Background

Cardiac tumors are rare and only 20% of them are malignant. (Bakeen et al. 2003) Metastatic tumors of heart are more frequent than primary tumors. (Araoz et al. 1999) It was reported that the prevalence of primary cardiac tumors is between 0.001 to 0.28% in autopsy series. (McCallister Jr 1979) In heart, the most common primary tumor is sarcoma that angiosarcoma, a histopathological sarcoma type, accounts around for 30% of malignant primary lesions of the heart. (Kodali and Seetharaman 2006; Silverman 1980; Janigan et al. 1986) Angiosarcoma is most commonly found in the right atrium and it is usually asymptomatic or associated with nonspecific symptoms until the tumor becomes large. (Fletcher et al. 2013; Herrmann et al. 1992; Mich et al. 1985; Neuville et al. 2014) Middle-aged adult males are the most affected although is there a study of series of primary cardiac sarcomas that reported a higher incidence in females. (Neuville et al. 2014; Dhull et al. 2015) The diagnosis is usually difficult and tardy as the initial symptoms are nonspecific and includes fever and weight loss. (Rettmar et al. 1993) Here, we report an unusual case of cardiac angiosarcoma in a female adolescent patient which is not in accordance with epidemiology.

Case presentation

A previously healthy 17-year-old female patient was admitted to the emergency service with a recent history of cough, hemoptysis, myalgia, malaise and diarrhea. Laboratory tests do not have any changes of relevance but she progressed with oxygen desaturation and syncope. Besides, chest x-ray revealed a diffuse interstitial lung infiltration and treatments for pneumonia was started. Whereas the patient had no improvement with an antibiotic therapy, she was referred to a tertiary-level general hospital with the intention of proceeding with the propaedeutic. The patient was submitted to a thoracic computed tomography (CT) scan which that demonstrated a right atrial mass, multiple bilateral pulmonary nodules and osteolytic destruction of vertebral bodies, left scapula, right humerus, manubrium, and sternum body.

She was referred to our institution for biopsy the right atrial mass where a radioguided procedure was successfully performed, after confirmation of absence of bronchial invasion by endoscopic ultrasound study. The anatomopathological study demonstrated the possibility of vascular neoplasia. Then, an immunohistochemistry was carried out to confirm an angiosarcoma. Immunohistochemical staining of the tumor specimen revealed that it was positive for erythroblast transformation specific related gene (ERG) and platelet endothelial cell adhesion molecule (PECAM-1 or CD31) (Table 1). Therefore, the histology and immunohistochemistry were both consistent with cardiac angiosarcoma, which was the definitive diagnosis. On the following days, the patient developed chest pain, dyspnea and bleeding complication related to a tracheostomy. A new CT scan was done considering the strong possibility of a correlation of the current clinical condition with the neoplastic etiology of the cardiac mass. Then, it was decided to start an urgent oncologic treatment of palliative chemotherapy with doxorubicin.

Table 1 Immunohistochemical reactions
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Radiological findings

Two-dimensional echocardiography revealed a right atrial mass with heterogeneous appearance measuring 6.5 ;× ;5.1 ;cm, with a component moving through the tricuspid valve during the cardiac cycle and contiguous echogenic component with the inferior vena cava, reducing the filling and emptying of this chamber. An urgent chest CT was performed and identified a normal-sized heart with an infiltrative, well-defined, expansive lesion, invading pericardium space and pericardial leaflets, measuring approximately 6.8 ;× ;6.7 ;× ;5.3 ;cm. It was hypodense on the pre-contrast scan and with heterogeneous augmentation after the use of it (Fig. 1). Such lesion still deflected the anterior wall of the superior vena cava, suggesting its invasion (Fig. 2).

Fig. 1
figure 1

Axial computed tomography scan of the thorax in the mediastinal window demonstrating lesion centered in the right atrium, infiltrating the pericardium

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Fig. 2
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Sagittal remodeling of the thorax computed tomography in the mediastinal window demonstrating direct atrial injury, invading the superior vena cava

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The appearance of CT images suggests a cardiac sarcoma. Were identified numerous solid nodules with spiky projection which some of them poorly defined. The nodular images were randomly and diffusely distributed with varied sizes and symmetrically located on bilateral pulmonary parenchyma, more present in basal regions. The presence of nodules contrast augmentation is suggestive of secondary neoplastic involvement (Fig. 3).

