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• W2157778779 abstract "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. 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. 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. 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. 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. 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 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).View Large Image Figure ViewerDownload Hi-res image Download (PPT) 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. 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.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar, 2Hughes JC Votaw ML Pleural effusion in multiple myeloma.Cancer. 1979; 44: 1150-1154Crossref PubMed Scopus (47) Google Scholar, 3Al-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: 259-264PubMed Google Scholar, 4Kawahara 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: 217-219Crossref PubMed Google Scholar, 5Chauveau D Choukroun G Bence Jones proteinuria and myeloma kidney.Nephrol Dial Transplant. 1996; 11: 413-415Crossref PubMed Google Scholar, 6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar Nevertheless, the presence of anemia and renal insufficiency omitted further consideration of solitary plasmacytoma.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar Hyperparathyroidism was also unlikely in the setting of normocalcemia and normophosphatemia.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar 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.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar, 5Chauveau D Choukroun G Bence Jones proteinuria and myeloma kidney.Nephrol Dial Transplant. 1996; 11: 413-415Crossref PubMed Google Scholar 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.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar, 7Kyle RA Gertz MA Witzig TE et al.Review of 1027 patients with newly diagnosed multiple myeloma.Mayo Clin Proc. 2003; 78: 21-33Abstract Full Text Full Text PDF PubMed Scopus (1602) Google Scholar, 8Angtuaco EJ Fassas AB Walker R Sethi R Barlogie B Multiple myeloma: clinical review and diagnostic imaging.Radiology. 2004; 231: 11-23Crossref PubMed Scopus (212) Google Scholar Nevertheless, approximately 15% of patients with MM have only monoclonal κ or λ light chain in the serum (BJP).8Angtuaco EJ Fassas AB Walker R Sethi R Barlogie B Multiple myeloma: clinical review and diagnostic imaging.Radiology. 2004; 231: 11-23Crossref PubMed Scopus (212) Google Scholar In this instance, SPEP may be normal, and serum immunofixation electrophoresis (as done in the present case), can help in the diagnosis.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar, 8Angtuaco EJ Fassas AB Walker R Sethi R Barlogie B Multiple myeloma: clinical review and diagnostic imaging.Radiology. 2004; 231: 11-23Crossref PubMed Scopus (212) Google Scholar 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.9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 12Kim 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: 108-111Crossref PubMed Scopus (26) Google Scholar 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.3Al-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: 259-264PubMed Google Scholar, 6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 12Kim 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: 108-111Crossref PubMed Scopus (26) Google Scholar 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.9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 12Kim 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: 108-111Crossref PubMed Scopus (26) Google Scholar, 13Inoue 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: 715-718Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 14Feng 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: 751-753Crossref PubMed Scopus (8) Google Scholar, 15Palmer HE Wilson CS Bardales RH Cytology and flow cytometry of malignant effusions of multiple myeloma.Diagn Cytopathol. 2000; 22: 147-151Crossref PubMed Scopus (31) Google Scholar To date, fewer than 30 cases of bilateral MPEs have been reported in the English literature.2Hughes JC Votaw ML Pleural effusion in multiple myeloma.Cancer. 1979; 44: 1150-1154Crossref PubMed Scopus (47) Google Scholar, 3Al-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: 259-264PubMed Google Scholar, 6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 16Makino S Yamahara S Nagake Y Kamura J Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy.Intern Med. 1992; 31: 617-621Crossref PubMed Scopus (16) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 18Yokoyama 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: 1917-1920Crossref PubMed Scopus (18) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar 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.6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 16Makino S Yamahara S Nagake Y Kamura J Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy.Intern Med. 1992; 31: 617-621Crossref PubMed Scopus (16) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 18Yokoyama 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: 1917-1920Crossref PubMed Scopus (18) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar 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.6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar Of note, elevation of pleural adenosine deaminase and LDH levels has been reported in MPEs.3Al-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: 259-264PubMed Google Scholar, 6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar 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.