This is one of the sarcomas that combine histologic features of both a carcinoma and a sarcoma. It may have epithelioid cells, mimicking carcinoma, intimately admixed with spindled sarcoma cells. Because of these features, the pathologist may have to differentiate between a poorly differentiated carcinoma and this tumor. It is a critical distinction but with the advent of immunohistochemistry, a confident distinction can now be made. These tumors are have spindle cells which are positive for vimentin and epithelial components positive for cytokeratin.
Rare variants may occur in non-soft tissue locations such as the larynx, heart, pericardium, pleura, lung, mediastinum, and peritoneal cavity. Recently cases have also been described in the kidney. Histologically, these tumors may mimic clear cell sarcomas or cellular mesoblastic nephromas. These tumors exhibit a characteristic translocation.
DISEASE ASSOCIATIONS CHARACTERIZATION Pregnancy Acta Oncol 1998;37:721–7.
PATHOGENESIS CHARACTERIZATION t(X;18)
Nat Genet 1994;7:502–8.
A characteristic chromosomal translocation t(X;18) (p11.2;q11.2) is present in most cases
Detailed cloning analysis of the breakpoints has revealed that the SYT gene at 18q11 is fused with the distal potion of one of two duplicated genes at Xp11, SSX1,or SSX2. This SYT-SSX fusion is present in >95% of cases and is a sensitive test for synovial sarcoma. The types of fusion transcripts may play a role in prognosis.
In a study of 19 cases, patients with SYT-SSX1 type fusion, high Ki-67 expression, and high mitotic rate correlated with shorter metastasis-free survival compared with SYT-SSX2 type fusion.
Mod Pathol 2000;13:1253-1263
Until recently, this translocation was thought to be specific for synovial sarcoma, this paper describes 15/20 (75%) of cases positive for this translocation
MAGE antigen expression in monophasic and biphasic synovial sarcoma.
Antonescu CR, Busam KJ, Iversen K, Kolb D, Coplan K, Spagnoli GC, Ladanyi M, Old LJ, Jungbluth AA.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; the Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY; and the Departments of Surgery and Research, University of Basel, Basel, Switzerland.
Hum Pathol 2002 Feb;33(2):225-229 Abstract quote
Synovial sarcomas are high-grade malignant mesenchymal tumors carrying a pathognomonic cytogenetic alteration t(X;18) involving the SYT gene on chromosome 18 and either SSX1 or SSX2 on chromosome X. Morphologically, biphasic (BSS) and monophasic (MSS) variants can be distinguished. Cancer/testis (CT) antigens are expressed in a variety of malignant tumors, but not in normal tissues except in germ cells, primarily of the testis. Anti-MAGE monoclonal antibody (mAb) 57B previously showed a high incidence and homogenous reactivity pattern in a preliminary analysis of synovial sarcomas.
This study was performed to analyze the expression of MAGE by immunohistochemistry with mAb 57B in 25 synovial sarcomas (12 monophasic, 13 biphasic), which were typed for the t(X;18)-derived fusion transcript by reverse transcriptase polymerase chain reaction (19 SYT-SSX1, 6 SYT-SSX2). 57B immunoreactivity was present in 22 of 25 (88%) cases, and antigen expression was homogeneous in 14 of 22 57B-positive cases. Both morphological variants and both translocation types were immunoreactive; three SYT-SSX1 tumors (one MSS, two BSS) were 57B negative.
Our study demonstrates that MAGE is frequently and homogeneously expressed in synovial sarcomas of both morphological variants and both translocation types, making these tumors an attractive target for MAGE antigen-based immunotherapy.
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION General VARIANTS KIDNEY CYSTIC SYNOVIAL SARCOMA
Cystic synovial sarcoma.
Morrison C, Wakely PE Jr, Ashman CJ, Lemley D, Theil K.
Department of Pathology, Ohio State University, Columbus, OH 43210, USA.
Ann Diagn Pathol 2001;5:48-56 Abstract quote
The tumor presented in a 53-year-old white woman who noticed a lump on the upper aspect of her back.
