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Postgraduate Education Corner: Chest Imaging and Pathology for Clinicians |

A 76-Year-Old Man With Anemia, Bone Pain, and Progressive DyspneaMan With Anemia, Bone Pain, and Dyspnea FREE TO VIEW

Thitiporn Suwatanapongched, MD; Prapaporn Pornsuriyasak, MD; Wasana Kanoksil, MD; Thotsaporn Morasert, MD; Warapat Virayavanich, MD
Author and Funding Information

From the Division of Diagnostic Radiology (Drs Suwatanapongched and Virayavanich), Department of Diagnostic and Therapeutic Radiology, Division of Pulmonary and Critical Care (Drs Pornsuriyasak and Morasert), Department of Medicine, and Department of Pathology (Dr Kanoksil), Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Correspondence to: Thitiporn Suwatanapongched, MD, Division of Diagnostic Radiology, Department of Diagnostic and Therapeutic Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, Ratchathewi, Bangkok 10400, Thailand; e-mail: ratrspoom@yahoo.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(4):913-918. doi:10.1378/chest.13-1662
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Published online

A 76-year-old man presented with left-sided hip pain radiating to the leg and foot for 4 weeks. He was a former smoker. The patient’s medical history included coronary artery disease, benign prostatic hypertrophy, and mild chronic renal impairment (serum creatinine, 1.5 mg/dL). Other previous blood chemistry tests and chest radiographs obtained 6 months earlier were unremarkable. The plain radiographs of the lumbosacral spine revealed only mild degenerative changes.

Two weeks later, the patient developed progressive dyspnea and dry cough without fever, orthopnea, or paroxysmal nocturnal dyspnea. On examination, he looked distressed and was tachypneic. Fine crepitations were heard bilaterally in the lower lungs. Both legs were edematous. There was a hard, nonpainful palpable mass at the sternum. Other physical examinations and neurologic signs were normal.

Clinical Findings

CBC revealed the following values: hemoglobin, 10.5 g/dL; hematocrit, 31.8%; mean corpuscular volume, 87.6 fL; WBC count, 6,460/μL (neutrophils, 70%; lymphocytes, 20%; monocytes, 9%; eosinophils, 1%); and platelet count, 185,000/μL. Blood chemistry tests revealed the following values: total protein, 90 g/L; serum albumin, 20.8 g/L; corrected serum calcium, 9.3 mg/dL (normal range, 8.5-10.1 mg/dL); serum phosphorus, 3.6 mg/dL (normal range, 2.5-4.9 mg/dL); serum lactate dehydrogenase (LDH), 556 U/L (normal range, 100-190 U/L); BUN, 23 mg/dL; serum creatinine, 1.89 mg/dL; and serum sodium, 129 mmol/L. Serum prostatic-specific antigen level was 4.2 ng/mL (normal range, 0-4 ng/mL), and serum CA-125 level was 80.3 U/mL (normal range, 0-35 U/mL). A heat precipitation test for Bence-Jones proteinuria (BJP) was negative. Other laboratory tests were within normal limits. Urine electrophoresis and serum protein electrophoresis (SPEP) were not done.

Radiologic Findings

MRI of the lumbosacral spine performed 2 weeks after initial presentation revealed multiple gadolinium-enhanced T1-hypointense lesions involving the spine (Fig 1), iliac bones, femoral heads, and lower ribs with associated extraosseous soft-tissue masses. Epidural extensions at the T12 level to the L1 level and the sacrum were noted.

Figure Jump LinkFigure 1. A, B, Sagittal precontrast T1-weighted (A) and postgadolinium fat-suppressed T1-weighted (B) MRIs demonstrating multifocal gadolinium-enhanced hypointense lesions within the vertebral bodies and posterior elements of the sacrum and lumbar vertebrae. Note the presence of presacral, epidural, and posterior paraspinal soft-tissue masses (arrows). The intervertebral discs are spared.Grahic Jump Location

Chest radiograph (Fig 2) showed multiple bilateral extrapulmonary masses with small bilateral pleural effusions. The bony thorax appeared intact. Bilateral pleural effusions increased rapidly as seen on follow-up chest radiographs.

