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Show / ol/ mal of Clinical Nellro- ol'htlwlmoh1gy gel: 98- J04. 1989. Ghost- Cell Tumor of the Optic Chiasm Primary eNS Lymphoma Roger S. Gray, M. D., James J. Abrahams, M. D., Thierry J. Hufnagel, M. D., Jung H. Kim, M. D., Robert L. Lesser, M. D., and Dennis D. Spencer, M. D. © 1989 Raven Press, Ltd., New York A case of steroid- responsive malignant lymphoma of the optic chiasm is reported in a 58- year- old woman presenting with subacute vision loss, headaches, and decreased hearing. The exquisite sensitivity of magnetic resonance imaging ( MRI) of the parasellar area and the usefulness of MR- directed stereotactic biopsy in identifying a chiasmatic lesion are shown. Primary CNS lymphomas are briefly reviewed. Ophthalmologists will be asked to evaluate patients with malignant lymphoma of the optic chiasm with increased frequency in the future, as CNS lymphomas are expected to be the most common neurological neoplasm by 1991. Key Words: Malignant lymphoma- Optic chiasm. From the Department of Ophthalmology and Visual Science ( R. S. G., T.}. H., R. L. L.), and the Sections of Neuroradiology a. J. A.), Neuropathology ( T.}. H., }. H. K.), and Neurosurgery ( D. D. s.), Yale University School of Medicine, New Haven, Connecticut. Address correspondence and reprint requests to Dr. Roger S. Gray, Yale University, Depar~ ment of Ophthalmology, School of Medicin", 330 Cedar Stref'!, New Haven, CT 06510- 8061, U ' C, P. 98 Primary CNS lymphomas are uncommon tumors, accounting for less than 1% of primary brain tumors ( 1- 3). However, the incidence of these lesions has tripled in the last decade, partly as a result of the increased use of immunosuppressive therapy with organ transplantation and partly due to the AIDS epidemic ( 2- 4). Most commonly, primary CNS lymphomas are seen in the basal ganglia and frontal lobes ( 2). The association of a primary CNS lymphoma with uveal and vitreal disease is well known, yet symptomatology from anterior optic pathway involvement is distinctly unusual and solitary chiasmatic involvement has not previously been shown. Radiologic regression as shown by computed tomography ( CT) and clinical improvement of the primary CNS lymphoma ( ghost tumor) following steroid treatment have been reported ( 5- 21). Chastcell tumors is used to describe such phenomena. To our knowledge, ghost- cell tumors have not been demonstrated using MRI. We report a unique case of a ghost- cell tumor of the optic chiasm presenting as subacute monocular visual loss. Successive MRI scans exquisitely demonstrated the chiasmatic lesion's decrease in size in response to steroid treatment. Diagnosis was obtained by MRIdirected stereotactic biopsy. CASE REPORT A 58- year- old white woman presented to her ophthalmologist in August 1987 with complaints of decreasing vision in the left eye, left- sided headache, and left- sided hearing loss. Visual acuity was 20/ 20 in the right eye and 20/ 30 in the left eye. Over the following 4 weeks, her vision deteriorated to 20/ 200 in the left eye. A CT scan at that time revealed an enhancing mass in the region of the optic chiasm ( Fig. 1); an MRI scan demonstrated the OPTIC GHOST- CELL TUMOR 99 FIG. 1. Axial CT scan through level of optic chiasm ( September 28,1987). A: Unenhanced CT scan demonstrates increased attenuation ( whiter) and enlargement of the optic chiasm ( open white arrows). The small white arrows show the suprasella cistern. B: An enhanced CT scan demonstrates enhancement of the optic chiasmatic lesion ( open white arrows). The short white arrow shows the middle cerebral artery. The long white arrow shows the anterior cerebral artery. A lesion of increased attenuation on the unenhanced CT scan that homogeneously enhances after i. v. contrast is typical of a lymphoma. lesion to be encompassing the chiasm ( Fig. 2). The patient was started on high- dose oral prednisone; 2 weeks later, she underwent a diagnostic craniotomy. No tumor mass was encountered. The headache disappeared but her vision and hearing loss remained unchanged. A repeat MRI scan 3 months later Oanuary 14, 1988) revealed that the mass had regressed significantly ( Fig. 3). The patient became Cushingoid secondary to steroids, and prednisone therapy was therefore tapered. Six weeks later, another MRI scan was performed for recurrent headaches and demonstrated further enlargement of the mass ( Fig. 4). The patient's steroids were then restarted, and she was admitted to our institution for an MRI- directed stereotactic biopsy. The patient's past medical history was unremarkable; family