Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare benign histiocytic proliferative disorder. Rosai-Dorfman disease usually appears in childhood and early adulthood (mean age of 20.6 years) and is somewhat more frequent in males (male predominance of 1.4:1). Classically, the patients present with prominent bilateral, massive, painless cervical lymphadenopathy, low-grade fever, weight loss, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Extranodal involvement of at least one site is identified in 25% to 43% of Rosai-Dorfman disease cases, and only 23% have exclusively extranodal disease. Skin is the most common site for extranodal involvement. Other documented sites of extranodal involvement include the respiratory tract, the skeletal system, the genital and urinary system, the central nervous system, the ocular system, the oral cavity, the salivary glands, breasts, and the cardio-vascular system. Bone marrow is rarely involved. Cutaneous disease without involvement of lymph nodes or other organs is rare and is known as cutaneous Rosai-Dorfman disease.
Rarely, Rosai-Dorfman disease may be associated with other diseases including large B-cell lymphoma, myelodysplastic syndrome, plasmacytoma, idiopathic hypereosinophilic syndrome, Hodgkin's lymphoma, sickle cell disease, and giant cell hepatitis. Other associated dermatologic conditions reported in the past include mycetoma, morphea, erythroderma, and Langerhans cell histiocytosis.
Etiology is not fully understood. It has been speculated that the initial histiocytic proliferation could be a result of an asymptomatic chronic infection or an abnormal exaggerated immune response to yet unknown antigen(s). Human herpes virus 6 (HHV6) has been isolated from the involved tissue of few patients. Raised Epstein-Barr virus (EBV) and herpes simplex virus (HSV) antibody titers have also been reported. Associations with Klebsiella, Brucella, parvovirus B19, and cytomegalovirus have been suggested. Rosai-Dorfman disease has also been reported in HIV-positive patients.
About a third of patients with Rosai-Dorfman disease have mutually exclusive mutations in KRAS and MAP2K1.
Treatment is not necessary, as the disease is self-limiting in most cases. Treatment is mainly needed to halt the natural progression only in a minority of patients where massive nodal or extranodal enlargement interferes with organ function or threatens life. The ideal treatment for Rosai-Dorfman disease is as yet undefined.
ICD10CM: D76.3 – Other histiocytosis syndromes
SNOMEDCT: 34287003 – Sinus histiocytosis with massive lymphadenopathy
Differential Diagnosis & Pitfalls
Massive cervical lymphadenopathy should raise the suspicion of lymphoproliferative malignancies such as:
It is prudent to differentiate Rosai-Dorfman disease from these diseases with poor prognosis. Cytologic atypia and the aggressive clinical course of these diseases establish the diagnosis in most cases, while Rosai-Dorfman disease will show classic histopathologic features including emperipolesis.
Other conditions that may be included in the differential: