AB1144 Histology of rosai-dorfman disease in a subset of patients with erdheim-chester disease: a distinct entity mainly driven by map2k1

Background Diagnosis of Erdheim-Chester disease (ECD) is based on characteristic imaging of bone, retroperitoneal and/or cardiovascular involvement.1 Biopsy is mandatory to exclude other diagnoses and confirm infiltration of histiocytes, but histology is not specific.2 By contrast diagnosis of Rosai-Dorfman disease (RDD), a rare histiocytosis, is based on histology, which is characterised by infiltration by CD68 +CD1 a- S100+ histiocytes with large nuclei and abundant lesions of emperipolesis.2 Up to 70% of ECD have BRAF or MAP2K1 mutations,3 which are rare in RDD. Objectives We investigated patients harbouring an ECD phenotype but RDD histology. Methods We reviewed records of ECD patients followed in Pitie-Salpetriere hospital (Paris, France) and Memorial Sloan Kettering Cancer Centre (New-York, NY, USA) between 2007 and 2018. Biopsy samples of the patients were systematically investigated for mutations of genes of MAP kinase pathway. Results Among 209 patients with ECD, we found 10 (4.7%) patients who had RDD histology. These 10 patients had typical ECD clinical and radiological presentation, in particular bones (n=7), vascular (n=5) and peritoneal (n=6) involvements. Patients also had typical neurological involvement of ECD (n=6). All patients except one had at least one biopsy with a compatible histology of ECD at diagnosis. ECD biopsies showed non-specific fibrosis (n=5), foamy CD 68+CD1 a- histiocytes (n=3) and/or Touton cells (n=1). Biopsies disclosing RDD histology were performed during the course of the disease involving testes (n=5), stomach (n=1), tibia (n=2), cheek (n=1) and omentum (n=1). All tissues showed lympho-plasmocytic infiltrate with large histiocytes infiltration. Histiocytes were CD68 +CD1 a- S100 +with large nuclei and abundant lesions of emperipolesis. Five patient harboured MAP2K1 mutation and one patient had PIK3CA mutation. None of the patients had BRAF mutation. Conclusions Some patients with ECD may also present the iconic histological lesions described by Rosai and Dorfman. Overlap forms of such distinct histiocytoses between ECD and RDD is mainly driven by MAP2K1 but not by BRAF. References [1] Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood. 2014;124:483–92. [2] Emile J-F, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672–81. [3] Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012;120:2700–3. Disclosure of Interest None declared