10 Review Article Page 1 of 10 Primary mediastinal synovial sarcomas Katherine Syred1, Annikka Weissferdt2 1Department of Pathology, Derriford Hospital, University Hospitals Plymouth NHS Trust, Plymouth, UK; 2Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Contributions: (I) Conception and design: A Weissferdt; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Annikka Weissferdt, MD, FRCPath. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 085, Houston, TX 77030, USA. Email: [email protected]. Abstract: Synovial sarcoma is a malignant mesenchymal neoplasm that accounts for approximately 10% of all soft tissue sarcomas. These tumors most commonly occur in the extremities of young adults but are not restricted to this site and can arise in virtually any organ system. Synovial sarcomas originating in the mediastinum are exceptionally rare and are often mistaken for other, more common neoplasms in this location, especially since there are no specific imaging characteristics or clinical manifestations. Contrary to synovial sarcomas of the extremities, mediastinal tumors more commonly affect male patients. Histologically, these tumors can be divided into monophasic, biphasic and poorly differentiated variants, further complicating the diagnostic process. Recent advances in immunohistochemical and molecular techniques have provided useful tools to confirm the diagnosis and distinguish these tumors from other mediastinal neoplasms. The treatment of mediastinal synovial sarcomas often requires multimodal therapy, including surgery, chemotherapy and radiation. Despite this, the prognosis for synovial sarcomas in this location appears to be worse than for their analogues in the soft tissue, likely related to the often large size of the lesions and close proximity to critical anatomic structures making complete surgical resection difficult to achieve. This review summarizes the clinicopathological, immunohistochemical and molecular characteristics of these rare neoplasms. Keywords: Mediastinum; sarcoma; synovial sarcoma; thoracic; translocation Received: 29 April 2020; Accepted: 03 June 2020; Published: 30 June 2020. doi: 10.21037/med-20-19 View this article at: http://dx.doi.org/10.21037/med-20-19 Introduction These tumors primarily affect a younger patient population, including adolescents and young adults (7,8). Apart from Synovial sarcoma derives its name from the initial assumption the soft tissues, synovial sarcomas have been recognized that the tumor originated from synovial cells, after a frequent in most anatomic sites, including the thoracic cavity. Most association with joints, tendons and bursal structures of the thoracic cases occur in the pleuropulmonary system was noted in early reports (1,2). Recognition of cases not while the mediastinum is an exceptionally rare site (9-13). associated with such structures and identification of variable In largest series to date, reporting 21 cases, the incidence epithelial differentiation in these tumors has subsequently of mediastinal synovial sarcomas was estimated at 11.2% of led investigators to believe that synovial sarcomas are likely all thoracic synovial sarcomas (11). Histologically, synovial derived from pluripotent mesenchymal cells capable of sarcomas can display a spectrum of growth patterns, divergent differentiation (3,4). Synovial sarcomas most including monophasic, biphasic and poorly differentiated commonly arise from the deep soft tissues of the extremities, types, adding diagnostic difficulty to their recognition, accounting for 5–10% of all soft tissue sarcomas (5,6). especially in sites not commonly associated with these © Mediastinum. All rights reserved. Mediastinum 2020;4:13 | http://dx.doi.org/10.21037/med-20-19 Page 2 of 10 Mediastinum, 2020 neoplasms. The discovery that 95% of synovial sarcomas are Clinical features characterized by a specific translocation t(X;18)(p11;q11) that Synovial sarcomas of the mediastinum can occur in any age can be detected by fluorescence in situ hybridization (FISH) group (range, 3–83 years) but are most commonly detected or reverse transcription polymerase chain reaction (RT-PCR) in the 4th decade of life. Contrary to their soft tissue is a powerful tool in the differential diagnosis with other, analogues which show no gender bias, mediastinal primaries more common neoplasms in the mediastinum and molecular are more common among male patients (9-13). Although confirmation remains the gold standard in the diagnosis of the spectrum of presenting symptoms is wide (Table 1), these tumors. This review provides a summary of the current most