Extraskeletal Osteosarcoma of the Heart Presenting as Infective Endocarditis

Introduction

Extraskeletal osteosarcomas (EsOSAs) are rare mesenchymal tumors arising in various soft tissues without primary bone involvement. The patient described in this report had a large mass on the posterior mitral valve leaflet and clinical signs compatible with infective endocarditis (IE). Endocarditis was ruled out on postmortem histopathology and culture. Histopathology was consistent with an osteosarcoma (OSA). There have been two reports of dogs with intracardiac OSAs and one report of an intracardiac OSA mimicking IE in human medicine, but to the authors’ knowledge, this is the first report of EsOSA in veterinary medicine.

Case Report

A 7 yr old castrated male Labrador retriever that weighed 35.6 kg was examined because of an acute onset of vomiting. The patient had no prior past medical history. The initial physical examination on presentation revealed that the dog was quiet but alert with a rectal temperature of 103.8°F and a heart rate of 150 beats/min. The remainder of the physical examination was unremarkable. Blood was collected and submitted for a complete blood count (CBC) and biochemistry panel. Thoracic radiographs, taken due to concerns for aspiration pneumonia, revealed a mild left atrial enlargement, a mild perihilar interstitial pattern, and a faint pleural fissure line between the right cranial and right caudal lung lobes. The patient was discharged from the hospital with empirical treatment for the fever (amoxicillin trihydrate/clavulonate potassium^a, 15.8 mg/kg per os q 12 hr).

The next day, the patient returned for evaluation of inappetence and lethargy. Results of the CBC performed the previous evening showed a moderate thrombocytopenia (98,000 cells/μL; reference range, 170×10³–400×10³ cells/μL). The serum biochemical analysis was unremarkable. The physical examination revealed that the patient was dull with a rectal temperature of 103.8°F and a heart rate of 150 beats/min. A repeat CBC showed a mild, toxic neutrophilia (13,345 cells/μL; reference range, 2,060–10,600 cells/μL) with a mild, toxic left shift (471 bands/μL; reference range, 0–300 cells/μL). An accurate platelet count could not be obtained due to clumping. Urinalysis, obtained by cystocentesis, was unremarkable, and culture was pending. Ehrlichia canis and Rocky Mountain spotted fever titers were negative via serology. A Lyme titer was 1:64. Abdominal ultrasound, performed by a board certified internist, revealed no abnormalities. The patient was hospitalized and administered isotonic crystalloids^b with 20 mEq/L potassium chloride^c at a rate of 3.6 mL/kg/hr, enrofloxacin^d (4.7 mg/kg intravenously [IV] q 12 hr), and a metoclopramide^e constant rate infusion (0.04 mg/kg/hr).

On day 3 after initial presentation, the patient's temperature had decreased to 102.4°F, but the patient was more tachycardic (the heart rate was 180 beats/min). Physical examination revealed petechiation on the inner pinnae of both ears and mild effusion of both tarsal joints. Repeat thoracic radiographs revealed severe left atrial enlargement, enlarged pulmonary vessels, a pronounced diffuse interstitial pattern, and a prominent fissure line in the right pleural space consistent with early left-sided heart failure. An echocardiogram was performed by a board certified cardiologist which showed a large 3 cm × 4 cm vegetation on the atrial surface of the posterior mitral valve cusp with a few calcified areas within the mass (Figure 1). Mild mitral regurgitation was noted by color flow Doppler and moderate left atrial enlargement was present. Blood, aseptically collected from the left and right jugular veins 1 hr apart, was negative on both aerobic and anaerobic culture. Arthrocentesis was performed on both carpi and tarsi, and joint cytology revealed marked suppurative inflammation. A coagulation profile revealed mild hyperfibrinogenemia (460 mg/dL; reference range, 150–400 mg/dL), a marked elevation in D-dimer (1,000–2,000 ng/dL; reference range, <250 ng/dL), and a normal prothrombin time and partial thromboplastin time. Congestive heart failure secondary to IE was suspected. The IV fluids were discontinued and the dog was prescribed furosemide^f (2.1 mg/kg IV q 6 hr) and ampicillin^g (14 mg/kg IV q 6 hr) to broaden the antibiotic spectrum. Enrofloxacin (4.7 mg/kg IV q 12 hr) and the metoclopramide constant rate infusion (0.04 mg/kg/hr) were continued.

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On days 4 and 5 after initial presentation, a subcutaneous swelling along the left jugular furrow with overlying bruising was noted (Figure 2). A Grade 2/6 systolic heart murmur was auscultated for the first time since the dog had been originally examined. The heart murmur was consistent with the echocardiogram findings of mild mitral regurgitation. Repeat radiographs revealed persistent cardiomegaly; however, the pulmonary edema and pleural effusion had resolved. Abnormalities on a repeat CBC included a mild, normochromic, normocytic, nonregnerative anemia (the hematocrit was 27%; reference range, 36–60%), an increasing moderate neutrophilia (33,540 cells/μL) with a toxic left shift (2,150 bands/μL), and a moderate monocytosis (3,010 cells/μL; reference range, 0–840 cells/μL). A serum biochemistry panel revealed elevations in blood urea nitrogen (49 mg/dL; reference range, 6–25 mg/dL), creatinine (1.4 mg/dL; reference range, 0.5–1.6 mg/dL), phosphorus (9.3 mg/dL; reference range, 2.5–6.0 mg/dL), amylase (9,100 IU/L), and lipase (2,120 IU/L). The coagulation panel revealed a normal prothrombin time and partial thromboplastin time, hypofibrinogenemia (102 mg/dL), and a markedly increased D-dimer (1,000–2,000 ng/mL). Due to the concern of developing disseminated intravascular coagulation, heparin therapy was initiated (224 IU/kg subcutaneously q 6 hr).

