Figure 2:Tumor Size

KM Curve. Survival as a function of tumor size.

Clinicopathologic Factors and Adjuvant Treatment Effects on Survival in Adult Head & Neck Synovial Cell Sarcoma

2013 Mayo Foundation for Medical Education and Research

Matthew G. Crowson1, Ian Lalich, M.D.1, Michael G. Keeney, M.D.2, Joaquin J. Garcia, M.D.2, Daniel L. Price, M.D.1 1 Department of Otorhinolaryngology - Head and Neck Surgery, 2 Department of Laboratory Medicine and Pathology

Mayo Clinic, Rochester, Minnesota

• This is the second largest single institutional case series of synovial sarcoma of the head and neck.

• Our patients demonstrated an overall survival of 12.25 years. • Tumor size greater than 4 cm and distant metastases on

presentation significantly decreased survival. • Surgery remains the mainstay of treatment . Our results

suggest that adding chemotherapy to post-operative radiotherapy may not confer a survival or control benefit.

Conclusions

1. Sturgis EM, Potter BO. Sarcomas of the head and neck region. Current opinion in oncology.2003;15(3):239–52. 2. Roth JA, Enzinger FM, Tannenbaum M. Synovial sarcoma of the neck: a followup study of 24 cases. Cancer. 1975;35(4):1243–53. 3. Bukachevsky RP, Pincus RL, Shechtman FG, Sarti E, Chodosh P. Synovial sarcoma of the head and neck. Head & Neck. 1992;14(1):44–48. 4. 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(8):731–40. 5. 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. The American journal of surgical pathology. 2009;33(10):1494–503. 6. Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM. Synovial Sarcoma: A Clinicopathologic, Staging, and Prognostic Assessment. J. Clin. Oncol. 2000;18(22):3794–3803..7. Mullen JR, Zagars GK. Synovial sarcoma outcome following conservation surgery and radiotherapy. Radiotherapy and Oncology. 1994;33(1):23–30. 8. Simunjak B, Petric V, Bedekovic V, Cupić H, Hat J. Dimensions and outcome of synovial sarcoma of the head and neck: case presentation and review of the literature. The Journal of otolaryngology.2005;34(6):420–3. 9. O’Sullivan PJ, Harris AC, Munk PL. Radiological features of synovial cell sarcoma. The British journal of radiology. 2008;81(964):346–56. 10. Moore DM, Berke GS. Synovial sarcoma of the head and neck. Archives of otolaryngology--head & neck surgery. 1987;113(3):311–3.

References

Objective. To investigate clinicopathologic factors and management on survival in primary synovial sarcoma of the head and neck.

Design. Retrospective case series.

Setting. Academic tertiary medical center.

Patients. Records of 28 patients diagnosed and treated with primary head and neck synovial sarcoma at The Mayo Clinic from 1960 to 2012.

Main Outcome Measures. Overall survival and local recurrence related to tumor size, histologic sub-type, metastases, nodal involvement, and adjuvant management strategy.

Results. Twenty-eight patients with primary synovial sarcoma of the head and neck were identified. Mean patient age was 35 years old (range, 11-80). Subtypes included 22 monophasic (79%), 4 biphasic (14%), and 2 indeterminate (7%). Six (22%) patients presented with metastases, and 4 (15%) presented with nodal involvement. Eleven (39%) of all patients developed metastases. All patients had surgery in attempt to remove the primary lesion. Nine (32%) patients received adjuvant radiation therapy, 2 (7%) received chemotherapy, and 14 (50%) receive chemoradiation therapy post-operatively. Ten (36%) patients died at a mean 38.3 months from time of diagnosis. Mean age at death was 44.2 years. Mean overall survival time was 12.25 years. Presence of metastases on initial presentation (p = 0.015), and tumor size greater than 4cm (p = 0.040) decreased survival. No significant effect on overall survival or local tumor recurrence with histologic subtype, lymph node involvement at diagnosis, tumors larger than 5 cm, or when comparing adjuvant therapy types.

Conclusions. While surgery remains the mainstay of treatment, our results do not suggest that adding chemotherapy to post-operative radiotherapy confers a survival or control benefit.

