Osteosarcoma Tumor Thrombus

Abstract

Tumor thrombus arising from osteosarcoma is rare. We report the case of a 20-year-old man with proximal humerus osteosarcoma, accompanied by an extensive intravascular tumor thrombus extending into the heart. Our review of the literature found 14 previous reports on osteosarcoma with tumor thrombus. The combination of positron emission tomography and computed tomography is very useful in differentiating tumor thrombus from vascular thrombus, thereby avoiding unnecessary anticoagulation therapy. This same imaging combination can also be used to evaluate the response to treatment. Surgical resection of the tumor thrombus is highly recommended. The effect of tumor thrombus on survival is still unknown.

Osteosarcoma, the most common malignant tumor of bone, arises from primitive mesenchymal cells. Osteosarcoma tumor thrombus occurs very rarely.¹ The rationale behind this case report and literature review is to discuss how a finding of tumor thrombus might affect approaches to diagnosis and management.

Case Report

A 20-year-old man presented at an emergency department with left-shoulder pain. Plain radiography revealed an extensive permeative pattern of bone destruction involving the humeral head and diaphysis, with osteosarcoma as a primary consideration in the differential diagnosis. Ultrasonography revealed an apparent deep venous thrombosis in the left subclavian vein, brachiocephalic vein, and superior vena cava. A computed tomographic (CT) scan confirmed a proximal humerus bone lesion with soft-tissue extension into the subcutaneous tissues and chest-wall musculature. Enlarged nodes were present in the axilla, and indeterminate nodules suspect for pulmonary metastasis were noted. Right atrial and ventricular clots could not be specifically identified. A radionucleotide bone scan was negative for skeletal metastasis. A CT-guided needle biopsy of the primary tumor was performed, and the pathologic interpretation was consistent with high-grade chondroblastic osteosarcoma. The patient was started on anticoagulation therapy.

During his admission for scheduled neoadjuvant chemotherapy, a gallop was detected on chest auscultation. Cardiac echocardiography performed before initiating chemotherapy revealed mild tricuspid regurgitation and an apparently large thrombus in the right atrium, superior vena cava, and brachiocephalic vein. A CT angiogram of the chest confirmed a filling defect within the superior vena cava that extended into the right side of the heart (Fig. 1). Subsequent transthoracic echocardiograms 2 and 7 weeks later showed progression of the thrombus with extension through the tricuspid valve to within 0.5 cm of the pulmonary valve, despite anticoagulative therapy and chemotherapy (Fig. 2). A cardiothoracic surgeon removed the clot on cardiopulmonary bypass via median sternotomy. The surgeon reported that the thrombus emanated from the brachiocephalic vein, extended through the tricuspid valve, and could be resected only up to the orifice of the brachiocephalic vein. The histopathologic report identified the thrombus as a neoplasm consistent with chondroblastic osteosarcoma (Fig. 3). Anticoagulation was discontinued. Two months later, the patient was reevaluated and underwent a palliative forequarter amputation, because limb salvage was not possible due to the extent of the disease. The suspected remaining tumor thrombus was pulled out of the brachiocephalic vein. Pathologic evaluation of the primary tumor and the associated tumor thrombus confirmed high-grade chondroblastic osteosarcoma, with 44% tumor necrosis (Fig. 4).

Fig. 1 Computed tomographic angiogram (coronal view) of the chest reveals a filling defect (arrows) within the superior vena cava, extending into the right atrium.

Fig. 2 Transthoracic echocardiogram reveals a right atrial mass (arrows) consistent with thrombus that extends through the tricuspid valve into the right ventricle, ending up less than 0.5 cm from the pulmonary valve.

RA = right atrium; RV = right ventricle; TV = tricuspid valve

Fig. 3 Photomicrograph of the superior vena cava and right atrial tumor thrombus shows lacelike osteoid deposits intermingled with chondroid areas (H&E, orig. ×40).

Fig. 4 Histologic examination of the osteosarcoma from the primary site (left humerus) shows clusters of malignant cells with prominent nucleoli and a moderate amount of cytoplasm (Papanicolaou stain, cytologic preparation, orig. ×10).

