ORIGINAL ARTICLE
Clinicopathologic factors and adjuvant treatment effects on survival in adult head and neck synovial cell sarcoma Matthew G. Crowson, MD,1 Ian Lalich, MD,2 Michael G. Keeney, MD,3 Joaquin J. Garcia, MD,3 Daniel L. Price, MD2* 1
Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, 2Department of Otorhinolaryngology – Head and Neck Surgery, The Mayo Clinic, Rochester, Minnesota, 3Department of Laboratory Medicine and Pathology, The Mayo Clinic, Rochester, Minnesota.
Accepted 8 January 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23605
ABSTRACT: Background. Synovial cell sarcoma is a rare soft tissue sarcoma. The purpose of this study was to investigate clinicopathologic factors and management on survival in primary synovial sarcoma of the head and neck. Methods. We conducted a retrospective case series of medical records. Standard Kaplan–Meier survival analyses and accompanying log-rank tests were used. Results. Twenty-eight patients were identified. All patients had surgery in attempt to remove the primary lesion. Nine patients received adjuvant radiation therapy, 2 received chemotherapy, and 14 received chemoradiation therapy postoperatively. Metastases on initial presentation and
tumor size >4 cm decreased survival. No significant effect on overall survival or local tumor recurrence with histologic subtype, lymph node involvement at diagnosis, tumors >5 cm, or when comparing adjuvant therapy types. Conclusion. Although surgery remains the mainstay of treatment, our results do not suggest that adding chemotherapy to postoperative radioC 2014 Wiley Periodicals, therapy confers a survival or control benefit. V Inc. Head Neck 00: 000–000, 2014
INTRODUCTION
both spindle cells and glandular epithelioid components. The histopathological diagnosis of synovial cell sarcoma is challenging as a result of the variable cellular and architectural morphology and resemblance to other neoplastic processes common to the region. To improve diagnostic specificity, a number of groups have sought to identify pathognomonic ancillary indicators for synovial cell sarcoma. To date, the most definitive diagnostic tool is the demonstration of a characteristic chromosomal translocation (X;18) by conventional polymerase chain reaction (PCR) or immunophenotyping techniques.13–15 This translocation is present in over 90% of synovial cell sarcoma and creates a fusion product of an SYT/SS18 transcriptional activator and an SSX transcriptional co-repressor.14,16,17 A few clinicopathological factors have been shown to be linked to poor survival—older age, tumor size, >10 mitoses/High Powered Field (HPF), poor histologic differentiation, local bony extension, and incomplete excision.3,9,18,19 Lesions larger than 4 to 5 cm have been specifically linked to poor overall survival.3 In general, nearly all mortality attributed to synovial cell sarcoma is determined by hematogenous distant metastatic burden.9,20 Head and neck synovial cell sarcoma has a greater metastatic risk than in synovial cell sarcoma found in extremities.20 Regional metastases occur in 12.5% of patients with head and neck synovial cell sarcoma,21 and up to 25% of patients present with distant metastases.5 The primary mode of spread is thought to be hematogenous, but up to 20% of documented metastases show spread to adjacent lymph nodes.2,8
Synovial cell sarcoma is a rare soft tissue sarcoma found throughout the body. Sarcomas of the head and neck account for approximately 1% of all head and neck malignancies.1 Of all primary sarcomas of the head and neck, synovial cell sarcoma represents 5 cm had a median survival time of 45 months, which was not significantly different from patients with a tumor size .05). Tumor size of >4 cm had a median survival time of 42 months, and significantly decreased survival when compared with patients with a tumor size .05). There was no significant effect on overall survival or local tumor recurrence with lymph node involvement detected at diagnosis (p > .05). Median survival time for patients receiving surgery alone was 3.0 months. Median survival time for patients who received adjuvant radiation alone was 90 months, and median survival time for patients who received adjuvant chemoradiation was 31 months. There were insufficient follow-up data to calculate mean survival time for patients who received adjuvant chemotherapy alone. There were no significant overall survival relationships when comparing adjuvant therapy strategies (Figure 5; p > .05).
DISCUSSION Head and neck synovial sarcoma is an extremely rare malignancy representing approximately 0.1% of all head and neck cancers.1 Limited contemporary research exists that assess clinicopathological factors and management strategies as they relate to patient survival (Table 4).
