{"entity":{"id":"rosai-dorfman-disease","kind":"cancer","name":"Rosai-Dorfman-Destombes disease","aka":["Rosai-Dorfman disease","RDD","Sinus histiocytosis with massive lymphadenopathy","R-group histiocytosis","Destombes-Rosai-Dorfman disease"],"tldr":"Rosai-Dorfman disease is a rare histiocytosis in which large immune cells called histiocytes fill the neck lymph nodes or grow in the skin, bones, nose, brain coverings or kidneys. Many cases fade without treatment, so it is watched unless it threatens an organ, when surgery, steroids, sirolimus or, for the third with a growth-pathway mutation, MEK inhibitors such as cobimetinib are used.","summary":"Rosai-Dorfman-Destombes disease was described in 1965 and 1969 as sinus histiocytosis with massive lymphadenopathy: large S100-positive, CD68-positive, CD1a-negative histiocytes with abundant pale cytoplasm containing intact lymphocytes (emperipolesis) distend the sinuses of lymph nodes. The classical form presents in children and young adults with enormous painless cervical nodes, fever and raised inflammatory markers; extranodal disease, commoner in adults, affects the skin, nasal cavity and sinuses, bone, orbit, meninges (mimicking meningioma), kidneys and retroperitoneum, and can occur without any node involvement. Long thought reactive, it was found from 2017 onward to carry activating KRAS, MAP2K1 and other MAPK pathway mutations in about a third of cases, which places it in the R group of the 2016 histiocytosis classification and among the histiocytic neoplasms in the 2022 WHO classification. Associations include IgG4-related disease, autoimmune cytopenias, a familial form due to SLC29A3 mutations (H syndrome) and, rarely, lymphoma.\n\nBecause many cases regress spontaneously, the 2018 consensus recommendations (Blood) advise observation for asymptomatic nodal or cutaneous disease and treatment only for symptoms or organ threat. Surgery is curative for a single extranodal lesion and relieves compressive disease; corticosteroids shrink nodes but the disease returns as they are withdrawn; sirolimus with prednisone, cladribine, methotrexate, lenalidomide and rituximab (for the IgG4-associated form) have all produced responses in small series; radiotherapy is used for localised refractory lesions, particularly in the orbit and airway. For patients with MAPK pathway mutations or multifocal refractory disease, MEK inhibition works: the cobimetinib phase 2 trial included patients with Rosai-Dorfman disease among its responders, and the 2022 United States approval of cobimetinib for histiocytic neoplasms covers the disease. Central nervous system involvement, which can cause seizures and cranial nerve palsies, is treated more aggressively, and long follow-up is needed because the course is relapsing and remitting over years.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Rosai%E2%80%93Dorfman_disease","links":[{"label":"RDD consensus recommendations (Blood 2018)","url":"https://doi.org/10.1182/blood-2018-03-839753"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Rosai%E2%80%93Dorfman_disease"}],"tags":["subtype-page","haematologic"],"related":["erdheim-chester-disease","histiocytoses","lch-single-system"],"cancers":[],"sections":[],"technologies":["fdg-pet","cgp","mri","histopathology-ihc","kinase-inhibitors","active-surveillance","imrt-igrt"],"targets":["braf"],"drugs":["cobimetinib","cladribine","methotrexate","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["driver-mutation","retroperitoneum"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-who-2022-myeloid-khoury-leukemia-2022","paper-rosai-dorfman-destombes-consensus-recommendations-blood-2018","paper-emile-revised-classification-of-histiocytoses-blood-2016"],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"A rare disorder classically of children and young adults with huge painless neck nodes, and of older adults with extranodal disease; many cases resolve on their own and only a minority need systemic treatment.","subtypes":["Classical nodal Rosai-Dorfman disease (massive cervical lymphadenopathy, children and young adults)","Extranodal Rosai-Dorfman disease (skin, sinonasal, bone, orbit, kidney)","Neurological Rosai-Dorfman disease (meningeal or parenchymal, mimics meningioma)","Cutaneous-only Rosai-Dorfman disease (often self-limiting)","Rosai-Dorfman disease with KRAS or MAP2K1 mutations (MEK inhibitor responsive)","Familial Rosai-Dorfman disease (SLC29A3, H syndrome) and IgG4-associated disease"],"biomarkers":["S100 and CD68 positive, CD1a and langerin negative histiocytes with emperipolesis","KRAS, MAP2K1 and other MAPK pathway mutations (about a third)","FDG-PET/CT for extent and response","IgG4-positive plasma cells (IgG4-related overlap)","Immunoglobulin levels, autoimmune screen and SLC29A3 testing where familial disease is suspected","MRI of brain