Pleuro-Pulmonary Extramedullary Plasmacytomas in Multiple Myeloma: A 15-Year Experience from a Tertiary Center

<b>Background/Objectives</b>: Extramedullary involvement in multiple myeloma represents an aggressive disease phenotype, associated with reduced survival and an unfavorable prognosis. Thoracic manifestations are rare and remain poorly characterized in the literature. <b>Methods</b>: We conducted a retrospective, single-center study at the Fundeni Clinical Institute, including patients diagnosed with multiple myeloma between February 2010 and February 2025. The study cohort consisted of 34 patients with infiltration of the pulmonary parenchyma, pleura, or the presence of myelomatous pleural effusion. Diagnosis was confirmed using a combination of imaging modalities (computed tomography or magnetic resonance imaging), cytological examination, immunophenotyping, and histopathological confirmation whenever feasible. <b>Results</b>: Out of a total of 2012 patients with multiple myeloma, the incidence of pleuro-pulmonary extramedullary involvement was 1.6%. The median age at diagnosis was 58 years. Pleuro-pulmonary disease was present at initial diagnosis in 26.5% of cases, while 73.5% developed it at relapse. The most common presentation involved combined pleural involvement and myelomatous effusion (70.6%). Adverse prognostic markers included elevated β2-microglobulin levels (in over 80% of cases) and increased lactate dehydrogenase (LDH) in approximately 50%. Cytogenetic abnormalities such as del(17p), t(4;14), t(14;16), t(11;14), and 1q gain were identified. The median overall survival (OS) from the diagnosis of pleuro-pulmonary extramedullary disease was 16 months, with a 2-year survival rate of 25%. No patient survived beyond 5 years. The median progression-free survival (PFS) was 9 months. <b>Conclusions</b>: Our findings confirm the aggressive clinical course and poor prognosis of these disease manifestations, mainly when they occur at relapse. In the absence of standardized treatment guidelines, individualizing therapy and accessing novel strategies may be essential for improving patient survival.