FIGURE 5. Kaplan–Meier curve. Overall survival as a function of therapeutic management strategy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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HEAD & NECK—DOI 10.1002/HED
MONTH 2013
To the best of our knowledge, this study is the second largest single institutional case series of head and neck synovial cell sarcoma. We observed no significant survival benefit with adjuvant chemotherapy with or without adjuvant radiation therapy after initial surgical management. The mainstay of treatment of synovial cell sarcoma is complete excision with wide surgical margins. Achievement of negative margins is important in avoiding local recurrence.6,9 Lymph node metastases are rare, and, thus, prophylactic neck dissection is not indicated.22 However, synovial cell sarcoma has been shown to spread beyond the visible and palpable limits of the tumor,3 and this has solicited a role for postoperative radiation to facilitate locoregional control.5,19,23 No standard postsurgical radiation regimen exists, but a dose of 65 to 70 Gy has been used by numerous groups with some efficacy in rendering patients disease-free in short follow-up periods.2,6,19,24,25 The temporal sequence of surgery and radiation therapy has been shown to not significantly affect metastatic risk.20 The role of chemotherapy in the treatment of synovial sarcoma is exceedingly contested. Early studies have suggested that chemotherapy does not influence survival,20 but recent trials with ifosfamide and doxorubicin have demonstrated disease-free and overall survival benefits.22,26 Harb et al9 recommends neoadjuvant chemotherapy for all patients with tumors >5 cm in size, local extension, or if a lesion is in a high-risk surgical site. They also suggest that adjuvant postoperative chemotherapy may reduce the risk of distant disease recurrence. However, a recent expert review has suggested there is insufficient data to support the standardized use of chemotherapy.27 Overall 5-year survival rates of head and neck synovial cell sarcoma range between 40% and 50%.2,28,29 Two-year recurrence rates after successful surgery and radiation have been widely reported at 50%.19,30All of our patients initially treated at The Mayo Clinic underwent surgical resection of the primary tumor as initial management. Postoperative adjuvant therapy was heterogenous among our patient population with most patients receiving radiation with or without chemotherapy. Although our data did not suggest that adding chemotherapy to postoperative radiotherapy confers a survival or control benefit, the heterogeneity of treatment and tumor characteristics limits the conclusions that can be made. Tumor size >4 cm was significantly associated with decreased survival, but this relationship was not seen when the patients were stratified into groups at tumor size 5 cm. Tumor size >4 cm has previously been established as a negatively affecting survival.3 The overall trend observed in this study was that smaller tumors were associated with increased survival. When the analytic pivot point was set at 5 cm, the survival distribution was equivocal. The pivot point was also set to 4 cm, and an increase in the median survival was found to be significant. These incongruent results are likely attributable in part to the limited power of this study. Although we could report just the >4 cm and 4 cm and distant metastases on presentation significantly decreased survival. Although surgery remains the mainstay of treatment for these tumors, our results do not suggest that adding chemotherapy to postoperative radiotherapy confers a survival or control benefit. A steep challenge remains to definitively elucidate the optimal adjuvant therapy strategy, despite the rarity of this malignancy.
ACKNOWLEDGMENT The authors thank Nicole M. Tombers for her assistance with this project.
REFERENCES 1. Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol 2003;15:239–252. 2. Roth JA, Enzinger FM, Tannenbaum M. Synovial sarcoma of the neck: a followup study of 24 cases. Cancer 1975;35:1243–1253. 3. Bukachevsky RP, Pincus RL, Shechtman FG, Sarti E, Chodosh P. Synovial sarcoma of the head and neck. Head Neck 1992;14:44–48. 4. Carrillo R, Rodriguez–Peralto JL, Batsakis JG. Synovial sarcomas of the head and neck. Ann Otol Rhinol Laryngol 1992;101:367–370. 5. O’Sullivan PJ, Harris AC, Munk PL. Radiological features of synovial cell sarcoma. Br J Radiol 2008;81:346–356.
