Japanese Journal of Clinical Oncology 31:212-216 (2001)
© 2001 Foundation for Promotion of Cancer Research
Primary Synovial Sarcoma of the Lung: a Case Report Confirmed by Molecular Detection of SYT-SSX Fusion Gene Transcripts
1Clinical Laboratory, 5Diagnostic Radiology and 4Thoracic Surgical Division, National Cancer Center Hospital, 3Pathology Division, National Cancer Center Research Institute, Tokyo and 2Department of Radiology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentsREFERENCES |
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We report a rare case of primary synovial sarcoma of the lung. The patient was a 49-year-old woman who presented with a well-defined oval-shaped mass in the left upper lobe on a chest radiograph. A malignant pulmonary tumor was suspected and consequently a left upper lobectomy was performed. Grossly, the tumor measured 5 x 4 cm, was whitish–yellow in color and soft in consistency. Histologically, the tumor showed a dense proliferation of short spindle cells, partly arranged in interlacing fascicles. In some areas a hemangiopericytoma-like pattern, stromal myxoid change and necrosis of various sizes were noted. Numerous mitotic figures were also seen. Immunohistochemically, the tumor cells were positive for epithelial markers such as cytokeratin and epithelial membrane antigen. As these features suggested a monophasic fibrous type of synovial sarcoma, we examined for the presence of SYT-SSX fusion gene transcripts using RNA samples from the frozen tumor tissue. A reverse transcription polymerase chain reaction amplified a single 583-base pair fragment characteristic of synovial sarcoma. As no other tumorous lesions were found during a follow-up period of 1 year, primary synovial sarcoma of the lung was our final diagnosis. This tumor should be considered in the differential diagnosis of round to short spindle cell tumors arising in the lung.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentsREFERENCES |
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Synovial sarcoma is a morphologically well defined neoplasm that is most commonly found in soft tissue. This type of tumor accounts for about 10% of all soft tissue sarcomas (1). Histologically, it is classified into four subtypes: biphasic, monophasic fibrous, monophasic epithelial and poorly differentiated. However, the monophasic epithelial subtype is extremely rare (2). Synovial sarcoma occurs predominantly in the extremities, where it tends to arise in the vicinity of large joints, especially the knee region. The tumor is intimately related to tendons, tendon sheaths and bursal structures, usually just beyond the confines of the joint capsule. It is rare within the joint cavity itself. Its existence and microscopic resemblance to normal synovium have been described in early reports (1). However, normal synovial tissues do not stain for epithelial markers such as cytokeratin or epithelial membrane antigen, whereas synovial sarcoma stains for these markers with high frequency. Also, this tumor has been described in numerous locations unrelated to joint structures, including the head and neck, chest and abdominal wall (2). On the basis of these findings, it is currently thought that the origin of this tumor is unrelated to normal synovial tissues. In the new edition of ‘Histological Typing of Soft Tissue Tumours’ by the World Health Organization, synovial sarcoma is placed among the ‘miscellaneous soft tissue tumors’ (3).
Primary synovial sarcoma arising in the lung is rare. In this paper, we present a case of this tumor occurring in a 49-year-old woman, the diagnosis being proven by SYT-SSX fusion gene transcripts using the reverse transcription polymerase chain reaction (RT-PCR).
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentsREFERENCES |
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A 49-year-old woman was referred to our hospital because of an abnormal opacity in the left middle lung field on a routine chest radiograph (Fig. 1). The patient had a slight productive cough. Chest CT showed a well-defined oval shaped mass in the left upper lobe (measuring 5 x 4 cm) which displayed heterogeneous enhancement using intravenous contrast materials. The normal bronchovascular structures were strongly compressed. In the peripheral lung around the tumor, there were areas of irregularly increased attenuation due to secondary inflammatory change. However, bronchial obstruction was not visible on the CT scan. Transbronchial brushing cytology revealed that the tumor cells were small and uniformly rounded. However, it was uncertain whether the tumor was malignant or benign cytologically. As a malignant pulmonary tumor was suspected clinically, a left upper lobectomy with radical lymph node dissection was performed. The patient was discharged 10 days after the operation without any complications. Postoperatively, a general work-up of the patient was performed in search for a possible primary lesion, but none was found. The patient showed no signs of local recurrence or distant metastasis during a follow-up period of 1 year.
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Pathological Findings
Grossly, the tumor (measuring 5 x 4 cm) was located in the anterior (S3) to superior segment (S4) of the left upper lobe. It was well circumscribed, encapsulated and compressed the adjacent tissues on the cut surface (Fig. 2). The tumor was whitish–yellow in color and soft in consistency. There was no hemorrhage, cystic change or calcification in the tumor. At low-power magnification, the tumor was seen to be encapsulated by fibrous tissue. In some areas, endobronchial growth of the tumor was evident. At high-power magnification, the tumor was characterized by a dense proliferation of atypical short spindle cells with indistinct cytoplasm and short fusiform or small rounded nuclei (Fig. 3). The overall morphology was uniform, but a hemangiopericytoma-like pattern, stromal myxoid change and solid growth pattern with necrosis of various sizes were visible in some areas. An epithelioid appearance of the neoplastic cells was also evident in other areas (Fig. 4). Numerous mitotic figures (50/10 high-power fields) were seen. Immunohistochemical analyses revealed that a small number of tumor cells with epithelial-like morphology were positive for broad-spectrum keratin (AE1/AE3) (Fig. 5), keratin 7, keratin 19, epithelial membrane antigen (EMA) (Fig. 6) and synaptophysin. Neural cell adhesion molecule (NCAM) and bcl-2 protein (Fig. 7) were uniformly positive in the tumor. S-100 protein, vimentin and chromogranin A were negative. Based on all of these findings, we suspected that the tumor was a synovial sarcoma of the monophasic fibrous type.