Fig. 3
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Coronal reconstruction of chest computed tomography in the lung window demonstrating multiple bilateral solid nodules compatible with metastasis

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Clinical course

After a radioguided biopsy of the cardiac lesion (Fig. 4), the patient developed a shock syndrome treated with fluid resuscitation, vasoactive amines and corticoid administration. Cardiac tamponade was diagnosed by an emergencial echocardiogram (ECHO). Then, pericardiocentesis procedure was performed through a pericardial window that drainage of 800 ;ml of bloody pericardial. Results of cytological and bacteriological examinations of the fluid were negative. Evolution of the patient was satisfactory due to stabilization and clinical improvement. At this moment, the vasoactive drugs were gradually tapered and stopped. In addition, pericardial drain was removed. The ECHO control showed the absence of a stroke. Tracheostomy was performed and the patient transferred to progressive intensive care unit (ICU). Blood flow through the tracheostomy tube was detected and a new CT scan was performed (Figs. 1, 2 and 3). The CT images revealed a neoplastic etiology lesion. Thus, the oncological emergency treatment (chemotherapy) was started, reaching the clinical stability and hospital discharge. After, an outpatient chemotherapy was established and started. During outpatient treatment, the patient progressed with a worsening dyspnea, returning to the hospital with a clinical suspicion of pulmonary embolism (PE). It was confirmed by angiotomography which revealed filling defect in the pulmonary artery (Fig. 5). After treatment and another hospital discharge, the patient returned with pain and movement limitations in the right shoulder. An elective ultrasound scan identified a secondary bone involvement of the humeral head with adjacent soft tissue infiltration - synovial sheath of the long head of the biceps muscle. She was admitted with an aggravation of the breathing pattern and a new CT was performed. CT images showed consolidations in both lung bases that suspect an infectious process or secondary parenchymal lesions (Fig. 6). The patient died during this hospitalization period.

Fig. 4
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Axial computed tomography scan of the thorax in the mediastinal window demonstrating transthoracic biospherical needles through the left parasternal intercostal space

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Fig. 5
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Coronal reconstruction of chest computed tomography in a mediastinal window demonstrating a weak filling defect in the right lower lobe pulmonary artery

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Fig. 6
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Axial computed tomography scans of the thorax in the mediastinal and lung window demonstrating consolidations (a), suggestive of confluence of the secondary lesions or inflammatory/infectious process (b)

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Discussion

Our case demonstrated the difficulty of diagnosis of cardiac angiosarcoma due to initial symptomatology that is nonspecific and associated with fever and weight loss. Therefore, here, we report a case of angiosarcoma with pulmonary metastases who is not in accordance with epidemiological data: 17-year-old female patient. (Wang et al. 2017)

Our patient has in addition to these, malaise, diarrhea and hemoptysis which was mistakenly diagnosed with pneumonia. With the progression of the lesion, more specific symptoms of cardiovascular system occurred, mainly failure of the right chambers and tamponade. (Burke and Virmani 1996; Glancy et al. 1968; Jannigan et al. 1986) These manifestations are associated with one type of radiological findings that can develops and is represented by a well-defined mass creeping into the cardiac chamber, usually occupying the right atrium, directly infiltrating the pericardium, large vessels and rejecting the other chambers. (Jannigan et al. 1986; Shin et al. 1987; Hammoudeh et al. 1996; Heenan et al. 1996; Matheis and Beyersdorf 1995) In magnetic resonance imaging (MRI) and CT scans, these lesions may present areas of necrosis and hemorrhage, which in MRI exhibit high signal in the T2-weighted sequence and high signal in the T1 sequence respectively, besides the heterogeneous impregnation by means of contrast in the two imaging modalities, CT and MRI. (Mader et al. 1997; Bruna and Lockwood 1998; Crespo et al. 1993) This morphological type with heterogeneous aspect lesion (CT scan) secondary to necrosis was present in our case. In the second morphological type, the lesion diffusely infiltrates the pericardium. (Glancy et al. 1968) The pericardial space may be filled with necrotic or hematological material. In this case, CT imaging scan evidence effusion or pericardial thickening. (Burke and Virmani 1996; Walley and Masters 1994; Marafioti et al. 1993)

The late diagnosis is because oligosymptomatic forms or presence of mild and nonspecific symptoms. It implies in the prognosis as more than 50% of these patients present metastases at the time of diagnosis. Metastases are more common in the lungs, liver, brain and bones, but there are reports in the scientific literature of metastatic foci in the skin, lymph nodes, spleen, pancreas and kidneys. (Jain et al. 2015; Waness et al. 2015; Ramadhan et al. 2013)

