Cardiac angiosarcoma in acute pericardial tamponade with hemoptysis: A case report

Abstract

Primary cardiac angiosarcoma is a relatively rare tumor that frequently metastasizes by the time of diagnosis, with a poor prognosis. Currently, there is no uniform treatment, with surgical resection, radiotherapy, and chemotherapy being the mainstays of treatment. We report the case of a man in his early 30s who presented to the emergency department with hemoptysis and was found to have massive pericardial effusion and right atrial occupancy upon investigation. Subsequent examination revealed hypermetabolic foci in the lungs and femur, and a final biopsy confirmed the presence of a primary cardiac angiosarcoma. The patient died 3 days after diagnosis due to cardiopulmonary failure, with a survival period of 4 months from symptom onset to death. This report describes one of the few cases of cardiac tumor with respiratory symptoms.

Introduction

Primary cardiac tumor is a rare disease with an incidence of 1.38/100,000 people. ¹ In adults, approximately one-fourth of primary cardiac tumors are malignant, with primary cardiac angiosarcoma being the most common histologic subtype, originating from the endothelial cells of the cardiac vasculature, most commonly in the right atrium.^1,2 The absence of specific signs and symptoms makes the early detection, diagnosis, and treatment of primary cardiac tumors challenging. However, the degree of malignancy is high and progresses rapidly, with most patients exhibiting distant metastases in the lungs, liver, and bone by the time of presentation.^2,3 Moreover, the median survival period is only 6–12 months. ⁴ The initial diagnosis of cardiac angiosarcoma is mainly based on echocardiography, cardiac magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT); however, histopathology is still needed to confirm the diagnosis. ⁵ Currently, the genetic pathology of this disease remains unclear, and there is no clear standard treatment protocol, which results in poor clinical outcomes and poor patient prognosis. Herein, we report the emergency case of a patient admitted for pericardial tamponade with hemoptysis, which was finally diagnosed as primary cardiac angiosarcoma with multiorgan metastasis after completing the relevant examinations and detecting an intracardiac cavity occupancy. By reviewing the diagnostic and therapeutic processes of this case, we discussed the clinical features, pathologic characteristics, and related treatment options of this disease using the literature to provide reference for clinical treatment.

Case presentation

Herein, we reported a case of primary cardiac angiosarcoma treated in the Emergency Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, in November 2023. All identifiable patient information was removed in accordance with privacy protection guidelines. The patient provided informed consent for both treatment and publication, with study approval granted by the Institutional Ethics Committee. The reporting of this study conforms to the Case Report (CARE) guidelines. ⁶ The case presentation was as follows. The patient was a man in his early 30s who was admitted to the hospital with “intermittent hemoptysis for 3 months and chest tightness and shortness of breath for 6 days.” He had intermittent hemoptysis without any obvious triggers 3 months ago and showed no other systemic concomitant symptoms. He received treatment with antibiotics and hemostatic agents at a local hospital 1 month ago, but the therapeutic effect was not significant. Six days ago, he experienced worsening symptoms of hemoptysis and chest tightness, prompting a visit to our hospital for further medical attention. He had no history of chronic underlying diseases or family genetic history and had worked in a power exchange station 5 months prior to presentation, with a history of exposure to ethylene glycol, paint, and iron filings.

