What does this research mean for the field?

Multiple primary lung cancers can exhibit extreme genetic and PD-L1 heterogeneity within a single patient, requiring comprehensive molecular profiling to distinguish synchronous tumors from metastases and guide individualized therapy. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

To highlight the significance of intratumor PD-L1 heterogeneity in multiple primary lung adenocarcinomas.

May 20, 2026

D110-22 Nine Primary Lung Adenocarcinomas in a Single Patient: A Paradigm of Pd-L1 Heterogeneity and Tumor Microenvironment Diversity

Key Points

To highlight the significance of intratumor PD-L1 heterogeneity in multiple primary lung adenocarcinomas.
Case report of a 39-year-old woman with nine synchronous adenocarcinomas
Histopathological and molecular analyses of tumor specimens
Imaging techniques including PET-CT and chest CT scans for tumor evaluation.
Nine distinct primary adenocarcinomas confirmed through histopathology and genomic evaluation.
Substantial PD-L1 expression variability across tumors noted, complicating treatment decisions.
Patient achieved stable disease on Atezolizumab after a lobectomy.

Abstract

Abstract Introduction While lung cancer treatment has been significantly impacted by immune checkpoint inhibitor therapy, multiple primary lung cancers (MPLC) continue to complicate diagnostic and therapeutic work-up. A rare case of a 39-year-old woman with nine synchronous adenocarcinomas revealed substantial intratumor PD-L1 heterogeneity, emphasizing diagnostic and therapeutic challenges. Case Report The patient had a medical history significant for active smoking (25 pack-years) and secondhand exposure. Past medical history included cutaneous intraepithelial neoplasia of the right upper lip and total thyroidectomy 17-years earlier. At presentation, she was in good clinical condition with stable cardiopulmonary function. Initial imaging with chest computed tomography revealed a suspicious pulmonary nodule, which was further evaluated by PET-CT scan. Wedge resection performed in May 2019 confirmed the diagnosis of adenocarcinoma (AC 1). In June 2019, a follow-up CT revealed another suspicious nodule, and atypical resection confirmed a second adenocarcinoma (AC 2). Subsequent imaging in April 2020 identified two additional pulmonary nodules. Segmentectomy of the right S5 and atypical resection of the right S2 confirmed two further adenocarcinoma (AC 3 and 4). Histopathological and molecular analyses demonstrated that these four tumors were independent non-small cell lung cancers (NSCLCs) with heterogeneous genetic and molecular profiles. All were early-stage cancers, and adjuvant therapy was not indicated. The patient remained in stable disease on follow-up, with no evidence of recurrence until May 2024 when a PET-Scan showed suspicious tissue in the right upper lobe. A right upper lobectomy in July 2024 uncovered five additional synchronous adenocarcinomas. Detailed histomorphology and genomic evaluation confirmed these were distinct primary tumors, totaling nine primary lung cancers. Since September 2024, the patient received Atezolizumab with CT-imaging confirming stable disease. Discussion Histopathological and molecular analyses confirmed that all tumors were independent primary lung cancers rather than intrapulmonary metastases. This case highlights the important role of comprehensive genetic and molecular profiling in distinguishing between synchronous lung cancers and metastatic disease. The occurrence of nine tumors in a single patient underscores the genetic and histological heterogeneity of MPLCs, complicating therapeutic strategies due to major PD-L1 variations. Importantly, this case expands the understanding of MPLCs, emphasizing how genetic diversity can change treatment from active surveillance to systemic therapy. In the era of whole-genome sequencing and advanced genetic analyses, this case challenges the current understanding of synchronous lung cancer and should lead pulmonary teams to explore both refined diagnostic strategies and individualized treatment algorithms for this complex lung cancer cohort. This abstract is funded by: None

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