Keywords:
Histiocytosis, sinus - Proliferative disorder - Radiotherapy - Surgery
Descritores:
Histiocitose sinusal - Transtorno histiocítico proliferativo - Radioterapia - Cirurgia
INTRODUCTION
Rosai–Dorfman disease (RDD) is an uncommon, often self-limiting benign, non–Langerhans-cell
histiocytic proliferative disorder, first described by Ro-sai and Dorfman in 1969
as sinus histiocytosis with lymphadenopathy. [1], [2] This rare benign histiocyte disorder can have nodal and extranodal manifestations,
the last one occurring occurring in up to 40% of patients. [3], [4] Extra nodal involvement occurs in up to 40% of cases and common sites of involvement
include the skin, upper and lower respiratory tract, soft tissue, bones, kidney, liver,
orbit and central nervous system. Treatment is not necessary in most instances, [5] but some patients, when symptomatic, may require medical intervention. In the absence
of established guidelines for the management of this condition, various therapeutic
modalities are used, including surgery, radiotherapy and or chemotherapy for disease
manifestations. [3]
PRESENTATION
Rosai–Dorfman disease is a benign disorder that usually affects young adults and children,
with no predilection by sex. More than 80% of patients present with painless cervical
lymphadenopathy, with or without fever. [1], [2] Other presentation sites include upper aero-digestive tract, orbits and the paranasal
sinuses.
Extra nodal involvement occurs in fewer than 40% of cases, being more common in elderly
patients. In this situation common sites of involvement include the skin, upper airway
and soft tissue. [6], [7]
Bones can also be affected, but are the less frequent presentation. [1], [3]
[Figures 1] and [2] show a CT scan of a lesion presenting in the left femur with important infiltration
of periosteal reaction and muscular and soft tissue infiltration.
Figure 1 Axial CT image of a lesion in left distal femur
Figure 2 Axial CT image of a lesion in the diaphysis of the left femur
The lesions presenting in the skin in general have a xanthomatous appearance, papular
or nodular, with no more than 4 cm in diameter. [8] However, lesions with size of up to 12 cm have been reported. [9]
Rosai–Dorfman disease also can occur in a variety of other sites, including the genitourinary
system, lower respiratory tract, oral cavity, and soft tissues. [10] Involvement of kidney, lower respiratory tract, or liver was found to be a poor
prognostic sign, and patients with associated immunologic disease often fared poorly.
[6]
Approximately 40% of cases present with extranodal disease and 10% have orbital involvement
with only one third of these having bilateral disease. Orbital involvement often presents
as painless proptosis.
Patients can present with lesions in the skin of the lids or other soft tissues of
the orbit. Difficulties with extra ocular movements and lid closure can follow with
more progressive disease. Corneal ulceration, decreased visual acuity and blindness
can occur eventually. [11] Involvement of the CNS remains, however, rare with 32 reported cases in the literature.
All patients underwent surgical treatment and the primary pre-operative diagnosis
was meningioma in 93% of the cases. [12]
In general, prognosis has been found to correlate both with the number of nodal groups
and with the number of extra nodal systems involved by RDD. [6]
HISTOLOGY
Rosai and Dorfman first described 4 cases of the clin-icopathologic entity known as
sinus histiocytosis with massive lymphadenopathy in 1969. [1], [2]
Histological studies include RDD cells in the macro-phage/histiocyte family, but their
exact origin is still unknown. Scattering, clusters or sheets of large polygonal histiocytes
intermingled with a florid, mixed inflammatory infiltrate. Patch and bandlike infiltrate
of numerous mature plasma cells around glands and vessels is a constant finding. [9] The presence of em-peripolesis of leukocytes, which can be highlighted by S-100
protein stain, and concurrent histiocytosis on pathology examination is mandatory,
histiocytes also have abundant cytoplasm. [1]
A report published by Eisen et al. showed that RDD cells can also express “pan-macrophage”
antigens such as EBM11, HAM 56, and Leu-M3, antigens functionally associated with
phagocytosis (Fc receptor for IgG, complement receptor 3), and lysosomal activity
(lysozyme, alpha 1-antichymotrypsin, and alpha 1-antitrypsyn), antigens associated
with early inflammation (Mac-387, 27E10), antigens commonly found on monocytes, but
not tissue macrophages (OKM5, Leu-M1), and “activation” antigens (Ki-1 and receptors
for transferrin and interleukin 2).
These data suggest that SHML cells are true functionally activated macrophages that
may be recently derived from circulating monocytes. [13]
TREATMENT
Currently, there are no clear guidelines and no ideal treatment protocol exists for
the management of RDD. The disease may have a benign course without therapy, but surgery
may be required to relieve obstructive symptoms.
Initial management usually consists of either inci-sional or excisional biopsy, followed
by observation in most cases. The surgical management is usually reserved for recurrent
lesions causing functional disability or obstruction of critical structures.
About one third of patients can achieve complete or partial response to the use of
corticosteroids alone.
In more symptomatic and advanced disease various chemotherapeutic regimens have been
tried so far. The combinations of vinca alkaloids, alkylating anti-neoplastic agents,
and or corticosteroids appear to be the most effectives. [5]
Treatments with acyclovir or interferon alpha have also being documented in the literature
with anecdotal responses. [14], [15]
There is a paucity of information in the literature describing techniques and doses
of radiation therapy (RT), despite its relative success, and probably due to its relationship
with potential malignant transformation. Advances in the planning and delivery of
RT in its various modalities, warrant the reporting of recent RT treatments.
The largest series reporting the use of RT in the treatment of RDD was published by
Komp et al. [5] RT treatments were documented in 34 out of 418 patients with RDD. Unfortunately,
RT dose was reported in only 18 patients, with no clear relationship between dose
and response. There were 5 patients who received doses between 30 Gy and 49 Gy, with
1 patient presenting complete response and another partial response, and 3 had no
response. Doses above 50 Gy were used in 2 patients, achieving partial response in
1 and no response in the second. The remaining 11 patients received doses of less
than 30 Gy, with 3 partial and 8 absence of response.
Modern RT techniques, such as intensity-modulated radiation therapy (IMRT), have been
introduced to minimize the risk of treatment-related toxicity, but they have not been
formally evaluated in this situation.
RT can also be prescribed as primary or postoperative treatment, and in some instances
to treat recurrent disease.
As the etiology of the heterogenic response rates of these tumors is still unclear,
we conclude that due the paucity of data and published papers mainl based on case
reports or small cohorts, a RT doseresponse relationship cannot currently be securely
suggested. Other factors that affect the definition of this relationship are poor
reporting of treatment plans and dosimetry, variation on schedule and dose fractionation
of radiotherapy, besides the rarity of the disease, patient inconvenience, in general
daily treatments over 2 weeks, expense and somewhat obscure mechanisms of action.
In conclusion, RDD is an uncommon, often self-limiting benign with no clear treatment
protocol. In most instances RDD does not require treatment, but some patients, when
symptomatic, may require medical intervention that can include: corticosteroids alone
in most situations. In more symptomatic and advanced disease chemotherapy or radiotherapy
are reasonable options and the surgical management is, generally, reserved for recurrent
disease.
Bibliographical Record
Antonio Cássio Assis Pellizzon. Radiotherapy and Rosai-Dorfman disease. Brazilian
Journal of Oncology 2017; 13: e-BJO20171346A99.
DOI: 10.26790/BJO20171346A99
