Primary cardiac tumors are rare, occurring less frequently than metastatic tumors (in a ratio of approximately 1:20–40) with an incidence in autopsy series ranging only from 0.001 to 0.03%, of which approximately 75% are histologically benign. Malignant tumors almost all of which are sarcomas, which may be of several histologic types, angiosarcoma 31%, rhabdomyosarcoma 21%, malignant mesothelioma 15%, and fibrosarcoma 11%. Primary cardiac synovial sarcoma (PCSS) was first described in 1978. PCSS accounts for approximately 4.2% of primary cardiac sarcomas.
In general, cardiac malignant tumors are characterized by rapid progression culminating in the patient's death within weeks to months from the time of presentation, as a result of hemodynamic compromise, local invasion, or distant metastasis.
Synovial sarcoma occurs most often in children and young adults and is an aggressive tumor with 10-year survival rates reported in some series as low as 0%–20%. It is divided into three subtypes: monophasic, biphasic, and poorly differentiated. Historically, these nonspecific histologic characteristics have made the establishment of a definitive diagnosis difficult. However, a characteristic chromosomal abnormality for synovial sarcoma has been identified for all morphologic subtypes: t (X;18).
PCSS with immunohistochemistry and cytological confirmation reported in very few cases in literature.
A 45-year-old premeopausal female admitted to our hospital with 3-month history of progressive dyspnea on exertion and pedal edema. Known smoker since childhood and known hypertensive for the past 1 year on treatment with calcium channel blockers.
G4 L1 (2 still births full term; one died 3rd month postnatally – all home deliveries)
No significant family history.
Initially admitted with similar complaints outside and treated as anemia 2 months back. Symptoms improved transiently and again reoccurred.
On physical examination, her pulse rate 70/min and blood pressure 110/70 mmHg both upper limbs.
Bilateral pitting pedal edema up to level of ankles and periorbital edema with facial puffiness present.
Jugular venous pressure elevated 6 cm above clavicle.
On cardiac examination S1 normal, loud P2 and no murmurs.
Investigations revealed thrombocytopenia with platelet count <50,000 cells/mm3 and microcytic normochromic anemia on peripheral smear.
12-lead electrocardiography -sinus rhythm with low voltage complexes.
Chest X-ray posteroanterior view – cardiomegaly present
Transthoracic two-dimensional echocardiography revealed heterogeneous large cystic mass with incomplete septations in right atrium (RA) and right ventricle (RV) across tricuspid valve occupying whole of RV cavity and extending into RV outflow tract and pulmonary artery with severe obstruction across tricuspid valve and moderate pericardial effusion. Dilated RA and RV with normal sized LA and LV [Figure 1].
Admitted for further investigation in view of cystic mass in right heart with differential diagnosis of hydatid cyst or myxoma with cystic degeneration.
MAGNETIC RESONANCE CARDIOGRAM
- large solid cystic space-occupying mass with septae measuring 7.9 cm × 2.9 cm × 4.3 cm noted in the RA in relation to the septum and floor of the RA which is seen prolapsing through the tricuspid valve into RV and right ventricular outflow tract and reaching up to the pulmonary valve and inferiorly bulging into inferior vena cava, posteriorly, and to left bulging into interatrial septum. There is mild-to-moderate contrast enhancement of solid component [Figure 4].
- Mild-to-moderate pericardial effusion
- Bilateral mild pleural effusion and mild ascites
Possibilities: (1) myxoma with a cystic component (more likely) and (2) hydatid cysts (less likely)
Computed tomography screening revealed a hypodense lesion in RA and RV with a HU of 31–38 devoid of calcification
Normal epicardial coronaries on coronary angiogram.
Referred to cardiothoracic surgeon for further management and patient underwent surgical excision of the mass [Figure 2]. At surgery, the patient was placed on cardiopulmonary bypass using bicaval cannulation through a median sternotomy approach. An irregular mass was observed arising from the right atrioventricular groove and extending to the anterior of the RA. By opening her RA, the surgeons observed that the main body of the tumor was located in the wall of the RA, extending into the RV causing functional tricuspid stenosis.
