Defining the needle in a haystack: A compendium of genomic, pathologic, and clinical characteristics of rare pulmonary tumors

A major paradigm shift in the diagnosis, management, and survival outcomes of early and advanced non-small cell lung cancer has transpired over the past few decades in thoracic oncology with the incorporation of molecular testing, targeted therapy, immunotherapy, neoadjuvant, and adjuvant approaches. However, transformation in the management and survival outcomes of rare lung tumors is lacking. Given the scarcity of these tumor types, randomized trials are rarely performed, and treatment is extrapolated from case series, tumor-agnostic trials, or cancers with similar histology. Literature informing the management of rare pulmonary tumors is typically limited to a single histology, unique features, or extraordinary responses to therapy. Few resources detailing genomic characteristics and delineating features of these tumors are available, often resulting in suboptimal treatment. Here, we explore the clinical, histopathologic, genomic features and potential therapies of five rare pulmonary tumors, namely adenosquamous, basaloid squamous, mucoepidermoid, carcinosarcoma, and NUT carcinoma, to build a resource for rare histological subtypes of the lung and emphasize knowledge gaps in the management of these tumors. Our recommendations are based on a comprehensive review of case reports and series, clinical trials, and the “Indiana University Experience.”