Gene alterations, smoking and histology: when the deeper means the rarer

Lung cancer is the leading cause of death for solid tumors worldwide with an annual mortality of over one million (1). Despite advances in defining the molecular mechanisms involved in lung oncogenesis and the remarkable efforts made to improve screening programs for secondary cancer prevention, patients’ prognosis remains poor. Lung carcinoma includes a series of different diseases which are roughly divided into two groups based on clinical and histo-pathological features: non-small-cell lung cancer (NSCLC), accounting for almost 80% of lung cancer diagnosis and small cell lung cancer (SCLC) responsible for the remaining 20%. NSCLCs were further classified as: adenocarcinoma (ADC, and its variants); squamous cell carcinoma (SCC) and large cell carcinoma (LCC)—comprising the neuro-endocrine variant (LCNEC).