Involvement of the central nervous system (CNS) in non-Hodgkin lymphoma (NHL) most commonly occurs as secondary spread from systemic disease rather than as a primary CNS malignant neoplasm and generally carries a poor prognosis.1 Optic nerve involvement is rare and the diagnosis is often elusive since the results of repeated lumbar punctures and neuro-imaging are frequently normal.1 We report a case in which a definitive diagnosis of lymphomatous optic neuropathy was made following optic nerve biopsy.
Following a flu-like illness, a 74-year-old woman was found to have mild lymphocytosis and marginal thrombocytopenia. She experienced intermittent monocular visual obscurations and 12 months later noticed inferotemporal visual field loss in the left eye that was confirmed on Amsler chart testing. Her visual acuity was 20/15 OU and she was found to have bilateral optic disc swelling (Figure 1), but no cells in the vitreous. An infiltrative optic neuropathy was suspected and a magnetic resonance imaging scan performed with contrast medium showed enlarged optic nerves that did not enhance. A bone marrow biopsy revealed a low-grade lymphoproliferative disorder and a chest radiograph showed no abnormality. Analysis of peripheral blood with lymphocyte markers was positive for B-cell markers CD19, CD20, and CD68 and for κ light chains and IgM. Two lumbar punctures were performed showing raised cerebrospinal fluid protein levels of 0.62 and 0.55 g/L. No cells were present in the samples from the first procedure. However, the second lumbar puncture samples yielded cerebrospinal fluid containing 4 mature lymphocytes. However, no evidence was noted of malignant neoplasms or atypia.
Top, Swelling of right and left optic discs at the initial visit. Bottom, Right and left optic disc atrophy 10 months after left optic nerve biopsy and receiving bilateral radiotherapy.
Four months later visual acuity had deteriorated to 20/30 OD and 20/80 OS with a left relative afferent pupillary defect. Advanced bilateral visual field constriction was noted with almost total loss of visual field in the left eye (Figure 2). A diagnostic left optic nerve biopsy was, therefore, performed using the optic nerve sheath fenestration method with a biopsy performed of the underlying optic nerve substance. Gross examination of the optic nerve sheath was not diagnostic, but material from the optic nerve substance showed infiltration by a low-grade B-cell NHL (Figure 3).
Top, Left and right Humphrey 24-2 visual fields performed 6 weeks before left optic nerve biopsy. Bottom, Left and right Goldmann visual fields performed 3 months after left optic nerve biopsy and 2 months after receiving bilateral radiotherapy to the optic nerves.
Optic nerve biopsy specimen with crush artefact (A) (hematoxylin-eosin, original magnification ×40) shows lymphomatous infiltration, but monomorphic cellular morphology is definitively seen in the peripheral optic nerve biopsy (B) (hematoxylin-eosin, original magnification ×400). C, View of the lower eyelid subcutaneous mass (hematoxylin-eosin, original magnification ×12.5). D, View shows a similar monomorphous cellular appearance (hematoxylin-eosin, original magnification ×400).
Immediately postoperatively visual acuity had deteriorated to light perception OS but improved to 20/60 over the next 5 months following low-dose radiotherapy to the optic nerves (total dose 30 Gy to the optic nerves in 15 fractions over 3 weeks). Goldmann visual fields 3 months after biopsy and 1 month after radiotherapy showed that progressive deterioration had been arrested (Figure 2). Eleven months after optic nerve biopsy, the optic discs had become atrophic (Figure 1) with a visual acuity of 20/40 OD and 20/80 OS. The patient has required local radiotherapy for a right lower eyelid lymphomatous mass, but no systemic therapy has been administered as the patient has remained otherwise well.
Central nervous system NHL most commonly involves the leptomeninges, nerve roots, cerebral parenchyma, and dura1 with optic nerve infiltration in just 5% of the patients. There are reports of isolated optic neuropathy occurring with other lymphoproliferative disorders, but we are aware of only 3 reported cases of CNS NHL seen with an isolated infiltrative optic neuropathy.2- 4 The patient described by Kansu et al2 was seen with an isolated infiltrative optic neuropathy with no other systemic or CNS involvement2; whereas, in the case reported by Strominger et al,3 the optic neuropathy was preceded by a 2-year history of leukopenia. According to Walsh and Shewmake,4 their patient developed third, fourth, and sixth cranial nerve palsies 3 weeks after the visual loss. In all 3 cases initial cerebrospinal fluid examination did not show lymphomatous cells and the diagnosis of NHL was made, respectively, on results from a craniotomy and optic nerve excisional biopsy,2 temporal artery biopsy,3 and biopsy of an abdominal lymph node following a jejunal perforation.4 It is perhaps surprising that findings from a biopsy of the optic nerve sheath in this case were not diagnostic given the predilection of NHL for dural spread over optic nerve involvement.1 To our knowledge, our case is the first such reported in which localized biopsy performed on the optic nerve substance was used to confirm the diagnosis of NHL; in the case reported by Kansu et al2 it appears that the optic nerve was sacrificed to allow histological examination.
Optic nerve biopsy carries a risk of permanent visual loss and may yield false-negative results since the size of the biopsy specimen is limited by the necessity of preserving vision. However, the case reported herein illustrates that diagnostic optic nerve biopsy can be invaluable in cases in which diagnosis of CNS lymphoma is impossible by any other means, eg, such as biopsy of lymph nodes, bone marrow, or masses. Despite temporary visual deterioration after the biopsy–presumably caused by neuropraxis–there was later improvement of optic nerve function to at least the prebiopsy level. Although there was a degree of subsequent visual decline owing to optic atrophy, this initial visual recovery suggests that optic nerve biopsy may be considered for diagnosis in enigmatic cases even when some visual function remains.
Corresponding author: John S. Elston, MD, FRCS, FRCOphth, Oxford Eye Hospital, Woodstock Road, Oxford OX1 6HE, England.
Dayan MR, Elston JS, McDonald B. Bilateral Lymphomatous Optic Neuropathy Diagnosed on Optic Nerve Biopsy. Arch Ophthalmol. 2000;118(10):1446–1449. doi: