Journal of Neuro-Ophthalmology, March 1984, Volume 4, Issue 1

Primary reticulum cell sarcoma of the brain presenting as steroid-responsive optic neuropathy.

A 23-year-old woman presented with subacute monocular visual loss clinically resembling optic neuritis. CT scan revealed a cerebellar mass, biopsy of which led to the diagnosis of reticulum cell sarcoma (RCS). Corticosteroid therapy resulted in improvement of vision and a decrease in disc edema; this resolution was documented radiographically. While optic nerve involvement is sometimes seen in association with systemic lymphoproliferative disease, optic neuropathy as a manifestation of primary cerebral RCS is rare.

J. Clin. Neuro-ophthalmol. 4: 15-23, 1984. Primary Reticulum Cell Sarcoma of the Brain Presenting as Steroid-Res­ponsive Optic Neuropathy VALERIE PURVIN, M.D. HENRY J. L. VAN DYK, M.D. Abstract A 23-year-old woman presented with subacute mo­nocular visual loss clinically resembling optic neu­ritis. CT scan revealed a cerebellar mass, biopsy of which led to the diagnosis of reticulum cell sar­coma (RCS). Corticosteroid therapy resulted in im­provement of vision and a decrease in disc edema; this resolution was documented radiographically. While optic nerve involvement is sometimes seen in association with systemic lymphoproliferative disease, optic neuropathy as a manifestation of pri­mary cerebral RCS is rare. Introduction Reticulum cell sarcoma is a malignant tumor of the lymphoreticular system. Since the first de­scription of this neoplasm by Ewing in 1913,1 there has been continuing controversy surround­ing its cell of origin. This controversy is reflected in the welter of synonyms by which the neoplasm is known, including microglioma, perithelial or perivascular sarcoma, histiocytic sarcoma, reticu­loendothelial sarcoma, and histiocytic lymphoma. Recent evidence from immunologic studies indi­cates that the tumor is in fact a lymphoma, usu­ally of B-cell origin, and is derived from neither true histiocytes, reticulum cells, nor microglia. 2 Nevertheless, we have elected to retain the term reticulum cell sarcoma in this report because (mis­~ omer that it is) it is the most widely used des­Ignator for this neoplasm. Two major varieties of reticulum cell sarcoma have been delineated: a systemic form usually arising in lymph nodes, bone marrow, or viscera; and a less common primary central nervous sys­tem (eNS) form, most commonly arising within the cerebral hemispheres. The CNS variety ac- From the Department of Ophthalmology, Louisiana State University Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans, Louisiana. March 1984 counts for approximately one-sixth of cases,3 al­though in certain subsets of patients, e.g., renal transplant recipients, the CNS form is more com­mon. While the systemic and primary CNS types are indistinguishable on histologic or immuno­logic grounds, they do exhibit distinctive behavior patterns, thus warranting such a classification.4 Primary reticulum cell sarcoma of the brain is generally a disease of adults, affecting both sexes equally.5 Evolution of symptoms is usually rapid averaging 2-3 months. Signs of focal cerebral dysfunction as well as increased intracranial pres­sure determine the clinical picture. Despite the extreme radiosensitivity of these neoplasms, prognosis remains grim, with only 4% of patients disease-free 5 years after diagnosis. 6 Involvement of the visual system by reticulum cell sarcoma may take a variety of forms. Optic nerve involvement is rare.8 • 9 We describe a pa­tient in which optic neuropathy was the present­ing sign of intracranial reticulum cell sarcoma. Case Report A 23-year-old black woman was admitted to New Orleans Charity Hospital with a 3-week history of progressive loss of vision in the right eye associated with occipital and vertex headache. Four days prior to admission she developed nau­sea and vomiting; vision declined to no light perception. She denied eye pain, difficulty with balance or coordination, weakness, or weight loss. Past medical history and family history were un­remarkable. There was no history of autoimmune disease or immunosuppressant drug therapy. Initial examination revealed a visual