Figure Jump LinkFigure 2. Anteroposterior chest radiograph showing two vague opacities with partially sharp and unsharp margins at the right-sided mid hemithorax. Also note multiple lentiform-shaped masses having a convex medial margin, tapered superior and inferior edges, and obtuse angles at the pleural interfaces bilaterally. A small amount of bilateral pleural effusions is present. No skeletal abnormality is seen.Grahic Jump Location

Cardiovascular diseases, especially congestive heart failure, myocardial ischemia, and acute pulmonary embolism, were considered as possible causes of the patient’s dyspnea; therefore, echocardiographic examination was performed. It revealed mild concentric hypertrophy of the left ventricle with good systolic function and mild diastolic dysfunction. Trivial mitral and tricuspid regurgitations were detected. There was no evidence of pulmonary hypertension or pericardial effusion. Color Doppler ultrasound of both legs showed no DVT.

CT scan of the chest (Fig 3) and abdomen performed subsequently confirmed the pleural effusions. Multiple bilateral extrapulmonary masses were found to be pleural and chest wall masses wrapping around the ribs and sternum without alteration of the shape or attenuation of the affected bones. Multiple enhanced extraosseous soft-tissue masses and osteolytic lesions involving the lumbosacral spine and iliac bones, corresponding to the MRI findings, were also noted. No pulmonary mass or thromboembolism was observed. Other intrathoracic and intraabdominal structures were normal.

Figure Jump LinkFigure 3. A, B, Axial chest CT scans with mediastinal window setting at the level of the main pulmonary artery (A) and T12 vertebral body (B) revealing moderate-sized bilateral pleural effusions with multiple noncalcified bilateral pleural masses and chest wall masses (white arrows), some of which wrap around the ribs and sternum. The masses show relatively homogeneous contrast enhancement, quite similar to the collapsed lungs (*), liver (L), and spleen (S). Extension into the right-sided intervertebral foramen and the spinal canal at the T12 level (black arrow) is also noted. All visualized thoracic bones are intact without alteration of their shape or attenuation.Grahic Jump Location
Pathologic Findings

Pleural fluid aspiration yielded 800 mL of serosanguinous fluid containing the following: RBC count, 86,000/mm3; WBC count, 4,584/mm3 (mononuclear cells, 95/mm3; polymorphonuclear cells, 5/mm3); LDH, 356 U/L; and total protein, 62 g/L. The results indicated exudative pleural effusion.

Cytologic examination of the pleural fluid (Fig 4) revealed many isolated pleomorphic tumor cells indistinguishable from lymphoma cells or poorly differentiated carcinoma cells. Subsequent cell block preparation of the pleural fluid (Fig 5A) clearly documented that these tumor cells were consistent with pleomorphic and immature plasma cells. Additional immunohistochemical staining (Figs 5B-D) showed marked positivity for CD-138 and monoclonal λ light-chain expression of these plasma cells. Approximately 80% of them showed a nuclear staining pattern for Ki-67, indicating a high proliferation index.

Figure Jump LinkFigure 4. Conventional preparation with Papanicolaou staining (original magnification ×400) of the pleural fluid revealing many medium to large single cells with convoluted nuclei and a minimal to moderate amount of cytoplasm. Note a histiocyte (arrow) in the center.Grahic Jump Location
Figure Jump LinkFigure 5. A, Cell block preparation of the pleural fluid with hematoxylin-eosin staining (original magnification ×400) revealing a loose cluster of multiple pleomorphic and immature plasma cells (seen on the right side of the image and outlined by arrowheads) having eccentric pleomorphic nuclei, amphophilic cytoplasm, and perinuclear hof admixed with RBCs. Note a mesothelial cell (large arrow) and a histiocyte (small arrow). B-D, Immunohistochemical staining (original magnification ×400) showing numerous neoplastic cells marked with CD-138 in their cytoplasmic membranes (B) and positive λ light-chain expression in their cytoplasm (C) compared with the negative immunoreactivity to κ light chain (D).Grahic Jump Location

Flow cytometry of the pleural fluid showed cytoplasmic λ light-chain restriction of the plasma cells. Serum immunofixation electrophoresis was also positive for IgG-λ.

