INTRODUCTION:

RDD was first described by Destombes¹ in 1965 as a rare, separate entity of benign self-limiting sinus histiocytosis with massive lymphadenopathy later Rosai and Dorfman² in 1969, confirmed it as a separate clinic-pathologic entity. Although RDD may occur in any age group, it is most frequently seen in children and young adults. Isolated intracranial disease tend to occur older patients. The disease is more common in males and in individuals of African descent . The most frequent clinical manifestations include fever, night sweats and weight with bilateral massive cervical lymphadenopathy. Mediastinal, inguinal and retroperitoneal nodes may also be involved. RDD is potentially systemic disease and may affect extra nodal sites up to 43% of all RDD patients. The common extra-nodal sites include skin, upper respiratory tract, and bone. Skeletal involvement as a sole manifestation of RDD is extremely rare, occurring in fewer than 2% of all RDD patients and arise most frequently in long bones such as tibia, femur, humerus, clavicle and bones of the hands. CNS involvement is rare (5%), with 75% of cases involving the brain and 25% involving the spinal canal. Involvement of the CNS without concurrent nodal involvement is rare.³ Laboratory findings are non-specific with leucocytosis, neutrophil, elevation of erythrocyte sedimentation rate (ESR), hypergammaglobulinemia being the most common findings.

We present a rare case of vertebrae compression fracture due to extra-nodal RDD without lymphadenopathy later developed metastases to brain.

CASE REPORT:

A 45 year old lady presented with h/o sudden onset of paraplegia. Work –up was done and spinal mass was found. Later the patient underwent surgical debulking to releave her symptoms. The patient gradually improved. Histopathologically it was diagnosed as RDD. The patient was symptom free for 6 months, then she developed sudden onset of seizures and lower limb weakness. MRI showed multiple cranial and spinal metastasis, following which the patient underwent craniotomy. The patient was further treated with whole brain radiotherapy of 30Gy. There was no improvement of symptoms. The patient eventually expired 6 months following the completion of radiotherapy.

Discussion:

RDD in its classic form is a benign, self-limiting histiocytic proliferative disorder that is characterized by massive lymphadenopathy. Most patients with RDD are in their second or third decade of life, the mean age of onset of nodal disease is about 20years, with a male-to-female ratio of 1.4:1. It is commonly reported in African-Americans. The etiology of RDD remains unknown; immune system dysfunction and an autoimmune process or viral infection such as Epstein-Barr virus and human herpes virus type 6 have been attributed with the pathogenesis of RDD. The presentation of RDD can be categorised into three sub types: 1) those with only lymph nodes enlargement with sudden increase and spontaneous regression and without any further recurrences; 2) those with immunologic abnormalities at presentation have a more widespread nodal disease and a higher fatality rate^4,5 ; 3) those with several extra-nodal site involvement, multi-nodal disease and a protracted clinical course with multiple relapses and remissions for years. In these cases, the severity of disease depends on the type and number of extra-nodal sites.⁶

Patients who present with or subsequently develop intracranial involvement, become symptomatic at a later mean age (34.9 years), with a strong male predominance.⁷ Involvement of CNS is rare (5%), with 75% of reported cases involving the brain and 25% involving the spinal canal. Involvement of the CNS in the absence nodal involvement is rare.³ The most common intra cranial presentation is solitary dural based lesion, but multiple intracranial lesions have also been reported. The suprasellar region, cerebral convexity, para sagittal region, cavernous sinus, and petroclival regions are most common locations.⁷ Only 11 cases of spinal RDD have been reported, of which 10 patients had an extra-medullary tumor. Seven patients presented with epidural lesion, three presented with intra dural lesions.⁸ Spinal cord compression has been reported in a few patients with spinal involvement causing neurologic deficits.⁹ Compression fracture due to spinal involvement of RDD has not been reported. CNS RDD is a rare benign histiocytic proliferative disorder, with imaging findings typically showing a meningioma-like, dural-based extra-axial mass lesion, which can be solitary or multiple. Imaging studies typically show an enhancing meningeal-based mass with a variable amount of edema surrounding the lesion.

Skeletal involvement of RDD as a sole manifestation is extremely rare, occurs in less than 2% of all RDD patients and involves the long bones such as tibia, femur, humerus, clavicle and bones of the hands or skull, and is usually multiple. Skeletal lesions of RDD are intramedullary osteolytic with either poorly or sharply defined margins. Spinal Rosai-Dorfman disease can be misdiagnosed as meningioma when arising from dura or as metastatic disease of another cause when presenting as vertebral body disease.¹⁰ The most common differential diagnosis of a primary bone RDD includes bacterial osteomyelitis, fungal infections such as histoplasmosis and Langerhans cell histiocytosis.

Definitive diagnosis requires tissue examination. Microscopically, lymph node enlargement with sinuses containing prominent numbers of histiocytes with phagocytosed lymphocytes. This is a typical picture of RDD. Immunopositivity is expressed by these cells for both CD68 and S-100 protein, and negative for CD1a. RDD has a typical finding in histopathologic studies, that is emperioplesis; a phenomenon of phagocytosis of intact lymphocytes, plasma cells, erythrocytes or neutrophils.¹¹ LCH is a close differential diagnosis both on radiology and histology. Both histiocytes of RDD and LCH are positive for CD68 and S100, but CD1a is positive in LCH. Also Langerhans cell histiocytosis does not exhibit emperioplesis.

Treatment in the majority of cases is not indicated as it is a benign and self-limiting.^12,13 Therapy is indicated in patients with bulky extra nodal disease with involvement of vital organs or causing life threatening complications.¹³ Surgical resection or debulking can be considered as an option only when the nodal mass iss compressing airway or intra dural lesion.¹³ When complete resection cannot be achieved, adjuvant radiosurgery can be give successful partial resection.¹⁴ Surgical excision of resectable lesions induced complete remission (CR) in 8 out of 9 patients.¹³

The role radiotherapy in the treatment has not been established. Various medical alternatives in the management have been tried with limited results. Short term Systemic corticosteroids and prolonged course low dose oral prednisolone has been effectively used in RDD with skin and lymph nodal involvement with respiratory obstruction.¹⁵ Steroids tend to alleviate the symptoms and decrease nodal size, recurrences have been reported following withdrawal of steroids. Chemotherapeutic agents have been used without any encouraging results. Combination chemotherapy of low dose MTX and 6-MP, MTX/6MP/vinblastine/6-thioguanine and acyclovir with thalidomide have been tried with limited benefit to patients. It is possible that different patients with RDD may respond to different drugs. Targeted therapy in the form of imatinib, interferon- α, cladarabine and more recently rituximab has also been in the treatment of RDD.