DOI: 10.5137/1019-5149.JTN.4275-11.2

Case Report

Isolated Intracranial Rosai-Dorfman Disease:
Report of Two Cases and a Review of the Literature
İzole İntrakraniyal Rosai-Dorfman Hastalığı: İki Olgu Sunumu ve
Literatür Derlemesi
Mamdouh Abdel-Razek1, Ghazi Ahmed Matter1, Waleed Abdelfattah Azab1,
Kenneth Chukwuka Katchy2, Anupama Arora Mallık2
1Ibn Sina Hospital, Department of Neurosurgery, Kuwait
2Al-Sabah Hospital, Department of Pathology, Kuwait

Corresponding Author: Waleed Abdelfattah Azab / E-mail: [email-masked]

ABSTRACT
Rosai-Dorfman disease (RDD) is a rare but well-recognized idiopathic histioproliferative disease affecting the systemic lymph nodes. It is
characterized by an unusual proliferation of histiocytic cells. Intracranial localization is a rare manifestation of RDD. The clinical and radiological
differentiation from meningiomas is difficult, and can only be achieved after histological examination. This entity should be considered in the
differential diagnosis of dural based lesions mimicking meningioma. We report 2 cases of isolated intracranial RDD. The first patient had a
large frontal lesion in addition to smaller multiple intracranial lesions. The second patient had only one parasagittal lesion. The diagnosis was
confirmed on histopathological examination after surgical excision. The pertinent literature is also reviewed.
Keywords: Rosai-Dorfman disease, Meningioma, Sinus histiocytosis

ÖZ
Rosai-Dorfman hastalığı (RDH) sistemik lenf düğümlerini etkileyen nadir ama iyi bilinen bir idiopatik histiyoproliferatif hastalıktır. Olağandışı
histiyositik hücre proliferasyonuyla karakterizedir. İntrakraniyal lokalizasyon RDH’nin nadir bir görünümüdür. Meninjiyomlardan klinik ve
radyolojik ayırt etme zordur ve sadece histolojik inceleme ile yapılabilir. Bu hastalık, menenjiyoma benzeyen dural tabanlı lezyonların ayırıcı
tanısında dikkate alınmalıdır. İki izole intrakraniyal RDH olgusunu bildiriyoruz. Birinci hastanın birçok küçük intrakraniyal lezyona ek olarak
büyük bir frontal lezyonu vardı. İkinci hastanın sadece bir parasagittal lezyonu vardı. Tanı cerrahi eksizyon sonrasında histopatolojik incelemeyle
doğrulandı. İlgili literatür de gözden geçirilmiştir.
ANAHTAR SÖZCÜKLER: Rosai-Dorfman hastalığı, Menenjiyom, Sinüs histiyositozu

IntroductIon
Rosai-Dorfman disease or sinus histiocytosis with massive
lymphadenopathy was recognized as a unique histiolymphoproliferative disease of the lymph nodes by Rosai and
Dorfman in 1969 (3,30). It is a rare condition characterized by
massive cervical lymphadenopathy with fever, leukocytosis,
mild anemia, elevated erythrocytosis rate and polyclonal
hypergammaglobulinemia (34). Patients usually tend to be
young at the onset of the disease and usually run a prolonged
uncomplicated clinical course without treatment (21). Extranodal involvement either alone or in association with nodal
disease is seen in approximately 43% of cases (12). The common extranodal sites are the skin, orbit, respiratory tract and
bone (13,34). Isolated intracranial involvement is a very rare
manifestation (46).
Case 1
A 43-year-old male patient with a few months history of
headache and mild dizziness developed 2 episodes of
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generalized tonic-colonic convulsions. General examination
was unremarkable and the patient had no clinical evidence of
lymphadenopathy. He also had no neurological deficits apart
from a right inferior visual field defect. Brain MRI showed
multiple extra axial lesions that were isointense on T1weighted and low signal intensity on T2-weighted MR images
with vivid homogenous enhancement after IV contrast (Figure
1). The largest lesion was in the right frontal convexity causing
marked edema and mass effect. Another small convexity
lesion was seen in the left frontal region, 2 small lesions with
falcine attachment, a lesion in the vicinty of the anterior
clinoid process and one attached to the antero-superior
border of the right petrous bone. The radiological diagnosis
was that of multiple meningiomas. The patient underwent
a right frontal craniotomy for resection of the large frontal
lesion. The dura was vascular and the tumor was attached to
it, circumferential incision around the tumor attachment was
undertaken and a good arachnoid plane around the tumor was
found except for the deeper parts. The lesion had a nodular
grayish-pink appearance with firm consistency. It gave the

