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Sinus histiocytosis with massive lymphadenopathy
Other Resources UpToDate PubMed

Sinus histiocytosis with massive lymphadenopathy

Contributors: Kirti Kirti MD, Jag Bhawan MD
Other Resources UpToDate PubMed


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.


D76.3 – Other histiocytosis syndromes

34287003 – Sinus histiocytosis with massive lymphadenopathy

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Differential Diagnosis & Pitfalls

Massive cervical lymphadenopathy should raise the suspicion of lymphoproliferative malignancies such as:
  • Lymphoma
  • Hodgkin lymphoma
  • Malignant histiocytosis 
  • Monocytic leukemia
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:
  • Skin bacterial abscess
  • Cutaneous tuberculosis
  • Sarcoidosis
  • Acquired immune deficiency syndrome
  • Reactive sinus histiocytosis
  • Rhinoscleroma
  • Granulomatosis with polyangiitis
  • Viral infections
  • Hemophagocytic syndrome
  • Kikuchi-Fujimoto disease (rare, benign, self-limiting)
Cutaneous Rosai-Dorfman disease disease does not have any specific clinical manifestations. It should be histopathologically differentiated from:
  • Eruptive xanthoma
  • Juvenile xanthogranuloma
  • Multicentric reticulohistiocytosis
  • Leprosy
  • Langerhans cell histiocytosis
  • Hodgkin lymphoma
  • Tangier disease

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Last Updated:08/13/2019
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Sinus histiocytosis with massive lymphadenopathy
A medical illustration showing key findings of Sinus histiocytosis with massive lymphadenopathy : Cervical lymphadenopathy, Night sweats, Bilateral distribution, Hypergammaglobulinemia, Widespread distribution, ESR elevated, Low grade fever, Smooth papules, WBC elevated, Smooth nodules, Smooth plaques
Clinical image of Sinus histiocytosis with massive lymphadenopathy - imageId=1819171. Click to open in gallery.  caption: 'Scattered bright red papules and plaques on the trunk.'
Scattered bright red papules and plaques on the trunk.
Copyright © 2024 VisualDx®. All rights reserved.