Introduction

Pericardial effusion is the abnormal accumulation of fluid in the pericardial sac. Hemorrhagic pericardial effusion is most commonly classified as idiopathic.^1–4 However, it can result from trauma, neoplasia, coagulopathy, anticoagulant intoxication, or rupture of the left atrium secondary to mitral valve disease.^5–9 Neoplasia of the heart, heart base, or pericardium is considered to be the second most common cause of hemorrhagic pericardial effusion.^10–13 Hemangiosarcoma remains the most common cardiac tumor in dogs, followed by aortic body tumors (chemodectoma, lymphoma, and ectopic thyroid carcinoma).¹⁴ Pericardial tumors in dogs are rare and include mesothelioma and chondrosarcoma.^15–17 Pericardial hemangiosarcoma has not previously been reported in the published literature.

Hemangiosarcomas originate from the vascular endothelium. They have a high metastatic rate; thus, adjuvant chemotherapy is recommended to improve survival times in dogs.¹⁸ The most common surgical procedures performed for pericardial tumors are a subtotal pericardiectomy or a pericardial window to allow for drainage of the pericardial sac and procurement of a pericardial biopsy.¹⁹ The present study reports the clinical and pathological findings in a dog diagnosed with primary pericardial hemangiosarcoma.

Case Report

A 10 yr old 4.7 kg (10.6 lb) spayed female papillon was evaluated for a 4-day history of inappetence and an acute onset of lethargy and labored breathing. Initial diagnostic workup by the primary veterinarian included a complete blood count (CBC), biochemistry profile, three-view thoracic radiographs, and an electrocardiogram. Clinicopathologic abnormalities included a mild polycythemia (hematocrit 57.63%; reference range, 37–55%), mild lymphopenia (0.49 × 10⁹; reference range, 1–4.8 × 10⁹), mild hyperglycemia (114 mg/dL; reference range, 60–110), and a mildly decreased total protein (5.1 g/dL; reference range, 5.4–8.2). Thoracic radiographs revealed a subjectively enlarged cardiac silhouette, pleural effusion, and a diffuse bronchointerstitial pulmonary pattern. There was no evidence of pulmonary metastatic disease. A normal sinus rhythm was noted on electrocardiogram. The dog was referred to a specialty hospital.

On presentation, the dog was 5% dehydrated (minimal loss of skin turgor with semidry mucous membranes), tachypneic (respiratory rate of 88 breaths/min; 18–35 breaths/min), and mildly tachycardic (heart rate of 160 beats/min; 70–120 beats/min). Cardiac auscultation revealed muffled heart sounds. The dog was sedated with butorphanol (0.2 mg/kg [0.097 mg/lb], IV) and diazepam (0.2 mg/kg [0.097 mg/lb], IV). Pericardiocentesis was performed, and approximately 100 mL of hemorrhagic fluid was removed. The dog’s heart rate, respiratory rate, and respiratory effort improved immediately following the pericardiocentesis. Pericardial fluid was submitted for cytologic analysis. The pericardial fluid consisted of peripheral blood. There was no evidence of neoplasia. Echocardiogram following pericardiocentesis revealed a mild, generalized volume of pericardial effusion and no evidence of right atrial tamponade or a cardiac-associated mass. There was mild left atrial enlargement based on the left atrial-to-aortic root diameter ratio (ratio of 1.6:1.0; normal <1.6) and atrioventricular myxomatous valvular degeneration with associated mitral and tricuspid insufficiencies. Abdominal ultrasound revealed bilateral nephroliths. Complete blood count, biochemistry, and coagulation panel were within normal limits. A heartworm test was performed, the result of which was negative. Idiopathic pericardial effusion was suspected. The dog was hospitalized, and medical management was initiated. The dog continued to produce large amounts of pericardial effusion requiring repeat pericardiocentesis 2 days following the initial pericardiocentesis. Because additional pericardiocentesis was needed to resolve clinical signs, exploratory thoracotomy, palliative subtotal pericardiectomy, and biopsy of the pericardium was recommended. Preoperative and postoperative packed cell volume was 36 and 32% (35–57%), respectively.

A right fifth intercostal thoracotomy and subtotal pericardiectomy was performed. Approximately 80 mL of hemorrhagic pericardial fluid was evacuated from the pericardial sac. The pericardial tissue was diffusely mildly thickened. No gross cardiac, pulmonary, or thoracic cavity masses were evident. There was no gross evidence of lymph node involvement. A thoracostomy tube was placed and the thorax was closed routinely. The resected pericardial tissue was submitted for histopathology. Postoperative thoracic radiographs revealed appropriate placement of the thoracostomy tube, right pulmonary atelectasis, and a minimum volume of pleural effusion. Surgery and anesthesia were uneventful. The dog recovered well, and the thoracostomy tube was removed the following day. The dog was discharged from the hospital 2 days following surgery.

Histopathology results of the pericardium revealed areas of atypical spindle cells with fairly high mitotic activity forming irregular and disorderly blood-filled spaces and clefts. The nature, pattern, and distribution of the atypical spindle cells were consistent with hemangiosarcoma. The final histopathological interpretation was pericardial hemangiosarcoma.

