Discussion
Rosai-Dorfman Disease is a rare disease of lymph nodes often associated with extra nodal pattern and its characterized by benign histiocytic proliferation.1,4-6,10,13,17
RDD is commonly encountered in children and young adults and the trend is marked in those at their first to second decades of life and with slight male preponderance.5,9,12,13
The disease tend to present with various clinical features such as painless massive enlargement of cervical lymph nodes that may be accompanied by leukocytosis and elevated ESR, fever and hypergammaglobulinemia.4,5,8,10,16
Patients with RDD may present with concurrent involvement of extra nodal and nodal sites and such phenomenon may be challenging in terms of establishing its diagnosis and thus RDD may be missed during the first encounter.3,12
To date, the exact aetiopathogenesis of RDD has remained to be idiopathic though an aberrant exaggerated immune response to infectious agents especially viral aetiology may lead to proliferation of the histiocytes.8,12,13
Available studies have depicted the presence of Human Herpes Virus 6 genome through in situ hybridization as well as the relationship with Klebsiella, Epstein-Barr virus, Brucella, or Cytomegalovirus as the possible underlying aetiology.10,12,13
The pathognomonic histocytopathological feature of RDD is the presence of a phenomenon known as emperipolesis which is characterized by numerous large histiocytes with abundant, pale cytoplasm having variable number of intact lymphocytes within the cytoplasm.3,7,15,17-19
Histocytopathologically; In patients with RDD, the background is polymorphous comprising of lymphocytes, plasma cells and occasional neutrophils and all these features were present in the collected cytology and histopathology specimens.3,7,18,19
Although the histocytomorphological features are typical, diagnostic difficulties may sometimes arise. The major differential diagnosis of RDD upon FNAC of the lymph nodes or open lymph node biopsy include reactive lymphoid hyperplasia with sinus histiocytosis, Langerhans cell histiocytosis (LCH), Tuberculosis and Lymphoma which may be Hodgkin’s or Non-Hodgkin’s lymphoma.3,7,17-19
Regarding the differentials of RDD; Reactive sinus histiocytosis tend to show loose clusters of histiocytes, accompanied by germinal center cells, reactive lymphocytes, immunoblasts, and tingible body macrophages without emperipolesis. Such cytologic findings may sometimes mislead the cytologist for a simple diagnosis of reactive lymphadenopathy.3,10,11,18,19
Cytologically; Langerhans cells have grooved nuclei and the background shows eosinophilic microabscess and Immunoreactivity with CD1a tends to be positive and thus can differentiate RDD.3,18,19Tuberculous lymphadenitis shows epithelioid cell granuloma with or without caseous necrosis which are absent in Rosai–Dorfman disease.3,15,19 Hemophagocytic syndromes should be differentiated from Rosai–Dorfman disease on the basis of the presence of hemophagocytosis, absence of emperipolesis, and the presence of pancytopenia and hepatosplenomegaly.3,7
Hodgkin’s disease and some variants of Non-Hodgkin’s lymphoma show lymphocytes, plasma cells, histiocytes, eosinophils, and Reed– Sternberg cells.7,11,17
Histologically, apart from the mentioned known differential diagnoses, Gaucher’s disease, metastatic carcinoma and melanoma and histiocytic sarcoma can add up to other differentials though the classical histomorphology of histiocytic proliferation inclusive of emperipolesis can lead to a definitive diagnosis.19 Whenever a pathologist is in doubt then, immunohistochemistry with CD11, CD14, CD34, CD68 and S-100 protein7,13,19 may be of help to support the diagnosis of RDD.
In our case, we established the diagnosis of RDD due to massive bilateral cervical and submandibular lymphadenopathy coupled with the presence of emperipolesis in histocytopathology.
Regarding the treatment of RDD, usually it has a self -limiting course in majority of the patients 4,5,8,10,12 and therefore treatment is not necessary in majority of them. Our patient was treated using steroids which were provided by tapering the dose over two weeks for relief of symptoms and to reduce lymphadenopathy. Surgery is usually not required in patients with RDD 4,5,8 unless the lymphadenopathy is too massive and causing discomfort to patient. It should generally be limited to biopsy for confirmation of the diagnosis similar to what was done to our patient where open lymph node biopsy was done for confirmation of the diagnosis..
Depending on the affected anatomical site, the treatment options include surgery, chemotherapy, steroids and radiotherapy.5,20Medical therapy for RDD includes corticosteroids, cytotoxic agents or both. Combination of corticosteroids (prednisolone) along with agents like vinca alkaloids (vincristine and vinblastine), 6-mercaptopurine, methotrexate, or alkylating agent (cyclophosphamide) has shown promising outcomes.5,20 Generally, RDD has an indolent course with approximately 50% of them resolving without any residual disease. However in one-third of patients, residual adenopathy may be noted and remaining approximately 17% have unresolved symptoms even after 5–10 years.5,21 In our case the patient showed no residual disease or recurrence at 3-months follow up.