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Show ORIGINAL CONTRIBUTION Isolated Lymphoma of the Anterior Visual Pathway Diagnosed by Optic Nerve Biopsy Joseph R. Zelefsky, MD, Carolyn H. Revercomb, MD, George Lantos, MD, and Floyd A. Warren, MD Abstract: A 72- year- old previously healthy man developed rapidly progressive visual loss, and brain imaging showed features suggestive of a malignant glioma of the anterior visual pathway. Biopsy of one optic nerve yielded a diagnosis of lymphoma. There was no evidence of an extracranial non- Hodgkin lymphoma, so the conclusion was that this represented a primary central nervous system lymphoma ( PCNSL). PCNSL isolated to the optic chiasm has been described only once in an immunocompetent patient. Our patient is unusual in that the lymphoma involved the optic nerve, chiasm, and tract in an immunocompetent patient. { JNeuro- Ophthalmol 2008; 28: 36- 40) A nterior visual pathway involvement from lymphoma can be divided into three categories: primary intraocular lymphoma ( PIOL), primary central nervous system lymphoma ( PCNSL), and secondary metastatic involvement from systemic non- Hodgkin lymphoma ( NHL). Cases of isolated optic nerve involvement in the absence of PCNSL infiltration of the brain, retina, or vitreous, or extracranial signs of NHL have been rarely reported ( 1,2). We report a case of isolated lymphoma of the optic nerve, optic chiasm, and optic tract in an immunocompetent patient in whom the diagnosis was reached by optic nerve biopsy. CASE REPORT A 72- year- old man was referred to the neuro-ophthalmology clinic for progressive painless loss of vision in the right eye for 6 weeks. His past medical history Department of Ophthalmology ( JRZ, FAW) and Department of Pathology ( CHR), New York University School of Medicine, New York, New York; and Department of Radiology ( GL), Albert Einstein College of Medicine, Bronx, New York. Address correspondence to Joseph R. Zelefsky, MD, New York University Medical Center, Department of Ophthalmology, 462 First Ave., New York, NY 10016; E- mail: jzelefsk@ yahoo. com was significant for hypertension and newly diagnosed diabetes mellirus. He denied headache, weight loss, or other constitutional symptoms. Best- corrected visual acuity was count fingers at 1 foot in the right eye and 20/ 25 in the left eye. Confrontation visual field testing was suggestive of an inferior altirudinal defect in the right eye and was full in the left eye. Ishihara ION • • • • • • • • • • • • • • • • • • • • • » • • " • • • & • • • •• &. • • • u • » • » • • FIG. 1. Humphrey visual field of the left eye demonstrates a dense temporal hemianopia. 36 J Neuro- Ophthalmol, Vol. 28, No. 1, 2008 Lymphoma of the Anterior Visual Pathway J Neuro- Ophthalmol, Vol. 28, No. 1, 2008 FIG. 2. Coronal brain MRI. Row 1: precontrast T1; row 2: postcontrast T1; row 3: T2. Arrowheads demarcate areas of T1 enhancement and T2 high signal in the intracranial portion of right optic nerve ( column A), optic chiasm ( column B), right optic tract ( column C), and left optic tract/ lateral geniculate nucleus junction region ( column D). The T2 signal abnormalities ( row 3) are more extensive than the enhancement ( row 2), reflecting lesional edema. The right optic tract ( as best seen in row 2, column C) has a layered appearance reminiscent of the organization of the contained white matter fibers. color vision testing was normal in the left eye. There was an afferent pupillary defect in the right eye. On slit lamp examination, the anterior segments of both eyes were unremarkable. Dilated funduscopic examination demonstrated pallor of the right optic disc and a normal- appearing left optic disc. The vitreous was clear, and the retina and choroid were normal in both eyes. Results for a complete blood count ( CBC) with differential, erythrocyte sedimentation rate ( ESR), angioten-sin- converting enzyme ( ACE), rapid plasma reagin ( RPR), microhemagglutination- 7repo « e? wa pallidum ( MHA- TP), and Lyme titer ( enzyme- linked immunosorbent assay [ ELISA]) were within normal limits. C- reactive protein was elevated at 4.83 mg/ dL ( normal < 1 mg/ dL). The patient returned a few days later, reporting that the vision in his left eye was worsening. Automated visual field testing demonstrated a dense temporal hemianopic defect in that eye ( Fig. 1). Brain MRI ( Figs. 2 and 3) showed abnormal contrast enhancement of the intracranial portion of the right optic nerve and optic chiasm. Contrast enhancement