Heartbase tumor and pericardial effusion in a dog - NCBI

Heartbase tumor and pericardial effusion in

a

dog

Rocky DiFruscia, Marie-Antoinette Perrone, Norbert H. Bonneau and Luc Breton

Abstract Pericardial effusion and congestive heart failure occurred in a ten-year-old male Bouvier des Flandres dog. Signs included weakness, exercise intolerance and ascites. Echocardiography identified a heart base mass as a possible cause of the pericardial effusion. A large quantity (650 mL) of bloody fluid was removed by pericardiocentesis and was characterized at cytology as a nonseptic sanguineous exudate. There was no cytological evidence of neoplasia in the effusate. Pericardiocentesis caused dramatic clinical improvement and resolution of the signs of congestive heart failure. Surgical excision was attempted but the mass could not be resected since it invaded the entire dorsal wall of the right atrium as well as part of the aortic root. The cellular origin of the heartbase tumor could not be determined.

R6sume

a progressive limitation in ventricular diastolic filling, and a reduction of stroke volume are observed (1).

Acute tamponade generally results from trauma, atrial rupture or acute hemorrhage into the pericardial sac. Most of the canine cases are presented with signs related to chronic pericardial effusion which may or may not reach the point of tamponade (2). Signs of backward right ventricular failure (distention of jugular veins, increased central venous pressure, ascites, hepatomegaly, positive hepatojugular reflex, edema) and forward left ventricular failure (decreased stroke volume and blood pressure, weakness, prerenal azotemia) eventually occur (1,2). Pulmonary edema is not frequently observed because of the dramatic reduction of right ventricular output. Pulsus paradoxus, which is defined as an intermittent disappearance of palpable pulses during inspiration, may be identified in clinical cases of tamponade (1-4). Other clinical observations that can be found in pericardial effusion include: decreased amplitudes of R waves and electrical alternans electrocardiographically, enlarged cardiac silhouette with smooth edges radiographically and a fluid-filled space surrounding the heart echocardiographically.

Une masse A la base du coeur et une effusion p6ricardlque chez un chien. Une effusion pericardique et de l'insuffisance caretaient de la faiblesse, de l'intolerance a l'exercice et de l'ascite. L'echocardiographie a permis de mettre en evidence une masse localisee A la base du coeur. Une relation de cause a effet a ete etablie entre la presence de cette masse et l'effusion abondante. Une grande quantite de liquide sanguinolent (650 mL) fut retiree Case presentation and management par pericardiocentese et caracterisee a la cytologie A ten-year-old neutered male Bouvier des Flandres dog comme etant un exsudat sanguinolent aseptique. was referred to the Small Animal Hospital of the Aucune evidence de neoplasie ne fut identifiee dans University of Montreal because of weakness and exerle liquide d'effusion. La pericardiocentese a procure cise intolerance of three months duration. Signs were une amelioration importante des sympt6mes de con- progressively worsening and the owner also reported gestion et de l'etat genfral du chien. L'excision gradual distention of the dog's abdomen during the chirurgicale fut tent6e sans succes puisque la masse week prior to presentation. Coughing was present with envahissait une portion importante de la paroi dorsale mild exercise. Electrocardiograms (ECG) performed de l'oreillette droite ainsi que la racine aortique. with standard positioning by the referring veterinarian L'origine celHulaire de la masse neoplasique n'a pu etre six months and two weeks prior to presentation showed a dramatic decrease in the amplitude of the determinee a l'examen histologique. R waves. The following observations were made during Can Vet J 1989; 30: 150-154 physical examination: severely muffled cardiac sounds, weak, thready femoral pulse, resting heart rate of Introduction 132 beats per minute with a regular rhythm, pale The pericardium is a fibroelastic sac that has a poten- mucous membranes with a capillary refill time of two tial for marked stretching (1). The factors involved seconds, and moderate ascites. Pulmonary auscultain the development of cardiac tamponade relate tion was difficult to assess because of continuous pantdirectly to increased intrapericardial pressure and its ing. Rectal temperature was normal. The differential diagnoses for ascites included heart effect on diastolic filling of the heart, particularly the right ventricle (1). They include the absolute volume failure, hepatic disease, hypoproteinemia and abdomof effusion, the rate of accumulation, and the physical inal inflammation or neoplasia. Muffled heart sounds characteristics of the pericardium (1). Cardiac tam- associated with weak femoral pulses suggested periponade is defined as a rise in intrapericardial pressure cardial effusion or decreased cardiac contractility. Thoracic radiographs were taken and showed a to a point where an elevation in intracardiac pressures, markedly enlarged cardiac silhouette. On the lateral Departement de medecine (DiFruscia, Bonneau, Breton) and view (Figure 1), there was elevation of the trachea and Departement de pathologie et microbiologie (Perrone), the cardiac silhouette occupied more than four interFaculte de Medecine veterinaire de l'Universite de Montreal, costal spaces. On the ventrodorsal view (Figure 2), the C.P. 5000, Saint-Hyacinthe (Quebec) J2S 7C6. cardiac silhouette appeared very enlarged and rounded 150

