(P 317) SMARCB1-DEFICIENT SARCOMA OF THE GENITAL REGION/EPITHELIOID SARCOMA OF THE PROXIMAL TYPE VS EPITHELIOID SARCOMA OF THE DISTAL TYPE

Objective: To describe the clinical characteristics and treatment of SMARCB1-deficient sarcoma of the genital region.

Methods: Between 2015 and 2024 seven patients with a SMARCB-1 deficient sarcoma (epithelioid sarcoma, proximal type) of the genital region were diagnosed in our tertiary referral center for sarcoma in the Netherlands. Seven patients with epithelioid sarcoma of distal type served as a reference for this study.
Diagnosis of epithelioid sarcoma was confirmed by histopathological analysis showing epithelioid to spindled cytomorphology, keratin and/or EMA staining and loss of INI1 expression in all cases. Loss of 22q11 and/or SMARCB-1 deficiency was additionally demonstrated in 8 tumors by molecular analysis and/or whole genome sequencing.

Results: The median age at diagnosis was 36 years in the proximal group (range 21-55) and 38 in the distal group (range 21-74). Two of seven patients presented with synchronous metastases in the lungs in both groups. These patients received palliative treatment (either systemic medical treatment, radiotherapy or palliative amputation) and died of disease.
Five patients with proximal type epithelioid sarcoma received treatment with curative intent by wide local excision. The average tumor size was 50 mm (range 33-95 mm). Surgical excision margins varied between 0 and 0.8 mm. A role for adjuvant radiotherapy was discussed in our MDT, since these tumors have a tendency of recurring locally. However, this was omitted due to foreseen side effects in the genital area. One male patient with a subcutaneous tumor in front of the pubic bone received neoadjuvant radiotherapy (50Gy). Pathological response was scored in this case as partial with 50% remaining viable tumor cells.
The average tumor size in the distal group was 98 mm (range 32-220 mm). Two patients received neoadjuvant radiotherapy (50Gy) with a pathological response of < 5% and >90% viable cells. One patient received adjuvant radiotherapy (60Gy) after failing to obtain free surgical margins in a second attempt excision.
All patient treated with curative intent showed no evidence of disease during their (relatively short) follow-up with an average of 7 months (range 2-18 months) in the proximal tumor group. During a mean follow-up of 44 months of follow-up, one patient developed a local recurrence and one patient developed pulmonary metastases in the distal group.

Conclusion: SMARCB1-deficient sarcoma of the genital region arises preferably in female young adults. Surgical wide local excision is the cornerstone of treatment and although achieving tumor free margins is a challenge, radiotherapy should be applied with caution in this area.