Journal of Clinical Neuroscience 17 (2010) 1286–1288

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Journal of Clinical Neuroscience

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Clinical Study

Primary intracerebral Rosai-Dorfman disease

Jia-Tang Zhang *, Hui-Jun Tian, Sen-Yang Lang, Xiang-Qin WangDepartment of Neurology, The Chinese People’s Liberation Army (PLA) General Hospital, 28 Fuxing Road, Hai Dian District, Beijing 100853, China

a r t i c l e i n f o a b s t r a c t

Article history:Received 23 November 2009Accepted 4 January 2010

Keywords:Central nervous systemExtranodal sinus histiocytosis with massivelymphadenopathy (SHML)Rosai-Dorfman disease

0967-5868/$ - see front matter Crown Copyright � 2doi:10.1016/j.jocn.2010.01.048

* Corresponding author. Tel.: +86 10 68182255.E-mail address: thj96236@163.com (J.-T. Zhang).

Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease (RDD),is an idiopathic histiocytic disorder of lymph nodes and extranodal sites. Central nervous system (CNS)manifestations, particularly in the absence of nodal disease, are rare. Intracranial RDD clinically andradiologically resembles meningioma, and histologic examination is essential for a definitive diagnosis.We report four patients with RDD primary to the CNS without evidence of other sites of involvement,review the literature, and discuss the clinical manifestations, pathology, treatment and outcome.

Crown Copyright � 2010 Published by Elsevier Ltd. All rights reserved.

1. Introduction

Rosai-Dorfman disease (RDD), which is characterised bymarked dilatation of the lymph node sinuses containing histio-cytes, is a rare self-limited pseudolymphomatous disease of un-known etiology. It can affect any age group. It generally presentswith massive, painless cervical lymphadenopathy, fever, weightloss, and polyclonal hypergamma globulinemia.

More than 600 patients with RDD have been reported since itsoriginal description. The most commonly reported extranodal sitesinclude the skin,1 orbit2 and breast;3 but involvement of the centralnervous system (CNS), especially in the absence of nodal disease, isvery rare.4

Here we report four patients with intracranial dural-based RDDwith no concurrent clinical lymph node involvement. IntracranialRDD can be a diagnostic challenge because of its morphologic sim-ilarities to both benign and malignant processes. This study re-viewed the characteristics of four patients with RDD diagnosedduring a 6-year period from 2002 through 2007 in the General Hos-pital of the People’s Liberation Army (PLA), including clinical pre-sentations, histologic findings, associated diseases and outcomes.

2. Patients

2.1. Patient 1

A 27-year-old male was admitted to the hospital with a 3-month history of headaches and progressive binocular visualimpairment. Visual acuity of the left eye was markedly decreased

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to light perception only. His MRI showed a homogeneous isoin-tense mass lesion in the sellar region (Fig. 1A, B), which wasthought to be consistent with a meningioma. The patient under-went a craniotomy to remove the lesion. Microscopic examinationof the lesion showed fibrous tissue with an intense inflammatoryinfiltrate composed of histiocytes, lymphocytes, and plasma cells.Multiple histiocytes were contained within the cytoplasm of intactlymphocytes (emperipolesis) (Supplementary Fig. 1A). The histio-cytes stained positive for S100 and CD68, but negative for CD1a(Supplementary Fig. 1B, C). The histologic appearance of the lesionand the immunohistochemical findings were consistent with adiagnosis of RDD. Postoperatively, the patient did not receive anytreatment. At the latest follow-up (after 4 years) the patient had re-mained asymptomatic with no evidence of recurrence onneuroimaging.

2.2. Patient 2

A 38-year-old female was admitted to the hospital with a 2-week history of headaches, associated with nausea, and vomiting.MRI showed a hyperintense mass with an enhancing peripheralwall, arising from the pituitary fossa with a suprasellar extensionon the sagittal (Fig. 1C) and coronal post-contrast T1-weightedMRI. The patient underwent transsphenoidal surgery. Microscopicexamination of the lesion showed histologic features of RDD. Noadditional treatment was given. The patient was asymptomaticafter 2 years of follow-up.

2.3. Patient 3

A 26-year-old female was admitted to the hospital with a 4-month history of intermittent fever, headaches, nausea, and

ights reserved.

Fig. 1. (A) Patient 1. Sagittal T1-weighted MRI showing an isointense lesion in the sellar region. (B) Patient 1. Sagittal enhanced T1-weighted MRI showing a homogeneouslyenhancing lesion in the sellar region. (C) Patient 2. Sagittal enhanced T1-weighted MRI showing a ring-enhancing lesion in the sellar region.

