Fibromyxosarcoma of the pulmonary artery

Fibromvxosarcoma J

of the Pulmonary

Associated with Syncope, Polycythemia J.

Intractable

J

Artery

J

Heart Failure,

and Thrombocytopenia*

RUSSELL GREEN, JR., M.D., LAMAR E. CREVASSE, M.D. and DOUGLAS R. SHANKLIN, MB. Gainesville,

T

HE purpose of this report is to describe the clinical and pathologic findings in an unusual case of intractable heart failure. This case is the third reported case of a fibromyxosarcoma of the pulmonary artery. CASE PRESENTATION This 47 year old white man entered the University Hospital in January 1961 complaining of weakness and fainting. He had been well until July 1960, when he suddenly became profoundly weak and unsteady. He fell to the ground without loss of consciousness, but after a few moments resumed normal activity. Following this incident, he was well until three months prior to admission, when he experienced a syncopal episode. Although he did not experience shortness of breath, orthopnea, ankle edema, or chest pain, administration of a digitalis preparation and chlorothiazide resulted in a 20pound diuresis. He remained well until one month before admission, when he suddenly became weak, lost consciousness and had clonic movements of his arms. He denied visual or auditory aura, palpitations, shortness of breath and fecal or urinary incontinence. After 10 minutes, the patient once more felt well. Two weeks before admission, he again experienced such an attack; however, this one was preceded by nausea and vomiting and was accompanied by cyanosis. The syncopal episodes always ocurred when the patient was in the upright position and were precipitated by emotional or physical stress. From the beginning of his illness he complained of persistent weakness. He stopped working seven months prior to A review of admission because of his weakness. systems was essentially negative. A past medical history revealed that a heart murmur of uncertain His weight 5 years significance was noted at age 12. before admission was 200 pounds, and at admission it was 197 pounds. There was no family history of neoplasm or heart disease. Physical Examination: He was a well developed,

Florida

well nourished man in no distress. The blood pressure was 112/90 bilaterally in the supine position, with no postural change. The pulse was 94 and the respirations were 18 and regular. No regular; clubbing or edema was present. The face was slightly plethoric, and the ears became cyanotic after minimal exertion. There was no adenopathy. The pupils were equal and active; the ocular fundi appeared normal. The thyroid was not enlarged. There were prominent venous pulsations in the neck. The chest was clear to percussion and auscultation. Examination of the heart revealed the left border to be 12.5 cm. from the mid-sternal line in the fifth intercostal space. A marked left parasternal heave indicated right ventricular hypertrophy. The aortic second sound was normal. The pulmonic second sound was soft, normally split and appeared to vary conventionally with respiration. There was a grade 2 systolic ejection murmur heard best at the second and third left intercostal space. A protodiastolic gallop was noted, the intensity of which increased with inspiration. No diastolic murmur was heard. Examination of the abdomen revealed the liver edge to be 4 cm. below the right costal margin, with the upper border in the fifth intercostal space. The peripheral pulses were palpable but weak. The neurologic examination was normal. Accessory Clinical Findings: The hemoglobin was 17.5 gm. y0 with a hematocrit of 58. The white blood cell count was 10,2OO/cu. mm. The differential count revealed three band cells, 62 polymorphonucleocytes, 22 lymphocytes and 13 monocytes. The red blood cells appeared normal, and the initial smear revealed adequate platelets. Five days after the initial laboratory work, a direct platelet count was 5O,OOO/cu. mm. ; 11 days later it was 11,000. Urinalysis was negative, as was a test for syphilis. Electrolytes were normal with the exception of a slightly decreased chloride level and a blood urea nitrogen of 33 mg. %. Blood protein studies, bleeding time and clotting time were normal. The according to the arm-to-tongue circulation time,

* From the Departments of Medicine and Pathology, University of Florida College of Medicine, Gainsville, Fla. This paper was supported in part by grants from the Suncoast Heart Association and the Florida Heart Association. APRIL

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Green.