AbstractHead & Neck Synovial Sarcoma:Synovial cell sarcoma (SS) is a rare soft tissue sarcoma found throughout the body. Sarcomas of the head and neck comprise approximately 1% of all head and neck malignancies.1 Of all primary sarcomas of the head and neck, SS represents less than 10% of cases.1 There are two main histological subtypes: monophasic and biphasic. In the head & neck, SS are often found in the parapharyngeal, retropharyngeal, and the prevertebral planes from the skull base to the hypopharynx.2,3

Clincopathological Factors: Factors linked to poor survival – older age, tumor size, more than 10 mitoses/HPF, poor histologic differentiation, local bony extension and incomplete excision.3,4,5,6 Nearly all mortality attributed to SS is determined by hematogenous distant metastatic burden.4,7 Regional metastases occur in 12.5% of patients with head and neck SS,8 and up to 25% of patients present with distant metastases.9 The primary mode of spread is hematogenous, but up to 20% of metastases show spread to adjacent lymph nodes.2,10

Background

• Mean overall survival time of 12.3 yr., age at death 44.2 yr.• SYT-SSX RT-PCR translocation assays were performed, which

demonstrated two SYT-SSX1 translocations, two SYT-SSX2 translocations, and one SYT-SSX1/2 translocation.

• All had surgery in attempt to remove primary lesion. Nine (32%) received adjuvant radiation therapy alone, 2 (7%) received adjuvant chemotherapy alone, and 14 (50%) received adjuvant chemoradiation therapy. Three (11%) received no adjuvant therapy of any kind. The typical adjuvant radiation regimen used included 1-2 courses of 50-70 Gray (Gy).

• Presence of distant metastases on initial presentation had a mean overall survival of 42.0 mo, without distant metastases had increased survival of 206.5 mo. (p = 0.0151).

• Tumor size of > 4 cm had a mean survival time of 128.2 mo, and significantly decreased survival when compared to tumor size < 4 cm and mean survival time of 223.2 mo (Figure 2, p = 0.0396).

• No significant effect (p > 0.05) on overall survival or local tumor recurrence with:• Histologic subtype. • Lymph node involvement detected at diagnosis.• When comparing adjuvant therapy strategies (Figure 3).

Results

The purpose of this case series is to characterize head and neck synovial cell sarcoma over the last 50 years through a review of key clinicopathologic, treatment response, and survival trends.

Objective

This case series was approved under the Mayo Clinic IRB protocol. All patients with pathology-confirmed diagnoses were included. Pertinent clinical and pathologic data were obtained from the medical record (Table 1).

Paraffin-embedded surgical specimens from 36 cases of synovial sarcoma were retrieved. All of the cases were reviewed by two experienced head and neck pathologists (JJG, MGK). Tumors were classified as monophasic if they were composed exclusively of spindled cells and biphasic if they showed a composite of spindled and epithelial cells (Figure 1). In select cases, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect SYT-SSX1 and SYT-SSX2 fusion transcripts to confirm the diagnosis.

Standard Kaplan-Meier survival analyses and accompanying log-rank tests using the JMP statistical software package (Cary, North Carolina USA) were used to evaluate overall survival and local recurrence as they relate to tumor size, histologic sub-type, metastases, nodal involvement on initial presentation, and adjuvant management strategy.

Design, Setting, & Measures

Table 1: Patient & Tumor Factors Figure 3: Adjuvant Therapy

KM Curve. Survival as a function of adjuvant therapy strategy.

Descriptive Statistics Result (n)Average Follow-Up Period 83.4 months (26)Average Age; Gender 35.3 years (28); 15 female, 13 male (28)Primary Lesion Site 11 neck, 5 larynx, 4 spine, 3 oral cavity, 2

salivary gland, 2 thyroid, 1 scalpSS Histological Subtypes Monophasic 22, Biphasic 4, Indeterm. 2Tumor Size Staging (T) TX 2, T1 16, T2 10, T3, T4 0 (28)AJCC Sarcoma Staging 9 IA, 2 IB, 3 IIA, 1 IIB, 5 III, 7 IV (28)Metastases on initial diagnosis 21 No, 6 Yes (27)Most common met sites (initial) 4 lung, 1 lung & bone, 1 bone (6)Nodal involvement on diagnosis 23 No, 4 Yes (27)Metastases after diagnoses 11 Yes, 17 No . Sites 10 lung, 1 bone (28)

Figure 1: Patient histology illustrating Monophasic (A) and biphasic (B) synovial sarcoma subtypes.