Pleural effusion aetiology, presentation, treatment and outcome in haematological diseases: a review Pleural effusions in haematologic diseases

Main Article Content

Alberto Fantin
Nadia Castaldo
Paolo Vailati
Giuseppe Morana
Daniele Orso
Luigi Vetrugno
Vincenzo Patruno


pleural effusion, hematologic disorders, lung ultrasound, thoracoscopy


Background and aim: Pleural effusions (PE) can complicate the course of hematologic disorders (HD) and may arise in the form of malignant PE or as a consequence of non-neoplastic complications. While a certain amount of data has been published regarding infectious and iatrogenic HD-associated PE (HPE), no comprehensive review regarding the other types of HPE has ever been conducted. To address this issue, we performed a systematic review of the literature regarding HPE, focusing on the clinical and chemical characteristics of PE, therapeutic approaches and ì outcomes at the one-year follow-up.

Methods: We conducted our review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Overall, 283 manuscripts and 1216 cases were included. In summary, PE frequently signals an underlying HD, especially Hodgkin’s lymphoma and IgG4-related disease; it mainly consists of exudate, although chylothorax is diagnosed in some cases. Although cytological examination has a discrete diagnostic yield, it is generally insufficient to render a definitive diagnosis; pleural biopsy remains an important diagnostic means in such cases. Invasive diagnostic procedures are not frequently performed because of an increased risk of haemorrhagic complications. The majority of PE are resolved by means of systemic therapy. When local treatments are attempted, the most frequently adopted procedures are evacuative thoracentesis and indwelling chest tube placement

Conclusions: This review highlights the need for well-designed prospective studies comparing diagnostic means and therapeutic interventions for HPE to increase the quality of available data.  (