Subsequent echocardiograms were normal. A postoperative positron emission tomographic/computed tomographic (PET/CT) scan did not show residual tumor thrombus. At the time of submission of this case report, our patient was undergoing chemotherapy and had survived for more than 19 months after tumor thrombus removal in May 2010. Subsequently, in September 2012, he developed progression of the tumor with recurrent tumor thrombus and metastatic lung nodules. That thrombus was also removed, and the patient is undergoing palliative chemotherapy.

Discussion

A review of the literature revealed 14 cases of tumor thrombus that arose from osteosarcoma, the earliest reported in 1957 and the latest in 2007 (Table I).^2–15 Of the 14 cases, only 2 described osteosarcoma of the humerus with a distal tumor thrombus.^2,9 Ours is the only report of a proximal humerus osteosarcoma with extensive direct intravascular extension of a tumor thrombus from the primary site to the heart.

TABLE I. Comparison of Case Reports on the Basis of Patient, Tumor, and Tumor Thrombus Variables

The diagnosis of tumor thrombus is generally an incidental finding during staging of the disease. An early clinical sign of S₃ or a “plop” during cardiac auscultation must be promptly investigated, because it arouses high suspicion of intracardiac tumor thrombus.¹⁵ The earliest case report, by Laurain in 1957,² described tumor thrombus as a retrospective diagnosis upon autopsy. In the 1970s, venography was used to diagnose tumor thrombus. Surgical resection of the primary tumor invading the adjacent vasculature also confirmed tumor thrombus.^3,4 In the 1990s, CT, magnetic resonance imaging, and ultrasonography became popular imaging techniques, although they did not definitively differentiate between vascular and tumor thrombi.⁶ Our literature review revealed that, most recently, fluorodeoxyglucose (FDG)-PET scanning has led to the accurate diagnosis of FDG-avid tumor thrombus arising from solid tumors, and that fused CT and PET images can accurately delineate all the blood vessels involved.¹⁶ This current imaging technique, although costly, can prove very beneficial because it can differentiate between vascular and tumor thrombus and in this manner avoid anticoagulation. In our patient, a PET scan was not used initially to identify the extensive tumor thrombus. Rather, PET scanning was performed sequentially after adjuvant chemotherapy to evaluate residual tumor thrombus in the deep vessels.

Surgical resection of the intravascular/intracardiac tumor thrombus seems to be the preferred method of management. It is important to urgently remove the intracardiac tumor thrombus in order to prevent pulmonary embolism.⁹ As in many cases, cardiopulmonary bypass was used in our patient to resect all of the intracardiac and superior vena caval tumor thrombus. The application of deep hypothermia and circulatory arrest, before surgical resection of the tumor thrombus, has also met with success.¹²

The 5-year survival rate for pediatric osteosarcoma is better than 60%.¹⁷ The prognostic factors for poor survival of osteosarcoma are vascular invasion, metastatic disease, poor response to chemotherapy, and local recurrence.^1,3,18 In a case of osteosarcoma with intravascular tumor thrombus (as in our patient), the prospect of survival is poor. On the basis of the few survival data available from the reported cases, it appears that such patients generally do not survive for more than 12 or 13 months.

Conclusion

Osteosarcoma with an extensive tumor thrombus is very rare. This presentation shows aggressive features and the late stage of the disease. When there is reason for suspicion, we suggest using Doppler ultrasonography of the extremity in order to discover the extent of thrombus, and then using PET/CT scanning to differentiate vascular from tumor thrombus. Neoadjuvant chemotherapy with urgent surgical resection of the tumor thrombus might be the best approach to prevent pulmonary embolism and sudden death.⁷ Successful management of these complex cases relies on a careful, multidisciplinary approach coordinated by the oncology team. Further investigation is needed to determine whether the survival rate increases after surgical management of the tumor thrombus.

Acknowledgments

We extend special thanks to the University of Mississippi Medical Center staff: Dr. Charles Gaymes, pediatric cardiologist, for contributing the echocardiogram and Dr. Ronald Gray, radiologist, for recommending reproduction of the computed tomographic angiogram for the manuscript.