Rosai-Dorfman Disease Presenting With Diplopia

This case report describes a 43-year-old woman with orbital Rosai-Dorfman disease (RDD) presenting with progressive diplopia, orbital pain, and decreased visual acuity, requiring orbital biopsy for definitive diagnosis. Published in the Journal of Neuro-Ophthalmology in 2023, this report highlights the importance of including RDD in the differential diagnosis of retrobulbar orbital masses.

Background

Rosai-Dorfman disease (RDD), formerly known as sinus histiocytosis with massive lymphadenopathy, is a rare nonmalignant condition characterized by histiocytes infiltrating lymph nodes or extranodal tissues. The hallmark histopathological feature is emperipolesis -- the engulfment and passage of intact lymphocytes through the cytoplasm of large histiocytes.

The etiology of RDD remains unclear, although infectious, autoimmune, and genetic causes have been proposed. While the classical presentation involves cervical and other lymph node groups, extranodal involvement -- including skin, upper respiratory tract, bone, and orbit -- occurs in more than 40% of cases. Ocular and orbital manifestations are relatively rare, accounting for approximately 10% of all RDD cases. Among ophthalmic presentations, orbital involvement is the most common. The median age for ophthalmic RDD is 40 years, with a male-to-female ratio of 3:4.

The diagnostic challenge with orbital RDD is that the masses are often initially suspected to be lymphoma or orbital inflammatory disease of unknown etiology, and the correct diagnosis is only established after histopathological evaluation of biopsy tissue.

The Patient

A 43-year-old woman presented with right eye swelling and orbital pain that had been progressive for 8 months. She had been diagnosed with early-stage Type 2 diabetes but was otherwise healthy.

Symptom Progression

• Initial symptoms: Itchiness and liquid discharge from the right eye
• Progressive worsening: Sensation of significant pressure within the right orbit
• Development of diplopia (double vision)

Examination Findings

• Visual acuity: 20/30 right eye, 20/20 left eye
• Motility: Significant diplopia at right and left gazes; mild exotropia at primary gaze
• Extraocular movement deficit: -2 adduction, abduction, and elevation deficit in the right eye
• External examination: Swelling of the lower lid and medial canthal area including lacrimal sac; resistance to retropulsion medially
• Intraocular pressure: Mildly elevated at 21 mm Hg OD (vs. 19 mm Hg OS), treated with timolol drops twice daily
• OCT: Normal retinal nerve fiber layer thickness (99 micrometers OD, 100 micrometers OS)
• Visual field testing: 24-2 showed enlarged blind spot visual field defect in the right eye
• Dilated slit-lamp examination: Unremarkable

Diagnostic Workup

Imaging

CT imaging of the orbits identified:

• Infiltration over the right orbital floor extending toward the medial wall of the orbit
• Medial and inferior rectus muscle involvement with enlargement
• Lacrimal sac involvement
• Right unilateral orbital mass visible on external photography

Laboratory Studies

Bloodwork including:

• Complete blood count: Normal
• Thyroid function testing: Normal
• Acetylcholine receptor antibody titers: Normal (ruling out myasthenia gravis)

Histopathology

Biopsy of the orbital mass was diagnostic for RDD. Key pathological findings included:

• H&E staining: Variable regions of alternating pale histiocytic and darker lymphoplasmacytic aggregates
• Emperipolesis: Lesional histiocytes with ill-defined, foamy, pale cytoplasm demonstrating engulfment of several intact lymphocytes -- the hallmark feature of RDD
• S100 immunostain: Large S100-positive histiocytes containing a characteristic "halo" of negatively stained lymphocytes, confirming the diagnosis

Results

Clinical Course

• 2-month follow-up: Visual acuity worsened to 20/40 OD (stable at 20/20 OS) with progressive diplopia
• Prednisone initiated: Dose escalated to a stable 80 mg per day
• 3-week follow-up on steroids: Orbital inflammation decreased; patient reported reduced pressure sensation in the orbital region
• Visual acuity improved to 20/30 OD and 20/20 OS
• Diplopia persisted but remained stable (not worsening)
• Slit-lamp examinations: Unchanged throughout follow-up

Ongoing Management

The patient continues to be monitored while on prednisone therapy with minimal improvement. She manages her persistent double vision by wearing a patch over the affected eye.

Clinical Significance

This case carries several important messages for neuro-ophthalmologists and general ophthalmologists:

1. RDD should be included in the differential diagnosis of retrobulbar orbital masses, even when lymphoma, orbital inflammatory disease, or metastasis seem more likely clinically
2. Orbital biopsy is essential for definitive diagnosis -- imaging and laboratory studies alone cannot distinguish RDD from other orbital pathologies
3. Corticosteroids provide partial benefit by reducing mass size and inflammation, but may not resolve diplopia or fully eliminate symptoms
4. Further systemic workup is warranted -- additional imaging should be considered to rule out extranodal or lymph node involvement elsewhere, as RDD can affect multiple sites
5. Recurrence is common -- lymphadenopathy and other RDD manifestations can recur after immunosuppressive therapy, necessitating long-term monitoring
6. Treatment escalation options include surgical resection and involved-field radiotherapy for aggressive cases; chemotherapy is generally less effective than immunosuppressive therapy

Citation

Manasyan A, Khachikyan N, Gaytan S, Lee T, Brynes RK, Hashemi N. Rosai-Dorfman disease presenting with diplopia. J Neuro-Ophthalmol. 2023;00:1-2.

References