1. GENERAL INFORMATION
1.1 Epidemiological data
Rosai-Dorfman disease most commonly affects young adults – males more often than females -, with a peak age around 20 years (Foucar 1990). World-wide it is a sporadic disease, with occasional clusters, which suggest either an infective precipitant or genetic predisposition.
1.2 Etiologic and risk factors
Etiology is unknown. The lesional cell derivation from circulating mononuclear cells suggests a reactive disorder and the increased incidence of serum auto-immune antibodies during active disease suggests a possible pathogenic correlation with an immune dysregulatory process. HHV-6 and EBV have been implicated in some cases.
2. PATHOLOGY AND BIOLOGY
2.1 Biological data
The abnormal cells in tissue infiltrates are activated macrophages that express Leu-M3 and HAM-56 surface antigens as well as receptors for transferrin, interleukin-2, Fc and C3 (Eisen 1990; Chan 1993).
Histiocytes with abundant pale cytoplasm and round-to-oval nuclei with a single nucleolus massively engorge sinuses and interfollicular areas of lymphnodes, usually with evidence of lymphocytophagocytosis (Pritchard 2001).
There is no generally accepted grading system for Rosai-Dorfman disease.
3.1 Signs and symptoms
In Rosai-Dorfman disease, bilateral painless cervical and paratracheal lymphadenopathy, which can be massive, is the presenting symptom in the vast majority (approximately 90%) of cases (Foucar 1990; Chan 1993). Inguinal and axillary lymphadenopathies are less common (approximately 20% of patients). Other sites of lymph node enlargement involvement include mediastinum and upper para-aortic nodes (10-15%), The most common sites of extranodal involvement are the skin, upper respiratory tract, Waldeyer’s ring, and bone. Compared with patients with systemic Rosai-Dorfman disease, patients with primary cutaneous Rosai-Dorfman disease are older, women are more commonly affected, and whites are more likely than blacks to be afflicted (Frater 2006). Systemic symptoms are rare. Bone marrow, liver and spleen are usually spared.
3.2 Diagnostic strategy
Lymph node biopsy is the basis for the diagnosis of Rosai-Dorfman disease.
3.3 Pathological diagnosis
Diagnosis rests entirely on pathological examinations (Weitzman 2005). In addition to light microscopy, it is recommended that specimens are prepared for immunological investigation (Eisen 1990). Given the necessity of performing some diagnostic tests on snap-frozen sections (S-100 staining), prompt interaction between the surgeon and the pathology laboratory is mandatory in order to appropriately process the biopsy material, as it is the case with all histiocytosis syndromes (Schmitt 1992).
4.1 Staging classifications
There is no accepted staging system for Rosai-Dorfman disease.
4.2 Staging procedures
When Rosai-Dorfman disease is diagnosed, in addition to a thorough clinical examination, recommended investigations are hemoglobin and/or hematocrit, WBC and differential, platelet count, liver function tests including serum transaminases, alkaline phosphatase, bilirubin, albumin and total protein, coagulation studies (PT, PTT, fibrinogen), as well as chest radiograph (PA and lateral) and an ultrasound or CT of the abdomen. Particular clinical features or early laboratory results may suggest further studies.
5.1 Natural history
In Rosai-Dorfman disease, the clinical course is usually indolent for many years, with spontaneous regression in the majority of patients. It does not usually threaten life or organ function. In a few patients the disease may become progressive and require treatment. In such cases, the histology should be carefully reviewed. There are only anecdotal reports of deaths due to the disease or associated complications.
5.2 Prognostic factors
Involvement of certain extranodal organs such as kidneys and lungs or widespread nodal dissemination are considered poor prognostic factors, but in these cases the histopathology must be reviewed.
6.1 Treatment of asymptomatic disease
As yet, there are no national or international protocols for this disease. Most patients with Rosai-Dorfman disease are asymptomatic and an initial wait-and-see approach is a standard option, on a type C basis, since spontaneous regression may occur and treatment is often causes more side-effects than benefit (Pulsoni 2002).
6.2 Treatment of symptomatic disease
For patients with progressive or symptomatic presentation or for those requiring treatment because of cosmetic problems, standard treatment on a type C basis is corticosteroid therapy, usually prednisone at high doses (initially 2 mg/kg daily). Surgery, radiation therapy and/or chemotherapy (usually with vinca alkaloids or 6-mercaptopurine and oral methotrexate) may be suitable for individual clinical use on a type R basis in patients not adequately controlled with steroid treatment (Pulsoni 2002 ). Associated autoimmune conditions usually resolve as the primary condition responds to standard therapy, though both processes may be slow (Foucar 1990; Komp 1990; Chan 1993;Pritchard 2001).
7. LATE SEQUELAE
7.1 Treatment of late effects and sequelae
A few patients need prolonged or intermittent treatment with corticosteroids, with consequent long-term steroid side-effects (Foucar 1990; Allen 1992; Koduru 1995).
7.2 Related and secondary tumours
It is very rare to find second tumours associated either with the disease itself, or related to treatments, although concurrent lymphoma has been reported (Shoda 2004).
8.1 General principles and objectives
The aim of follow-up is to monitor disease evolution and to detect functionally significant complications, especially airway compression, at an early stage.
8.2 Suggested protocols
Follow-up examination should include clinical examination and chest X-ray. Frequency of follow up should be related to the manner in which the disease evolves.
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Prof. Jan-Inge Henter (Author)
Karolinska Hospital – Stockholm, Sweden
Prof. Jon Pritchard (Reviewer)
Passed away on January 20th, 2007
Dr. Carlo Tondini (Editor)
START Clinical Editor – Ospedali Riuniti – Bergamo, Italy