Unfortunately, the patient deteriorated rapidly and died 4 weeks after presentation. Bone marrow examination was not performed.

What is the diagnosis?
Diagnosis: Bilateral myelomatous pleural effusions with extramedullary plasmacytomas
Clinical Discussion

With the key clinical and laboratory features in this patient, the differential diagnoses were broadened and encompassed various diseases, including multiple myeloma (MM); solitary plasmacytoma; brown tumors (osteitis fibrosis cystica) in hyperparathyroidism; metastatic disease from osteosarcoma, lung cancer, or prostate cancer (albeit pleural metastasis is uncommon); lymphoma/leukemia; amyloidosis; TB; sarcoidosis; and other granulomatous diseases.1-6 Nevertheless, the presence of anemia and renal insufficiency omitted further consideration of solitary plasmacytoma.1 Hyperparathyroidism was also unlikely in the setting of normocalcemia and normophosphatemia.1 Hence, a serum parathyroid hormone test was not done.

Although MM was initially considered, the negative BJP and normocalcemia in this patient hindered the diagnosis. However, it should be mentioned that BJP is found in only 20% of patients with MM at initial manifestation, and a urinary dipstick test for BJP often is negative.1,5 Identification of a monoclonal or M protein in the serum or urine is the mainstay for the diagnosis. Hence, SPEP should be performed when MM is suspected because it demonstrates a local peak of M protein (M spike) in > 80% of patients with MM.1,7,8 Nevertheless, approximately 15% of patients with MM have only monoclonal κ or λ light chain in the serum (BJP).8 In this instance, SPEP may be normal, and serum immunofixation electrophoresis (as done in the present case), can help in the diagnosis.1,8

The rapid development and progression of bilateral pleural effusions also decreased our concern about MM because direct pleural involvement by MM in the form of either myelomatous pleural effusion (MPE) or extramedullary plasmacytomas (EMPs) is rare. MPE accounts for only 0.8% to 2.6% of pleural effusions in patients with MM.9-12 Pleural effusions occurring in MM are usually a result of other etiologies, including congestive heart failure, renal failure, pulmonary thromboembolism, infection, amyloidosis, and second malignancy.3,6,9-12 MPE usually manifests as a late complication several months after the diagnosis of MM and as a unilateral pleural effusion, most of which is left sided.9-15

To date, fewer than 30 cases of bilateral MPEs have been reported in the English literature.2,3,6,9-11,16-20 Approximately 40% of patients with bilateral MPEs presented with an initial manifestation (as in the present case) or within 1 month after the diagnosis of MM.6,11,16-20 Most of the patients were men in their sixth to seventh decades (age range, 36-82 years). All had preceding anemia with common presenting symptoms, including progressive dyspnea, chest pain, and bone pain, or symptoms related to nerve root or cord compression.6,20

Of note, elevation of pleural adenosine deaminase and LDH levels has been reported in MPEs.3,6,11,17 Most patients also had elevated serum LDH levels (as in the present case), β2-microglobulin, or C-reactive protein, suggesting high tumor burden and poor outcomes.1,3,6,8,10-12,18-20 Of interest, elevated serum CA-125 level, as in the present case, has been reported in bilateral MPEs,6 and its presence might raise the concern for MPE. Nonetheless, serum CA-125 level can be elevated in various malignant and benign conditions, such as hepatic cirrhosis, heart failure, and ovarian, endometrial, breast, lung, pancreatic, and other malignancies.21

Like in the present case, the overall prognosis of patients having MPE with or without EMPs is poor. Despite aggressive local treatment (pleurodesis) and systemic chemotherapy, a median survival time after the development of MPE is < 4 months.2,3,10-12,17-19

