Abstract
Primary cardiac neoplasms are rare in animals. Hemangiosarcoma is the most common primary cardiac tumour in the dog, but has not been reported in the cat.
We describe the clinical signs, the gross examination, and the morphological and immunohistochemical features of a haemangiosarcoma in the right atrium of a 13-year-old domestic shorthair cat. In addition, a distant metastasis was found in the liver.
Haemangiosarcoma (HSA) is a malignant vascular neoplasm of endothelial origin (MacEwen 1996). In cats, it has been reported to affect the abdominal cavity (most frequently the spleen), nasal cavity, thoracic cavity and cranial mediastinum, tongue and hard palate (MacEwen 1996, Ogilvie & Moore 1995, Scavelli et al 1985, Spangler & Culberston 1992). Cats with intrathoracic haemangiosarcoma usually show dyspnoea secondary to pleural effusion. Primary cardiac haemangiosarcoma in the cat has not been reported before according to the knowledge of the authors. The only primary cardiovascular system tumours found in the feline species are chemodectomas and one case of mesothelioma of the pericardium. In dogs the right atrium is the third most common site of occurrence of haemangiosarcoma; it is most frequently solitary, but can be multiple, also affecting the spleen and liver (Ogilvie & Moore 1995). Most affected dogs have signs of right heart failure, with dysrhythmias, dyspnoea, ascites and syncope.
Case report
A 13-year-old female neutered domestic short-hair cat had an acute onset of dyspnoea and tachypnoea, after anorexia for a few days. The cat had rapid shallow breathing with evidence of increased inspiratory effort. The mucous membranes were pale and the pulse was weak. Auscultation revealed diminished pulmonary and cardiac sounds in the ventral region of the thorax, and cardiac arrhythmia. Pleural effusion was suspected and ultrasonographic-guided thoracocentesis was performed with the patient in sternal recumbency.
The complete fluid analyses were indicative of a modified trasudate: clear, yellow red-tinged aspect, 6900 nucleated cell/mm3; total protein 3.0 g/dl, albumin 1.61 g/dl, alfa1 0.29 g/dl, alfa2 0.46 g/dl, beta 0.38 g/dl, globulin 0.25 g/dl and A/G ratio 1.16. The cytological examination showed few erytrocytes, some macrophages, non-degenerate neutrophils and mesothelial cells, some of which were clustered. Screening blood and biochemistry tests revealed increased PVC (52%) and a mild increase in AST (124 U/l, reference range <100 U/l) and creatinine (2.1 mg/dl, reference range <1.6 mg/dl) levels. The differential diagnoses were neoplasia, chronic heart failure and diaphragmatic hernia. Additional ultrasonographic findings were a small amount of pericardial fluid and a rounded 2-cm diameter heterogeneous mass in the right atrium. Due to the patient conditions it was not possible to carry out a complete echocardiographic examination.
After these examinations and oxygen supplementation, furosemide (2 mg/kg/8 h SC) was administered, to reduce pleural effusion. Two days later the cat's condition was deteriorating and it was euthanised at the owners' request.
The post mortem examination showed a slightly thickened pericardium containing a small amount of fluid and a mass in the right atrium, involving the auricle, a nodule on the liver and another in the right accessory lung lobe.
The right atrial mass was 1.5×1.8 cm (Fig 1) and irregular in shape with haemorrhagic appearance, including blood filled vascular spaces. On cut surface the myocardium of the right atrium and auricle was diffusely mottled reddish tan and contained large, well demarcated tan/dark foci.
Macroscopic aspect of the heart with neoplasia evidence in the right atrium.
The hepatic nodule was 0.8 cm in diameter, dark red and irregular, similar to the mass in the right atrium.
The pulmonary nodule was 0.5 cm in diameter, yellow and regularly oval shaped. The rest of the abdominal organs appeared to be free from disease.
Selected specimens obtained from the involved organs were fixed in 10% neutral buffered formalin, routinely processed and embedded in paraffin wax. Sections were cut 5 μm thick and stained with haematoxylin and eosin (HE).
The histopathological examination revealed an invasive malignant mesenchymal neoplasm with vascular differentiation infiltrating the right atrium with extension to the auricle, consistent with haemangiosarcoma. Irregular vascular spaces and capillary-like structures infiltrated the interstitium dissecting the myocardial fibres that maintained normal cross striations and nuclei [Fig 2 (a, b)].
Sections from right atrium (haematoxylin and eosin). (a) Myocardial fibres (arrow) entrapped within the neoplastic sarcomatous proliferation (bar=9 μm). (b) Irregular vascular spaces and capillary-like structures lined by tumour cells with large pleomorphic nuclei and prominent nucleoli (bar=23 μm).
