Metastatic Pericardial Tumors in a Dog With Equivocal Pericardial Cytological Findings

Introduction

Pericardial tumors are relatively uncommon in humans and domestic animals and are usually associated with pericardial effusion.^1–3 Primary intrapericardial neoplasms are more frequent than intrapericardial metastases in dogs.^1,2 Echocardiography is an accurate, noninvasive tool for diagnosing even small amounts of pericardial effusion, and it may determine the inciting cause of the effusion, particularly when a mass is visualized. ^4–6 In vivo diagnosis of the etiology of pericardial effusion is often uncertain; however, it cannot always be achieved solely on clinical assessments.^4–6

Reports describing the clinical and ultrasonographic findings of dogs with metastatic pericardial tumors are scarce.^7–9 The purpose of this report is to describe the clinical, echocardiographic, and pathological findings of a dog with pericardial effusion from metastatic pericardial neoplasia.

Case Report

A 6-year-old, 28-kg, female, mixed-breed dog was referred for evaluation of abdominal and pleural effusion. One year before, leishmaniasis was diagnosed based on results of serological testing, and the dog had been treated with meglumine antimonide and allopurinol for 3 months.

On physical examination, the dog was lethargic and in poor body condition (body condition score 3/9). Dyspnea was evident (respiratory rate of 44 breaths per minute), and on auscultation lung sounds were absent over the ventral third of the thorax on both sides. Peripheral pulses were weak, and heart sounds were muffled with a heart rate of 148 beats per minute. The dog’s abdomen was mildly distended, and a fluid wave was palpable. Complete blood count showed mild anemia (packed cell volume 30%, reference range 35% to 57%). Results of serum biochemical analyses were normal. A six-lead electrocardiogram demonstrated sinus rhythm, with a heart rate of 140 beats per minute and low-voltage QRS complexes.

Survey thoracic radiographs showed mild pleural and abdominal effusion and globoid enlargement of the cardiac silhouette. Transthoracic ultrasonography^a was performed from standard right and left parasternal positions. Two-dimensional real-time and M-mode echocardiography revealed a wide, anechoic space between the parietal pericardium and the epicardium, and diastolic collapse of the right atrium and ventricle. Multiple, round, well-marginated echogenic masses of different sizes (maximal diameter 2 cm) were visible protruding from the parietal and visceral pericardial surfaces into the pericardial space [Figures 1A, 1B]. Portions of these masses demonstrated to-and-fro oscillatory movements during the cardiac cycle. Mild pleural and abdominal effusion was also detected.

Pericardiocentesis was performed under ultrasonographic guidance using a 16-gauge central venous catheter,^b and 200 mL of serosanguineous fluid (total protein 4.4 g/dL) was removed from the pericardial sac. Bacterial and fungal culture of the pericardial fluid yielded no growth. Cytopathological evaluation of the fluid revealed 15 × 10³ nucleated cells/μL, including numerous activated and foamy macrophages with anisocytosis and anisokaryosis. These cytological features were consistent with an inflammatory etiology, although a neoplastic origin could not be excluded. A presumptive diagnosis of pericardial effusion secondary to pericardial malignancy was made, based on echocardiographic findings. Owing to the poor prognosis, the owner denied further clinical investigation, and the dog was euthanized.

Postmortem examination revealed multiple masses of variable shapes and dimensions attached to both the visceral and parietal pericardium [Figure 2]. A nonulcerating, firm thickening of most of the gastric wall was also noted. The other abdominal viscera were grossly normal. Samples of pericardial sac, gastric wall, and mesenteric lymph nodes were histologically examined. In the pericardium, an extensive proliferation of the mesothelial surface associated with necrosis and infiltration of hemosiderophages was noted. Lymphatics were filled with neoplastic cells that were round in shape and had scarce cytoplasm, large and convoluted nuclei, and prominent multiple nucleoli [Figure 3]. The same cell population infiltrated the connective and muscular layers of the gastric wall and involved the basal layer of the mucosa. In the mesenteric lymph nodes, many neoplastic cells adopted a signet-ring morphology (i.e., tumor cells with eccentric nuclei and distended cytoplasm filled with mucin) typical of gastric and enteric adenocarcinoma.¹⁰ On immunohistochemistry, these cells showed strong vimentin and weak pancytokeratin immunoreactivity, with lack of expression of cell lymphoid markers CD3 and CD79a, used for the identification of T cells and B-lineage cells, respectively.