C:re\,asse

and

Shanklin

Right ventricular and pulmonary artery enlargement were noted, but the hilar vessels did not appear enIt was felt, however, that the pulsations gorged. of the right pulmonary artery were less than those ‘The peripheral vascuof the left pulmonary artery. lature was decreased (Pig. 1). An electrocardiogram demonstrated normal sinus rhythm; the QRS forces were directed to the right indicating right ventricular hypertrophy and strain (Fig. 2). A vectorcardiogram revealed the P loop to be large and inferior, suggesting right atria1 enlargement; the QRS vector was anterior, inferior and almost entirely to the right, indicating right ventricular hypertrophy (Fig. 2). A phonocardiogram revealed that the first heart sound was split to 0.05 sec. at the fourth left interthis remained split throughout the costal space; A systolic ejection murmur was of respiratory cycle.

FIG. 1. Posteroanterior roentgenogram of the chest. Note enlarged central pulmonary arteries and reduced peripheral vasculature. sodium decholate method, was 55 sec.; the venous pressure was 170 mm. of saline, Chest ~uoroscopu and x-ray films revealed the diaphragms moved well, and no pleural fluid was present. The cardiac pulsations were definitely diminished.

aVR

maximal intensity at the second left intercostal space. The second sound was split 0.03 sec., and the components moved conventionally with respiration (Fig. 3). The initial clinical impression Course in Hospital: was primary pulmonary hypertension or pulmonary hypertension due to multiple pulmonary emboli. The patient was given a low salt diet, 0.25 mg. of digoxin each day, 500 mg. of chlorothiazide twice daily and potassium chloride, 1 gm. three times daily. Three 500 cc. phlebotomies were performed without a change in the level of hematocrit or in symptomatology. On the thirteenth hospital day, the patient appeared icteric. Laboratory examinations

aVL

aVF

v6

FIG. 2. Standard 12-lead electrocardiogram, and vectorcardiogram showing the horizontal, sagittal Note the marked rightward and anterior shift of the QRS vector, and its reversal of inscription planes. zontal plane.

and frontal in the hori-

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Fibromyxosarcoma

of the

Pulmonar!~

Artery

EXP

Note the pulmonic FIG. 3. Phonocardiogram. the first heart sound and a soft systolic murmur. A = aortic sound; and P = pulmonic sound.

yielded

the

following

values:

bilirubin,

second sound is very hard to identify. There is fixed splitting of M = mitral sound: T = tricuspid sound; S.M = systolic murmur:

4 mg.%;

alkaline phosphatase, thymol turbidity, 3.8 units; cephalin flocculation, 5.2 King-Armstrong units; uric acid, 12.5 mg.‘%; serum 2$, at 48 hours; glutomic oxalacetic transaminase, 87 units; lactic dehydrogenase, 690 units; reticulocyte count, 2.8%; cryoglobulins, not present; calcium, 10 mg.O/o; indirect and direct Coombs test, negative; and phosphorus, 3.8 mg.ojo. The arterial blood was 927, saturated; following 20 minutes of 100% oxygen administration, it rose to 94%. Chromiums*-tagged red cell studies revealed an increased blood volume and blood cell mass. The total blood volume was 89.24 ct./kg. (normal 70 to 75 ct./kg.). The total plasma volume was 38.25 cc/kg. (normal 35 to 40 ct./kg.), and the red cell mass was 50.99 ct./kg. (normal 30 to 55 ct./kg.). A bone marrow examination revealed erythroid hyperplasia; the megakaryoFurther studies included cytes appeared normal. examinations for lupus erythematosus, normal serum electrophoresis and normal intravenous pyelogram. Because the platelets were depressed, chlorothiazide and potassium chloride were discontinued. The patient became progressively weaker and despondent. During his later hospital course, purpura developed over his thorax. He had three episodes of syncope in the hospital. These attacks were usually precipitated by apprehension accompanying venipuncture. During his syncopal attack, he would become cyanotic, sweaty and unresponsive for 10 to 30 seconds. He would gradually recover in a few minutes. After these attacks, he experienced great fear and He was continually nauseated and apprehension. vomited frequently during his hospital course. APRIL

1964

Eighteen died.

days after

admission,

the patient

suddenl)

