Multiple myeloma (now known as plasma cell myeloma) is a malignant disease caused by a proliferation of clonal 
plasma cells associated with a monoclonal protein 
or light chain in the serum and/or urine.1 Patients 
with plasma cell myeloma commonly present with 
hypercalcaemia, renal insufficiency, anaemia and/ 
or bony lesions.2 However, the disease can present 
with a wide variety of clinical manifestations as a 
result of the involvement of various organ systems, 
due to either direct infiltration by plasma cells or 
the deposition of monoclonal proteins or light 
chains.3 Pleural effusions are seen in a minority of 
patients with myeloma. However, effusions directly 
related to infiltration of the pleura by plasma 
cells, i.e. myelomatous pleural effusions (MPE), 
are extremely rare. In this paper, we report a case 

of an Omani patient with relapsed myeloma who 
developed a true myelomatous pleural effusion. We 
also present a review of the relevant literature.

Case Report
A 55 year-old man was diagnosed with Durie-
Salmon stage IIIA IgG kappa plasma cell myeloma 
in 2004. He was treated for three months with a 
combination of thalidomide and steroids-based 
therapy and achieved a partial response. He was 
subsequently lost to follow-up and presented 
again in 2007 with progressive disease with severe 
anaemia and multiple lytic lesions. He was then 
treated with four cycles of bortezomib, thalidomide 
and dexamethasone and achieved complete 
remission. This was followed by melphalan-based 

SQU Med J, May 2011, Vol. 1, Iss. 2, pp. 259-264, Epub. 15th May 11
Submitted 26th Aug 09
Revision ReQ. 23rd Nov 09, Revision Recd. 2nd Jan 10
Accepted 3rd Feb 2010

Departments of 1Haematology, 2Pathology, 3Biochemistry, 4Radiology & Molecular Imaging, Sultan Qaboos University Hospital, 
Muscat, Oman.
*Corresponding Author email: khalilf@squ.edu.om

�Î �Á�œ �fl÷]<9fl¢]<h^fífi˜]
l^ÈeÅ_<Ì√q]Ü⁄Ê<Ì÷^u<‡¬<ÜËÜœi



 
 55 




        :مفتاح الكلمات

aBstract: Plasma cell myeloma is an uncommon disease which, besides primarily involving the bone marrow, 
has a tendency to involve other organs thus presenting with different clinical manifestations. While pleural 
effusions are infrequent in this disease, true myelomatous pleural effusions are extremely rare. We report the case 
of a middle-aged Omani man with relapsed plasma cell myeloma who developed bilateral pleural effusions. The 
diagnosis of myelomatous pleural effusion was made by finding many abnormal plasma cells as well as a high level 
of a monoclonal protein (IgG κ) in the pleural fluid. In spite of a good initial response to therapy, the patient had 
progressive disease and died 6 months later with bacterial sepsis. We present a review of the literature that indicates 
the rarity of such a manifestation and its association with poor prognosis and short survival.

Keywords: Multiple myeloma; Plasma cells; Pleural effusion; Case report ; Oman

Myelomatous Pleural Effusion
Case report and review of the literature

*Khalil Al-Farsi,1 Ibrahim Al-Haddabi,2 Nafla Al-Riyami,3 Rashid Al-Sukaiti,4 Salam Al-Kindi1

CASE REPORT



Myelomatous Pleural Effusion 
Case report and review of the literature

260 | SQU Medical Journal, May 2011, Volume 11, Issue 2

high dose chemotherapy and autologous stem cell 
transplantation (ASCT) in April 2008. His disease 
progressed a year after the transplant and he was 
treated with lenalidomide and dexamethasone. 
After five months of therapy, the treatment was 
interrupted as he developed severe cytopenias. He 
presented in January 2010 with shortness of breath 
and dry cough. His temperature was 38.5 oC, pulse 
was 124/min, respiratory rate was 22 breaths/min, 
blood pressure was 140/68 mmHg and oxygen 
saturation 91% on room air. A chest examination 
revealed decreased breath sounds in both infra-
scapular areas with dullness to percussion on both 
sides. A complete blood count (CBC) revealed a 
white blood cell (WBC) count of 2.2 x 109/L, absolute 
neutrophil count of 0.5x109/L, Hb of 8.7 g/dL and 
platelet count of 36 x109/L. The peripheral blood 
film showed rouleaux formation and confirmed 
the thrombocytopenia and neutropenia noted on 
the CBC. There were no circulating plasma cells or 
other abnormal cells. Blood chemistry tests showed 
albumin of 26 g/L, total protein 89 g/L, glucose 5.7 
mmol/L, lactate dehydrogenase (LDH) 301 U/L, ß2 
microglobulin 12.4 mg/L and C-reactive protein 121 
mg/L. Serum calcium, creatinine, uric acid, thyroid 

