Journal of Neuro-Ophthalmology, June 2001, Volume 21, Issue 2

Primary Central Nervous System Lymphoma Involving the Optic Chiasm in AIDS

OBJECTIVE: To report visual loss resulting from chiasmal involvement by primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: Case report. RESULTS: A patient with the acquired immune deficiency syndrome (AIDS) presented with visual loss resulting from PCNSL involving the optic chiasm. The clinical findings, neuroimaging, pathology, and treatment of this patient are described. CONCLUSIONS: Although rare, clinicians should consider PCNSL in the differential of a hypothalamic/chiasmal mass, especially in a patient with AIDS.

Journal ofNeuro- Ophthalmology 21( 2): 95- 98, 2001. © 2001 Lippincott Williams & Wilkins, Inc., Philadelphia Primary Central Nervous System Lymphoma Involving the Optic Chiasm in AIDS Andrew G. Lee, MD, Rosa A. Tang, MD, Dwayne Roberts, MD, Jade S. Schiffman, MD, and Anne Osborne, MD Objective: To report visual loss resulting from chiasmal involve­ment by primary central nervous system lymphoma ( PCNSL). Materials and Methods: Case report. Results: A patient with the acquired immune deficiency syn­drome ( AIDS) presented with visual loss resulting from PCNSL involving the optic chiasm. The clinical findings, neuroimag-ing, pathology, and treatment of this patient are described. Conclusions: Although rare, clinicians should consider PCNSL in the differential of a hypothalamic/ chiasmal mass, especially in a patient with AIDS. Primary central nervous system lymphoma ( PCNSL) is an uncommon intracranial lesion representing less than 0.7% of all malignant lymphomas and less than 1% of all intracranial tumors. PCNSL is more common in immu­nocompromised patients, such as those with acquired im­mune deficiency syndrome ( AIDS). PCNSL typically presents as focal or multifocal lesion( s) of the cerebral hemispheres involving the basal ganglia, cortical- white matter junction, thalamus, and periventricular areas. Vi­sual loss in PCNSL has been reported, but direct optic nerve or chiasmal involvement is rare. We report a case of PCNSL involving the optic chiasm in a patient with AIDS and review the selected English language literature ( 1- 22). CASE REPORT A 42- year- old man presented with severe headaches and bilateral visual loss. Past medical history was sig­nificant for positive human immunodeficiency virus ( HIV) test in December 1996 but no AIDS- defining ill- Manuscript received March 25, 2001; accepted April 5, 2001. This work was supported in part by an unrestricted grant from Re­search to Prevent Blindness, Inc., New York, New York. From the Departments of Ophthalmology, Neurology, and Neuro­surgery ( AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa; the Department of Ophthalmology ( RAT, DR, ISS), The University of Texas Medical Branch, Galveston, Texas; and the De­partment of Neuroradiology ( AO), The University of Utah School of Medicine, Salt Lake City, Utah. Address correspondence and reprint requests to Andrew G. Lee, MD, 200 Hawkins Drive, PFP, The University of Iowa Hospitals and Clin­ics, Iowa City, IA 52242; e- mail: andrew- lee@ uiowa. edu. ness. CD4 count was 209 on March 20, 1997. Medica­tions included 400 mg of ritonavir twice daily, 400 mg of saquinavir twice daily, one Bactrim ( Roche Laboratories, Nutley, NJ) daily, 150 mg of lamivudine twice daily, 40 mg of stavudine twice daily, and 100 mg of didanosine twice daily. Past ocular history was noncontributory, and results from previous eye exams were normal. He developed the acute onset of bilateral simultaneous progressive visual loss, headache for the previous 3 weeks, and intermittent vague diplopia. On September 15, 1997, the visual acuity was 20/ 20 OD and 20/ 40 OS. Pupil, slit lamp, motility, and ophthalmoscopic exam re­sults were normal. The visual loss continued to progress, however, and he was admitted to the hospital on Sep­tember 19, 1997. At that time, he had symptoms of in­creased somnolence, mental status changes, fever, and chills. Ophthalmologic examination now revealed a vi­sual acuity of