilar adenopathy. Subsequent Positron Emission Tomography-Computed Tomography (PET-CT) showed uptake in the right upper lobe (RUL) (SUV 12.2) and RLL (standard uptake value (SUV) 2.5) masses and mediastinal lymph nodes, but no distant metastases. Bronchoscopic biopsy of the RUL mass and 4R lymph node were positive for poorly differentiated adenocarcinoma, and molecular analysis revealed Epidermal Growth Factor Receptor (EGFR) L858R mutation. Subsequent Electromagnetic Navigation (EMN) biopsy of the RLL lesion also showed adenocarcinoma, but with an EGFR exon-19 deletion. Both were negative for T790M mutation. She was therefore diagnosed with two separate primaries instead of intrathoracic metastases. She started erlotinib and after 4 months, repeat PET-CT showed complete response (CR) in the RLL and partial response (PR) in the RUL. Decision was made to pursue surgery with RUL/RLL bilobectomy. Pathology showed evidence of N2 disease; therefore, at time of surgery she was stage IIIA, presumably from the RUL mass. The RLL mass was presumed to be stage I. These were successfully resected, and she was deemed to have no evidence of disease (NED) post-operatively. Discussion Although co-mutations within the same tumor have been reported in up to 12% of patients,28 we are not aware of other cases in which a single patient was diagnosed with two separate primary lung tumors based on genetic profiles. Consequently, she was able to be treated with curative rather than palliative intent.

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