Orbital rosai-dorfman disease in a five-year-old boy.

Rosai-Dorfman disease (RDD) is characterized by histiocytic proliferation and massive cervical lymphadenopathy, although some patients have extra-nodal involvement. We report a case of extranodal RDD in a five-year-old child, initially misdiagnosed as orbital inflammatory disease and treated with oral steroids. A subsequent orbital biopsy three years later confirmed the diagnosis of Rosai Dorfman disease.

INTRODUCTION

Rosai Dorfman disease is characterized by histiocytic proliferation and massive cervical lymphadenopathy. About 40% of patients have extra-nodal involvement of the skin, orbit, central nervous system, visceral organs and respiratory system. Histopathological and immunohistochemical confirmation are essential in establishing the diagnosis. We report a challenging case of extranodal Rosai Dorfman disease in a five-year-old child, initially misdiagnosed as orbital inflammatory disease. The child's first orbital biopsy showed non-specific chronic inflammation and he was treated with oral steroids for at least one year. A subsequent orbital biopsy three years later confirmed the diagnosis of Rosai Dorfman disease.

CASE REPORT

A previously healthy two-year-old male presented to a pediatric ophthalmologist with a history of acute proptosis of the left eye associated with fever. Examination showed that he could follow and fixate well with both eyes. He had prominent proptosis of the left eye and no palpable lymph node enlargement was noted. The rest of his ophthalmic examination was unremarkable. A computerized tomography (CT) scan of the orbits done at that time revealed a left retro-orbital soft tissue mass with minimal contrast enhancement. His white blood count was elevated (15.9 × 109/L).

He was diagnosed with orbital cellulitis and treated with a course of intravenous ciprofloxacin with little improvement. He was also non-responsive to a trial of oral dexamethasone. An orbital biopsy was performed via a lower lid approach. Histopathology showed tissue infiltrated by lymphocytes, plasma cells, hemosiderin-laden macrophages and histiocytes with mild stromal fibrosis. Immunohistochemical staining showed a mixture of B and T lymphocytes. A presumptive diagnosis of fibrosing orbital inflammatory disease was made and he prescribed oral prednisone (30 mg/day) 1 mg per kilogram with some improvement. Shortly afterwards, the patient was lost to follow-up.

Three years later the patient presented to our unit with recurrent proptosis of the left eye and lid swelling, which could be felt as two firm palpable masses in the upper lid and one in the lower lid [Figure 1]. Best corrected visual acuity was 20/40 in both eyes and he had mild limitation of abduction of the left eye. Pupillary reactions were normal as were the anterior and posterior segments of both eyes. Magnetic resonance imaging (MRI) of the orbits showed extensive soft retro-orbital tissue mass, extending to the left cavernous sinus, iso-intense on T1 and T2 with diffuse post-contrast enhancement [Figure 2].

Figure 1

Lid swelling of the left upper and lower lid with globe dystopia

Figure 2

Axial T1-weighted Gadolinium-enhanced MRI showing proptosis and enhancing a retrobulbar lesion involving left lacrimal gland and subcutaneous tissue

Another orbital biopsy was performed through an upper and lower lid skin approach, along with an adenoidectomy and biopsy of the left inferior turbinate. Histopathological examination revealed an infiltrate of lymphocytes (both B and T), polyclonal plasma cells and histiocytes; however, no eosinophils were present. The histiocytes had large round nuclei, prominent nucleoli and vacuolated cytoplasm. Some of the histiocytes contained numerous intact mononuclear cells, plasma cells and erythrocytes in their cytoplasm. A few reactive lymphoid follicles were seen. No Reed-Sternberg cells, Dutcher bodies or micro-organisms (using Periodic-acid Schiff, Gram, Ziehl–Neelson and Wade–Fite stains) were seen. The biopsy was also negative for Epstein–Barr virus staining, Bcl-2 and CD1a. However, it was positive for S100 and weakly positive for CD68. All of the histopathological and immunohistochemistry characteristics ruled out possible malignancy or infection and the findings were consistent with RDD.

Due to the large extension of the lesion and the cosmetic appearance, the child was referred to a pediatric oncologist for further evaluation and treatment. However, the family did not complete this follow-up.

DISCUSSION

RDD (sinus histiocytosis with massive lymphadenopathy) is characterized by massive painless bilateral lymph node enlargement in the neck. It was first described by Destombes and later by Azoury and Reed; however, the condition was named after Rosai and Dorfman, who described four cases in 1969.1 This entity usually affects males in their first to second decade of life.

The exact pathogenesis of RDD is unknown. However, some studies suggest that human herpes virus type 6 (HHV-6) and Epstein-Barr virus may play a role.2 Most patients present with massive cervical lymphadenopathy, but about 40% of patients will have extra-nodal manifestations involving the skin, nasal cavity and paranasal sinus, eye and ocular adnexa, bone, central nervous system, liver and heart.3 Systemic manifestations include fever, leukocytosis, elevated erythrocyte sedimentation rate and hypergammaglobulinemia. Ophthalmological manifestations occur in 10% of cases, and these include eyelid thickening, swelling of the lacrimal gland, proptosis and anterior granulomatous uveitis.4

A definite diagnosis of RDD requires histopathological and immunohistochemical confirmation. The disease is characterized clinically by massive lymph node enlargement showing sinus histiocytosis. However in extranodal disease, the infiltrate can be polymorphous, composing of small mature lymphocytes, plasma cells and histiocytes. Emperipolesis, in which the histiocyte's cytoplasm contains small lymphocytes, is a very typical pathological finding of RDD [Figure 3]. The histiocytes are usually positive for S100 protein and CD68, but negative for CD1a, which is a differentiating feature from Langerhans cell histiocytosis. In addition, Langerhans cells usually show a distinctive nuclear grooving and contain Birbeck granules when examined under electron microscopy.

Figure 3

Pathological section of the patient demonstrating emperipolesis (arrow)

RDD is considered benign and mild and localized cases can be observed. In more severe cases, surgical excision, radiation therapy, corticosteroid and other immunosuppressive therapies should be considered. In contrast to idiopathic orbital inflammatory syndrome in which medical treatment is the initial management of choice, surgical excision can be considered as a first-line therapy in RDD and may be curative.5 Corticosteroids have been found to produce resolution after surgical excision.6 Various chemotherapeutic agents have been used, with vinca alkaloids being reported as the most effective in combination with corticosteroids.7

Our patient presented with a picture resembling orbital inflammatory disease, which led to diagnostic confusion, even after radiographic imaging. Hence, even patients diagnosed with orbital inflammatory disease should be closely followed and evaluated to ensure that it is not a masquerading disease. Other possibilities considered in our patient were infectious causes and neoplasms such as rhabdomyosarcoma, leukemia and lymphoma. Initial biopsy was suggestive of non-specific inflammation and hence the patient was treated as a case of orbital inflammatory disease. Treatment with steroids for a prolonged period of time was not effective. Due to absence of follow-up for a considerable amount of time the inflammatory lesion had extended into adjacent tissues and intracranially making complete surgical excision impossible. It is likely that the first biopsy was not representative of the actual pathology. Hence the role of a repeated biopsy if necessary in such difficult clinical situations cannot be overemphasized. Rare diseases present with the most challenging cases. Persistence and a systematic approach are keys to proper management of such cases.