Cardiac Myxoma of the Tricuspid Valve in a Dog

J. Comp. Path. 2003, Vol. 129, 320–324 doi: 10.1016/S0021-9975(03)00049-5, available online at http://www.sciencedirect.com on

SHORT PAPER

Cardiac Myxoma of the Tricuspid Valve in a Dog N. Machida, K. Hoshi*, M. Kobayashi*, S. Katsuda† and Y. Yamane* Departments of Veterinary Pathology and *Surgery, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, and †Department of Physiology, Fukushima Medical University School of Medicine, 1 Hikari-ga-oka, Fukushima 960-1295, Japan

Summary A case of cardiac myxoma arising from the tricuspid valve is described in an 8-year-old dog that had suffered intermittent episodes of syncope. At surgical operation, a large, irregular, gelatinous mass was found attached to the septal leaflet of the tricuspid valve. The excised tumour, measuring 5 £ 4 £ 3.5 cm, had a grey-to-yellow, friable, mucoid, multilobulated and polypoid appearance, with focal haemorrhage. Histologically, the tumour consisted of a hypocellular mass of a myxoid matrix, rich in acid mucopolysaccharides, with a supporting structure of spindle-like, elongated or stellate cells scattered in an abundant stroma. The surface of the mass was covered by a single layer of endothelial-like cells. Immunohistochemistry revealed that the surface cells of the mass were positive for the endothelial marker CD34 and the constituent cells within the mass reacted positively and uniformly with antibodies to vimentin and a-smooth muscle actin. The dog died 36 h after the operation and, at necropsy, wide dissemination of myxomatous embolization to the intrapulmonary arteries was found. q 2003 Elsevier Ltd. All rights reserved. Keywords: cardiac myxoma; dog; tricuspid valve; tumour

Cardiac myxoma is an endocardial neoplasm originating from multipotential mesenchymal cells that occur in the subendocardial layer and are capable of differentiating into various cell types (Ferrans and Roberts, 1973; Tanimura et al., 1988; Lie, 1989). It is the most common primary cardiac tumour in adult human patients and accounts for almost half of all benign cardiac tumours and a quarter of all tumours and cysts of the heart and pericardium (McAllister and Fenoglio, 1978), but is extremely rare in animals, including dogs. In dogs, the first case was reported by Roberts (1959), followed by sporadic subsequent reports (Darke and Gordon, 1974; Liu et al., 1989; Bright et al., 1990). The purpose of this paper is to describe the gross, light microscopical, and immunohistochemical examination of a canine case of cardiac myxoma arising from the tricuspid valve. 0021–9975/03/$ - see front matter

An 8-year-old spayed Labrador retriever (20.0 kg) was presented for evaluation of intermittent episodes of syncope. Physical examination revealed jugular vein distension and weak femoral pulses. The dog had a distended abdomen with abdominal effusion. The cardiac rhythm was regular (140 beats/min), but a grade V/VI pansystolic murmur with multiple systolic clicks was heard in the tricuspid area. Results of a complete blood count were within reference ranges. Abnormal blood biochemistry parameters included an alanine aminotransferase value of 776 IU/litre (reference range, 10 to 90) and alkaline phosphatase of 264 IU/litre (reference range, 20 to 200). Thoracic radiographs revealed mild cardiomegaly, a prominent caudal vena cava, and increased pulmonary vascular markings. Two-dimensional echocardiography demonstrated a large intracavitary mass with irregular borders attached to the septal leaflet q 2003 Elsevier Ltd. All rights reserved.

Cardiac Myxoma of the Tricuspid Valve in a Dog

Fig. 1. Excised mass of cardiac myxoma of the tricuspid valve, 5 £ 4 £ 3.5 cm, with a smooth, glistening, gelatinous and multilobulated appearance and focal haemorrhage. Scale, 1 mm.