PATHOLOGY Autopsy was performed six hours after death. Significant findings were limited to the heart, lungs, pulmonary artery, liver, spleen and bone marrow. Some 1,500 cc. of clear, straw-colored fluid was found in the peritoneal cavity; 800 cc. of serosanguineous fluid was present in the left hemithorax. Only 150 cc. of similar fluid was present in the right pleural space and 65 cc. in the pericardial space. The heart and lungs were removed together. A longitudinal incision into the main pulmonary artery revealed a nodular, fatty-like mass which protruded through the incision. A polypoid clustering of yellowish-grey masses had their greatest bulk in the sinuses of Valsalva of the pulmonary artery (Fig. 4); these extended into the left lung hilus at which point they split and extended into the lower lobe along two adjacent arteries about halfway toward the pleural surface at the diaphragm. There was a short extension in the right main pulmonary artery which terminated abruptly after 2 to 3 cm. (Fig. 5). When the right ventricle was opened, several more sessile nodules on the endocardium of the outflow tract were revealed. The right ventricle was dilated and thickened. It ranged 6 to 8 mm. in thickness while the left ventricle, arrested in systole, measured 18 mm. The right atrium presented no abnormalities; the tricuspid valve had a circumference of 13 cm. The pulmonic valve cusps were thickened and the edges slightly rolled ; the circumference was 12 cm. The mitral valve was thin and pliable and measured

Green,

550

Crevasse

and Shanklin

FIG. 4. This photograph sho\zs the large polypoid turmx mass lilling the pulIZV = right \-cntriclr; V = prilmonir \-alvc cusps: and manic valve cusps. T = tumor.

FIG. 5. This photograph reveals the tumor extension in the pulmonary in a longitudinal section. PV = pulmonic valve; SV = sinus of Valsalva; pulmonary artery; and T = tumor. 10 cn n. in aortic valve

rcumference. ‘I’he left ventricle and normal. The aortic valve circumference measured 10 cm. The ascending aorta and arch were free of sclerosis; the great vessels had a normal pattern of origin and distribution. Ci

M rere

artery PA =

Mild atelectasis was present in the lower lobes was of the lungs. No mucus or other obstruction present in the bronchial tree. The liver weight was 2,200 gm. It was firm, reddish-brown with yellow stippling. The surface was THE

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JOURNAL

OF

CARDIOLOGY

Fihromyxosarcoma

ol the Pulmonary

‘l‘hc frc.shly cut surface bulged above the margin and \vas dark red with no oozing of ‘l’he spleen \veighed 125 gm. and was blood. of the tissue elicited a smooth and fi1.m. Sectioning gritty sound. ‘l’hc surface was dark purple-red and firm. The vertebral marrow was deep red and finely

smooth. capsule

granuldr. Sections of the tumor reMi~roscofiic Firiciiliq~: vealed a generally m)-xoid pattern with zones of exSmall mutinous islands were trcme cellularity. present at irregular intervals. The points of attachment were all intimal. On the surface and intermingled in crevices of the tumor were recent and At every point, these largely fibrinous thrombi. Nuclear were sharply demarcated from the tumor. pleomorphism was extreme in the highly cellular areas. Collagen was demonstrated by special stains, but elastic tissue was not found. PAS-positive mucopolysaccharide was present in the cells, but not in the stroma. The liver showed extremely severe central passive congestion with destruction of central liver tissue. The spleen showed a diffuse increase in collagenous tissue. The adrenals were moderately depleted of lipid and the marrow showed an extensive and severe erythroid hyperplasia. Megakaryocytes were adequate in number.