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RT-PCR Findings
We then performed an RT-PCR analysis using RNA samples extracted from the fresh tumor tissue. The sequences of the primers used for RT-PCR were 5'-CAACAGCAAGATGCTACCA-3' for SYT and 5'-CACTTGCTATGCACCTGATG-3' for SSX, as described previously (4). To determine whether the PCR products were derived from the SYT-SSX1 or SYT-SSX2 sequence (5,6), the PCR products were digested with either SmaI or NspV restriction endonucleases and further analyzed by electrophoresis. The results are shown in Fig. 8. A single 583-base pair fragment corresponding to the SYT-SSX chimeric transcripts specific for synovial sarcoma was detected (Fig. 8, lane 1). The products were digested by NspV (Fig. 8, lane 5), but not by SmaI (Fig. 8, lane 4), thus revealing the SYT-SSX1 fusion gene. The final diagnosis was synovial sarcoma of the monophasic fibrous type arising in the lung.
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X174/HincII. A single 583-base pair fragment corresponding to the SYT-SSX chimeric transcripts was detected (lane 1). The PCR products were digested by NspV (lane 5), but not by SmaI (lane 4), thus revealing the SYT-SSX1 fusion gene. |
DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentsREFERENCES |
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Pulmonary sarcoma is very rare in comparison with carcinoma of the lung. The most frequent subtypes have been reported to be malignant fibrous histiocytoma, fibrosarcoma and leiomyosarcoma. They may arise within the parenchyma, bronchial tree or the pulmonary artery. Morphologically, sarcomas arising in the lung resemble their soft tissue counterpart (7). Before the advent of immunohistochemistry and electron microscopy, primary synovial sarcoma of the lung was considered extremely rare. In recent times, it has been recognized as one of the more common subtypes, accounting for a greater percentage of primary pulmonary sarcomas (7,8). The differential diagnosis for synovial sarcomas is broad, making it difficult to make a correct diagnosis when the tumors lack characteristic morphology or occur at unusual sites.
Immunohistochemically, epithelial markers such as cytokeratin and EMA stain positive in most cases of synovial sarcoma. In contrast, poorly differentiated types may or may not stain positive (2). Zeren et al. reported that these epithelial markers were diffusely positive in nearly all of the 25 cases of primary pulmonary sarcomas with features of monophasic synovial sarcoma (8). The present case stained positive for cytokeratin and EMA and also for bcl-2, synaptophysin and NCAM. The bcl-2 protein expression is seen in 79% of synovial sarcomas. However, other spindle cell sarcomas, including leiomyosarcoma, malignant peripheral nerve sheath tumor and fibrosarcoma are negative (9). The bcl-2 protein is involved in the 14;18 chromosomal translocation present in follicular lymphoma. The biological significance of bcl-2 expression in synovial sarcoma is currently unclear, but it may be involved in regulating apotosis in the tumor (9). NCAM and synaptophysin are associated with neural or neuroendocrine differentiation. The biological significance of these findings is also unknown, but it clearly indicates that one must be cautious in interpreting the positivity of these markers in the differential diagnosis of short spindle cell tumors.
Molecular diagnosis has been successfully performed by RT-PCR analysis, using RNA extracted from frozen materials and from archival paraffin-embedded specimens (10,11). Until now, five cases of primary synovial sarcoma of the lung have been reported, with molecular confirmation showing characteristic translocation (Table 1) (11–14). The patients were all female. Histologically, most of the tumors were of the monophasic subtype. Epithelial markers such as cytokeratin and/or EMA stained positive in all cases. The t(X;18) (p11.2;q11.2) translocation commonly found in synovial sarcomas results from fusion of the SYT gene on chromosome 18 to either of two closely related genes, SSX1 and SSX2, on chromosome X. Currently, there are five different related SSX gene transcripts (SSX1 to SSX5) which have been identified (15). It has been suggested that a patient with a tumor bearing the SYT-SSX1 gene has a worse prognosis than a patient with a tumor bearing the SYT-SSX2 gene (16). The SYT-SSX1 gene has been associated with a high Ki-67 expression and high mitotic rate (16). Survival analysis has shown that the presence of the SYT-SSX1 gene, a high Ki-67 index and increased mitotic activity are correlated with a shorter metastasis-free survival (16). Also, the SYT-SSX fusion gene was correlated with the histological subtype. The biphasic subtype was strongly associated with the SSX-SYT1 gene. The monophasic subtype may have either one of the two SYT-SSX fusion transcripts, but all tumors with the SYT-SSX2 gene showed monophasic morphology (17). The present case displayed some features that are associated with a poor prognosis, such as high mitotic activity and the SYT-SSX1 fusion gene.
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Our case presented as an intrapulmonary tumor, with no signs of local recurrence or distant metastasis during a follow-up period of 1 year. There was also no clinical evidence of soft tissue neoplasms in any other location. However, it is known that synovial sarcomas may have a long, indolent course followed by late metastases. The period of time that may elapse between resection and metastases varies, but can be as long as 10–15 years (2,8). Our patient should be followed up carefully in the future.
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Acknowledgments |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentsREFERENCES |
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The authors thank Dr H. Sonobe for a synovial sarcoma cell line, HS-SY-II and Ms T. Shimizu for excellent technical assistance.
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FOOTNOTES |
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+ For reprints and all correspondence: Toshiro Niki, Pathology Division, National Cancer Center Research Institute, 1–1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: tniki@gan2.ncc.go.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentsREFERENCES |
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10 Tsuji S, Hisaoka M, Morimitsu Y, Hashimoto H, Shimajiri S, Komiya S, et al. Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues. Am J Pathol 1998;153:1807–12.
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Received November 27, 2000; accepted January 31, 2001.
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