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Familial myxomas in four siblings
Familial myxomas in four siblings Familial myxomas of the heart are very rare, with only two previous reports noted in the literature. This report documents four siblings with myxomas, and three of these patients had two or more myxomas. One sibling had four myxomas excised. The clinical findings, history, examination, and surgical treatment are described. George A. Liebler, M . D . , George J. Magovern, M . D . , Sang B. Park, M . D . , William J. Cushing, M . D . , Frank R. Begg, M . D . , and Claude R. Joyner, M . D . , Pittsburgh, Pa.
c
■ ardiac myxomas are rare, occurring in less than 0.5 per cent of all tumors. Familial occurrence of myxomas was first reported by Krause and associates 1 in 1971. The only other report of myxoma in siblings was in 1973 by Heydorn and associates. 2 This report is of four siblings with myxomas of the heart. Two of these patients have previously been reported. 1, 3 Three of these patients have had multiple myxomas. The family history is seen in Fig. 1 and Table I.
Case reports CASE 1. This case was previously reported by Fisher and Hellstrom.3 The patient was a 25-year-old male sibling, J. L., who died of a left atrial myxoma confirmed at autopsy. CASE 2. This 42-year-old male sibling, J. L., was admitted on Jan. 21, 1972, because of three-pillow orthopnea and the onset of a dry, nonproductive cough. This patient had previously had a resection of a right ventricular myxoma and replacement of the pulmonary valve with a ball-valve prosthesis in 1967. On physical examination, his pulse was 80 and regular and he was afebrile. Prosthetic valve sounds were normal and no other murmurs were present in any position. He was in sinus rhythm. His lungs showed some basilarrhonchi. Examination of the abdomen was normal. There was no pedal edema. Laboratory data. Hemoglobin (Hb) was 14.3 and hematocrit (Hct) was 45.2 per cent on admission. Serum protein electrophoresis was normal, with total protein being slightly low at 5.8 Gm. per 100 ml. (normal, 6 to 8 Gm.). Chest x-ray showed left ventricular hypertrophy, pulmonary congestion, and a small right pleural effusion. Electrocardiogram (ECG) showed sinus tachycardia (108), frequent atrial and ventricular ectopic beats, and left ventricular hypertrophy. From the Divisions of Thoracic Surgery and Cardiology, Allegheny General Hospital, Pittsburgh, Pa. Received for publication Aug. 25, 1975. Address for reprints: George A. Liebler, M.D., Department of Surgery, Allegheny General Hospital, Pittsburgh, Pa. 15212.
FATHER
M.L
MOTHER
R.L.
J.L.
J.L
M
M
M
D.L.
W.L
R.L M
MYXOMA Fig. 1. Graphic form of family tree. M indicates myxoma patients. Hospital course. The cardiac failure was treated with digoxin and Lasix. He developed atrial flutter, which converted spontaneously. Cardiac catheterization showed a left atrial myxoma, a normal functioning prosthetic valve, and biventricular failure. He was scheduled for surgery the following day but died suddenly on the morning of surgery. An autopsy confirmed the left atrial myxoma. No evidence of the previously resected right ventricular myxoma was found. CASE 3. This 34-year-old male sibling, R. L., was admitted on Nov. 18, 1972, for evaluation of a recently discovered heart murmur. His only complaint was a vague heaviness in his chest, unrelated to exertion. He was admitted for evaluation and catheterization in view of the fact that his two brothers (Cases 1 and 2) had myxomas. On physical examination he was afebrile. He was in sinus rhythm. A Grade 2/6 systolic murmer was heard at the second left intercostal space. Si was loud. Laboratory data. Hb was 13.6 and Hct was 41 per cent on admission. Total protein was normal at 7.6 Gm. per 100 ml. Protein electrophoresis was also normal. Immunoglobulins were normal. Chest x-ray showed right ventricular enlargement and possibly right atrial enlargement. ECG showed incomplete right bundle branch block. Chromosome pattern was normal. Hospital course. The patient underwent a heart catheterization on Nov. 22, 1972. This showed filling densities 605
606
Liebler et al.