6
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MONTH 2013
6. Amble FR, Olsen KD, Nascimento AG, Foote RL. Head and neck synovial cell sarcoma. Otolaryngol Head Neck Surg 1992;107:631–637. 7. Pai S, Chinoy RF, Pradhan SA, D’Cruz AK, Kane S V, Yadav JN. Head and neck synovial sarcomas. J Surg Oncol 1993;54:82–86. 8. Moore DM, Berke GS. Synovial sarcoma of the head and neck. Arch Otolaryngol Head Neck Surg 1987;113:311–313. 9. Harb WJ, Luna MA, Patel SR, Ballo MT, Roberts DB, Sturgis EM. Survival in patients with synovial sarcoma of the head and neck: association with tumor location, size, and extension. Head Neck 2007;29:731–740. 10. Ladanyi M, Antonescu CR, Leung DH, et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res 2002;62:135–140. 11. Oda Y, Hashimoto H, Tsuneyoshi M, Takeshita S. Survival in synovial sarcoma. A multivariate study of prognostic factors with special emphasis on the comparison between early death and long-term survival. Am J Surg Pathol 1993;17:35–44. 12. Singer S, Baldini EH, Demetri GD, Fletcher JA, Corson JM. Synovial sarcoma: prognostic significance of tumor size, margin of resection, and mitotic activity for survival. J Clin Oncol 1996;14:1201–1208. 13. Roberts CA, Seemayer TA, Neff JR, Alonso A, Nelson M, Bridge JA. Translocation (X;18) in primary synovial sarcoma of the lung. Cancer Genet Cytogenet 1996;88:49–52. 14. Shipley J, Crew J, Birdsall S, et al. Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma. Am J Pathol 1996;148:559–567. 15. Cihak RA, Lydiatt WM, Lydiatt DD, Bridge JA. Synovial sarcoma of the head and neck: chromosomal translation (X;18) as a diagnostic aid. Head Neck 1997;19:549–553. 16. Turc–Carel C, Dal Cin P, Limon J, Li F, Sandberg AA. Translocation X;18 in synovial sarcoma. Cancer Genet Cytogenet 1986;23:93. 17. Smith S, Reeves BR, Wong L, Fisher C. A consistent chromosome translocation in synovial sarcoma. Cancer Genet Cytogenet 1987;26:179–180. 18. Al-Daraji W, Lasota J, Foss R, Miettinen M. Synovial sarcoma involving the head: analysis of 36 cases with predilection to the parotid and temporal regions. Am J Surg Pathol 2009;33:1494–1503. 19. Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM. Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol 2000;18:3794–3803. 20. Mullen JR, Zagars GK. Synovial sarcoma outcome following conservation surgery and radiotherapy. Radiother Oncol 1994;33:23–30. 21. Simunjak B, Petric V, Bedekovic V, Cupic´ H, Hat J. Dimensions and outcome of synovial sarcoma of the head and neck: case presentation and review of the literature. J Otolaryngol 2005;34:420–423. 22. Dei Tos AP, Dal Cin P, Sciot R, et al. Synovial sarcoma of the larynx and hypopharynx. Ann Otol Rhinol Laryngol 1998;107:1080–1085. 23. de Almeida–Lawall M, Mosqueda–Taylor A, Bologna–Molina RE, et al. Synovial sarcoma of the tongue: case report and review of the literature. J Oral Maxillofac Surg 2009;67:914–920. 24. Luksic´ I, Virag M, Manojlovic´ S, Obradovic´ B, Macan D, Stepan J. Primary synovial sarcoma of the parotid gland in 15-year-old boy. J Craniomaxillofac Surg 2011;39:445–448. 25. Mariano FV, Oliveira Gondak R, da Costa MV, Corr^ea MB, Lopes MA, de Almeida OP. Primary synovial sarcoma involving the submandibular gland. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e61–e65. 26. Santoro A, Tursz T, Mouridsen H, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 1995;13:1537–1545. 27. Lee N, Shin E. Treatment outcomes for patients with synovial sarcoma of the head and neck. Expert Rev Anticancer Ther 2008;8:371–373. 28. Kartha SS, Bumpous JM. Synovial cell sarcoma: diagnosis, treatment, and outcomes. Laryngoscope 2002;112:1979–1982. 29. Tilakaratne WM. Synovial sarcoma of the mandible. J Oral Pathol Med 2006;35:61–63. 30. Jay A, Hutchison I, Piper K, Farthing PM, Richards PS. Synovial sarcoma presenting as a parotid mass: case report and review of literature. Head Neck 2008;30:1654–1659. 31. Nilsson G, Skytting B, Xie Y, et al. The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res 1999;59:3180–3184. 32. Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 1998;338:153–160.
