Supplementary Material for: 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 positive, termed ALK, 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-positive (EGFR) 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.

尽管多数肺癌患者仅罹患单发原发性肿瘤，但部分患者会出现不同克隆起源的多灶性肺部肿瘤。及时识别同步多原发肺癌（synchronous multifocal primary lung cancer, MPLC），可针对每一处肿瘤独特的基因型特征与发病部位制定差异化治疗方案。然而，由于多灶性病变的检出率较高，同步MPLC的诊断颇具挑战。本文报告1例确诊为间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）阳性转移性肺腺癌的患者，其随访计算机断层扫描（computed tomography, CT）影像显示，自初次就诊时便存在的一处病灶与其余病灶对治疗的响应存在显著差异。活检结果证实该病灶为另一独立的MPLC：表皮生长因子受体（epidermal growth factor receptor, EGFR）阳性肺腺癌，且未检测到ALK突变。针对该EGFR阳性病灶，我们以根治为目的实施了手术切除；而ALK阳性病灶则通过靶向治疗采取姑息性管理方案。据我们所知，目前尚无关于两例同步发生、均为腺癌亚型且携带完全不同EGFR与ALK驱动基因突变的MPLC的相关报道。本案例凸显了连续随访影像结合对治疗响应异常的病灶进行活检的重要性，该方法可用于识别同步MPLC并调整治疗方案以优化患者预后。