Mineralized, obstructive cardiac myxoma with chondroid differentiation in a cocker spaniel

Abstract

A 12-year-old castrated male cocker spaniel dog was referred for evaluation of signs consistent with right-sided heart failure. Thoracic radiography revealed mineralization in the region of the right atrium. Echocardiography identified a mass partially filling the right atrium and right ventricle and obstructing flow through the right heart. These findings were confirmed at necropsy and histopathologic features were consistent with myxoma with chondroid differentiation.

Case description

A 12-year-old castrated male cocker spaniel dog was referred for evaluation and treatment of progressive lethargy for the preceding month, a cough of 1 wk duration, and inappetence of 3 d duration. The dog had been evaluated by its veterinarian 4 d before referral and treated with amoxicillin-clavulanic acid; 12 mg/kg, PO, q12h (Aventi-Clav; Aventix Animal Health, Burlington, Ontario). Over the next 2 d, the dog’s owner noted an improvement in the cough but also an increase in respiratory effort and worsening lethargy. This change led to a second visit to its veterinarian. Thoracic radiographs were taken, which showed moderate pleural effusion. Treatment with furosemide was initiated by injection (single dose) and orally thereafter (0.6 mg/kg, PO, q12h). The dog had no known previous health conditions, no history of travel, and was up-to-date on vaccinations and deworming medications.

When seen at our institution, the dog was lethargic but responsive, uninterested in its environment, and unwilling or unable to stand. Body temperature was 37.4°C, heart rate was 102 beats/min, and the respiratory rate was 48 breaths/min without panting. Heart and lung sounds were muffled on auscultation and the femoral pulse quality was weak. Mucous membranes were pink and tacky and the capillary refill time was < 2 s. The oscillometric systolic blood pressure was 170 mmHg.

The dog was sedated with butorphanol 0.2 mg/kg, IV (Torbugesic; Zoetis, Kirkland, Quebec) and a thoracocentesis was performed, yielding 700 mL of fluid from the left side and 300 mL of fluid from the right side. The fluid was yellow, blood-tinged, and clear, with a total solids content of 3.0 g/100 mL. It was suspected to be a modified transudate based on these characteristics and was not submitted for further analysis. A focused thoracic ultrasound examination identified that some pleural effusion was still present, as well as pericardial effusion and abdominal effusion. Three-view thoracic radiographs were performed immediately following thoracocentesis (Figure 1). Mild to moderate bilateral pleural effusion was present despite the recent thoracocentesis. A focal area of mineralization was noted on both lateral projections over the region of the heart, but this was not clearly visible on dorsoventral views. A Board-certified radiologist’s principal differential diagnosis was a neoplasm arising from the thoracic wall or middle lung fields. Hepatomegaly was suspected based on marked extension of the liver caudal to the costal arch. A complete blood (cell) count and biochemistry identified several mild to moderate non-specific changes that were not considered to be diagnostically valuable.

Figure 1.

Thoracic radiographs obtained immediately following thoracocentesis. a — Left lateral projection. The thoracic cavity contains mild to moderate pleural effusion. A focal area of mineralization can be seen overlying the heart (magnified in inset, arrow). b — Right lateral projection showing similar findings. c — Dorsoventral projection showing evidence of bilateral pleural effusion, but not of the focal area of mineralization.

An echocardiogram identified a large, irregular, mixed-echogenicity, circumscribed mass obstructing the tricuspid valve and extending to occupy part of the right atrium and most of the right ventricle, except the right ventricular outflow tract [(Video 1: https://youtu.be/lZx0Ypv-PqA); (Video 2: https://youtu.be/Tf5QtUkWlXM); (Video 3: https://youtu.be/wGDfhxr3REc); available from the CVMA website]. The mass interfered with intracardiac blood flow, causing an abnormal pressure gradient in the right ventricle (Figure 2). Three-dimensional echocardiography revealed that the mass had both fixed and mobile components (Video 3). The mass’s location and appearance made neoplasia the most likely etiology, but a blood clot or other type of mass could not be ruled out from echocardiography alone. A small amount of pericardial effusion was present, but no echocardiographic evidence of cardiac tamponade was seen. Due to the severity of clinical signs and poor prognosis associated with an intracardiac mass that was suspected to be nonresectable, the dog was euthanized.