Download data is not yet available.
Abstract 22 |


Moher D, Liberati A, Tetzlaff J, Altman DG, Group P, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement, PLoS Med, vol. 6, no. 7, p. e1000097, Jul 21 2009.doi:10.1371/journal.pmed.1000097.
[2] Etiology of pleural effusions in a general hospital.
[3] Berkman N, Breuer R, Kramer MR, Polliack A, Pulmonary involvement in lymphoma, Leuk Lymphoma, vol. 20, no. 3-4, pp. 229-37, Jan 1996.doi:10.3109/10428199609051612.
[4] Manoharan A, Pitney WR, Schonell ME, Bader LV, Intrathoracic manifestations in non-Hodgkin's lymphoma, Thorax, vol. 34, no. 1, pp. 29-32, Feb 1979.doi:10.1136/thx.34.1.29.
[5] Das DK, Gupta SK, Ayyagari S, Bambery PK, Datta BN, Datta U, Pleural effusions in non-Hodgkin's lymphoma. A cytomorphologic, cytochemical and immunologic study, Acta Cytol, vol. 31, no. 2, pp. 119-24, Mar-Apr 1987.
[6] Higgins JP, Shuttari M, Demmy T, Loy T, Calaluce R, Diffuse large cell lymphoma of the lung: an unusual cause of complete opacification of the hemithorax, South Med J, vol. 87, no. 11, pp. 1183-5, Nov 1994.doi:10.1097/00007611-199411000-00029.
[7] Havelock T, Teoh R, Laws D, Gleeson F, Group BTSPDG, Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural Disease Guideline 2010, Thorax, vol. 65 Suppl 2, pp. ii61-76, Aug 2010.doi:10.1136/thx.2010.137026.
[8] Vetrugno L, Guadagnin GM, Orso D, Boero E, Bignami E, Bove T, An easier and safe affair, pleural drainage with ultrasound in critical patient: a technical note, Crit Ultrasound J, vol. 10, no. 1, p. 18, Aug 1 2018.doi:10.1186/s13089-018-0098-z.
[9] Khattab T, Smith S, Barbor P, Ghamdi SA, Abbas A, Fryer C, Extramedullary relapse in a child with mixed lineage acute lymphoblastic leukemia: chylous pleuropericardial effusion, Med Pediatr Oncol, vol. 34, no. 4, pp. 274-5, Apr 2000.doi:10.1002/(sici)1096-911x(200004)34:4<274::aid-mpo12>;2-s.
[10] Naseer A ,Saeed W, Chylothorax in a case of Non-Hodgkin's lymphoma, J Coll Physicians Surg Pak, vol. 13, no. 2, pp. 108-10, Feb 2003.doi:02.2003/JCPSP.108110.
[11] Sivakumaran M, Qureshi H, Chapman CS, Chylous effusions in CLL, Leuk Lymphoma, vol. 18, no. 3-4, pp. 365-6, Jul 1995.doi:10.3109/10428199509059633.
[12] Ampil FL, Burton GV, Hardjasudarma M, Stogner SW, Chylous effusion complicating chronic lymphocytic leukemia, Leuk Lymphoma, vol. 10, no. 6, pp. 507-10, Aug 1993.doi:10.3109/10428199309148211.
[13] Faiz SA, Pathania P, Song J, Li L, Balachandran DD, Ost DE, Morice RC, Shannon VR, Bashoura L, Eapen GA, Jimenez CA, Indwelling Pleural Catheters for Patients with Hematologic Malignancies. A 14-Year, Single-Center Experience, Ann Am Thorac Soc, vol. 14, no. 6, pp. 976-85, Jun 2017.doi:10.1513/AnnalsATS.201610-785OC.
[14] Paul T, Yadav DK, Alhamar M, Dabak V, Primary Pleural Extranodal Marginal Zone Lymphoma Presenting as Bilateral Chylothorax, Case Rep Oncol, vol. 13, no. 2, pp. 929-34, May-Aug 2020.doi:10.1159/000508704.
[15] O'Callaghan AM ,Mead GM, Chylothorax in lymphoma: mechanisms and management, Ann Oncol, vol. 6, no. 6, pp. 603-7, Jul 1995.doi:10.1093/oxfordjournals.annonc.a059251.
[16] Elis A, Blickstein D, Mulchanov I, Manor Y, Radnay J, Shapiro H, Lishner M, Pleural effusion in patients with non-Hodgkin's lymphoma: a case-controlled study, Cancer, vol. 83, no. 8, pp. 1607-11, Oct 15 1998.
