Primary Mediastinal Synovial Sarcoma with Pericardial Involvement: A Case Report

Sarcomas are rare soft tissue tumors (accounting for approximately 1% of all tumors [1]) that are derived from mesodermal tissue. These tumors often present in the extremities of adolescents or young adults and most commonly metastasize to the lung and to bone. Even rarer are sarcomatous tumors, which originate in the mediastinum [2]. Complicating the diagnosis, primary mediastinal sarcomas can present as pericardial effusions with negative cytology with no clear mass on some imaging modalities, particularly early in the clinical course [3]. Here we present the rare case of a 29-year-old male patient who presented with dyspnea on exertion and leg swelling who was found to have a large pericardial effusion of initially unclear etiology with a subsequent diagnosis of a primary mediastinal synovial sarcoma.

The patient was a 29-year-old male who originally presented to his primary care provider with 3 weeks of back pain, dyspnea on exertion, leg swelling, and orthopnea. He did not endorse any weight loss, night sweats, fevers, or chills. He had no active chronic medical conditions other than obesity (body mass index 48), no significant past medical history, no family history of cancer, and took no medications. His vital signs at that time showed a blood pressure of 118/90, a heart rate of 88 bpm, respiratory rate of 23, and an oxygen saturation of 96%; his physical exam was unrevealing except for mild, bilateral lower extremity edema, which was new. An echocardiogram was ordered, which demonstrated a large pericardial effusion with early tamponade physiology; he was referred to a local community hospital where he was admitted to the ICU for close monitoring. While admitted, he underwent a pericardiocentesis that yielded serosanguinous fluid. He was subsequently transferred to the cardiology service at our tertiary care hospital for further management.

Repeat pericardiocentesis here initially returned with a lymphocytic predominance (Table 1), negative flow cytometry, and cytology, which demonstrated atypical cells, which were favored to represent reactive mesothelial cells. Computed tomography (CT) scans of the chest, abdomen, and pelvis were negative for lymphadenopathy or detectable mass although poor visualization of the left atrial appendage was noted. Complete blood count and chemistries were normal. The pericardial fluid ultimately grew Staphylococcus lugdunensis, which was felt to possibly be a contaminant. After a second pericardiocentesis demonstrated no additional fluid re-accumulation, he was subsequently discharged from the hospital on 2 weeks of penicillin G with plans to follow up with cardiology and infectious disease in the outpatient setting for what was presumed to be an idiopathic/post-viral pericardial effusion.

At his cardiology and infectious disease appointments 2 months later, he endorsed significantly improved symptoms despite a repeat outpatient echocardiogram that demonstrated recurrence of the large pericardial effusion. In light of his improved symptoms, only an outpatient rheumatologic workup was recommended at that time. Before this workup could be pursued and 5 months from his initial presentation, the patient re-presented to the emergency department with worsening dyspnea on exertion and orthopnea. Vital signs were within normal limits and exam again revealed lower extremity edema and distant heart sounds. His laboratories revealed an elevated BNP of 155 with normal chemistries and complete blood counts. He was admitted to the inpatient cardiology service and a CT of the chest was again read as a high-density pericardial effusion with significant increase from the scan 5 months prior. Cardiac magnetic resonance imaging (MRI) was obtained, which revealed a large mediastinal mass with internal necrosis invading the pericardium with a large extension adjacent to the left heart with likely left lateral basilar invasion of the myocardium (Fig. 1a, b).

Cardiothoracic surgery completed an open sternotomy core biopsy revealing a dense, bulky, and invasive tumor encasing the heart and aortopulmonary root. A core biopsy was obtained and histopathology returned a high-grade spindle cell malignancy, histologically and immunohistochemically suggestive of either a BCOR-CCNB3 fusion sarcoma, synovial sarcoma, or less likely an undifferentiated round cell sarcoma with CIC-DUX4 translocation (Fig. 2). A Mayo Clinic sarcoma next-generation sequencing panel (Mayo Test ID: SARCP) was sent to further elucidate the pathological results, which returned positive for a rearrangement of the SS18 gene, a finding felt diagnostic of synovial sarcoma in this setting.

Abdominal CT and brain MRI were obtained to complete staging with no metastatic disease present. PET-CT revealed an infiltrative and multinodular soft tissue mass within the pericardial cavity (Fig. 1c). Due to the complexity of the patient’s case in the setting of his severe volume overload, preload-dependent tamponade physiology, mass encasing critical cardiopulmonary structures, potential need for high volumes of fluid with some chemotherapy regimens, and large sternotomy wound that would require time to heal before treatment, a multidisciplinary discussion took place between the patient, his family, and the care team (hematology/oncology, cardiothoracic surgery, cardiology, and radiation oncology). As synovial sarcomas are often chemosensitive [4] and his tumor was inoperable, it was decided that he would undergo dose-reduced infusional doxorubicin (12.5 mg/m²) daily for 4 days despite his significantly reduced cardiac function as a result of the tumor. After receiving one cycle of treatment, the patient unfortunately re-presented within a week of discharge in septic shock from skin/soft tissue infection and passed away from pre-existing obstructive (restrictive cardiac physiology) and septic shock.

Here we describe a rare case and presentation of primary mediastinal synovial sarcoma. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000542680). Sarcomas, in general, are rare and aggressive tumors. Those within and around the heart are even rarer and carry an even poorer prognosis by the time they are diagnosed due to their proximity to critical structures and subsequent inability to be adequately resected upon discovery. A large series of 1,000 cases of all mediastinal sarcomas (including non-synovial) reported a 5-year overall survival rate of just 15% [5]. Those sarcomas that initially present as a pericardial effusion are diagnostically challenging as a critical amount of time can often pass if they are not identified quickly.