Can Vet J Volume 30, February 1989

Figure 1. Left lateral chest radiograph showing an enlarged and rounded cardiac silhouette.

Figure 3. Ultrasound imaging of the base of the heart showing a large mass (M), the aortic root (a), severe pericardial effusion (e), and what appears to be a smaller mass adjacent to the larger one (arrow).

Figure 2. Ventrodorsal view demonstrating severe enlargement of the cardiac silhouette with a smooth, rounded border suggesting pericardial effusion.

with smooth edges; it occupied the entire width of the thoracic cavity. The appearance of the cardiac silhouette on these radiographs was compatible with pericardial effusion, or severe, dilated cardiomyopathy. Echocardiography was performed and identified the presence of pericardial effusion. A large amount of fluid was observed within the pericardial sac. Also, a 6 x 7 cm mass with homogeneous echogenicity was observed near the aortic root and situated in the area of the right atrium. There appeared to be another small mass adjacent to the large one (Figure 3). MeasureCan Vet J Volume 30, February 1989

ments of the left ventricular cavity showed a marked reduction in both systolic and diastolic dimensions with a normal shortening fraction (38.7 Wo). The reduction of the left ventricular chamber associated with signs of right-side congestive heart failure were suggestive of tamponade. A six-lead ECG tracing demonstrated sinus tachycardia and R waves of 1.3 mV in amplitude. The low amplitude R waves were attributed to the pericardial effusion. Electrical alternans was not present. A pericardiocentesis was performed at the right sixth intercostal space with ECG monitoring (to avoid puncturing the heart or coronary arteries) and a large amount (650 mL) of a bloody, port-wine colored fluid was removed. Immediately obtained data concerning the fluid showed a hematocrit of 0.21 L/L and xanthochromia of the plasma. Samples of the fluid were submitted for cytology in EDTA while others were allowed to clot in tubes without anticoagulants. The latter samples failed to show clotting even up to 30 minutes later. Blood was also obtained for hematological, biochemical and clotting evaluation. A sample of the fluid was submitted (in heparin) along with a jugular venous sample for pH determination

and comparison. Postpericardiocentesis radiographs of the thoracic cavity showed a significant decrease in the size of the cardiac silhouette and there was a suggestion of a soft tissue density located at the cranial waist of the heart. Echocardiography also showed a small residual amount of fluid still present in the pericardial sac. The dog's heart rate slowed, femoral pulses and precordial beat were stronger. Because the risk of traumatic bleeding in the pericardial sac was considered, the dog was monitored hourly for heart rate, hematocrit and capillary refill time for the next 24 hours. Maintenance fluids (lactated Ringer's solution) were administered carefully 151

through a jugular catheter with central venous pressure monitoring. The dog's general condition improved rapidly over the next 24 hours and the ascites had decreased significantly without the use of diuretics. The peripheral blood hematocrit was low normal (0.38 L/L) and the plasma was clear. There was a moderate neutrophilic leukocytosis (WBC = 28.6 x 109/L) indicating the presence of an inflammatory process. Clinical biochemistry was normal except for a mild hyperglycemia. A clotting profile, consisting of prothrombin time, partial thromboplastin time and platelet count, was normal. Cytology of the pericardial fluid demonstrated the presence of a large number of intact red blood cells, white blood cells (WBC = 15.4 x 109/L, mostly neutrophils), with a few macrophages, mesothelial cells and an occasional mast cell. Platelets, erythrophagia or hemosiderin were not observed. Neutrophils were well-preserved and neither bacteria nor neoplastic cells were observed. The cytological interpretation of the fluid was a sanguineous nonseptic exudate. The pH of the pericardial fluid was 7.32 and the pH of the simultaneously obtained jugular venous sample was 7.39. The cause of congestive heart failure was then related to the pericardial effusion caused by the presence of a heartbase mass. An inflammatory process was probably associated with the presence of the mass either from necrosis or damage to adjacent tissues. Surgical exploration was recommended to determine if the mass(es) could be excised and to obtain a biopsy sample for a definitive diagnosis. Using controlled ventilation and isoflurane anesthesia, a left thoracotomy was made by resecting the fifth rib. A small amount of bloody fluid was present in the pleural cavity. The pericardium was distended with fluid but otherwise appeared normal. Avoiding the phrenic nerve, a large window was created in the pericardium after suction of a moderate amount of bloody fluid. A large (approximately 8 cm diameter), spongy mass was located at the base of the heart. It invaded the entire dorsal wall of the right atrium and bled easily. The size and location of the mass and its apparent extensive invasion of the right atrial wall made its surgical excision impossible. Because of the poor prognosis, the owner elected euthanasia and the dog was submitted for necropsy.

