Moving through rare lung cancer histologies: a narrative review on diagnosis and treatment of selected infrequent entities

Background and Objective: In recent years, improvements in histological subtyping led to a better characterization of newly diagnosed non-small cell lung cancers (NSCLC). Of these, 5% has a rare histology according to the 2021 World Health Organization (WHO) Classification of thoracic tumors. Besides being infrequent, rare lung cancers are often difficult to diagnose, especially when dealing with small specimens, resulting in a scarce number of prospective evidences for their correct clinical management. However, the increased awareness of such entities, along with the advent of high-throughput sequencing techniques, has brought to a deeper understanding of the biological and molecular mechanisms underlying lung neoplasms formation, paving the way for a personalized medicine even for rare lung malignancies. The aim of this review is to summarize the current knowledge of main rare lung epithelial neoplastic entities in order to help physicians in everyday clinical practice. Methods: We conducted a search on the two major online scientific databases, PubMed and EMBase, selecting English articles regarding epithelial lung tumors with rare histology published from 2010 onward. Key Content and Findings: We compiled a narrative review on clinical, pathological and therapeutic aspects of the main rare epithelial lung cancer histologies according to the 2021 WHO Classification. Conclusions: Rare lung cancers diagnosis is often difficult and evidences on their correct clinical management are rather scanty. Improved diagnostic techniques have led to greater awareness of these entities. Molecular characterization of such neoplasms may guide treatment choice for personalized treatments in some subsets of rare tumors.