Discussion
Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, a rare disease with a variable presentation and course. Specific incidence and prevalence is not known for this disease with only about 1000 reported cases worldwide.(5) It is common in males than in females 4:1 and it affects all age groups but more frequently reported in young children and adolescents especially in the first two or three decades. Its pathogenesis remains unknown, though there is no clear causative agent in most cases, a link between human herpes virus 6 (HHV-6), Epstein-Barr virus (EBV) and parvovirus B19 has been suggested, though not conclusive (4)
The clinical presentation of RDD has several predictable signs and symptoms, the most common nodal site being painless bilateral cervical lymphadenopathy reported in nearly 90% of cases.(1),(4)
Extra- nodal involvement is observed in approximately 40% of cases and can occur anywhere in the body with the most common sites including the skin, gastrointestinal tract, eyes, external and internal ear, skeletal system, upper and lower respiratory tracts, oral cavity, nasal and paranasal cavities, and the central nervous system(1),(3),(6),(7) CNS involvement is rare, and the constitutional symptoms are absent, this poses a therapeutic challenge as spontaneous remission is rare and there is no standard therapeutic protocol for its treatment. From a case series of 6 patients with CNS involvement all underwent surgical excision, followed by chemotherapy and steroids. (7)
Our case was a young female who presented fevers and multiple cervical, sublingual, submandibular and supra clavicular lymphadenopathy, with leukocytosis, neutrophilia, anemia, thrombocytosis, an elevated C- RP and ESR. However, the possibility of Rosai-Dorfman disease was not considered clinically till FNAC cytology reports were available. In our setting this presentation can easily be misdiagnosed as it mimics common infections like TB adenitis and malignancy like lymphoma. The differentials include reactive lymphadenitis, tuberculosis, lymphoma, metastatic carcinoma, hemophagocytic syndrome, and Gaucher’s disease. Our patient was initially diagnosed as TB adenitis and kept on Anti TB medication for 1 month without any resolution of symptom’s . Due to its rare occurrence this poses a diagnostic challenge. We screened her for viral etiology like EBV, CMV and herpes virus which have been linked to the etiology of this disease, the results were negative.
Our patient was diagnosed using FNAC, When compared to surgical core or excisional biopsy, FNAC can at times be misinterpreted due to limited or non-representative sampling and, as it does not permit examination of the tissue architecture, diagnosis can be further confounded.
Despite these limitations, FNAC is still a very useful tool for the diagnosis of RDD. (8),(9),(10)
Histology findings include alteration of the normal lymph node architecture by massive sinusoidal dilation that contains histiocytes, lymphocytes, and plasma cells. Emperipolesis within the histiocyte cytoplasm is the classical finding in RDD. The histiocytes will be positive for immunohistochemical stains CD68 and S100 and are typically negative for CD1a.
There is no unified therapeutic protocol for the treatment of this disease, spontaneous remission is observed, therefore “ wait and watch” approach is recommended. (4)
Our patient was treated with steroids at a dose of 10mg twice daily per day (2mg/kg) for 2 weeks and then taper off over 4 weeks. She was asymptomatic after 3 weeks of starting the treatment. Surgery remains the mainstay treatment for RDD. For symptomatic patients requiring systemic therapy steroids are first-line therapeutic option that produces responses in both nodal and extra-nodal disease; however, the reliability and durability of these responses is unpredictable, furthermore the duration of treatment is also not known. Very limited clinical trials have been done using chemotherapy and radiotherapy therefore the effectiveness of these methods is still uncertain. In cases of disseminated disease chemotherapy has been used with agents such as vinca-alkaloids, anthracyclines, and alkylating agents with varying response rates. Radiotherapy is considered a palliative method in patients with symptomatic disease. (2) (4)
RDD has been postulated to remit and relapse, however the recurrence rate is unknown. We are following up our patient every 3 monthly for at least 2 years to assess for the possibility of future relapse.
The parents of this child were losing hope in the beginning, as they could not see any difference in their child’s symptoms despite of all the medication and investigations that were taken. But later once she was on steroids and after thorough counselling them, they were very co-operative and appreciated our efforts to help their child.