hand motions OU, a bitemporal hemian-opic visual field defect to confrontational testing, poorly reactive pupils OU, and optic disc edema OU. The visual loss progressed to no light perception OU. He developed diabetes insipidus. Computed tomogra­phy ( CT) scan of the head showed a suprasellar mass. Magnetic resonance imaging ( MRI) of the head revealed a hypothalamic mass with homogenous enhancement and involvement of both optic nerves and the optic chi­asm ( Fig. 1 and Fig. 2). Right and left internal carotid artery and left vertebral artery cerebral angiogram were normal. Lumbar puncture revealed normal cerebrospinal fluid ( CSF) analysis, including normal protein, cell count, and glucose levels. CSF cryptococcal antigen and CSF cytology were negative for malignancy. Immuno­globulin ( Ig) G for toxoplasmosis was negative. Neuro­surgery performed a right craniotomy with biopsy of the lesion. Pathology was nondiagnostic and showed only gliosis and hemorrhage but no malignancy. The patient was treated with 4 mg of intravenous dexamethasone four times daily with marginal improvement of vision. During the next few weeks, the patient's vision con­tinued to deteriorate, and on October 8, 1997, the visual acuity was no light perception OD and hand motion OS. The pupils were sluggishly reactive OU, and there was a right relative afferent papillary defect. Ophthalmoscopy 95 96 A. G. LEEETAL. FIG. 1. Axial postcontrast T1- weighted MRI of the brain reveals a suprasellar mass with enhancement of the optic chiasm and both optic nerves ( arrow). showed optic atrophy OU. Single photon emission CT ( SPECT) was normal. Stereotactic biopsy of the lesion on October 11, 1997, demonstrated monotonous sheets of lymphocytes with enlarged pleomorphic nuclei con­sistent with lymphoma ( Fig. 3). Monoclonal antibodies against CD20 were positive for B cells and were negative for CD3 ( T- cell markers). A diagnosis of primary central nervous system lymphoma was made. The patient was treated with palliative radiation therapy to the brain ( 30 Gy in ten fractions), chemotherapy, and dexamethasone. He was transferred to a skilled nursing facility after discharge. FIG. 2. Coronal postcontrast T1- weighted MRI of the brain dem­onstrates the enhancing optic nerves bilaterally ( arrow). FIG. 3. Medium power photomicrograph of monotonous sheets of lymphocytes with enlarged pleomorphic nuclei ( arrow). DISCUSSION Infection with HIV is associated with PCNSL, and the incidence of PCNSL has increased with the advent and spread of AIDS ( l^ t). The reported incidence of non- Hodgkin lymphoma in AIDS patients ranges from 2.9 to 14.5%, and it is the AIDS- defining illness in as many as 16% of cases ( l^ t, 8- 10). Goplen et al. ( 10) reported 29 adult cases in 225 ( 19%) patients with AIDS, and 19 patients ( 12%) had PCNSL. PCNSL is the most common noninfectious mass lesion in AIDS and is a major threat to long- term survival in patients ( fourth leading cause of death) ( 3,8). Primary central nervous system lymphoma in AIDS patients may differ from those that occur in immuno­compromised but non- AIDS patients. The features of PCNSL in AIDS patients include few or no neurologic symptoms, multifocal necrotic lesions, frequent associa­tion with opportunistic infections or HIV encephalitis, and B- cell origin with high- grade pathology ( 2). Ep-stein- Barr virus ( EBV) has been associated with PCNSL in AIDS patients, but the exact pathogenesis of EBV in PCNSL remains to be completely defined ( 2). Our pa­tient was HIV- positive. Involvement of the optic apparatus by PCNSL is rare. Visual loss resulting from lymphoma may occur with intraocular involvement ( 5,6,11,12,14,17,18). The older literature referred to these intraocular cases as " reticu­lum cell sarcoma," but the pathology is large B- cell lymphoma ( 18). In addition, PCNSL may affect the intraorbital or in­tracranial optic nerves, chiasm, radiations, or visual cor­tex. Cavernous sinus or superior orbital fissure involve­ment and direct infiltrative or compressive lesion ( e. g., optic nerve, chiasm, and tract) have also been