The primary objective: to develop technical and operating procedures for detection mutations of histiocytosis during clinical practice of no-specialized molecular platforms, for diagnosis and follow-up of the disease.

The secondary objectives: to describe therapeutic target mutations in histiocytosis patients, and to develop the cellular tests to evaluate in vitro the sensibility of these mutations drive to inhibitors.

The study is ancillary of the French "Gene Histio" cohort (patients already included) and "HISTIO target 2020" cohort (patients recruited since may 2020).

The data base of the French registry of histiocytoses is held by Dr J. Donadieu, and localized in Trousseau hospital (APHP) 75012 Paris, France, where server and backup are kept.

5 teams contributes to the study with different role: Team 1 is responsible for histology diagnosis, selection of histiocyte- rich areas, extraction of nucleic acids and detection of the BRAF p.V600E mutations. This group is also responsible of the tissue and nucleic acids biobank.

Team 2 is responsible for the collection of clinical data and tissue and blood samples of the children. This group is also responsible of the clinical data base.

Team 3 is responsible for the collection of clinical data and tissue and blood samples of the adult patients.

Team 4 is responsible for the development and validation of the new methods of detection of genetic somatic alterations described in project, and will perform most of the molecular analyses and interpretations.

Team 5 is responsible for regulatory requirements preparation and submissions and takes care of replying to regulatory comments and amendments until getting approvals. The project manager will also take care of the coordination of all activities related to the database setting and utilization, liaising between researchers, doctors and operational team. Team 5 will be in charge of the data management of the database and will ensure collection tools, integration and availability of data at appropriate quality. The data manager ensures that data is collected, validated, complete, and consistent, to provide a high quality and comprehensive database to the statistics team. Team 5 includes also a statistician who will perform data analysis according to a detailed statistical analysis plan to be developed once the project is approved.

Inclusion Criteria:

• Histologically proven histiocytosis;
• Informed consent form signed by patients (or parents/legal tutors of children) to participate"Gene Histio" or "HISTIO target 2020".

Exclusion Criteria:

- Patient refusal.

Paediatric and adult patients with histologically proven histiocytosis, included in either "Gene Histio" or "HISTIO target 2020" cohorts between 1997 and 2023.