- Email: [email protected]
A 42-Year-Old Man With Shortness of Breath, Fever, and Pleural Effusions
[
Pulmonary, Critical Care, and Sleep Pearls
]
A 42-Year-Old Man With Shortness of Breath, Fever, and Pleural Effusions Jessica K. Millar, BS; Lauryn A. Benninger, DO; Ying Li, MD; and Ali Ataya, MD
A 42-year-old man with a history of progressive multiple myeloma and chronic kidney disease presented with worsening shortness of breath and fever. He was scheduled for a planned admission for chemotherapy on the day of presentation and had developed these symptoms the night before. He had also developed worsening fatigue but denied any new cough, sputum production, or abdominal pain. The patient had been previously admitted 3 weeks prior for neutropenic fever and colitis during his first cycle of chemotherapy. CHEST 2019; 155(5):e141-e144
CASE PRESENTATION:
Physical Examination Findings The patient’s vital signs showed the following: temperature, 38.7 C; heart rate, 122 beats/min; respirations, 25 breaths/min; BP, 112/59; and oxygen saturation, 96% on room air. The patient had
diminished breath sounds along the lung bases bilaterally. He had a large protruding mass from his right posterior-lateral chest wall that was firm, nonmobile, nonerythematous, and mildly tender on palpation without any ulcerations. He was grossly anasarcic.
Figure 1 – Chest radiograph showing diffuse bilateral pulmonary infiltrates with right pleural effusion.
Figure 2 – CT scan of the chest revealed bilateral pleural effusions, larger on the right, with bony destruction of the right ninth rib.
AFFILIATIONS: From the College of Medicine (Ms Millar), the Division of Pulmonary, Critical Care and Sleep Medicine (Drs Benninger and Ataya), and the Department of Pathology, Immunology and Laboratory Medicine (Dr Li), University of Florida, Gainesville, FL. CORRESPONDENCE TO: Ali Ataya, MD, University of Florida, Division of Pulmonary, Critical Care and Sleep Medicine, 1600 SW Archer Rd, M452, P.O. Box 100225, Gainesville, FL 32610; e-mail: [email protected]
Copyright Ó 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2018.10.035
chestjournal.org
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Figure 3 – A, Pleural fluid cytology revealed neoplastic plasma cells at an original magnification of 400. B-D, These cells stained positive for CD138 (B) and l light chains (D), but were negative for k light chains (C), HHV8, EBV, and ALK1 (original magnification, 400). ALK1 ¼ activin receptorlike kinase 1; EBV ¼ Epstein-Barr virus; HHV8 ¼ human herpesvirus 8.
Diagnostic Studies Laboratory testing revealed pancytopenia, with a leukocyte count of 600/mm3 and an absolute neutrophil count of 460/mm3. A chest radiograph revealed diffuse bilateral pulmonary infiltrates (Fig 1), and a CT scan of the chest showed bilateral pleural effusions and bony destruction of the right ninth rib without evidence of any infiltrates or nodules (Fig 2). Pleural fluid analysis of the right pleural effusion revealed a noncomplicated exudative effusion with pleural fluid lactate dehydrogenase (LDH) of 234 U/L and protein of 3.0 g/ dL with serum LDH of 578 U/L and protein of 5.7 g/dL. Pleural fluid pH was 7.45. Pleural fluid cell count revealed 39% polymorphonuclear leukocytes,
e142 Pulmonary, Critical Care, and Sleep Pearls
20% lymphocytes, 22% monocytes, and 19% other cells. Cytology and hematopathology studies revealed large neoplastic cells with morphologic features of plasma cells along with small lymphocytes, granulocytes, and mesothelial cells. Immunohistochemistry studies of the pleural fluid cells were positive for CD138 and restricted l light chain, but negative for activin receptor-like kinase 1 (ALK1), human herpesvirus 8 (HHV8), Epstein-Barr virus (EBV), and k light chain (Fig 3). Flow cytometry of the pleural fluid revealed abnormal plasma cells with aberrant expression of CD56 and dim CD30, without CD19 and CD20.
What is the diagnosis?