pulmonary lobes. The liver was enlarged and congested, suggesting right-sided heart failure. All other tissues and organs appeared normal. Microscopically, the mass consisted of large, rounded, closely packed, pleomorphic cells, arranged in small clusters and surrounded by delicate strands of fibrovascular tissue. Groups of these clusters were occasionally surrounded by thicker bands of mature fibrous tissue (Figure 4). The neoplastic cells contained large, vesicular, often irregular nuclei with prominent central nucleoli (Figure 5). Their cytoplasm was deeply eosinophilic, scant to abundant and finely granular, with occasional coarser granules. Several mononuclear giant cells and focal accumulations of lymphocytes were also seen. Necrosis, hemorrhage and severe inflammation were evident in the portion of the mass extending over the right atrium; tumor cells in this area were dividing and markedly pleomorphic. Neoplastic cells also invaded the surrounding epicardium, the lung, and the regional lymph nodes. Positive identification of the tumor as an aortic body, ectopic thyroid or parathyroid carcinoma by electron microscopy was not possible because the formalin-fixed sections were unsuitable for detailed ultrastructural analysis.

Discussion The clinical presentation of this case was relatively typical of congestive heart failure induced by massive pericardial effusion and tamponade. Muffling of cardiac sounds, although not specific for pericardial effusion, is one of the most frequently reported signs (2-5). Attenuation of acoustic transmission of heart sounds by pericardial fluid and decreased cardiac con-

Necropsy findings The thoracic cavity and pericardial sac contained approximately 200 mL of bloody fluid; the source of this effusion was a large, gray, lobulated mass, measuring 4 x 6 x 12 cm, located at the base of the heart, between the ascending aorta and the pulmonary artery. One third of this mass extended cranially into the right atrial wall, close to the cranial vena cava. The mass had a spongy consistency and marbled appearance when sectioned. A large, fibrinous thrombus was attached to the endocardium of the right atrial wall, where the tumor infiltrated the myocardium. A few hard, white nodules, 1 to 2 mm in diameter, were randomly distributed in the left cranial and middle 152

Figure 4. Histological appearance of the tumor showing clusters of neoplastic cells surrounded by thin strands of connective tissue. HPS. Can Vet J Volume 30, February 1989

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Figure 5. Histological section of tumor illustrating neoplastic cell morphology. A giant cell is visible in the upper left corner (arrowhead). HPS.

tractility resulting from impairment of diastolic filling of the heart are responsible for this observation. The increased resting heart rate is a consequence of catecholamine release in response to decreased cardiac output and blood pressure. Systemic vascular resistance also increases at the expense of cardiac output to maintain blood pressure. Although central venous pressure was not taken before pericardiocentesis, it is usually elevated in pericardial effusion and tamponade. This measurement is not specific for pericardial effusion and will be elevated in any disease causing increased diastolic filling pressure of the right ventricule (decompensated congestive heart failure). Electrocardiographic changes can also be a very useful tool to diagnose pericardial effusion in the dog. Decreased amplitude of the R waves can be associated with pericardial or pleural effusion (2-6). Serial ECG recordings in this case showed a decrease in the amplitude of R waves as compared to their amplitude observed six months prior to presentation. Electrical alternans, or variations in the amplitude of the R waves in the same lead, has been reported with pericardial effusion in the dog (2-7). It is now generally agreed that it results from anteroposterior motion of the heart that occurs in a 2:1 pattern (6-8). This case did not have electrical alternans. Also, it was recently demonstrated that pericardial effusion with blood caused no significant changes in the QRS complex because of its cellular rich medium compared to a significant decrease in the amplitude of the QRS caused by a relatively cell-free medium such as saline (9). This observation may explain why the R waves in this case were not more attenuated in amplitude since the effusion was large, but highly cellular. Left preCan Vet J Volume 30, February 1989

