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Show Journal of Nniro- Ophlluilmolo/ iy 18( 2): 150- 152, 1998. © 1998 IJppincolt- Ravcn Publishers, Philadelphia Lymphomatoid Granulomatosis Presenting as an Isolated Unilateral Optic Neuropathy A Clinicopathologic Report Scott Forman, M. D., and Pearl S. Rosenbaum, M. D. A 41- year- old woman presented with a unilateral optic neuropathy that progressed to no light perception 7 weeks later. The patient was hospitalized for progressive dyspnea; respiratory failure ensued and the patient died 10 days after admission. Antemortem pulmonary biopsies and the results of necropsy revealed lymphomatoid granulomatosis with extensive involvement of the lungs and left optic nerve. This is the first case report of lymphomatoid granulomatosis presenting as a unilateral optic neuropathy. Key Words: Lymphomatoid granulomatosis- Angiocentric immunoproliterative lesions- Optic neuropathy- Lymphoma- Epstein- Barr virus. Lymphomatoid granulomatosis ( LG) is an angiocentric, angiodestructive, lymphoproliferative disorder predominantly affecting the lungs. Extranodal sites such as the kidneys, skin, and central nervous system may also occur, the latter being involved in 20% to 40% of cases. Ocular and neuro- ophthalmologic findings are distinctly uncommon. We present a case of biopsy- proven LG presenting as an isolated unilateral optic neuropathy. CASE REPORT A 41- year- old, right- handed white woman presented with a 1- week history of monocular visual loss OS associated with pain on eye movement. There were no other neurologic symptoms. Medications included 1 g of carbamazepine daily for a seizure disorder and 25 mg of chlorpromazine at night for manic- depressive illness. Review of systems disclosed a circular, red, nonpruritic rash below the left buttock. On ophthalmologic examination, corrected visual acuities measured 20/ 15 OD and 20/ 100 OS. She interpreted Manuscript received December 2, 1997; accepted February 20, 1998. From the Departments of Ophthalmology and Neurology ( S. F.), New York Medical College, Westchester County Medical Center, Valhalla, and the Departments of Ophthalmology and Visual Sciences and Pathology ( P. S. R.), Monlefiorc Medical Center, Albert Einstein College of Medicine, Bronx, New York, U. S. A. Address correspondence and reprint requests to Scott Forman, M. D., Department of Ophthalmology, Westchester County Medical Center, Valhalla, NY 10595, U. S. A. 6/ 6 American Optical Hardy- Rand- Rittler color plates correctly on the right but 0/ 6 correctly on the left. There was a 1.9 log unit left- relative afferent pupillary defect. Tangent screen visual fields were normal to a 2- mm white/ 1,000- mm target on the right and demonstrated a moderately dense superior altitudinal field defect on the left. Dilated fundus examination of the right eye was unremarkable; optic disc edema was noted on the left ( Fig. I). Cranial and orbital magnetic resonance imaging disclosed enhancement of the orbital portion of the left optic nerve and sheath ( Fig. 2). Neuroimaging of the brain was negative. Follow- up examination 1 week later showed further loss of visual acuity to finger counting at 1 foot and progression of the superior altitudinal defect on the left. Edema of the left optic disc appeared unchanged. Significant laboratory findings included a Wcstcrgrcn sedimentation rate of 36 mm/ hour and an increased alpha2- globulin on serum protein electrophoresis. Progressive dyspnea prompted hospitalization, where bilateral nodular infiltrates were noted on chest radiography. Serum anti- nuclear antibodies, anti- cardiolipin antibodies, C-and P- ANCA, and rheumatoid factor were negative. Results of the ophthalmic examination 7 weeks after the initial presentation remained normal OD, but visual