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On day 6, the patient was euthanized due to his poor clinical appearance. A partial cosmetic necropsy was performed and only the heart was obtained. The vegetative mass was firm and irregular, arising from the posterior mitral valve leaflet (Figure 3). Anaerobic and aerobic cultures of the mass were negative. Histopathology revealed a dense population of spindle cells with a high mitotic index embedded in a pale, myxoid matrix with some bone production. These findings were consistent with OSA.

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Discussion

EsOSAs are mesenchymal, osteoid producing neoplasias without primary bone involvement. EsOSAs are rare tumors, representing less than 1% of soft tissue sarcomas and only 12.6% of all OSAs.^1,2 Previous EsOSAs reported in dogs have been identified in the mammary gland, genitourinary tract, spleen, gastrointestinal tract, respiratory tract, liver, muscle, eye , thyroid gland, adrenal gland, salivary gland, meninges, and the heart.^2–16 Although a primary osseous lesion located in the skeleton was never ruled out in this case because a full necropsy was not performed, there was no evidence of additional neoplasia noted on either the physical examinations or diagnostic imaging. As such, it is likely that this intracardiac tumor was a primary EsOSA; however, metastatic disease still remains a possibility.

In a retrospective study of 169 dogs with EsOSA, the median age of patients diagnosed with soft tissue OSAs was 9.7 yr with no sex predilection.² Rottweilers and beagles were overrepresented breeds. The most common clinical signs of EsOSAs included depression or lethargy, abdominal distension, difficulty breathing, pyrexia, and gastrointestinal signs such as anorexia and vomiting. These clinical signs varied widely based on the location of the primary tumor.² In human medicine, there are multiple reports of EsOSAs causing heart failure and recurrent peripheral arterial emboli.^17–20

The most common clinical signs of intracardiac neoplasia in dogs include pericardial effusion with cardiac tamponade and right heart failure.²¹ Hemangiosarcoma of the right atrium and chemodecoma and ectopic thyroid carcinoma at the heart base are the most common intracardiac tumors reported in dogs.²¹ Specifically, two cases of intracardiac OSAs of dogs have been reported: one originating in the left atrium causing congestive heart failure and another in the right atrium resulting in bicavitary effusion and hepatic congestion.^15,22

The patient described in this report had unusual clinical signs for cardiac neoplasia that closely resembled signs of endocarditis. The patient met the criteria for possible IE (i.e., being a large dog weighing >15 kg with a fever) and had supporting evidence of embolic and immunologic disease.²² Sykes et al. (2006) reported that 53% of dogs with endocarditis developed lameness from immune-mediated polyarthritis, septic arthritis, or peripheral arterial embolism, and 44% had evidence of suspicious thromboembolic disease.²³ The patient described herein developed presumptive immune-mediated polyarthritis based on the suppurative joint cytology. The ventral cervical swelling may have been due to an embolic event, although immune-mediated vasculitis, heart failure, an obstructive primary or metastatic neoplasm, and hematoma were also differentials. The increases in blood urea nitrogen, creatinine, and phosphorus were suspected to be due to renal ischemic damage from thromboembolic disease. Other differentials for these abnormalities included prerenal azotemia secondary to furosemide administration and glomerulonephritis leading to acute renal failure or tubular damage.

There is one report in human medicine involving a metastatic osteogenic sarcoma in the left atrial cavity presenting as IE.²⁴ IE was suspected due to a positive blood culture; however, upon necropsy, a necrotic sinus track extending from the tumor to the esophagus was noted, which led to subsequent septicemia. The dog described in this report had an intracardiac neoplasm that also closely resembled IE, but ultimately congestive heart failure, thromboembolic disease from tumor emboli, and disseminated intravascular coagulation were attributed to the intracardiac tumor. In any patient with signs of endocarditis, the possibility of intracardiac neoplasia should be considered.

Due to the low number of case reports of dogs with primary cardiac tumors, treatment options and prognosis remain unknown. In human medicine, standard treatment of EsOSA of the heart involves surgical resection and adjuvant chemotherapy. The reported survival time is 1 yr.²⁵ In general, the median survival time for soft tissue OSAs in dogs is 25 days, with the major cause of death being local recurrence.²

Conclusion

EsOSAs are rare, mesenchymal neoplasias without primary bone involvement. Two cases of intracardiac EsOSAs of dogs have been reported, both associated with clinical signs of heart failure. The patient described in this report had unusual clinical signs for cardiac neoplasia that closely resembled signs of endocarditis, including fever, immunologic, and thromboembolic complications. In any patient with signs of endocarditis, the possibility of intracardiac neoplasia should be considered. More studies are needed to investigate treatment options and the prognosis for dogs with intracardiac neoplasia because only a small number of cases of dogs with primary cardiac tumors have been reported.