Figure 2.

Echocardiogram, right parasternal short-axis view, aortic/left atrial level. This continuous-wave spectral Doppler recording shows abnormally elevated flow velocities within the right ventricle immediately beyond the mass, indicating intraventricular obstruction to blood flow. Peak systolic velocity (S), 1.8 m/s (reference interval for flow across pulmonic valve, 1.05 +/— 0.19 m/s) (32). Mean diastolic pressure gradient = 8.3 mmHg. The apposition of the E wave to the A wave can be explained by delay in onset of flow in early diastole due to the space-occupying nature of the mass.

Results

On necropsy, free fluid was identified in the thorax (~200 mL), pericardial sac (~40 mL), and abdominal cavity (~400 mL). The lungs were affected by atelectasis, especially in the right cranial and middle lobes. The liver was diffusely enlarged, had rounded edges, was dark red in color, and had a lobular pattern, all suggesting chronic passive congestion. A firm, multinodular, dark red and pale-yellow mass was present in the right side of the heart (Figure 3). It was partially attached to the ventricular septum and the free wall of the atrium and completely engulfed the septal portion of the tricuspid valve (Figure 3). The mass extended into the right atrium and ventricle, as noted echocardiographically. Subjectively, the mass occupied most of both the right atrial and right ventricular cavities. Clotted blood and fibrin partially covered the dark red portion of the mass. No other abnormalities were noted on necropsy.

Figure 3.

Heart and lungs from post-mortem examination. The right atrium (RA) and right ventricle (RV) have been opened, revealing a firm, multinodular, dark red (white asterisk) and pale yellow (black asterisk) mass bridging the tricuspid valve and occupying most of the lumens of the right atrium and right ventricle. The Metzenbaum scissors are coursing through the cranial vena cava.

Histopathologic assessment of the mass identified it to be a myxomatous spindle cell tumor with areas of chondroid differentiation (Figure 4). The mass was sparsely cellular and was made up of interweaving streams of spindle and stellate cells throughout a matrix of abundant pale myxomatous material. This matrix stained positive with alcian blue, indicating glycosaminoglycan composition. Mild anisocytosis and anisokaryosis were noted and 2 mitotic figures were counted in 10 arbitrarily selected high-power fields, suggesting the mass was likely morphologically benign. The dark red portion of the mass contained abundant dilated blood-filled vascular channels and extramedullary hematopoiesis was observed in these sections. Sections of the pale-yellow portion of the mass had areas of chondroid differentiation, characterized by neoplastic cells often occurring within rounded lacunae surrounded by abundant, faintly blue-gray extracellular matrix. These areas stained strongly positive with alcian blue and safranin O, indicating both glycosaminoglycan and chondroid matrix within the tissue. There was no evidence of mineralization within examined sections, likely because sampling did not include mineralized areas.

Figure 4.

Histopathologic evaluation of the mass. a — Areas with a typical myxoma appearance consisting of spindle to stellate cells in a blue myxoid matrix. b — Areas of chondroid differentiation stained by safranin O special stain to highlight the cartilage matrix. Spindle-shaped cells are located within lacunae.

Discussion

This report documents features of cardiac myxoma that have not been noted in earlier reports of this neoplasm in dogs. First, mineralization associated with this cardiac mass was unusual: it has been reported in a cat (1). In general, mineralized cardiac masses in dogs are rare, with single case reports of osteosarcoma (2) and of a right atrial mass (histologic diagnosis unknown) (3) in publication. Its distinctive appearance on radiographs was unique among case reports of cardiac myxomas in dogs and could help with the clinical recognition of cardiac masses of this type in future. Second, the intraventricular pressure gradient that was demonstrated echocardiographically provides proof of intracardiac obstruction to blood flow caused by the mass. Third, the presence of both fixed and mobile elements of a cardiac myxoma has not been demonstrated previously in dogs using three-dimensional echocardiography. Fourth, this cardiac myxoma contained extensive areas of chondroid differentiation which, to the authors’ knowledge, has not been previously described in dogs.