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impression of a meningioma (Figure 2). The tumor was totally
removed and the patient had a smooth postoperative course.
Histopathological examination of the specimen demonstrated meningeal infiltration by large pale cells mixed with
lymphocytes and plasma cells. The lesion demonstrated
dense fibrosis. The cell infiltration was conspicuous around
blood vessels and extended into the brain parenchyma. The
large pale cells were positive for CD68 and S100 protein, but
negative for EMA and GFAP. Emperipolesis was identified and
a diagnosis of Rosai-Dorfmans disease was made.
Case 2
A 38-year old female patient presented to the emergency
room with a generalized seizure for the first time that
lasted for a few minutes. General physical examination was
unremarkable. No neurological deficits were detected. Her
fundus examination revealed bilateral early papiledema. MRI
brain showed an isointense right parietal parasagittal mass
with perifocal edema. The lesion enhanced intensely after IV
contrast injection. The superior sagittal sinus was patent and
the lesion was diagnosed as a meningioma. The tumor was
approached through a right high parietal craniotomy. It was
brownish-gray in color with firm consistency and moderate
vascularity. It was attached to the convexity dura with
partial attachment to the superior sagittal sinus. It was easily
dissected from the surrounding brain tissue through a good
plane of cleavage and was completely excised along with
the dural convexity attachment. Histological examination
revealed sheets of histiocytes intermingled with many reactive
plasma cells (Some with Russell Bodies), lymphocytes and
neurtrophils. They were arranged in vague nodules in some
areas and separated with hyalinised collagen. The cytoplasm
of the histiocytes was pale to foamy with eosinophilic
granular with lipofuschin pigment in some. The nuclei were
round to oval in shape with vesicular chromatin and small
nucleoli. There were some multinucleated giant cells (Figure
3). Immune stains were done for S-100 protein, CD 68, EMA
and SMA. The pale large histiocytes were S-100 positive and
displayed emperipolesis.

Discussion
In 1969, Rosai and Dorfman described a newly recognized
benign histioproliferative disorder characterized by massive
cervical lymphadenopathy, fever, and leukocytosis (30).
Pathologically the lymph nodes showed enlarged sinuses
containing large histiocytes with phagocytosed lymphocytes
and the entity was named sinus histiocytosis with massive
lymphadenopathy (SHML) or Rosai-Dorfman disease (30).
RDD is classified among idiopathic or reactive histiocytoses
(5, 12, 44). Occasionally, patients present with only extranodal
disease with no lymphadenopathy; accordingly, the originally proposed term “sinus histiocytosis with massive
lymphadenopathy” may not be precise (11). Molecular studies
have shown that RDD is a polyclonal and reactive process
rather than a neoplastic one, however, the origin of RDD is not
clear (26, 32, 38). It often occurs in the setting of nonspecific
immune dysfunction and many cases occur after a viral illness
(31). Epstein-Barr virus was demonstrated in about 50% of
cases in serological studies (40). Nevertheless, the presence
of Epstein-Barr virus was not documented in histiocytes and
lymphocytes by in situ hybridization technique. The increased
serological titers may be the result of a nonspecific host
immune response and not the cause of RDD (11,39).
Isolated central nervous system (CNS) involvement is
extremely rare (2,6,4,10,13,15,17-19,21-23,28,33,35,36,38,46).
In a large series of RDD including 200 cases there were only 3
cases with intracranial manifestations (9).
Rosai-Dorfman disease involving the CNS occurs most
commonly in patients between 22 and 63 years of age,
with a clear male predominance (4, 10). The mean age at
presentation is 41 and that is almost the same age like in our
cases. Deodhare et al. noticed that the age of onset in patients
with intracranial localization of RDD differ from those with
nodal-based RDD (37.5 yr versus 20.6 yr) (11). The average age
of patients at admission is in the second decade. Only one
patient at the young age of 5-years was treated for clinical
manifestations of RDD (35).

Figure 1: Axial T1-Weighted with contrast (left and right), T2-Weighted (middle) MRI images of case 1, showing the dural-based lesions.

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Clinically, patients with intracranial RDD usually present with
headaches, seizures, numbness, and paraplegia (4). In a metaanalysis of 32 cases by Petzold et al (28) there was 25% incidence
of visual symptoms, which were the presenting feature in 19%
of all cases. One of the main symptoms in our first case was
impairment of vision. Seizures were among the symptoms in
that case and were the only symptom at presentation for our
second case. Massive and painless cervical lymphadenopathy
was noticed in 90% of reported cases (35). None of our
patients had lymphadenopathy. Other manifestations like
anemia, leukocytosis, polyclonal hypergammaglobulinemia,
and raised erythrocyte sedimentation rate are common but
are not always present (12, 34). Extra nodal involvement, such
as the eyes and its appendages, skin, upper respiratory tract,

Figure 2: Gross appearance of the mass in case 1. Round
lobulated mass attached to the dura.

