REVIEW ARTICLE

Isolated cerebellar intraparenchymal Rosai–Dorfman disease – Casereport and review of literature

VILI BEROS1, KARLO HOURA1, KRESIMIR ROTIM1, DARIO JOSIP ZIVKOVIC1,

HRVOJE CUPIC2 & ANDRO KOSEC3

1Department of Neurosurgery, University Hospital ‘Sisters of charity’, Vinogradska 29, 10000 Zagreb, Croatia, 2Department of

Pathology, University Hospital ‘Sisters of charity’, Vinogradska 29, 10000 Zagreb, Croatia, and 3Medical School Zagreb,

Salata 3b, 10000, Croatia

AbstractBackground. Rosai–Dorfman disease (sinus histiocytosis with massive lymphadenopathy) rarely affects intracranial structureswithout involvement of other sites. We herein review the tumour characteristics, differential diagnosis and treatment policy ofthis rare disease.Method. We conducted a PUBMED search using a combination of words ‘Rosai–Dorfman disease’, ‘Central nervoussystem’, and identified 42 cases of such a disease infecting exclusively central nervous system. Out of those cases only onecase was reported to be purely intracerebellar making our case the second one in the literature. Clinical features, differentialdiagnosis, treatment details and follow-up were discussed. We also described the case of 41-year-old man presented withvertiginous symptoms and mild cerebellar ataxia who was diagnosed with a solitary lesion localised deep in the rightcerebellar hemisphere. Immunohistological findings revealed Rosai–Dorfman disease.Findings. The most common locations of the tumour were frontal and parietal region, but CNS lesions have commonlyinvolved the skull base with a leptomeningeal component too. The median age at presentation was in the third decade,ranging from 3 to 78 years. There is a slight male predominance. The follow-up ranged from 1 month to 11 years.Recurrence was not observed in the cases where total surgical excision was performed.Conclusion. Though Rosai–Dorfman disease is a rarity, one should take it into a consideration when treating solitaryintracerebellar lesion. Thorough preoperative evaluation is mandatory and biopsy should be done whenever feasible. Surgicaltreatment of this type of tumour is not always necessary, however, it is essential for postulating the right diagnosis. When totaltumour removal is achieved, the outcome is generally better, with minimal risk of recurrence and with no need for furtheradditional therapy.

Key words: Cerebellum, Rosai–Dorfman, surgery, neuronavigation.

Introduction

Rosai–Dorfman disease (sinus histiocytosis with

massive lymphadenopathy) was first described in

1969 as a benign proliferative lesion with systemic

symptoms: massive bilateral cervical lymphadeno-

pathy, fever and leukocytosis.1 It is characterised by

dilatation of the lymphatic sinuses due to proliferat-

ing histiocytes with emperipolesis (lymphocytopha-

gocytosis).2,3

Rosai–Dorfman disease commonly involves cervi-

cal lymph nodes.4 Involvement of the central nervous

system is rare and isolated involvement of the central

nervous system (CNS) is even less likely to hap-

pen.4,5–7 Among these cases only one previous case

of intracerebellar involvement in an adult patient was

published so far.8 Classic features of Rosai–Dorfman

disease may not be evident in the central nervous

system lesions. In some analyses 63% patients with

CNS involvement had no associated massive lympa-

denopathy. When this disease involved central

nervous system the dura mater, epidural or subdural

compartment was involved in 93% of the cases.9–11

The aetiology and pathogenesis of this disease are

still unknown.12 It often occurs in the setting of

nonspecific immune dysfunction, but many cases

occur following a viral illness such as infection with

Epstein–Barr or herpes virus.13 Possibility of recur-

rence of these lesions is well described in litera-

ture.6,14 The optimal treatment for intracranial

Rosai–Dorfman disease has not been standardised,

but complete surgical resection of the lesion is the

most effective treatment option.

Correspondence: Karlo Houra, M.D., PhD, Department of Neurosurgery, University Hospital ‘Sisters of charity’, Vinogradska 29, 10000 Zagreb, Croatia.