[17] Nonami A, Yokoyama T, Takeshita M, Ohshima K, Kubota A, Okamura S, Human herpes virus 8-negative primary effusion lymphoma (PEL) in a patient after repeated chylous ascites and chylothorax, Intern Med, vol. 43, no. 3, pp. 236-42, Mar 2004.doi:10.2169/internalmedicine.43.236.
[18] Asuquo BJ ,Gould GA, Recurrent chylothorax in a patient with non-Hodgkins lymphoma: case report, East Afr Med J, vol. 81, no. 4, pp. 215-7, Apr 2004.doi:10.4314/eamj.v81i4.9159.
[19] Podder S, Mora M, Patel V, Sivamurthy S, A rare case of bilateral chylothorax: a diagnostic challenge--follicular lymphoma versus primary effusion lymphoma, BMJ Case Rep, vol. 2015, Aug 17 2015.doi:10.1136/bcr-2015-211935.
[20] Ozsoy IE ,Tezcan MA, T-Cell Lymphoma Presenting With Bilateral Chylothorax, J Coll Physicians Surg Pak, vol. 30, no. 11, pp. 1220-22, Nov 2020.doi:10.29271/jcpsp.2020.11.1220.
[21] Karkoulias K, Sampsonas F, Kaparianos A, Tsiamita M, Tsoukalas G, Spiropoulos K, Urinothorax: an unexpected cause of pleural effusion in a patient with non-Hodgkin lymphoma, Eur Rev Med Pharmacol Sci, vol. 11, no. 6, pp. 373-4, Nov-Dec 2007.
[22] Blazquez M, Haioun C, Chaumette MT, Gaulard P, Reyes F, Soule JC, Delchier JC, Low grade B cell mucosa associated lymphoid tissue lymphoma of the stomach: clinical and endoscopic features, treatment, and outcome, Gut, vol. 33, no. 12, pp. 1621-5, Dec 1992.doi:10.1136/gut.33.12.1621.
[23] Lossos IS, Intrator O, Berkman N, Breuer R, Lactate dehydrogenase isoenzyme analysis for the diagnosis of pleural effusion in haemato-oncological patients, Respir Med, vol. 93, no. 5, pp. 338-41, May 1999.doi:10.1016/s0954-6111(99)90315-3.
[24] Faiz SA, Bashoura L, Lei X, Sampat KR, Brown TC, Eapen GA, Morice RC, Ferrajoli A, Jimenez CA, Pleural effusions in patients with acute leukemia and myelodysplastic syndrome, Leuk Lymphoma, vol. 54, no. 2, pp. 329-35, Feb 2013.doi:10.3109/10428194.2012.713478.
[25] Murray JC, Gmoser DJ, Barnes DA, Oshman D, Hawkins HK, Gresik MV, Dreyer ZE, Isolated bone relapse during hematologic remission in childhood acute lymphoblastic leukemia: report of a metatarsal relapse and review of the literature, Med Pediatr Oncol, vol. 23, no. 2, pp. 153-7, 1994.doi:10.1002/mpo.2950230217.
[26] Ahmed S, Siddiqui AK, Rossoff L, Sison CP, Rai KR, Pulmonary complications in chronic lymphocytic leukemia, Cancer, vol. 98, no. 9, pp. 1912-7, Nov 1 2003.doi:10.1002/cncr.11736.
[27] van den Berge M, Tinga CJ, Bieger R, A 73-year-old man with chronic lymphocytic leukaemia and a haemorrhagic pleural effusion, Ann Hematol, vol. 80, no. 3, pp. 183-6, Mar 2001.doi:10.1007/s002770000266.
[28] Bitran J, Ganapathy R, Ultmann JE, Golomb HM, Malignant pleural effusion as complication of chronic lymphocytic leukaemia, Lancet, vol. 2, no. 7982, pp. 414-5, Aug 21 1976.doi:10.1016/s0140-6736(76)92425-9.
[29] Zhai K, Lu Y, Shi HZ, Tuberculous pleural effusion, J Thorac Dis, vol. 8, no. 7, pp. E486-94, Jul 2016.doi:10.21037/jtd.2016.05.87.
[30] Bourantas KL, Tsiara S, Panteli A, Milionis C, Christou L, Pleural effusion in chronic myelomonocytic leukemia, Acta Haematol, vol. 99, no. 1, pp. 34-7, 1998.doi:10.1159/000040713.
[31] Hu L, Zheng B, Fu L, Hu M, Chronic myelomonocytic leukemia (CMML)-0 with pleural effusion as first manifestation: A case report, Medicine (Baltimore), vol. 99, no. 44, p. e23030, Oct 30 2020.doi:10.1097/MD.0000000000023030.
[32] Saif MW, Hopkins JL, Gore SD, Autoimmune phenomena in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia, Leuk Lymphoma, vol. 43, no. 11, pp. 2083-92, Nov 2002.doi:10.1080/1042819021000016186.
