Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease)
Definition & Epidemiology
- Rare, non-neoplastic histiocytic disorder characterized by massive lymphadenopathy
- Typically affects children and young adults (mean age: 20.6 years)
- Slight male predominance
- Higher incidence in African and Caribbean populations
Pathophysiology
- Characterized by accumulation of activated histiocytes (S100+ CD68+ CD1a-)
- Hallmark feature: Emperipolesis (intact lymphocytes within histiocytes)
- Associated with:
- Immune dysregulation
- Viral infections (HHV-6, EBV)
- Genetic mutations (SLC29A3, KRAS, MAP2K1)
Key Molecular Markers
- S100 protein positive
- CD68 positive
- CD1a negative
- Increased inflammatory markers (ESR, CRP)
- Polyclonal hypergammaglobulinemia
Schematic classification of Rosai-Dorfman disease according to the Histiocyte Society.4 AIHA, autoimmune haemolytic anaemia; ALPS, autoimmune lymphoproliferative syndrome; ECD, Erdheim-Chester disease; IJA, idiopathic juvenile arthritis; LCH, Langerhans cell histiocytosis; MH, malignant histiocytoses; NOS, not otherwise specified; SLE, systemic lupus erythematosus. (source)
Clinical Manifestations
Common Presentations
- Massive, painless cervical lymphadenopathy (90% of cases)
- Constitutional symptoms:
- Fever
- Night sweats
- Weight loss
- Fatigue
- Extranodal involvement (43% of cases)
Extranodal Manifestations
- Skin (10%): Xanthomatous lesions, nodules
- Nasal cavity and paranasal sinuses
- Orbit and eyelids
- Central nervous system
- Bone lesions
- Respiratory tract
Disease Course
- Natural history:
- Self-limiting in 50% of cases
- Chronic/relapsing course in others
- Mortality rate: 7% (higher with CNS involvement)
- Complications:
- Orbital compression
- Airway obstruction
- CNS manifestations
- Growth retardation
Diagnostic Approach
Laboratory Studies
- Complete blood count
- Normocytic anemia
- Neutrophilia
- Elevated ESR
- Serum chemistry
- Polyclonal hypergammaglobulinemia
- Elevated CRP
- Flow cytometry
- Viral studies (EBV, HHV-6)
Imaging
- CT scan
- Homogeneous lymphadenopathy
- No necrosis or calcification
- MRI for CNS involvement
- PET-CT for disease extent
Definitive Diagnosis
- Excisional lymph node biopsy showing:
- Expanded sinuses with large histiocytes
- Emperipolesis
- Immunohistochemistry: S100+, CD68+, CD1a-
H&E 200×. Nodal Rosai-Dorfman disease showing characteristic cells with abundant wispy cytoplasm and admixed inflammatory cells including lymphocytes and plasma cells. Emperipolesis is seen. (source)
Treatment Approach
Observation
- Appropriate for mild, asymptomatic cases
- Regular monitoring of disease progression
- Follow-up imaging as needed
First-Line Treatments
- Surgical excision
- For diagnostic purposes
- Relief of compressive symptoms
- Systemic corticosteroids
- Prednisone 1-2 mg/kg/day
- Gradual taper based on response
Second-Line Treatments
- Chemotherapy
- Vinblastine
- 6-Mercaptopurine
- Methotrexate
- Targeted therapy
- Sirolimus
- Cobimetinib (for MAP2K1 mutations)
- Radiation therapy for localized disease
Monitoring
- Regular clinical assessment
- Serial imaging studies
- Laboratory monitoring
- CBC, ESR, CRP
- Immunoglobulin levels
Further Reading
Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease)
- What is the eponym for Sinus Histiocytosis With Massive Lymphadenopathy?
Answer: Rosai-Dorfman Disease - Which cell type is characteristically proliferated in Rosai-Dorfman Disease?
Answer: Histiocytes - What is the typical age group affected by Rosai-Dorfman Disease?
Answer: Children and young adults - Which lymph node region is most commonly involved in Rosai-Dorfman Disease?
Answer: Cervical lymph nodes - What is the characteristic microscopic finding in Rosai-Dorfman Disease?
Answer: Emperipolesis (lymphocytes within histiocytes) - Is Rosai-Dorfman Disease typically considered a malignant or benign condition?
Answer: Benign - What is the typical clinical presentation of Rosai-Dorfman Disease?
Answer: Painless lymphadenopathy, often with fever and weight loss - Can Rosai-Dorfman Disease affect extranodal sites?
Answer: Yes - Which immunohistochemical marker is consistently positive in Rosai-Dorfman Disease histiocytes?
Answer: S100 protein - What is the typical course of untreated Rosai-Dorfman Disease?
Answer: Self-limiting with spontaneous resolution in most cases - Is Rosai-Dorfman Disease associated with any specific ethnic group?
Answer: No, it affects all racial and ethnic groups equally - What is the male to female ratio in Rosai-Dorfman Disease?
Answer: Slight male predominance (1.4:1) - Which cytokine is thought to play a key role in the pathogenesis of Rosai-Dorfman Disease?
Answer: Macrophage colony-stimulating factor (M-CSF) - Can Rosai-Dorfman Disease be familial?
Answer: Rarely, familial cases have been reported - What is the first-line treatment for symptomatic Rosai-Dorfman Disease?
Answer: Corticosteroids - Is surgical excision typically necessary for Rosai-Dorfman Disease?
Answer: No, except for cases with airway obstruction or vital organ compression - What percentage of Rosai-Dorfman Disease cases involve extranodal sites?
Answer: Approximately 40% - Which imaging modality is most useful for evaluating the extent of Rosai-Dorfman Disease?
Answer: CT scan or MRI - Is Rosai-Dorfman Disease associated with any specific viral infections?
Answer: No consistent association has been established - What is the typical ESR (erythrocyte sedimentation rate) finding in active Rosai-Dorfman Disease?
Answer: Elevated - Can Rosai-Dorfman Disease affect the central nervous system?
Answer: Yes, but it's rare - What is the typical serum immunoglobulin finding in Rosai-Dorfman Disease?
Answer: Polyclonal hypergammaglobulinemia - Is bone marrow involvement common in Rosai-Dorfman Disease?
Answer: No, it's rare - What is the role of chemotherapy in treating Rosai-Dorfman Disease?
Answer: Reserved for severe or refractory cases - Can Rosai-Dorfman Disease recur after initial resolution?
Answer: Yes, recurrence is possible - What is the typical CD markers profile of histiocytes in Rosai-Dorfman Disease?
Answer: CD68+, CD163+, CD1a- - Is Rosai-Dorfman Disease classified as a neoplastic or reactive condition?
Answer: Generally considered a reactive condition - What is the mortality rate associated with Rosai-Dorfman Disease?
Answer: Very low, most patients have excellent long-term prognosis - Can Rosai-Dorfman Disease be associated with autoimmune disorders?
Answer: Yes, associations have been reported - What is the typical duration of the active phase of Rosai-Dorfman Disease?
Answer: Several months to years
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