reported ( 6,7,11,13,14,16,18,20- 22). Purvin and Van Dyk ( 18) reported a case of PCNSL presenting as a steroid-responsive optic neuropathy with an enlarged optic nerve. Corticosteroids may cause transient clinical or ra- / Neuro- Ophthalmol, Vol. 21, No. 2, 2001 PRIMARY CNS LYMPHOMA INVOLVING THE OPTIC CHIASM IN AIDS 97 diologic improvement of PCNSL, and steroid respon­siveness of a lesion does not exclude lymphoma from the differential diagnosis. Bullock et al. ( 6) reported non- Hodgkin lymphoma invading the optic nerve in one pa­tient. Sakai et al. ( 20) reported primary meningeal lym­phoma presenting with visual loss resulting from a sellar/ chiasmal mass. A suprasellar mass is rarely caused by focal PCNSL, and to our knowledge, our case is unique in that it was the presenting sign of lymphoma in a patient diagnosed with AIDS ( 16,22). In most cases of PCNSL in AIDS, the lesions are multifocal. In our case, there was a focal suprasellar mass involving the hypothalamus and optic chiasm/ nerves. The differential for such a mass includes infiltrating neo­plasm ( e. g., hypothalamic glioma, lymphoma), inflam­matory lesion ( e. g., sarcoid, granulomatous disease), or eosinophilic granuloma. In a patient with AIDS, the most common intracere­bral lesions are toxoplasmosis, PCNSL, and progressive multifocal leukoencephalopathy. The neuroimaging characteristics of toxoplasma encephalitis and PCNSL are well described ( 15,19). Unfortunately, in the majority of cases ( 50- 80%), it is not possible to differentiate the two lesions radiographically, and both may present with focal or multifocal, ring or nodular enhancing masses with surrounding edema that are located in the superfi­cial ( e. g., corticomedullary junction) or deep ( e. g., basal ganglia, thalamus) cerebral hemispheres. The MRI characteristics for PCNSL and toxoplasmo­sis include isointensity to gray matter on T2- weighted images. The rim of PCNSL lesions may appear isoin-tense to gray matter on T2- weighted images with a hy-perintense center. Although ring enhancement in PCNSL is common, solid enhancement may also be seen, as in our case. The suprasellar mass lesion in our case was unusual for either toxoplasmosis or PCNSL ( 15,19). Although the major neuroimaging differential diag­noses for a contrast enhancing mass in a patient with AIDS are toxoplasmosis and PCNSL, other primary brain ( 1,4,15) neoplasms ( e. g., glioblastoma multiforme) and other less common lesions should be considered ( e. g., metastatic Kaposi sarcoma, herpes simplex virus, cryptococcoma, mycobacterial, Nocardia, Candida, as­pergillosis abscess). Toxoplasmosis is the most frequent ( 50- 70%) cause of a mass lesion of the brain in AIDS, and therefore many centers empirically treat for toxoplasmosis and then follow the patients with serial neuroimaging for treatment response ( up to 85% response within 1 week). Patients with atypical neuroimaging characteristics or those who fail empiric antitoxoplasmosis therapy usually are considered for stereotactic biopsy to exclude tumors, including PCNSL ( 15). Thallium- 201 SPECT and 18F- fluoro- 2- deoxyglucose ( FDG)- positron emission tomography ( PET) have been proposed as imaging modalities that may allow differen­tiation of PCNSL from toxoplasma encephalitis ( 15,19). Our patient underwent a SPECT study that was negative; the significance of this finding is uncertain. The histopathology of lymphoma includes large cells with scant cytoplasm, coarse nuclear chromatin, and prominent nucleoli. Cytochemical markers and immu-nophenotyping are able to define the cell type ( B cell or T cell) and demonstrate clonality for lymphoma. Most PCNSLs are of B- cell origin, but T- cell PCNSL has also been reported ( 3). A higher man- to- woman ratio and a more frequent infratentorial location are seen in T- cell PCNSL ( 4). Our patient had a large B- cell lymphoma. The main management of PCNSL is whole- brain ra­diation therapy ( 9). Chemotherapy may have a less prominent role for patients already immunocompromised by AIDS ( 3). 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