Ann Thorac Surg 2002;73:628-630
© 2002 The Society of Thoracic Surgeons
Case report
Mediastinal synovial sarcoma: report of two cases with molecular genetic analysis
Jacqueline K. Trupiano, MDa,
Thomas W. Rice, MDb,
Kevin Herzog, MDa,
Frederic G. Barr, MDc,
Janet Shipley, PhDd,
Cyril Fisher, MDe,
John R. Goldblum, MD*a
a Department of Anatomic Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
b Cardiothoracic Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
c Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
d Section of Molecular Carcinogenesis, Institute of Cancer Research, Haddow Laboratories, Belmont, Sutton, United Kingdom
e Histopathology Department, Royal Marsden Hospital, London, United Kingdom
Accepted for publication June 23, 2001.
* Address reprint requests to Dr Goldblum, Cleveland Clinic Foundation, 9500 Euclid Ave, L25, Cleveland, OH 44195, USA
e-mail: goldblj{at}ccf.org
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Abstract
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Synovial sarcoma occurs predominantly in the paraarticular regions of the extremities. Synovial sarcoma of the mediastinum is an exceedingly rare neoplasm that has overlapping histologic and immunophenotypic features with other tumors in the differential diagnosis. We describe two cases. One is a 67-year-old patient who presented with chest pain and shortness of breath. Diagnostic imaging revealed a mediastinal mass extending over the cardiac apex. Histopathology, immunohistochemistry, and molecular genetic analysis confirmed the diagnosis of synovial sarcoma. The patient underwent surgical resection and postoperative radiation therapy. He is alive and well 18 months after diagnosis. This case illustrates the importance of proper procurement of frozen tissue for molecular genetic analysis for the identification of the t(X;18), characteristic of synovial sarcoma. Detection of this translocation is of paramount importance to confirm this diagnosis, particularly when this neoplasm arises in atypical locations outside the extremities.
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Introduction
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Synovial sarcoma is a malignant neoplasm predominantly affecting the soft tissues of the extremities of adolescents and young adults [1]. This neoplasm has been described in a wide variety of other locations including the mediastinum [2]. Herein, we report 2 additional cases of mediastinal synovial sarcoma with molecular analysis.
Case 1 is a 67-year-old man who presented with a 1-week history of left chest subscapular pain and progressive shortness of breath. A chest computed tomographic scan revealed a 9.0 cm soft tissue mass extending over the entire cardiac apex. At surgery, the mass was firmly adherent to the pericardium, and a partial pericardectomy was performed. Case 2 is a 30-year-old woman in whom an incidental 17-cm anterior mediastinal mass was found on imaging following a motor vehicle accident. The patient underwent partial resection of the tumor, pericardectomy, and wedge resection of the left upper lobe of lung. Physical examination and additional imaging studies failed to reveal other masses in the trunk or extremities in either patient.
Histologically, both tumors demonstrated a biphasic malignant neoplasm with areas of epithelial differentiation with pseudoglandular spaces intimately admixed with well-oriented, plump spindle-shaped cells with a prominent hemangiopericytoma-like vascular pattern (Fig 1).
Immunohistochemistry in Case 1 showed focal immunoreactivity for a variety of epithelial markers including cytokeratins (AE1/3, CAM 5.2, cytokeratins 7, 19) and epithelial membrane antigen. Immunostains commonly positive in malignant mesothelioma, including Leu-M1, B72.3, BER-EP4, and CEA were negative. Case 2 was negative for all of the aforementioned markers.
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Fig 1. Biphasic synovial sarcoma (Case 1), characterized by an admixture of malignant spindle cells and glandlike structure with intraluminal eosinophilic secretions (original magnification, x500).