Fig. 2. Gross specimens of the four cardiac myxomas. The largest myxoma is from the right ventricle. compatible with myxomas in the right atrium, right ventricle, and left atrium. The right ventricular myxoma protruded through the pulmonic valve during systole. The left atrial myxoma passed into the left ventricle. The patient was taken to the operating room on Nov. 22,1972 and, under cardiopulmonary bypass, a myxoma was removed from the left atrium, one from the right ventricle, and two from the right atrium (Fig. 2). Thus, four separate myxomas were excised. Pathological examination and electron microscopy confirmed the diagnosis of myxoma (Figs. 3 and 4). He made an uneventful postoperative recovery. A repeat catheterization was performed prior to discharge and was essentially normal. He has been well to this date. CASE 4. This 46-year-old male sibling, R. L., was admitted on Oct. 9, 1974, for evaluation for possible cardiac myxoma. His local physician had noted a murmur which was not present previously. He had a cerebrovascular accident (CVA) in 1958. Following the CVA he underwent a bilateral cervical sympathectomy at another institution for "cerebral spasm." In 1972, he underwent a heart catheterization because of his family history of myxomas and this was normal. The pertinent physical findings were confined to his
The Journal of Thoracic and Cardiovascular Surgery
Fig. 3. Microscopic section of cardiac myxoma showing polyhedral lepidic cells. (x650.)
neurological examination and the heart. The blood pressure was 135/80 mm. Hg; the pulse was 92 and regular. The left pupil did not react to light and fundoscopic examination showed optic atrophy. Esotropia was present on the left. Both findings were from his previous CVA in 1958. Examination of the heart revealed the point of maximal impulse in the fifth left intercostal space in the midclavicular line. A Grade 3/6 systolic murmur was heard at the lower left sternal border. A Grade 2/6 blowing diastolic murmur was heard at the right lower sternal border which increased with inspiration. Laboratory data. Hb was 15.6 and Hct 49.3 per cent; serum protein electrophoresis was normal. Chromosome pattern was normal. ECG showed sinus rhythm and a complete right bundle branch block (unchanged from 1972). Chest x-ray was normal. An echocardiogram indicated the possibility of a tumor in the right ventricle and showed a tumor in the left atrium (Fig. 5). A heart catheterization performed on Oct. 11, 1974, showed a filling defect in the right ventricle which protruded through the pulmonic valve on ventricular systole (Fig. 6). The levoangiocardiogram showed a mass in the left atrium. A right atriogram showed a possible filling defect in the right atrium. Hospital course. He underwent surgery on Oct. 18, 1974,
Volume 71 Number 4 April, 1976
Familial myxomas
607
Table I. Family history Father Mother M.L. Richard L. James L.
John L. D.L. William L. Robert L.
Fig. 4. Electron microscopy of cardiac myxoma showing lepidic cell with abundant endoplasmic reticulum. (x 13,000.) under cardiopulmonary bypass. A large myxoma was excised from the right ventricle, weighing 23 grams and measuring 3.5 by 3 cm. A second myxoma was excised from the left atrium, weighing 1.5 grams and measuring 2 by 1.5 cm. Exploration of the right atrium revealed no evidence of a myxoma and was normal. The postoperative course was uneventful and he was discharged on Nov. 2, 1974. He was readmitted on Nov. 5, 1974, for atrial flutter which spontaneously reverted to sinus rhythm. He has been well since that time.
Discussion Familial myxomas have rarely been described; only three previous reports were found in the literature. The familial incidence is felt to be due to an autosomal recessive trait. Three of our four patients were found to have multiple myxomas; one of these had four myxomas. This is the only report, to our knowledge, of four myxomas being found simultaneously. A careful family history and a high index of suspicion are essential in the recognition of this entity.