Magnetic resonance imaging of the cervical spine showed a heterogeneous paraspinal mass with well-defined margins and a multilocular quality with foci of hemorrhage. Fine needle aspiration of the mass showed clusters of polygonal cells admixed with a scattered spindle cell component. Surgical excision of the mass showed a well-circumscribed but nonencapsulated tumor that showed multiple small cystic structures on cross-section. Histologic examination showed a biphasic neoplasm characterized by bland-appearing glandular elements embedded in a moderately cellular spindle cell stroma. The tumor contained multiple cysts of varying size. Immunohistochemical studies showed the glandular component to be positive for cytokeratin and epithelial membrane antigen. The spindle cell component was immunoreactive for cytokeratin, vimentin, bcl-2, and CD99. Stains for muscle-specific actin, smooth muscle actin, S-100 protein, and CD34 were negative. Cytogenetic analysis showed a balanced reciprocal translocation involving chromosomes X and 18, in addition to other clonal abnormalities.
Synovial sarcoma should be considered in the differential diagnosis of cystic lesions involving the soft tissues. Magnetic resonance imaging is considered the procedure of choice for the evaluation of soft tissue tumors because of its superior soft tissue contrast and multiplanar imaging capability. While the imaging features of soft tissue tumors are often nonspecific, magnetic resonance imaging may provide helpful clues, thus narrowing the differential diagnosis. Immunohistochemical studies and cytogenetic analysis may be very helpful for establishing the correct diagnosis in cases with this unusual presentation.
Primary Renal Synovial Sarcoma Molecular and Morphologic Delineation of an Entity Previously Included Among Embryonal Sarcomas of the Kidney
Pedram Argani, M.D.; Paulo A. Faria, M.D.; Jonathan I. Epstein, M.D.; Victor E. Reuter, M.D.; Elizabeth J. Perlman, M.D.; J. Bruce Beckwith, M.D.; Marc Ladanyi, M.D.
From The Johns Hopkins Hospital and National Wilms Tumor Study Group Pathology Center, Baltimore, Maryland, U.S.A. (P.A., J.I.E., E.J.P., J.B.B.); Instituto Nacional do Cancer, Rio de Janeiro, Brazil (P.A.F.); Loma Linda University, Loma Linda, California, U.S.A. (J.B.B.); and Memorial Sloan-Kettering Cancer Center, New York, NY, U.S.A. (V.E.R., M.L.).
Am J Surg Pathol 2000;24:1087-1096 Abstract quote
We report 15 primary renal neoplasms with morphologic, immunohistochemical, and molecular features identical to those of synovial sarcoma.
These tumors form a distinct subset of the entity previously designated as embryonal sarcoma of the kidney. Most were diagnosed between the ages of 20 and 50 years. On gross examination, tumors are large, partially necrotic, and usually contain smooth-walled cysts. Microscopically, tumors are characterized by mitotically active, monomorphic plump spindle cells with indistinct cell borders growing in short, intersecting fascicles. Grossly identified cysts are lined by mitotically inactive polygonal eosinophilic cells with apically oriented nuclei (``hobnailed epithelium''). The spindle cells are immunoreactive for vimentin, often immunoreactive for EMA, but typically non-immunoreactive for desmin, actin, S100, or cytokeratins, whereas the cyst epithelium is cytokeratin-positive. These findings are consistent with monophasic, spindled synovial sarcoma encircling dilated native renal collecting ducts. The presence of an SYT-SSX gene fusion resulting from the t(X;18) characteristic of synovial sarcoma was demonstrated by reverse transcriptase polymerase chain reaction in three of three tumors in which adequate RNA could be obtained from paraffin blocks. An additional case demonstrated the characteristic t(X;18) translocation on cytogenetic analysis, but adequate material to perform molecular studies was not available in this case or the remaining 11 cases.
Primary renal synovial sarcoma is a distinctive clinicopathologic entity confirmed by molecular detection of SYT-SSX fusion transcripts.
