Pb2243: rosai-dorfman disease -a single centre experience of a rare histiocytic disorder

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Rosai-Dorfman disease (RDD) is a rare histiocytic disorder which presents with painless massive lymphadenopathy. Extranodal involvement occurs in more than 40% of patients. Pathologically, lymph nodes show accumulation of histiocytes and lymphocytes. Emperipolesis in histiocytes that express S100 in the appropriate clinical setting is considered diagnostic. The disease has an unpredictable course but is usually self-limiting. It may be associated with a chronic course characterised by episodic exacerbation and remission. Treatment is indicated if there is vital organ compromise, otherwise ‘watch and wait’ policy is reasonable. Aims: Describe current variation in practice regarding management of this unusual histioproliferative disorder, and describe disparities in presentation, treatment, and outcomes. Methods: A retrospective and descriptive review of paediatric patients diagnosed with RDD at the Royal Marsden Hospital, between 2012 and 2022. Data regarding age, symptoms, nodal/extranodal involvement, treatment and outcome were collected. Results: Eight patients were identified and followed up at RMH; seven males and one female. Age range was 23 months to 15 years, with a mean age at diagnosis of 7 years and 11 months. Three had solely cervical node involvement. Five had extranodal disease; two with splenomegaly, one exhibiting subcutaneous lesions and two with bony deposition. Of note one patient presented with solely extra-nodal disease with a soft tissue lesion in the midline of the frontal-glabellar junction and associated extra-dural involvement. All patients had elevated gamma delta T-cells, a marker of immune dysregulation. One patient had family history significant for a sibling with RDD. The clinical overlap with autoimmune lymphoproliferative syndrome (ALPS) necessitates immunological evaluation in all cases, with only one case requiring ongoing Immunology team follow up. Next Generation Sequencing (NGS) was performed on the biopsy tissue in two patients, with no targetable mutations identified. Four patients required surveillance only. One had surgical resection of an enlarged cervical node due to symptoms. The patient with isolated calcaneal lesion had curettage with complete symptomatic resolution. The CNS lesion was excised, with subsequent local recurrence effectively treated with steroids. One had constitutional symptoms and was treated with steroids and Sirolimus. Sirolimus, showed significant symptomatic improvement with reassessment PET CT showing good response. 5 years follow up remains standard of care for those under ‘watch and wait’, whilst the exceptional cases requiring therapy or intervention have ongoing clinical review. Summary/Conclusion: These cases confirm what is published in the literature, that RDD generally runs an indolent course. Treatment is only indicated if there is vital organ dysfunction. Steroids and other agents can be used if there is disease progression or surgery is not feasible, however there is significant variation in practice if response to steroids is inadequate. RDD can be seen as a presenting feature of ALPS, and part of the workup of new cases should be exclusion of underlying immune dysregulation. Identification of somatic MAP-ERK mutations in RDD have led to its addition to the group of histiocytic neoplasms in the most recent revision of the WHO classification of haematolymphoid tumours. Lesional tissue should be assessed by NGS for such mutations, which may be targetable by MEK-inhibitors, for cases which fail to respond to conventional therapies. Keywords: Clinical data, MAP kinase, Histiocytosis, Pediatric