[
155#5 CHEST MAY 2019
]
Diagnosis: Myelomatous pleural effusion Discussion Myelomatous pleural effusion is a rare manifestation and complication of multiple myeloma. Pleural effusion in multiple myeloma may be a consequence of end-organ damage (heart failure secondary to hyperviscosity, cardiomyopathy related to treatment, pulmonary embolism, infection, nephrotic syndrome, or chronic renal failure) or a sign of thoracic involvement. Pleural effusions affect about 6% of all patients diagnosed with multiple myeloma. However, myelomatous pleural effusion is much rarer, affecting < 1% of patients with multiple myeloma. It is theorized that myelomatous pleural effusion may be the result of direct extension of plasma cells from adjacent chest wall or pulmonary lesions, direct infiltration of tumor deposits on the pleura, hematogenous spread, and/or lymphatic obstruction from mediastinal lymph node infiltration. Myelomatous pleural effusion is most commonly associated with IgG multiple myeloma, has an equal sex distribution, and often presents on the left side. Myelomatous pleural effusion is often a sign of advanced disease and has rarely been reported as the initial presenting feature of multiple myeloma. The response rate with aggressive treatment is often low, with an overall median survival time of 4 months following diagnosis. Because of its significantly worse prognosis and overall survival, it is extremely important to differentiate myelomatous pleural effusions from secondary pleural effusions in patients with multiple myeloma. Diagnosis of myelomatous pleural effusion often relies on the cytology/histopathology, immunohistochemistry, and/or flow cytometry of either the pleural effusion itself or a pleural biopsy. At present, there is a lack of consensus for the definitive diagnosis of myelomatous pleural effusion; however, suggested diagnostic criteria include the detection of large numbers of clonal plasma cells or abnormal plasma cells (expressing aberrant surface markers, such as CD56) in the pleural fluid. If only small numbers of clonal or abnormal plasma cells are detected, further histologic and immunohistochemical confirmation via a pleural biopsy or cell block of pleural effusion fluid may be required. Elevated adenosine deaminase due to high immunologic activity in the pleural fluid may also serve as a useful diagnostic tool as it will often exceed the upper limits for tuberculous pleural effusions and may be helpful for detection at an
chestjournal.org
early stage. There is a high risk of false negative results with pleural effusion analysis due to the often-limited number of malignant plasma cells within the fluid and potential in vitro degeneration during sample processing. Pleural biopsy is a relatively safe procedure that could be used to improve the diagnosis rate; however, it is specific but not sensitive because of the patchy nature of the disease. Diagnosis is therefore dependent on high clinical suspicion and a multimodal diagnostic approach. There is currently no standard treatment strategy for myelomatous pleural effusion, and a majority of cases have been associated with a high resistance to therapy. Following a diagnosis of a myelomatous pleural effusion, aggressive treatment with autologous stem cell transplant and the utility of novel chemotherapeutic agents should be discussed with the patient and his or her family in addition to palliative end-of-life care. There have been a few case reports documenting a positive response to novel therapy, such as intrapleural injection of bortezomib resulting in the resolution of myelomatous pleural effusion; this may be a reasonable treatment option in those wanting to pursue aggressive treatment. Clinical Course
After admission, the patient was started on broad-spectrum antibiotics and antifungal treatment. An infectious workup was performed, with negative results. His scheduled course of chemotherapy was held because of his pancytopenia and need for multiple blood and platelet transfusions. After undergoing thoracentesis, the patient’s clinical status continued to decline with worsening somnolence, tachycardia, dyspnea, and worsening renal failure. After an extensive discussion with the patient and his family, a decision was made to pursue a palliative care approach. He was discharged home with home hospice.
Clinical Pearls 1. Although rare, myelomatous pleural effusion should be considered in the differential diagnosis of any patient with multiple myeloma. 2. Cytology, immunohistochemistry, flow cytometry, electrophoresis, and pleural biopsy can all be used as a multimodal approach to diagnosis. 3. Myelomatous pleural effusion is associated with a poor prognosis, and treatment is directed at treating the underlying multiple myeloma.
e143
Financial/nonfinancial disclosures: None declared.
Cho YU, Chi HS, Park CJ, et al. Myelomatous pleural effusion: a case series in a single institution and literature review. Korean J Lab Med. 2011;31(4):225-230.
Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Klanova M, Klener P, Trneny M, Straub J, Spicka I. Intrapleural bortezomib for the therapy of myelomatous pleural effusion: a case report. Case Reports Immunol. 2012;2012:978479.
Suggested Readings
Oudart JB, Maquart FX, Semouma O, et al. Pleural effusion in a patient with multiple myeloma. Clin Chem. 2012;58(4):672-674.
Kamble R, Wilson CS, Fassas A, et al. Malignant pleural effusion of multiple myeloma: prognostic factors and outcomes. Leuk Lymphoma. 2005;46(8):1137-1142.
Zhang L-L, Li Y-Y, Hu C-P, Yang H-P. Myelomatous pleural effusion as an initial sign of multiple myeloma: a case report and review of literature. J Thorac Dis. 2014;6(7):E152-E159.
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.
Soh KT, Tario JD, Wallace PK. Diagnosis of plasma cell dyscrasias and monitoring of minimal residual disease by multiparametric flow cytometry. Clin Lab Med. 2017;37(4):821-853.