Primary Synovial Sarcoma of the Kidney
Duck-Hwan Kim, M.D.; Jin H. Sohn, M.D.; Min C. Lee, M.D.; Gilho Lee, M.D.; Ghil-Suk Yoon, M.D.; Hiroshi Hashimoto, M.D.; Hiroshi Sonobe, M.D.; Jae Y. Ro, M.D.
From the Department of Pathology (D.H.K., J.H.S.), Hallym University College of Medicine, Seoul, Korea; the Departments of Pathology (M.C.L.) and Urology (G.L.), Dankook University Hospital, Cheonan, Korea; the Department of Pathology (G.S.Y., J.Y.R.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; the Department of Pathology and Oncology (H.H.), School of Medicine, University of Occupational and Environmental Health, Kitakushu, Japan; and the Department of Pathology (H.S.), Kochi Medical School, Japan.
Am J Surg Pathol 2000;24:1097-1104 Abstract quote
The authors present two cases of primary synovial sarcoma of the kidney.
Both patients had a mass in the upper part of the right kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were soft to rubbery masses measuring 5.5 cm and 5 cm in diameter, respectively. Histologically, both tumors were poorly differentiated synovial sarcoma. The lesions exhibited a hypercellular solid or lobular growth of round, oval, or short spindle cells in variably solid sheets, in intersecting fascicles, or in a haphazard fashion. Areas of solid aggregation or fascicles of the tumor cells alternating with hypocellular myxoid tissues, together with areas displaying a prominent hemangiopericytoma-like pattern, were found. Immunohistochemically, vimentin was diffusely positive and a few tumor cells were positive for cytokeratin, epithelial membrane antigen, and neurofilament. The tumor cells were negative for S-100 protein, CD34, smooth muscle actin, and desmin, whereas CD56 and CD99 were positive.
In both cases, reverse transcription–polymerase chain reaction using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX2 fusion gene transcripts, which are characteristic molecular findings of synovial sarcoma. One patient died 10 months after diagnosis.
These tumors are unique cases of primary synovial sarcoma of the kidney confirmed by molecular study.
Synovial sarcoma of the larynx and hypopharynx.
Dei Tos AP, Dal Cin P, Sciot R, Furlanetto A, Da Mosto MC, Giannini C, Rinaldo A, Ferlito A.
Department of Pathology, Regional Hospital, Treviso, Italy.
Ann Otol Rhinol Laryngol 1998 Dec;107(12):1080-5 Abstract quote
Synovial sarcoma represents a mesenchymal malignancy of unknown histogenesis that most often occurs in the lower limbs of young adults. The head and neck region is a relatively rare location, in which the hypopharynx and larynx are, respectively, the most and least often affected anatomic sites.
Histologically, synovial sarcomas are classified into monophasic and biphasic variants. Immunohistochemistry plays a major part in the differential diagnosis, enabling the demonstration of epithelial differentiation. Both monophasic and biphasic synovial sarcomas are characterized cytogenetically by the reciprocal translocation t(X;18)(p11.2;q11.2) between chromosomes X and 18.
Two cases of synovial sarcoma arising in the larynx and in the hypopharynx and in which cytogenetic analysis detected a diagnostic t(X;18) chromosome aberration are reported here.
Synovial sarcoma of the larynx in a child: case report and histological appearances.
Morland B, Cox G, Randall C, Ramsay A, Radford M.
Department of Paediatric Oncology, Birmingham Children's Hospital, United Kingdom.
Med Pediatr Oncol 1994;23(1):64-8 Abstract quote
Synovial sarcoma of the larynx is extremely rare having been reported only six times previously in the literature. We add another case report, which to our knowledge is the first recorded case in a child.
We discuss the alternative approach of combination chemotherapy and radiotherapy which in this case led to a remission lasting about 3 years. The immunohistological and ultrastructural characteristics of the tumour are also presented.
Synovial sarcoma of the larynx.
Miller LH, Santaella-Latimer L, Miller T.
Trans Am Acad Ophthalmol Otolaryngol 1975 Sep-Oct;80(5):448-51 Abstract quote
There have been several reports in the literature2-5 of synovial sarcomas of the head and neck. The consensus of these authors is that the tumor is not as aggressive in this localization as in the extremities, where the recurrence rate is 60% to 70%, and the five-year long-term follow-up of such cases should be made available.