acuity of 20/20 in the left eye and no light perception in the right eye. Pupils were 5 mm in diameter with a normal consensual response, but no direct re­sponse to light in the right eye. Ophthalmoscopy revealed a markedly swollen right optic disc with soft exudates, capillary hyperemia, and opacifi­cation of the nerve fiber layer. Retinal striae were seen temporal to the disc (Fig. 1). The left fundus was normal (Fig. 2). There was no proptosis or 15 Primary Reticulum Cell Sarcoma of Brain Figure 1. Black and white reproduction of color photograph of right fundus taken on day 7 when vision had improved to 20/200. Nerve fiber opacification, disc edema, and capillary hyperemia are still visible. Scattered hard exudates are seen temporal to the disc. Figure 2. Normal left disc. Journal of Clinical Neuro-ophthalmology Purvin, Van Dyk Figure 3. Axial CT scan following intravenous contrast infusion. A large enhancing mass seen in the left cerebellar hemisphere (arrow). There is compression of the fourth ventricle and early hydrocephalus. lid edema. Slit lamp examination revealed a clear anterior chamber and vitreous. There was a small right exotropia with full ductions and versions. Detailed neurologic evaluation revealed some dif­ficulty with tandem gait and some minimal clum­siness of the left upper extremity. General medical examination was negative; specifically, there was no lymphadenopathy, palpable abdominal masses, or visceromegaly. Laboratory data included a complete blood count, chemistries, urinalysis, serology, chest ra­diograph, and EKG, all of which were normal. Serum immunoelectrophoresis was not obtained. A computerized tomographic (CT) scan was per­formed before and after intravenous contrast in­fusion. Ten-millimeter axial sections of the brain and 5-mm axial and coronal sections of the orbits were obtained. A large enhancing mass was seen in the left cerebellar hemisphere with compres­sion of the fourth ventricle and moderate enlarge­ment of the third and lateral ventricles (Fig. 3). In addition, smaller enhancing masses were seen in the right cerebellum and in the right parasellar region (Fig. 4). The proximal portion of the right intraorbital optic nerve was diffusely enlarged (Figs. 5 and 6). The patient was started on Decadron immedi­ately following the CT scan. Some return of vision in the right eye was noted on the second hospital day. On the third day an occipital craniotomy March 1984 was performed with resection of the left cerebel­lar hemisphere. Examination of permanent sec­tions confirmed the frozen section diagnosis of reticulum cell sarcoma (Fig. 7). Visual acuity im­proved to count fingers on the fourth hospital day, and to 20/200 by day 6. Disc edema was also seen to diminish concomitant with the im­provement in vision. Orbital B-scan at that time showed slight elevation of the right optic nerve head as well as some widening of the optic nerve pattern. As measured by A-scan ultrasonography, the diameter of the right optic nerve was 5.6 mm just behind the globe and 7.5 mm in the posterior orbit. The left optic nerve measured 4.6 mm, which is within the normal range. The internal reflectivity of the right optic nerve was lower than that of the left. Ten days after craniotomy, visual acuity was still 20/200 in the right eye; Goldmann perimetry showed a relative central scotoma in the right eye and a full field in the left eye. A second orbital CT scan was obtained 2 weeks after craniotomy, this time with 3-mm sections. This study showed definite enlargement of the right optic canal, but the optic nerve appeared normal (Fig. 8). The patient received 6,000 rads of cranial ra­diation over a 4-week period. Examination fol­lowing the completion of radiotherapy revealed visual acuity of 20/30 in the right eye and 20/20 17 Primary Reticulum Cell Sarcoma of Brain Figure 4. Axial CT scan after contrast administration demonstrating additional masses in right cerebellum, right temporal lobe. and right parasellar region (arrows). Figure 5. Nonenhanced axial CT scan of orbits, showing kinking of right optic nerve and diffuse enlargement in apical portion. Journal of Clinical Neuro-ophthalmology Purvin, Van Dyk Figure 6. Coronal CT scan of posterior orbit demonstrating increased optic nerve diameter on right. ;1-. - ,.