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

TL;DR

This study analyzes 13 cases of Langerhans cell sarcoma, a rare cancer, to understand its clinical features, genetic mutations, and treatment outcomes.

Contribution

The study provides new clinical and genomic insights into LCS through a rare patient cohort and evaluates the efficacy of targeted therapies.

Findings

CBL mutations were detected in 33.3% of LCS patients.

Targeted therapies showed promising efficacy in relapsed or refractory LCS cases.

The 2-year progression-free survival rate was 32.9%, indicating poor PFS in LCS patients.

Abstract

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.

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%.

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.

Not applicable.

The online version contains supplementary material available at 10.1186/s13023-026-04199-4.

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