stimulating hormone (TSH) and liver enzymes  
}were normal. Serologies for HIV, hepatitis B 
and hepatitis C were negative. Serum protein 
electrophoresis and immunofixation showed a 
monoclonal IgG κ of 30.9 g/L with normal levels  
of uninvolved immunoglobulins. The most recent 
24-hour urine test showed a total protein of only  
0.13 g/24hour. The chest X-ray showed bilateral 
pleural effusions. A computed tomography (CT) 
scan of the chest confirmed the presence of bilateral 
pleural effusions [Figure 1]. It also showed multiple 
rib, sternal and thoracic vertebral osseous lytic 
lesions. There were also multiple sub-centimetre 
mediastinal lymph nodes. There was no evidence of 
pulmonary embolism. An echocardiography showed 
no significant abnormalities. The left ventricular 
ejection fraction was 70%. A thoracocentesis was 
performed and about 1 L of pleural fluid was drained 
from the right side. Analysis showed glucose of 6.0 
mmol/L, protein of 50 g/L and LDH of 172 U/L. The 
cytological examination revealed many abnormal 
plasma cells that constituted around 20% of the 
total nucleated cell in the pleural aspirate [Figure 2]. 
Although flow cytometry suggested that these cells 
were positive for CD38, the results were of poor 

Figure 1: Computed tomography scan of the chest showing bilateral pleural effusions.



Khalil Al-Farsi, Ibrahim Al-Haddabi, Nafla Al-Riyami, Rashid Al-Sukaiti and Salam Al-Kindi

Case Report | 261

quality due to the suboptimal quality of the sample 
and therefore difficult to interpret, especially with 
regards to light chain restriction. However, protein 
electrophoresis and immunofixation on the pleural 
fluid showed 16.7 g/L of IgG κ monoclonal protein 
[Figures 3 and 4]. A Gram stain, acid fast bacilli 
(AFB) stain and cultures (bacterial, fungal and TB 
cultures) were all negative. He was treated with 
high dose dexamethasone followed by one cycle of a 
combination of liposomal doxorubicin, bortezomib 
and dexamethasone. The pleural effusion resolved 
completely. However, the disease started to 
progress systemically over the following month,  
and his performance status deteriorated. He 
developed refractory cytopenias and became 
transfusion dependent. The effusions recurred 
bilaterally within 4 months. He was managed 
with palliative supportive care and died due to 
Escherichia coli sepsis in the setting of progressive 
disease in July 2010. A post-mortem examination 
was not performed. 

Discussion
Although plasma cell myeloma is mostly a bone 

marrow based disease, it can produce a variety of 
clinical presentations through the involvement 
of different extramedullary sites. One of these 
manifestations is pleural effusion. Pleural effusions, 
caused by several aetiologies, are reported to occur 
in 6% of patients with myeloma during the course 
of their disease.4 Myelomatous pleural effusions are 
rare and only about 80 cases have been reported in 
English medical literature.

Pleural effusions in patients with myeloma often 
results from non-malignant causes, some of which 
are treatable. The most common cause is congestive 
cardiac failure due to amyloidosis.4 Heart failure 
can also result from hyperviscosity and from 
cardiomyopathy related to the use of anthracyclines, 
commonly used in the treatment of myeloma in the 
past. Other causes include pulmonary embolism, 
infections, nephrotic syndrome and chronic renal 
failure.5 In addition, secondary neoplasms occurring 
in patients with myeloma, like carcinomas of the 
breast and lung and mesothelioma, can cause 
malignant pleural effusions.6 A detailed systematic 
approach to investigating pleural effusions, as 
demonstrated in our case report, is therefore 
important to exclude these alternative diagnoses. 

Figure 2: Cytological examination of the pleural fluid showing clusters of abnormal malignant-looking plasma cells.