of the tricuspid valve. On right heart angiography, a large filling defect was seen in the right ventricle. On the basis of ultrasonographic and angiographic findings, intracavitary neoplasia arising from the tricuspid valve was suspected. On cardiopulmonary bypass, the right atrial cavity was explored and a large, irregular and gelatinous mass was found attached to the septal leaflet of the tricuspid valve. The mass was excised with a surrounding cuff of the valve leaflet. The excised mass, measuring 5 £ 4 £ 3.5 cm, was multilobulated with a glossy surface (Fig. 1). It was composed of grey-to-yellow mucoid tissue, and contained haemorrhagic areas. Most of the septal leaflet (the distal three-quarters) was completely enclosed within the basal portion of the mass. Despite being placed in the intensive care unit after the surgical procedure, the dog died 36 h later. At necropsy, there was serosanguinous fluid in the abdominal (1380 ml) and thoracic (950 ml) cavities. The liver was markedly congested and enlarged, with fibrin tags on its surface. The lungs were uniformly purplish-red, and the pleural surfaces were wrinkled. On the cut surfaces, numerous masses of grey-white, gelatinous tissue up to 10 mm in diameter were seen in the lumina of the intrapulmonary arteries throughout all lobes of the lung; most of these were firmly lodged in the vessels (Fig. 2). In the heart, moderate right atrial and right ventricular eccentric hypertrophy was observed, but no other significant abnormalities were noted. Tissue samples from the heart, lungs, tracheobronchial lymph nodes, thyroid glands, parathyroid glands, oesophagus, stomach, small and large intestines, pancreas, liver, mesenteric lymph nodes,

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Fig. 2. Sectioned surfaces of the caudal lobe of the left lung. Widely disseminated myxomatous embolization to intrapulmonary arteries is seen. Scale, 1 mm.

spleen, adrenal glands, kidneys, urinary bladder, brain, spinal cord and skin were fixed in 10% buffered formalin for routine processing, embedded in paraffin wax, sectioned at 5 mm, and stained with haematoxylin and eosin (HE). Selected sections of the cardiac mass and lung tissues were also stained by periodic acid-Schiff (PAS), alcian blue (pH 2.5), toluidine blue for metachromatic substances, Masson’s trichrome, elastica van Gieson, Wilder’s reticulum, and Perls’ Prussian blue techniques. Immunohistochemical procedures were additionally performed for identification of cytokeratin (MNF116; Dako Corp., Santa Barbara, CA, USA), vimentin (V9; Dako), desmin (D33; Dako), a-smooth muscle actin (1A4; Dako), a-sarcomeric muscle actin (Alpha-Sr-1; Dako), an endothelial marker CD34 (QBEnd10; Dako), macrophages (KP1; Dako), and S-100 protein (Dako). The avidin – biotin – peroxidase method (Vectastain; Vector Laboratories, Burlingame, CA, USA) was used to “visualize” the reaction product, with haematoxylin as a counterstain. Microscopically, the excised cardiac mass was composed of an abundant, faintly eosinophilic, myxoid matrix throughout which were scattered spindle-like, elongated or stellate cells with scant eosinophilic cytoplasm and a small round to ovoid or elongated nucleus (Fig. 3). The myxoid matrix was weakly positive with PAS, strongly positive with alcian blue, and metachromatically stained with toluidine blue, revealing that it contained acid mucopolysaccharides. This matrix also contained variable numbers of haphazardly arranged collagenous, elastic and reticular fibres, which were identified by Masson’s trichrome, elastica van Gieson, and Wilder’s reticulum stain. The cells

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Fig. 3. Histological section of the mass. An acid mucopolysaccharide myxoid matrix and embedded spindle-like, elongated or stellate cells with scant eosinophilic cytoplasm are seen. HE. £ 260.

embedded within the myxoid matrix were arranged singly, often forming a coarse network. Mitoses were not found. The surface of the mass was covered by elongated and flattened cells resembling endothelial cells, with single, long, narrow nuclei and little cytoplasm (Fig. 4). These cells also formed vascular-like slits or lumina that invaginated the superficial part of the mass. The capillary-like channels, with or without eosinophilic material and sometimes containing small numbers of blood cells, often extended deep into the myxoid matrix of the mass. Small to large foci of haemorrhage were present throughout the mass. Numerous macrophages contained brownish pigment granules, most of which showed a positive reaction with

Fig. 4. Histological section through the surface of the mass. Flattened lining cells with elongated nuclei simulating endothelium are seen. These cells frequently form vascular-like slits or lumina that invaginate the superficial part of the mass. HE. £ 260.

