Pleural Effusion Due to Multiple Myeloma

SAFA, VAN ORDSTRAND

246 9 Winkelmann RK, Mulder DW, Lambert EH, et al: Course of dermatomyositis-polymyositis: comparison of untreated and cortisone-treated patients. Mayo Clin Proc 43:545-556, 1968 10 Fowler NO: High cardiac output states. In The Heart. (Hurst JW, Logue RB, eds). New York, McGraw Hill Book Co, 1970 11 Luft R, lkkos D, Palmieri G, et al: A case of severe hypermetabolism of non-thyroid origin with a defect in the maintenance of the mitochondrial respiratory control. J Clin Invest 41:1776-1804,1962 12 Gorlin R: The hyperkinetic heart syndrome. JAMA 182: 823-827, 1962 13 Shuster S: High output cardiac failure from skin disease. Lancet 1:1338-1340, 1963 14 Pepine CJ, Winer L, Stout BD: Management of hyperthyroidism with combined alpha and beta sympathetic blockade. Med Times 100:114-124, 1972 15 Pimstone M, Marine N, Pimstone B: Beta adrenergic blockade in thyrotoxic myopathy. Lancet 2:1219-1220, 1968

Pleural Effusion Due to Multiple Myeloma* Ali M. Safa, M.D. •• and H. S. Van Ordstrand, M.D., F.C.C.P.t

A case of multiple myeloma with massive pleural involvement is reported. The diagnosis was made by tbe finding of high protein content, high specific gravity, and many plasma cells in the pleural ftuid. The diagnosis was further confirmed on examination of the pleural biopsy specimen (by Cope needle). Protein electrophoresis of pleural ftuid revealed a sharp-spiked peak in gamma globulin.

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hest pains and recurrent pneumonia are frequent in multiple myeloma, but intrathoracic plasmacytoma is uncommon. Pleural involvement is extremely rare. We report a case of pleural plasmacytoma with massive pleural effusion.

skull, pelvis, and femurs. The white blood count was 3600/mm3 with a normal differential count; total serum protein was 11.6 gm/100 ml, serum paper electrophoresis showed albumin 4.6 gm, alpha-1 globulin 0.3 gm, alpha-2 globulin 0.7 gm, beta globulin 0.6 gm, and gamma globulin 5.3 gm/100 ml with a sharp "M" spike. Urinalysis showed specific gravity of 1.004 and pH of 6.5. Protein, sugar, and urinary sediment were negative. Serum alkaline phosphatase was 6.4 King-Armstrong units, serum uric acid was 4.6 mg, and serum calcium was 9.7 mg/ 100 mi. Result of blood serology for syphilis was negative. Bone marrow aspirations revealed 34 percent plasma cells, consistent with the diagnosis of multiple myeloma. Quantitative immunoglobulin determination showed marked increase in gamma G, 5700 mg/100 ml (normal, 500 to 1500), gamma A 49 mg, and gamma M 31 mg/100 mi. The myeloma type was gamma G, type Kappa. Initially, the patient was treated with melphalan and sodium fluoride, and her condition improved. In July 1969 the therapeutic regimen was changed to melphalan, prednisone, and procarbazine hydrochloride with good initial response. Total protein was 7.4 gm/100 ml, gamma globulin was 1.7 gm/100 ml, hemoglobin was 9.3 gm/ 100 ml, and white blood count was 2800/mma. In February 1969 procarbazine was discontinued and in June 1971, melphalan and prednisone were discontinued; the patient was then given 5-fluorouracil and prednisone. In May 1971, five weeks before her second hospital admission, progressive coughing, fever, chest pain and dyspnea developed. On physical examination her temperature was 99.8•F. There was a sinus tachycardia of 120 beats per minute, a massive left pleural effusion, and slight tenderness of the left lower posterior chest wall. The chest roentgenogram confirmed massive pleural effusion in the left side ( Fig 1 ) . An intermediate PPD skin test was negative. Repeated thoracenteses revealed sterile bloody effusions with protein content of 8.5 and 5.5 gm/100 ml on two occasions. The specific gravity of the pleural fluid was 1.030, red blood cell count 20,000/mms, atypical white blood cells 2000/mma, and a smear of pleural fluid contained numerous plasma cells. The lactic dehydrogenase ( LDH) measurement on the pleural fluid was 160 units, amylase was 39 units, sugar was 29 mg/100 mi. The protein electrophoretic pattern of the pleural fluid showed a sharp-spiked peak in gamma globulin of 4 gm/ 100 ml (Fig 2). The urine protein electrophoresis

CASE REPORT

A 56-year-old white woman was admitted to the Cleveland Clinic Hospital in August 1971, because of progressive shortness of breath and cough for seven days. Multiple myeloma was diagnosed by bone marrow examination in May 1967. At that time the patient had pain in her ribs and coughing after exercise. Results of physical examination were normal. Roentgenograms between April and July 1967 demonstrated multiple lytic lesions of the ribs, spine, °From the Department of Pulmonary Disease and the Division of Medicine, The Cleveland Clinic Foundation and The Cleveland Clinic Educational Foundation, Cleveland, Ohio. 0 °Fellow, Division of Medicine, The Cleveland Clinic Foundation. t Head, Department of Pulmonary Disease, The Cleveland Clinic Foundation. Reprint requests: Dr. Safa, Cleveland Clinic Foundation, Cleveland 44106

FIGURE 1. Chest x-ray film taken on admission, August I, 1971, which shows massive pleural effusion in left side.