DISCUSSION This case is the third reported case of a fibromyxosarcoma of the pulmonary artery. Yater,’ in 1923, reviewed 143 cases of tumors involving the heart and pericardium; he found 5 that involved the pulmonary artery. None of these pulmonary artery tumors was a fibromyxosarcoma. Pollia and GogoJ2 in 1936, reviewed the incidence of cardiac abnormalities in 46,072 autopsies and found 154 primary and 220 secondary tumors. In 1945, Mahaim3 reviewed the literature and reported 329 primary tumors In 1949, Whorton4 studied 100 of the heart. primary tumors of the heart and discovered 6 involving the pulmonary artery; again, none of these was a fibromyxosarcoma. Diebold, in a 1930 review of tumors, stated that Von Albers, in 1835, described a fibromyxosarcoma of the pulmonary artery. Haythorn, in 1941, reported the second such case. The possibility of this type of tumor existing is indicated by the general classification of soft somatic tumors by Ariel and Pack.’ Although this type tumor was mentioned by these authors in their general classification, it is not listed in their frequency tables. The possibility exists, however, that if Ariel and Pack had any specific experience with this type of tumor, it was classified as a fibrosarcoma or as a type for which the APRIL

1964

ori+

\V;IS Ilot

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.Artcr) detcrtnincd.

refer

to tumors

The).

did

not

spe-

of tllis t)-l)r in relation to blood \~~cls. The consensus is that an) variety ol” tissue types, and frequently- a niixture of types, will occur in a sarcomatous process: classification, thvreforc, is according to tht* tissue of origin or to the tissue t),prs produced in the specific case. The use of tissue types is the most practical basis for classification. Thr principal malignant tumors of blood vessels arc leiomyosarcoma and fibrosarcoma.Y When these tumors arise they are similar to identical lrsions arisin,q in other sites. The most commonl>. mentioned sites include the aorta, inferior vena cava, the carotid, axillary, femoral and popliteal arteries. In this case, the designation fibro~~~yx~~~rcon~a indicates the duality of tissue potential which is demonstrated when the tumor is studied in detail. T/IV clinical diagnosis in this case was thought to be primar)- pulmonar)- hypertension. The signs and symptoms of primary pulmonar) hypertension and of obstruction of the pulmonary artery as well as those of pulmonar) venous and mitral valve obstruction ma); be .4 short duration of cardiac debility, a similar. relentless progression of congestive heart failure in spite of adequate therapy, and periods of marked anxiety frequentl>associated with syncope characterized the history of this patient. Patients with primary pulmonary hypertension or left atria1 obstruction reveal at physical examination evidence of right ventricular hypertrophy, a prominent pulmonar)- artery, and an accentuated pulmonic second sound. This patient had evidence of right \.entricular hypertrophy and pulmonary artery prominence, but the pulmonic second sound was diminished. This combination of findings suggests an obstruction of the pulmonary- outflow tract. A low intensity systolic ejection murmur, as noted in this case, ma)- be present in severe obstruction of pulmonary outflow in relation to the severit) of obstruction and reduced cardiac output. Chest fluoroscopy in patients with pulmonar) hypertension usually reveals symmetrically enlarged central pulmonary arteries with peripheral arterial constriction. Fluoroscopy in this case revealed this, but most important to the correct diagnosis was the observation of decreased pulsation in the right pulmonary artery. Intractable right heart failure, syncopal attacks and enlargement of the pulmonary artery occur in several conditions. However, the

cificall!;

Green,

552

(h-evasse and Shanklin

diminished puhnonic second sound lvith the fluoroscopic evidence of differential pulsations of the pulmonary arteries suggest, in retrospect, the diagnosis of puhnonary artery obstruction. Right heart catheterization and angiography would have made possible the antemortem diagnosis. Secondary polycythemia was present in this case. Polycythemia is rarely present in primary pulmonary hypertensiong-I1 and in cases with severe pulmonary stenosis with congestive heart failure and a patent foramen ovale. Likewise, the occurrence of polycythemia is rarely present in patients with severe mitral stenosis, left atria1 myxoma and ball-valve thrombi. Polycythemia associated with right atria1 myxoma has recently been reported.12 Of particular interest was the occurrence of thrombocytopenia. It is well documented that chlorothiazide can induce platelet depression; however, when the drug is discontinued, the platelets return to normal levels in a few This patient’s blood demonstrated days.r3-16 persistent thrombocytopenia two weeks after cessation of chlorothiazide. Thrombocytopenia is known to occur with malignant tumors with or without bone marrow invasion and in some cases with benign hemangiomas.16 It is interesting, then, to speculate that intractable right ventricular failure, recurrent syncope, polycythemia and thrombocytopenia comprise a syndrome secondary to a fibromyxosarcoma of the pulmonary artery, with the full realization that “Ein fall ist kein fall.“* SUMMARY

