Clinical characteristics, genomic profiling, treatments, and outcomes of Langerhans cell sarcoma.

BACKGROUND: Langerhans cell sarcoma (LCS), an exceptionally rare and aggressive neoplasm, remains poorly characterized due to its scarcity. To address this knowledge gap, we conducted a retrospective analysis of 13 LCS patients. This retrospective study included patients ≥ 18 years old with biopsy proven LCS from October 2015 to April 2025. RESULTS: The median age at diagnosis was 59 years (range: 33–71). The most commonly affected organs were the subcutaneous soft tissue (61.5%), followed by lymph nodes (53.8%), skin (30.8%), and bone (23.1%). CBL was the most common mutation, detected in four patients (33.3%). Notably, first-line treatment options included surgery and chemotherapy, with an overall response rate of 53.8%. Among all the relapsed or refractory patients, three eventually received targeted therapies (two trametinib and one niraparib), demonstrating promising efficacy with all patients achieved partial remission. With a median follow-up of 18.2 months (range: 2.6–93.1), the estimated 2-year overall survival rate was 92.3%, while the estimated 2-year progression-free survival (PFS) rate stood at 32.9%. CONCLUSIONS: In our cohort of LCS, we found that the PFS of LCS was poor. Genetic sequencing and the use of targeted therapies may offer a survival advantage for patients with LCS. CLINICAL TRIAL REGISTRATION: Not applicable.