Langerhans cell sarcoma is a clinically, biologically, and prognostically heterogeneous "malignant" histiocytosis: a systematic review of 88 cases from the literature.

Malignant histiocytoses are rare histiocytic neoplasms that exhibit aggressive clinical and histopathological features. One of these entities, Langerhans cell sarcomas (LCS), shares some histopathological features with Langerhans cell histiocytosis but is distinguished by its overtly malignant cytologic features. The literature on LCS is mostly limited to short reports and a few reviews, while a complete revision of its nosology is lacking. This study aims to fill this gap in the knowledge on LCS, explore potential prognostic factors, and propose a clinical subclassification for better patient stratification, which could guide future treatment investigations. A systematic review of the literature was conducted following PRISMA guidelines. From each included patient, a complete set of clinical and pathological features was collected. Descriptive and association statistics, as well as survival analysis, were performed using R Studio. A cohort of 88 patients was analyzed, the majority being adult males with multisystem pictures often involving skin and lymph nodes. pERK pathway gene mutations were reported in around half. Overall prognosis was poor, even though the association with another hematological neoplasm displayed a significant negative prognostic impact (p = 0.0017). Moreover, in primary cases, a significant difference was observed dividing patients into single system vs multisystem (p = 0.012). Despite treatment modalities being highly heterogeneous, statistical analyses provided insights into the relevance of treating patients according to disease spread (e.g., treating localized masses with surgery alone leads to frequent complete remission, p = 0.0002). This study provides an extensive analysis of LCS nosology and prognostic factors, underscoring the importance of distinguishing LCS from LCH and other histiocytoses, as well as adopting a unified system to define disease spread and guide therapeutic management.