Abstract Case Description A 60-year-old woman with a 48-pack-year smoking history, COPD, and a prior diagnosis of stage IV non-small cell lung carcinoma (NSCLC) with hepatic metastases in 2020 initially achieved a complete metabolic response on PET imaging after treatment with pemetrexed, carboplatin, and pembrolizumab. Therapy was discontinued following pembrolizumab-induced interstitial nephritis, and she remained in remission until 2024.On routine surveillance imaging in 2024, new spiculated nodules in the right upper lobe were identified. She underwent right video-assisted thoracoscopic surgery (VATS) converted to open thoracotomy with right upper lobectomy. Pathologic examination revealed three distinct primary lung malignancies within the same lobe: invasive lepidic adenocarcinoma, invasive acinar adenocarcinoma, and small cell carcinoma. No lymph-node involvement was detected.Her postoperative course was complicated by prolonged respiratory failure, recurrent lung collapse, multifocal pneumonia, and hydropneumothorax requiring extended ventilatory support. She was successfully extubated and subsequently received carboplatin-etoposide chemotherapy for the small-cell component, with lurbinectedin planned for progression. Over the following months, her condition declined with recurrent episodes of acute hypoxemic respiratory failure and pneumonia, and she was transitioned to comfort measures only after a multidisciplinary discussion. Discussion The coexistence of three histologically distinct primary lung cancers within a single lobe is exceptionally rare. The simultaneous presence of two adenocarcinomas and a small cell carcinoma in one anatomic region illustrates the profound heterogeneity of lung cancer biology. This likely represents field cancerization, where chronic tobacco exposure promotes multiple independent neoplastic clones rather than intrapulmonary spread of a single malignancy.Accurate histopathologic distinction is critical, as misinterpreting these lesions as metastatic disease could lead to incorrect staging and suboptimal management. Each tumor in this case represented a separate lineage, requiring individualized therapeutic consideration. The patient’s history of complete PET-confirmed remission followed by the emergence of three new, genetically distinct primaries shows the unpredictable nature of lung cancer evolution and its capacity for multiclonal transformation.This case highlights the complexity of thoracic oncology, where different tumor types may coexist and progress independently within the same lobe. It serves as a striking reminder of the biological diversity of lung carcinogenesis and the need for precise tissue diagnosis and personalized management strategies in multifocal pulmonary malignancies. This abstract is funded by: none
Phadke et al. (Fri,) studied this question.