Small cell lung cancer with SYN2::PPARG fusion

Abstract

Introduction: Small cell lung cancer (SCLC) accounts for 15% of lung cancers worldwide. It is an aggressive tumor that is typically diagnosed at an advanced stage. Treatment involves chemo-immunotherapy and/or radiotherapy. Identifying druggable targets activated by specific genetic alterations represents a significant challenge in improving patient outcomes.

Methods: We conducted a retrospective examination of molecular findings in lung cancer patients' records from 2021 to 2022. We discovered a unique case of SCLC harboring the SYN2-PPARG fusion. Histopathological analysis confirmed the diagnosis of SCLC.

Case report: A 60-year-old woman, a heavy smoker, came to our attention due to a persistent cough with slight hemoptysis. Imaging, including axial contrast-enhanced computed tomography, revealed an advanced disease with extra-thoracic spread. Tumor histology showed a sheet-like proliferation of small-sized cells with a neuroendocrine phenotype and a high proliferation tumor cell fraction. Molecular genetic analysis using NGS approach revealed a fusion involving the SYN2 and PPARG genes.

Conclusion: The SYN2-PPARG fusion has recently been documented in sinonasal adenocarcinoma and has been reported in only a single SCLC case previously. Highlighting the molecular heterogeneity within this aggressive form of lung cancer could potentially aid in the selection of specific therapies.

Keywords: Gene fusion; Small cell lung cancer.