Female Genital melanomas: A clinicopathologic and PD-L1 expression study

Abstract

Background: Genital melanomas (GMs) account for 3 to 7 % of female malignant melanomas. Unlike cutaneous melanomas (CMs), GMs are not developed on sun-exposed skin and have different pathogenesis that is less well understood. GM is treated similarly as CM, but overall response is poor. Immune checkpoint inhibitors have been found useful in treating patients with advanced CMs but limited data are available for GMs. Design: Clinicopathologic features were analyzed and immunohistochemical studies were performed on whole tissue sections of 54 genital melanomas using 2 clones of PD-L1 antibodies (Roche SP263 and Dako 28-8 by using automated platforms). Seventeen cutaneous melanomas were also included for comparison. Tumor cells staining was evaluated using cutoff scores of 0%, <5%, 5-24% and ≥25%. Results: Median age of patients was 65 years. The tumors consisted of 20 vulval, 31 vaginal and 3 cervical melanomas with median tumor size of 20 mm (range 2 - 50). Median Breslow thickness was 6.45 mm (range 2.4 – 130). Tumors were composed of spindle cells in 50% of cases (27/54), epithelioid cells in 33.3% (18/54) and 16.7% of cases (9/54) were mixed. Median mitotic count was 13.1/10 high power fields. Peritumoral lymphocytes were present in 72.2 % (39/54) and tumor infiltrating lymphocytes (TILs) were present in 79.6% (43/54) (median TILs, 40.5/10 high power fields). For GMs, PD-L1 cutoff scores of 5-24% and ≥25% were 29.6% and 14.8% respectively when SP263 clone was used, and were 25.9% and 9.3% respectively when 28-8 clone was used. For CMs, the frequencies of PD-L1 expression at each cutoff score were similar to GMs (Table). The vulval tumors were resected with wide local excision and 13 vaginal/cervical tumors were treated by radical surgery. Fourteen were inoperable. Adjuvant/palliative radiation therapy was administered to 28. Three had adjuvant chemotherapy (including cisplatin, dacarbazine, carboplatin and paclitaxel). One had C-KIT inhibitor imatinib. Median follow-up was 15 months (range 2 to 197). Forty-three patients (79.6%) died of disease, 5 (9.3%) were alive with tumor and 2 (3.7%) were alive with no tumor. Conclusion: GMs are aggressive, with high mortality and the management of these patients using conventional therapy is largely ineffective. The frequent expression of PD-L1 supports the use of PD-L1 inhibitors in selected patients.