AB1144 Histology of rosai-dorfman disease in a subset of patients with erdheim-chester disease: a distinct entity mainly driven by map2k1
Authors: J. Razanamahery, E. Diamond, F. Cohen-Aubart, P. Karl-Heinz, F. Charlotte, Z. Helias-Rodzewicz, A. Dogan, O. Abdel-Wahab, B. Durham, N. Ozkaya, Z. Amoura, J.-F. Emile, J. Haroche
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Diagnosis of Erdheim-Chester disease (ECD) is based on characteristic imaging of bone, retroperitoneal and/or cardiovascular involvement.<sup>1</sup> Biopsy is mandatory to exclude other diagnoses and confirm infiltration of histiocytes, but histology is not specific.<sup>2</sup> 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<i>+</i> histiocytes with large nuclei and abundant lesions of emperipolesis.<sup>2</sup> Up to 70% of ECD have <i>BRAF</i> or <i>MAP2K1</i> mutations,<sup>3</sup> which are rare in RDD. <h3>Objectives</h3> We investigated patients harbouring an ECD phenotype but RDD histology. <h3>Methods</h3> We reviewed records of ECD patients followed in Pitié-Salpêtrière 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. <h3>Results</h3> 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 <i>MAP2K1</i> mutation and one patient had <i>PIK3CA</i> mutation. None of the patients had <i>BRAF</i> mutation. <h3>Conclusions</h3> 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 <i>MAP2K1</i> but not by <i>BRAF</i>. <h3>References</h3> [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, Hélias-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. <h3>Disclosure of Interest</h3> None declared