□
CASE REPORT
□
A Patient with Primary Pericardial Synovial Sarcoma who Presented with Cardiac Tamponade: A Case Report and Review of the Literature Michishige Ohzeki 1, Shu-ichi Fujita 1, Hirota Miyazaki 1, Hideaki Morita 1, Sachiko Kanki 2, Hideki Ozawa 2, Takahiro Katsumata 2, Yoshitaka Kurisu 3, Motomu Tsuji 3, Jun Tanigawa 1, Koichi Sohmiya 1, Masaaki Hoshiga 1 and Nobukazu Ishizaka 1
Abstract A 36-year-old man presented with near-syncope. He was found to have massive pericardial effusion with a giant pericardial tumorous lesion. The pericardial effusion exhibited a bloody nature; however, neither malignant cells nor infectious organisms were detected. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed an increased uptake of FDG in the pericardial tumor only. Although the tumor was not resectable, thoracotomy and tissue sampling were performed. A histological analysis showed CD99 positivity and SYT gene rearrangement, leading to a diagnosis of synovial sarcoma arising from the left lateral pericardial surface. The patient is now receiving chemotherapy. Key words: synovial sarcoma, pericardial effusion, cardiac tamponade, fluorescence in situ hybridization, gene rearrangement (Intern Med 53: 595-601, 2014) (DOI: 10.2169/internalmedicine.53.1749)
Introduction Malignancy is a common cause of pericardial effusion, which can result from either pericardial malignancy or a non-malignant disease process, such as radiation pericarditis or opportunistic infections (1). Cardiac tamponade may also be present, occurring at a rate of approximately 2-15% in patients with idiopathic pericarditis and a rate of approximately 60% in patients with neoplastic pericarditis (2). Ma et al. recently reported that malignancy (39%) and tuberculosis (27%) are the most common causes of large areas of pericardial effusion requiring drainage in Chinese patients and that cancer cells in the pericardial fluid are negative in approximately one-fourth of patients with malignant pericardial effusion (3). Compared with lesions of a metastatic etiology, primary pericardial tumors, including mesotheliomas, fibrosarcomas, angiosarcomas, teratomas, hemangiomas,
neurofibromas and lipomas, are considered to be extremely rare (4). We herein report the case of a 36-year-old man who presented with cardiac tamponade symptoms caused by primary pericardial synovial sarcoma.
Case Report A 36-year-old man presented to his doctor with appetite loss and easy fatigability in June, 201X. Six days later, echocardiography performed at a nearby hospital showed massive pericardial effusion with a tumorous region in the pericardial space, and the patient was referred to our hospital for a further evaluation and treatment. He had been well until approximately one week previously. On admission, the patient exhibited a rapid pulse (133 beats per minute); however, his systolic blood pressure was steady at 150 mmHg. His jugular veins were dilated, although there was no apparent edema in the lower extremi-
１
Department of Cardiology, Osaka Medical College, Japan, ２Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Japan and ３Division of Pathology, Osaka Medical College, Japan Received for publication September 12, 2013; Accepted for publication October 6, 2013 Correspondence to Dr. Nobukazu Ishizaka,
[email protected]
595
Intern Med 53: 595-601, 2014
A
DOI: 10.2169/internalmedicine.53.1749
B
Figure 1. A chest roentgenogram and electrocardiogram obtained on admission. A: The chest roentgenogram showed cardiomegaly with a cardiothoracic ratio of 63%. B: On the electrocardiogram, no elevation of the ST segment was apparent.
A
B
D
E
C
Figure 2. Echocardiography, computed tomography (CT) and magnetic resonance (MR) imaging. A: Echocardiography showed a solid mass (5×7 cm) of inhomogeneous echogenicity touching the anterior left ventricular wall (arrow). B: CT without contrast enhancement. A large amount of pericardial effusion was observed. C: CT with contrast enhancement. The tumorous lesion was stained weakly (arrows). D: Reconstructed coronary CT image. Left anterior descending (LAD) and right coronary artery (RCA) indicate the left anterior descending artery and right coronary artery, respectively. Feeding arteries arising from the LAD were observed (arrowheads). E: Short-axis T1-weighted MR image showing the pericardial mass, suggestive of a hematoma. The scale bars indicate 5 cm.