Acknowledgments
e144 Pulmonary, Critical Care, and Sleep Pearls
[
155#5 CHEST MAY 2019
]
Pulmonary, Critical Care, and Sleep Pearls
]
A 42-Year-Old Man With Shortness of Breath, Fever, and Pleural Effusions Jessica K. Millar, BS; Lauryn A. Benninger, DO; Ying Li, MD; and Ali Ataya, MD
A 42-year-old man with a history of progressive multiple myeloma and chronic kidney disease presented with worsening shortness of breath and fever. He was scheduled for a planned admission for chemotherapy on the day of presentation and had developed these symptoms the night before. He had also developed worsening fatigue but denied any new cough, sputum production, or abdominal pain. The patient had been previously admitted 3 weeks prior for neutropenic fever and colitis during his first cycle of chemotherapy. CHEST 2019; 155(5):e141-e144
CASE PRESENTATION:
Physical Examination Findings The patient’s vital signs showed the following: temperature, 38.7 C; heart rate, 122 beats/min; respirations, 25 breaths/min; BP, 112/59; and oxygen saturation, 96% on room air. The patient had
diminished breath sounds along the lung bases bilaterally. He had a large protruding mass from his right posterior-lateral chest wall that was firm, nonmobile, nonerythematous, and mildly tender on palpation without any ulcerations. He was grossly anasarcic.
Figure 1 – Chest radiograph showing diffuse bilateral pulmonary infiltrates with right pleural effusion.
Figure 2 – CT scan of the chest revealed bilateral pleural effusions, larger on the right, with bony destruction of the right ninth rib.
AFFILIATIONS: From the College of Medicine (Ms Millar), the Division of Pulmonary, Critical Care and Sleep Medicine (Drs Benninger and Ataya), and the Department of Pathology, Immunology and Laboratory Medicine (Dr Li), University of Florida, Gainesville, FL. CORRESPONDENCE TO: Ali Ataya, MD, University of Florida, Division of Pulmonary, Critical Care and Sleep Medicine, 1600 SW Archer Rd, M452, P.O. Box 100225, Gainesville, FL 32610; e-mail: [email protected]
Copyright Ó 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2018.10.035
chestjournal.org
e141
Figure 3 – A, Pleural fluid cytology revealed neoplastic plasma cells at an original magnification of 400. B-D, These cells stained positive for CD138 (B) and l light chains (D), but were negative for k light chains (C), HHV8, EBV, and ALK1 (original magnification, 400). ALK1 ¼ activin receptorlike kinase 1; EBV ¼ Epstein-Barr virus; HHV8 ¼ human herpesvirus 8.
Diagnostic Studies Laboratory testing revealed pancytopenia, with a leukocyte count of 600/mm3 and an absolute neutrophil count of 460/mm3. A chest radiograph revealed diffuse bilateral pulmonary infiltrates (Fig 1), and a CT scan of the chest showed bilateral pleural effusions and bony destruction of the right ninth rib without evidence of any infiltrates or nodules (Fig 2). Pleural fluid analysis of the right pleural effusion revealed a noncomplicated exudative effusion with pleural fluid lactate dehydrogenase (LDH) of 234 U/L and protein of 3.0 g/ dL with serum LDH of 578 U/L and protein of 5.7 g/dL. Pleural fluid pH was 7.45. Pleural fluid cell count revealed 39% polymorphonuclear leukocytes,
e142 Pulmonary, Critical Care, and Sleep Pearls
20% lymphocytes, 22% monocytes, and 19% other cells. Cytology and hematopathology studies revealed large neoplastic cells with morphologic features of plasma cells along with small lymphocytes, granulocytes, and mesothelial cells. Immunohistochemistry studies of the pleural fluid cells were positive for CD138 and restricted l light chain, but negative for activin receptor-like kinase 1 (ALK1), human herpesvirus 8 (HHV8), Epstein-Barr virus (EBV), and k light chain (Fig 3). Flow cytometry of the pleural fluid revealed abnormal plasma cells with aberrant expression of CD56 and dim CD30, without CD19 and CD20.
What is the diagnosis?
