Background: Lung is the third most frequent identified site of malignancy and lung cancer is the most lethal type of cancer in the world. Several benign lung diseases or proliferations may mimic lung carcinoma in its clinical, pathological, and radiological presentation, which makes the differential diagnosis life changing. This case series was designed to describe the main diagnosis encountered in a multidisciplinary emergency hospital during the last years in Romania. Results: The most challenging cases encountered during the recent years were those of lung hamartoma associated with eosinophilic pneumonia because of the multicentricity of the disease and the suspicion for metastasis in the clinical setting, pulmonary aspergillosis that presented as a cystic lesion with a 9 mm mural nodule, actinomycosis discovered as firm nodule showing aspects of false pleural invasion, cryptococcosis – a hilar mass for which a pneumectomy was prepared, pulmonary parasitosis that presented as a nodule with irregular borders, causing pleural retraction, one case of inflammatory myofibroblastic tumor of the lung, one case of tumorlet type neuroendocrine lesion in a patient with history of melanoma and renal oncocytoma, admitted under the suspicion of lung metastasis. Conclusions: These are some of the main mimickers of primary or secondary lung cancers and one must be aware of these similitudes to avoid higher cost procedures, psychological stress for the patient and higher mortality.

(1) Background: This study investigates the tumor immune microenvironment, focusing on immune cell distribution in lung adenocarcinoma. (2) Methods: We evaluated fifty cases of lung adenocarcinoma, and suitable areas for further studies were annotated on the histological slides. Two tumor cores per case were obtained, one from the tumor’s center and another from its periphery, and introduced into three paraffin receptor blocks for optimized processing efficiency. The 4-micrometer-thick tissue microarray sections were stained for H&E and for CD68, CD163, CD8, CD4, and PD-L1; (3) Results: Our investigation revealed significant correlations between PD-L1 expression in tumor cells and the presence of CD163+ macrophages, between CD4+ cells and CD8+, CD68+, and CD163+ cells, and also between CD8+ T cells and CD163+ cells. Additionally, while we observed some differences in cellular components and densities between the tumor center and periphery, these differences were not statistically significant. However, distinct correlations between PD-L1 and immune cells in these regions were identified, suggesting spatial heterogeneity in the immune landscape. (4) Conclusions: These results emphasize the intricate interactions between immune cells and tumor cells in lung adenocarcinoma. Understanding patient spatial immune profile could improve patient selection for immunotherapy, ensuring that those most likely to benefit are identified.