Radiologic Discussion

On chest radiograph in the present case, the presence of masses projected en face to the x-ray beam showing partially sharp and partially unsharp margins (the so-called incomplete border sign) and masses with the inner margin projected tangential to the x-ray beam having convex medial margin, tapered superior and inferior edges, and obtuse angles at the pleural interfaces (the so-called tapered border sign) suggested that the masses were in the intrathoracic, extrapulmonary compartment.22 The differential diagnoses included loculated pleural effusions, metastatic tumors, lymphoma, mesothelioma, EMPs, brown tumors, and TB.1,22,23 Unless associated rib or bone involvement is present, it is impossible to distinguish pleural lesions from extrapleural (chest wall) lesions. In the present case, this prompted a subsequent CT scan with IV contrast administration, despite the risk posed by renal impairment, to clarify the location, extent, and nature of the masses and to evaluate coexistent pulmonary thromboembolism and other associated abnormalities that might help in the diagnosis.

Up to now, there have been limited data regarding CT scan findings of MPE.2,3,6,10,13,14,16-18,20,24 Similar to the present case, associated pleural thickening or masses and chest wall masses caused by EMPs have been reported in patients with either bilateral or unilateral MPEs.2,6,10,13,14,16,17,20 Associated lung parenchymal lesions and mediastinal masses or lymphadenopathy can also be seen.10,11,13,17,20

As shown in the present case and in previous studies, alteration of the affected bones (generalized loss of bone density, alteration of bone texture, punched-out lesions, expanding lesions) may not be depicted on the chest radiograph and chest CT scan,2,9,16,17,20 even in the presence of an extraosseous soft-tissue mass (the so-called wrap-around sign previously reported by Moulopoulos et al23) as a specific sign for lymphoma. Therefore, a skeletal survey using MRI may be required in an atypical case to assess extrathoracic skeletal or marrow involvement by MM.1,8 The important radiologic pitfalls in the present patient were the MRI findings of the lumbosacral spine mimicking metastatic disease and the presence of bilateral pleural effusions and bilateral extrapulmonary masses without typical alteration of the affected bones found in MM.

Pathologic Discussion

MPEs are almost always exudative and vary from bloody,9-11,16,20 to serosanguinous,2,9-11,19,23 to yellow or straw10,15,19 color, indistinguishable from other more common malignant and tuberculous pleural effusions. The pathogenesis of MPE remains unclear. Possible mechanisms have been proposed, including direct extension from adjacent skeletal, lung parenchymal, or mediastinal tumors into the pleural space; direct infiltration or implantation of tumor nodules into the pleura; and lymphatic obstruction secondary to mediastinal lymph node involvement.3,9,16 We speculated that exudative characteristics of MPE might be attributed to impaired lymphatic flow, leading to reduced reabsorption and subsequent accumulation of the M or light-chain proteins produced by the neoplastic plasma cells or local inflammation with increased capillary permeability on the involved pleura.24,25

The diagnosis of MPE requires the presence of atypical plasma cells in the pleural fluid, the demonstration of M protein by pleural fluid electrophoresis, or histopathologic confirmation by a pleural biopsy sample or by autopsy.24 Because cytologic examination under conventional preparation with Papanicolaou staining is sometimes difficult to distinguish MPE from other malignancies, particularly non-Hodgkin’s lymphoma, acute and chronic lymphocytic leukemia, or poorly differentiated carcinoma,15,19,20 further analysis with the air-dried, Diff-Quik-stained (Romanoswky-stained) smears and cell block preparation of the pleural fluid should be performed for better demonstration and characterization of plasma cell morphology and immunophenotype.15 When pleural biopsy cannot be done, cytologic examination of the pleural fluid or cell block preparation with additional immunohistochemical staining for plasma cells and flow cytometry can confirm the diagnosis of MPE, as in the present case.3,10,11,15,19

We report a fatal case in which the diagnosis of direct pleural involvement in MM was delayed because of some important clinical and radiologic pitfalls. Therefore, both radiologists and clinicians should be aware of direct pleural involvement in MM, albeit rare, as a possible cause of unilateral or bilateral exudative pleural effusions with or without associated pleural or chest wall mass, even without alteration of the affected bones or BJP, in any patients having anemia, renal insufficiency, and bone pain. Further investigations for MM, particularly SPEP and a skeletal survey for marrow abnormalities using MRI, are necessary. Nevertheless, the definitive diagnosis of direct pleural involvement in MM requires histopathologic confirmation or at least cytologic examination of the pleural fluid or pleural fluid cell block preparation with additional immunohistochemical staining for plasma cells and flow cytometry.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The authors thank Phienvit Tantibhedhyangkul, MD, PhD, and Amnuay Thitapandha, MD, PhD, for comments and suggestions and Pitsanu Detakarat, MS, for help in preparing the images presented in this article. CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Nau KC, Lewis WD. Multiple myeloma: diagnosis and treatment. Am Fam Physician. 2008;78(7):853-859.
 
