Journal of Neuro-Ophthalmology, June 2007, Volume 27, Issue 2

Lymphoplasmacyte-Rich Meningioma Mimicking Idiopathic Hypertrophic Pachymeningitis

A 24-year-old man presented with long-term headache and progressive visual loss. Neuro-ophthalmic manifestations included finger counting acuity in both eyes, weakly reactive pupils, pale optic discs, and increased deep tendon reflexes. Brain MRI showed meningeal thickening that involved the optic nerves and chiasm and enveloped and displaced the brainstem as far caudally as the foramen magnum. The diffuse extensive nature of the lesion suggested an inflammatory process such as idiopathic hypertrophic pachymeningitis (IHP), but anterior temporal brain biopsy disclosed a relatively high proportion of meningothelial cells with islands of polyclonal inflammatory reaction consistent with a diagnosis of lymphoplasmacyte-rich meningioma (LRM), a rare variant. Among the 19 reported cases of LRM, none has shown as extensive a mass as seen in our patient. Distinguishing between LRM and IHP is important because these entities are treated differently.

ORIGINAL CONTRIBUTION Lymphoplasmacyte- Rich Meningioma Mimicking Idiopathic Hypertrophic Pachymeningitis Parima Hirunwiwatkul, MD, Jonathan D. Trobe, MD, and Mila Blaivas, MD, PhD Abstract: A 24- year- old man presented with long-term headache and progressive visual loss. Neuro-ophthalmic manifestations included finger counting acuity in both eyes, weakly reactive pupils, pale optic discs, and increased deep tendon reflexes. Brain MRI showed meningeal thickening that involved the optic nerves and chiasm and enveloped and displaced the brainstem as far caudally as the foramen magnum. The diffuse extensive nature of the lesion suggested an inflammatory process such as idiopathic hyper­trophic pachymeningitis ( IHP), but anterior temporal brain biopsy disclosed a relatively high proportion of meningothelial cells with islands of polyclonal inflammatory reaction consistent with a diagnosis of lymphoplasmacyte- rich meningioma ( LRM), a rare variant. Among the 19 reported cases of LRM, none has shown as extensive a mass as seen in our patient. Distinguishing between LRM and IHP is important because these entities are treated differently. (/ Neuro- Ophthalmol 2007; 27: 91- 94) The distinction between a primary inflammatory dural disorder, called idiopathic hypertrophic pachymenin­gitis ( IHP) ( 1) and a meningioma evoking a florid inflam­matory reaction, called a lymphoplasmacyte- rich meningioma ( LRM), ( 2- 14) may be difficult even on histopathologic grounds ( 12- 14). We present a case in which the brain was encased by a diffuse meningeal process that was clinically suspected to be IHP but proved to be a LRM on biopsy. It is the most extensive example of a LRM to be reported. CASE REPORT A 24- year- old African- American man had had headaches for several years before developing slowly Departments of Ophthalmology and Visual Sciences ( PH, JDT), Neurology ( JDT), and Pathology ( Neuropathology) ( MB), University of Michigan, Ann Arbor, Michigan. Address correspondence to Jonathan D. Trobe, MD, Kellogg Eye Center 1000 Wall Street, Ann Arbor, MI 49105; E- mail: jdtrobe@ umich. edu progressive visual loss in both eyes. His medical and family histories were negative. He took no medications and used no recreational drugs. Best- corrected visual acuity was finger counting in both eyes. Pupils reacted minimally to direct light but normally to a near target. There was no afferent pupil defect. The ocular adnexal examination was normal. The eyes were aligned with full versions, smooth pursuit, and no nystagmus. The biomicroscopic examination was normal and tensions were 21,17. Ophthalmoscopy disclosed mark­edly and diffusely pale discs bilaterally without swelling or pathologic cupping. Mentation was normal and affect was appropriate. Cranial nerves, apart from the optic nerves, functioned normally. The motor and sensory examinations were normal. Deep tendon reflexes were increased in all four limbs but not at the jaw. There was no clonus. The plantar reflexes were equivocal. Brain MRI brain showed a diffusely enhancing extra-axial mass extending from the planum sphenoidale down along the clivus to the foramen magnum ( Fig. 1). The pons was indented and displaced dorsally On T2 images, the mass was of intermediate signal intensity. The lateral ven­tricles were slightly enlarged. Magnetic resonance angiog­raphy ( MRA) of the brain and CT scans of the chest, abdomen, and pelvis were normal. A complete blood count ( CBC), erythrocyte sedimentation rate ( ESR), coagulation profile, liver