This case represents the third reported case of a fibromyxosarcoma of the pulmonary artery. The diagnosis of pulmonary artery obstruction may be confused with primary pulmonary hypertension, atria1 myxoma and mitral valve obstruction. The rapid development of intractable right heart failure, syncopal attacks, soft to absent pulmonic sound and fluoroscopic evidence of differential pulmonary artery pulsations without left atria1 enlargement suggest the correct diagnosis. Cardiac catheterization and angiography are important adjuncts to the diagnosis. A syndrome comprised of intractable right ventricular failure, recurrent syncope, polycythemia and thrombocytopenia is suggested as being secondary to obstruction of the pulmonary artery. * One case is no case.

ADDENDUM

Since writing this case report, Puntl ct al.” have reported a primary cardiac rhabdom)-osarcoma presenting as pulmonary stenosis. The tumor, in this case, filled the sinuses of the pulmonary valve. The patient’s history and physical findings bear some similarity to the present case. REFERENCES Tumors of the heart aud pcri1. YATER, W. M. cardium. Arch. Int. Med., 48: 627, 1931. 2. POLLIA, J. A. and GOGOL, L. J. Some notes on malignancies of the heart. Am. J. Cuncer, 27: 329, 1936. 3. MAHAIM, I. Les Tumeurs et les Polypes du Coeur, Etude Anatomo-Clinique. Paris, 1945. Masson and Cie. 4. WHORTON, C. M. Primary the heart. Cancer, 2 : 245,

malignant 1949.

tumors

of

5. DIEBOLD, 0. Uber das primare Herzarkom. Ztschr. Kreislaufforosch., 22: 785, 1930. 6. HAYTHORN, S. R., RAY, W. B. and WOLFF, R. -1. Primary fibromyxosarcomas of the heart and pulmonary artery. Am. J. Path., 17: 261, 1941. 7. ARIEL, I. M. and PACK, G. T. Tumors of the soft somatic tissues. J. Mount Sinai Hosp., 26: 690, 1957. 8. LANDING, B. H. and FARBER, S. Tumors of the cardiovascular system, In: AFIP Fascicle Atlas of Tumor Pathology, Sec. III, Fascicle 7, p. 115. Washington, 1956. Armed Forces Institute of Pathology. 9. DRESDALE, D. T., SCHULTZ, M. and MICHTOM, R. J. Primary pulmonary hypertension. Am. J. Med., 11: 686, 1951. 10. EAST, T. Pulmonary 2: 189, 1940.

hypertension.

Brit. Heart J.,

11. KUIDA, H., DAMMIN,G. J., HAYNES, F. W., RAPAPORT, E. and DEXTER, L. Primary pulmonary hypertension. Am. J. Med., 23: 166, 1957. 12. SIGGILLINO,J. J., CRAWLEY, C. J., CLAUSS, R. H., REED, G. E. and TICE, D. A. Myxoma of the right atrium with polycythemia. Arch. Int. Med., 111: 178, 1963. 13. BALL, P. Thrombocytopenia and purpura in patients receiving chlorothiazide and hydrochlorothiazide. J.A.M.A., 173: 663, 1960. 14. LEE, R. E. et al. Therapeutically “refractory” hypertension : Causative factors and medical management with chlorothiazide and other agents. Ann. Znt. Med., 49: 1129, 1948. 15. GESINK, M. H. and BRADFORD, H. A. Thrombocytopenia purpura associated with hydrochloroJ.A.M.A., 172: 556-559,196O. thiazide therapy. 16. WINTROBE, M. M. Clinical Hematology, ed. 5, pp. 830-832. Philadelphia, 1961. Lea and Febiger. 17.

E. E., JR., COLLIER, T. M., and CUNNINGHAM, J. E., JR. Primary cardiac rhabdomyosarcoma presenting as pulmonary stenosis. Am. J. Cardiol., 12 :249, 1963.

F'UND,

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