ties. A chest roentgenogram showed cardiomegaly with a cardiothoracic ratio of 62% (Fig. 1A). Electrocardiography disclosed sinus tachycardia; however, the voltage was not low (Fig. 1B). Echocardiography demonstrated massive pericardial effusion and a solid tumor that was neighboring the anterior wall of the left ventricle (Fig. 2A, arrow). Computed tomography (CT) further revealed massive pericardial effusion with a small amount of bilateral pleural effusion
(Fig. 2B, C). The tumor appeared to be located in the pericardial space, with an estimated size of 7.0×4.8 cm. On contrast-enhanced CT, the presence of arteries feeding the tumor originating from the left coronary artery was suspected (Fig. 2C, arrows) and further confirmed on a reconstruction image of coronary CT (Fig. 2D, arrowheads). Cardiac magnetic resonance imaging also showed a large amount of pericardial effusion, which was therefore sugges-
596
Intern Med 53: 595-601, 2014
DOI: 10.2169/internalmedicine.53.1749
A
B
Figure 3. Coronary artery angiography. A: Right coronary artery. B: Left coronary artery. Small arteries presumably feeding the tumorous lesion arising from the left ascending coronary artery were observed (arrowheads).
A
B
C
Figure 4. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). A whole-body coronal maximum intensity projection image (A) in addition to coronal (B) and transverse (C) plane images are shown. An enhanced uptake can be seen in the pericardial mass.
tive of hematoma owing to an inhomogeneous high signal intensity lesion on a T1-weighted image (Fig. 2E). Laboratory studies showed a white blood cell count of 10,880 cells/μL, a hemoglobin level of 14.2 g/dL, a platelet count of 23.2×104 cells/μL, a C-reactive protein concentration of 4.91 mg/dL and a D-dimer level of 1.9 μg/mL. The serum soluble interleukin 2 receptor level was 320 U/mL. Owing to the patient’s progressive symptoms and the compression of the right atrium, pericardiocentesis was performed on the day of admission. Bloody fluid containing 5.2 g/dL of hemoglobin was drawn from the pericardial sac. The drainage tube was removed on the sixth hospital day; up to that point, a total of 1,200 mL of fluid was withdrawn. The pericardial fluid was cytologically tested twice; however, no malignant cells were detected on either test.
Cardiac catheterization performed on the seventh hospital day showed preserved systolic contractility (cardiac index: 3.37 L/min/min2) and a pulmonary capillary wedge pressure of 15 mmHg. Coronary angiograms showed no apparent coronary artery stenosis (Fig. 3), with small arteries feeding the tumorous lesion (Fig. 3B, arrowheads), as observed on coronary CT. Left ventriculography did not show any leakage of the contrast medium to the pericardial space. 18Ffluorodeoxyglucose positron emission tomography (FDGPET) showed an abnormal uptake in the pericardial region corresponding to the tumor; however, no distant hypermetabolic lesions were observed (Fig. 4). A surgical approach was taken for further diagnosis and management. Through a median sternotomy and midpericardial incision, the tumor was observed to be located
597
Intern Med 53: 595-601, 2014
DOI: 10.2169/internalmedicine.53.1749
on the right ventricle (RV) anterior wall between the parietal and visceral pericardium (Fig. 5). Due to adhesion of the tumor to the parietal pericardium, dissection from the parietal pericardium was limited; thus, it was not possible to see the extension to the tumor on the left side. Moreover, the tumor
LeŌ parietal
pericardium
Head visceral pericardium
Figure 5. Intraoperative photograph. An intraoperative photograph showing that the tumor was present on the right ventricular anterior wall between the visceral and parietal pericardium. Because the tumor adhered strongly to the visceral pericardium and moderately to the parietal pericardium, its extension to the left side could not be clarified.
strongly adhered to the visceral pericardium over the left anterior descending coronary artery from the right ventricular to the left ventricular anterior wall and appeared to invade the myocardium. Because the tumor exhibited hypervascularity, tissue sampling of even a small amount of the lesion caused bleeding. Based on an intraoperative histological examination of the tumor with malignant features and the intraoperative observations, the mass could not be resected. A histological analysis showed fibroblast-like spindle cells with mitotic figures (Fig. 6A, B). As a result, the tumor was diagnosed to be a spindle cell-type sarcoma. An immunohistochemical analysis showed that the tumor cells were positive for factor p53 and the Ki-67 proliferative index was 22.7% (Fig. 6C); however, staining for S100 proteins, CD34, CD31, α-smooth muscle antigens, muscle-specific actin (HHF35) and desmin was negative (data not shown). These immunological characteristics suggested that the possibility of angiosarcoma, rhabdomyosarcoma or leiomyosarcoma was rather remote. On the other hand, bcl-2 (Fig. 6D) and CD99 (Fig. 6E) were positive, and fluorescence in situ hybridization revealed a high prevalence (89.9%) of cells with interruption of the SYT gene (Fig. 6F, arrows). Therefore, a diagnosis of monophasic synovial sarcoma with poorly differentiated areas was made (5), and the patient was started on adriamycin-based chemotherapy.