After admission, CT suggested bilateral lung inflammation, multiple plasma cavity effusions (thoracic, abdominal, and pelvic), and pericardial effusion and hematochezia (Figure 1). On the day of admission, an echocardiogram suggested the presence of a large pericardial effusion. At that time, there was no obvious intracardiac cavity occupancy. A follow-up echocardiogram 1 week later showed hyperechoic occupancies in the pericardial cavity and right atrium (Figure 2). Due to hemoptysis, we performed bronchoscopy post-admission, and the results indicated the distribution of localized mucosal filaments in the bronchi and thin, small submucosal vessels. However, no mucosal swelling, active bleeding, or neoplastic formation was noted. A small amount of bloody secretion was observed at the luminal orifice of the anterior segment of the right upper lobe and part of the basal segment of the lower lobe. On the fifth day of admission, we conducted cardiac-enhanced MRI, and the results indicated an anterior right atrial occupancy and right atrial diverticulum with intraluminal thrombosis (Figure 3). On the 10th day of admission, we conducted PET/CT, and the results showed the following: (a) enlargement of the right atrium, with clustered hypermetabolic foci in its inner upper, left, and posterior walls, which combined with the features of significant metabolic increase, was first considered to indicate a malignant lesion, which may have been a lymphoma or tumor of a vascular endothelial origin; (b) a patchy metabolic increase in the left eighth posterior rib and left femur; and (c) hypermetabolic nodules in the posterior segment of the upper lobe of the right lung (Figure 4). Because of the high risk of intrapulmonary nodule puncture, a bone marrow aspiration biopsy of the homologous lesion in the left femur was later performed.

Figure 1.

Imaging manifestations at different time points. Computed tomography at admission indicating pericardial effusion and lung inflammation (a,b). The progression of lung inflammation in the second and third weeks after admission (c,d).

Figure 2.

Echocardiography suggesting a space-occupying lesion in the cardiac cavity.

Figure 3.

Cardiac MRI suggesting a space-occupying lesion in the right atrium (a,b). Femoral MRI suggesting a signal change in the left femoral head (c). MRI: magnetic resonance imaging.

Figure 4.

Positron emission tomography/computed tomography of the right atrium, left femur, and the nodule in the upper lobe of the right lung showing high metabolic changes.

After the biopsy, the patient and his family requested a transfer back to the local hospital for continued treatment. One week later, the pathological report of the patient’s femur indicated that heterogeneous cells were observed in a sheet-like distribution in the tissue sent for examination, and nuclear schizophrenic images were readily visible. This primarily indicated a malignant tumor of the lymphohematopoietic system. Two weeks later, further immunohistochemistry suggested the presence of tumor cells with vimentin (+), CD31 (+), CD34 (+), ERG (+), Ki67 (high at approximately 60%+), H3K27Me3 (protein expression), EMA (−), AE1/AE3 (−), MDM2 (−), SMA (−), S-100 (−), desmin (−), HMB45 (−), HBME-1 (−), MyoD1 (−), myogenin (−), SATB 2 (−), SOX-10 (−), calretinin (−), CD20 (−), CD79a (−), CD3 (−), CD5 (−), CD30 (−), ALK (−), and EBV in situ hybridization EBER (−). Molecular test revealed negative result for MDM2 amplification probe detection. Based on immunohistochemistry and molecular testing, these findings were consistent with those of high-grade angiosarcoma (Figure 5).

Figure 5.

Hematoxylin and eosin staining revealed atypical tumor cells (a,b). On immunohistochemistry, the tumor cells were positive for CD34, ERG, and Ki67 (c,d,e).

Upon admission with symptoms of hemoptysis and dyspnea, the patient was initially suspected to have respiratory system disorders such as infection-induced pneumonia or bronchiectasis. Empirical treatment with antibiotics and glucocorticoids (methylprednisolone) was initiated. Subsequent diagnostic investigations included tuberculosis screening, metagenomic next-generation sequencing of blood and sputum samples for pathogen identification, and pulmonary artery CT angiography to exclude pulmonary embolism. Considering concurrent imaging abnormalities in the lungs and pericardial effusion, rheumatologic autoimmune diseases were considered, prompting relevant immunological testing. Cardiac ultrasonography subsequently revealed a ventricular mass, possibly thrombotic, leading to the initiation of anticoagulation therapy. As prior examinations yielded negative results, PET/CT was ultimately performed, revealing hypermetabolic lesions in the right ventricle, right lung lobes, and left femur. A bone biopsy of the femoral lesion was conducted, with histopathological confirmation of high-grade angiosarcoma. Following discharge for supportive care at a local hospital, the patient continued to experience hemoptysis and dyspnea. Pathological confirmation of cardiac angiosarcoma was obtained 2 weeks post-discharge. The patient’s condition rapidly deteriorated, culminating in death from cardiopulmonary failure 3 days after definitive diagnosis, despite aggressive resuscitation efforts. From the onset of symptoms to death, the patient’s overall survival period was 4 months.