Died at age 62 of myocardial infarct Living with angina, age 71 Died at age 25 with rheumatic fever; autopsy Stroke at age 27; cath. 1972, suspicious of atrial myxoma; recath. 1974, myxoma of right ventricle and left atrium; surgical excision October 1974 Right ventricular myxoma and SBE involving myxoma and pulmonary valve destroyed. Surgery 1967 with excision of myxoma and pulmonic valve. Recath. 1972, left atrial myxoma; died suddenly on day prior to surgery Died in 1959 at age 25 with myxoma; autopsy Living; has murmur; had radical mastectomy 7 years ago; free of disease Living and well at age 38 Recent onset of murmur, no previous cardiac difficulties and asymptomatic. Two myxomas found in right atrium, one myxoma in left atrium, one myxoma in right ventricle
The clinical diagnosis is, of course, no different from that of other cardiac myxomas. Right-sided myxomas have been confused with tricuspid valvular disease, pericarditis, and congestive failure. Left atrial myxomas are usually confused with mitral valvular disease. However, myxoma patients usually present in sinus rhythm and have long symptom-free intervals between bouts of congestive failure. The recent onset of a murmur, as in our Case 4, is very suggestive of myxomas, although uncommonly found. The reader is referred to the excellent papers of Thomas, Winchill and Varco4 and May and associates5 for a review of the clinical presentations and diagnostic procedures. Echocardiography can be of great value in the diagnosis of myxomas. This modality was not available to use in the first three cases. In our Case 4 the echocardiogram effectively diagnosed the left atrial myxoma and was suggestive of the right ventricular myxoma. We feel that echocardiography is a very useful technique in the diagnostic workup of suspected myxoma patients. Cineangiography is the most definitive method of diagnosis. A complete heart catheterization and cine study are essential to visualize all chambers of the heart. Our Cases 3 and 4 are good examples of this, where unsuspected myxomas were found. Summary Familial myxomas have been presented in four siblings. Three siblings had multiple myxomas; one patient had four separate myxomas. A careful family history and high index of suspicion are necessary.
608
The Journal of Thoracic and Cardiovascular Surgery
Liebler et al.
Fig. 5. Echocardiogram showing left atrial myxoma (large arrow) behind mitral valve. Smaller arrow indicates the right ventricular myxoma. Open arrow shows paradoxical septal motion.
Fig. 6. Cineangiogram showing the myxoma in the right ventricle. REFERENCES Krause, S., Adler, L. N., Reddy, P. S., and Magovern, G. J.: Intracardiac Myxoma in Siblings, Chest 60: 404, 1971. Heydorn, W. H., Gomez, A. C , Kleid, J. J., and Haas, J. M.: Atrial Myxoma in Siblings, J. THORAC. CARDIOVASC. SURG. 65:484, 1973.
Fisher, E. R., and Hellstrom, H. R.: Evidence in Support of the Neoplastic Nature of Cardiac Myxoma, Am. Heart J. 60: 630, 1960.
4 Thomas, K. E., Winchill, C. P., and Varco, R. L.: Diagnostic and Surgical Aspects of Left Atrial Tumors, J. THORAC. CARDIOVASC. SURG. 53: 535,
1967.
5 May, I. A., Kimball, K. G., Goldman, P. W., and Dugan, D. J.: Left Atrial Myxoma, J. THORAC. CARDIOVASC. SURG. 53: 805,
1967.
c
■ ardiac myxomas are rare, occurring in less than 0.5 per cent of all tumors. Familial occurrence of myxomas was first reported by Krause and associates 1 in 1971. The only other report of myxoma in siblings was in 1973 by Heydorn and associates. 2 This report is of four siblings with myxomas of the heart. Two of these patients have previously been reported. 1, 3 Three of these patients have had multiple myxomas. The family history is seen in Fig. 1 and Table I.
Case reports CASE 1. This case was previously reported by Fisher and Hellstrom.3 The patient was a 25-year-old male sibling, J. L., who died of a left atrial myxoma confirmed at autopsy. CASE 2. This 42-year-old male sibling, J. L., was admitted on Jan. 21, 1972, because of three-pillow orthopnea and the onset of a dry, nonproductive cough. This patient had previously had a resection of a right ventricular myxoma and replacement of the pulmonary valve with a ball-valve prosthesis in 1967. On physical examination, his pulse was 80 and regular and he was afebrile. Prosthetic valve sounds were normal and no other murmurs were present in any position. He was in sinus rhythm. His lungs showed some basilarrhonchi. Examination of the abdomen was normal. There was no pedal edema. Laboratory data. Hemoglobin (Hb) was 14.3 and hematocrit (Hct) was 45.2 per cent on admission. Serum protein electrophoresis was normal, with total protein being slightly low at 5.8 Gm. per 100 ml. (normal, 6 to 8 Gm.). Chest x-ray showed left ventricular hypertrophy, pulmonary congestion, and a small right pleural effusion. Electrocardiogram (ECG) showed sinus tachycardia (108), frequent atrial and ventricular ectopic beats, and left ventricular hypertrophy. From the Divisions of Thoracic Surgery and Cardiology, Allegheny General Hospital, Pittsburgh, Pa. Received for publication Aug. 25, 1975. Address for reprints: George A. Liebler, M.D., Department of Surgery, Allegheny General Hospital, Pittsburgh, Pa. 15212.