and kidney chemistries, syphilis serology, angiotensin- converting enzyme ( ACE), antineutrophilic cytoplasmic antibodies ( ANCA), and urinalysis were normal. Continuous intracranial pressure monitoring for 48 hours showed normal pressure. Anterior temporal brain biopsy disclosed multiple small fragments of dura heavily and diffusely infiltrated by CD3- positive T lymphocytes, CD20- positive B- lymphocytes, and polyclonal plasma cells ( Fig. 2). Scattered throughout were conspicuous clusters of meningotheliomatous cells, some with whorls and psammoma bodies. The cells stained positively for vimentin and epithelial membrane antigen ( EMA). A larger portion of the biopsy showed features of meningotheliomatous and transitional meningioma with few lymphocytes; the meningiomatous cells again stained well for vimentin and EMA and demonstrated a low J Neuro- Ophthalmol, Vol. 27, No. 2, 2007 91 J Neuro- Ophthalmol, Vol. 27, No. 2, 2007 Hirunwiwatkul et al FIG. 1. MRI of the lesion. A. PrecontrastTI axial MRI shows a lesion isointense to brain that permeates the anterior, middle, and posterior fossae, involving the suprasellar cistern and cavernous sinuses and compressing the brain stem. B. Postcontrast T1 axial MRI shows strong homogeneous enhancement of the lesion. C. T2 axial MRI shows that the lesion is again isointense to brain. D. Postcontrast T1 coronal MRI shows symmetrical compression of the brain stem and extension into the foramen magnum. E. Precontrast T1 sagittal MRI shows that the mass displaces brain structures backwards and extends from the planum sphenoidale along the clivus to the foramen magnum. The signal characteristics of the lesion are consistent with meningioma or inflammation; the symmetry suggested inflammation. proliferation index of about 7% on Ki67 stain. No microorganisms or granulomas were detected. The biopsy was consistent with a diagnosis of LRM, a rare variant. Because there was a substantial inflammatory component, the patient was given 60 mg/ day prednisone and later 150 mg/ day azathioprine. However, after 6 months of this treatment, visual acuity declined to hand move­ments in both eyes although imaging features remained unchanged. Fractionated radiotherapy was begun. Six months later, visual function and general neurologic status were unchanged. Brain imaging showed a very slight reduction in the size of the mass. DISCUSSION Our patient had an extensive enhancing mass that wrapped the cerebrum and brain stem. Its principal clinical effect was progressive optic neuropathy, presumably from encasement of the optic nerves. The diffuse nature of the mass led to the clinical suspicion of a meningeal inflam­matory process, which was proved histologically to be wrong. The correct diagnosis was LRM, a process that is unresponsive to anti- inflammatory therapy. In our patient, islands of meningeal cells staining positively for vimentin and EMA indicated meningothelial proliferation. The exuberant meningeal inflammatory 92 © 2007 Lippincott Williams & Wilkins Idiopathich Hypertrophic Pachymeningitis J Neuro- Ophthalmol, Vol. 27, No. 2, 2007 FIG. 2. Histopathology from right temporal biopsy of the lesion. A. Lymphoplasmacytic inflammation of the dura with small clusters of meningioma cells ( arrows) ( hematoxylin and eosin stain, 200x). B. The predominantly lymphocytic inflammatory infiltrate stains positively ( brown) for common leukocytic antigen. The unstained islands are made up of meningioma cells ( immunoperoxidase stain, 200x). C. One of the large clusters of meningioma cells stains positively ( brown) for vimentin, an intermediate filament found in meningiothelial cells ( immunoperoxidase stain, 200x). D. The same cluster of meningioma cells has a low proliferation index, indicated by the sparse number of nuclei staining brown with Ki67, a measure of mitotic activity ( immunoperoxidase stain, 200x). reaction, believed to be a reaction to tumor antigens ( 5,11), is rare in meningioma but is a feature of LRM ( 2). This variant has been reported in 19 cases, which have had histopathologic features identical to those of our case ( 3- 14). The proportion of inflammatory and meningothelial components varies greatly among the reported cases ( 10). LRM tends to occur in younger patients, with the mean age of onset being 34 years ( 3). Most reported cases are much less extensive than ours, showing a nodular enlargement of the convexity or tentorial meninges. One case ( 12) was described as involving the skull base extensively, but imaging did not display its full extent. Our case is apparently much more extensive than