Discussion

Primary cardiac tumors are rare solid tumors with an autopsy incidence of 0.001%–0.300%. ⁷ Approximately 25% of such tumors are malignant, with cardiac angiosarcoma being the most common histologic subtype, and 75% of angiosarcomas are located in the right atrium.^1,2,7 The disease tends to affect younger patients, with a median age range of 39–48.9 years and a male predominance. ³

Primary cardiac angiosarcoma is clinically rare, has a poor prognosis, and lacks specificity in clinical symptoms, which depend on location, size, and degree of infiltration. Dyspnea, chest pain, and heart failure are common symptoms, while pericardial effusion, vena cava obstruction, pulmonary embolism, and hemoptysis are relatively rare.^8,9 As patients do not experience hemodynamic disturbances in the early stage, they usually do not have obvious clinical signs and symptoms, making malignant tumors easy to be overlooked or missed. Due to the high degree of malignancy and rapid progression of primary cardiac angiosarcoma, the rates of local recurrence and metastasis are extremely high. Approximately 66%–89% of patients have metastasis at the time of diagnosis, and the most common sites of metastasis are the lungs, liver, bone, lymph nodes, and brain. ³ The patient in this case presented with pericardial effusion, hemoptysis with fever, and night sweats with chest tightness, and shortness of breath, and the tumor was found to have metastasized to the lung tissue and the femoral head on subsequent examination, which is consistent with that reported in the literature. ⁹

One of the main difficulties in this case was that the patient presented to the emergency department with symptoms of pericardial tamponade with hemoptysis. In patients with pericardial effusion, we tend to first consider infectious factors such as tuberculosis, bacteria, and viruses as well as rheumatoid immune disorders such as rheumatoid arthritis, systemic lupus erythematosus, and scleroderma or metabolic disorders, including uremic pericarditis and hypothyroidism. Furthermore, tumor-related disorders such as lung cancer, breast cancer, and lymphoma are considered. As reported by Pourkia et al., ¹⁰ a patient initially treated for tuberculosis presented with findings suggestive of right heart enlargement and pericardial effusion. After ruling out pulmonary embolism and constrictive pericarditis, the final diagnosis was primary cardiac angiosarcoma. Similarly, Durani et al. ¹¹ reported the case of a patient initially diagnosed with viral pericarditis, who was eventually found to have pleural epithelioid angiosarcoma after recurrent pleural effusions. Therefore, when patients present with effusions, infectious etiologies are often considered first. In our case, there were no obvious abnormalities in the patient’s infection and inflammation indexes, organ function levels, and autoimmune indexes. The level of glycan antigen 125, a tumor marker, was abnormally high, while the rest of the indexes showed no obvious abnormalities following the patient’s admission. CT at the time of admission did not show any obvious occupying manifestations of various organs, and cardiac ultrasound only revealed a large amount of pericardial effusion without any obvious cardiac occupying manifestations, and the subsequent pericardial drainage fluid did not show any obvious abnormalities. Subsequent examination of pericardial drainage fluid also did not reveal the basis of tumor cells, which further made the diagnosis challenging. In addition, hemoptysis itself is rare in patients with primary cardiac tumors and is more commonly seen in patients with tuberculosis, lung cancer, bronchiectasis, pneumonia, pulmonary embolism, and cardiac valvular disease. CT at the time of admission did not show any obvious abnormality, and bronchoscopy at follow-up did not show any obvious active hemorrhage or neoplastic formation, which made further diagnosis of the disease difficult. Follow-up cardiac ultrasound revealed pericardial and intracardiac spaces, which provided evidence for subsequent diagnosis and treatment, and helped confirm the final diagnosis. It is clear that a rational and effective choice of examination modality is crucial for subsequent diagnosis and treatment.

