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.