BritishJournal ofOphthalmology 1993; 77: 313-314 313 PERSPECTIVE Br J Ophthalmol: first published as 10.1136/bjo.77.5.313 on 1 May 1993. Downloaded from Orbital meningiomas: surgery, radiotherapy, or hormones? Orbital meningiomas generally arise from the sphenoid and Radiotherapy cause ophthalmic problems by virtue of an expanding mass As with many slowly dividing tumours, high doses of near the orbital apex. These benign tumours often have a soft radiotherapy (between 50 and 100 Gy) appear necessary to tissue component within the orbit, cranium, or temporalis affect the growth of meningiomas."245 Such doses carry two fossa (Fig 1) and may induce hyperostosis of the postero- small, but significant, risks - namely, the induction of lateral wall ofthe orbit. malignant transformation within the parent meningioma and Symptoms are generally caused by displacement of the the formation of new tumours, either meningiomas or globe - with diplopia or progressive proptosis - or compres- sarcomas. sion ofnerves and vessels at the orbital apex. Embarrassment Adequate radiotherapy for sphenoidal meningiomas is of flow through orbital veins can lead to enlargement of the further complicated by the intimate relationship between the episcleral vessels and chemosis, while compression of the tumour and the optic nerve. Visual failure from neoplastic third to the sixth cranial nerves at the superior orbital fissure compressive optic neuropathy becomes evident only after may cause neurological deficit. Narrowing of the optic canal marked loss of optic nerve microvasculature and neurons; by tumour or hyperostosis causes the serious complication of yet further damage to the optic nerve blood supply from visual loss; such loss is frequently slow and steadily progres- tumour irradiation is, therefore, likely to exacerbate visual sive, but may show periods offaster progression ('stuttering' loss. visual loss). Treatment of sphenoidal meningiomas may not be required in the elderly or where the symptoms are minor and Hormones and tumour growth only slowly progressive. However, the currently available Epidemiological evidence gained over several decades has treatments are often unsatisfactory for younger patients with suggested that growth of intracranial meningiomas is significant visual impairment and for patients with grossly influenced by female hormones. The tumours are more than disfiguring proptosis. twice as common in women as in men36 and the growth of(or symptoms caused by) some ofthese tumours increases during pregnancy and may lessen after the delivery or termination of Surgery pregnancy."-" Hormonal sensitivity for meningiomas is Surgical resection of intracranial meningiomas is generally further suggested by reports of an association between the recognised to be the treatment of choice, although such occurrence of meningiomas and breast cancer,6'3 14 a large surgery may be impossible or may carry high morbidity.'2 proportion ofbreast tumours having hormonal receptors and http://bjo.bmj.com/ Sphenoidal meningiomas are intimately related to the demonstrating sensitivity to oestrogens. Furthermore, anterior visual pathways, superior orbital fissure, and to the women with meningiomas, as with other hormonally sensi- frontal and temporal lobes; resection ofthese extensive, deep tive tumours (such as breast or endometrium'5), have an seated lesions is generally incomplete and the morbidity is increased incidence of obesity. 16 17 greater than that for many other intracranial meningiomas.3 A mechanism for the link between meningiomas and Where sphenoidal wing meningiomas are slow growing, sensitivity to female hormones was first suggested by the especially in the elderly, surgical efforts may usefully be demonstration ofoestrogen receptors in some meningiomas. 18 on September 25, 2021 by guest. Protected copyright. directed towards the 'camouflage' of proptosis and preven- However, later investigations'9-19 have shown such tumours tion ofcorneal exposure: adequate recession ofthe retractors to predominantly contain progesterone, rather than in the upper and the lower eyelids, together with closure of oestrogen, receptors (generally >70% and <20% of the lateral (and occasionally medial) canthus, are oculoplastic studied tumours, respectively); this is in contrast to breast procedures ofparticular value in such cases. cancer, where oestrogen receptors predominate. Other receptors, such as those for androgens,3031 somatostatin,32or epidermal growth factors,33 have been demonstrated within meningiomas. Tissue from meningiomas can be established in culture and has allowed the assessment of hormonal and autocoidal effects upon tumour growth.3'3110 Substances thus investigated include several progestogens (progesterone, medroxyprogesterone, norethisterone), oestradiol, dihydrotestosterone (an androgen), hydrocortisone, insulin, bromocriptine (a dopamine agonist), and various growth factors (epidermal, fibroblast, platelet derived). Many also report the effect of antagonists to these substances - to progestogens (RU486), oestrogens (tamoxifen), and to androgens (cyproterone and 1 a-hydroxyprogesterone). Unfortunately the results from in vitro studies are frequently contradictory, showing marked variation in the proportion of responsive tumours, marked variation between tumours in Figure I Right sphenoidal wing meningioma within the orbit, middle the sensitivity to drugs, and often opposite responses from cranialfossa, and temporalisfossa. different tumour lines. 314 Rose Hormones and clinical therapy cranial meningiomas occurring about the optic chiasm. Surg Clin North Am 1951; 31: 1225-33. The observation that patients with meningiomas often 9 Bickerstaff ER, Small JM, Guest IA. The relapsing course of certain worsen during pregnancy led to the premise that growth of meningiomas in relation to pregnancy and menstruation. J Neurol Neurosurg be sensitive to the levels of circulat- Psychiatry 1958; 21: 89-91. these tumours may high 10 Michelsen JJ, New PFJ. Brain tumours and pregnancy. J Neurol Neurosurg Br J Ophthalmol: first published as 10.1136/bjo.77.5.313 on 1 May 1993. Downloaded from ing progestogens. This view was strengthened by a study in Psychiatry 1969; 32: 305-7. 11 Manganiello PD, Meltz RC, Andros GJ. Probable parasellar meningioma in a which cells from a human meningioma were implanted into pregnant woman. Obstet Gynecol 1979; 53: 43-6. athymic, immunologically 'nude' mice: control mice showed 12 Roelvink NCA, Kamphorst W, van Alphen HA, Rao BR. Pregnancy-related primary brain and spinal tumors. Arch Neurol 1987; 44: 209-15. tumour growth, whereas those treated with an anti- 13 Schoenberg BS, Christine BW, Whisnant JP. Nervous system neoplasms and progesterone drug, mifepristone (RU38486 or RU486), primary malignancies of other sites. The unique association between meningiomas and breast cancer. Neurology 1975; 25: 705-12. demonstrated a significant reduction in tumour size.4' 14 Miller RE. Breast cancer and meningioma.J SurgOncol 1986; 31: 182-3. Clinical investigations have demonstrated that pretreat- 15 Henderson BE, Ross RK, Pike MC, Casagrande JT. Endogenous hormones as a major factor in human cancer. Cancer Res 1982; 42: 3232-9. ment of patients with the progesterone agonist medroxypro- 16 Schnegg JF, Gomez F, LeMarchand-Beraud T, de Tribolet N. Presence of sex gesterone acetate (MPA) reduces progesterone receptor steroid hormone receptors in meningioma tissue. Surg Neurol 1981; 15: 415-8. activity within meningiomas,4' but the agonist megestrol 17 Bellur SN, Chandra V, Anderson RJ. Association ofmeningiomas with obesity. would appear to be without effect on tumour growth when Ann Neurol 1983; 13: 346-7. 18 Donnell MS, Meyer GA, Donegan WL. Estrogen-receptor protein in intra- administered for periods of between 1 month and 1 year.43 In cranial meningiomas.J Neurosurg 1979; 50:499-502. the latter study there were several side effects and the drug 19 Tilzer LL, Plapp FV, Evans JP, Stone D, Alward K. Steroid receptor proteins in human meningiomas. Cancer 1982; 49:633-6. had to be discontinued in some patients. Likewise, treatment 20 Markwalder TM, Zava DT, Goldhirsch A, Markwalder RV. Estrogen and of patients with tamoxifen, an oestrogen antagonist, was progesterone receptors in meningiomas in relation to clinical and pathological features. SurgNeurol 1983; 20:42-7. without significant effect upon tumour growth.'" 21 Vaquero J, Marcos ML, Martinez R, Bravo G. Estrogen- and progesterone- More recently, however, it has been shown that some receptor proteins in intracranial tumors. Surg Neurol 1983; 19: 11-3. 22 MartuzaRL, Miller DC, MacLaughlin DT. Estrogen and progestin binding by patients get a useful response, either subjective (with cytosolic and nuclear fractions ofhuman meningiomas.I Neurosurg 1985; 62: improved symptoms) or objective (with reduced tumour size 750-6. 23 Ironside JW, Battersby RDE, Dangerfield VJM, Parsons MA, TimperleyWR, on computed tomography (CT)), in response to systemic Underwood JC. Cryostat section assay of oestrogen and progesterone mifepristone.45 Although a mild therapeutic response was receptors in meningiomas: a clinicopathological study. J Clin Pathol 1986; 39:44-50. observed in five of 13 patients, most experienced significant 24 Lesch KP, Fahlbusch R. Simultaneous estradiol and progesterone receptor side effects such as nausea, fatigue, hot flushes, alopecia, or analysis in meningiomas. Surg Neurol 1986; 26: 257-63. 25 Lesch KP, Schott W, EnglHG, Gross S, Thierauf P. Gonadal steroid receptors gynaecomastia.45