CHEST, VOL. 64, NO. 2, AUGUST, 1973

247

PLEURAL EFFUSION DUE TO MULTIPLE MYELOMA

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FIGURE 2. Paper electrophoresis of the pleural effusion. Note the sharp-spiked peak in gamma globulin. showed two separate peaks which migrated in motility range of beta and gamma (beta 47 percent and gamma 53 percent) . Again, the serum protein electrophoresis disclosed a total protein of 10 gm/100 ml with sharp "M" spike, 5.9 gm/100 ml (Fig 3). Urine protein measured 1857 mg/24 hours. Cope needle biopsy of the pleura confirmed the diagnosis of pleural plasmacytoma (Fig 4) . Nitrogen mustard, 10 mg, was injected into the pleural cavity with no improvement and subsequently, a chest tube was inserted in the left side of the chest with no benefit. The patient was also treated with another course of 5-fluorouracil 960 mg, administered intra-

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CHEST, VOL. 64, NO. 2, AUGUST, 1973

venously and prednisone, 125 mg given daily for five days. Multiple blood transfusions were given but the patient's condition deteriorated, and she died after seven weeks of hospitalization.

CoMMENTS Extraosseous involvement in multiple myeloma was first reported by Kudrewetzky 1 in 1892. The reported incidence of soft tissue plasmacytoma varies. Hayes and co-workers 2 reported extramedullary plasmacytoma in 71 percent of their cases of multiple myeloma, and Churg and Gordon 3 reported soft tissue involvement in 73 percent of their cases. Multiple myeloma occurs most frequently in the skull, spine, ribs, and pelvis. Solitary lesions are rare and usually become multiple before death.• Pulmonary involvement in multiple myeloma is uncommon. In a series of 57 cases reported by Kenny and Moloney, 5 there was no involvement of the respiratory tract. In 1943 Hellwig6 reviewed 128 cases of extramedullary plasma cell tumors of which 63 originated in the upper respiratory tract, 47 in conjunctiva, and 18 in the lymph nodes, tonsils, thyroid, intestine, ovary, kidney, spermatic cord, or skin. In 51 cases Meacham 7 found no isolated pleural manifestation. In 1965 Herskovic and associates• reviewed the records of 303 patients with multiple myeloma seen at the Mayo Clinic in a five-year period. Twenty-one ( 6.9 percent) of these patients had intrathoracic plasmacytoma, and in some cases the intrathoracic mass was the first presentation. Nineteen of these 21 patients had disseminated plasma-ceiJ myeloma at the time of diagnosis. The plasmacytoma presumably originated in the ribs in 16 patients, in the vertebrae in three, in the subcutaneous tissue of the thoracic cage in one, and in the mediastinum in one. In a review of English literature, five cases of pleural involvement due to multiple myeloma have been reported. Klose 9 in 1911 described the case of a 61-year-old man with multiple myeloma and pleurisy of the left side

248

FROM ET AL

for one year. Pleural effusion in this case was due to a large plasmacytoma of the chest wall. Galano 10 reported a case of pleural plasmacytoma in a 50-year-old man with chest pain. At autopsy the pleura was replaced by a tumor measuring 1 to 1.5 em in diameter. The tumor did not invade the lung. Favis and co-workers 11 described the case of a 60year-old woman with bilateral pleural effusion and many plasma cells in the pleural fluid, probably due to pleural plasmacytoma with subpleural and pulmonary parenchymal myelomatosis. Gabriel 12 reported a case of a 63-year-old woman with massive pleural effusion. The cytologic examination of pleural fluid and aspirated lung tissue showed a prevalence of plasma cells and paper electrophoresis of pleural fluid revealed a gamma globulin characteristic of myeloma in the beta range. Edwards and ZawadzkP 3 reported a case of pleural effusion in a 69-year-old man with multiple myeloma; involvement of the pleura was proved at postmortem examination. Intrathoracic structures such as lung, pleura, thymus, bronchi, hila, and mediastinum are well supplied with lymphatic tissues. The plasma cells are thought to be derived from lymphocytes or blasts in the lymphoid tissue, u so this may explain why the pleura may be involved in multiple myeloma. REFERENCES

