A 69-year-old man presented with recurrent bilateral pleural effusions of unclear etiology. He had undergone thoracocentesis more than 25 times over the last 2 years and had bilateral pleurodesis multiple times without success. Pleural fluid studies and a pleural biopsy were negative for malignancy or infection. He had no history of chest trauma, thoracic surgery, tuberculosis, lymphoma, cancer or significant exposure to asbestos. His renal, hepatic and cardiac function had been normal. He had smoked one-half pack cigarettes a day for 40 years and quit a year ago. He reported a chronic cough, exertional dyspnea, severe anorexia and weight loss of 30 kilograms in last 3 months. Due to his intractable pleural effusions of undetermined etiology, he was admitted for a lung biopsy and ligation of thoracic ducts.
The physical examination revealed a man with mild shortness of breath. He had generalized edema, decreased breath sounds over the lung bases and a normal cardiac examination. He was afebrile with normal respirations, a pulse of 86 beats per minute and blood pressure of 145/79 mm of Hg. White blood count was 8700 cells/mm3, hemoglobin was 10 g/dL, serum creatinine was 1.1 mg/dL and serum calcium was 8.8 mg/dL. Serum protein was 3.7 g/dL with albumin of 2.7 g/dL. Liver function tests were normal. Urinalysis showed 30 mg/dL protein in a spot sample. C-reactive protein was elevated at 50 mg/L. Anemia work up was consistent with anemia of chronic disease with normal serum B12 and folate levels. A chest x-ray showed bilateral pleural effusions. Echocardiogram showed normal left ventricular ejection fraction of 60% and there were no features of cardiac amyloidosis. Computed tomography of the chest and abdomen showed multiple calcified mediastinal lymphadenopathy and pleural effusions with atelectasis of the lung bases, but no obvious parenchymal lung lesions (Figure 1).
Pleural fluid was exudative with a white count of 212 cells/mm3 with 88% lymphocytes. Fluid triglycerides were elevated at 277 mg/dl, lactate dehydrogenase was 133 IU/L and fluid protein was 2800 mg/dL. The fluid was negative for infection, plasma cells or other tumor cells. Histopathology of biopsy of the right lung revealed pulmonary amyloidosis, mostly in a perivascular pattern, seen as hyaline deposits on Hematoxylin & Eosin stain (Figure 2). Apple-green birefringence was noted on Congo-red stain under polarized light. Mass spectroscopic subtyping revealed AL-kappa amyloid deposits.
Serum protein electrophoresis showed total protein of 3.3 g/dL with albumin 1.6 g/dL but absence of M-protein. Serum and urine immunofixation revealed presence of kappa free light chains. Serum free light chain analysis showed kappa free light chains of 47.2 mg/dL (ref 0.33-1.95 mg/dL) and a kappa to lambda light chain ratio of 41.4 (ref 0.26-1.65). Urine protein electrophoresis showed 24-hour urine protein of 1201 mg with M-protein of 40%. A bone marrow biopsy revealed 25% plasma cells comprised predominantly of kappa-expressing cells (Figure 3). A skeleton survey did not show any lytic or blastic lesions.
Our patient met the diagnostic criteria for MM based on bone marrow biopsy showing more than 10% plasma cells, monoclonal protein in the serum and urine, and presence of a myeloma-related organ dysfunction in the form of anemia. The etiology of his intractable effusion was felt to be pulmonary amyloidosis secondary to multiple myeloma. He did not have features of amyloidosis elsewhere such as cardiac failure, hepatomegaly, nephrotic syndrome and peripheral neuropathy. He was started on melphalan and bortezomib. His pleural effusions persisted despite thoracic duct ligation. His hospital course was complicated with acute renal failure, severe anasarca, deep vein thrombosis, congestive heart failure, myocardial infarction and sepsis. The diagnosis of MM as the cause of his intractable pleural effusion was terminal as the patient expired within a few weeks of diagnosis.
CT chest showing bilateral pleural effusions and clear lung parenchyma.