Myelomatous Pleural Effusion 
Case report and review of the literature

262 | SQU Medical Journal, May 2011, Volume 11, Issue 2

Our patient had normal cardiac and renal functions 
and no evidence of pulmonary embolism or 
nephrotic syndrome. In addition, there was no 
evidence of any infective aetiology and no evidence 
of secondary malignancies. 

A true myelomatous pleural effusion is rare and 
occurs in less than 1% of patients with myeloma.4,7 It 
is usually a sign of advanced disease, although there 
are a few reports of it being the initial presenting 
feature of myeloma in some patients.8-10 There are 
about 80 cases reported in English medical literature. 
Older reports indicate that most effusions are due 
to IgA myeloma.11 However, more recent reports 
indicate that the majority occur in patients with 
IgG myeloma, which is the most common type of 
myeloma, as was the case in our patient.7,12,13 These 
recent reviews also indicate that it has an equal 
gender distribution, is commonly haemorrhagic, 
more commonly affects the left side and that these 
patients usually have poor prognostic disease 
markers.7,12-14 Our patient had bilateral effusions at 
a late stage of his relapsed/refractory disease.

The pathogenesis of myelomatous pleural 
effusion is not well understood, but several possible 
mechanisms have been proposed. These include: 1) 
direct extension of the disease to the pleura from 
adjacent skeletal or lung parenchymal tumors; 2) 
direct infiltration or implantation of tumour deposits 
on the pleura, and 3) lymphatic obstruction from 
mediastinal lymph node inflitration.4 Extension 
from a mediastinal extramedullary plasmacytoma 
has also been suggested as one possible 
mechanism.13-16 It is possible that the myelomatous 

pleural effusion in our patient resulted from 
extension of his disease from the many lesions in his 
ribs, sternum and thoracic vertebrae. Whether he 
had direct infiltration of the pleura is hard to prove 
as he did not have a pleural biopsy and small areas 
of involvement might be missed on CT scans.

Diagnostic criteria have been suggested 
to confirm the myelomatous nature of pleural 
effusions. The criteria include: 1) detection 
of atypical plasma cells in the pleural fluid; 2) 
demonstration of a monoclonal protein on 
pleural fluid electrophoresis, and 3) histological 
confirmation using pleural biopsy specimens or 
autopsy.11 Our patient had an exudative effusion 
that had a high level of monoclonal IgG κ as well as 
many abnormal plasma cells. A pleural biopsy was 
not done because of his poor general condition and 
severe thrombocytopenia at that time. In fact, one 
could argue that a pleural biopsy is not an integral 
part of the diagnosis. Pleural biopsies are not always 
done in these patients and when done are not always 
diagnostic or helpful.7,12,15,17 The risk associated with 
the procedure as well as the patchy nature of disease 
involvement make it less attractive and less reliable 
as a diagnostic tool. 

Despite the proposed criteria, the diagnosis of 
myelomatous pleural effusions can be challenging. 
Reactive plasma cells may be seen in effusions 
secondary to cardiac surgery, tuberculosis, viral 
infections, connective tissue diseases, Hodgkin’s 
lymphoma and carcinomatosis.16,18 In addition, 
malignant plasma cells have a wide spectrum of 
appearances in fluid specimens and may be missed 

Figure 3: Protein electrophoresis on (A) serum and (B) 
pleural fluid, both showing a dense monoclonal band in 
the slow gamma region.

Figure 4: Immunofixation on pleural fluid showing an 
IgG κ monoclonal band.



Khalil Al-Farsi, Ibrahim Al-Haddabi, Nafla Al-Riyami, Rashid Al-Sukaiti and Salam Al-Kindi

Case Report | 263

as being of plasmacytic origin, especially if low in 
number. Furthermore, due to in vivo and in vitro 
degeneration and changes during sample processing, 
the morphology can be significantly altered leading 
to further difficulties in recognising these cells as 
malignant plasma cells.7 The characteristic clock-
faced condensed chromatic pattern is absent in these 
cases. Instead, the nuclei of these cells are round to 
oval or pleomorphic and have a coarse and irregular 
chromatin pattern with prominent nucleoli. These 
malignant cells also have dense cytoplasm with 
absent or inconspicuous perinuclear hof.19,17 
Pleural biopsies might not be feasible and are not 
always diagnostic. It has been suggested that flow 
cytometric studies should be used to supplement 
the diagnosis.7 It has been shown, however, that 
in some instances flow cytometry might not be 
helpful due to poor specimen quality causing non-
specific light-chain staining.17,19 It has also been 
suggested that cytogenetic analysis be done on 
the pleural aspirate to support the diagnosis as an 
abnormal cytogenetic karyotype in the pleural fluid 
can provide unequivocal evidence of malignancy;7 
however, this is not always possible. The diagnosis in 
most of the reported cases relied mainly on finding 
abnormal plasma cells and a monoclonal protein in 
the pleural fluid. 

