Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease)
Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease)
Rosai-Dorfman Disease (RDD), also known as Sinus Histiocytosis with Massive Lymphadenopathy, is a rare, benign proliferative disorder of histiocytes. It was first described by Juan Rosai and Ronald Dorfman in 1969. RDD primarily affects the lymph nodes, but extranodal involvement is observed in approximately 43% of cases. The disease typically presents in children and young adults, with a slight male predominance.
Etiology
The exact etiology of Rosai-Dorfman Disease remains unclear. However, several hypotheses have been proposed:
- Immune dysfunction: An aberrant immune response to an infectious agent or an autoimmune process may trigger the disease.
- Viral infections: Some studies have suggested a possible association with human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), although a definitive causal relationship has not been established.
- Genetic factors: Familial cases have been reported, suggesting a potential genetic predisposition in some patients.
- Neoplastic process: Recent studies have identified recurrent mutations in MAP2K1 and ARAF genes in some RDD cases, suggesting a possible neoplastic nature in a subset of patients.
Clinical Features
The clinical presentation of Rosai-Dorfman Disease can vary widely, ranging from asymptomatic lymphadenopathy to severe systemic symptoms. Key clinical features include:
- Lymphadenopathy: Massive, painless cervical lymphadenopathy is the most common presentation, often bilateral and symmetrical. Other lymph node groups may also be involved.
- Constitutional symptoms: Fever, night sweats, weight loss, and fatigue are common.
- Extranodal involvement: Can affect various organs, including skin, soft tissue, central nervous system, eyes, and bones.
- Laboratory findings: Elevated erythrocyte sedimentation rate (ESR), polyclonal hypergammaglobulinemia, and mild anemia are frequently observed.
Diagnosis
The diagnosis of Rosai-Dorfman Disease is based on a combination of clinical, radiological, and histopathological findings:
- Imaging studies: CT, MRI, or PET-CT scans can help assess the extent of lymphadenopathy and extranodal involvement.
- Histopathology: Lymph node or tissue biopsy is essential for definitive diagnosis. Characteristic features include:
- Expansion of lymph node sinuses by large histiocytes with abundant pale cytoplasm
- Emperipolesis: presence of intact lymphocytes within the cytoplasm of histiocytes
- Immunohistochemistry: S100 and CD68 positive, CD1a negative histiocytes
- Differential diagnosis: Includes Langerhans cell histiocytosis, lymphoma, and other reactive lymphadenopathies.
Treatment
Management of Rosai-Dorfman Disease is tailored to the individual patient, considering the extent of disease and clinical symptoms:
- Observation: Many cases are self-limiting and may resolve spontaneously, warranting a watch-and-wait approach for asymptomatic patients.
- Surgical excision: For localized disease or when biopsy is needed for diagnosis.
- Systemic therapy: For symptomatic or progressive disease:
- Corticosteroids: First-line treatment for most patients
- Chemotherapy: Cytotoxic agents like vinblastine, methotrexate, or cladribine for refractory cases
- Immunomodulators: Thalidomide, lenalidomide, or rituximab have shown efficacy in some cases
- Radiotherapy: May be considered for localized disease, particularly in CNS involvement.
- Targeted therapy: MEK inhibitors (e.g., cobimetinib) have shown promise in cases with MAP2K1 mutations.
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