Hughes JC, Votaw ML. Pleural effusion in multiple myeloma. Cancer. 1979;44(3):1150-1154. [CrossRef]
 
Al-Farsi K, Al-Haddabi I, Al-Riyami N, Al-Sukaiti R, Al-Kindi S. Myelomatous pleural effusion: case report and review of the literature. Sultan Qaboos Univ Med J. 2011;11(2):259-264.
 
Kawahara T, Taguchi H, Yamagishi T, Udagawa K, Ouchi H, Misaki H. A case of bilateral adrenal and pleural metastases from prostate cancer. Case Rep Oncol. 2009;2(3):217-219. [CrossRef]
 
Chauveau D, Choukroun G. Bence Jones proteinuria and myeloma kidney. Nephrol Dial Transplant. 1996;11(3):413-415. [CrossRef]
 
Xu XL, Shen YH, Shen Q, Zhou JY. A case of bilateral pleural effusion as the first sign of multiple myeloma. Eur J Med Res. 2013;18:7. [CrossRef]
 
Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21-33. [CrossRef]
 
Angtuaco EJ, Fassas AB, Walker R, Sethi R, Barlogie B. Multiple myeloma: clinical review and diagnostic imaging. Radiology. 2004;231(1):11-23. [CrossRef]
 
Kintzer JS Jr, Rosenow EC III, Kyle RA. Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases. Arch Intern Med. 1978;138(5):727-730. [CrossRef]
 
Kamble R, Wilson CS, Fassas A, et al. Malignant pleural effusion of multiple myeloma: prognostic factors and outcome. Leuk Lymphoma. 2005;46(8):1137-1142. [CrossRef]
 
Cho YU, Chi HS, Park CJ, Jang S, Seo EJ, Suh C. Myelomatous pleural effusion: a case series in a single institution and literature review. Korean J Lab Med. 2011;31(4):225-230. [CrossRef]
 
Kim YJ, Kim SJ, Min K, et al. Multiple myeloma with myelomatous pleural effusion: a case report and review of the literature. Acta Haematol. 2008;120(2):108-111. [CrossRef]
 
Inoue Y, Chua K, McClure RF, et al. Multiple myeloma presenting initially as a solitary pleural effusion later complicated by malignant plasmacytic ascites. Leuk Res. 2005;29(6):715-718. [CrossRef]
 
Feng PH, Huang CC, Wang CW, Wu YK, Tsai YH. Solitary pleural plasmacytomas manifested as a massive pleural effusion without evidence of monoclonal gammopathy. Respirology. 2008;13(5):751-753. [CrossRef]
 
Palmer HE, Wilson CS, Bardales RH. Cytology and flow cytometry of malignant effusions of multiple myeloma. Diagn Cytopathol. 2000;22(3):147-151. [CrossRef]
 
Makino S, Yamahara S, Nagake Y, Kamura J. Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy. Intern Med. 1992;31(5):617-621. [CrossRef]
 
Cabrera A, Klein JS. Bilateral pleural masses and shortness of breath associated with multiple myeloma. Chest. 1997;111(6):1750-1753. [CrossRef]
 
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(21):1917-1920. [CrossRef]
 
Choi YD, Kim SS, Han CW, et al. Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports. Korean J Pathol. 2009;43(4):382-385. [CrossRef]
 
Agrawal R, Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion. J Case Rep. 2012;2(2):48-50.
 