Thereby, a reasonably clear and effective modality of treatment could be recommoneded.
Primary Monophasic Synovial Sarcoma of the Pleura Five Cases Confirmed by the Presence of SYT-SSX Fusion Transcript Marie-
Christine Aubry, etal.
Am J Surg Pathol 2001;25:776-781 Abstract quote
This study reports five cases of primary pleural monophasic synovial sarcomas and assesses the role of the SYT-SSX fusion transcript in the differential diagnosis. Patients had a mean age of 47 years with no gender predilection. Chest pain and pleural-based masses with effusions characterized the clinical presentations. Each patient underwent a complete surgical resection of the mass. The mean follow-up was 9 months, available in four patients. They were all alive, with no evidence of disease.
Histologically, neoplasms were composed of densely packed fusiform cells focally alternating with less cellular areas. No epithelial differentiation was identified at the hematoxylin and eosin level. Keratin and epithelial membrane antigen reactivity was focal and present in four and two tumors, respectively. There was no immunoreactivity for CD34. RT-PCR studies for the presence of a SYT-SSX1 or SYT-SSX2 fusion transcript were positive in every tumor. In comparison, 10 localized fibrous tumors were immunohistochemically negative for keratin and epithelial membrane antigen and positive for CD34. A SYT-SSX fusion transcript was not identified in any of five localized fibrous tumors tested.
Identification of the synovial sarcoma-specific chimeric transcript (SYT-SSX1 or SYT-SSX2), in conjunction with immunoperoxidase studies, can be extremely helpful in identifying cases of pleural monophasic synovial sarcoma.
Primary cutaneous synovial sarcoma: a case report.
Flieder DB, Moran CA.
Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Am J Dermatopathol 1998 Oct;20(5):509-12 Abstract quote
We present a case of synovial sarcoma involving the cutaneous tissue of the knee in an 18-year-old woman.
The 2.5 cm tumor was locally excised and recurred six times over the following 24 years. The neoplasm involved the deep dermis with extension into the papillary dermis and superficial subcutis. The tumor was predominantly composed of spindle cells arranged in compact interdigitating fascicles and scattered epithelial nests were seen. Focal myxoid and hemangiopericytoma-like areas as well as numerous mast cells were identified. Spindle cells stained for vimentin, CAM 5.2, and epithelial membrane antigen, whereas epithelial nests only stained for CAM 5.2 and epithelial membrane antigen. Neither component was reactive for antibodies directed against desmin, muscle specific actin, smooth muscle actin, S-100 protein, CD-31, or CD-34.
This newly reported location for this morphologically heterogeneous tumor creates potential diagnostic confusion with other primary neoplasms in these areas
HISTOLOGICAL TYPES CHARACTERIZATION General Monophasic Biphasic VARIANTS MYXOID
Myxoid synovial sarcoma: an underappreciated morphologic subset.
Krane JF, Bertoni F, Fletcher CD.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Mod Pathol 1999 May;12(5):456-62 Abstract quote
Focal myxoid change is a well-recognized feature of synovial sarcoma, but the presence of a predominantly myxoid stroma is rare.
We describe seven cases of myxoid synovial sarcoma in which marked myxoid change initially obscured the diagnosis, leading to confusion (principally with malignant peripheral nerve sheath tumor). The median age (20 yr) and tumor location (four lower extremity, two upper extremity, and one head and neck region) were similar to those found in typical synovial sarcoma.