~\.-r ::. Ito.JIif" II.'~_ ;' /' ..~I II '~' ~ tl . ,~,••",,, "4.' _- t .':.1' ." ~,. ; ". -~ l. ...,., 4.... ''''i " J ~.'.. .~-..1 ,."',..,--.,'.-, ....;..~ .~.,.:, ' ~iI.,~' ••' • a., til' ,. W • .. " ..- ,,~ ....,. ~ ... "'\ 1P' " ~~ ·.,11, I.I..". '~....,.:,.. _,• ••,~,., I( " .\ .. ,t., :-,.} ,.,-il - ,W.' _ ....~ ""~ , ,,,.' .~- ".L-o#...."'•. • Figure 7. Light micrograph of biopsy specimen showing neoplastic cells diffusely infiltrating cerebellar parenchyma, Cells are relativPly pleomorphic. with round to oval nuclei and scanty cytoplasm, (H&E, original magnification X160.) March 1984 19 Primary Reticulum Cell Sarcoma of Brain Figure 8. Axial CT scan of orbits (3-mm section) after 2 weeks of steroid therapy, showing widened right optic canal (arrow), but normal diameter of optic nerves (apparent asymmetry is due to slight tilt of patient's head). in the left eye with mild disc pallor and relative afferent pupillary defect on the right. Pursuit to the left was saccadic, optokinetic nystagmus was absent with targets moving to the left, and there was gaze-evoked nystagmus on upward and on left lateral gaze. Discussion The afferent visual system may be affected by either systemic or primary brain reticulum cell sarcoma. The most common ophthalmologic presentation is uveitis (actually intraocular tumor with secondary inflammation), which occurs in association with reticulum cell sarcoma of the central nervous system.!O-12 In a smaller number of patients, intraocular tumor is an isolated find­ing or is seen in conjunction with the nodal/ visceral form. 13 Optic nerve infiltration may occur in this setting as an extension of the neoplastic process in the uveal tract, as described in two autopsied patients of Barr et al. I4 In both cases, the clinical picture was dominated by the cellular vitreous reaction, which was absent in our pa­tient. Signs of optic nerve compression may be ob­served in patients with orbital reticulum cell sar­coma. IS Almost all of these patients have associ­ated systemic tumor. It> The c1nical picture consists of proptosis, often with a palpable mass, lid swell-ing, and variable degree of pain, with loss of vision occurring in a minority.!t> Orbital signs were not present in our patient. Systemic reticulum cell sarcoma may cause cra­nial nerve dysfunction by diffuse spread through­out the meninges (so-called lymphomatous lep­tomeningitis).! 7 This entity usually produces signs of meningeal irritation and occurs largely in patients with advanced systemic diseaseY Optic nerve involvement in this setting is rare; it was seen in none of the 21 cases of lymphomatous meningitis described by Griffin et al., 17 and in only one of 13 patients reported by Bunn et al. I8 Walsh and Shewmake!9 reported a patient with systemic reticulum cell sarcoma in whom a rap­idly developing optic neuropathy was the initial manifestation of disease. Autopsy examination revealed diffuse infiltration of the dura lining the optic canal with extension into the nerve along the vessels. A similar case in which the tumor was a diffuse lymphocytic (T-cell) lymphoma has also been reported. 20 Optic nerve involvement in the absence of leptomeningitis has been described in several Iymphoproliferative disorders. Such involvement is a relatively common complication of acute lym­phoblastic leukemia.21,22 It has also been de­scribed in one patient with lymphosarcoma23 and in patients with Hodgkins' disease affectin~ the optic nerve, 23.24 the optic chiasm,2s or both.2 Journal of Clinical Neuro-ophthalmology Reticulum cell sarcoma may rarely arise pri­marily in the meninges, appearing in the literature under the more general term of Hmeningeal sar­comatosis. n Onofri027 reported eight cases of re­ticuloendothelial sarcoma of the meninges; none of these patients developed involvement of the optic nerve. Hogan et al. 28 added three similar cases, including a I-year-old child in whom retic­ulum cell sarcoma originated in the meninges of the optic nerve sheath. This was documented histologically in the enucleated specimen. While CT scan was not available to exclude other