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar, 3Al-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: 259-264PubMed Google Scholar, 6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 8Angtuaco EJ Fassas AB Walker R Sethi R Barlogie B Multiple myeloma: clinical review and diagnostic imaging.Radiology. 2004; 231: 11-23Crossref PubMed Scopus (212) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 12Kim 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: 108-111Crossref PubMed Scopus (26) Google Scholar, 18Yokoyama 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: 1917-1920Crossref PubMed Scopus (18) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar Of interest, elevated serum CA-125 level, as in the present case, has been reported in bilateral MPEs,6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar 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.21Miralles C Orea M España P et al.Cancer antigen 125 associated with multiple benign and malignant pathologies.Ann Surg Oncol. 2003; 10: 150-154Crossref PubMed Scopus (129) Google Scholar 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.2Hughes JC Votaw ML Pleural effusion in multiple myeloma.Cancer. 1979; 44: 1150-1154Crossref PubMed Scopus (47) Google Scholar, 3Al-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: 259-264PubMed Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 12Kim 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: 108-111Crossref PubMed Scopus (26) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 18Yokoyama 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: 1917-1920Crossref PubMed Scopus (18) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar 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.22Völk M Strotzer M Feuerbach S Case of the month. Intrapulmonary or extrapulmonary?.Br J Radiol. 2000; 73: 451-452Crossref PubMed Scopus (4) Google Scholar The differential diagnoses included loculated pleural effusions, metastatic tumors, lymphoma, mesothelioma, EMPs, brown tumors, and TB.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar, 22Völk M Strotzer M Feuerbach S Case of the month. Intrapulmonary or extrapulmonary?.Br J Radiol. 2000; 73: 451-452Crossref PubMed Scopus (4) Google Scholar, 23Moulopoulos 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: 179-184Crossref PubMed Scopus (23) Google Scholar 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.2Hughes JC Votaw ML Pleural effusion in multiple myeloma.Cancer. 1979; 44: 1150-1154Crossref PubMed Scopus (47) Google Scholar, 3Al-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: 259-264PubMed Google Scholar, 6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 13Inoue 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: 715-718Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 14Feng 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: 751-753Crossref PubMed Scopus (8) Google Scholar, 16Makino S Yamahara S Nagake Y Kamura J Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy.Intern Med. 1992; 31: 617-621Crossref PubMed Scopus (16) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 18Yokoyama 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: 1917-1920Crossref PubMed Scopus (18) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar, 24Oudart JB Maquart FX Semouma O Lauer M Arthuis-Demoulin P Ramont L Pleural effusion in a patient with multiple myeloma.Clin Chem. 2012; 58: 672-674Crossref PubMed Scopus (22) Google Scholar 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.2Hughes JC Votaw ML Pleural effusion in multiple myeloma.Cancer. 1979; 44: 1150-1154Crossref PubMed Scopus (47) Google Scholar, 6Xu 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: 7Crossref PubMed Scopus (11) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 13Inoue 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: 715-718Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 14Feng 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: 751-753Crossref PubMed Scopus (8) Google Scholar, 16Makino S Yamahara S Nagake Y Kamura J Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy.Intern Med. 1992; 31: 617-621Crossref PubMed Scopus (16) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar Associated lung parenchymal lesions and mediastinal masses or lymphadenopathy can also be seen.10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 13Inoue 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: 715-718Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar 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,2Hughes JC Votaw ML Pleural effusion in multiple myeloma.Cancer. 