Miralles C, Orea M, España P, et al. Cancer antigen 125 associated with multiple benign and malignant pathologies. Ann Surg Oncol. 2003;10(2):150-154. [CrossRef]
 
Völk M, Strotzer M, Feuerbach S. Case of the month. Intrapulmonary or extrapulmonary? Br J Radiol. 2000;73(868):451-452.
 
Moulopoulos LA, Dimopoulos MA, Vourtsi A, Gouliamos A, Vlahos L. Bone lesions with soft-tissue mass: magnetic resonance imaging diagnosis of lymphomatous involvement of the bone marrow versus multiple myeloma and bone metastases. Leuk Lymphoma. 1999;34(1-2):179-184.
 
Oudart JB, Maquart FX, Semouma O, Lauer M, Arthuis-Demoulin P, Ramont L. Pleural effusion in a patient with multiple myeloma. Clin Chem. 2012;58(4):672-674. [CrossRef]
 
Anevlavis S, Tzouvelekis A, Bouros D. Mechanisms of pleural involvement in orphan diseases. Respiration. 2012;83(1):5-12. [CrossRef]
 

Figures

Figure Jump LinkFigure 1. A, B, Sagittal precontrast T1-weighted (A) and postgadolinium fat-suppressed T1-weighted (B) MRIs demonstrating multifocal gadolinium-enhanced hypointense lesions within the vertebral bodies and posterior elements of the sacrum and lumbar vertebrae. Note the presence of presacral, epidural, and posterior paraspinal soft-tissue masses (arrows). The intervertebral discs are spared.Grahic Jump Location
Figure Jump LinkFigure 2. Anteroposterior chest radiograph showing two vague opacities with partially sharp and unsharp margins at the right-sided mid hemithorax. Also note multiple lentiform-shaped masses having a convex medial margin, tapered superior and inferior edges, and obtuse angles at the pleural interfaces bilaterally. A small amount of bilateral pleural effusions is present. No skeletal abnormality is seen.Grahic Jump Location
Figure Jump LinkFigure 3. A, B, Axial chest CT scans with mediastinal window setting at the level of the main pulmonary artery (A) and T12 vertebral body (B) revealing moderate-sized bilateral pleural effusions with multiple noncalcified bilateral pleural masses and chest wall masses (white arrows), some of which wrap around the ribs and sternum. The masses show relatively homogeneous contrast enhancement, quite similar to the collapsed lungs (*), liver (L), and spleen (S). Extension into the right-sided intervertebral foramen and the spinal canal at the T12 level (black arrow) is also noted. All visualized thoracic bones are intact without alteration of their shape or attenuation.Grahic Jump Location
Figure Jump LinkFigure 4. Conventional preparation with Papanicolaou staining (original magnification ×400) of the pleural fluid revealing many medium to large single cells with convoluted nuclei and a minimal to moderate amount of cytoplasm. Note a histiocyte (arrow) in the center.Grahic Jump Location
Figure Jump LinkFigure 5. A, Cell block preparation of the pleural fluid with hematoxylin-eosin staining (original magnification ×400) revealing a loose cluster of multiple pleomorphic and immature plasma cells (seen on the right side of the image and outlined by arrowheads) having eccentric pleomorphic nuclei, amphophilic cytoplasm, and perinuclear hof admixed with RBCs. Note a mesothelial cell (large arrow) and a histiocyte (small arrow). B-D, Immunohistochemical staining (original magnification ×400) showing numerous neoplastic cells marked with CD-138 in their cytoplasmic membranes (B) and positive λ light-chain expression in their cytoplasm (C) compared with the negative immunoreactivity to κ light chain (D).Grahic Jump Location

Tables

References

Nau KC, Lewis WD. Multiple myeloma: diagnosis and treatment. Am Fam Physician. 2008;78(7):853-859.
 
Hughes JC, Votaw ML. Pleural effusion in multiple myeloma. Cancer. 1979;44(3):1150-1154. [CrossRef]
 
Al-Farsi K, Al-Haddabi I, Al-Riyami N, Al-Sukaiti R, Al-Kindi S. Myelomatous pleural effusion: case report and review of the literature. Sultan Qaboos Univ Med J. 2011;11(2):259-264.
 