cordial leads, especially V3, were found to increase sensitivity for detecting pericardial effusion (9). Echocardiography is a sensitive, noninvasive diagnostic tool that can be very useful in the diagnosis of even small amounts of pericardial effusion. It also proved to be very useful in identifying the cause of the effusion in this case (heartbase mass). The presence of a large amount of anechoic fluid greatly facilitated visualization of the mass. Findings of necrosis, hemorrhage and inflammation within the tumor at histopathology explained well the cytological nature of the effusate and the neutrophilic leukocytosis found in this case. The marked blood contamination of the fluid was thought to originate from the tumor since lesions were not found on the epicardium or coronary arteries at necropsy that could have resulted from a traumatic pericardiocentesis. The large quantity of fluid removed and progressive clinical signs suggested that the accumulation probably occurred in small increments over a long period of time to allow gradual stretching of the pericardium. The physical state of the pericardium is important since it is reasonable to assume that a diseased or inflamed pericardium may not have its full potential of stretching. This case did not show any significant pericardial changes either grossly or histopathologically. The increase in intrapericardial pressure eventually reached the point of tamponade because of the following observations: elevation in diastolic filling pressure of the right ventricle resulting in backward congestive failure (ascites), marked decrease in systolic and diastolic diameters of the left ventricular cavity as well as a small aortic diameter reflecting decreased stroke volume and cardiac output. The left ventricular shortening fraction was normal and was probably maintained so by increased adrenergic tone. Echocardiography therefore provided additional valuable information concerning the degree of hemodynamic compromise in this case. It did not however, demonstrate the typical anteroposterior swinging of the heart associated with electrical alternans and pericardial effusion. Cytological evaluation of the pericardial fluid led us to believe that a certain amount of blood had been oozing from the tumor since the hematocrit was elevated, the plasma of the fluid was xanthochromic, the sample did not clot, and platelets were not seen (5). Blood contamination from cardiac puncture was ruled out. It is possible that a sudden increase in intrapericardial pressure caused by bleeding was responsible for the development of tamponade and heart failure some time prior to presentation. As expected for most malignant pericardial effusions in the dog, cellular examination failed to reveal neoplastic cells. This is supported by a number of studies of the diagnostic value of neoplastic pericardial effusions wherein the great majority of cases (> 74%) did not reveal neoplastic cells at cytology (3,5,1 1). One of the studies (11), also reports that 13 % of 31 nonneoplastic effusates were falsely diagnosed as positive or suspect for neoplasia. Determination of the fluid pH compared to a simultaneous arterial or venous sample has been advocated as a helpful test in differentiating inflammatory from 153

noninflammatory pericardial conditions (12). Although the number of cases of inflammatory causes (idiopathic hemorrhagic pericardial effusion, chronic fibrinopurulent pericarditis) was small (three cases), there seemed to be a significant difference in the pH values. The pH of inflammatory pericardial disease was markedly lower than either arterial or venous pH. Noninflammatory conditions on the other hand had a pH that was similar to venous or arterial pH. This may also help in identifying the possibility of inadvertent ventricular puncture during pericardiocentesis. Pericardiocentesis is the single most effective mode of initial treatment in pericardial effusion especially if signs of tamponade are present. The technique has been described (5) and is relatively safe, particularly if a large effusion separates the pericardium from the epicardium. Radiographs of the thorax can help choose which intercostal space to use. If echocardiography is not available, heartbase masses can be identified by a pneumopericardiogram (5). At surgery, the tumor invaded the right atrial wall extensively and seemed to originate from the aortic root, precluding excision. Hemangiosarcoma is the most frequently reported primary cardiac tumor and usually originates at the right atrial appendage (14-16). It is also a frequent cause of hemorrhage in the pericardial sac because of its tendency to spontaneously bleed, rupture or even cause a right atrial tear. The epicardium and visceral pericardium may be seeded with foci of neoplastic cells in these cases and should be examined carefully at surgery. Heartbase tumors are neoplasms of various histological types arising at the heart base in proximity to the origins of the great vessels (14). The chemodectoma (chemoreceptor cell tumor, nonchromaffin paraganglioma, aortic body tumor) is the most common histological type of heartbase tumors, while others include endocrine tumors (ectopic thyroid or parathyroid tumors), lymphosarcoma and connective tissue tumors (14). Although some cardiac tumors can be resected surgically if small and isolated (right atrial hemangiosarcoma), heartbase tumors represent a greater challenge to the surgeon because of their location. The presence of large nonresectable tumors or metastatic disease may justify the use of conservative therapy such as repeated pericardiocentesis or subtotal pericardiectomy (below the phrenic nerves). Although metastatic pulmonary tumors were not observed radiographically in this case, some small (1 to 2 mm) neoplastic nodules of the same tissue origin as the primary tumor were found in the left cranial and middle lung lobes. Another cause of bloody pericardial effusion that has a better long-term prognosis is idiopathic hemorrhagic pericardial effusion found in males of large or giant breed dogs (13). While this disease is considered an inflammatory, possibly immune-mediated condition, it is not possible to differentiate it, cytologically, from neoplastic conditons (13). Pericardiocentesis (sometimes repeated) or subtotal pericardiectomy provide means for successfully managing these cases. Table 1 lists some common causes of pericardial effusion in the dog. 154