[
155#5 CHEST MAY 2019
]
Diagnosis: Myelomatous pleural effusion Discussion Myelomatous pleural effusion is a rare manifestation and complication of multiple myeloma. Pleural effusion in multiple myeloma may be a consequence of end-organ damage (heart failure secondary to hyperviscosity, cardiomyopathy related to treatment, pulmonary embolism, infection, nephrotic syndrome, or chronic renal failure) or a sign of thoracic involvement. Pleural effusions affect about 6% of all patients diagnosed with multiple myeloma. However, myelomatous pleural effusion is much rarer, affecting < 1% of patients with multiple myeloma. It is theorized that myelomatous pleural effusion may be the result of direct extension of plasma cells from adjacent chest wall or pulmonary lesions, direct infiltration of tumor deposits on the pleura, hematogenous spread, and/or lymphatic obstruction from mediastinal lymph node infiltration. Myelomatous pleural effusion is most commonly associated with IgG multiple myeloma, has an equal sex distribution, and often presents on the left side. Myelomatous pleural effusion is often a sign of advanced disease and has rarely been reported as the initial presenting feature of multiple myeloma. The response rate with aggressive treatment is often low, with an overall median survival time of 4 months following diagnosis. Because of its significantly worse prognosis and overall survival, it is extremely important to differentiate myelomatous pleural effusions from secondary pleural effusions in patients with multiple myeloma. Diagnosis of myelomatous pleural effusion often relies on the cytology/histopathology, immunohistochemistry, and/or flow cytometry of either the pleural effusion itself or a pleural biopsy. At present, there is a lack of consensus for the definitive diagnosis of myelomatous pleural effusion; however, suggested diagnostic criteria include the detection of large numbers of clonal plasma cells or abnormal plasma cells (expressing aberrant surface markers, such as CD56) in the pleural fluid. If only small numbers of clonal or abnormal plasma cells are detected, further histologic and immunohistochemical confirmation via a pleural biopsy or cell block of pleural effusion fluid may be required. Elevated adenosine deaminase due to high immunologic activity in the pleural fluid may also serve as a useful diagnostic tool as it will often exceed the upper limits for tuberculous pleural effusions and may be helpful for detection at an
chestjournal.org
early stage. There is a high risk of false negative results with pleural effusion analysis due to the often-limited number of malignant plasma cells within the fluid and potential in vitro degeneration during sample processing. Pleural biopsy is a relatively safe procedure that could be used to improve the diagnosis rate; however, it is specific but not sensitive because of the patchy nature of the disease. Diagnosis is therefore dependent on high clinical suspicion and a multimodal diagnostic approach. There is currently no standard treatment strategy for myelomatous pleural effusion, and a majority of cases have been associated with a high resistance to therapy. Following a diagnosis of a myelomatous pleural effusion, aggressive treatment with autologous stem cell transplant and the utility of novel chemotherapeutic agents should be discussed with the patient and his or her family in addition to palliative end-of-life care. There have been a few case reports documenting a positive response to novel therapy, such as intrapleural injection of bortezomib resulting in the resolution of myelomatous pleural effusion; this may be a reasonable treatment option in those wanting to pursue aggressive treatment. Clinical Course
After admission, the patient was started on broad-spectrum antibiotics and antifungal treatment. An infectious workup was performed, with negative results. His scheduled course of chemotherapy was held because of his pancytopenia and need for multiple blood and platelet transfusions. After undergoing thoracentesis, the patient’s clinical status continued to decline with worsening somnolence, tachycardia, dyspnea, and worsening renal failure. After an extensive discussion with the patient and his family, a decision was made to pursue a palliative care approach. He was discharged home with home hospice.
Clinical Pearls 1. Although rare, myelomatous pleural effusion should be considered in the differential diagnosis of any patient with multiple myeloma. 2. Cytology, immunohistochemistry, flow cytometry, electrophoresis, and pleural biopsy can all be used as a multimodal approach to diagnosis. 3. Myelomatous pleural effusion is associated with a poor prognosis, and treatment is directed at treating the underlying multiple myeloma.
e143
Financial/nonfinancial disclosures: None declared.
Cho YU, Chi HS, Park CJ, et al. Myelomatous pleural effusion: a case series in a single institution and literature review. Korean J Lab Med. 2011;31(4):225-230.
Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Klanova M, Klener P, Trneny M, Straub J, Spicka I. Intrapleural bortezomib for the therapy of myelomatous pleural effusion: a case report. Case Reports Immunol. 2012;2012:978479.
Suggested Readings
Oudart JB, Maquart FX, Semouma O, et al. Pleural effusion in a patient with multiple myeloma. Clin Chem. 2012;58(4):672-674.
Kamble R, Wilson CS, Fassas A, et al. Malignant pleural effusion of multiple myeloma: prognostic factors and outcomes. Leuk Lymphoma. 2005;46(8):1137-1142.
Zhang L-L, Li Y-Y, Hu C-P, Yang H-P. Myelomatous pleural effusion as an initial sign of multiple myeloma: a case report and review of literature. J Thorac Dis. 2014;6(7):E152-E159.
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.
Soh KT, Tario JD, Wallace PK. Diagnosis of plasma cell dyscrasias and monitoring of minimal residual disease by multiparametric flow cytometry. Clin Lab Med. 2017;37(4):821-853.
Acknowledgments
e144 Pulmonary, Critical Care, and Sleep Pearls
[
155#5 CHEST MAY 2019
]