previously reported cases, as it covered the territory from the falx cerebri through all three cranial fossae as far caudally as the foramen magnum. Because of its large size and lack of nodularity, the lesion in our patient was initially presumed to be an inflammatory lesion, either sarcoidosis or IHP. Ancillary testing and histopathology ruled out sarcoidosis. In review­ing the histopathology, a thought was given to IHP because of three previously reported cases of IHP that showed small islands of meningothelial proliferation within in­flammatory cells ( 15,16). The inflammatory process in those cases was believed to have induced meningothelial hyperplasia ( 17). After extensive histopathologic review, however, we determined that our case is more consistent with LRM because of the relatively large portion of 93 J Neuro- Ophthalmol, Vol. 27, No. 2, 2007 Hirunwiwatkul et al meningotheliomatous/ transitional meningioma cells with a low proliferation index. The distinction between IHP and LRM is important because these conditions are treated differently. IHP is treated with corticosteroids and corticosteroid- sparing agents ( azathioprine and methotrexate) ( 18). These agents are often effective unless the process is sclerosing. Intra­ventricular cytarabine ( 18) and lymphocytapheresis ( 19) have also been used, but the results were not impressive. LRM, on the other hand, is treated with surgical debulking except when the tumor is as extensive as that seen in our patient. Radiation therapy, the choice in unresectable meningiomas, may arrest growth but typically does not restore vision. REFERENCES 1. Kupersmith MJ, Martin V, Heller G, et al. Idiopathic hypertrophic pachymeningitis. Neurology 2004; 62: 686- 94. 2. Kleihues P, Burger PC, Scheithauer BW, eds. Histological Typing of Tumours of the Central Nervous System, 2nd ed. Berlin: Springer- Verlag; 1993: 33- 7. 3. Bruno MC, Ginguene C, Santangelo M, et al. Lymphoplasmacyte rich meningioma: a case report and review of the literature. JNeurosurg Sci 2004; 48: 117- 24. 4. Mizushima M, Tanaka Y, Kawakami S, et al. Lymphoplasmacyte- rich meningioma: a case report with histological and immunohistochem-ical studies. Brain Tumor Pathol 1997; 14: 59- 62. 5. Loiseau H, Pedespan JM, Vital A, et al. Lymphoplasmacyte- rich meningioma in a child: case report. JNeurosurg 1995; 83: 1075- 9. 6. Gi H, Nagao S, Yoshizumi H, et al. Meningioma with hyper­gammaglobulinemia: case report. J Neurosurg 1990; 73: 628- 9. 7. Stam FC, van Alphen HA, Boorsma DM. Meningioma with conspicuous plasma cell components: a histopathological and immunohistochemical study. Acta Neuropathol ( Berl) 1980; 49: 241- 3. 8. Banerjee AK, Blackwood W. A subfrontal tumour with the features of plasmocytoma and meningioma. Acta Neuropathol ( Berl) 1971; 18: 84- 8. 9. Yoneyama T, Kasuya H, Kubo O, et al. Lymphoplasmacyte- rich meningioma: a report of three cases and a review of the literature ( in Japanese). No Shinkei Geka 1999; 27: 383- 9. 10. Horten BC, Urich H, Stefoski D. Meningiomas with conspicuous plasma cell- lymphocytic components: a report of five cases. Cancer 1979; 43: 258- 64. 11. Rich JR, Winters WD. Tumour associated antigen in human meningioma. N EnglJ Med 1974; 290: 164. 12. Yamaki T, Ikeda T, Sakamoto Y, et al. Lymphoplasmacyte- rich meningioma with clinical resemblance to inflammatory pseudotu­mor: report of two cases. J Neurosurg 1997; 86: 898- 904. 13. Deprez M, Born J, Hauwaert C, et al. Idiopathic hypertrophic cranial pachymeningitis mimicking multiple meningiomas: case report and review of the literature. Acta Neuropathol ( Berl) 1997; 94: 385- 9. 14. Johnson MD, Powell SZ, Boyer PJ,. Dural lesions mimicking meningiomas. Hum Pathol 2002; 33: 1211- 26. 15. Kleiter I, Hans VH, Schuierer G, et al. Intraventricular cytarabine in a case of idiopathic hypertrophic pachymeningitis. J Neurol Neurosurg Psychiatry 2004; 75: 1346- 8. 16. Mirra SS, Tindall SC, Check IJ, et al. Inflammatory meningeal masses of unexplained origin. An ultrastructural and immunological study. J Neuropathol Exp Neurol 1983; 42: 453- 68. 17. Reichenthal E, Rubinstein AB, Shevach I, et al. Meningioma presenting at a site of a previously aspirated brain abscess. Acta Neurochir 1991; 109: 142^ k 18. Dumont AS, Clark AW, Sevick RJ, et al. Idiopathic hypertrophic pachymeningitis: a report of two patients and review of the literature. Can J Neurol Sci 2000; 27: 333^ 0. 19. Yamamoto T, Goto K, Suzuki A, et al. Long- term improvement of idiopathic hypertrophic cranial pachymeningitis by lymphocytaphe­resis. TherApher 2000; 4: 313- 6. 94 © 2007 Lippincott Williams & Wilkins