Genome Sequencing of Multiple Primary Lung Cancers Harbouring Mixed Histology and Spontaneously Regressing Small-Cell Lung Cancer

TL;DR

This paper reports a rare case of multiple primary lung cancers with mixed histology and spontaneous regression of small-cell lung cancer, analyzed through genome sequencing.

Contribution

The study presents a unique case with mixed histology and spontaneous regression, supported by whole-genome sequencing insights.

Findings

The patient had multiple primary lung cancers with mixed histology of NSCLCa and SCLC.

Spontaneous regression of SCLC was observed without treatment.

Genomic profiles of the tumors were distinct, suggesting the need for targeted therapies.

Abstract

Up to 15% of lung cancer patients present two or more anatomically separate primary lung lesions, known as multiple primary lung cancers (MPLCs). While surgical resection or stereotactic body radiation therapy (SBRT) is the standard of care for most early-stage lung cancer cases, this may not be an option for patients with widespread tumours, highlighting the need for the improved targeted management of MPLC patients, which remains challenging. Moreover, the spontaneous regression (SR) of small-cell lung cancer (SCLC) is rare, with only four cases accounted for between 1988 and 2018. We report a rare MPLC case harbouring the mixed histology of non-small-cell lung cancer adenocarcinoma (NSCLCa) and SCLC and the SR of SCLC without treatment. The patient was diagnosed in 2015 with MPLCs, identified as NSCLCa and SCLC. In 2016, a restaging PET/CT scan prior to the start of treatment showed SCLC SR. In 2018, a further tumour was detected in the patient’s mandible, and a re-biopsy of the SCLC revealed histology consistent with NSCLCa. Whole-genome sequencing (WGS) analysis identified a high expression of programmed death ligand-1 (PDL-1) in the NSCLCa, which was treated with pembrolizumab. WGS revealed distinct genomic profiles and mutational mechanisms in MPLCs, suggesting the need for distinct targeted therapies to improve the management of MPLC patients and highlighting the importance of precision evaluation.

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