[33] Kintzer JS, Jr., Rosenow EC, 3rd, Kyle RA, Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases, Arch Intern Med, vol. 138, no. 5, pp. 727-30, May 1978.
[34] Rodriguez JN, Pereira A, Martinez JC, Conde J, Pujol E, Pleural effusion in multiple myeloma, Chest, vol. 105, no. 2, pp. 622-4, Feb 1994.doi:10.1378/chest.105.2.622.
[35] Urrutia A, Ribera JM, Rey-Joly C, Foz M, [Myelomatous pleural effusion with elevated adenosine desaminase activity], Med Clin (Barc), vol. 96, no. 6, p. 236, Feb 16 1991. Derrame pleural mielomatoso con actividad de adenosina desaminasa elevada.
[36] Riveiro V, Ferreiro L, Toubes ME, Lama A, Alvarez-Dobano JM, Valdes L, Characteristics of patients with myelomatous pleural effusion. A systematic review, Rev Clin Esp, vol. 218, no. 2, pp. 89-97, Mar 2018. Caracteristicas de los pacientes con derrame pleural mielomatoso. Revision sistematica.doi:10.1016/j.rce.2017.11.001.
[37] Garcia-Riego A, Cuinas C, Vilanova JJ, Ibarrola R, Extramedullary hematopoietic effusions, Acta Cytol, vol. 42, no. 5, pp. 1116-20, Sep-Oct 1998.doi:10.1159/000332098.
[38] Aessopos A, Tassiopoulos S, Farmakis D, Moyssakis I, Kati M, Polonifi K, Tsironi M, Extramedullary hematopoiesis-related pleural effusion: the case of beta-thalassemia, Ann Thorac Surg, vol. 81, no. 6, pp. 2037-43, Jun 2006.doi:10.1016/j.athoracsur.2006.01.026.
[39] Kupferschmid JP, Shahian DM, Villanueva AG, Massive hemothorax associated with intrathoracic extramedullary hematopoiesis involving the pleura, Chest, vol. 103, no. 3, pp. 974-5, Mar 1993.doi:10.1378/chest.103.3.974.
[40] Bartlett RP, Greipp PR, Tefferi A, Cupps RE, Mullan BP, Trastek VF, Extramedullary hematopoiesis manifesting as a symptomatic pleural effusion, Mayo Clin Proc, vol. 70, no. 12, pp. 1161-4, Dec 1995.doi:10.4065/70.12.1161.
[41] Ryu JH, Sekiguchi H, Yi ES, Pulmonary manifestations of immunoglobulin G4-related sclerosing disease, Eur Respir J, vol. 39, no. 1, pp. 180-6, Jan 2012.doi:10.1183/09031936.00025211.
[42] Zen Y ,Nakanuma Y, IgG4-related disease: a cross-sectional study of 114 cases, Am J Surg Pathol, vol. 34, no. 12, pp. 1812-9, Dec 2010.doi:10.1097/PAS.0b013e3181f7266b.
[43] Fujinaga Y, Kadoya M, Kawa S, Hamano H, Ueda K, Momose M, Kawakami S, Yamazaki S, Hatta T, Sugiyama Y, Characteristic findings in images of extra-pancreatic lesions associated with autoimmune pancreatitis, Eur J Radiol, vol. 76, no. 2, pp. 228-38, Nov 2010.doi:10.1016/j.ejrad.2009.06.010.
[44] Shrestha B, Sekiguchi H, Colby TV, Graziano P, Aubry MC, Smyrk TC, Feldman AL, Cornell LD, Ryu JH, Chari ST, Dueck AC, Yi ES, Distinctive pulmonary histopathology with increased IgG4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology, Am J Surg Pathol, vol. 33, no. 10, pp. 1450-62, Oct 2009.doi:10.1097/PAS.0b013e3181ac43b6.
[45] Yamashita K, Haga H, Kobashi Y, Miyagawa-Hayashino A, Yoshizawa A, Manabe T, Lung involvement in IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis: report of 3 cases and review of the literature, Am J Surg Pathol, vol. 32, no. 11, pp. 1620-6, Nov 2008.doi:10.1097/PAS.0b013e318172622f.
[46] Zen Y, Inoue D, Kitao A, Onodera M, Abo H, Miyayama S, Gabata T, Matsui O, Nakanuma Y, IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases, Am J Surg Pathol, vol. 33, no. 12, pp. 1886-93, Dec 2009.doi:10.1097/PAS.0b013e3181bd535b.