1 Kudrewetzky B: Cited by Hayes et al.2 Ztschr Heilk 13:300, 1892 2 Hayes DW, Bennett W A, Heck FJ: Extramedullary lesions in multiple myeloma: review of literature and pathologic studies. Arch Path 53:262-272, 1952 3 Churg J, Gordon AJ: Multiple myeloma, lesions of the extra-osseous hematopoietic system. Am J Clin Path 20: 934-945, 1950 4 Batts M Jr: Multiple myeloma; review of 40 cases. Arch Surg 39:807-823, 1939 5 Kenny JJ, Moloney WC: Multiple myeloma: diagnosis and management in a series of 57 cases. Ann Intern Med 46:1079-1091, 1957 6 Hellwig CA: Extramedullary plasma cell tumors as observed in various locations. Arch Path 36:95-111, 1943 7 Meacham GC: Plasma cell myeloma. Ann Intern Med 38:1035-1047, 1953 8 Herskovic T, Andersen HA, Bayrd ED: Intrathoracic plasmacytoma; presentation of 21 cases and review of literature. Dis Chest 47:1-6, 1965 9 Klose H: Cited by Kilburn eta!: Uber das plasma cytom der pleura. Beitr klin Chir 74:20, 1911 10 Galgano AR: Unusual features of multiple myeloma. Radium Ther Nucl Med 74:304-314, 1955 11 Favis EA, Kerman HD, Schildecker W: Multiple myeloma manifested as a problem in the diagnosis of pulmonary disease. Am J Med 28:323-327, 1960 12 Gabriel S: Multiple myeloma presenting as pulmonary infiltration: report of a case. Dis Chest 47:123-126, 1965 13 Edwards GA, Zawadzki ZA: Extraosseous lesions in plasma cell myeloma: a report of six cases. Am J Med 43:194205, 1967 14 Davidsohn I, Henry JB ( eds): Todd-Sanford Clinical Diagnosis by Laboratory Methods (14th ed). Philadelphia, W. B. Saunders Company, 1969, p 188

Ebstein' s Malformation of the Tricuspid Valve Associated with Valvular Stenosis and Cor Triatriatum * Arthur H. L. From, M.D.; William F. Mazzitello, M.D., F.C.C.P.; Allen S. Judd, M.D.; and ]esse E. Edwards, M.D.

The case of a 39-year-old man with Ebstein's malformation, valvular pulmonary stenosis, atrial septal defect, ostium secundum type, and cor triatriatum is reported. The patient bad cyanosis throughout his life but only moderate functional impairment of the heart. The mode of death suggested paradoxic embolization with the right atrium a possible source of the emboli.

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bstein's malformation of the tricuspid valve tends to occur as an isolated condition except for the common association of a patent foramen ovale. Nevertheless, several other conditions may be associated with Ebstein's anomaly. These include ventricular septal defect, 1 pulmonary stenosis with or without a ventricular septal defect, 2 pulmonary atresia with intact ventricular septum, 3 and several transposition syndromes. • Most of these anomalies are not commonly associated with Ebstein's malformation, and pulmonary valvular stenosis is rare in the absence of ventricular septal defect. 5 The purpose of this report is to describe the clinical and pathologic features of a case of Ebstein's malformation associated with a rare combination of anomalies, namely, valvular pulmonic stenosis and cor tria tria tum.

CAsE REPoRT Clinical Features The patient, a 39-year-old man, was admitted to St. Mary's Hospital for diagnostic cardiac catheterization. He had a lifelong history of mild cyanosis and a cardiac murmur. The major complaints were those of mild exertional dyspnea, increased ease of fatigability, and questionable exertional precordial distress. Pertinent physical findings included moderate cyanosis, clubbing of the fingers and toes, a left precordial bulge, a left parasternal lift, and a systolic ejectipn murmur, grade 3/4, which was heard best along the left sternal edge. The first cardiac sound was normal, and the second was thought to be single. There were no diastolic murmurs or gallop sounds. The concentration of hemoglobin was 19 gm/100 ml of blood. Urinalysis gave negative results. A thoracic roentgenogram ( Fig 1 ) revealed a mild degree •From the Departments of Medicine and Pathology, The University of Minnesota Hospitals and St. Mary's Hospital, Minneapolis, Minnesota, and the Department of Pathology, Miller Division, United Hospitals, Inc., St. Paul. This study was supported by Public Health Service Research Grant 5 ROl HL05694 and Research Training Grant 5 TOI HL05570 from the National Heart and Lung Institute, by the Minnesota Heart Association and the Minnesota Medical Foundation. Reprint requests: Dr. Edwards, United Hospitals, Miller Division, 125 West College Avenue, St. Paul55102

CHEST, VOL. 64, NO. 2, AUGUST, 1973