patients complain of chest or shoulder pain, shortness knowledge concerning these unusual tumors and compares of breath, cough and pericardial effusion. Notably, each their clinicopathologic characteristics to those of their soft patient’s clinical history and physical examination should tissue analogues. include assessment of prior history or concurrent soft tissue tumor in order to exclude a metastatic process. Table 1 Common presenting symptoms of primary mediastinal synovial sarcomas Radiological features Chest pain Shoulder pain Mediastinal synovial sarcomas can arise in any mediastinal compartment, most commonly the anterior mediastinum, Shortness of breath followed by the posterior mediastinum and middle and Cough superior compartments (10,11,13). The radiological Pericardial effusion appearance of mediastinal synovial sarcomas is non- specific, often precluding separation from other mediastinal Pleural effusion neoplasms. On chest radiographs, the tumors appear as well Fatigue circumscribed neoplasms with sharply marginated borders Weakness or as ill-defined infiltrative lesions. Computed tomography Weight loss (CT) scanning will reveal large tumor masses with homogeneous or heterogeneous enhancement that show Fever high uptake on positron emission tomography (PET) (Figure SVC obstruction 1A,B). At magnetic resonance imaging (MRI), the tumors SVC, superior vena cava. typically demonstrate heterogeneous signal intensity on A B Figure 1 Imaging features of a primary synovial sarcoma of the mediastinum. (A) On a CT scan of the chest, the tumor is apparent in the left superior mediastinum; (B) high uptake is seen on PET scan. CT, computed tomography; PET, positron emission tomography. © Mediastinum. All rights reserved. Mediastinum 2020;4:13 | http://dx.doi.org/10.21037/med-20-19 Mediastinum, 2020 Page 3 of 10 T1- and T2-weighted images and may contain fluid-fluid Pathological features levels due to hemorrhage or necrosis within cystic tumor Grossly, synovial sarcomas arising in the mediastinum are components. Cyst formation, areas of calcification, necrosis large tumors with reported sizes ranging from 5 to 23 cm and hemorrhage are common findings (10,12,14). and an average size around 12 cm (9-11). The tumors may be well circumscribed and surrounded by a thin fibrous capsule or poorly delineated masses that infiltrate surrounding anatomic structures (Figure 2). The cut surface is gray-white to tan and can have a soft or firm consistency. Areas of calcification, cystic degeneration, gelatinous change, hemorrhage or necrosis can often be identified in varying proportions (9,10). Histologically, the tumors can be divided into three different subtypes: monophasic, biphasic and poorly differentiated synovial sarcoma. Monophasic tumors are characterized by a monotonous, highly cellular spindle cell proliferation Figure 2 Gross features of a primary mediastinal synovial sarcoma. growing in sheets, fascicles or storiform patterns (Figure The tumor is multinodular, relatively circumscribed and lined by a 3A,B). In some areas, a palisading nuclear pattern thin fibrous membrane. reminiscent of Verocay bodies or a tigroid appearance A B C D Figure 3 Histopathological features of monophasic synovial sarcoma. (A) Low power view shows a neoplasm composed of sheets of monomorphic spindle cells (H&E, ×4); (B) in some cases, the tumor cells are arranged in fascicles (H&E, ×10); (C) alternating hypo and hypercellular areas are a common finding in these tumors (H&E, ×4); (D) the mitotic activity is typically increased (H&E, ×20). © Mediastinum. All rights reserved. Mediastinum 2020;4:13 | http://dx.doi.org/10.21037/med-20-19 Page 4 of 10 Mediastinum, 2020 A B C D Figure 4 Frequent stromal changes associated with mediastinal synovial sarcomas. (A) Prominent stromal hyalinization in a mediastinal synovial sarcoma (H&E, ×4); (B) hemangiopericytoma-like blood vessels are a characteristic finding in these tumors (H&E, ×10); (C) cystic changes are another very common feature in synovial sarcoma (H&E, ×4); (D) stromal mast cells (arrows) are frequently seen in these neoplasms (H&E, ×40). and a scant rim of eosinophilic cytoplasm. Cytologic atypia is not a feature of these tumors but the mitotic activity is typically increased, ranging from 2 to more than 20 mitoses per 10 high power fields (HPF) (Figure 3D). Frequent stromal changes include myxoid change or hyalinization (Figure 4A), a hemangiopericytic (staghorn) vascular pattern (Figure 4B), foci of calcification, cystic change (Figure 4C), and areas of necrosis or hemorrhage. Another characteristic finding is the