The neoplasm showed well differentiated to poorly differentiated aspects. Tumour cells had elongated to large round hyperchromatic nuclei with prominent nucleoli and a small amount of cytoplasm.
The hepatic nodule was histologically similar and was considered to be a metastasis.
The pulmonary nodule was an encapsulated benign epithelial growth showing a papillary structure; the cells were cuboidal to columnar supported by connective tissue stalks. The histological appearance was consistent with a primary adenoma of the lung.
Factor VII-related antigen (von Willebrand's factor) and CD31 antigen were tested for the identification of endothelial cells in sections obtained from cardiac, hepatic and pulmonary neoformations.
A pan-specific cocktail of anti-cytokeratin AE1/AE3 was performed on the sections from pulmonary nodule to determine the epithelial origin of the neoplastic cells.
Methods
Immunohistochemical staining was performed on paraffin-embedded sections 5 μm in thickness using the avidin biotin peroxidase complex method (ABComplex, Dako). All incubations were at room temperature. After deparaffinisation and rehydration, the slides were incubated 30 min in 0.5% H2O2 to inhibit endogenous peroxidases. Sequential incubations in 2% bovine serum (15 min), primary antibody (30 min), secondary biotinylated antobody (30 min) and avidin-biotin complex reagent (30 min) followed. The sections were then exposed to the chromagen reaction solution (10% 3-Amino-9-ethylcarbazole, Sigma, in acetate buffer) for 10 min and counterstained with Harris' haematoxylin.
Staining for CD31 required previous boiling tissue sections in 1 mM EDTA, pH 8.0 for 10 min followed by cooling at room temperature for 20 min.
For Factor VIII and anti-cytokeratin AE1/AE3, sections were pretreated with 0.05% solution of protease (Protease XIV, Sigma) in phosphate-buffer saline (PBS) for 30 s.
Sources and dilutions of primary antibodies were as follows: rabbit anti-human von Willebrand factor (1:200, Dako), monoclonal mouse antibody CD31/PECAM-1 (1:20, Neo-Markers) and monoclonal mouse anti-human cytokeratin AE1/AE3 (1:70, Dako).
Negative and positive control sections were included. In particular, sections of human skin were used as positive control.
Tumour cells from cardiac and hepatic neoplasms were weakly positive for CD31 and positive for factor VIII-related antigen (Fig 3).
Section from the right atrium (immunohistochemical staining). Neoplastic cells expressed factor VIII-related antigen (bar=23 μm).
The neoplastic cells in the pulmonary nodule were positive for cytokeratine AE1/AE3 and negative for endothelial markers.
Discussion
Haemangiosarcoma, also known as angiosarcoma, is a malignant neoplasm arising from vascular endothelial cells (MacEwen, 1996).
In one study on 1383 cases of canine cardiac tumours, haemangiosarcoma was the most common (Ware & Hopper, 1999). It is most frequently solitary but can be multiple with involvement of atrium and auricle. The right atrium is the third most common site of occurrence of the canine haemangiosarcoma, accounting for about 17% of all haemangiosarcomas in dogs according to four different studies (Ware & Hopper 1999, Ogilvie & Moore 1995).
Clinical signs are variable, ranging from acute collapse to non-specific signs as lethargy and weakness. The most frequently reported are ascites, dyspnoea, pulse deficit, jugular pulse and syncope. In people, haemangiosarcoma most commonly arises from the right atrium and pericardium.
Haemangiosarcoma is a rare tumour in cats, accounting for less than 2% of all reported feline malignancies, that arises from abdominal organs, subcutis, thoracic cavity and nasal chambers. Primary feline haemangiosarcomas have been reported in cranial mediastinum, tongue, hard palate, intestine, liver and spleen (Chun 1999, Ogilvie & Moore 1995, Patnaik et al 1975, Post & Patnaik 1992, Scavelli et al 1985, Spangler & Culberston 1992, Swayne et al 1989). A recent report documents the clinical and pathologic features of four cases of intestinal haemangiosarcoma in the cat (Sharpe et al 2000).
Primary feline cardiac tumours of the vascular system reported in literature are lymphomas, one case of pericardial mesothelioma, four cases of chemodectoma (Kisseberth 1996, Paola et al 1994, Tillson et al 1994) and one endocardial ossifying mixoma (Campbell & Gelberg 2000). Metastatic haemangiosarcoma to the heart has been reported (Kisseberth 1996). Clinical signs were similar to those reported in dogs and included dyspnoea, pale mucous membranes, cardiac arrhythmia and pulse deficit.
Based on a literature search, this appears to be the first reported primary cardiac feline haemangiosarcoma with hepatic metastasis. Immunohistochemical staining for Factor VIII-related antigen confirmed the diagnosis (Ferrer et al 1995).