Tel: þ385 1 3787522. Fax: þ385 1 3768273. E-mail: khoura@kbsm.hr

Received for publication 29 April 2010. Accepted 2 December 2010.

British Journal of Neurosurgery, April 2011; 25(2): 292–296

ISSN 0268-8697 print/ISSN 1360-046X online ª 2011 The Neurosurgical Foundation

DOI: 10.3109/02688697.2010.546899

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Review of literature

An internet Medline literature research was con-

ducted utilising the Medline search engine

(www.pubmed.gov) based on the following key-

words; Rosai Dorfman, Sinus histiocytosis, neuro-

navigation, cerebellum, central nervous system and

surgery. Additional searches were conducted utilising

ISI Web of Knowledge (www.isiwebofknowledge.

com/) and SCOPUS (www.scopus.com) search

engines, respectively. Selected papers in the past 10

years (Table I) were reviewed and their references

examined for additional articles.

Illustrative case

A 41-year-old man was admitted to our department

after neuroradiological verification of a solitary lesion

localised deep in the right cerebellar hemisphere.

The patient presented with vertiginous symptoms,

mild cerebellar ataxia and adiadochokinesis in the

right hand which started 6 months earlier. The

working diagnosis was a metastatic tumour regard-

less of the fact that the patient did not show any signs

of other malignant diseases and that there was no

metastasis-characteristic oedema on the MRI scans.

The classical features of Rosai–Dorfmans disease

were not present. There were no signs of lymphade-

nopathy in the cervical region or in other parts of the

body.

The significant laboratory tests were within normal

limits including erythrocyte sedimentation and C

reactive protein. Cerebrospinal fluid (CSF) revealed

no abnormality. Cytology of cerebrospinal fluid was

also negative. MR imaging showed a round lesion

with well-defined edges, centrally located in the right

cerebellar hemisphere that was homogeneously en-

hanced after contrast application. The lesion mea-

sured 12 mm in diameter with no perifocal oedema.

The differential diagnosis in this case includes

metastasis, glioma, granulomatous disease (tubercu-

losis, sarcoidosis) and other histiocytoses like Lan-

gerhans cell histiocytosis and haemophagocytic

lymphohistiocytosis.

The patient underwent right-sided suboccipital

paramedial craniectomy. Given the size of the lesion

and its deep localisation, before the dura opening we

performed lesion punctuation through a minimal

dural incision using a long biopsy needle associated

with a neuronavigational system (Fig. 1). This was

done in order to avoid miss-targeting of the lesion

caused by displacement of the cerebellar structures

after dural opening and CSF release.

After the lesion punctuation, we opened the dura

in a typical manner and reached the lesion following

a channel which we previously formed. Using a

TABLE I. Summary of isolated intracranial Rosai–Dorfman disease cases in past 10 years.

Authors Sex Age(years) Location Treatment Follow-up (months)