and spine for neurological disease"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"Excisional biopsy with immunohistochemistry and MAPK pathway sequencing; FDG-PET/CT; MRI where neurological disease is suspected; immunoglobulins and autoimmune screen.","refs":["histopathology-ihc","cgp","fdg-pet","mri"],"guideline":{"version":"Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018)","url":"https://doi.org/10.1182/blood-2018-03-839753"}},{"setting":"Asymptomatic nodal or cutaneous disease","approach":"Observation, because spontaneous regression is common.","refs":["active-surveillance"],"guideline":{"version":"Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018)","url":"https://doi.org/10.1182/blood-2018-03-839753"}},{"setting":"Single or compressive extranodal lesion","approach":"Surgical excision or debulking; radiotherapy for unresectable localised disease (orbit, airway).","refs":["imrt-igrt"],"guideline":{"version":"Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018)","url":"https://doi.org/10.1182/blood-2018-03-839753"}},{"setting":"Multifocal or organ-threatening disease","approach":"Corticosteroids for rapid control; sirolimus with prednisone, cladribine, methotrexate or lenalidomide; rituximab for IgG4-associated disease.","refs":["cladribine","methotrexate","rituximab"],"guideline":{"version":"Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018)","url":"https://doi.org/10.1182/blood-2018-03-839753"}},{"setting":"MAPK-mutant or refractory disease","approach":"Cobimetinib (approved 2022 for histiocytic neoplasms) or trametinib.","refs":["cobimetinib","ras-mapk","kinase-inhibitors"],"guideline":{"version":"Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018)","url":"https://doi.org/10.1182/blood-2018-03-839753"}}],"stateOfArt":["The discovery of MAPK mutations moved the disease from reactive to neoplastic and opened MEK inhibition.","Observation remains correct for many patients because the disease often resolves.","Cobimetinib's 2022 approval is the first drug approval covering Rosai-Dorfman disease."],"history":[{"year":1965,"title":"Destombes describes the disease in Paris","refs":[]},{"year":1969,"title":"Rosai and Dorfman define sinus histiocytosis with massive lymphadenopathy","refs":[]},{"year":2016,"title":"Revised histiocytosis classification creates the R group for Rosai-Dorfman disease","refs":[]},{"year":2017,"title":"KRAS and MAP2K1 mutations identified, establishing a neoplastic subset","refs":["ras-mapk"]},{"year":2018,"title":"First consensus recommendations for diagnosis and treatment (Blood)","refs":[]},{"year":2022,"title":"Cobimetinib approved for histiocytic neoplasms; WHO lists Rosai-Dorfman disease among histiocytic neoplasms","refs":["cobimetinib"]}],"pipeline":["cobimetinib"],"openProblems":["Which patients will regress spontaneously cannot be predicted.","Two thirds of cases have no identified driver mutation.","All systemic treatments rest on case series; there has never been a randomised trial.","Neurological disease can leave permanent deficits despite treatment."],"parent":"histiocytoses"},"route":"/cancers/rosai-dorfman-disease/","neighbours":{"cancer":[{"id":"erdheim-chester-disease","kind":"cancer","name":"Erdheim-Chester disease","route":"/cancers/erdheim-chester-disease/"},{"id":"histiocytoses","kind":"cancer","name":"Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms","route":"/cancers/histiocytoses/"},{"id":"lch-single-system","kind":"cancer","name":"Single-system Langerhans cell histiocytosis (bone, skin or one other organ)","route":"/cancers/lch-single-system/"}],"technology":[{"id":"active-surveillance","kind":"technology","name":"Active surveillance","route":"/technologies/active-surveillance/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"drug":[{"id":"cladribine","kind":"drug","name":"Cladribine","route":"/drugs/cladribine/"},{"id":"cobimetinib","kind":"drug","name":"Cobimetinib","route":"/drugs/cobimetinib/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"retroperitoneum","kind":"term","name":"Retroperitoneum","route":"/terms/retroperitoneum/"}],"paper":[{"id":"paper-rosai-dorfman-destombes-consensus-recommendations-blood-2018","kind":"paper","name":"Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease","route":"/key-papers/paper-rosai-dorfman-destombes-consensus-recommendations-blood-2018/"},{"id":"paper-emile-revised-classification-of-histiocytoses-blood-2016","kind":"paper","name":"Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages","route":"/key-papers/paper-emile-revised-classification-of-histiocytoses-blood-2016/"},{"id":"paper-who-2022-myeloid-khoury-leukemia-2022","kind":"paper","name":"WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms","route":"/key-papers/paper-who-2022-myeloid-khoury-leukemia-2022/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}]}}