Clinicopathologic factors and adjuvant treatment effects on survival in adult head and neck synovial cell sarcoma Matthew G. Crowson, MD,1 Ian Lalich, MD,2 Michael G. Keeney, MD,3 Joaquin J. Garcia, MD,3 Daniel L. Price, MD2* 1
Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, 2Department of Otorhinolaryngology – Head and Neck Surgery, The Mayo Clinic, Rochester, Minnesota, 3Department of Laboratory Medicine and Pathology, The Mayo Clinic, Rochester, Minnesota.
Accepted 8 January 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23605
ABSTRACT: Background. Synovial cell sarcoma is a rare soft tissue sarcoma. The purpose of this study was to investigate clinicopathologic factors and management on survival in primary synovial sarcoma of the head and neck. Methods. We conducted a retrospective case series of medical records. Standard Kaplan–Meier survival analyses and accompanying log-rank tests were used. Results. Twenty-eight patients were identified. All patients had surgery in attempt to remove the primary lesion. Nine patients received adjuvant radiation therapy, 2 received chemotherapy, and 14 received chemoradiation therapy postoperatively. Metastases on initial presentation and
tumor size >4 cm decreased survival. No significant effect on overall survival or local tumor recurrence with histologic subtype, lymph node involvement at diagnosis, tumors >5 cm, or when comparing adjuvant therapy types. Conclusion. Although surgery remains the mainstay of treatment, our results do not suggest that adding chemotherapy to postoperative radioC 2014 Wiley Periodicals, therapy confers a survival or control benefit. V Inc. Head Neck 00: 000–000, 2014
INTRODUCTION
both spindle cells and glandular epithelioid components. The histopathological diagnosis of synovial cell sarcoma is challenging as a result of the variable cellular and architectural morphology and resemblance to other neoplastic processes common to the region. To improve diagnostic specificity, a number of groups have sought to identify pathognomonic ancillary indicators for synovial cell sarcoma. To date, the most definitive diagnostic tool is the demonstration of a characteristic chromosomal translocation (X;18) by conventional polymerase chain reaction (PCR) or immunophenotyping techniques.13–15 This translocation is present in over 90% of synovial cell sarcoma and creates a fusion product of an SYT/SS18 transcriptional activator and an SSX transcriptional co-repressor.14,16,17 A few clinicopathological factors have been shown to be linked to poor survival—older age, tumor size, >10 mitoses/High Powered Field (HPF), poor histologic differentiation, local bony extension, and incomplete excision.3,9,18,19 Lesions larger than 4 to 5 cm have been specifically linked to poor overall survival.3 In general, nearly all mortality attributed to synovial cell sarcoma is determined by hematogenous distant metastatic burden.9,20 Head and neck synovial cell sarcoma has a greater metastatic risk than in synovial cell sarcoma found in extremities.20 Regional metastases occur in 12.5% of patients with head and neck synovial cell sarcoma,21 and up to 25% of patients present with distant metastases.5 The primary mode of spread is thought to be hematogenous, but up to 20% of documented metastases show spread to adjacent lymph nodes.2,8
Synovial cell sarcoma is a rare soft tissue sarcoma found throughout the body. Sarcomas of the head and neck account for approximately 1% of all head and neck malignancies.1 Of all primary sarcomas of the head and neck, synovial cell sarcoma represents 5 cm had a median survival time of 45 months, which was not significantly different from patients with a tumor size .05). Tumor size of >4 cm had a median survival time of 42 months, and significantly decreased survival when compared with patients with a tumor size .05). There was no significant effect on overall survival or local tumor recurrence with lymph node involvement detected at diagnosis (p > .05). Median survival time for patients receiving surgery alone was 3.0 months. Median survival time for patients who received adjuvant radiation alone was 90 months, and median survival time for patients who received adjuvant chemoradiation was 31 months. There were insufficient follow-up data to calculate mean survival time for patients who received adjuvant chemotherapy alone. There were no significant overall survival relationships when comparing adjuvant therapy strategies (Figure 5; p > .05).
DISCUSSION Head and neck synovial sarcoma is an extremely rare malignancy representing approximately 0.1% of all head and neck cancers.1 Limited contemporary research exists that assess clinicopathological factors and management strategies as they relate to patient survival (Table 4).