Currently, X-ray, echocardiography, CT, MRI, and PET/CT are all used clinically as imaging methods for primary cardiac tumors, with CT and MRI being the main diagnostic methods. ⁹ Echocardiography can be used to evaluate the morphology and function of all four cardiac chambers, which can accurately determine the location, size, morphology, and activity of cardiac tumors, clarify hemodynamic changes, and provide a basis for preliminary qualitative diagnosis. CT and MRI can be used to observe the size of cardiac tumors and the relationship between tumors and surrounding blood vessels, providing a basis for the selection of surgical approaches. Cardiac MRI can better characterize soft tissues and tumors and has high specificity in identifying pseudotumors, thrombi, and lipomas. It has advantages in showing tumor infiltration of the myocardium and pericardium, but it cannot be used to distinguish residual lesions. PET/CT can differentiate benign from malignant tumors and indicate whether local and systemic tumors are invasive and metastatic. ¹² In addition, the presence of hemorrhagic pericardial fluid strongly suggests the malignant nature of this tumor. In our patient, bleeding pericardial fluid was drained after pericardiocentesis, and cytology of the pericardial fluid showed no malignant or atypical cells, emphasizing the limited diagnostic value of this test. ¹³ Therefore, malignant tumors, including cardiac angiosarcoma, should not be ruled out in patients with unexplained pericardial effusions, even if the pericardial fluid cytology is negative.

In this case, the diagnosis of cardiac angiosarcoma was confirmed via immunohistochemical staining for endothelial markers. Hemangiosarcoma is histologically characterized by mesenchymal cells derived from the endothelium with a combination of highly differentiated vascular channels and areas of low differentiation containing epithelioid and spindle cells. ¹⁴ Immunohistochemistry for CD31 and FLI-101 is highly sensitive (90% and 100%, respectively), and both are specific markers for vascular tumors. Other markers such as CD34, vascular hemophilic factor, factor VIII, cytokeratins, and wave proteins may be useful.^9,12,14 In our case, the diagnosis of angiosarcoma was confirmed via positive staining for CD31, CD34, ERG, and vimentin waveform protein, providing evidence regarding a vascular tumor.

Due to the aggressive nature of hemangiosarcoma and the high rate of metastasis at the time of diagnosis, treatment options are limited, and surgical resection alone results in poor outcomes. Currently, surgery with or without adjuvant radiotherapy or chemotherapy is the mainstay of treatment for angiosarcomas. Surgical treatment reduces intracardiac obstruction, and adjuvant radiotherapy after surgical resection reduces patient mortality compared with surgery alone. ¹⁵ However, even surgical treatment is largely a temporary remedy and has no definitive efficacy. Postoperative complications, such as potential unresectable and metastatic spread of the sarcoma as well as a negligible increase in patient survival and a disproportionate decrease in quality of life, remain a possibility. The prognosis for patients with cardiac angiosarcoma remains poor. A multimodal combination of therapies, including surgery, radiotherapy, adjuvant chemotherapy, and immunotherapy, may be promising for improving survival in some patients. As the disease progresses rapidly and most patients have distant metastases at the time of diagnosis that cannot be surgically resected, drug therapy remains one of the most important therapeutic tools. Currently, there is no uniform standard for the drug treatment regimen for hemangiosarcomas, and the clinically available drugs include paclitaxel, platinum, doxorubicin, and gemcitabine. Molecularly targeted drugs, such as anilotinib, imatinib, sorafenib, and bevacizumab, may play a certain therapeutic role.

Conclusion

Primary cardiac angiosarcoma is extremely rare, and diagnosis is often delayed because of nonspecific clinical symptoms, making early recognition of cardiac malignancy particularly important. When a patient presents to the hospital with hemoptysis and pericardial effusion, clinicians should consider the possibility of neoplastic disease when none of the conventional differential diagnoses explain the patient’s condition. Due to the rarity of this condition, there are no recognized treatment guidelines. For clinicians, in the face of the disease, even if the disease is no longer curable by existing medical means, it is still necessary to provide adequate humane care to patients and their families to help them choose the most appropriate treatment options.