Synovial sarcoma is a malignant neoplasm, approximately 90% of which arise in the extremities, with a predilection for the regions adjacent to large joints. Occasionally, the tumor may involve unusual sites throughout the body including the head and neck, heart, pleura, abdomen, kidney, prostate, and vulva, which may be difficult to correctly diagnose.
PCSS occurs infrequently. Wang and Li reviewed 54 isolated literature reports before 2012 and found that there were sixty patients with PCSS, and only 16 cases of intracardiac sarcomas.
PCSS may occur at any age (from 13 to 70 years), although it more frequently occurs during the fourth decade with a mean age of 37 years, and a male/female ratio of approximately 3:1. The most common symptom is dyspnea (in 68% of patients). The patients with PCSS more readily exhibit gastrointestinal and systemic symptoms, and they frequently also have pericardial effusions compared to patients with benign cardiac tumors. The tumor often displays a larger tumor size of more than 5 cm in diameter. The most common location is the pericardium. Other locations include the RA, left atrium, tricuspid valve, RV, left ventricle, mitral valve, and pulmonary valve sequentially and the tumor readily involves the pericardium.
The clinical presentation of cardiac synovial sarcoma is nonspecific, so the diagnosis is almost always at advanced stage in most of the cases. Patients usually present with more than one symptom such as shortness of breath, dyspnea, chest pain, and weight loss and features of congestive heart failure. Patient of left-sided tumor presents earlier than right-sided tumor due to their mass effect and obstruction to pulmonary veins. Tumors proliferate rapidly and often cause death through widespread infiltration of the myocardium or obstruction of flow within the heart.
Macroscopically, the tumor was often polypoid or lobulated with a smooth or well-circumscribed surface and a broad base with size of tumor varies from 2.9 to 15 cm. Left-sided tumors are comparatively small.
Microscopically, cardiac synovial sarcoma displays two histological patterns, monophasic and biphasic. Monophasic pattern shows only one type of cells pattern whereas biphasic tumor was composed of two types of cells, fibrosarcoma-like spindle cells and epithelial cells resembling those of carcinoma. The availability of a frozen section during surgery allows the diagnosis of sarcoma, while for more specific diagnosis, immunohistochemistry is required.
Wang and Li reviewed 51 reported occurrences with pathological information, among which 27 (52.9%) were monophasic and 24 (47.1%) were biphasic PCSS. It is difficult to discriminate biphasic sarcoma from metastatic carcinosarcoma by the morphologic features alone, particularly at frozen section; moreover, mesothelioma, myoepithelial carcinoma, and malignant peripheral nerve sheath tumor (MPNST) with epithelial differentiation must also be considered in the differential diagnosis. Although the immunohistochemical stains, such as CK19, S-100, BCL-2, CD99, and calponin, could aid in making the diagnosis, the role of immunohistochemical staining is limited.
For diagnosis, immunohistochemical staining for both mesenchymal and epithelial markers and molecular testing for specific mutation is gold standard. Expression of both cytokeratin and vimentin is seen in most synovial sarcoma with biphasic histology with cytokeratin and vimentin and epithelial and mesenchymal components. In monophasic synovial sarcoma, tumor cells diffusely stain for vimentin and variably positive for epithelial proteins in cells that do not appear epithelial on hematoxylin eosin staining. TLE1 is a useful marker because it is negative in carcinosarcoma, although TLE1 shows limited specificity in the diagnosis of synovial sarcoma as it is expressed in several neoplasms in the differential diagnosis, particularly those of peripheral nerve sheath origin. Because mesothelioma shares expression of epithelial markers, WT-1 and calretinin, mesothelioma could be excluded because WT-1 and calretinin were negative in the tumor. Myoepithelial carcinoma exhibits tubular and ductal elements resembling biphasic SS, which may be a pitfall, and also often expresses S-100, SMA, and epithelial markers; Although MPNST with epithelial differentiation is rare, and mostly occurs in patients with neurofibromatosis type 1, it must be distinguished in the differential diagnosis from SS. There is no satisfactory differential diagnostic marker because S-100, epithelial markers, TLE1, and SOX 10 could be positive in both tumors.