FATHER
M.L
MOTHER
R.L.
J.L.
J.L
M
M
M
D.L.
W.L
R.L M
MYXOMA Fig. 1. Graphic form of family tree. M indicates myxoma patients. Hospital course. The cardiac failure was treated with digoxin and Lasix. He developed atrial flutter, which converted spontaneously. Cardiac catheterization showed a left atrial myxoma, a normal functioning prosthetic valve, and biventricular failure. He was scheduled for surgery the following day but died suddenly on the morning of surgery. An autopsy confirmed the left atrial myxoma. No evidence of the previously resected right ventricular myxoma was found. CASE 3. This 34-year-old male sibling, R. L., was admitted on Nov. 18, 1972, for evaluation of a recently discovered heart murmur. His only complaint was a vague heaviness in his chest, unrelated to exertion. He was admitted for evaluation and catheterization in view of the fact that his two brothers (Cases 1 and 2) had myxomas. On physical examination he was afebrile. He was in sinus rhythm. A Grade 2/6 systolic murmer was heard at the second left intercostal space. Si was loud. Laboratory data. Hb was 13.6 and Hct was 41 per cent on admission. Total protein was normal at 7.6 Gm. per 100 ml. Protein electrophoresis was also normal. Immunoglobulins were normal. Chest x-ray showed right ventricular enlargement and possibly right atrial enlargement. ECG showed incomplete right bundle branch block. Chromosome pattern was normal. Hospital course. The patient underwent a heart catheterization on Nov. 22, 1972. This showed filling densities 605
606
Liebler et al.
Fig. 2. Gross specimens of the four cardiac myxomas. The largest myxoma is from the right ventricle. compatible with myxomas in the right atrium, right ventricle, and left atrium. The right ventricular myxoma protruded through the pulmonic valve during systole. The left atrial myxoma passed into the left ventricle. The patient was taken to the operating room on Nov. 22,1972 and, under cardiopulmonary bypass, a myxoma was removed from the left atrium, one from the right ventricle, and two from the right atrium (Fig. 2). Thus, four separate myxomas were excised. Pathological examination and electron microscopy confirmed the diagnosis of myxoma (Figs. 3 and 4). He made an uneventful postoperative recovery. A repeat catheterization was performed prior to discharge and was essentially normal. He has been well to this date. CASE 4. This 46-year-old male sibling, R. L., was admitted on Oct. 9, 1974, for evaluation for possible cardiac myxoma. His local physician had noted a murmur which was not present previously. He had a cerebrovascular accident (CVA) in 1958. Following the CVA he underwent a bilateral cervical sympathectomy at another institution for "cerebral spasm." In 1972, he underwent a heart catheterization because of his family history of myxomas and this was normal. The pertinent physical findings were confined to his
The Journal of Thoracic and Cardiovascular Surgery
Fig. 3. Microscopic section of cardiac myxoma showing polyhedral lepidic cells. (x650.)
neurological examination and the heart. The blood pressure was 135/80 mm. Hg; the pulse was 92 and regular. The left pupil did not react to light and fundoscopic examination showed optic atrophy. Esotropia was present on the left. Both findings were from his previous CVA in 1958. Examination of the heart revealed the point of maximal impulse in the fifth left intercostal space in the midclavicular line. A Grade 3/6 systolic murmur was heard at the lower left sternal border. A Grade 2/6 blowing diastolic murmur was heard at the right lower sternal border which increased with inspiration. Laboratory data. Hb was 15.6 and Hct 49.3 per cent; serum protein electrophoresis was normal. Chromosome pattern was normal. ECG showed sinus rhythm and a complete right bundle branch block (unchanged from 1972). Chest x-ray was normal. An echocardiogram indicated the possibility of a tumor in the right ventricle and showed a tumor in the left atrium (Fig. 5). A heart catheterization performed on Oct. 11, 1974, showed a filling defect in the right ventricle which protruded through the pulmonic valve on ventricular systole (Fig. 6). The levoangiocardiogram showed a mass in the left atrium. A right atriogram showed a possible filling defect in the right atrium. Hospital course. He underwent surgery on Oct. 18, 1974,
Volume 71 Number 4 April, 1976
Familial myxomas
607
Table I. Family history Father Mother M.L. Richard L. James L.
John L. D.L. William L. Robert L.
