Abstract Background Primary Pulmonary Lymphoma (PPL) is a rare malignancy of pulmonary origin, with no evidence of extrapulmonary disease at diagnosis or within 3 months. It accounts for less than 1% of all primary lung malignancies and 0.4% of malignant lymphomas. Its non-specific clinical and radiologic features often lead to misdiagnosis as pulmonary infection or carcinoma, especially in regions where tuberculosis is common. This case series highlights the spectrum of clinical, radiologic, and histopathologic findings of PPL in a tertiary care setting. The rationale for this case series is to enhance clinical awareness of this uncommon disease and contribute regional data to the limited global literature. Methods Four patients with biopsy-proven PPL treated at a tertiary care hospital in Karachi, Pakistan, were retrospectively reviewed. Data on clinical presentation, imaging, biopsy results, treatment regimens, and outcomes were collected and reported. Results The study included a total of four patients, all of whom were female. Ages ranged from 20 to 57 years, with three patients aged between 20 and 28 years. The common presenting symptoms were cough, fever, hemoptysis, and weight loss. Imaging revealed variable findings, including lobar opacities, cavitary lesions, lung mass, and atelectasis. Diagnosis was achieved through CT-guided or bronchoscopy-guided biopsy. Histopathology showed Classical Hodgkin’s lymphoma in three patients (one syncytial variant) and Diffuse Large B-Cell lymphoma in one patient. All patients received chemotherapy—ABVD or R-CHOP being the primary regimens. One patient required second-line ICE, Brentuximab, and Bendamustine due to refractory disease. Three patients achieved complete metabolic response on follow-up PET-CT, while one was transitioned to palliative treatment. Conclusion This case series underscores the diagnostic challenge of PPL due to its rarity and overlapping features with other pulmonary conditions, particularly in a region such as Pakistan where infectious etiologies dominate pulmonary disease differentials. Early tissue diagnosis should be pursued in patients with non-resolving lung lesions for appropriate identification and timely initiation of therapy. Notably, mucosa-associated lymphoid tissue (MALT) type is the most common PPL worldwide; our experience showed Hodgkin and high-grade B-cell variants requiring more aggressive chemotherapy, suggesting a potential regional difference. Greater clinical awareness and multidisciplinary management are crucial to improving outcomes in this rare malignancy. This abstract is funded by: None
Naseem et al. (Fri,) studied this question.