A
B
C
D
E
F
Figure 6. Histological and immunohistochemical analysis of the sampled tumor tissue. The tumor was composed of densely cellular interlacing fascicles with spindle cells. The tumor cells showed abnormal mitosis Hematoxylin and Eosin staining ×100 (A), ×400 (B). The tumor cells were positive for Ki-67(C), bcl-2 (D) and CD99 (E) F: Fluorescence in situ hybridization showed separated red and green signals, indicating SYT gene rearrangement (arrows). The scale bars indicate 100 μm. 598
599
15
64
26
22
29
19
19
35
76
59
49
(24)
(25)
(26)
(27)
(28)
(29)
(30)
(31)
(32)
(33)
(34)
M dyspnea, chest pain
M N/A
F found incidentary at autospy
F chset pain, nausea, dyspnea
M shortness of breath
F dyspnea, fatigue
M acute breathlessness
F shortness of breath, cough
M signs of cardiac tamponade
F shortness of breath
M cough, tight chest
M N/A
M malaise
F fever, cough
F cough, dyspnea
M dyspnea
F malaise, fever, chest pain
M fever, nocturnal sweating
M chest distress. shortness of breath
M fever, night sweats, chest pain
M fever, cough
M autopsy (found dead)
N/A: not available
66
(23)
61
(20)
29
54
(19)
(23)
37
(11)
70
38
(18)
41
31
(18)
(21)
31
(18)
(22)
61
(17)
no
adriamycin, ifosfamide
Chemotherapy/radiothrapy cytokeratin, vimentin
EMA, vimentin, bcl-2
Immunohistochemically positive antigens SYT-SSX1 fusion transcript
N/A
Molecular analysis
N/A
no (refused)
chemotherapy
N/A
biopsy
N/A
no
yes
N/A
EMA, vimentin, bcl-2
N/A
N/A
N/A
N/A
N/A EMA, vimentin, BER EP4, bcl2, cytokeratin (AE1/AE3), EMA, cytokeratin (AE3)
EMA, vimentin
N/A
chemotherapy
N/A
no
N/A
EMA, cytokeratin (AE1/AE3), bcl2
N/A
EMA, cytokeratin 5/6,7, thrombomodulin
N/A
N/A
vimentin (EMA negative)
chemotherapy, radiotherapy EMA, CD99
yes
adriamycin, ifosfamide, doxorubicinehydrochloride, EMA, vimentin, cytokeratins radiotheraphy
no (poor health status)
imcomplete excision radiotherapy
complete excision
near total excision
yes
yes
yes
cisplatin, doxorubicin, imcomplete excision cyclophosphamide, etc
N/A
imcomplete excision chemotherapy
complete excision
complete excision
yes
imcomplete excision ifosphamide
imcomplete excision no (refused)
N/A
N/A
N/A
N/A
SYT-SSX fusion gene
SYT-SSX1 transcript
N/A
SYT-SSX2 expression
SYT/SSX transcripts
N/A
SYT-SSX fusion gene
N/A
N/A
N/A (supportive care)
N/A
Died 10-d after admission
N/A
no evidence of disease at 12-m
Died 7-m after discharge
Alive at 13-m
No reccurrence at 12-m post-operation
Alive >4.5-y
N/A
Died 31-m from the initial diagnosis
N/A
Alive at 13-m
N/A
Died 79-d after the operation
SYT-SSX2 fusion gene N/A
Alive at 2-m after the operation
Died 26-m after the initial presentation
Died 15-d later
Awaiting heart transplantation
Died 27-m after the presentation
Alive at theat the 12-m follow-up
(found dead)
N/A
Outcome
N/A
SYT-SSX fusion gene
N/A
no (refused) EMA, cytokeratin 7,19, pankeratin AE1/AE3 rearrangement of SYT gene ifosfamide, doxorubicin, imcomplete excision vimentin, bcl-2, calponin, CD99 rearrangement of SYT gene diamminedichloroplatinum biopsy N/A vimentin, bcl-2, calponin, CD99 rearrangement of SYT gene
biopsy
no
complete excision
45
(16)
F dyspnea, cough, night sweats
Surgical excision
Reference Age Sex Presentation
Table. Cases of Synovial Sarcoma Reported in the Pertinent English Literature
Intern Med 53: 595-601, 2014 DOI: 10.2169/internalmedicine.53.1749
Intern Med 53: 595-601, 2014
DOI: 10.2169/internalmedicine.53.1749
Discussion We herein reported a patient who was referred to our hospital due to symptoms of cardiac tamponade. He was found to have a large bloody pericardial effusion and pericardial mass that was diagnosed to be a pericardial synovial sarcoma due to its histologic characteristics, including rearrangement of the SYT gene. Soft tissue sarcoma is a rare malignancy, comprising less than 1% of malignant neoplasms; this proportion may be much less (