Gaetani et al.8 F 67 Cerebellar Surgery 1

Morandi et al.15 F 22 IV ventricle floor Surgery 36

Natarajan et al.16 F 45 R frontal Surgery 5

Andriko et al.17 (11 patients) M 7 10 intracranial Surgery 2–42

F 4 3 spinal Surgery

Kitai et al.10 (2 patients) M 36 Frontal Surgery NA

F 42 Petroclival Surgery

Petzold et al.18 M 47 Planum sphenoidale Surgery Recurrence at 12

Wu et al.14 M 35 L occipital Surgery 60

Franco-Paredes and Martin5 F 57 Diffuse leptomeningeal Biopsy 3

Juric et al.12 M 39 R temporal Surgery 10

Konishi et al.19 F 68 L frontal Surgery 21

Griffiths et al.20 M 9 R frontal Surgery 18

Kinoshita et al.9 M 69 L frontal Surgery NA

Ture et al.21 M 29 R anterior cranial fossa,

orbit and paranasal sinuses

Surgery,

chemotherapy

NA

Toh et al.22 (2 cases) M 59 L cerebllopontine angle Surgery NA

F 60 L frontal parafalcine Surgery

Purav et al.23 (10 cases) 8 M From 18 to 60 6 parietal, 2 Frontal,

2 multiple

Surgery 3–72

2 F

Sharma et al.24 M 40 L sphenoid wing Surgery 3

Gupta et al.13 M 15 R parasellar and petroclival Surgery 12

Di Rocco et al.25 F 13 L frontal Surgery 12

Kumar et al.11 M 45 L temporoparietal Surgery NA

Scumpia et al.26 M 22 R middle cranial fossa

with orbital extension

Surgery NA

Hinduja et al.7 M 42 L middle cranial fossa

and L orbit

Surgery, radiation

therapy

NA

Present case M 41 R cerebellar Surgery 36

M, male; F, female; L, left; R, right.

Isolated cerebellar Rosai–Dorfman disease 293

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micro-neurosurgical technique, the lesion was totally

removed with adequate haemostasis. The tumour

tissue was greyish, firm, well circumscribed and was

sent to a pathohistological laboratory for an analysis.

On gross examination the tissue was greyish-yellow

and firm, measuring up to 1.2 cm in the largest

diameter. Histological analysis revealed diffuse cel-

lular infiltrates of large cells with pale eosinophillic,

focally vacuolated cytoplasm and ovoid excentric

nuclei admixed with lymphocytes and plasma cells.

The aforementioned large cells with pale eosinophil-

lic cytoplasm were immunoreactive to CD68 (Fig.

2a), S-100 protein, vimentin and GFAP and CD1a

negative, which is consistent with non-Langerhans

cell histiocytes. Well-preserved lymphocytes were

observed within the cytoplasm of histiocytes (Fig.

2b), indicating emperipolesis, which is a typical

feature of Rosai–Dorfman disease.

The consecutive follow-up MRI scans, last per-

formed 36 months after the operation, showed no

signs of lesion in neither the operated field nor

anywhere else in the central nervous system. The

patient was well with improvement in neurological

status on further follow-up examinations.

Discussion

Isolated intracranial Rosai–Dorfman disease has

been documented in less than 45 previous cases

(Table I)4,7,10–13,15–17,20,21,23–29 but only one case

published by Gaetani et al.8 was reported to be

purely intracerebellar with the lesion situated in the

right cerebellar lobe. The rarity of this type of

tumour and its intracerebellar localisation may

result in misdiagnosis and inadequate and/or in-

appropriate therapy. Three authors reported poster-

ior fossa localisation of isolated Rosai–Dorfman

disease.10,13,22 In two patients the petroclival region

was involved and the cerebellopontine angle was

involved in the third one. In one patient the lesion

occupied the foramen magnum region together with

cervical extension.29

FIG. 1. Image of the tumour in the right cerebellar parenchima presented with neuronavigational system used for targeting.

294 V. Beros et al.

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The condition tends to occur in older age groups

than the commoner systemic disease. The sex

distribution is similar in both forms, being 1.5:1

(male to female).13 The isolated CNS lesions tend to

present with mass effect, cranial nerve palsies,

pituitary dysfunction or seizures depending on their

localisation. The aetiology of Rosai–Dorfman disease

is still unknown, although an infectious agent, such

as the Ebstein–Barr virus or a herpes virus, might

play some role in its pathogenesis.24

Imaging in cases with intracranial involvement

typically shows a space-occupying intracranial lesion

of dura-based origin with homogenous contrast

enhancement resembling most commonly meningio-

mas. Various degrees of perifocal oedema surround-

ing the mass lesion can be seen.