acuity OS declined further to no light perception. There was an amaurotic pupil, pallid disc edema, and diffuse vascular sheathing in the posterior pole of the left eye. Progressive respiratory failure ensued. A pulmonary biopsy was performed. The patient died 10 days later. Postmortem examination, including the eyes, was performed. PATHOLOGIC FINDINGS Histopathologic examination of the lung biopsy disclosed nodular foci of interstitial and airspace disease, with an infiltration of small lymphocytes, plasma cells, histiocytes, and larger, atypical lymphoid cells with pleomorphic, convoluted nuclei and prominent nucleoli. In other areas, particularly in perivascular regions, the atypical lymphoid cells formed confluent sheets and infiltrated vascular walls. Frequent mitotic figures were 150 LYMPHOMATOID GRANULOMATOSIS 151 FIG. 1. Left eye. Ophthalmoscopic appearance of left optic disc at presentation showing disc elevation, blurred margins, hyperemia, and splinter hemorrhages on the disc surface. FIG. 2. T1- weighted, gadolinium- enhanced coronal magnetic resonance image of the head and orbits shows enhancement of the intraorbital position of the left optic nerve ( arrow) and sheath ( arrowhead). seen. The exudate- filled alveoli contained alveolar macrophages as well as the atypical lymphoid cells. Multifocal areas of pulmonary necrosis were noted. The atypical cells were immunopositive for T- cell markers ( UCHL- 1) and immunonegative for B- cell markers ( L26). A histopathologic diagnosis of LG was made. Postmortem examination of the lungs disclosed multifocal areas of infarction as well as the atypical lym- FIG. 3. A: Histopathologic cross- section of the intraorbital optic nerve demonstrates total necrosis of the nerve as well as thickening of the nerve sheath. ( Hematoxylin- eosin, original magnification x4.). B: The pia- arachnoid septa ( left) as well as the necrotic nerve bundles ( right) are infiltrated by small, mature-appearing lymphocytes and larger, atypical lymphocytes with pleomorphic, convoluted nuclei ( arrowheads). ( Hematoxylin-eosin, original magnification x160.) phoid infiltrate noted on the antemortem pulmonary biopsy. The right and left globes were harvested with 34.5 and 22 mm of optic nerve attached, respectively. Histopathologic examination of both globes and of the right optic nerve were unremarkable. The left optic nerve ( sampled along its length at 2- mm intervals), however, was diffusely necrotic and the nerve sheath thickened ( Fig. 3a). An infiltrate consisting of small, mature- appearing lymphocytes as well as larger, atypical cells with pleomorphic, convoluted nuclei was present throughout the pia-arachnoid septa and the necrotic nerve bundles ( Fig. 3b). The atypical cellular infiltrate was strongly immunopositive for T- cell markers ( UCHL- l; Fig. 4) and immunonegative for B- cell markers ( L26). DISCUSSION Liebow et al. ( I) first described LG as an angioccntric, angiodestructive, lymphoproliferative disorder predominantly affecting the lungs, but also involving such sites as the upper respiratory tract, skin, kidneys, and central nervous system. Lymphomatoid granulomatosis is distinguished histopathologically from Wegener's granulomatosis by its angiocentricity, with angiodestructive in- ./ Neiiro- Ophllialniol. Vol. IS, Na. 2. IWS 152 S. FORM AN AND P. S. ROSENBAUM FIG. 4. A: Immunohistochemical analysis for T- cell markers shows a strongly positive immunoreaction within the pia-arachnoid septa ( S) and in the nerve bundles ( asterisks). B: A high- power view of a necrotic nerve bundle shows marked im-munopositivity of the individual atypical lymphocytes. ( A and B: UCHL- 1, avidin- biotin complex method, hematoxylin counter-stain; original magnifications, A: x32, B: x250.) filtration of