The hallmark of diagnosis of synovial sarcomas is the detection of the translocated chromosome t (X; 18) (p11.2; q11.2), which gives rise to a fusion gene, SS18 (SYT)-SSX (SSX1 or SSX2, or both), which is present in more than 90% of the synovial sarcomas w5x. Molecular diagnosis of synovial sarcoma by cytogenetics or RT-PCR is a valuable when it is from an uncommon location such as in the heart, whereas carcinosarcoma and MPNST lack SS18-SSX fusions.
Some cases have of chromosomal abnormality that include t (X; 18) (p1; p1) X2, del-4, -13, -14, -16, +17, +18, +4, +7, +8 and del (13;15) (q10; q10), del (1) t (1;8) (q10; q10).
Cardiac magnetic resonance imaging (MRI) may be a useful modality in evaluation of cardiac masses in view of providing superior soft-tissue contrast resolution on extension into myocardium.
Histopathological section of the specimen shows a monophasic hypercellular spindle cell neoplasm arranged in fascicles and sheets with little intervening stroma. The neoplastic cells are monotonous short spindly with oval-to-spindle vesicular nuclei, evenly dispersed chromatin, inconspicuous nucleoli- and scant cytoplasm. Myxoid change is noted with no definite epithelial differentiation with no areas of necrosis.
IHC features were positive for TLE-1, BCL 2, and MIC-2 (diffuse and strong) and are immunonegative for SMA, S-100 protein, desmin, and CD34. The Mib-1 labeling index is approximately 10% in areas of highest proliferative activity [Figure 3].
The final pathological diagnosis was synovial sarcoma favor monomorphic spindle cell subtype. FNCLCC Grade – at least grade 2.
The definitive feature of synovial sarcoma is the presence of t (X: 18), which could not be completed in our case.
Although few reports exist of palliation with surgery, radiotherapy, and/or chemotherapy, the response of cardiac sarcomas to these therapies is generally poor.
Complete surgical resection may not be feasible in many cases due to its location and extensive spread by the time of presentation there is no consensus regarding the adjuvant modality to be used after primary surgical resection. Most case reports have indicated the use of adjuvant chemotherapy but there is no standard regimen, although adriamycin and ifosfamide-based chemotherapy is commonly used. Both of these chemotherapeutic agents are toxic and if there is metastasis, no standard therapy is clearly superior to others. Role of radiotherapy is presently not clear.
Novel therapeutic agents targeting translocation t (X; 18) with the resulting SYT/SSX fusion protein makes synovial sarcoma an ideal candidate for molecular therapy.
Contrasting outcomes have been reported regarding heart transplantation for the management of primary cardiac sarcoma. Despite the fact some authors did not find improvement of survival rates in comparison with conventional treatment, other authors have discovered a more prolonged survival after transplantation, inpatients small intracardiac synovial sarcomas occurring in young patients with adjuvant chemoradiotherapy, followed by total artificial heart implantation and subsequent transplantation. In this respect, a role for heart transplantation for lower grade and less aggressive cardiac sarcomas has recently been advocated by Li et al.
Prognosis of patients with primary cardiac sarcoma is poor, most of them dying within a few months after diagnosis and surgery with mean survival of 9–16.5 months. As cardiac synovial sarcomas are rare, prognostic factors are hard to ascertain, but the absence of complex chromosomal abnormalities, younger age, and pericardial origin of the tumor seem to be favorable factors.
In analysis of sixty cardiac synovial sarcoma patients derived from 54 articles present in the literature, Wang and Li found that overall survival was affected by patient's age (<30 years) and chemotherapy. However, in their analysis, the overall patient's outcome was poor, due to frequent relapses and metastases.
Differential diagnosis of cardiac synovial sarcoma includes malignant mesothelioma, carcinosarcoma, hemangiopericytoma, leiomyosarcoma, and MPNST. Unlike other tumors, synovial sarcoma usually has a low-grade histologic appearance, with no or little cytologic atypia and cellular pleomorphism. In addition, immunohistochemistry helps in these differential diagnoses.
PCSS is very rare. Radiographic evaluation preferably by MRI should be done in all cardiac masses. IHC and molecular analyses play an important role in the pathological confirmation of sarcomas. Resection of the tumor by surgery is the primary modality of treatment. No consensus is available regarding adjuvant management with chemotherapy and radiotherapy.
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