The case reported in this article already presented, at the time of diagnosis, an extensive bilateral pulmonary metastasis, as well as sternum skeleton, cervical spine, scapular girdle and local extension to the pericardium. It is noteworthy that the first mode of imaging usually used is transthoracic ECHO, with studies demonstrating sensitivity and specificity for mass detection of respectively 93 and 97%. (Chen 2017) Although imaging tests are very important, the definitive diagnosis is based on the analysis of biopsied material. (Liu et al. 2018) Several methods have been used to replace thoracotomy such as transvenous biopsy, ultrasound-guided transesophageal biopsy and transthoracic biopsy guided by ultrasonography or CT. These techniques are less invasive than thoracotomy. (Liu et al. 2018) Besides this, although transthoracic biopsy is potentially risky due to the strong possibility of rupture of the generally thin atrial wall, this was the method chosen in the present clinical case considering risks and benefits associated. (Bruce 2011) The procedure was performed with an 18G semi-automatic needle, inserted in the left sternal intercostal space through the 17G coaxial under local anesthesia with 1% xylocaine, without vasoconstrictor.

Although the patient had a brief history of cardiac tamponade, it was resolved after thoracentesis and drainage of approximately 800 ;ml of blood content. This material was successfully collected and a definitive immunohistochemical diagnosis was possible. The most common histological type is the angiosarcoma, neoplasm of mesenchymal origin and is in accordance of microscopically findings of this case (Fig. 7). This histological type exhibits large epithelioid cells with abundant eosinophilic cytoplasm, large eosinophilic nucleolus and some focal cells presenting intracytoplasmic vacuoles. (Burke et al. 1996; Becker 2000) During immunohistochemical analysis, is expected that the fragment strongly reacted with the CD31 antibody. (Becker 2000) There are also studies that admit the positivity in the reaction with CD31 and CD34 antibodies as definitive diagnosis for angiosarcoma. (Matzke et al. 2011) Our case revealed a positive staining for CD31 antibody. Besides this, ERG was typically extensively expressed in angiosarcomas then, it was evaluated. (Miettinen et al. 2011) Sullivan et al., (2015) reported that positive staining for CD31 and ERG antibodies is highly suitable for the cytological diagnosis of angiosarcoma (Sullivan et al. 2015). These aspects are in accordance with this case reported.

Fig. 7
figure 7

Histopathological features. a Fragment of tumor biopsy. Magnification × ;40. b and c Fragment of mesenchymal neoplasia exhibiting proliferation of atypical epithelioid cells with solid pattern and lining irregular vascular channels and papillary structures. Magnification × ;200

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The prognosis of angiosarcoma patient is poor due to the aggressiveness of the lesion, as well as the high incidence of metastasis at the time of diagnosis, with a median survival of 6 to 11 ;months and it was better in men than in women. (Antonuzzo et al. 2009; Pacini et al. 2015) There has been a 30-month survival report in patients with combined treatment of chemotherapy, radiotherapy, surgery and transplant. (Kakizaki et al. 1997; Stein et al. 1994; Baay et al. 1994) Surgical treatment remains the therapy of choice if no metastasis is evident and if myocardial resection is reparative. (Fukunaga et al. 2017) Chemotherapy as treatment for angiosarcoma is controversial as there is no randomized study comparing the evolution of metastatic diseases with and without chemotherapy. (Liu et al. 2018) However, there are a review of literature that demonstrated that combined treatment with doxorubicin and ifosfamide was effective in treating metastatic soft tissue angiosarcoma regardless of the primary site. (Batzios et al. 2006) Multimodality therapy which includes surgery, radiation therapy, and chemotherapy was associated with improved survival (Randhawa et al. 2016). In our case, the chemotherapy treatment was chosen by the clinical team but it was interrupted due to several hospitalizations which, mostly, breathing decompensations, among acute PE, were present. The patient died approximately 4 ;months after the clinical presentation.

Conclusion

Cardiac angiosarcoma is a rare disease with difficulty in diagnosis due to the initial nonspecific symptoms. Despite their rarity, primary cardiac lesions should be considered as possible manifestations of cardiac malignancies. Then, is, mostly, associated with poor prognosis because is almost always a disseminated disease at the time of definitive diagnosis. In our case, there was a complicating factor: the patient did not match typical epidemiology (age and sex) of the disease. Imaging exams are very important in the diagnostic suspicion and research of systemic disease, which can modify the therapeutic course. However, the definitive diagnosis is based on the histopathological analysis of the material collected by biopsy. This was one of the rare recent cases in which transthoracic biopsy guided by CT was chosen, obtaining satisfactory material enabling definitive diagnosis and urgent oncologic treatment. The patient, however, with a systemic disease at diagnosis, died shortly after. This case report can be used to draw the professional’s attention to raise the suspicion of primary cardiac lesions in female adolescent with nonspecific symptoms. In addition, it is clear the need for early diagnosis and a definition of optimized treatment in order to extend the survival of these patients.