FIGURE 5. Kaplan–Meier curve. Overall survival as a function of therapeutic management strategy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
4
HEAD & NECK—DOI 10.1002/HED
MONTH 2013
To the best of our knowledge, this study is the second largest single institutional case series of head and neck synovial cell sarcoma. We observed no significant survival benefit with adjuvant chemotherapy with or without adjuvant radiation therapy after initial surgical management. The mainstay of treatment of synovial cell sarcoma is complete excision with wide surgical margins. Achievement of negative margins is important in avoiding local recurrence.6,9 Lymph node metastases are rare, and, thus, prophylactic neck dissection is not indicated.22 However, synovial cell sarcoma has been shown to spread beyond the visible and palpable limits of the tumor,3 and this has solicited a role for postoperative radiation to facilitate locoregional control.5,19,23 No standard postsurgical radiation regimen exists, but a dose of 65 to 70 Gy has been used by numerous groups with some efficacy in rendering patients disease-free in short follow-up periods.2,6,19,24,25 The temporal sequence of surgery and radiation therapy has been shown to not significantly affect metastatic risk.20 The role of chemotherapy in the treatment of synovial sarcoma is exceedingly contested. Early studies have suggested that chemotherapy does not influence survival,20 but recent trials with ifosfamide and doxorubicin have demonstrated disease-free and overall survival benefits.22,26 Harb et al9 recommends neoadjuvant chemotherapy for all patients with tumors >5 cm in size, local extension, or if a lesion is in a high-risk surgical site. They also suggest that adjuvant postoperative chemotherapy may reduce the risk of distant disease recurrence. However, a recent expert review has suggested there is insufficient data to support the standardized use of chemotherapy.27 Overall 5-year survival rates of head and neck synovial cell sarcoma range between 40% and 50%.2,28,29 Two-year recurrence rates after successful surgery and radiation have been widely reported at 50%.19,30All of our patients initially treated at The Mayo Clinic underwent surgical resection of the primary tumor as initial management. Postoperative adjuvant therapy was heterogenous among our patient population with most patients receiving radiation with or without chemotherapy. Although our data did not suggest that adding chemotherapy to postoperative radiotherapy confers a survival or control benefit, the heterogeneity of treatment and tumor characteristics limits the conclusions that can be made. Tumor size >4 cm was significantly associated with decreased survival, but this relationship was not seen when the patients were stratified into groups at tumor size 5 cm. Tumor size >4 cm has previously been established as a negatively affecting survival.3 The overall trend observed in this study was that smaller tumors were associated with increased survival. When the analytic pivot point was set at 5 cm, the survival distribution was equivocal. The pivot point was also set to 4 cm, and an increase in the median survival was found to be significant. These incongruent results are likely attributable in part to the limited power of this study. Although we could report just the >4 cm and 4 cm and distant metastases on presentation significantly decreased survival. Although surgery remains the mainstay of treatment for these tumors, our results do not suggest that adding chemotherapy to postoperative radiotherapy confers a survival or control benefit. A steep challenge remains to definitively elucidate the optimal adjuvant therapy strategy, despite the rarity of this malignancy.
ACKNOWLEDGMENT The authors thank Nicole M. Tombers for her assistance with this project.
REFERENCES 1. Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol 2003;15:239–252. 2. Roth JA, Enzinger FM, Tannenbaum M. Synovial sarcoma of the neck: a followup study of 24 cases. Cancer 1975;35:1243–1253. 3. Bukachevsky RP, Pincus RL, Shechtman FG, Sarti E, Chodosh P. Synovial sarcoma of the head and neck. Head Neck 1992;14:44–48. 4. Carrillo R, Rodriguez–Peralto JL, Batsakis JG. Synovial sarcomas of the head and neck. Ann Otol Rhinol Laryngol 1992;101:367–370. 5. O’Sullivan PJ, Harris AC, Munk PL. Radiological features of synovial cell sarcoma. Br J Radiol 2008;81:346–356.