The final diagnosis was primary gastric adenocarcinoma that had metastasized to the pericardial sac and lymph nodes. The morphological features of the tumor cells, lack of glandular structure of the primary tumor, and immunohistochemistry results were compatible with an anaplastic gastric adenocarcinoma.¹⁰

Discussion

Pericardial diseases account for 1% to 8% of all cardiovascular disorders in dogs, and most affected dogs have pericardial effusion.^4,11 Recognized causes of canine pericardial effusion include peritoneopericardial diaphragmatic hernia, pericardial cysts, infection, trauma, primary cardiac diseases, uremia, neoplasia, and idiopathic disorders.^4–6 Intrapericardial neoplasia, idiopathic hemorrhagic pericarditis, and left atrial rupture secondary to chronic mitral regurgitation are the most common causes of pericardial effusion in the dog.¹² Pericardial tumors are relatively uncommon in dogs, and primary intrapericardial neoplasms occur more frequently than intrapericardial metastases.^1,2 Hemangiosarcoma and chemodectoma are the most common primary intrapericardial tumors causing pericardial effusion in dogs.^1,2,13 Mesothelioma, ectopic thyroid carcinoma, rhabdomyoma, epithelial thymoma, lymphosarcoma, and fibrosarcoma are less common causes.^1,2,13 Hemangiosarcoma and lymphoma are the most frequent canine metastatic intrapericardial tumors, followed by fibrosarcoma and rhabdomyosarcoma.^1,2,13

The in vivo differentiation between neoplastic and non-neoplastic causes of pericardial effusion is often challenging. ¹⁴ Cytopathology of pericardial fluid may not differentiate neoplastic from nonneoplastic etiologies, because many neoplasms (e.g., heart base tumors) do not exfoliate cells easily, and differentiation among reactive mesothelium, malignant mesothelioma, and metastatic adenocarcinoma is a major problem.^1,14–16 Data regarding the overall sensitivity of pericardial fluid cytology for diagnosing the etiology of the effusion are lacking in dogs.^4,14

Diagnostic imaging is particularly useful for diagnosing pericardial effusion associated with cardiac masses.^7,8,12,17 The sensitivity of transthoracic echocardiography for identification of cardiac tumors depends on the dimension, location, and type of neoplasm; different, separate studies show a sensitivity ranging between 16.7% and 91.6% in dogs.^{1,8,15,18–24} Echocardiography is especially good at identifying the most common primary cardiac tumors (i.e., hemangiosarcoma, heart base tumors), but it has low sensitivity for the less common tumors (i.e., mesothelioma and lymphoma).^12,19

Serial echocardiographic examinations using different scan planes from both left- and right-sided locations may be necessary, however, before a mass is correctly identified on the heart.^{1,4,12,22–25} In dogs, three types of lesions are most commonly identified: right atrial masses (e.g., hemangiosarcoma), heart base masses (e.g., chemodectoma), and other masses within the heart or pericardial sac.¹² Large masses are relatively easy to image, but small ones may be difficult to find or distinguish from normal structures, such as pericardial or periaortic fat.⁴ Furthermore, thrombi, abscesses, granulomas, pericardial cysts, blood clots, and cystic hematomas within the pericardial space can be incorrectly diagnosed as tumor, although these conditions are rare.^4–6 The multiple small masses observed in the dog described here protruded from both pericardial surfaces and demonstrated an oscillatory motion during the cardiac cycle. Their ultrasonographic features (i.e., round shape, clearly distinguishable margins, and homogeneously echoic texture) suggested a neoplastic etiology.^1,7,12,17

Other diagnostic imaging techniques have been proposed for the detection and morphological evaluation of cardiac masses and pericardial disorders in humans, namely transesophageal echocardiography and magnetic resonance imaging.^26,27 No description of transesophageal echocardiographic or magnetic resonance imaging diagnosis of pericardial tumors has been reported to date in dogs, and neither was performed in the present case.

The dog reported here had clinical and radiographic signs of pericardial effusion. A large volume of pericardial fluid was identified by echocardiography, and multiple echogenic masses were attached and visible on both pericardial layers. Although other disease processes were considered as causes of pericardial effusion (i.e., thrombi, abscesses, granulomas, cystic masses, and blood clots), malignancy was considered the most likely based on the ultrasonographic appearance of the masses. Results of cytological evaluation of pericardial fluid were suggestive of idiopathic hemorrhagic pericardial effusion, since inflammatory cells predominated in the specimen, and necropsy with histopathology was required to confirm the diagnosis.

Conclusion

Multiple echogenic masses adherent to both pericardial membranes were diagnosed in a 6-year-old dog with pericardial effusion, and they were suggestive of a neoplasm; however, pericardial cytology suggested a non-neoplastic etiology. Pathological findings confirmed the presence of metastatic pericardial gastric adenocarcinoma. Further studies with a larger number of cases are warranted to determine the sensitivity of pericardial fluid cytology for diagnosing the etiology of pericardial effusion in dogs.

Acknowledgments

We are grateful to Professor P.S. Marcato (Department of Veterinary Public Health Animal Pathology, University of Bologna) and Professor G.N. Martinelli (Clinical Department of Radiological and Histocytopathological Sciences, University of Bologna) for valuable comments and helpful discussion about histological interpretation.