A 59-year-old woman with no past medical history presented with 1-week symptoms of atypical chest pain and mild dyspnea. Upon physical examination, her heart rate, respiration rate, blood pressure, and body temperature were 102 beats per minute (bpm), 22 breaths per minute, 110/60 mm Hg, and 36.1 C, respectively. No moist rales or wheezing sound in lungs and no cardiac murmur or pericardial rub were detected. Laboratory tests showed the level of d-dimer as 6,440 mug/L (reference range, 0-550 mug/L) and brain natriuretic peptide as 107.52 ng/L (reference range, 0-100 ng/L). Arterial blood gas analysis in room air showed severe hypoxemia (pH 7.393, Pao2 = 60 mm Hg, Paco2 = 43.3 mm Hg,  = 25.8 mmol/L). Myocardial enzymes, tumor markers, thyroid function tests, T-SPOT, tuberculosis antibody, hepatitis virus, human immunodeficiency virus, syphilis, and autoimmune panel were all negative. An electrocardiogram showed a fast sinus rhythm of 102 bpm, with flat T-wave in precordial leads. Computed tomography pulmonary angiography (CTPA) showed multiple embolisms of bilateral pulmonary arteries and a mild-sized pericardial effusion (Figure 1A). Color Doppler ultrasound showed left calf muscular venous thrombosis. Upon clinical examination and tests, the patient was diagnosed of acute pulmonary thromboembolism (PTE) (intermediate risk) and left muscular calf vein thrombosis (diagnosed on December 16, 2019). First line of treatment included hypodermic injection of low-molecular-weight heparin as anticoagulation therapy.
However, 2 days posttherapy, the patient complained of progressive development of dyspnea, fatigue, chest tightness, and palpitations, to later experience transient loss of consciousness. Her heart rate increased to 125 bpm, whereas blood pressure and pulse pressure were slightly decreased (96/69 and 27 mm Hg, respectively). Jugular venous distention and muffled heart sounds were present. Both transthoracic echocardiogram (TTE) and thoracic CT were significant for severe large-scale pericardial effusion (Figure 1B). No obvious mass was identified either in the pericardium or heart. Therefore, acute pericardial tamponade was considered as a differential diagnosis. Emergency pericardiocentesis and drainage were performed, draining 210 mL of bloody effusion in total. Repeated thoracic CT the following day was significant for bilateral pleural effusion, which was greatly increased in amount (Figure 1C). Further left thoracentesis and thoracic drainage were performed, draining another 710 mL of pleural effusion (the first two times, collected effusion was bloody; the third time, effusion was examined as pale yellow). Symptoms of dyspnea and palpitations were also immediately improved after a third round of drainage. Additional pericardial effusion cultures for bacteria and acid-fast bacilli were repeated twice, obtaining negative reports each time. Repeated cytological examination of the pericardial effusion did not show any malignant cells. Repeated thoracic CT prior to discharge showed mild bilateral pleural effusion and pericardial effusion (documented on December 30, 2019; Figure 1D). Patient was followed up in the outpatient department.
Half a month later (January 15, 2020), although she was asymptomatic, her levels of d-dimer were spiked to 10,740 mug/L. TTE showed a mild pericardial effusion. Given that PTE is prone to relapse, she suffered an acute pericardial hemorrhage after anticoagulation, where low-dose rivaroxaban (10 mg every day) was later administered from January 15, 2020, onward. The levels of d-dimer were decreased significantly (1,450 mug/L) after 2 months of oral rivaroxaban, and there were no bleeding events recorded during this period.
Four months later, the patient complained of progressive hemoptysis and dyspnea (May 2, 2020). She did not stop taking the administered oral rivaroxaban until the embolisms were absent by CTPA on May 18, 2020. However, CTPA also showed a large mixed mass, occupying the right pericardium (4.5 x 8.5 cm; Figure 1E), and she was readmitted. On physical examination, mucocutaneous color was pale, and medium moist rales in lungs was detected. The levels of CA-125 and neuron-specific enolase (NSE) were markedly elevated (117.5 U/mL [reference range, 0-35 U/mL]; 46.96 ng/mL [reference range, 0-24 ng/mL], respectively). The hemoglobin content was 68 g/L (reference range, 115-150 g/L); the plasma d-dimer level was 4,160 mug/L; arterial pressure of oxygen was 56 mm Hg (reference range, 80-100 mm Hg). Dual-source coronary CT angiography (CCTA) showed the mass infiltrated and communicated with the RA, with heterogeneous thickened pericardium and localized moderate pericardial effusion (Supplementary Movie 1). No stenosis was seen in the coronaries, and there was no communication of the tumor with the coronaries. CCTA also showed a mild left pleural effusion, enlarged mediastinal and hilar lymph nodes, multiple and scattered ground-glass opacity [diffuse alveolar hemorrhage (DAH)] nodules over bilateral lung field, and multiple bipleural nodules (Figure 1F, May 21, 2020). TTE showed a huge mass in the pericardium, surrounding and compressing the RA and right ventricle. Mild blood flow signals were also observed in the mass (Figure 2A) (May 20, 2020). The tumor was significantly larger than before with a strip-like hyperechoism within the RA (Figure 2B, recorded on June 18, 2020). Contrast-enhanced ultrasound showed the mass and chamber were filled with contrast agent almost simultaneously (Figures 2C1-C3 and Supplementary Movie 2). Axial Fiesta (Figure 2D) and 4CH-2D (Figure 2E) of cardiac magnetic resonance (CMR) showed an irregular, large tumor (size up to 10 x 5.5 cm) with heterogeneous distinction diffusely within the pericardium (10 x 5.5 cm), mainly located outside the right cardiac chamber system, compressing the right heart. Positron emission tomography scan exhibited a heterogeneous mass located at the right margin of pericardium, poorly demarcated from the RA and superior vena cava (Figures 3A-C). Distant metastases were found in both lungs and bilateral pleura (Figures 3B,D), nodules in hilar and mediastinal lymph nodes (Figures 3E,F).
Ultrasound-guided biopsy was performed for a definitive diagnosis. The biopsy specimen showed a malignant tumor in histopathologic examination (Figure 4A) and positive immunohistochemical staining for CD31 (Figure 4B) and CD34 (Figure 4C), but negative for CEA, CK, CK5/6, CR, D2-40, desmin, and MC, indicating poorly differentiated angiosarcoma. Surgery was not a suitable option for the patient because of metastasis. Unfortunately, she refused treatment with radiotherapy, chemotherapy, or immunotherapy, where the clinical condition of the patient deteriorated rapidly after. She died on June 28, 2020, while waiting for the pathologic results due on June 29, 2020. The patient survived for 6 months from the first episode of PTE. The progression and examination of the clinical course are shown in Figure 5.
Progression and examination of the clinical course. PTE, pulmonary thromboembolism; BNP, brain natriuretic peptide; CTPA, computed tomography pulmonary angiography; TTE, transthoracic echocardiogram; CMR, cardiac magnetic resonance; PET, positron emission tomography; CCTA, coronary computed tomography angiography.