Herein, we reported a case of cardiac angiosarcoma with the chief complaint of cough, diarrhea, and a history of chest trauma 3 weeks before, whose chest imaging was normal and not compatible with rheumatologic diseases or COVID-19; and in the end, RA rupture occurred with the pathologic findings leading to the final diagnosis. Diagnosis of morbidities during the COVID-19 pandemic is of significant importance, especially those which share common clinical and/or paraclinical features with coronavirus infection. COVID-19 pandemic has brought diagnostic challenges regarding differentiating SARS-CoV-2 infection from other diagnostic entities. There are several cases reported in the literature describing complexities that hinder the diagnosis and management of many other infectious and non-infectious conditions in the COVID-19 pandemic era (9–12); among these is a case of cardiac liposarcoma recurrence with symptoms of dyspnea, palpitation, fever, and sore throat (10). Unfortunately, many cases of cardiac angiosarcoma are not timely diagnosed despite multimodality workups such as echocardiography, chest CT scan, HRCT, and biopsy, due to a broad spectrum of differential diagnoses such as benign tumors, viral, mycobacterial, or rheumatologic diseases being investigated (13).
There are reports of cardiac angiosarcoma in literature, most of which involved the right atrium with metastasis to the lung. The most prevalent symptoms were dyspnea, chest pain, tachycardia, pleural and pericardial effusion (7, 14–19). There were also cases presented with left atrium mass (20, 21), ascites (16), SVC involvement (8, 19, 22, 23), valvular complications (18, 20), tamponade and shock (24, 25), involvement of coronary vessels (26, 27), or heart rhythm abnormalities (20). In our patient, a rupture in the atrial wall was discovered which was assumed to be the underlying cause for her symptoms. There are similar cases reported in the literature in whom perforations in the cardiac chambers’ walls were encountered (28). Reviewing the available literature regarding management strategies, some patients underwent surgery, along with radiotherapy and chemotherapy with regimens containing various drugs such as Ifosfamide, Epirubicin, and Taxanes. Most of these treatments failed to control the disease and prolong survival (7, 8, 17, 19, 29–31). A case report has proposed complete resection of the tumor and aggressive reconstruction of the involved structures as a successful strategy to prolong patient survival for up to two years (21).
Among sarcomas, 40 percent are angiosarcomas which are composed of malignant cells forming vascular channels. Angiosarcomas arise predominantly in the right atrium (32). Sarcomas tend to proliferate rapidly and cause death via the widespread infiltration of the myocardium, blood flow obstruction, and even invasion and metastasis. Men are at least two times more likely than women to be diagnosed with primary cardiac angiosarcomas, knowing that it mostly affects the young. However, a multicenter cohort demonstrated no difference in 30-day and late mortality between males and females (3).
Echocardiography remains the major diagnostic tool with high sensitivity for cardiac mass detection and evaluation, identifying size, shape, location, attachment, and mobility of the mass. Meanwhile, a CT scan offers better recognition of the tumor anatomy and systemic metastasis. Cardiac MRI is a strategy to understand soft tissue and myocardium and to discern tumors from thrombi (33). Another practical approach is pericardiocentesis and tissue biopsy, keeping in mind that endomyocardial biopsy is a poor diagnostic tool (34). All of these strategies were performed as part of our diagnostic approaches. Majority of reported cases in the literature have performed chest CT-scan, TTE, and cardiac MRI for diagnosis. Histopathological studies following surgical (30, 35) or even core-needle biopsy (23) have been utilized to diagnose angiosarcoma. Besides, recently positron emission tomography-CT (PET/CT) scan using fluorodeoxyglucose (FDG) have helped further characterization of the tumor and systemic evaluation of the patient (30, 31, 36–39).
Surgery is a particular therapy, especially in the case of localized disease. Wide resection is considered a principal treatment approach as it not only enables a definite histological diagnosis, but also alleviates symptoms caused by cardiac output obstruction. Some of the tumors were reported presumably inoperable due to multiple metastases or adhesion to the RV (23, 29, 39). Alternative strategies such as orthotopic heart transplantation in the patients with high-grade angiosarcomas, especially in young patients for whom we do not have other options, have also been explored (34). Chemotherapy, both neoadjuvant and adjuvant, is sometimes utilized to augment the poor outcome of resection alone (22, 29–31, 35), or in cases which resection of the tumor is no feasible, long courses of chemotherapy with different agents might be helpful. For example, one center started chemotherapy with paclitaxel and bevacizumab for almost one year, which led to a decrease in tumor size, and finally pazobanib, ifosfamide, and doxorubicin were administered due to detection of pulmonary and liver metastasis (39). A recent case presentation also involved using immunotherapy with pembrolizumab as part of management of primary cardiac angiosarcoma with pulmonary nodules and bone destruction (31). Although not so common, radiation therapy has also been used in angiosarcomas, mainly in the setting of metastases (22, 30, 31, 40). A young boy with angiosarcoma was managed using MR-guided radiotherapy and demonstrated acceptable tolerance and a stable disease for two months (41). According to the fact that treatments for angiosarcomas are not standardized, a combination of aforementioned modalities might be favored (42). However, it is noteworthy that the primary site of the tumor and stage at the time of diagnosis influences the plan of therapy (34).
Most patients end up with recurrent disease and death even in case of complete tumor resection (43, 44). The median survival is considered to be 6–12 months (45); however, there are reports of cases with longer survival rates and also better prognosis in cases with complete surgical resection or lack of metastasis on presentation (22, 46, 47). On the other hand, with heart transplantation, the mean survival rate could be about 12 months. In general, no established prognostic factors have been recognized in these patients.
Angiosarcomas are sometimes asymptomatic, yet, may present with constitutional symptoms such as shortness of breath, fatigue due to anemia, malaise, weight loss, with dyspnea being the most common complaint. This nonspecific symptomatology and rarity of the disease leads to difficulties in diagnosis, even though more characteristic symptoms may develop later as the disease progresses related to involvement of cardiac wall, neighboring structures, infiltration, and also disease extension and metastases (31, 34). In more advanced angiosarcomas, myocardial wall necrosis and rupture, pericardial involvement and effusion, and cardiac tamponade, right-sided congestive heart failure, and systemic symptoms due to blood flow obstruction may manifest in the course of the disease (29, 34). Likewise, our patient was first suspected of being infected with SARS-CoV-2 despite negative COVID-19 PCR, but later during the follow-up, symptoms did not still comply with the viral disease until her condition was emergent, leading to the following interventions and diagnoses. Finally, despite surgery, the patient unfortunately suffered invasive tumor complications that put an end to her life.
In conclusion, due to rarity and fatality of primary cardiac angiosarcomas, early diagnosis and possible management seem crucial for prolonged survival. Involving cardiac angiosarcoma in the initial differential diagnosis can warrant timely diagnosis and assessment of various therapies for cure or palliative care.