extended posteriorly to the right optic tract and toward the left lateral geniculate body. Of interest, the enhancement of the lesion demonstrated a " layered" appearance, reminiscent of the histologic organization of the lateral geniculate nucleus. Given the imaging findings and the poor vision in the right eye, the patient underwent transcranial biopsy of the right optic nerve. Microscopic examination ( Fig. 4) revealed a tumor composed of closely packed cells with frequent mitotic figures. Immunohistochemical staining revealed that most cells had membranous positivity for the B- cell antigen CD20. The tumor cells were also positive for bcl- 2, but negative for CD5, CD 10, and bcl- 1. An MIB- 1 immu-nostain, which labels the Ki- 67 proliferation- associated antigen, labeled more than 50% of the large tumor cells. Admixed small T lymphocytes were marked by 37 J Neuro- Ophthalmol, Vol. 28, No. 1, 2008 Zelefsky et al FIG. 3. Axial brain MRI. Row 1: precontrast T1; row 2: postcontrast T1; row 3: FLAIR. There is enhancement and high signal on the FLAIR images in the optic chiasm ( column A), right optic tract ( column B), left optic tract ( column C), and left optic tract/ lateral geniculate nucleus junction region ( column D) ( arrowheads). As on theT2 images in Fig. 2, the signal changes on the FLAIR images ( row 3) are more extensive than the enhancement ( row 2) owing to lesional edema. antibodies to the T- cell antigens CD3 and MT- 1 ( CD43). The light microscopic appearance and immunohistochem-ical profile established the diagnosis of non- Hodgkin lymphoma of diffuse small B- cell type. The immunophe-notype was consistent with origin from follicular center cells. CT scans of the chest, abdomen, and pelvis did not show any evidence of systemic lymphoma or other medical conditions. Further tests with normal results included a CBC with differential, a complete metabolic panel, and an HIV titer. Treatment with high- dose methotrexate, leuco-vorin, and prednisone was initiated. Over the next few weeks, the patient's condition deteriorated and he died 3 months later. DISCUSSION Lymphomatous involvement of the optic nerve most often occurs as a result of metastatic spread of systemic 38 © 2008 Lippincott Williams & Wilkins Lymphoma of the Anterior Visual Pathway J Neuro- Ophthalmol, Vol. 28, No. 1, 2008 • •• XTJTt FIG. 4. Optic nerve biopsy. A. The densely cellular tumor has frequent mitotic figures and surrounds blood vessels ( hematoxylin and eosin; original magnification: X400). B. Immunohistochemical staining for the B lymphocyte marker CD20 marks the majority of cells in the tumor. C. Immunostaining for the T cell marker CD3 labels admixed small T lymphocytes. D. Immunostaining for MIB- 1, a marker of cell proliferation, labels more than 50% of the tumor cells. NHL ( 3). PCNSL of the optic nerve is rare, and isolated PCNSL involvement of the anterior visual pathway is even rarer. There have been scant case reports of optic nerve involvement in patients with NHL ( 1,4- 6). PCNSL infiltration of the optic nerve and chiasm has been reported in patients with AIDS ( 2,7), in whom the incidence of PCNSL is increased ( 8- 11). Gray et al ( 12) reported a patient with headaches, loss of hearing, and loss of vision, who had a PCNSL of the optic chiasm. To our knowledge, our case is unusual in that PCNSL involved the optic nerve, chiasm, and tract in an otherwise asymptomatic patient without AIDS or other systemic immuno-suppressed state. Although the histopathologic characteristics of PCNSL and NHL metastatic to the intracranial space are practically indistinguishable, PCNSL most often involves the brain parenchyma, typically near the ventricles, whereas NHL with secondary central nervous system ( CNS) involvement usually presents in the leptomeninges or dura ( 13). The lack of dural or meningeal involvement in our patient, together with the absence of any extracranial manifestations of NHL noted on his systemic workup, suggests that his lymphoma falls into the category of PCNSL. In our patient, the relatively rapid and progressive visual loss in both eyes in a previously healthy older man, coupled with the imaging abnormalities, suggested malignant glioma of the optic nerve and chiasm. This case demonstrates the importance of considering the diagnosis of lymphoma in this setting. REFERENCES 1. Behbehani RS, Vacarezza N, Sergott RC, et al. Isolated optic nerve lymphoma diagnosed by optic nerve biopsy. 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