Fig. 4. Electron microscopy of cardiac myxoma showing lepidic cell with abundant endoplasmic reticulum. (x 13,000.) under cardiopulmonary bypass. A large myxoma was excised from the right ventricle, weighing 23 grams and measuring 3.5 by 3 cm. A second myxoma was excised from the left atrium, weighing 1.5 grams and measuring 2 by 1.5 cm. Exploration of the right atrium revealed no evidence of a myxoma and was normal. The postoperative course was uneventful and he was discharged on Nov. 2, 1974. He was readmitted on Nov. 5, 1974, for atrial flutter which spontaneously reverted to sinus rhythm. He has been well since that time.
Discussion Familial myxomas have rarely been described; only three previous reports were found in the literature. The familial incidence is felt to be due to an autosomal recessive trait. Three of our four patients were found to have multiple myxomas; one of these had four myxomas. This is the only report, to our knowledge, of four myxomas being found simultaneously. A careful family history and a high index of suspicion are essential in the recognition of this entity.
Died at age 62 of myocardial infarct Living with angina, age 71 Died at age 25 with rheumatic fever; autopsy Stroke at age 27; cath. 1972, suspicious of atrial myxoma; recath. 1974, myxoma of right ventricle and left atrium; surgical excision October 1974 Right ventricular myxoma and SBE involving myxoma and pulmonary valve destroyed. Surgery 1967 with excision of myxoma and pulmonic valve. Recath. 1972, left atrial myxoma; died suddenly on day prior to surgery Died in 1959 at age 25 with myxoma; autopsy Living; has murmur; had radical mastectomy 7 years ago; free of disease Living and well at age 38 Recent onset of murmur, no previous cardiac difficulties and asymptomatic. Two myxomas found in right atrium, one myxoma in left atrium, one myxoma in right ventricle
The clinical diagnosis is, of course, no different from that of other cardiac myxomas. Right-sided myxomas have been confused with tricuspid valvular disease, pericarditis, and congestive failure. Left atrial myxomas are usually confused with mitral valvular disease. However, myxoma patients usually present in sinus rhythm and have long symptom-free intervals between bouts of congestive failure. The recent onset of a murmur, as in our Case 4, is very suggestive of myxomas, although uncommonly found. The reader is referred to the excellent papers of Thomas, Winchill and Varco4 and May and associates5 for a review of the clinical presentations and diagnostic procedures. Echocardiography can be of great value in the diagnosis of myxomas. This modality was not available to use in the first three cases. In our Case 4 the echocardiogram effectively diagnosed the left atrial myxoma and was suggestive of the right ventricular myxoma. We feel that echocardiography is a very useful technique in the diagnostic workup of suspected myxoma patients. Cineangiography is the most definitive method of diagnosis. A complete heart catheterization and cine study are essential to visualize all chambers of the heart. Our Cases 3 and 4 are good examples of this, where unsuspected myxomas were found. Summary Familial myxomas have been presented in four siblings. Three siblings had multiple myxomas; one patient had four separate myxomas. A careful family history and high index of suspicion are necessary.
608
The Journal of Thoracic and Cardiovascular Surgery
Liebler et al.
Fig. 5. Echocardiogram showing left atrial myxoma (large arrow) behind mitral valve. Smaller arrow indicates the right ventricular myxoma. Open arrow shows paradoxical septal motion.
Fig. 6. Cineangiogram showing the myxoma in the right ventricle. REFERENCES Krause, S., Adler, L. N., Reddy, P. S., and Magovern, G. J.: Intracardiac Myxoma in Siblings, Chest 60: 404, 1971. Heydorn, W. H., Gomez, A. C , Kleid, J. J., and Haas, J. M.: Atrial Myxoma in Siblings, J. THORAC. CARDIOVASC. SURG. 65:484, 1973.
Fisher, E. R., and Hellstrom, H. R.: Evidence in Support of the Neoplastic Nature of Cardiac Myxoma, Am. Heart J. 60: 630, 1960.
4 Thomas, K. E., Winchill, C. P., and Varco, R. L.: Diagnostic and Surgical Aspects of Left Atrial Tumors, J. THORAC. CARDIOVASC. SURG. 53: 535,
1967.
5 May, I. A., Kimball, K. G., Goldman, P. W., and Dugan, D. J.: Left Atrial Myxoma, J. THORAC. CARDIOVASC. SURG. 53: 805,
1967.