Chronic Obstructive Pulmonary Disease (COPD) and lung cancer are strictly related. To date, it is unknown if COPD-associated cancers are different from the tumors of non-COPD patients. The main goal of the study was to compare the morphological/molecular profiles of lung adenocarcinoma (LUAD) samples of COPD, non-COPD/smokers and non-COPD/non-smokers, and to investigate if a genetic instability also characterized non-pathological areas. This study included 110 patients undergoing surgery for a LUAD, divided into three groups: COPD/smoker LUAD (38), non-COPD/smoker LUAD (54) and non-COPD/non-smoker LUAD (18). The tissue samples were systemically evaluated by pathologists and analyzed using a 30-gene Next Generation Sequencing (NGS) panel. In a subset of patients, tissues taken far from the neoplasia were also included. The non-COPD/smoker LUAD were characterized by a higher proliferative index (p = 0.001), while the non-COPD/non-smoker LUAD showed higher percentages of lepidic pattern (p = 0.008), lower necrosis, higher fibrosis, and a significantly lower mutation rate in the KRAS and PIK3CA genes. Interestingly, the same gene mutations were found in pathological and normal areas exclusively in the COPD/smokers and non-COPD/smokers. COPD/smoker LUAD seem to be similar to non-COPD/smoker LUAD, particularly for the genetic background. A less aggressive cancer phenotype was confirmed in non-COPD/non-smokers. The genetic alterations detected in normal lungs from smokers with and without COPD reinforce the importance of screening to detect early neoplastic lesions.

In the diagnostic setting of head and neck squamous cell carcinoma (HNSCC), there is an unmet need for robust histological prognosticators, since grading alone is considered to be of disputed clinical relevance. In this context, the present study assessed site-specific and tumor compartment characteristics as potential histological risk factors in HNSCC. Morphological and immunophenotypic (such as CD8 and PD-L1) characteristics of tumor cells, the immune microenvironment and the invasive margin (IM) were assessed in 248 patients with HNSCC who were followed up for >20 years, to determine their site specificity and impact on the overall survival of patients. Laryngeal and hypopharyngeal carcinomas were characterized by keratinization, cell cannibalism and anaplastic features; oropharyngeal carcinoma was characterized by a high grade and necrosis; and oral carcinomas was characterized by keratin pearls, eosinophil infiltrates and perineural invasion (P<0.05). CD8 distribution homogeneity, tumor center and/or IM perineural invasion, and sparse lymphocytic host response in the IM (LHR-IM) were unfavorable prognosticators (P<0.05). Among these parameters, only LHR-IM and perineural invasion throughout the tumor independently predicted an unfavorable prognosis, along with disease stage. Grade, keratinization, anaplastic features, cell cannibalism, necrosis-related features, eosinophils, worst pattern of invasion (the most aggressive pattern of tumor cell proliferation found at the invasive front), tumor lymphocytic and CD8 + T-cell infiltrates, and primary site were not associated with prognosis in the present study. In conclusion, perineural invasion and LHR-IM were confirmed as histological risk factors in HNSCC, which should be included in pathology reports. To revise the assessment of HNSCC tumor grade, the aforementioned site-specific histological characteristics may be used in deep learning algorithms.