Kawahara T, Taguchi H, Yamagishi T, Udagawa K, Ouchi H, Misaki H. A case of bilateral adrenal and pleural metastases from prostate cancer. Case Rep Oncol. 2009;2(3):217-219. [CrossRef]
 
Chauveau D, Choukroun G. Bence Jones proteinuria and myeloma kidney. Nephrol Dial Transplant. 1996;11(3):413-415. [CrossRef]
 
Xu XL, Shen YH, Shen Q, Zhou JY. A case of bilateral pleural effusion as the first sign of multiple myeloma. Eur J Med Res. 2013;18:7. [CrossRef]
 
Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21-33. [CrossRef]
 
Angtuaco EJ, Fassas AB, Walker R, Sethi R, Barlogie B. Multiple myeloma: clinical review and diagnostic imaging. Radiology. 2004;231(1):11-23. [CrossRef]
 
Kintzer JS Jr, Rosenow EC III, Kyle RA. Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases. Arch Intern Med. 1978;138(5):727-730. [CrossRef]
 
Kamble R, Wilson CS, Fassas A, et al. Malignant pleural effusion of multiple myeloma: prognostic factors and outcome. Leuk Lymphoma. 2005;46(8):1137-1142. [CrossRef]
 
Cho YU, Chi HS, Park CJ, Jang S, Seo EJ, Suh C. Myelomatous pleural effusion: a case series in a single institution and literature review. Korean J Lab Med. 2011;31(4):225-230. [CrossRef]
 
Kim YJ, Kim SJ, Min K, et al. Multiple myeloma with myelomatous pleural effusion: a case report and review of the literature. Acta Haematol. 2008;120(2):108-111. [CrossRef]
 
Inoue Y, Chua K, McClure RF, et al. Multiple myeloma presenting initially as a solitary pleural effusion later complicated by malignant plasmacytic ascites. Leuk Res. 2005;29(6):715-718. [CrossRef]
 
Feng PH, Huang CC, Wang CW, Wu YK, Tsai YH. Solitary pleural plasmacytomas manifested as a massive pleural effusion without evidence of monoclonal gammopathy. Respirology. 2008;13(5):751-753. [CrossRef]
 
Palmer HE, Wilson CS, Bardales RH. Cytology and flow cytometry of malignant effusions of multiple myeloma. Diagn Cytopathol. 2000;22(3):147-151. [CrossRef]
 
Makino S, Yamahara S, Nagake Y, Kamura J. Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy. Intern Med. 1992;31(5):617-621. [CrossRef]
 
Cabrera A, Klein JS. Bilateral pleural masses and shortness of breath associated with multiple myeloma. Chest. 1997;111(6):1750-1753. [CrossRef]
 
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(21):1917-1920. [CrossRef]
 
Choi YD, Kim SS, Han CW, et al. Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports. Korean J Pathol. 2009;43(4):382-385. [CrossRef]
 
Agrawal R, Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion. J Case Rep. 2012;2(2):48-50.
 
Miralles C, Orea M, España P, et al. Cancer antigen 125 associated with multiple benign and malignant pathologies. Ann Surg Oncol. 2003;10(2):150-154. [CrossRef]
 
Völk M, Strotzer M, Feuerbach S. Case of the month. Intrapulmonary or extrapulmonary? Br J Radiol. 2000;73(868):451-452.
 
Moulopoulos LA, Dimopoulos MA, Vourtsi A, Gouliamos A, Vlahos L. Bone lesions with soft-tissue mass: magnetic resonance imaging diagnosis of lymphomatous involvement of the bone marrow versus multiple myeloma and bone metastases. Leuk Lymphoma. 1999;34(1-2):179-184.
 
Oudart JB, Maquart FX, Semouma O, Lauer M, Arthuis-Demoulin P, Ramont L. Pleural effusion in a patient with multiple myeloma. Clin Chem. 2012;58(4):672-674. [CrossRef]
 
Anevlavis S, Tzouvelekis A, Bouros D. Mechanisms of pleural involvement in orphan diseases. Respiration. 2012;83(1):5-12. [CrossRef]
 
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