TABLE

Common causes o~~~fvpicrIa e...ffusonI peertngtam - eti:bacteia fu.pi . - nonseptic: i~diopath ic heorhai. priar.l.ffsin .congestiv h...ear alr

hypoproteinemia~~~~~~~~~. . . .e....opei. adia hernia

...tra..uma

...w....

..

.p.

- neopasia hemangosarcma, heribas tumoS) left atrial -ruptuie clotting - abnormalities~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

The exact tissue origin of the heartbase tumor in this case could not be conclusively determined because of the high degree of anaplasia. Possibilities included a chemodectoma or ectopic thyroid or parathyroid cvi tumor.

References 1. Lorell BH, Braunwald E. Pericardial disease. In: Braunwald E, ed. Heart Disease. A Textbook of Cardiovascular Medicine. 2nd ed. Philadelphia: WB Saunders, 1984: 1470-1527. 2. Matthiesen DT, Lammerding J. Partial pericardiectomy for idiopathic hemorrhagic pericardial effusion in the dog. J Am Anim Hosp Assoc 1985; 21: 41-47. 3. Berg RJ, Wingfield W. Pericardial effusion in the dog: A review of 42 cases. J Am Anim Hosp Assoc 1984; 20: 721-729. 4. de Madron E. Pericarditis with cardiac tamponade secondary to feline infectious peritonitis in a cat. J Am Anim Hosp Assoc 1986; 22: 65-69. 5. Jones CL. Pericardial effusion in the dog. Compend Contin Educ Pract Vet 1979; 9: 680-685. 6. Tilley LP. Analysis of common canine cardiac arrhythmias. In: Essentials of Canine and Feline Electrocardiography. 2nd ed. Philadelphia: WB Saunders, 1985: 184-185. 7. Bonagura JD. Electrical alternans associated with pericardial effusion in the dog. J Am Vet Med Assoc 1981; 178: 574-579. 8. Sbarbaro JA, Brooks HL. Pericardial effusion and electrical alternans. Postgrad Med 1978; 68: 105-112. 9. Hamlin RL, Rush JE, Kramer DA. Effects of pericardial or pleural effusion on the amplitude of QRS in dogs. Proc 3rd Annu Conf Am Coll Vet Inter Med 1985: 131. 10. Thomas WP, Sisson D, Bauer TG, Reed JR. Detection of cardiac masses in dogs by two-dimensional echocardiography. Vet Radiol 1984; 25: 65-72. 11. Sisson D, Thomas WP, Ruehl WW, Zinkl JG. Diagnostic value of pericardial fluid analysis in the dog. J Am Vet Med Assoc 1984; 184: 51-55. 12. Edwards NJ, Hawe RS, Johnson JT, Krauer KW. The diagnostic value of pericardial pH determinations. Proc 4th Annu Conf Am Coll Vet Inter Med 1986: 111-113. 13. Berg JR, Wingfield WE, Hoopes PJ. Idiopathic hemorrhagic pericardial effusion in eight dogs. J Am Vet Med Assoc 1984; 185: 988-992. 14. Thomas WP. Pericardial disease. In: Ettinger SJ, ed. Textbook of Veterinary Internal Medicine. Disease of the Dog and Cat. 2nd ed. Philadelphia: WB Saunders, 1983: 1080-1095. 15. Aronsohn M. Cardiac hemangiosarcoma in the dog: a review of 38 cases. J Am Vet Med Assoc 1985; 187: 922-925. 16. Fees DL, Withrow SJ. Canine hemangiosarcoma. Compend Contin Educ Pract Vet 1981; 12: 1047-1051.

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