6
HEAD & NECK—DOI 10.1002/HED
MONTH 2013
6. Amble FR, Olsen KD, Nascimento AG, Foote RL. Head and neck synovial cell sarcoma. Otolaryngol Head Neck Surg 1992;107:631–637. 7. Pai S, Chinoy RF, Pradhan SA, D’Cruz AK, Kane S V, Yadav JN. Head and neck synovial sarcomas. J Surg Oncol 1993;54:82–86. 8. Moore DM, Berke GS. Synovial sarcoma of the head and neck. Arch Otolaryngol Head Neck Surg 1987;113:311–313. 9. Harb WJ, Luna MA, Patel SR, Ballo MT, Roberts DB, Sturgis EM. Survival in patients with synovial sarcoma of the head and neck: association with tumor location, size, and extension. Head Neck 2007;29:731–740. 10. Ladanyi M, Antonescu CR, Leung DH, et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res 2002;62:135–140. 11. Oda Y, Hashimoto H, Tsuneyoshi M, Takeshita S. Survival in synovial sarcoma. A multivariate study of prognostic factors with special emphasis on the comparison between early death and long-term survival. Am J Surg Pathol 1993;17:35–44. 12. Singer S, Baldini EH, Demetri GD, Fletcher JA, Corson JM. Synovial sarcoma: prognostic significance of tumor size, margin of resection, and mitotic activity for survival. J Clin Oncol 1996;14:1201–1208. 13. Roberts CA, Seemayer TA, Neff JR, Alonso A, Nelson M, Bridge JA. Translocation (X;18) in primary synovial sarcoma of the lung. Cancer Genet Cytogenet 1996;88:49–52. 14. Shipley J, Crew J, Birdsall S, et al. Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma. Am J Pathol 1996;148:559–567. 15. Cihak RA, Lydiatt WM, Lydiatt DD, Bridge JA. Synovial sarcoma of the head and neck: chromosomal translation (X;18) as a diagnostic aid. Head Neck 1997;19:549–553. 16. Turc–Carel C, Dal Cin P, Limon J, Li F, Sandberg AA. Translocation X;18 in synovial sarcoma. Cancer Genet Cytogenet 1986;23:93. 17. Smith S, Reeves BR, Wong L, Fisher C. A consistent chromosome translocation in synovial sarcoma. Cancer Genet Cytogenet 1987;26:179–180. 18. Al-Daraji W, Lasota J, Foss R, Miettinen M. Synovial sarcoma involving the head: analysis of 36 cases with predilection to the parotid and temporal regions. Am J Surg Pathol 2009;33:1494–1503. 19. Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM. Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol 2000;18:3794–3803. 20. Mullen JR, Zagars GK. Synovial sarcoma outcome following conservation surgery and radiotherapy. Radiother Oncol 1994;33:23–30. 21. Simunjak B, Petric V, Bedekovic V, Cupic´ H, Hat J. Dimensions and outcome of synovial sarcoma of the head and neck: case presentation and review of the literature. J Otolaryngol 2005;34:420–423. 22. Dei Tos AP, Dal Cin P, Sciot R, et al. Synovial sarcoma of the larynx and hypopharynx. Ann Otol Rhinol Laryngol 1998;107:1080–1085. 23. de Almeida–Lawall M, Mosqueda–Taylor A, Bologna–Molina RE, et al. Synovial sarcoma of the tongue: case report and review of the literature. J Oral Maxillofac Surg 2009;67:914–920. 24. Luksic´ I, Virag M, Manojlovic´ S, Obradovic´ B, Macan D, Stepan J. Primary synovial sarcoma of the parotid gland in 15-year-old boy. J Craniomaxillofac Surg 2011;39:445–448. 25. Mariano FV, Oliveira Gondak R, da Costa MV, Corr^ea MB, Lopes MA, de Almeida OP. Primary synovial sarcoma involving the submandibular gland. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e61–e65. 26. Santoro A, Tursz T, Mouridsen H, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 1995;13:1537–1545. 27. Lee N, Shin E. Treatment outcomes for patients with synovial sarcoma of the head and neck. Expert Rev Anticancer Ther 2008;8:371–373. 28. Kartha SS, Bumpous JM. Synovial cell sarcoma: diagnosis, treatment, and outcomes. Laryngoscope 2002;112:1979–1982. 29. Tilakaratne WM. Synovial sarcoma of the mandible. J Oral Pathol Med 2006;35:61–63. 30. Jay A, Hutchison I, Piper K, Farthing PM, Richards PS. Synovial sarcoma presenting as a parotid mass: case report and review of literature. Head Neck 2008;30:1654–1659. 31. Nilsson G, Skytting B, Xie Y, et al. The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res 1999;59:3180–3184. 32. Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 1998;338:153–160.