In humans, cardiac tumors are considered “exceedingly rare” (4), with a prevalence of approximately 200 per 1 million autopsies or 0.02% (5). Of these, myxomas are the most widely encountered type, accounting for > 85% of human cardiac tumors in one large case series (6). Human cardiac myxomas have an estimated incidence of 0.5 cases per million person-years (7). By contrast, in dogs, cardiac tumors are encountered more often, with a prevalence of 0.12 to 3.1% (8–10). The most frequent type is hemangiosarcoma, followed by aortic body tumor (9–11). Other types of cardiac tumors include lymphoma, ectopic thyroid carcinoma, adenocarcinoma, osteosarcoma, chondrosarcoma, mesothelioma, mastocytoma, and various others (9–11). Most canine cardiac tumors are primary; the remainder are metastatic, although the possibility of hemangiosarcoma originating from bone marrow-based stem cells (12) may bring reconsideration of whether hemangiosarcomas constitute primary cardiac tumors.

There are few published cases of cardiac myxoma in dogs, and all descriptions consist of single case reports (n = 10) (13–22). In 3 retrospective case series totalling 1775 dogs with cardiac tumors, no cases of myxoma were identified specifically (9–11). Reports of dogs with cardiac myxoma have identified it in the right side of the heart [n = 8; 6 on the tricuspid valve (13,14,16–18,21) and 2 in the right ventricular outflow tract (15,22)] and in the left side of the heart [n = 2; 1 on the mitral valve (19) and 1 in the left ventricular outflow tract (20)]. Three cases describe evidence of embolization or dissemination to the lungs (13,14,17), with 1 noted immediately following the attempted surgical removal of the mass (17). In 2 cases, the tumor was removed surgically, with one case dying 2 d after surgery in association with embolization to the lungs (17), and the other case surviving for 2 y without evidence of recurrence (15). One case documented minimal changes in the echocardiographic appearance of the myxoma for 11 mo, although this is the only case that described long-term monitoring of a cardiac myxoma (15).

In humans, myxomas are slow growing and benign masses (4,23,24). Surgical removal is the recommended treatment and complete removal usually is curative (25). However, some cardiac myxomas could have fragments that embolize to distant locations such as within the pulmonary vasculature (4). There is controversy concerning whether cardiac myxomas can evolve to become malignant (24,26). The malignant form of this disease, myxosarcoma, has also been documented in dogs (27–29) with cases showing evidence of metastasis to areas such as the lungs and within the myocardium (27,28). In the current case, no evidence of metastasis or thromboembolism was noted macroscopically, and the mass appeared benign histologically.

The histogenesis of cardiac myxomas remains unclear, but it is believed that these tumors originate from primitive mesenchymal cells with multipotential differentiation abilities (24,30,31). This may explain the areas of chondroid differentiation in the cardiac myxoma of the present case. Cardiac myxomas with chondroid differentiation have been described previously in humans (30). Chondroid differentiation within a cardiac myxoma does not appear to affect the neoplasm’s clinical behavior or the individual’s prognosis.

The clinical effects of cardiac myxomas vary based on the size of the mass and its location. In humans, the most common effects of cardiac myxoma consist of symptoms caused by heart failure, embolization, and non-specific constitutional symptoms (4,23,24). Cardiac myxomas may affect blood flow by occluding valves, which raises venous pressures and causes congestive heart failure; by interfering with valvular function, which results in valvular regurgitation; or by a space-occupying effect in the heart that prevents complete filling of heart chambers and reduces the forward flow of blood (24). In the current case, the mass was occupying much of the right atrium and ventricle, resulting in inadequate filling of the right side of the heart (forward heart failure) and raising systemic venous pressures, which caused bicavitary effusion (backward/congestive heart failure), resulting in lethargy, inappetence, and respiratory distress.