history was significant for breast and lung cancer. Her best corrected vision was 201 25 in the right eye and 20/ 100 in the left. Pupils were symmetric, and no afferent pupillary defects were present. Left- sided hearing loss and headaches continued. Slit- lamp examination, applana-tion pressures, Amsler grid testing, and Goldman fields were all normal. Octopus automated perimetry revealed very mild depression in both eyes, thought to be nonspecific for a neurological defect ( Fig. 5). Color vision was abnormal in both eyes as measured by HRR plates. Fundus examination revealed the vitreous to be clear and both discs to be slightly pale, the left paler than the right. Maculas, vessels, and periphery were normal. General physical examination was noncontributory; no lymphadenopathy or organomegaly was present. All blood studies were normal. Chest x- ray film was clear. Lumbar puncture revealed scattered small T lymphocytes, mainly Leu- 4- positive with a few scattered kappa- and lambda- positive cells present. A gallium scan was positive in the parachiasmatic area. After 2 weeks of steroid therapy, an MRI scan was performed in preparation for the stereotactic biopsy, again revealing significant regression in tumor size ( Fig. 6). An MRI- guided stereotactic biopsy was then performed on the remaining small mass emerging from the superior aspect of the I Ctill Neuro- ophthalmol. Vol. 9. No. 2, 1989 100 R. S. GRAY ET AL. FIG. 2. MRI of optic chiasm demonstrating enlargement of the chiasm ( October 7,1987). A: Sagittal T1- weighted image. Seen are the chiasmatic lesion ( curved arrows), infudibulum ( long arrow), and pituitary gland ( open arrow). B: Coronal T1- weighted image. See are the chiasmatic lesion ( black arrows), infundibulum ( long arrow), pituitary gland ( open arrow), and cavernous carotid artery ( bold white arrows). chiasm and presenting in the floor of the third ventricle. Pathological examination revealed fragments of white matter infiltrated by large and round hyperchromatic neoplastic lymphocytes with scant cytoplasm and occasional prominent nucleoli, consistent with eNS lymphoma. The tumor cells showed a prominent perivascular arrangement with permeation through vascular walls. Smaller lymphocytes were sprinkled throughout the tissue sampled. Immunohistochemistry revealed a strong positive reaction by tumor cells for leukocyte common antigen ( Fig. 7). The patient's postoperative course was complicated by diverticulitis and a perforated colon; sections from the surgical repair of the colon were negative for lymphoma. The patient underwent cranial- spinal irradiation with 5,600 rads and a tapering dose of corticoste- FIG. 3. MRI of optic chiasm ( January 14,1988). Note that in response to steroids, the lesion has diminished in size; compare to Fig. 2. A: Sagittal T1- weighted image. Seen are the chiasm ( curved white arrow), infundibulum ( long arrow), and pituitary gland ( open arrow) B: Coronal T1- weighted image. Seen are the optic chiasm ( white arrowhc;;: vlc.) , nf"',,:'; rJ'Ji'Jrn iI,., n'l cJrrO'N) and pituitary gland ( open arrow). B FIG. 4. MAl of optic chiasm ( February 26, 1988) demonstrating that the lesion has again increased in size in response to steroid tapering. A: Sagittal T1- weighted image. Seen are the chiasmatic lesion ( curved white arrows), infundibulum ( long arrow). and pituitary gland ( open arrow). B: Coronal T1- weighted image. The chiasmatic lesion is seen ( small arrowheads). Notice that the chiasmatic lesion has caused partial obstruction of the foramen of Monro with resultant enlargement of the left lateral ventricle ( bold solid arrowhead). Also seen are the infundibulum ( long arrow), pituitary gland ( open arrowhead), cavernous carotid artery ( curved solid arrow), and supraclinoid carotid artery ( curved open arrow). 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C; f'LUc; UA.; lOPrOS ( R. M. S.): 4.108 OIFFfIU. PrOO: ;'~ IIU ( SOFl1: AL MIp\ US AC;- UA. U • ~ YIA.; IOPrO (- 4 08 o O[ V 1A.;' IO" ~ ••••• 08 • ~ VIA":' IUPrO 1" ••• 19 011 • O[ YIA":' IOPrO ) 19 01 • US. Df.' EC;- Huc: UA;' IOLlo: S ( R.":. S.): 1. SD8 FIG. 5. A: Central 30 0 fields reveal mild scattered los~ in no diagnostic patt~ rn. B: Periphera. 1 60° fields reveal mild svmmetricaLnasaJ loss and very mild temporal loss In both eyes, not speCifiC for neurological defect. 