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Fig 2. Representative nuclei from interphase fluorescent in situ hybridization analysis of Case 1. (A) Adjacent red and green signals indicating that the cosmid from chromosome X (green) and the YAC from chromosome 18 are juxtaposed. This is consistent with the presence of the derivative X chromosome associated with synovial sarcoma. The additional red signal is assumed to be from a normal chromosome 18. (B) A green signal from the X centromere probe (red) and the cosmid (green) which lies between the two main breakpoint regions at the SSX1 and SSX2 gene loci. As these signals are adjacent, the breakpoint appears to be above the cosmid marker consistent with disruption of the SSX1 gene. (C) The relative position of these markers on a derivative X chromosome (chromosome 18 material shown in gray) with disruption in the SSX1 region. (X centr = X centromere; X cos = X cosmid; 18 Yac = yeast artificial chromosome from chromosome 18.)
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Fluorescent in situ hybridization was performed on frozen tissue in Case 1 (Fig 2) and the polymerase chain reaction was performed on tissue obtained in Case 2. Both studies revealed evidence of an SSX1-SYT fusion transcript indicative of a t(X;18) characteristic of synovial sarcoma.
Patient 1 completed radiation therapy (total dose 4,000 Cgy) and is alive without evidence of disease 19 months since presentation. Patient 2 underwent multiagent chemotherapy but expired 10 months after initial presentation from progressive disease.
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Comment
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The mediastinum is host to a vast array of both primary and metastatic neoplasms, the differential diagnosis of which is extensive and depends upon the mediastinal compartment involved, clinical history, presentation, and age of the patient. The anterior compartment is the most common area in which mediastinal tumors arise and includes diverse lesions such as thymoma, lymphoma, and germ cell tumors. In the middle compartment, foregut cysts, lymphoma, and metastatic tumor to lymph nodes constitute the majority of lesions. Most posterior compartment lesions are tumors of neurogenic origin, although other mesenchymal and lymphatic tumors may also arise in this location.
Synovial sarcoma is a rare mesenchymal neoplasm that primarily affects the deep soft tissues of the extremities and predominates in adolescents and young adults between 15 and 40 years of age [1]. Although synovial sarcoma has been reported to metastasize to the mediastinum [3], its occurrence as a primary neoplasm in this location is rare and has only recently been recognized [2, 4]. Because of its rarity in this location, this tumor may be mistaken for other neoplasms that are more common in this location, in particular, malignant mesothelioma.
Synovial sarcoma is composed of two types of cells that form a characteristic biphasic pattern: epithelial cells, resembling those of carcinoma, and fibrosarcoma-like spindle cells. Depending on the relative prominence of these two elements, synovial sarcoma can be classified into four subtypes: (1) biphasic type, (2) monophasic fibrous type, (3) monophasic epithelial type, and (4) poorly differentiated (round cell) type. Biphasic synovial sarcoma has a relatively limited differential diagnosis when it occurs in the extremities. However, the differential diagnosis is more extensive when this tumor arises in atypical locations such as the mediastinum. In the latter site, biphasic malignant mesothelioma is a major diagnostic consideration.
Molecular techniques are particularly useful in cases of synovial sarcoma that may be difficult to distinguish histologically from other biphasic or spindle cell tumors, especially for those arising in unusual locations. The availability of frozen tissue procured at the time of surgery allows for the molecular genetic identification (fluorescent in situ hybridization or polymerase chain reaction) of the t(X;18) which is found in over 90% of synovial sarcoma [5]. This translocation involves the SYT gene on chromosome 18 and either the SSX1 or SSX2 gene on the X chromosome [6, 7]. Although this translocation has been described in rare examples of fibrosarcoma [8] and malignant fibrous histiocytoma [9], such reports likely represent misdiagnosed synovial sarcomas since this translocation has yet to be convincingly demonstrated in any other tumor type [10]. Furthermore, the specific fusion product (SSX1/SYT versus SSX2/SYT) has been found by some authors to be of independent prognostic significance [11].
In summary, we document the light microscopic, immunohistochemical, and molecular genetic features of 2 unusual cases of synovial sarcoma arising in the mediastinum to emphasize its unique features that allow for its distinction from other more common tumors in this location, as well as the proper handling of tissue at the time of frozen section for appropriate molecular genetic analysis.
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References
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Abstract
Introduction