Histologically, five cases were monophasic spindle cell lesions with a lacy appearance in areas with a prominent Alcian blue-positive myxoid stroma. Each case had foci with more typical features of synovial sarcoma, including a fascicular growth pattern with a variably collagenized stroma, stromal mast cells, a hemangiopericytoma-like vascular pattern, and calcification. Two cases showed small foci of glandular (biphasic) differentiation. Immunohistochemically, all of the seven cases were positive for epithelial membrane antigen, four of six were positive for pan-keratin, three of six were positive for S-100, two of four were positive for CD99, and six of six were negative for desmin. Clinical follow-up in six cases ranged from 8 to 48 months (median, 21 mo). Local recurrence developed in three patients at 9, 20, and 24 months, respectively. In one of these three patients, lung metastases developed at 13 months, and the patient died of disseminated disease at 23 months. In another of the three patients, lung metastases developed at 27 months. Three patients had no evidence of disease at 8, 15, and 15 months.
Our data are too limited to indicate any clinical differences between myxoid synovial sarcoma and conventional synovial sarcoma Recognition of this rare histologic variant of synovial sarcoma is important because it can easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting in suboptimal therapy.
SPECIAL STAINS/IMMUNOPEROXIDASE/OTHER CHARACTERIZATION Special stains Immunoperoxidase CALRETININ
Calretinin and Other Mesothelioma Markers in Synovial Sarcoma Analysis of Antigenic Similarities and Differences With Malignant Mesothelioma
Markku Miettinen, etal.
Am J Surg Pathol 2001;25:610-617 Abstract quote
Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial differentiation. SS commonly metastasizes to lung and pleura, and has also been reported as the primary in these locations. The histologic distinction of SS from mesothelioma may be difficult because of the combination of epithelioid and spindle cells, potentially shared locations, and antigenic expression.
In this study the authors examined 103 well-documented SSs including 41 biphasic, 44 monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields or foci of calretinin-positive tumor cells. The spindle cell components were more often positive (55%), whereas 14% of tumors had positive epithelial cells.
The monophasic and poorly differentiated SSs commonly had foci of calretinin-positive cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly detected in biphasic SS and EM (100% and 87% respectively). Among the other sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12 of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs typically showed prominent membrane staining in epithelial cells. Simple epithelial keratins were present in all epithelial cells of biphasic SS and mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases), whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered positive cells.
The potentially shared calretinin patterns in SS and mesothelioma require the use of other markers. The discriminating features include extensive BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns of K14 expression may also be helpful.
Matrix metalloproteinase-2 expression correlates with morphological and immunohistochemical epithelial characteristics in synovial sarcoma.
Saito T, Oda Y, Sakamoto A, Tamiya S, Iwamoto Y, Tsuneyoshi M.
Department of Anatomic Pathology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan, Department of Orthopaedic Surgery, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.
Histopathology 2002 Mar;40(3):279-85 Abstract quote
Matrix metalloproteinase-2 expression correlates with morphological and immunohistochemical epithelial characteristics in synovial sarcoma
Aims: Synovial sarcoma is a unique mesenchymal tumour characterized by the presence of epithelial differentiation, although the mechanism involved in the epithelial morphology is still unclear. The aim of this study was to evaluate the function of matrix metalloproteinase-2 (MMP-2) in synovial sarcoma, in order to assess whether MMP-2 expression plays an important role in epithelial differentiation, or whether it contributes to a poor clinical outcome.
Methods and results: Immunohistochemical stainings for MMP-2, cytokeratins (CKs) 7, 8, 18 and 19, and E-cadherin were performed for 58 (44 monophasic and 14 biphasic) cases of synovial sarcoma, and we compared the expression of these proteins with the histological and clinical findings. MMP-2 and E-cadherin expression was observed in 43 cases (74.1%) and in 18 cases (31.0%), respectively. Expression of these proteins was preferentially observed in the glandular components of biphasic tumours or the epithelioid areas of monophasic tumours. Statistically significant correlations were recognized between MMP-2 expression and E-cadherin expression of biphasic subtype. Moreover, there were statistically significant correlations between monophasic tumours with epithelioid areas and MMP-2 expression or E-cadherin expression. MMP-2 expression was correlated with epithelial differentiation as assessed by CK immunoreactivity. The expression of MMP-2 did not affect the overall survival rate in synovial sarcoma.
