Primary Cardiac Angiosarcoma

Abstract

This is a report of a primary cardiac angiosarcoma in a woman who, several years earlier, had undergone repair of an aortic dissection with a Dacron graft prosthesis. Dacron prostheses have rarely been associated with neoplasia, and this, to our knowledge, is the first reported case of primary cardiac angiosarcoma in association with Dacron. Our patient presented with extensive metastases. If tumors are localized, they can be treated successfully with a combination of surgical resection, chemotherapy, and radiotherapy. Cardiac transplantation can also be beneficial, but the overall prognosis remains poor.

We describe a case of primary cardiac angiosarcoma that developed in a woman who had undergone an aortic dissection repair with a Dacron graft prosthesis 9 years earlier. Dacron prostheses have rarely been associated with neoplasia, and no causal relationship has been established. This, to our knowledge, is the first reported case of primary cardiac angiosarcoma in association with a Dacron aortic prosthesis. We illustrate the clinical presentation, diagnosis, and management of this rare cardiac malignancy.

Case Report

In February 2009, a 60-year-old woman presented with worsening shortness of breath and upper-back pain of 1 month's duration. She had also experienced fatigue and a 15-lb weight loss over the preceding month. She denied chest pain, orthopnea, or lower-extremity swelling. She was afebrile, without chills or night sweats.

Her medical history was significant for spontaneous dissection of the aortic root, ascending aorta, and aortic arch, which had been repaired 9 years earlier with a Dacron graft (Hemashield® vascular graft, Boston Scientific Corporation; Natick, Mass). She also had a history of hypertension, hypothyroidism, and osteopenia. She had systemic lupus erythematosus, complicated by lupus nephritis (this had been in remission for more than 10 years). Her medications included metoprolol, amlodipine, losartan, hydroxychloroquine, and levothyroxine. Her family history was positive for thoracic aortic dissection and intracranial hemorrhage, but negative for carcinoma. She had a 15 pack-year cigarette-smoking history but had quit using tobacco products 13 years before and denied any alcohol or narcotic use.

On presentation, she had a temperature of 97.5 °F, a pulse of 92 beats/min, a blood pressure of 130/70 mmHg, and a respiratory rate of 16 breaths/min. Auscultation revealed a few rales at the lung bases bilaterally and distant—but regular—heart sounds, without murmurs, gallops, or rubs. Her extremities showed trace periankle edema, and the peripheral pulses in both upper and lower extremities were equal and normal.

Portable chest radiography revealed numerous bilateral pulmonary nodules that raised suspicions of metastatic disease. Transthoracic echocardiography (Fig. 1) showed a large (>5 cm) echodensity within the right atrium, involving the interatrial septum. A large circumferential pericardial effusion, without echocardiographic evidence of cardiac tamponade, was also noted. Computed tomography of the chest and abdomen with radiocontrast medium revealed a large heterogeneous right atrial mass, measuring 7.5 cm in diameter. Multiple pulmonary nodules—as well as right hepatic, left renal, and adrenal lesions that were suspected for metastases—were detected. A burst fracture of the 7th thoracic vertebral body was noted, with associated spinal canal stenosis. An unchanged Stanford type B aortic dissection was seen to originate distal to the origin of the left subclavian artery and to involve the entire descending aorta and abdominal aorta. There was anatomic proximity of the previously placed Dacron prosthetic graft to the atrial mass (Fig. 2). Biopsy of the right hepatic lesion under computed tomographic guidance yielded histologic evidence of a malignant vascular tumor consistent with primary cardiac angiosarcoma (Fig. 3).

Fig. 1 Transthoracic echocardiography shows a large right atrial mass (arrow) that involves the interatrial septum: A ) apical 4-chamber and B ) subxiphoid views.

Fig. 2 Computed tomography of the chest with radiocontrast medium shows a right atrial mass (arrow): A ) axial and B ) coronal planes.

Fig. 3 Photomicrographs of lesion show A ) malignant vascular tissue (arrow) (H & E, orig. ×40), and B ) infiltrating angiosarcoma (arrow) (immunofluorescence stain for CD31, orig. ×10).

It was our conclusion that the patient had a primary cardiac angiosarcoma with extensive multiorgan metastases and consequent pathologic thoracic vertebral fracture. Her chronic aortic dissections and the aortic prosthetic graft were stable.

She was started on paclitaxel chemotherapy. In addition, she underwent 6 sessions of radiation therapy to her thoracic spine. Her clinical condition remained stable for 2 weeks but deteriorated thereafter, characterized by worsening fatigue and back pain. She chose to discontinue chemo- and radiotherapy in favor of hospice care. She died 1 week later.

