positive for both neurilemmomas and neurofibromas; however, neurilemmomas show a more generalized and stronger staining pattern than neurofibromas, since S-100 stain does not stain fibroblasts. Under electron microscopy examination, the Lüse bodies are seen in neurilemmomas and not in neurofibromas; Lüse bodies are aggregates of long-spaced or broad-banded collagen with an axial periodicity of 130 nm [186]. They were considered in the past as pathognomonic of neurilemmomas, but it is now known that they occur in other tumors, such as basal and squamous carcinomas and nevoid tumors.

Since surgical removal of neurilemmoma may lead to rupture, the possibility of donor sclera homografting must always be kept in mind [186].

8.4.7Pigmented Tumors

Pigmented tumors of the episclera are common. The differential diagnosis must include congenital episcleral melanosis, acquired episcleral melanosis, and nerve loops of Axenfeld. Melanocytes are normally present in the episclera and in sclera lamellae adjacent to and along the course of vascular and neuronal transcleral channels. An increased number of melanocytes may exist in these locations in association with these congenital and acquired benign pigmentations.

Ocular melanocytosis (melanosis oculi) is a congenital unilateral pigmentation of episclera, sclera, and uveal tract. There is an increased incidence of uveal melanomas in the involved eye. Oculodermal melanocytosis (nevus de Ota) is ocular melanocytosis associated with ipsilateral pigmentation of the periocular tissues. It occurs more often in the nonwhite races. Malignant transformation is not common.

Acquired melanosis is a flat, diffuse, and slowly growing melanotic lesion which may appear either in the skin or in the conjunctivaepisclera. Biopsy should be performed before therapy is planned. Management is conservative unless there is malignant transformation. In the conjunctiva-episclera, 17% of the melanosis may progress to melanoma; mortality in patients with these melanomas is up to 40% [187].

A branch of the long posterior ciliary nerve (intrascleral nerve loop of Axenfeld) may loop out through the sclera in the region between the limbus and the insertions of the recti muscles, forming a nodule which is often darkened with melanocytes. The nerve loop, may be mistaken clinically for a melanotic tumor or for a foreign body [188], and histologically for a neurofibroma, especially when the nerve is associated with neurilemmal or connective tissue proliferation.

8.4.7.1 Nevus

This lesion is present at birth but may not be noticed until middle childhood. Approximately 33% of conjunctival–episcleral nevi are not pigmented. Both pigmented or nonpigmented nevi are diffuse and flat lesions localized close to the limbus and sometimes they may look like nodular episcleritis. More than 50% of conjunctival– episcleral nevi have epithelial cysts which can be clinically evident [189]. Increased melanogenesis in nevi can result from pituitary stimulation (puberty, pregnancy, adrenal insufficiency), physical irritation (sun exposition, trauma, inflammation), and coexisting malignant melanoma. Malignant transformation of nevi to melanomas is rare; a great increase in vascularity without obvious growing and increase in pigmentation may be the first signs before extension in the conjunctiva–episclera and to the sclera occurs. The episcleral vessels radiate from the mass rather than skirt it, as in inflammatory conditions, such as necrotizing scleritis [38]. Biopsy should be performed before therapy is planned. Management of nevi requires photography at regular intervals to look for the possibility of malignant transformation. Therapy is conservative unless it is cosmetically intolerable, in which case surgical removal is the proper treatment. Surgical removal also eliminates the remote chance of malignant change.

8.4.7.2 Melanocytoma

Melanocytoma of the conjunctiva–episclera may arise from nevi, from acquired melanosis, or without preexisting lesion. They also may result from extension of melanoma arising in ciliary body, or the skin or mucous membranes anywhere