Neurology India, Vol. 59, No. 3, May-June, 2011, pp. 443-446
Isolated intracranial Rosai Dorfman disease
Venkidesh Krishnamoorthy1, Chirag F Parmar2, Dilip Panikar1
1 Department of Neurosurgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
Correspondence Address: Venkidesh Krishnamoorthy Manas, Madathilparambu, Palace Ward, Alappuzha - 688 011, Kerala India firstname.lastname@example.org
Date of Submission: 20-Oct-2010
Code Number: ni11127
AbstractRosai Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a benign histiocytic proliferative disorder mainly affecting the lymph nodes. Although several cases of extra-nodal involvement have been reported previously, central nervous system involvement, particularly in the absence of nodal disease is extremely rare. We report a case of isolated intracranial RDD occurring in a relatively elder patient, which was shown by histological examination to have a dura-based involvement.
Keywords: Emperipolesis, histiocytosis, lymphadenopathy, Rosai-Dorfman
Sinus histiocytosis with massive lymphadenopathy (SHML), a rare but well-defined clinicopathological entity first described in 1969, affects children and adolescents predominantly. The most common presentation is bilateral painless cervical lymphadenopathy. , An extra-nodal manifestation of the disease occurs in up to 43% of the patients; and occurs in the absence of lymphadenopathy in 23% of the patients. The most common extra-nodal sites affected are the soft tissues of the head and neck and the paranasal sinuses and nasal cavity.  Isolated central nervous system (CNS) involvement without nodal involvement is extremely rare; only few cases have been reported in literature so far.
A 51-year-old male presented with unsteadiness of gait, of four months' duration, occasional episodes of low grade fever, of three months' duration, and a recent onset of blurring of vision, of three weeks' duration. On neurological examination there was left-sided spastic hemiparesis. Clinically he had no lymph node enlargement. Non-contrast computerized tomography (CT) of the brain revealed an ill-defined, extra-axial mass lesion involving the right frontal region with peri-lesional edema. Contrast magnetic resonance imaging (MRI) revealed a dural-based, brightly enhancing lesion, involving the right frontal region, suggestive of convexity meningioma [Figure - 1]a-c. CT of the chest and abdomen did not reveal any lymph node enlargement. Ultrasound examination of the neck was unremarkable. He underwent right frontal craniotomy and excision of the lesion. Pre-operatively the dura was found to be very much thickened, with a nodular inner surface that was impinging on the brain surface. There was a good pial plane between the tumor and the brain surface. The postoperative course was uneventful. Microscopic examination [Figure - 2]a and b revealed dura infiltrated with sheets of histiocytes, lymphocytes, and plasma cells, and focally by polymorphs. The histiocytes showed features of emperipolesis. There was no nuclear grooving or convolutions in the histiocytes. No eosinophils or granuloma or meningothelial cell clusters were seen. Immunohistochemistry for the S-100 protein and CD68 antibody confirmed the presence of histiocytes. Based on these histological features a diagnosis of Rosai Dorfman disease was made. He was discharged on low-dose steroids for a month. MRI done at the end of three months showed no evidence of any residual or recurrent lesion [Figure - 3] a-c and his spasticity involving the left upper and lower limb had significantly improved. ,
The term SHML was first introduced by Ronald F. Dorfman and Juan Rosai based on four cases, published in 1969, in the Archives of Pathology journal, with the title 'Sinus histiocytosis with massive lymphadenopathy: A newly recognized benign clinicopathologic entity'.  The synonym of this condition is Destombes-Rosai-Dorfman syndrome, named after Pierre-Paul Louis Lucien Destombes, Juan Rosai, and Ronald F. Dorfman.
The disease is characterized by massive, painless, bilateral cervical lymphadenopathy, often associated with fever, leukocytosis, mild anemia, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia.  Although extra-nodal involvement has been reported in diverse sites, CNS involvement, particularly in the absence of nodal disease is rare .  The most common presentations of CNS involvement, in the largest series, include headaches, seizures, numbness, and paraplegia. , Frequent lesion locations include cerebral convexities, para-sagittal, supra-sellar, cavernous sinus, and petroclival regions. ,,,,, Purely intraparenchymal lesions have also been reported. , There are isolated case reports involving the orbit, pituitary, cerebellar, and cervical extradural involvement. ,,,, The other extra-nodal sites include skin, soft tissues, respiratory system, genitourinary system, bones, orbit, thyroid, and breast. ,,,,,, Male to female ratio is about 1.4 : 1. , The etiology, pathogenesis, and natural history of Rosai-Dorfman disease are still unknown. Although an infection has been suggested as an underlying cause, a definitive agent has never been isolated.  Molecular studies using polymorphic regions of the human androgen receptor locus have demonstrated that RDD is a polyclonal disorder, , in contrast to Langerhans cell histiocytosis, which is a monoclonal disorder. 
Histologically, Rosai Dorfman disease is characterized by large histiocytes, which often show apparently viable and intact hematopoietic cells (mostly lymphocytes) within the cytoplasm without undergoing degenerative changes, a phenomenon known as Emperipolesis (lymphophagocytosis), derived from the Greek word 'em + peripolesis' = going about. On immunohistochemical examination, these are positive for S-100 protein and negative for CD1a, a marker of Langerhans histiocytosis. ,
There are no definitive treatment guidelines for Rosai Dorfman disease. A majority of these undergo spontaneous regression. The mortality rate is approximately low, 7%. Major complications include airway obstruction, immunological disorder, and infection. Usually, concomitant immune dysfunction is present.  The prognosis of CNS Rosai Dorfman disease is not bad. Petzold et al. found tumor regrowth or recurrence of symptoms in 14% of the 29 patients, with a mean follow-up of 10.1 years. Only 52% of these patients had undergone brain imaging at follow-up. They concluded that a five-year follow-up with brain imaging was essential and advocated low-dose radiation to treat patients with sub-total resection and recurrence. Although a variety of treatment modalities had been used, including steroid therapy and radiation, surgical resection appeared to be the most appropriate approach. ,, There have been some reports of success in treating Rosai-Dorfman disease with a combination of cytotoxic agents such as alkylating agents, vinca alkaloids, and prednisone.  Decision to follow-up the patient with serial imaging is an accepted modality. Our patient was maintained on low steroids postoperatively, for a month. A repeat MRI done at the end of three months did not reveal any residual or recurrence involving the operative bed.
Copyright 2011 - Neurology India
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