Conclusions: MMP-2 expression seemed to have an important role to play in the epithelial differentiation of tumour cells in synovial sarcoma, through remodelling of the extracellular matrix and by changing the cytoskeletal interaction between the extracellular matrix and tumour cells.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors BETA-CATENIN
Prognostic significance of histologic grade and nuclear expression of beta-catenin in synovial sarcoma
Tadashi Hasegawa, etal.
Hum Pathol 2001;32:257-263.
Synovial sarcoma, which has a wide spectrum of biologic behavior, warrants accurate grading to assess the patient's prognosis.
We studied the clinicopathologic and immunohistochemical features of 44 cases of synovial sarcoma in patients treated primarily or secondarily at the National Cancer Center, Tokyo, to identify independent prognostic factors.
There were local recurrences in 16 patients (36%), and 25 (57%) developed metastases, primarily to the lungs. The estimated cumulative 5-year and 10-year survival rates were 68% and 41%, respectively.
Variables associated with an adverse outcome included tumor size > 6.7 cm; initial treatment outside the National Cancer Center; poorly differentiated subtype; high nuclear atypia; mitosis count > 27/10 high-power fields; tumor necrosis; absence of stromal calcification; nuclear expression of -catenin, which was found in 25 cases (57%); Ki-67 (MIB-1) index > 27%; and histologic grade 3. Nuclear accumulation of -catenin as a cell-signaling event may play an important role in the progression of synovial sarcoma and therefore might be predictive of short survival.
However, multivariate analysis clearly showed that only histologic grade, as defined by using categorized variables for the MIB-1 index and tumor necrosis, was an independent prognostic factor. Most variables were correlated with lung metastasis and histologic grade.
High-grade synovial sarcoma assessed by a histologic grading system based on the proliferative activity of the neoplastic cells can be viewed as high risk with the patients most likely to die of disease within 10 years after surgery and in need of improved chemotherapy.
SYT-SSX FUSION GENE Detection of SYT-SSX Fusion Gene in Peripheral Blood From a Patient With Synovial Sarcoma
Am J Surg Pathol 2001;25:406-410
This report describes a case involving a 22-year-old pregnant woman with synovial sarcoma in the thigh. The patient recognized an elastic hard mass accompanied by a dull pain in the anteromedial portion of the right thigh. Magnetic resonance imaging delineated a deep soft-tissue mass measuring 9 × 7 × 6 cm.
Histologic diagnosis of poorly differentiated synovial sarcoma was made based the results of an open biopsy.
In this patient, the SYT-SSX fusion gene transcript was detected by nested polymerase chain reaction (PCR) in the peripheral blood collected before biopsy. Two months after wide local resection of the tumor, multiple lung metastases developed.
This is the first reported case in which tumor cells were detected by nested PCR in the peripheral blood of a patient with synovial sarcoma. These findings suggest that circulating tumor cells should be monitored because they may serve as a prognostic indicator for synovial sarcoma.
Impact of SYT-SSX Fusion Type on the Clinical Behavior of Synovial Sarcoma: A Multi-Institutional Retrospective Study of 243 Patients.
Ladanyi M, Antonescu CR, Leung DH, Woodruff JM, Kawai A, Healey JH, Brennan MF, Bridge JA, Neff JR, Barr FG, Goldsmith JD, Brooks JS, Goldblum JR, Ali SZ, Shipley J, Cooper CS, Fisher C, Skytting B, Larsson O.
Departments of Pathology [M. L., C. R. A., J. M. W.], Epidemiology and Biostatistics [D. H. L.], and Surgery [A. K., J. H. H., M. F. B.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Res 2002 Jan 1;62(1):135-40 Abstract quote
Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive.
To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively.
Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival.
The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8).
In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ratio of SYT-SSX1 cases was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2.
Overall, SYT-SSX fusion type appears to be the single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the associations of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.
TREATMENT Wide excision
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
Mod Pathol 2000;13:482-488.
Am J Surg Pathol 2000;24;1087-1096.
Am J Surg Pathol 2000;24:1097-1104.
Monophasic-Predominately one histologic pattern, either epithelioid or sarcomatoid.
Biphasic-Two histologic patterns.
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