J.-T. Zhang et al. / Journal of Clinical Neuroscience 17 (2010) 1286–1288 1287

vomiting. Physical examination revealed no systemic lymphade-nopathy, hepatosplenomegaly, or other focal lesions. The cerebro-spinal fluid (CSF) studies showed polymorphonuclear pleocytosiswith mildly elevated protein and low glucose. Her CT scans showedcerebral edema. Tuberculous meningitis was suspected, and anti-mycobacterial drugs were administered. The MRI showed a hyperin-tense mass with an enhancing peripheral wall arising from thepituitary fossa with a suprasellar extension on the sagittal post-con-trast T1-weighted MRI. The patient underwent transsphenoidal sur-gery. Microscopic examination of the lesion showed a densecollagenous matrix containing histiocytes, plasma cells, and smalllymphocytes surrounded by aggregates of larger histiocytes (emper-ipolesis). There was no evidence of malignancy. The histiocytic nat-ure of the larger cells was confirmed with S100 and CD68immunostaining. No reactivity was present with CD1a. These find-ings were considered to be most consistent with RDD. The patienthad an uneventful postoperative course. There has been no recur-rence after 3 years of follow-up.

2.4. Patient 4

A 30-year-old male was admitted to the hospital with a 2-yearhistory of recurring headaches, right nasal obstruction, and epi-staxis. Physical examination revealed a mass in the right nasal cav-ity, and no cranial nerve defects. MRI showed multiple enhancingmasses in the right maxillary sinus, right nasal cavity, orbit, andanterior cranial fossa. A craniotomy was performed, with excisionof the lesions. Histological examination confirmed the RDD. Noadjuvant therapy was given after surgery. His postoperative recov-ery was uneventful, but he has been lost to follow-up.

3. Discussion

RDD is rarely found intracranially; however, its ability to mimicmeningioma, as well as other pathologies, underlines its impor-tance. More experience will be necessary before its clinical presen-tation and prognosis can be clearly outlined.

The presenting symptoms depend on the site of involvementand included cranial nerve deficits, seizures, and increased intracra-nial pressure. Intracranial involvement by RDD usually occurs in theform of a subarachnoid, subdural, or epidural mass in the convexityor in the suprasellar, parasagittal, or petroclival regions, causingheadaches and hearing or vision loss. Intracranial RDD usually man-ifested on imaging as one or more enhancing, dural-based, extra-axial masses with perilesional cerebral edema. Thus, the diseaseclosely mimics meningiomas clinically and radiologically.5,6

Histology and immunophenotyping are essential to reach a cor-rect diagnosis. In RDD, on microscopic examination, the polymor-phic infiltrate consists of histiocytes, lymphocytes, and plasmacells. Emperipolesis, signifying the phagocytosis of lymphocytes,may be more difficult to identify in extranodal sites such as theCNS.7 Emperipolesis is present in only 70% of cases.8 As seen in pa-tient 1, emperipolesis, although present, may not be prominent.The results of immunophenotypic studies in our patients are sim-ilar to those previously reported.9 Immunohistochemical stainingis useful in differentiating RDD from other histiocytic lesions. Thehistiocytes of RDD are thought to be activated macrophages de-rived from circulating monocytes, and they are usually stronglyreactive to S100 and CD68 protein, and not reactive to CD1a. Thehistological differential diagnosis includes Langerhans histiocyto-sis, inflammatory pseudotumor, and lymphoproliferative disor-ders. In RDD the lymphocytes are bland, polyclonal, and show amixture of B and T phenotypes.

Most instances of RDD that involve the CNS are treated surgi-cally. Andriko et al. followed 10 patients with surgically treatedCNS disease and found that nine patients had no evidence of dis-ease progression. Most patients (58%) were alive with persistentdisease, whereas only two patients (2/43, 4.7%) had died of RDD–CNS or related operative complications.10 Our patients receivedno further treatment after surgical resection of the mass. No recur-rence or any lymphadenopathy was noted in a follow-up period.Petzold et al. found intracranial tumour regrowth or recurrenceof symptoms in 14% (4 out of 29) of patients with a mean fol-low-up of 10.1 years. Of those patients described as ‘‘stable”, only52% had undergone brain imaging at follow-up. They concludedthat a 5-year follow-up with brain imaging was essential and advo-cated local low-dose radiation to treat patients with subtotal resec-tion or recurrence.5 Although a variety of treatment modalitieshave been used, including steroid therapy and radiation, surgicalexcision, radical if possible, is likely to be the appropriate treat-ment.11,12 Finally, more needs to be known about this disease:long-term, and broad follow-up and investigation is required, par-ticularly for detection of local recurrence, and to determine if adju-vant treatment would be beneficial for patients with a localrecurrence. Extranodal disease does not clearly portend a poorerprognosis, although the presence of disseminated nodal disease,multiple organ system involvement, and underlying immune dys-function are considered unfavorable prognostic factors.

In summary, intracranial RDD is rare, requiring knowledge ofits main clinical manifestations for a correct diagnosis. Pathologistsand neurosurgeons should include RDD in the differential diagno-sis of dural-based lesions that clinically and radiologically resem-ble meningiomas. Other examinations might be useful. Therapy

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remains controversial and follow-up is necessary to avoidrelapses.

Appendix A. Supplementary material

Supplementary data associated with this article can be found, inthe online version, at doi:10.1016/j.jocn.2010.01.048.

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