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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
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.
Because 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extranodal lesion and relieves compressive disease; corticosteroids shrink nodes but the disease returns as they are withdrawn; sirolimus with prednisone, cladribine, methotrexate, lenalidomide and rituximab (for the IgG4-associated form) have all produced responses in small series;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.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis and staging | Excisional biopsy with immunohistochemistry and MAPK pathway sequencing; FDG-PET/CT; MRI where neurological disease is suspected; immunoglobulins and autoimmune screen. | not mapped |
| Asymptomatic nodal or cutaneous disease | Observation, because spontaneous regression is common. | not mapped |
| Single or compressive extranodal lesion | Surgical excision or debulking; radiotherapy for unresectable localised disease (orbit, airway). | not mapped |
| Multifocal or organ-threatening disease | Corticosteroids for rapid control; sirolimus with prednisone, cladribine, methotrexate or lenalidomide; rituximab for IgG4-associated disease. | not mapped |
| MAPK-mutant or refractory disease | Cobimetinib (approved 2022 for histiocytic neoplasms) or trametinib. | not mapped |