1979; 44: 1150-1154Crossref PubMed Scopus (47) Google Scholar, 9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 16Makino S Yamahara S Nagake Y Kamura J Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy.Intern Med. 1992; 31: 617-621Crossref PubMed Scopus (16) Google Scholar, 17Cabrera A Klein JS Bilateral pleural masses and shortness of breath associated with multiple myeloma.Chest. 1997; 111: 1750-1753Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar even in the presence of an extraosseous soft-tissue mass (the so-called wrap-around sign previously reported by Moulopoulos et al23Moulopoulos 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: 179-184Crossref PubMed Scopus (23) Google Scholar) 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.1Nau KC Lewis WD Multiple myeloma: diagnosis and treatment.Am Fam Physician. 2008; 78: 853-859PubMed Google Scholar, 8Angtuaco EJ Fassas AB Walker R Sethi R Barlogie B Multiple myeloma: clinical review and diagnostic imaging.Radiology. 2004; 231: 11-23Crossref PubMed Scopus (212) Google Scholar 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. MPEs are almost always exudative and vary from bloody,9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 16Makino S Yamahara S Nagake Y Kamura J Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy.Intern Med. 1992; 31: 617-621Crossref PubMed Scopus (16) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar to serosanguinous,2Hughes JC Votaw ML Pleural effusion in multiple myeloma.Cancer. 1979; 44: 1150-1154Crossref PubMed Scopus (47) Google Scholar, 9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar, 23Moulopoulos 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: 179-184Crossref PubMed Scopus (23) Google Scholar to yellow or straw10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 15Palmer HE Wilson CS Bardales RH Cytology and flow cytometry of malignant effusions of multiple myeloma.Diagn Cytopathol. 2000; 22: 147-151Crossref PubMed Scopus (31) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar 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.3Al-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: 259-264PubMed Google Scholar, 9Kintzer Jr, JS Rosenow III, EC Kyle RA Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases.Arch Intern Med. 1978; 138: 727-730Crossref PubMed Scopus (159) Google Scholar, 16Makino S Yamahara S Nagake Y Kamura J Bence-Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy.Intern Med. 1992; 31: 617-621Crossref PubMed Scopus (16) Google Scholar 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.24Oudart JB Maquart FX Semouma O Lauer M Arthuis-Demoulin P Ramont L Pleural effusion in a patient with multiple myeloma.Clin Chem. 2012; 58: 672-674Crossref PubMed Scopus (22) Google Scholar, 25Anevlavis S Tzouvelekis A Bouros D Mechanisms of pleural involvement in orphan diseases.Respiration. 2012; 83: 5-12Crossref PubMed Scopus (10) Google Scholar 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.24Oudart JB Maquart FX Semouma O Lauer M Arthuis-Demoulin P Ramont L Pleural effusion in a patient with multiple myeloma.Clin Chem. 2012; 58: 672-674Crossref PubMed Scopus (22) Google Scholar 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,15Palmer HE Wilson CS Bardales RH Cytology and flow cytometry of malignant effusions of multiple myeloma.Diagn Cytopathol. 2000; 22: 147-151Crossref PubMed Scopus (31) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar, 20Agrawal R Kumar P Multiple myeloma presenting as bilateral malignant pleural effusion.J Case Rep. 2012; 2: 48-50Crossref Google Scholar 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.15Palmer HE Wilson CS Bardales RH Cytology and flow cytometry of malignant effusions of multiple myeloma.Diagn Cytopathol. 2000; 22: 147-151Crossref PubMed Scopus (31) Google Scholar 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.3Al-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: 259-264PubMed Google Scholar, 10Kamble R Wilson CS Fassas A et al.Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.Leuk Lymphoma. 2005; 46: 1137-1142Crossref PubMed Scopus (74) Google Scholar, 11Cho 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: 225-230Crossref PubMed Scopus (19) Google Scholar, 15Palmer HE Wilson CS Bardales RH Cytology and flow cytometry of malignant effusions of multiple myeloma.Diagn Cytopathol. 2000; 22: 147-151Crossref PubMed Scopus (31) Google Scholar, 19Choi YD Kim SS Han CW et al.Cytologic diagnosis of malignant pleural effusion in multiple myeloma: two case reports.Korean J Pathol. 2009; 43: 382-385Crossref Scopus (2) Google Scholar 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." @default.
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• W2157778779 title "A 76-Year-Old Man With Anemia, Bone Pain, and Progressive Dyspnea" @default.
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