Pericardial effusions in the general population are a common cardiac manifestation of disease, but as often as 40% of the time, no clear etiology is found at the time of presentation. Causes can range widely encompassing autoimmune, metabolic, drug-related, neoplastic, viral, fungal, or bacterial etiologies. In terms of infectious sources of pericardial effusions, those secondary to Tuberculous mycobacterium (TB) can be as high as 60% of all new effusions in areas where TB is endemic [6]. This is in stark contrast to developed countries where pericardial effusions secondary to any infectious etiology (including non-TB) fall to less than 30% [7]. In the case of our patient, his pericardial fluid cultures grew S. lugdunensis, but these results were felt to be a potential contaminant from instrumentation during the pericardiocentesis. In the absence of convincing culture or clinical data, additional diagnostic work-up with advanced imaging should be pursued. While CT and echocardiogram are often used in an initial pericardial effusion evaluation, depending on how early in the disease course that these studies are obtained, they can fail to reveal the mass such as was the case with our patient. Other reports note similar periodic early failure of cardiac mass detection with echocardiogram and CT [8]. PET and MRI remain the gold standard for mass detection by imaging [9].

Cytology and even pericardial biopsy (or a combination of the two) can also be helpful in the diagnosis of presumed malignancy involving the heart and pericardial space with some studies demonstrating sensitivities as high as 92% for cytology alone [10]. However, the literature still demonstrates a false-negative rate with pericardial effusion cytology alone as high as 14.7% [11], which can have profound effects on morbidity and mortality such as with our case (negative cytology on admission). In the general population, metastatic lung cancer is the most common cause of a malignant pericardial effusion in both men and women (75% and 52%, respectively) with the second most common in women being breast cancer (39%) [11]. However, in AYA-aged patients, further diagnostic investigation with alternative imaging modalities (MRI/PET) and/or tissue biopsy should be pursued due to concern for rare, occult malignancies in otherwise idiopathic, recurrent pericardial effusions.

Typically used in the evaluation of lymphoproliferative disease, flow cytometry has a significant and well-established role in the workup of different types of serous effusions including pleural and peritoneal [12]. However, a paucity of data exists regarding the diagnostic accuracy and utility of flow cytometry in the evaluation of new pericardial effusions; most of these data exist solely in case reports [13]. For this reason, there are little data on the positive or negative predictive value of flow cytometry results in diagnosing lymphoproliferative disease arising within the pericardium. Our patient had negative flow cytometry on initial pericardiocentesis, as would be expected with a diagnosis of sarcoma. Nonetheless, in patients where there is high clinical suspicion, flow cytometry should be sent as part of the routine analysis to most effectively obtain the necessary diagnosis and initiate early treatment.

Furthermore, despite their rarity, a range of different genetic subtypes of mediastinal sarcomas exist including synovial, angiosarcoma, and undifferentiated high-grade sarcoma making classic histopathological diagnosis difficult. For this reason, molecular genetic and cytogenetic analysis has become an important pillar of accurate diagnosis and therefore treatment [14]. While the majority of synovial sarcomas feature the characteristic sweeping, dense fascicles of spindled cells with high nuclear to cytoplasm ratios, the undifferentiated form of synovial sarcoma displays sheets of small, epithelioid to subtly spindled, round blue cells with no evidence of line of differentiation. The current case showed areas of spindled cells but also showed areas of more epithelioid, small, undifferentiated cells (Fig. 2a, b). This unique morphology brings up a differential that includes synovial sarcoma, BCOR-CCNB3 fusion sarcoma, and an undifferentiated CIC-rearranged sarcoma. For the pathologist, immunohistochemistry can be helpful in differentiating these tumors but is often nonspecific. Synovial sarcoma characteristically is positive for TLE1 and keratin while negative for BCOR, cyclin D1, SATB2, and CD99; the current case was TLE1, SATB2, BCOR, and cyclin D1 positive with negative keratin staining (Fig. 2c, d) [15]. Due to the significant overlap in morphology and immunohistochemistry, genetic testing is a mainstay for these challenging cases and can assist in parsing out genetic underpinnings to elucidate an accurate diagnosis.

Mediastinal synovial sarcomas are rare, highly aggressive, and highly morbid neoplasms that affect AYA-aged patients. In some cases, they may present late and insidiously due to their sole presenting clinical manifestation being pericardial effusion. Particular care should be taken to rule out malignancy with possible combination of cytology, flow cytometry, MRI or PET-guided imaging, and surgical exploration in the AYA-aged population when idiopathic, recurrent pericardial effusion is found. Next-generation sequencing can be helpful in solidifying the particular diagnosis.

This case report presents a completely de-identified patient presentation and clinical course that does not include human subjects research, materials, or data. Ethical approval is not required for this study in accordance with local/national guidelines. Written informed consent was obtained from the patient’s next of kin (mother) for publication of the details of their medical case and any accompanying images.

No authors have any conflicts to disclose.

The authors did not receive support from any organization for the submitted work. No funding was received to assist with the preparation of this manuscript.

Kenan Michaels: writing – original draft, conceptualization, and visualization. Sean Dougherty: writing – review and editing, visualization, and conceptualization. Brett Kurpiel: writing – original draft and visualization. Michael Douvas: writing – review and editing and supervision.

The data represented with this study are not publicly available due to the data containing information that could compromise the privacy of the patient represented within this case. Data could be provided upon reasonable request to the corresponding author (Michael Douvas, MD) with written consent from the patient’s next of kin.