Intracardiac Mass in a Man Infected With Human Immunodeficiency Virus

A 36-year-old man was admitted to the hospital with complaints of a 2-week history of chest pain and worsening shortness of breath. He had long-standing human immunodeficiency virus (HIV) disease with a recent CD4 count of 351 cells/μL and a viral load of 242 214 copies/mL, but was not receiving antiretroviral therapy. The patient had a remote history of cutaneous Kaposi sarcoma, but otherwise denied any current acquired immunodeficiency syndrome–defining illnesses. A screening transthoracic echocardiogram demonstrated an echo-dense mass emanating from the interatrial septum. Transesophageal echocardiography confirmed the presence of a large echo-dense mass involving the interatrial septum and protruding into the right atrium (Figure 1, arrow; AV indicates aortic valve; RA, right atrium).On surgical exploration, the mass involved the interatrial septum and was adherent to the posterior wall of the right atrium and entered the superior vena cava. The tumor was debulked and presented to pathology for histologic evaluation. The fragmented mass measured 5.5 × 1.8 × 1.2 cm and had a soft, tan appearance. Microscopic examination showed anastomosing vascular channels composed of pleomorphic and hyperchromatic spindle cells (Figure 2). Mitotic figures were easily identified. In addition, destruction of myocardium by the invasive spindle cells was observed.What is your diagnosis?When faced with a tumor involving the myocardium it should be noted that secondary (or metastatic) tumors are 20 to 40 times more frequent than primary tumors, and that benign tumors are 3 times more likely to occur than malignant tumors.1–3 In our case, the poorly differentiated appearance of the tumor cells obviously places the tumor into a malignant category. Angiosarcomas as a group are extremely rare, representing less than 2% of all soft tissue sarcomas.4 However, angiosarcomas are the most frequent primary malignancy of the heart.5Clinically, cardiac angiosarcomas occur in middle-aged men and present with cough, syncope, or dyspnea, similar to the symptoms reported by our patient.4–6 They are most commonly found in the right atrium, but frequently extend into the pericardium, vena cava, or tricuspid valve, occasionally leading to tamponade and/or obstruction to cardiac venous return. Metastases are common at the time of diagnosis and have a reported incidence of up to 89%. The most common sites of metastases are the lung and liver.6 Most patients die within a few months after the onset of symptoms.56The histologic appearance of angiosarcomas can vary greatly, depending on the level of differentiation. However, by definition, the tumor cells must show some evidence, either at the light microscopic level or via immunohistochemistry, of vascular differentiation. There are 3 main patterns of growth, including a spindle cell pattern, an angiomatous pattern, or an undifferentiated or solid pattern. This case is demonstrative of a spindle cell pattern. Poorly differentiated tumors show pleomorphic and hyperchromatic spindle-shaped cells with abundant mitotic activity. The vascular channels formed in angiosarcomas often anastomose, forming dilated sinusoids. A reticulin stain may be of value in delineating these channels and showing the tumor cells lying within the luminal side of the vessels.The most specific endothelial cell marker used for the diagnosis of angiosarcoma is CD31 (Figure 3). The platelet-endothelial adhesion molecule (CD31) is nonreactive in nonvascular soft tissue tumors and is invaluable in the diagnosis of angiosarcomas. CD34 is also expressed by most angiosarcomas, but may be positive in epithelioid sarcomas as well. Factor VIII is often used to highlight cells of vascular differentiation, but fewer than 1 in 4 angiosarcomas will be immunoreactive for this antigen. Thrombomodulin immunostaining is usually positive in angiosarcomas, but can also be positive in trophoblastic tumors and some carcinomas.7The differential diagnosis of cardiac angiosarcomas varies, depending on the level of differentiation. Included in the differential diagnosis is Kaposi sarcoma, hemangioma, hemangioendothelioma, pyogenic granuloma, malignant melanoma, and papillary endothelial hyperplasia. Well-differentiated tumors may resemble hemangioendothelioma with distinct vascular channels lined by flattened endothelial cells, while angiosarcoma tends to form anastomosing channels and dilated sinusoids. Poorly differentiated angiosarcomas, including the spindle cell or undifferentiated pattern, may resemble other spindle cell sarcomas, such as malignant fibrous histiocytomas and fibrosarcoma.78 The diffuse positivity of CD31; negativity for CD45, cytokeratin, and S100; the poorly differentiated morphology; and myocardial invasion helped confirm the diagnosis of poorly differentiated angiosarcoma.Initially, the patient's HIV status and remote history of cutaneous Kaposi sarcoma led to a high clinical suggestion of Kaposi sarcoma. However, the preserved CD4 count and lack of systemic involvement argued against this diagnosis.8 Also, in Kaposi sarcoma of the heart, clinical symptoms are usually not prominent. Histologically, the infiltrative nature of this tumor, the architectural pattern, and the degree of cellular pleomorphism were inconsistent with Kaposi sarcoma, which tends to be small and primarily epicardial in location, with minimal myocardial infiltration. Although Kaposi sarcoma of the skin in patients with acquired immunodeficiency syndrome is common, cardiac involvement is uncommon, occurring in only about 5% of autopsied patients. Rarely is the heart the only site of involvement.8 To our knowledge, there is no increased incidence of cardiac angiosarcomas in HIV-positive patients.In summary, our patient presented with an invasive right atrial tumor consistent with poorly differentiated angiosarcoma. We initially suspected Kaposi sarcoma, given the patient's HIV status and remote history of cutaneous Kaposi sarcoma. Histologically, however, the tumor was highly aggressive and showed marked myocardial invasion, a common histologic feature of cardiac angiosarcomas but exceedingly rare in Kaposi sarcoma. Despite surgical resection and chemotherapy, the patient's condition deteriorated during the next month and he died of inanition and cardiac failure.