intra­cranial lesions, follow-up after 1 year found the patient in good health with no evidence of sys­temic or central nervous system tumor. We were able to find only two previous reports of primary CNS reticulum cell sarcoma associated with optic neuropathy. Hautzer et al. 27 reported a patient with primary histiocytic lymphoma of the spinal cord in whom postmortem examination revealed tumor infiltrating both optic nerves and tracts. Unfortunately, there was little clinical in­formation regarding the visual system. Fine and Mani3\ reported a 63-year-old man with reticu­lum cell sarcoma of the right temporal lobe, bi­lateral visual loss, and papilledema. CT scan had not been done. Necropsy revealed extensive in­filtration of the leptomeninges surrounding one optic nerve and demyelination with preservation of axis cylinders in the other nerve, with only occasional tumor cells. Amaurosis was thought to be secondary to both compression of the optic nerve by tumor and sustained, increased intra­cranial pressure. Optic disc swelling occurs in some patients with reticulum cell sarcoma of brain as a consequence of increased intracranial pressure. While intra­cranial pressure was undoubtedly elevated in our patient, the unilaterality of the disc edema, the profound loss of vision, and the appearance of the optic nerve on CT scan made this an unten­able explanation for her optic neuropathy. Al­though there was no optic nerve specimen for pathologic examination, we believe our patient's visual loss was secondary to infiltration of the intraorbital optic nerve by reticulum cell sarcoma. Tumor in this location, well-described in patients with leukemia, typically produces profound vis­ualloss with optic disc swelling due to the inelas­ticity of the dural sheath surrounding the nerve.2\ In our case, it is not clear whether the tumor spread to the optic nerve from a primary lesion in the cerebellum via the subarachnoid space or arose independently in multiple sites. This ques­tion has been addressed in the literature and there is evidence for both forms of dissemination. Au­topsy commonly shows widespread leptomenin­geal infiltration with encroachment on cranial nerves and invagination into parenchyma along March 1984 Purvin, Van Dyk blood vessels. 7 Such meningeal spread may not always be manifested clinically and may have been present, but unseen in our patient. Alter­natively, there are cases in which multiple lesions are found with no contiguity between tumor foci. n It has been suggested that primitive lym­phocytes in multiple locations undergo malignant transformation in response to some exogenous stimulus, possibly a virus. The concept of Heco_ taxisH has also been developed to account for the simultaneous occurrence of this tumor in remote sites. According to this theory, a clone of abnor­mal lymphocytes contains receptors for certain tissues, enabling them to disperse to sf,ecific lo­cations, e.g., uveal tract or conjunctiva. 6 Other possible causes of optic neuropathy to which a patient with lymphoma might be predis­posed, such as opportunistic infection,33 radiation necrosis,34 or toxicity of chemotherapeutic agents,35 are not applicable to our patient, whose visual loss occurred early in the course of her disease. One other possibility that must be con­sidered is that our patient may have had an unrelated, coincident attack of idiopathic optic neuritis, a situation that was reported in one of Schaumberg's patients.3 Our patient's age and the time course and reversibility of the visual loss were compatible with this diagnosis. Complete loss of light perception and absence of eye pain, however, are unusual features of idiopathic optic neuritis; the former occurs in only 2% of such cases and the latter in 13%.36 While swelling of the optic nerve is sometimes seen on CT scan in patients with optic neuritis,37 the enlargement of the optic canal in our case was not compatible with that diagnosis. One feature of our patient's clinical course de­serving of special mention was the dramatic re­sponse to corticosteroids. Vision began to improve within 24 hours after therapy was initiated, and continued to improve for several weeks. While it is possible that reduction of intracranial pressure by resection of the tumor in the posterior fossa contributed to improvement in optic nerve func­tion, we also have definite radiologic evidence of tumor regression prior to radiation therapy. Such sensitivi~y to steroids has been noted previ­ously, 28,38, 39,40 including one case with sustained benefit lastin& several years after medication was discontinued.