The lack of alternative diagnosis and the 
presence of malignant-appearing plasma cells in the 
pleural fluid support the diagnosis of myelomatous 
pleural effusion in our patient. In addition, the lack 
of circulating plasma cells in his peripheral blood, 
while there were many in his pleural fluid, argues 
strongly against the monoclonal protein in his 
pleural fluid being the result of contamination with 
peripheral blood. Flow cytometry was attempted, 
but the suboptimal quality of the sample precluded 
interpretation of the results. The pleural fluid was 
not subjected to cytogenetic analysis in our patient. 
Such analysis is not necessary for routine diagnosis.7 
In addition, cytogenetic studies in myeloma patients 
can be difficult because few mitoses are often 
obtained.18,20 Overall, with the clinical presentation 
and the findings on pleural fluid analysis, there is 
no doubt that our patient had a true myelomatous 
pleural effusion.

The diagnosis of myelomatous pleural effusion 
carries a poor prognosis despite aggressive 
treatment. The literature suggests that the  
median survival of these patients is about 4 

months. Several treatments have been tried 
including different combinations of systemic 
chemotherapy,7,12,21 as well as intra-pleural 
injections of different agents like adriamycin and 
interferon.19,20,22,23 Despite some reported responses, 
the majority of these were transient and recurrences 
were common. There seems to be no added benefit 
from salvage chemotherapy followed by high dose 
therapy and ASCT in these patients.7 There appears 
to be some hope, however, with the use of novel 
agents. Bortezomib, a novel proteasome inhibitor 
which has been shown to overcome some of the poor 
prognostic factors in myeloma, has proven to be safe 
and effective in patients with relapsed/refractory 
myeloma, especially if combined with other novel 
agents like liposomal doxorubicin.21,24 Some have 
reported encouraging responses to systemic as well 
as intra-pleural bortezomib.22,23,25,26 Our patient was  
exposed to all available novel drugs including 
thalidomide, lenalidomide and bortezomib and 
did have a good response to systemic treatment 
with bortezomib, liposomal doxorubicin and 
dexamethasone. As his effusions resolved, no 
intra-pleural therapy was given. Unfortunately, 
the response was transient and he was not able to 
tolerate further therapy. He eventually died within 
6 months of developing the myelomatous pleural 
effusion.  

Conclusion
Pleural effusions in patients with multiple  
myeloma result from different aetiologies, each 
requiring a different type of treatment. Due to the 
important therapeutic and prognostic implications 
of finding a myelomatous pleural effusion, 
diagnostic throracocentesis with careful cytological 
examination and protein electrophoresis with 
immunofixation should be performed whenever 
possible. Supplemental studies with flow  
cytometry and cytogenetics should also be 
considered.

References
1. McKenna RW, Kyle RA, Kuehl WM, Grogan TM, 

Harris NL, Coupland RW.  Plasma Cell Neoplasms. 
In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, 
Pileri SA, Stein H et al, Eds. WHO Classification 
of Tumors of Hematopoietic and Lymphoid Tissue. 
IARC: Lyon 2008. Pp. 200−13. 



Myelomatous Pleural Effusion 
Case report and review of the literature

264 | SQU Medical Journal, May 2011, Volume 11, Issue 2

2. The International Myeloma Working Group. Criteria 
for the classification of monoclonal gammopathies, 
multiple myeloma and related disorders: A report 
of the International Myeloma Working Group. Br J 
Haematol 2003; 121:749−57. 

3. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, 
Dispenzieri A, et al. Review of 1026 patients with 
newly diagnosed multiple myeloma. Mayo Clin Proc 
2003; 78:21−33.

4. Kintzer JS, Rosenow EC, Kyle RA. Thoracic and 
pulmonary abnormalities in multiple myeloma: 
A review of 958 cases. Arch Intern Med 1978; 
138:727−30.