[47] Karadeniz C, Guven MA, Ruacan S, Demirbilek S, Sagbil S, Akhan O, Primary pleural lymphoma: an unusual presentation of childhood non-Hodgkin lymphoma, Pediatr Hematol Oncol, vol. 17, no. 8, pp. 695-9, Dec 2000.doi:10.1080/08880010050211411.
[48] Bibby AC, Dorn P, Psallidas I, Porcel JM, Janssen J, Froudarakis M, Subotic D, Astoul P, Licht P, Schmid R, Scherpereel A, Rahman NM, Cardillo G, Maskell NA, ERS/EACTS statement on the management of malignant pleural effusions, Eur Respir J, vol. 52, no. 1, Jul 2018.doi:10.1183/13993003.00349-2018.
[49] Ahmad SR, Lee PJ, Ghasemi M, Sosa AF, Follicular Lymphoma Diagnosed With Medical Thoracoscopy, J Bronchology Interv Pulmonol, vol. 23, no. 1, pp. 79-82, Jan 2016.doi:10.1097/LBR.0000000000000199.
[50] Koegelenberg CF ,Diacon AH, Image-guided pleural biopsy, Curr Opin Pulm Med, vol. 19, no. 4, pp. 368-73, Jul 2013.doi:10.1097/MCP.0b013e32835f4c23.
[51] Bass J ,White DA, Thoracentesis in patients with hematologic malignancy: yield and safety, Chest, vol. 127, no. 6, pp. 2101-5, Jun 2005.doi:10.1378/chest.127.6.2101.
[52] Bodey GP, Buckley M, Sathe YS, Freireich EJ, Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia, Ann Intern Med, vol. 64, no. 2, pp. 328-40, Feb 1966.doi:10.7326/0003-4819-64-2-328.
[53] Harris B ,Geyer AI, Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation, Clin Chest Med, vol. 38, no. 2, pp. 317-31, Jun 2017.doi:10.1016/j.ccm.2016.12.008.
[54] Hoffman PC, Immune hemolytic anemia--selected topics, Hematology Am Soc Hematol Educ Program, pp. 80-6, 2009.doi:10.1182/asheducation-2009.1.80.
[55] Morell-García D, Bauça JM, López Andrade B, Leukemic Pleural Effusion: Diagnostic Approach and Controversies in Pleurodesis, Archivos de Bronconeumología (English Edition), 10.1016/j.arbr.2014.06.010 vol. 50, no. 8, pp. 371-72, 2014.doi:10.1016/j.arbr.2014.06.010.
[56] Iannitto E, Minardi V, Tripodo C, Use of intrapleural bortezomib in myelomatous pleural effusion, Br J Haematol, vol. 139, no. 4, pp. 621-2, Nov 2007.doi:10.1111/j.1365-2141.2007.06735.x.
[57] Elkadi D, Wiernik PH, Tong TR, Resolution of massive pleural effusion due to lymphoma with intrapleural interleukin-2, Am J Hematol, vol. 85, no. 9, pp. 711-2, Sep 2010.doi:10.1002/ajh.21604.
[58] Law MF, Yip SF, Poon WL, Chan HN, Lai HK, Ha CY, Ng CS, Yeung YM, Intrapleural rituximab for the treatment of malignant pleural effusion due to B-cell lymphomas, Leuk Lymphoma, vol. 53, no. 1, pp. 156-7, Jan 2012.doi:10.3109/10428194.2011.602769.
[59] Weick JK, Kiely JM, Harrison EG, Jr., Carr DT, Scanlon PW, Pleural effusion in lymphoma, Cancer, vol. 31, no. 4, pp. 848-53, Apr 1973.doi:10.1002/1097-0142(197304)31:4<848::aid-cncr2820310413>;2-5.
[60] Jenkins PF, Ward MJ, Davies P, Fletcher J, Non-Hodgkin's lymphoma, chronic lymphatic leukaemia and the lung, Br J Dis Chest, vol. 75, no. 1, pp. 22-30, Jan 1981.doi:10.1016/s0007-0971(81)80004-6.
[61] Clive AO, Kahan BC, Hooper CE, Bhatnagar R, Morley AJ, Zahan-Evans N, Bintcliffe OJ, Boshuizen RC, Fysh ET, Tobin CL, Medford AR, Harvey JE, van den Heuvel MM, Lee YC, Maskell NA, Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score, Thorax, vol. 69, no. 12, pp. 1098-104, Dec 2014.doi:10.1136/thoraxjnl-2014-205285.
[62] Harding W, Jimenez C, Salamo O, Zavalla K, Warner M, Eapen G, Bashoura L, Grosu H, Faiz S, SURVIVAL OUTCOMES OF HEMATOLOGIC MALIGNANCIES USING THE LENT SCORE, Chest, vol. 158, no. 4, Supplement, p. A1190, 2020/10/01/ 2020.doi:

Most read articles by the same author(s)