lymphocytes, plasmacytoid cells, histiocytes, and atypical reticuloendothelial cells. The term " angiocentric immunoproliferative lesion" ( AIL) was coined by Jaffe ( 2) as an alternative to LG because it conveys the cytologic composition, the proliferative nature of the lesion, and the angiocentricity, a process which is a unique and distinguishing characteristic. Lipford et al. ( 3) showed that AIL represents a spectrum of T- cell proliferation from lack of atypia to frank angiocentric lymphoma. More recent studies suggest that Epstein- Barr virus may be involved in the transformation of low- grade AIL to angiocentric malignant lymphoma ( 4). The clinical presentation of LG is variable. The central nervous system is involved in 20% to 40% of cases ( 5). Ocular and neuro- ophthalmic findings are uncommon and include periocular infiltration ( 6), retinal and choroidal vasculitis ( 7,8), tonic pupil ( 9), Pancoast's syndrome ( 10), scleritis and optic atrophy ( 11), orbital infiltration ( 12), and multiple cranial neuropathies ( 13). Our case is unusual in that the patient presented with ocular signs and symptoms typical of idiopathic optic neuritis. However, there was progressive loss of vision to no light perception, and a rapidly progressive respiratory failure resulted in the patient's demise. The diagnosis of AIL should thus be considered in the differential diagnosis of progressive optic neuropathy of unknown etiology- Acknowledgments: Supported in part by an unrestricted grant to the Department of Ophthalmology and Visual Sciences, Montefiore Medical Center, Albert Einstein College of Medicine, from Research to Prevent Blindness, Inc., New York, New York. The authors thank Dennis Matzkin, M. D., who obtained and submitted the postmortem enucleation specimens for histopa-thology. References 1. Liebow AA, Carrington CRB, Friedman RJ. Lymphomatoid granulomatosis. Hum Pathol 1972; 3: 457- 8. 2. Jaffe ES. Pathologic and clinical spectrum of post- thymic T- cell malignancies. Cancer Invest 1984; 2: 413- 26. 3. Lipford EH, Margolick JB, Longo DL, Fauci AS, Jaffe ES. Angiocentric immunoproliferative lesions: a clinico- pathologic spectrum of post- thymic T- cell proliferations. Blood 1988; 72: 1674- 81. 4. Medeiros JL, Jaffe ES, Chen YY, Weiss LM. Localization of Ep-stcin- Barr viral genomes in angiocentric immunoproliferative lesions. Am J Surg Pathol 1992; 16: 439- 47. 5. Kleinschmidt- DeMasters BK, Filley CM, Bitter MA. Central nervous system angiocentric, angiodestructive T- cell lymphoma ( lymphomatoid granulomatosis). Surg Neurol 1992; 37: 130- 7. 6. Font RL, Rosenbaum PS, Smith JL Jr. Lymphomatoid granulomatosis of eyelid and brow with progression to lymphoma. J Am. Acad Dermatol 1990; 23: 334- 7. 7. Kinijoun JL, Kalina RE, Klein MC. Choroidal involvement in systemic necrotizing vasculitis. Arch Ophthalmol 1987; 105: 939- 42. 8. Person ADJ, Craft NW, Howe JM. Choroidal involvement in lymphomatoid granulomatosis. Br J Ophthalmol 1991; 75: 688- 9. 9. Haider S. Tonic pupil in lymphomatoid granulomatosis. Journal of Clinical Neuro- ophthalmology 1993; 13: 38- 9. 10. Dolan GL, Smith J, Reilly JT. Extrapulmonary lymphomatoid granulomatosis presenting as Pancoast's syndrome. Postgrad Med .1 1991; 67: 914- 5. 11. McKay D, Ell J, Williams R, Taylor F. Lymphomatoid granulomatosis presenting as sudden blindness. Aust N Z J Ophthalmol 1990; 18: 215- 9. 12. Sordillo PP, Epremian B, Koziner B, Lacher M, Lieberman P. Lymphomatoid granulomatosis: an analysis of clinical and immunologic characteristics. Cancer 1982; 49: 2070- 6. 13. Brazis P, Menke DM, Meleish WM, et al. Angiocentric T- cell lymphoma presenting with multiple cranial nerve palsies and retrobulbar optic neuropathy. J Neuro- ophthalmol 1995; 15: 152- 7. ./ Neiim- Ophlhalmol, Vol. IS, No. 2, 1998 |