5. Hughes JC, Votaw ML. Pleural effusion in multiple 
myeloma. Cancer 1979; 44:1150−4.

6. Law I, Blom J. Second malignancies in patients with 
multiple myeloma. Oncology 1977; 34:20−4.

7. Kamble R, Wilson CS, Fassas A, Desikan R, Siegel 
DS, Tricot G, et al. Malignant pleural effusion of 
multiple myeloma: Prognostic factors and outcome. 
Leuk Lymphoma 2005; 46:1137−42.

8. Inoue Y, Chua K, McClure RF, Jimenez MC, Gocke 
CD, Badros AZ, et al. Multiple myeloma presenting 
initially as a solitary pleural effusion later complicated 
by malignant plasmacytic ascites. Leuk Res 2005; 
29:715−18.

9. Dhingra KK, Singhal N, Nigam S, Jain S. Unsuspected 
multiple myeloma presenting as bilateral pleural 
effusion – A cytological diagnosis. Cytojournal 2007; 
4:17−19.

10. Yokoyama T, Tanaka A, Kato S, Aizawa H. Multiple 
myeloma presenting initially with pleural effusion 
and a unique paraspinal tumor in the thorax. Intern 
Med 2008; 47:1917−20.

11. Rodriguez JN, Pereira A, Martinez JC, Conde J, Pujol 
E. Pleural effusion in multiple myeloma. Chest 1994; 
105:622−4.

12.  Kim YJ, Kim SJ, Min K, Kim HY, Kim HJ, Lee YK, 
et al. Multiple myeloma with myelomatous pleural 
effusion: A case report and review of the literature. 
Acta Haematol 2008; 120:108−11.

13. Fekih L, Fenniche S, Hassene H, Abdelghaffar H, 
Yaalaoui S, El Menzi F et al. Multiple myeloma 
presenting with multiple thoracic manifestations. 
Indian J Chest Dis Allied Sci 2010; 52:47−9.

14. Huang TC, Chao TY. Myelomatous pleural effusion. 
QJM 2010; 103:705−6.

15. Alexandrakis MG, Passam FH, Kyriakou DS, Bouros 
D. Pleural effusions in hematologic malignancies. 
Chest 2004; 125:1546−55.

16. Pacheco A, Perpina A, Escribano L, Sanz I, Bellas 
C. Pleural effusion as first sign of extramedullary 
plasmacytoma. Chest 1992; 102:296−7.

17. Meoli A, Willsie S, Fiorella R. Myelomatous pleural 
effusion. South Med J 1997; 90:65−8. 

18. Bedrossian CWM. Malignant effusions: A 
multimodal approach to cytologic diagnosis. New 
York: Igaku-Shoin, 1994. Pp. 54−6.

19. Palmer HE, Wilson CS, Bardales RH. Cytology and 
flow cytometry of malignant effusions of multiple 
myeloma. Diagn Cytopathol 2000; 22:147−51.

20. Smadja NV, Louvet C, Isnard F, Dutel JL, Grange 
MJ, Varette C, et al. Cytogenetic study in multiple 
myeloma at diagnosis: Comparison of two 
techniques. Br J Haematol 1995; 90:619−24.

21. Malhotra KP, Agrawal V, Prasad N. Myelomatous 
pleural effusion: A diagnostic challenge. Indian J 
Cancer 2010; 47:351−2.

22. Iannitto E, Scaglione R, Musso M, Abbadessa V, 
Licatta G. Intrapleural adriyamycin in treatment 
of myelomatous pleural effusion: A case report. 
Haematologica 1988; 73:325−6.

23. Makino S, Yamahara S, Nagake Y, Kamura J. Bence-
Jones myeloma with pleural effusion: Response to 
α-interferon and combined chemotherapy. Inter 
Med 1992; 31:617–21.

24. Sonneveld P, Hajek R, Nagler A, Spencer A, Blade 
J, Robak T, et al. Combined pegylated liposomal 
and bortexomib is highly effective in patients with 
recurrent or refractory myeloma who received prior 
thalidomide/lenalidomide therapy. Cancer 2008; 
112:1529−37.

25. Mangiacavalli S, Varettoni M, Zappasodi P, Pica 
G, Lazzarino M, Corso A. A striking response to 
bortezomib in a patient with pleural localization of 
multiple myeloma. Leukemia Res 2009; 33:577−8.

26. Iannitto E, Minardi V, Tripodo C. Use of intrapleural 
bortezomib in myelomatous pleural effusion. Br J 
Haematol 2007; 139:621−2.