bone, salivary gland, testis, and meninges of the cranium and
spine are seen in one third of the cases (34).
Radiologically, intracranial lesions in cases of RDD appear to
be attached to the dura and radiologically resemble meningioma. (1, 9) The surgical and neuroradiological features seen
in our patient resembled those of a meningioma. Nonetheless, Sze and Zimmerman (37) suggested that the low signal
intensity on T2-weighted MR imaging is a very unlikely a
characteristic of meningioma and may reflect the presence of
free radicals produced by macrophages during active phagocytosis. Focal necrosis, fibrosis, and erythrophagocytosis
may also contribute to low signal intensity on T2-weighted
MR imaging. This low intensity of the lesion on T2-wieghted
images was similarly demonstrated in our cases. Moreover,
N-isopropyl-P-[123I] iodoamphetamine ([123I] IMP) singlephoton emission computerized tomography (SPECT) reveals
a hot lesion on early and delayed images in RDD and is not a
feature of meningiomas (41).
Typical nodal Rosai–Dorfman disease has a pathognomonic,
histopathological cytoarchitecture consisting of massive
expansion of the sinusoids by numerous large histiocytes
with large vesicular nuclei and abundant pale eosinophilic
cytoplasm with ill-defined borders. The histiocytes contain
intact lymphocytes or erythrocytes in their cytoplasm, a
phenomenon known as emperipolesis (X) lymphoplasmacytic
inflammatory cell infiltrate is evident (4,25,45) and is
immunoreactive for kappa and gamma light chains (4,11). The
histopathological differential diagnosis of intracranial RDD
includes Langerhans cell histiocytosis (LCH) or histiocytosis
X, infectious processes, lymphoproliferative disorders, and
plasma cell granulomas, which are well described in other
papers (7,42,43). Langerhans cell histiocytosis may produce
meningeal and dural lesions (20). However, the diagnosis of
RDD is based on the morphological characteristics. There are

Figure 3: Case 2. Histopathological findings. (Left) Sheets of pale histiocytes mixed with plasma cells. Note the perivascular location
of plasma cells. Emperipolesis is seen in some histiocytes (H&E x100). (Right) Higher magnification highlighting emperipolesis (H&E x
400).
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other disease conditions with predominance of histiocytes, like
some cases of leukemia, lipid storage disease, and histiocytosis
X. Nevertheless, the classical findings of dilated nodal sinuses
filled with foamy histiocytes, phagocytosed lymph nodes,
and plasma cells make the diagnosis of this disease apparent
(12). The histological differentiation between Langerhans
cell histiocytosis and RDD is based on the presence of the
following features in the former; Langerhans cells with nuclear
indentation and grooves, positive CD1a is only positive in
LCH, and a confirmatory presence Birbeck’s granules (41).
Abscess formation and fibrosis can be seen in some cases of
RDD. However, prominent emperipolesis and S-100 protein–
positive histiocytes are rarely seen in the infectious process.
In RDD the lymphocytic infiltrate is usually mild and consists
of a mixture of T and B lymphocytes (11). Cases of plasma cell
granulomas demonstrate a polymorphic cellular infiltrate,
composed of lymphocytes, plasma cells, histiocytes, and
foamy macrophages and are associated with fibrosis (8). In
RDD the plasma cells are polyclonal (immunoreactive for k
and c light chains) (4,11). Necrotic areas may also be found
(11, 45). In contrast to RDD cells characterized by S-100
positivity (4,11,29), plasma cell granulomas do not show
S-100 protein–positive histiocytes or lymphophagocytosis
(27). Immunophenotypical studies show that the cells in RDD
share the features of both mononuclear phagocytic cells and
dendritic cells (interdigitating reticulum or Langerhans cells)
(24,26,35). Mononuclear and dendritic cells commonly show
positive expression for CD68, alpha-1-antitrypsin, and alpha1-antichymotrypsin. But S-100 protein expression is only
positive in dendritic cells. However, dendritic cells typically
showing CD1a expression are not observed in any cells of
RDD (24).
Most of the patients with intracranial lesions were treated
surgically. At surgery, Rosai–Dorfman disease lesions in
the central nervous system are firm, lobular, whitish gray
or yellowish tan in color and adherent to the dura. The
diagnosis can only be confirmed by histopathological/
immunohistochemical examination of affected tissues.
Intraoperative pathological diagnosis can be misleading (3).
Some patients received corticosteroid treatment (35),
chemotherapy (16), and radiotherapy was used in some
cases (12). Involvement of the central nervous system in RDD
especially in the absence of nodal disease seems to have a
benign prognosis. Surgery is essential for diagnosis (3,46),
and when total removal is achieved, the outcome is generally
good without risk of recurrence (14).
Conclusion
Rosai-Dorfman disease is an uncommon condition that
rarely involves the brain. In spite of the absence of massive
lymphadenopathy in some cases, it should be considered
in the differential diagnosis of any dural-based lesions on
imaging studies including meningiomas. Low signal intensity
on T2-weighted MR imaging is a very unlikely characteristic
of meningioma and [123I] IMP uptake are characteristics of
RDD. Even with the absence of enough follow-up information,

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surgical excision seems to be the most appropriate treatment
of these lesions when they start causing symptoms.
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