-8CT documentation of such tumor regression has been published in one previous case, involving a patient with reticulum cell sar­coma of the posterior fossa. 4o Some in vitro stud­ies seem to indicate that lymphoreticular tumors may be particularly sensitive to the cytotoxic ef­fects of glucocorticoids.41 There is some evidence that the incidence of CNS reticulum cell sarcoma is increasing.4 Reports of a disproportionate number of 21 Primary Reticulum Cell Sarcoma of Brain cases in renal transplant recipients,~2 patients with congenital immunodeficiency,~3 and pa­tients with acquired immunodeficiency syndrome (AIDS)~S'44 support the theory that immuno­suppression predisposes to the development of this neoplasm. Although primary reticulum cell sarcoma of brain is still a rare entity, it may be that, as organ transplantation becomes more widespread and improved ~mmunosuppression therapy permits longer survival times in such patients, we will be seeing more of this type of malignancy in the future. References 1. Ewing, J.: Endothelioma of lymph nodes. J. Med. Res. 28: 1, 1913. 2. Houthoff, H.J., Popema, 5., Ebels, E.J., and Elema, J.D.: Intracranial malignant lymphomas: A mor­phologic immunocytologic study of twenty cases. Acta Neuropathol. (Berl) 44: 203, 1978. 3. Schaumburg, H. H., Plank, e. R., and Adams, R. D.: The reticulum cell sarcoma-microglioma group of brain tumors. Brain 95: 199, 1972. 4. Adams, RD.: Certain notable clinical attributes of the histiocytic sarcoma of the central nervous sys­tem. Acta Neuropathol. (Berl) Suppl. 6: 177-180, 1975. 5. Henry, J.M., Heffner, RR, Dillard, S.H., Earle, K.M., and Davis, RL.: Primary malignant lympho­mas of the central nervous system. Cancer 34: 1293, 1974. 6. Littman, P., and Wang, e.e.: Reticulum cell sar­coma of the brain: A review of the literature and a study of 19 cases. Cancer 35: 1412, 1975. 7. Rubenstein, L.J.: Tumors of the Central Nervous System. In Atlas of Tumor Pathology (2nd seT., fase. 6). Armed Forces Institute of Pathology, Washing­ton D.e., 1972, pp. 215-235. 8. Currie,S., and Henson, RA: Neurological syn­dromes in the reticuloses. Brain 94: 307, 1971. 9. Williams, H.M., Diamond, H.D., Crower, L.F., and Parsons, H.: Neurologic Complications of Lympho­mas and Leukemias (1st ed.). Charles C Thomas, Springfield, Illinois, 1959, pp. 77; 81. 10. Sloas, H.A., Starling, J., Harper, D.G., and Cup­ples, H.P.: Update of ocular reticulum cell sarcoma. Arch. Ophthalmol. 99: 1048, 1981. 11. Neault, R.W., Van Scoy, R.E., Okazaki, H., and MacCarty, e.S.: Uveitis associated with isolated reticulum cell sarcoma of the brain. Am. J. Ophthal­mol. 73: 431, 1972. 12. Vogel, M.H., Font, RL., Zimmerman, L.E., and Levine, R.A: Reticulum cell sarcoma of the retina and uvea: Report of 6 cases and review of the literature. Am. f. Ophthalmol. 66: 205, 1968. 13. Klingele, T.G., and Hogan, M.J.: Ocular reticulum cell sarcoma. Am. f. Ophthalmol. 79: 39, 1975. 14. Barr, e.e., Green, W.R, Payne, J.W., Knox, D.L., Jensen, AD., and Thompson, RL.: Intraocular re­ticulum cell sarcoma: Clinicopathologic study of four cases and review of the literature. Surv. Ophthalmol. 19: 224, 1975. 15. Mortada, A.: Orbital reticulum cell sarcoma. Report of nine cases. Br. f. Ophthalmol. 45: 365, 1961. . 16. Jakobiec, F.A, Williams, P., and Wolff, M.: Retic­ulum cell sarcoma (histiocytic lymphoma) of the orbit. Surv. Ophthalmol. 22: 255, 1978. 17. Griffin, JW., Thompson, RW., Mitchinson, M.J., de Kiewiet, J.e., and Welland, F.H.: Lymphoma­tous leptomeningitis. Am. f. Med. 51: 200, 1971.. 18. Bunn, P.A, Schein, P.5., Banks, P.M., and De VIta, U.T.: Central nervous system complications in pa­tients with diffuse histiocytic and undifferentiated lymphoma. Leukemia revisited. Blood 47: 3, 1976. 19. Walsh, F.B., and Shewmake, B.J.: An unusual case of reticulum cell sarcoma. Am. f. Ophthalmol. 