1. Role of Sentinel Lymph Node Biopsy in the Staging of Synovial, Epithelioid, and Clear Cell Sarcomas. Ugwuji N. Maduekwe, Francis J. Hornicek, Dempsey S. Springfield, Kevin A. Raskin, David C. Harmon, Edwin Choy, Andrew E. Rosenberg, G. Petur Nielsen, Thomas F. DeLaney, Yen-Lin Chen, Mark J. Ott, Sam S. Yoon. Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 Harvard Medical School, 260 Longwood Ave, Boston, MA 02214

2. Most soft tissue sarcomas uncommonly metastasize to regional lymph nodes. Certain subtypes reportedly have a higher frequency of regional nodal metastases. These include synovial, epithelioid and clear cell sarcoma. Soft Tissue Sarcomas and Lymph Node Metastases Frequency of lymph node metastasis for these subtypes ranges from 11 – 44% 1-3. 1. Fong et al. Ann Surg. 1993;217:72-77. 2. Wagner et al. Strahlenther Onkol. 1994;170:91-99. 3. Deenik et al. Cancer. 1999;86:969-975.

3. Methods Since 1998, we have performed SLNB for patients with synovial, epithelioid, clear cell sarcoma without definitive clinical or radiological evidence of metastatic disease. SLNB was usually performed during the definitive surgical procedure. Technetium-99 labelled sulfur lymphoscintigraphy was performed on the day of surgery. Lymphazurin blue dye was also injected at the time of surgery. Sentinel lymph node was defined as blue node and/or node with ex vivo count > 10X background We undertook a retrospective review of patients between 1998 to 2007. Median follow up was 29 months.

4. Sentinel Node Pathological Evaluation Initial Examination Each node was bivalved and stained with hematoxylin and eosin. Re-evaluation Each node was serially step-sectioned, evaluated by H&E and IHC Epithelioid sarcoma – keratin Synovial sarcoma – EMA Clear cell sarcoma – S100

5. Demographics/Presentation CharacteristicNumber Total number of patients29 Median age (yrs) at initial presentation35 (11 - 73) Sex, n (%) Male20 (69%) Female9 (31%) Presence of mass, n(%)27 (93%) Presence of symptoms, n(%)15 (52%) Disease at presentation, n(%) Primary disease23 (79%) Local recurrence6 (21%)

6. Tumor Characteristics CHARACTERISTICn (%) Histology Synovial16 (55%) Epithelioid10 (35%) Clear cell3 (10%) Size  5cm 20 (69%) > 5cm9 (31%) Location Hand8 (28%) Upper extremity (excluding hand)4 (14%) Lower extremity17 (59%) Grade I0 II27 (93%) III2 (7%)

7. Diagnostic studies MODALITYN (%) Chest CT scans performed29 Suspicious0 Negative19 (66%) Indeterminate10 (34%) Abdomen/Pelvis CT scans performed10 Suspicious0 Negative7 (70%) Indeterminate3 (30%) PET scans performed20 Suspicious1 (5%) Negative17 (85%) Indeterminate2 (10%)

8. Sentinel Lymph Node Biopsy Characteristicn (%) Sentinel lymph node biopsy Positive1 (3.4%) Negative27 (93.1%) Not identified1 (3.4%) Total number of nodes58 Number of sentinel nodes/patient2 (1 - 4)

9. Sentinel lymph node biopsy results Initial H&E analysis identified 1 positive patient and 27 negative patients. Subsequent step-sectioning with IHC identified 2 additional patients with micrometastases. One patient with a negative SLNB developed a subsequent lymph node metastasis. No other SLNB negative patients developed a nodal recurrence.

10. Positive sentinel nodes Pt 1Pt 2Pt 3 Age223326 Tumor size (cm)8.3125.5 SexMale Tumor siteRight thighRight forearmRight hand HistologySynovialEpithelioidSynovial GradeII Surgery Radical rsxn + SLNB Other treatment MAID + radiotherapy None Recurrence Pulmonary metastases at 5 months None Status Dead from disease at 18 months Disease free at 11 months Disease free at 88 months

11. H & E stain Positive on initial examination EMA stain Positive on re-examination Representative Positive Sentinel Lymph Node Stain in Synovial Sarcoma

12. Treatment MODALITYn (%) Surgical resection margin Grossly positive0 (0%) Microscopically positive1 (3%) Microscopically negative28 (97%) Chemotherapy a Yes7 (25%) No21 (75%) Radiation a Yes17 (61%) No11 (39%) a Total of 28 patients. One patient lost to follow up.

13. Overall Survival 5 year overall survival: 91.6% Two patients died of disease. Years 109876543210 Overall Survival 100% 75% 50% 25% 0% 5 year recurrence free survival: 68.5% 8 patients developed recurrent disease. Recurrence Free Survival Years 109876543210 Recurrence free survival 100% 75% 50% 25% 0%

14. Years 109876543210 Locoregional recurrence free survival 100% 75% 50% 25% 0% Locoregional RFS 5 year locoregional RFS: 84.5% Developed in 4 patients. Years 109876543210 Distant recurrence free survival 100% 75% 50% 25% 0% 5 year distant RFS: 78% Developed in 5 patients. Distant RFS

15. Univariate Analysis Of Recurrence-Free Survival Factorn(%)5 year RFS (%)p-value Histology0.53 Synovial16 (55%)72 Epithelioid10 (35%)57 Clear cell3 (10%)100 Sex0.04 Male20 (69%)56 Female9 (31%)100 Presentation0.75 Primary23 (79%)66 Recurrent6 (21%)80 Tumor size0.0005  5cm 20 (69%)90 > 5cm9 (31%)16 Tumor grade0.023 II27 (93%)75 III2 (7%)0 Location0.27 Proximal7 (24%)48 Distal22 (76%)74 SLNB status0.72 Positive3 (10%)67 Negative26 (90%)69

16. Tumor Size > 5cm  5cm p-value 0.0005 Years 109876543210 Recurrence free survival 100% 75% 50% 25% 0% Tumor Histology CLEAR CELL SYNOVIAL EPITHELIOID p-value 0.53 Years 109876543210 Recurrence-free survival 100% 75% 50% 25% 0%

17. Conclusion Sentinel lymph node biopsy is feasible in patients with synovial, epithelioid and clear cell sarcoma. Incidence of lymph node metastasis in patients with negative imaging may be lower than reported. Sentinel lymph node evaluation should be performed with step sectioning and IHC. The utility of SLNB is unclear.

18. Limitations Small sample size Site of technetium or lymphazurin injection for sentinel lymph node identification. Pathological assessment of sentinel lymph node.

20. Dr. Sam Yoon MGH Sarcoma Group Dr. Rosenberg Dr. Nielsen Scholars in Clinical Science Program at Harvard Medical School. ACKNOWLEDGEMENTS