102 R. S. GRAY ET AL. FIG. 6. MRI of optic chiasm ( March 10, 1988) shows that the lesion has again diminished in size in response to steroids; compare with Fig. 4. A: Sagittal T1- weighted image. Seen are the optic chiasm ( curved arrow), infundibulum ( long arrow), and pituitary gland ( open arrow). B: Coronal T1- weighted image. Seen are the optic chiasm ( short solid arrows), infundibulum ( long arrow), and pituitary gland ( open arrow). roids. Six months after surgery, the vision and leftsided hearing losses have remained unchanged. She has had no further headaches. DISCUSSION Chiasmatic lymphoma accounting for acute decrease in vision has been described elsewhere by Miller and Iliff ( 22). In their case, the patient presented with visual loss secondary to a chiasmatic mass as the initial symptom of systemic Hodgkin's disease. With our patient, visual fields at the time of the large chiasmatic tumor were atypically normal. No pupiJlarv abnormalities were present. Opti, nerve invnh, ppwnt was indicated bv abnormal color vision and disc pallor. The patient's headaches and hearing loss are probably explained by leptomeningeal involvement within the posterior fossa, undetected by the MRI and CT scans. Mechanisms postulated for the nonsustained oncolytic effects of steroids seen on CT imaging of primary CNS lymphomas include direct edema of surrounding tissue, direct lysis of lymphocytes, and inhibition of lymphocyte cellular metabolism ( 10,23,24). Because CNS lymphomas occur in greater frequency in immunosuppressed patients, it is possible that corticosteroids alter the biological activity of the tumor, the response varying as a function of the immunologic competence of the host ( 6,25). Sequential MR imaging revealed significant regression of the tumor mass secondary to steroid therapy. Other entities besides lymphomas that are sensitive to the oncolytic effects of steroids include atypical brain infarctions, multiple sclerosis ( 26), sarcoidosis ( 27), and primary and secondary metastatic brain tumors ( 28). In this patient, primary CNS lymphoma and CNS sarcoidosis were considered the most likely diagnoses. MRIdirected stereotactic brain biopsy was used to differentiate between them. Over the years, nosologic controversies have led to confusion in the naming and recognition of primary CNS lymphomas. With the advent of immunohistochemical techniques, these tumors, which had variously been termed reticulum- cell sarcoma, III icrogliollla, or perithelial sarcoma, have been recognized as non- Hodgkin's lymphomas. Most of them are B cell lymphomas although they can show T cell markers ( 1,3,29). Upon routine histopathology, their morphology recapitulates that of their systemic counterparts ( i. e., lymphocytic, histiocytic, or immunoblastic) ( 1,3). However, two cardinal features are virtually diagnostic of primary CNS lymphoma: the concentric infiltration of tumor cells around blood vessels, as observed in our case, and the presence of concentric rings of dense perivascular reticulin fibers. Most primary CNS lymphomas present as solitary or multicentric supratentorial nodules, but they may appear restricted to the leptomeninges, Virchow- Robin spaces, or periventricular area. Yet, as illustrated in our case, preoperative cerebrospinal fluid cytology is rarely positive. The close association between intraocular and CNS lymphoma has been emphasized in a study by Rockwood et al, suggesting a multicentric origin of the " reticulum- cell sarcoma" of the eye and CNS ( 30). In reported cases of combined intraocular and CNS lymphoma, ocular symptomatology OPTIC GHOST- CELL TUMOR 103 FIG. 7. Tumor cells permeating through blood vessel ( arrow) show strong staining for leukocyte common antigen ( immunoperoxidase. x 100). preceded CNS signs in 77.8% of cases; CNS involvement preceded ocular symptomatology in 19.4% of cases. CNS disease developed from 5 months to 4.5 years prior to the onset of eye disease. Of note is that following hemiparesis, papilledema is the most common presenting sign of all primary CNS lymphomas ( 1). Primary CNS lymphomas are aggressive tumors and invariably recur. Treatment with whole- brain irradiation is associated with median survivals of less than 1 year ( 3). The use of combination chemotherapy with blood- brain barrier modification may increase survival in the future. In conclusion, this case describes a steroidresponsive, primary CNS chiasmatic lymphoma accounting for a relatively rapid decrease in vision. It illustrates the exquisite sensitivity afforded by MR imaging of the parasellar area and the usefulness of MRI- directed stereotactic brain biopsy in identifying a chiasmatic lesion. Finally, vision loss with an intracerebral mass responsive to steroids should alert the ophthalmologist to the possibility of a primary CNS lymphoma. 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