Primary and secondary tumours of the optic nerve, with emphasis on invasion of uveal malignant melanoma

Abstract

Tumours of the optic nerve may originate in the optic nerve itself (i.e. primary tumours) or in structures adjacent to the optic nerve (i.e. secondary tumours). Furthermore, leukaemic infiltration and tumour metastases from distant solid tumours are also found in the optic nerve (i.e. secondary tumours). Large surveys have described primary optic nerve tumours and their treatment modalities whereas secondary tumours have received little attention. Most reported work-ups have been based on material from referral centres and specialized departments. The correlation between invasion of the optic nerve in uveal melanoma and the risk of dying from the disease is not fully elucidated. The impact on prognosis may be correlated with tumour cells left in the proximal nerve after enucleation. In addition, melanomas with secondary invasion of the optic nerve may be a highly malignant invasive subcategory of uveal melanomas. Clinical factors that should make the ophthalmologist aware of optic nerve invasion when investigating a uveal melanoma would be most important. Melanomas with invasion of the optic nerve may histopathologically display different invasive patterns and represent different types of uveal melanoma. A subtype of uveal melanoma with preponderance for neural invasion may exist. Such a subtype has been identified for cutaneous melanoma (desmoplastic/neurotropic). In order to investigate tumours of the optic nerve in a known population, we studied all surgically removed tumours of the optic nerve in Denmark during a study period of 25 years. Furthermore, in order to elucidate questions of secondary invasion of the optic nerve in uveal melanoma, all eyes enucleated with a uveal melanoma and optic nerve invasion in Denmark between 1942 and 2001 (n = 157) were investigated. Tumours of the optic nerve in children were dominated by optic glioma and invasion from retinoblastoma, whereas tumours in adults mainly comprised optic nerve sheath meningioma and invasion from uveal melanoma. Optic nerve invasion of uveal melanoma was found in 1 in 20 patients. Increased intraocular pressure and juxtapapillary location were associated with both prelaminar/laminar and postlaminar invasion of the optic nerve. Furthermore, age older than 70 years, reduced vision to light perception, non-visible fundus and large tumour size were associated with postlaminar invasion. Only patients with optic nerve invasion had metastases to the CNS, kidney and heart. Histopathological features associated with optic nerve invasion were focal retinal invasion, neovascularization of the chamber angle and scleral invasion. Furthermore, non-spindle cell type and rupture of the inner limiting membrane were both associated with postlaminar invasion. The optic nerve was invaded in four different ways: 1) by tumour extension from the neuroretina through the lamina cribrosa 2) by direct extension into the optic nerve head between Bruch's membrane and the border tissue of Elschnig 3) by direct invasion through the border tissue of Elschnig and 4) by spreading along the inner limiting membrane to the optic nerve head and through the lamina cribrosa. Most melanomas with invasion of the optic nerve were large juxtapapillary tumours invading the nerve because of their close location to the nerve, but a subcategory of neurotropic uveal melanomas with a diffuse invasive growth pattern was also found. These tumours invade the optic nerve and retina regardless of tumour size and location. Invasion of the optic nerve had no impact on the prognosis per se, but was seen in association with a series of other prognostic factors (e.g. cell type, extrascleral extension). I wish to express my sincere gratitude to my invaluable mentors Associate Professor Steffen Heegaard MD and Professor Jan Ulrik Prause MD for introducing me to the fascinating world of ophthalmology. Their optimism and encouraging guidance in the fields of research and pathology has been a great inspiration. This study was made possible by grants from The Danish Cancer Society, Værn om Synet, Synoptikfonden, Købmand M. Kristian Kjær og hustru Margrethe Kjær født la Cour-Holmen's Fond, Overlærer Svend Hansen's Fond, Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mlndelegat, Alcon and H:S Generelle Forskningspulje.