Perls’ Prussian blue for ferric iron. In addition, an inflammatory cell infiltrate, consisting of neutrophils, lymphocytes, plasma cells and fibroblast-like cells, was identified in the mass. In the intrapulmonary elastic and muscular arteries of various sizes, emboli of neoplastic tissue similar to that in the cardiac tumour were frequently observed, causing severe narrowing or total occlusion of the lumina. Involvement of the vascular wall itself and the formation of aneurysms were occasionally observed (Fig. 5). Around the vessels, which were markedly distended by the neoplasm, pulmonary collapse was present. In the liver, the veins and lymphatics were dilated, and the periportal hepatocytes were swollen and vacuolated. The remaining organs were normal. Immunohistochemically, positive labelling for CD34 was limited to the surface cells of the cardiac mass and the capillary-like channel-lining cells (Fig. 6), but it was present in only a small proportion of the cells. These cells were strongly labelled for vimentin. The spindle-like, elongated or stellate cells embedded in the myxoid matrix were diffusely positive for vimentin, as well as desmin and a-smooth muscle actin (Fig. 6). Cytokeratin, a-sarcomeric muscle actin, and KP1 were negative in all types of constituent cell. The light microscopical appearance of the cardiac mass was similar to that of the cardiac myxomas previously described in dogs and man: a hypocellular mass of amorphous acid mucopolysaccharide matrix covered by a single layer of endothelial-like cells with a supporting structure of spindle-like, elongated and stellate cells scattered in an abundant stroma (Roberts, 1959; Ferrans and

Fig. 5. Histological section of the lung, showing embolic lesion of cardiac myxoma in an intrapulmonary artery, with active invasion of the media and formation of an aneurysm. HE. £ 135.

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Cardiac Myxoma of the Tricuspid Valve in a Dog

Fig. 6. Immunolabelling shows abundant vimentin (A) and asmooth muscle actin (B) in the cytoplasm of the tumour cells within the mass; surface cells of the mass express CD34, an antigen found in endothelial cells and their precursors (C). Haematoxylin counterstain. £ 260.

Roberts, 1973; Darke and Gordon, 1974; Wold and Lie, 1980; Liu et al., 1989; Bright et al., 1990; Burke and Virmani, 1993; Reynen, 1995). These distinctive histological features are shared by no other cardiac neoplasm, and a diagnosis of cardiac myxoma was made. Cardiac myxomas in man may be sporadic or familial (Carney, 1985). Most cases of cardiac myxoma are sporadic and occur as a single tumour; in less than 5% of patients there is a familial history of atrial tumours and various extracardiac lesions. The familial form is more often multiple, recurrent and right-sided than the sporadic form (Burke and Virmani, 1996). The present canine case possibly corresponded to the sporadic form of cardiac myxoma in man. Previous reports of human cases of cardiac myxoma describe varied immunohistochemical and histological findings (Burke and Virmani, 2001), probably because the cells giving rise to the tumour are capable of differentiating into endothelial cells, smooth muscle cells, angioblasts, fibroblasts, cartilage cells and myoblasts (McAllister and Fenoglio, 1978; Lie, 1989; Reynen, 1995). In our immunohistochemical study, the surface cells of the mass were positive for CD34. Myxoma cells embedded within the mass reacted positively and uniformly with antibodies to vimentin, which proved their mesenchymal nature, and with antibodies to a-smooth muscle actin, indicating a tendency towards smooth muscle differentiation; however, undifferentiated cells best classified as primitive mesenchymal cells were also present. These findings were similar to those of Landon et al.

(1986), who reported that surface cells and cells lining the vascular structures within cardiac myxomas express endothelial antigens, and that tumours are vimentin-positive and sometimes smooth muscle actin-positive. Wide dissemination of myxomatous emboli to the intrapulmonary arteries occurred in the present case. Similar embolic lesions of the intrapulmonary arteries were reported in canine cases of cardiac myxoma by Roberts (1959) and Darke and Gordon (1974). In man, systemic tumour embolization occurs in 40 to 50% of patients with left atrial myxoma (Peters et al., 1974; Wold and Lie, 1980). In right-sided myxomas, embolic tumour phenomena occur relatively infrequently, but pulmonary embolism has been reported (Reynen, 1995; McAllister et al., 1999). Because such embolic cardiac myxomas do not have the histological characteristics of malignant neoplasms, and do not cause tumour deposits in viscera or lymph nodes, the intravascular deposits are not interpreted as true metastases (Burke and Virmani, 1996).

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