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James R. Cameron, MRCOphth; Peter Cackett, FRCOphth

Arch Ophthalmol. 2007;125(5):712-713.

Lymphomatoid granulomatosis (LYG) was first described by Liebow et al¹ in 1972. It is a necrotizing lymphoproliferative disorder primarily affecting the lungs. The skin, kidneys, and nervous system may be involved, but ocular involvement is unusual. We present the case of a 39-year-old man who developed bilateral exudative macula detachments 16 years following onset of LYG. Prompt management with systemic steroids resulted in complete resolution with no long-term sequelae.

Report of a Case
A 39-year-old man attended the ophthalmology department with a 3-day history of bilateral blurring of vision with no other ocular symptoms. There was no ophthalmological history.

He had been examined because of cough, dyspnea, and a skin rash 16 years previously and was subsequently diagnosed with LYG. Chest x-ray film had shown bilateral infiltrates with bronchoscopic biopsy yielding granulomatous material with perivascular lymphoid infiltrates. A skin biopsy helped confirm the diagnosis of LYG. At the time of his initial ophthalmological examination, he was taking 20 mg of prednisolone daily to control the pulmonary symptoms of LYG.

On examination, his visual acuities were 20/60 OD and 20/40 OS. Fundus examination revealed bilateral dome-shaped smooth elevations of the macula with subretinal fluid visible, consistent with exudative retinal detachments. No retinal breaks, vasculitis, or vitritis was present. Fluorescein angiography demonstrated bilateral multifocal pinpoint leakage throughout the macula and extensive subretinal fluid (Figure).

View larger version (55K): [in this window] [in a new window] [as a PowerPoint slide]   Figure. Late-stage fundal fluorescein angiogram of the patient's fundi revealing extensive bilateral macula leakage consistent with subretinal fluid.

The patient's dose of prednisolone was increased to 60 mg daily. Within 4 weeks, visual acuities had returned to 20/20 OU with normal Amsler test results. Fundus examination now revealed complete resolution of the subretinal fluid and flat retinae bilaterally with no obvious sequelae of the exudative detachments seen.

The dose of prednisolone was thereafter reduced in 5 mg increments, and 5 months later, with the dose back at 20 mg, vision had remained stable with no recurrence of the subretinal fluid. Two years of follow-up have seen no further ocular involvement, but further skin lesions and arthralgia in the patient have also responded to systemic steroid therapy.

Comment
Lymphomatoid granulomatosis is an uncommon granulomatous inflammatory syndrome closely related to Wegener granulomatosis and to malignant lymphoma. It requires histopathological diagnosis because its clinical features are often difficult to distinguish from those of other granulomatoses, so it is frequently misdiagnosed as sarcoidosis.² Clinical features are usually fever, cough, malaise, weight loss, and dyspnea. Men are more affected than women (3:2), and it may appear at any age.

Systemic involvement is predominantly pulmonary (>80%) with both interstitial and alveolar tissue affected. Central and peripheral nervous system involvement is common with skin and renal tissue involvement also seen. Radiographically, multiple variable-sized nodules are seen within the lung fields. Histologically, these appear as regions of necrosis and granulomatous inflammation with focal areas of vascular infiltration by atypical lymphocytes (possibly malignant B cells) and plasma cells. This appearance has led to its dual classification as a primary vasculitis and also as a lymphoma precursor. The absence of multinucleated giant cells or palisading epithelioid cells excludes the diagnosis of Wegener granulomatosis. Etiology remains unclear; however, in situ hybridization techniques have confirmed the presence of Epstein-Barr virus in many pathological samples.³ Epstein-Barr virus is a known factor in the pathogenesis of nasopharyngeal carcinoma and a number of proliferative lymphoid conditions. Progression to lymphoma frequently occurs, carrying a very poor prognosis and an associated mortality of 60% to 90%.

Ocular involvement in LYG is rare but appears to follow either cranial nerve involvement (tonic pupil,⁴ optic neuropathy⁵) or direct ocular granulomatous inflammation (posterior uveitis,⁶ choroidal vasculitis^7-8). Choroidal involvement of LYG has been described only as a vasculitis without breach of the blood-retinal barrier. Our case is unique in reporting the occurrence of subretinal fluid secondary to presumed choroidal involvement of LYG.

No controlled trials of treatment exist. Immunosuppression and chemotherapy have both been used to manage ophthalmological manifestations as well as pulmonary disease. Recent studies have looked at other possible treatments with some success demonstrated with monoclonal antibody therapy such as rituximab.⁹

This case represents an unusual presentation of LYG with bilateral exudative retinal detachments that showed prompt resolution with systemic steroid therapy. To the best of our knowledge, this is the first reported case of LYG manifesting in this way.

AUTHOR INFORMATION
Correspondence: Dr Cameron, Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh EH3 9HA, Scotland (docjim{at}gmail.com).

Financial Disclosure: None reported.

REFERENCES
1. Liebow AA, Carrington CB, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol. 1972;3:457-558. ISI | PUBMED 2. Fitch PS, Smith MEF, Davies MG, Prentice AG. A case of lymphomatoid granulomatosis mimicking sarcoidosis. Respir Med. 1998;92:966-968. FULL TEXT | ISI | PUBMED 3. Loughrey M, Trivett M, Lade S, Murray W, Turner H, Waring P. Diagnostic application of Epstein-Barr virus-encoded RNA in situ hybridisation. Pathology. 2004;36:301-308. FULL TEXT | ISI | PUBMED 4. Haider S. Tonic pupil in lymphomatoid granulomatosis. J Clin Neuroophthalmol. 1993;13:38-39. PUBMED 5. Forman S, Rosenbaum PS. Lymphomatoid granulomatosis presenting as an isolated unilateral optic neuropathy: a clinicopathologic report. J Neuroophthalmol. 1998;18:150-152. PUBMED 6. Tse DT, Mandelbaum S, Chuck DA, Nichols PW, Smith RE. Lymphomatoid granulomatosis with ocular involvement. Retina. 1985;5:94-97. FULL TEXT | ISI | PUBMED 7. Pearson AD, Craft AW, Howe JM. Choroidal involvement in lymphomatoid granulomatosis. Br J Ophthalmol. 1991;75:688-689. FREE FULL TEXT 8. Kinyoun JL, Kalina RE, Klein ML. Choroidal involvement in systemic necrotizing vasculitis. Arch Ophthalmol. 1987;105:939-942. ABSTRACT 9. Jordan K, Grothey A, Grothe W, Kegel T, Wolf HH, Schmoll HJ. Successful treatment of mediastinal lymphomatoid granulomatosis with rituximab monotherapy. Eur J Haematol. 2005;74:263-266. FULL TEXT | ISI | PUBMED

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