Macroscopically, the lesion usually presents as a

soft tissue mass which is greyish-white, fleshy and

rubbery. Histopathological examination is charac-

terised by abundant sheets of large and medium-

sized vacuolated histiocytes, interspersed with

chronic inflammatory cells. A feature of the condi-

tion is the presence of lymphophagocytosis (emper-

ipolesis). The histiocytes typically stain positive for S

100 and CD 68 and negative for CD1a.26

Histologic differential diagnostic considerations

include several haematopoietic and primary CNS

lesions such as lymphoplasmacytic meningioma,

multiple myeloma, lymphoma, plasmacytoma, plas-

ma cell granuloma and infection.19 Intracranial

infections including mycobacterial and fungal ones

can be excluded by specialised stains and cultures.

Plasma cell granuloma is typified by a mixed

inflammatory infiltrate with polyclonal plasma cells

and S 100 histiocytes are not seen. Lymphoplasma-

cytic meningioma differs from Rosai–Dorfman dis-

ease with areas of meningothelial or fibrous

meningioma with lymphocytic and plasma cell

infiltrates. Because of the presence of fibrosis,

Rosai–Dorfman disease in the CNS may have a

distinctly nodular appearance suggestive of the

nodular sclerosing variant of Hodgkin’s disease.

Hodgkin’s disease occurring in the CNS, however,

is extremely rare and is typically associated with

relapses.17

No specific therapy is available and due to its rare

occurrence, the optimal treatment has yet to be

established. Current treatment includes surgery,

radiation therapy, chemotherapy, steroids and im-

munosuppressants.7,18,30 No reports of recurrence

have been published after complete surgical resec-

tion. Surgery is also the most acceptable procedure

for intracranial lesions in cases of unclear diagnosis.

Radiotherapy has been given postoperatively in

couple of cases after subtotal clearance, but with

limited benefit. Although generally ineffective, cases

exist where patients responded to chemotherapy, but

many times the disease undergoes spontaneous

resolution. McPherson et al. reported a case of

multiple skull-base Rosai–Dorfman disease that was

successfully treated with corticosteroid agents, re-

presenting the first CNS Rosai–Dorfman disease case

to demonstrate definitive resolution of nonsurgically

treated intracranial Rosai–Dorfman disease after

corticosteroid therapy.30 An insidious course can

develop over several years, even decades. Fatal cases

have been reported.10 The longest documented

follow-up in isolated intracranial Rosai–Dorfman

disease was 11 years, but in our case 3 years is in

our opinion, enough time to conclude that the

patient was permanently cured.

Additionally, our intention was to emphasise the

technical detail of using the long biopsy needle

combined with the neuronavigational tracking system

in the posterior cranial fossa surgery to avoid

displacement of neural structures after dura opening.

In order to prevent the neural shift after dura opening

and cerebrospinal fluid leakage, we have first

punctuated the lesion through the minimal dura

opening using the biopsy needle associated with

FIG. 2. (A) Expression of CD68 (MSIP, 2006). (B) Emperipolesis (arrow), (H&E, 4006).

Isolated cerebellar Rosai–Dorfman disease 295

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neuronavigational system and then we have opened

the dura in typical manner. The tumour was found

following our own punctuation channel.

Conclusion

In this case report, we presented the second known

case of isolated, purely intraparenchymal cerebellar

Rosai–Dorfman disease in an adult patient who was

histopathologically and immunohistochemically con-

firmed and operated on using the neuronavigational

system. Given the benign character of the lesion, one

can argue if the surgical treatment of this type or

tumour was necessary or not, but in our case it was

essential for postulating the right diagnosis and

eliminating the mass effect. When total tumour

removal is achieved, the outcome is generally better,

with minimal risk of recurrence and with no need for

additional therapy. In our case we have modified

slightly the intraoperative approach since we first

performed the lesion biopsy with a special long

biopsy needle coupled with the neuronavigational

system. Only after biopsying the lesion, the dura was

opened and the tumour was removed in a micro-

surgical manner. Although Rosai–Dorfman disease is

a rare disease process, it should be included in the

differential diagnosis of fibrotic chronic inflammatory

lesions of the CNS.

Declaration of interest: The authors report no

conflicts of interest. The authors alone are respon-

sible for the content and writing of the paper.

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