{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T08:44:37Z","timestamp":1766393077618,"version":"3.48.0"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: 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. Methods: 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. Results: 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 \u03b22-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. Conclusions: 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.<\/jats:p>","DOI":"10.3390\/cancers18010019","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T08:35:27Z","timestamp":1766392527000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pleuro-Pulmonary Extramedullary Plasmacytomas in Multiple Myeloma: A 15-Year Experience from a Tertiary Center"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1507-2547","authenticated-orcid":false,"given":"Sorina","family":"Badelita","sequence":"first","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinziana","family":"Barbu","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camelia","family":"Dobrea","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cerasela","family":"Jardan","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Popescu","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7638-3285","authenticated-orcid":false,"given":"Codruta Delia","family":"Popa","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0596-2122","authenticated-orcid":false,"given":"Claudia","family":"Toma","sequence":"additional","affiliation":[{"name":"Clinical Pneumology Department, \u201cDr. Marius Nasta\u201d Hospital, 050159 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larisa","family":"Zidaru","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai Emanuel","family":"Himcinschi","sequence":"additional","affiliation":[{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Biochemistry Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horia Mihail","family":"Sandu","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didona","family":"Vasilache","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2282-6802","authenticated-orcid":false,"given":"Adelina","family":"Vlad","sequence":"additional","affiliation":[{"name":"Physiology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Coriu","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Myelomatous Meningitis\u2014A diagnostic and therapeutic challenge","volume":"1","author":"Barbu","year":"2023","journal-title":"Doc. Haematol.-Rev. Romana De Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"536","DOI":"10.25122\/jml-2025-0104","article-title":"Beyond the bone marrow: A review of therapeutic approaches for extramedullary disease in multiple myeloma and the significance of MRD assessment","volume":"18","author":"Diaconescu","year":"2025","journal-title":"J. Med. Life"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.14740\/jmc3428","article-title":"Myelomatous Pleural Effusion: A Rare Involvement in Myeloma","volume":"11","author":"Alkan","year":"2020","journal-title":"J. Med. Cases"},{"key":"ref_4","first-page":"177","article-title":"Extramedullary Pulmonary Manifestations of Relapsed\/Refractory Multiple Myeloma: A Case Series and Brief Review of the Literature","volume":"4","author":"Kumar","year":"2024","journal-title":"J. Respir."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/s41408-021-00527-y","article-title":"Extramedullary disease in multiple myeloma","volume":"11","author":"Bansal","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41408-022-00643-3","article-title":"Extramedullary disease in multiple myeloma: A systematic literature review","volume":"12","author":"Beksac","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15330338221132370","DOI":"10.1177\/15330338221132370","article-title":"Clinical Characteristics and Prognosis of Multiple Myeloma With Myelomatous Pleural Effusion: A Retrospective Single-Center Study","volume":"21","author":"Gao","year":"2022","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3892\/mco.2021.2401","article-title":"Pleural effusion and multiple myeloma\u2014More than meets the eye: A case report","volume":"15","author":"Ramos","year":"2021","journal-title":"Mol. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4103\/jcrt.jcrt_2730_22","article-title":"Myelomatous pleural effusion: An atypical initial presentation","volume":"21","author":"Thakkar","year":"2025","journal-title":"J. Cancer Res. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41408-024-01068-w","article-title":"Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy","volume":"14","author":"Dima","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1080\/16078454.2021.2005310","article-title":"Research progress on treatment of extramedullary multiple myeloma","volume":"26","author":"Chen","year":"2021","journal-title":"Hematology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S228","DOI":"10.1016\/S2152-2650(23)00876-5","article-title":"POSTER: MM-372 A Phase III, Two-Stage, Randomized Study of Mezigdomide, Bortezomib, and Dexamethasone (MeziVd) Versus Pomalidomide, Bortezomib, and Dexamethasone (PVd) in Relapsed\/Refractory Multiple Myeloma (RRMM): SUCCESSOR-1","volume":"23","author":"Richardson","year":"2023","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102017","DOI":"10.1016\/j.eclinm.2023.102017","article-title":"Impact of minimal residual disease standardised assessment by FDG-PET\/CT in transplant-eligible patients with newly diagnosed multiple myeloma enrolled in the imaging sub-study of the FORTE trial","volume":"60","author":"Zamagni","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6580","DOI":"10.1158\/1078-0432.CCR-21-0308","article-title":"The Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma","volume":"27","author":"Manjunath","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/bjh.17338","article-title":"Expert review on soft-tissue plasmacytomas in multiple myeloma: Definition, disease assessment and treatment considerations","volume":"194","author":"Beksac","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/01.HS9.0000829504.35798.64","article-title":"EXTRAMEDULLARY DISEASE","volume":"6","author":"Beksac","year":"2022","journal-title":"Hemasphere"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101834","DOI":"10.1016\/j.artd.2025.101834","article-title":"Extramedullary Relapse of Multiple Myeloma After Total Knee Arthroplasty: Implications for Orthopaedic Surgeons\u2014A Case Report and Literature Review","volume":"35","author":"Hefelfinger","year":"2025","journal-title":"Arthroplast. Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.3324\/haematol.2020.278272","article-title":"A real world multicenter retrospective study on extramedullary disease from Balkan Myeloma Study Group and Barcelona University: Analysis of parameters that improve outcome","volume":"106","author":"Beksac","year":"2021","journal-title":"Haematologica"},{"key":"ref_19","first-page":"890","article-title":"Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: A study from the Chronic Malignancies Working Party of the EBMT","volume":"108","author":"Gagelmann","year":"2023","journal-title":"Haematologica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41408-019-0191-y","article-title":"Natural history of multiple myeloma with de novo del(17p)","volume":"9","author":"Lakshman","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4999\/uhod.247803","article-title":"Risk Factors and Prognosis of Extramedullary Disease in Newly-Diagnosed Multiple Myeloma Patients","volume":"34","year":"2024","journal-title":"Int. J. Hematol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s12185-025-03958-6","article-title":"Extramedullary disease in multiple myeloma at diagnosis and over the course of the disease","volume":"122","author":"Guliyev","year":"2025","journal-title":"Int. J. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"McAvera, R., Quinn, J., Murphy, P., and Glavey, S. (2023). Genetic Abnormalities in Extramedullary Multiple Myeloma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411259"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13256-023-03765-9","article-title":"Extramedullary relapse of Immunoglobulin A-kappa myeloma manifesting as plasmacytoma of the pleura without bone marrow involvement and following autologous bone marrow transplant: A case report","volume":"17","author":"Rezvani","year":"2023","journal-title":"J. Med. Case Rep."},{"key":"ref_25","first-page":"101777","article-title":"Pleural plasmacytomas in a patient with multiple myeloma relapse","volume":"40","author":"Ali","year":"2022","journal-title":"Respir. Med. Case Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1053\/j.seminhematol.2025.02.001","article-title":"Extramedullary myeloma in the era of CAR T-cell and bispecific antibody therapies","volume":"62","author":"Sanchez","year":"2025","journal-title":"Semin. Hematol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/1\/19\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T08:41:52Z","timestamp":1766392912000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/1\/19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,20]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["cancers18010019"],"URL":"https:\/\/doi.org\/10.3390\/cancers18010019","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,20]]}}}