Discussion

Cardiac tumors are uncommon, and a large majority of them (30 times as many) are secondary. Among primary cardiac tumors, malignant lesions constitute 25%. Hence primary malignant tumors of the heart are extremely rare.^1,2

Clinical Presentation

Patients with primary cardiac malignancies present with a triad of symptoms: constitutional symptoms, symptoms arising from embolic phenomena, and symptoms arising from direct cardiac invasion or mass effect.³ Constitutional symptoms are likely to be secondary to inflammatory cytokine release from tumor cells, which results in fever, malaise, and cachexia. Inflammatory markers, such as sedimentation rate and C-reactive protein, are elevated. Embolic phenomena, depending on the location of the tumor and the presence of interatrial shunts, can manifest as pulmonary emboli, with progression to cor pulmonale, or as visceral infarction—including transient ischemic attack, cerebrovascular accident, myocardial infarction, and limb ischemia.³ Cardiac tumors can also cause arrhythmias and conduction disturbances, obstruction of blood flow through the ventricular outflow tracts or atrioventricular valves, and impaired cardiac relaxation. The physical examination might show evidence of pulmonary venous congestion and low cardiac output with a split 2nd heart sound and a 4th heart sound. In atrial myxoma, a “tumor plop” might be audible as an early diastolic sound. If significant pulmonary hypertension develops, clubbing, polycythemia, and hypoxia may develop.³

Diagnosis

Intracardiac masses are frequently visualized by means of 2-dimensional transthoracic echocardiography.⁴ Contrast echocardiography can be used to evaluate the vascularity of a cardiac mass; benign masses are relatively avascular.⁵ Features favoring a metastatic tumor, rather than a primary cardiac neoplasm, are epicardial location and pericardial involvement. Transesophageal echocardiography⁴ both improves visualization of cardiac anatomic details and increases the sensitivity and specificity of diagnosis. Computed tomographic scanning of the chest is useful in determining the size and extension of the tumor, and the presence of metastases. Cardiac magnetic resonance imaging provides the best information on the size, shape, and composition of cardiac tumors.⁶ Cardiac catheterization can be performed in order to obtain a biopsy sample of the tumor and to establish its blood supply, although diagnostic catheterization involves a substantial risk of tumor embolization.

Primary Cardiac Malignancies in Association with Dacron

Primary malignant cardiac tumors are almost always sarcomas. Angiosarcomas constitute about a third of the cardiac sarcomas and are located in the right atrium in 90% of cases.⁷ Hemorrhagic pericardial effusions can develop as a sequela of this tumor. A familial variety of cardiac angiosarcoma has been described.⁸

A few case reports in the literature describe an association between Dacron graft placement and the subsequent development of primary angiosarcoma.^9–13 Most of the documented cases involve tumor development at the site of graft placement. Foreign material such as Dacron rarely is associated with the development of sarcomas; fibrous histocytoma¹² and fibrosarcoma¹³ are the other malignant neoplasms reported, in addition to angiosarcoma. The induction of sarcoma formation by Dacron is believed to be related to its 3-dimensional polymeric structure and has been well established in animal models.¹⁴ In Dacron, a pore diameter of less than 0.4 μm is believed to increase tumorigenicity.¹³ Other than Dacron, foreign material implanted in the body—such as silicone breast implants, orthopedic implants, and dialysis shunts—is associated (rarely) with primary angiosarcoma.¹⁵

There are 2 reported cases of malignant cardiac tumors (malignant fibrous histiocytoma¹⁶ and cardiac lymphoma¹⁷) associated with a Dacron mitral valve prosthesis (Table I). To the best of our knowledge, ours is the first reported case of a primary cardiac angiosarcoma in a patient with prior implantation of a Dacron aortic prosthesis. Our patient had undergone repair of the aortic root, ascending aorta, and aortic arch with a Dacron graft; the polymeric prosthetic material was in anatomic proximity to the subsequent tumor site. Because we did not have opportunity to conduct an autopsy, histologic continuity of the tumor with the Dacron graft was not established. However, in consideration of the placement of the Dacron prosthesis 9 years before the tumor occurrence, the anatomic proximity of the tumor to the prosthesis, and the association (albeit rare) between angiosarcoma and Dacron in the medical literature, it seems logical to infer that this unusual malignancy in our patient was associated with the Dacron prosthesis. Although a causal relationship has not been established and the percentage of patients with Dacron graft implants who develop this tumor is very small, physicians involved in the care of such patients should be aware of this unusual potential complication.¹³

TABLE I. Reported Cases of Primary Cardiac Tumors in Association with Dacron Prostheses

Management

When the malignant cardiac tumor has been localized, a combined approach to treatment—surgical resection, chemotherapy, and radiotherapy—has been used with reported success.^18–20 Novel chemotherapeutic regimens, guided by immunohistochemical tumor analysis, have also met with some success.²¹ Chemotherapeutic regimens for cardiac angiosarcoma include the use of cyclophosphamide, vincristine, doxorubicin, dacarbazine, and docetaxel, as well as newer agents such as trastuzumab, imatib, and recombinant interleukin-2.^19–21 Unfortunately, like most primary malignant cardiac tumors, cardiac angiosarcomas have a very poor prognosis and are usually unresectable due to the early and extensive involvement of cardiac tissue.²¹

There is no evidence that cardiac tumors associated with Dacron prosthetic material differ in any way, with respect to prognosis or response to treatment, from those without such association. If resection is performed, chemotherapy and radiation therapy may slow tumor progression, without a decrease in the mortality rate.³ Tumor resection is undertaken sometimes as palliation for symptoms of obstruction. Cardiac transplantation can be undertaken in cases of localized cardiac sarcomas, but the data on prolonged survival with this mode of therapy are few.²²

Acknowledgments

The authors thank Dawn Heagley, MD, and Lincoln Wong, MD, for assistance with images.