What is Rosai Dorfman Disease [Pathology Infographic]
disease (RDD), originally known as sinus histiocytosis with massive
lymphadenopathy, is a non-Langerhans cell histiocytosis that was first
described in 1965 by Destombes and subsequently recognized as a
distinct entity by Rosai and Dorfman in 1969.
Patients with this rare
and nonmalignant disorder often present with painless cervical
lymphadenopathy, fever, and leukocytosis.
Usually affects healthy
young adults and adolescents.
often manifests in the lymph nodes of the head and neck, but it may
also present in extranodal sites, skin, respiratory tract, bone,
genitourinary system, oral cavity, central nervous system,
eyes/orbit/ocular adnexa, salivary gland, tonsil, breast, soft tissue
The bone marrow is
The etiology of RDD is
unknown though it has been speculated that chronic infection or
an immune response to an infectious agent or an antigen causing the initial histiocytic proliferation.
The classic histology is
characterized by effacement of nodal architecture and dilatation of
lymph node sinuses by lymphocytes, plasma cells and numerous
characteristic histiocytes with large vesicular nuclei and abundant
Many of these
histiocytes, also known as RDD cells, contain intact lymphocytes, and
sometimes plasma cells, neutrophils and red blood cells, within their cytoplasm.
This process whereby cells enter and transit through a cell evading
cellular degradation is known as emperipolesis and was first described
by Humble et al.
sites are involved, similar morphologic features to the nodal
counterpart are seen although with more fibrosis, fewer typical RDD
histiocytes, and less prominent emperipolesis.
Immunohistochemical stains :
stains are useful when diagnosing RDD as the RDD cells have been found
to express pan-macrophage antigens (CD68, HAM56, CD14, etc.), antigens
associated with phagocytosis (CD64, Fc receptor for immunoglobulin G),
lysosomal activity (lysozyme alpha 1-antitrypsin,
alpha1-antichymotrypsin), and immune activation and adhesion molecules
(transferring receptor, interleukin 2 receptor).
consistent and reliable phenotype for RDD is S100(+), CD68(+) and
The term (cutaneous
Rosai-Dorfman disease) CRDD is used to describe the forms of RDD that
only involve the skin.
It presents as
erythematous to brown papules, plaques, or nodules.
CRDD differs from RDD
in that RDD exhibits systemic involvement.
Unlike RDD, more commonly
in young adult males, CRDD typically occurs in older females.
There is no predilection for site and patients with CRDD are free from
systemic manifestations .
Approximately 10% of
RDD patients exhibit skin lesions, and in 3% of cases, the disease
presents exclusively in the skin .
was reported for the first time by Thawerani
et al in 1978 in a
48-year-old male patient who presented with a solitary nodule on the
in CRDD are usually similar to those in RDD.
epidermis is normal.
In the dermis, a diffuse infiltrate of histiocytes is
accompanied by a background infiltrate of lymphocytes and plasma
Lymphoid follicles with
reactive germinal centers may also be present.
The phenomenon of emperipolesis, which represents the presence of intact lymphocytes
within histiocytes, is common in CRDD.
Less often, the cytoplasm may
contain plasma cells, neutrophils and red blood cells.
nuclear atypia are rare, while necrosis is absent.
stain positively for S100 protein and CD68, but negatively for CD1a,
which can be used to confirm the diagnosis of CRDD.
microscopy of CRDD tissue reveals no signs of Birbeck granules, which
eliminates the possibility of Langerhans cell histiocytosis.
diagnoses of RDD-type lesions include lymphoreticular malignancies
when cervical lymphadenopathy is present or soft tissue sarcomas when
patients present with extranodal disease.
A lack of cytologic
atypia typically dispels more malignant diagnoses, and
immunohistochemistry profiles will demonstrate a macrophage-induced
histiocytosis with emperipolesis.
It is also important
to clearly distinguish RDD-similar S-100-positive histiocytoses such
as malignant histiocytosis and LCH.
histiocytosis demonstrates marked cytologic atypia as well as high
mitotic activity, while LCH tends to be CD1a positive with microscopic
evidence of Birbeck granules.
In addition, neither
malignant histiocytosis nor LCH demonstrate the hallmark finding of
The more rare
reticulohistiocytoma may be S-100-positive; however, this disease
shows prominent ground glass appearance, abundant periodic acid
Schiff-positive stain and fewer inflammatory cells in the background.
differences are useful in providing a definitive diagnosis.
Most patients with RDD
have a complete and spontaneous remission.
Some may experience
recurrent or persistent but stable lymphadenopathy.
In rare cases, the
disease follows an aggressive course and may be fatal.
Involvement of kidney,
lower respiratory tract, or liver has been found to be a poor