The dog was referred to the oncology department for discussion of chemotherapy options. Chemotherapy commenced 12 days following surgery at the time of suture removal. A baseline CBC and three-view thoracic radiographs were performed. The CBC results were within normal limits. Thoracic radiographs revealed a small volume of pleural effusion and a mild, generalized, unstructured interstitial pulmonary pattern. Portions of the interstitial pattern had a more patchy appearance with a questionable structured interstitial pulmonary pattern. The structured interstitial pulmonary pattern was suspicious for metastatic disease. Follow-up thoracic radiographs were recommended in 3 wk. The dog was premedicated with maropitant citrate^a (1 mg/kg, subcutaneous), diphenhydramine (2 mg/kg, intramuscular), and dexamethasone SP (0.14 mg/kg, IV) prior to administering the doxorubicin (30 mg/m², IV, every 3 wk, for a total of five doses).

Chemotherapy administration was uneventful. Maropitant citrate (3.4 mg/kg [1.6 mg/lb], per os, q 24 hr) for nausea and metronidazole (13 mg/kg [6.1 mg/lb], per os, q 12 hr) for soft stool was dispensed for the patient. The next follow-up appointment for a repeat CBC, three-view thoracic radiographs, and the second doxorubicin injection was scheduled for 3 wk later.

Six days following the initiation of chemotherapy, the dog presented to the emergency hospital for lethargy and difficulty breathing. Upon presentation, the dog was tachypneic and cyanotic. The owners elected euthanasia of the dog at the time because of a declining quality of life. A necropsy was not performed.

Discussion

Hemangiosarcoma remains the most common cardiac tumor in dogs (69%), followed by aortic body tumors including chemodectoma (8%), lymphoma (4%), and ectopic thyroid carcinoma (1%).¹⁴ Dogs with pericardial effusion that were evaluated for cardiac tumors revealed hemangiosarcoma (55%) to be the most common histopathologic diagnosis, followed by mesothelioma (23%), chemodectoma (14%), ectopic thyroid carcinoma (9%), and lymphosarcoma (5%).²⁰Additional, but rare, reported cardiac tumors in dogs include rhabdomyosarcoma, rhabdomyoma, neurofibrosarcoma, adenocarcinoma, fibrosarcoma, paragliomas, chondrosarcoma, thyroid adenoma, melanoma, mast cell tumor, blastoma, granular cell tumor, myxoma, myxosarcoma, mesenchymoma, undifferentiated sarcoma, leiomyoma, leiomyosarcoma, osteosarcoma, peripheral nerve sheath tumor, hamartoma, and lipoma.^14,19–56 Primary pericardial tumors are rare in both humans and animals. In humans, reported primary pericardial tumors include mesothelioma, angiosarcoma, undifferentiated sarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma, synovial cell sarcoma, lipoblastoma, lipoma, pericardial cyst, paraganglioma, germ cell tumor, hemangioma, fibroma, lymphoma, primitive neuroectodermal tumor, and inflammatory pseudotumor.^57,58 In dogs, pericardial mesothelioma and chondrosarcoma have been reported.^15–18

Primary pericardial hemangiosarcoma has yet to be reported in either species. Although a shortened survival time did not allow for long-term evaluation of the dog in this case report, this case is clinically important in describing a novel neoplasia of the pericardium and should be included as a differential for pericardial effusion.

Reported clinical signs consistent with cardiac hemangiosarcoma or pericardial mesothelioma are usually secondary to pericardial effusion and include muffled heart sounds, tachycardia, pale mucous membranes, weak femoral pulses, ascites, exercise intolerance, and labored breathing.^19,61 Echocardiography and/or advanced imaging should be performed to evaluate for the presence of a cardiac tumor and/or other cardiac abnormalities. Echocardiography has been shown to be moderately accurate when determining tumor location.⁶²

A sample of pericardial effusion should be collected for analysis. However, it has been shown that the diagnostic utility of cytologic analysis of canine pericardial effusion is variable and the diagnostic yield is greater when the hematocrit of the effusion sample is <10%.⁶³ Definitive diagnosis of tumor type is by histopathology, which can be obtained by surgical incisional biopsy or excisional biopsy of the mass. Pericardial window, subtotal pericardiectomy, or total pericardiectomy is commonly performed to relieve clinical signs of cardiac tamponade. In the dog described in this report, subtotal pericardiectomy was successful for treating the clinical signs. The dog had an uneventful recovery from surgery and was clinically normal the day following surgery.

Adjuvant chemotherapy is recommended in patients diagnosed with hemangiosarcoma because of the high metastatic rate. Protocols involving doxorubicin have been reported to have moderate efficacy, whereas protocols that do not include doxorubicin have been shown to have limited to no efficacy in dogs with hemangiosarcoma.⁶⁴ The dog in this report survived 18 days from the time of diagnosis and only received one dose of doxorubicin. Thus, the efficacy of chemotherapy on pericardial hemangiosarcoma cannot be commented on. In the few cases of human pericardial angiosarcoma, pericardiectomy, radiation therapy, and chemotherapy have been recommended to improve mean survival time; however, standard treatment guidelines currently do not exist.^59,60

Conclusion

To our knowledge, this is the first published report of primary pericardial hemangiosarcoma. Clinical signs developed in this dog secondary to the accumulation of pericardial effusion. Because this is the first report of hemangiosarcoma involving the pericardium, treatment protocols have not been established. Treatment for this dog was extrapolated from that used for cardiac hemangiosarcoma and pericardial mesothelioma and angiosarcoma and included surgery and chemotherapy. Subtotal pericardiectomy was performed to resolve the signs secondary to the accumulation of pericardial effusion and for procurement of a biopsy sample. Chemotherapy included doxorubicin administered intravenously. This dog had a short survival time of 18 days and likely succumbed to metastatic disease.