74: 741, 1972. 20. Kattah, J.e., Suski, E.T., and Killen, J.Y. Smith, E.P., and Limaye, S.R: Optic neuritis and systemic lymphoma. Am. J. Ophthalmol. 89: 431, 1980. 21. Rosenthal, AR., Egbert, P.R, Wilbur, J.R, and Probert, J.e.: Leukemic involvement of the optic nerve. f. Pediatr. Ophthamol. Strabismus 12: 84, 1975. 22. Allen, RA, and Straatsma, B.R: Ocular involve­ment in leukemia and allied disorders. Arch. Ophthamol. 66: 490, 1961. 23. Kraus, AM., and O'Rourke, J.: Lymphomatous optic neuritis. Arch. Ophthalmol. 70: 173, 1963. 24. Walsh, F.B., and Hoyt, W.F.: Clinical Neuro-Oph­thalnlOlogy, Vol. 3. William & Wilkins, Baltimore, 1969, Case 12.145, pp. 2305-2306. 25. Miller, N.R, and Iliff, W.J.: Visual loss as the initial symptom in Hodgkin's disease. Arch. Ophthalmol. 93: 1158, 1975. 26. Litvak, J., Leder, M., and Kauvar, AJ.: Hodgkin's disease involving optic nerve and brain. f. Neuro­surg. 21: 798, 1964. 27. Hautzer, N.W., Aiyesimoju, A, and Robitaille Y.: 'Primary" spinal intramedullary lymphomas: A re­view. Ann. Neural. 14: 62, 1983. 28. Williams, R.5., Crowell, RM., and Fisher, e.M., Davis, K., Lavyne, M.H., Ropper, AH., and Bre­mer, A.M.: Clinical and radiologic remission in reticulum cell sarcoma of the brain. Arch. Neural. 36: 206, 1979. 29. Onofrio, B.M., and Kernohan, J.W.: Primary me­ningeal sarcomatosis. A review of the literature and report of 12 cases. Cancer 15: 1197, 1962. 30. Hogan, M.J., Spencer, W.H., and Hoyt, W.F.: Pri­mary reticuloendothelial sarcomas of the orbital and cranial meninges. Am. f. Ophthalmol. 61: 1146, 1966. 31. Fine, E.j., and Mani, 5.5.: Amaurosis and primary reticulum cell sarcoma of the brain: Clinicopath­ologic study of a case. South. Med. f. 71: 338, 1978. 32. Burstein, S.D., Kernohan, J.W., and Uihlein, A: Neoplasms of the reticuloendothelial system of the brain. Cancer 6: 289, 1963. 33. Marmor, M.F., Egbert, R.P., Egbert, B.M., and Mar­mor, J.B.: Optic nerve head involvement with cy­tomegalovirus in an adult with lymphoma. Arch. Ophthalmol. 96: 1252, 1978. 34. Sanderson, P.A, Kwabara, T., and Cogan D.: Optic neuropathy presumably caused by vincristine ther­apy. Am. f. Opthalmol. 81: 146, 1976. 35. Fishman, M.L., Beau, S.e., and Cogan, D.: Optic Journal of Clinical Neuro-ophthalmology atrophy following prophylactic chemotherapy and cranial irradiation for acute lymphocytic leukemia. Am. /. Ophthalmol. 82: 571, 1976. 36. Perkins, D.G., and Rose, F.C: Optic Neuritis and Its Differential Diagnosis. Oxford University Press, 1979, pp. 32; 43. 37. Moseley, I.F., and Sanders, M.D.: Computerized Tomography in Neuro-opthalmology. W.B. Saunders, Philadelphia, 1982, p. 171. 38. Wallack, E.M., Reavis, W.M., and Hall, CD.: Pri­mary brain stem reticulum cell sarcoma causing dementia. Dis. Nerv. Syst. 38: 744, 1977. 39. Ruff, R.L., Petito, C, Rawlinson, D.G.: Primary cerebral lymphoma mimicking multiple sclerosis. Arch. Neurol. 36: 598, 1979. 40. Singh, A, Strobos, R.J., and Singh, B.M., Roth­baller, AB., Reddy, V., Puljic, S., and Poon, T.P.: Steroid-induced remissions in CNS lymphoma. Neurology 32: 1267, 1982. 41. Baxter, J.D., Harris, AW., Tomkins, G.M., and Cohen, M.: Glucocorticoid receptor in lymphoma cells in culture: Relationship of glucocorticoid kill­ing activity. Science 171: 189, 1971. 42. Penn, I.: Malignant Tumors in Organ Transplant March 1984 Purvin, Van Dyk Recipients. Springer, Berlin, Heidelberg, New York, 1970. 43. Louie, S., and Schwartz, R.S.: Immunodeficiency and the pathogenesis of lymphoma and leukemia. N. Engl. J. Med. 15: 117, 1978. 44. Snider, W.O., Simpson, D.M., Aronyk, K.E., and Nielsen, S.L.: Primary lymphoma of the nervous system associated with acquired immunodefi­ciency syndrome. N. Engl. J. Med. 308: 45, 1983. 45. Weekly Clinicopathological Case No. 32-1983, N. Engl. J. Med. 309: 359, 1983. Acknowledgment This work was supported in part by a fellowship award (Dr. Purvin) from Fight for Sight, Inc., New York, New York, in tribute to the memory of Hermann M. Burian, M.D. Write for reprints to: Valerie Purvin, M.D., Depart­ment of Ophthalmology, 702 Rotary Circle, Indiana University School of Medicine, Indianapolis, Indiana 46223. 23