Discussion
Rosai-Dorfman Disease (RDD) which is also referred to as sinus
histiocytosis with massive lymphadenopathy, is an exceedingly rare
non-Langerhans cell reactive histiocytic disorder that was initially
described in 1969 2, 8. The prevalence of RDD is
approximately 1:200,000 in the United States, and may present with
fever, neutrophilia, increased serum erythrocyte sedimentation rate,
leukocytosis, lymphopenia, polyclonal hyperglobulinemia, and anemia. In
most cases, however, there is no apparent or specific symptom9-13.
In its most recent revised classification in 2016, the writing group of
the Histiocyte Society has classified RDD into the following subtypes:
familial RDD, classical RDD, extranodal RDD, neoplasia-associated RDD,
and immune disease-associated RDD 14. Classic RDD
presents with massive painless cervical lymphadenopathy in children and
young adults, with a slight (58%) male predominance and a benign
self-limiting course 8, 13, 15, 16. Older age and
underlying immunologic abnormalities (autoimmune hemolytic anemia,
Wiskott-Aldrich syndrome, glomerulonephritis, rheumatoid arthritis) are
associated with a more extensive disease and chronic relapsing course17.
The pathologic features of nodal RDD include the sinus expansion of
large histiocytes, described by Destombes as possessing “watery-clear”
cytoplasm with a large foamy nucleus and prominent nucleolus. Consistent
features, regardless of the site, include the cytomorphology of the
large pale histiocytes and their immunophenotype. Emperipolesis, the
trafficking of intact leukocytes through the cytoplasm, is a helpful
finding but is not required for diagnosis, because it can be focal,
especially at extranodal sites, and may be seen focally in other
histiocytoses such as juvenile xanthogranuloma, and malignant
histiocytoses. Extranodal lesions are usually associated with more
fibrosis, fewer RDD histiocytes and less emperipolesis. In such cases,
immunostains are needed to highlight the residual RDD histiocytes in a
rich lymphoplasmacytic background with stromal fibrosis and a variable
xanthomatous histiocytic reaction. The immunophenotype of the large RDD
histiocytes is characterized by cytoplasmic and nuclear S100 and fascin
positivity, with CD68 and variable CD163 and CD14 positivity. The cells
are CD1a−/CD207− in contrast to Langerhans cell histiocytosis18-22.
Extranodal involvement is common and may occur in more than 40% of
patients, sometimes without associated lymphadenopathy, and only 23% of
patients have exclusive extranodal disease 13, 23, 24.
Virtually every organ can be affected by RDD (respiratory, bone, CNS,
genitourinary, orbit, soft tissue, visceral organs, nasal cavity, etc.)
and in contrast to isolated lymphadenopathy, the mortality of extranodal
RDD is higher in patients with lower respiratory tract, hepatic, or
renal involvement (30%, 33%, and 40%, respectively)13. Intraabdominal extranodal disease is uncommon,
with an incidence of 4% 25. The gastrointestinal (GI)
system is one of the least commonly affected sites (<1%); we
are aware of only 41 examples reported in the English literature7, 13, 25-40. The GI disease mostly affects
middle-aged females. Most digestive system cases arise in the tubular GI
tract with most cases being located beyond the pylorus40. Pancreatic or hepatic involvement is reported but
extremely rare 13, 34, 41. Hepatic lesions tend to
present in younger patients; all but the 1 reported patient has had
systemic disease 25, 29, 33. To our knowledge, our
case is the first adult patient reported with solitary liver RDD,
without lymphadenopathy.
No uniform approach has been delineated for RDD, and treatment is best
tailored to the individual clinical circumstances. Therapeutic
strategies in literature include: observation, steroids (prednisone
40-70mg per day, followed by taper), surgical
resection/debulking, radiotherapy, chemotherapy, Sirolimus, Thalidomide,
Rituximab and Imatinib 42-49. In our case, the patient
had a partial response to steroids and her symptoms have been improving.
The authors do not expect a complete resolution of the disease, however
in cases such as these we recommend beginning with steroids and
escalating to other treatments only if the disease is non-responsive to
steroids and difficult to manage or life threatening. We encourage
serial imaging and follow-up for any changes.