Synchronous Primary Lung Cancers Containing Discrete Driver Mutations in a Never-Smoker: Case Report

Although most lung cancer patients present with one primary cancer, some present with multiple lung cancers of different clonal origin. Timely recognition of synchronous multifocal primary lung cancer (MPLC) enables distinct treatment regimens that reflect the unique genotypic makeup and location of each cancer. However, recognition of synchronous MPLCs is challenging given the prevalence of multifocal disease. Here, we report a case of a patient diagnosed with anaplastic lymphoma kinase, termed ALK, positive metastatic lung adenocarcinoma whose follow-up computerized tomography (CT) imaging identified one lesion, present since the patient's initial presentation, with a distinctly different response to treatment than other lesions. Biopsy results showed a distinct MPLC, an epidermal growth factor receptor (EGFR)-positive adenocarcinoma with no evidence of an ALK mutation. The EGFR lesion was treated with curative intent via surgical resection while the ALK disease was managed with palliative intent via targeted therapy. To our knowledge, there have been no other reports of two synchronous MPLCs of an adenocarcinoma subtype with completely distinct EGFR and ALK driver mutations. This case highlights the importance of serial follow-up imaging, combined with biopsy of lesions with atypical treatment responses, as a method for identifying synchronous MPLCs and adjusting treatment to optimize patient outcomes.