Conjunctival melanoma and melanocytic intra-epithelial neoplasia

Abstract

The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred in recent years. Primary acquired melanosis is now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia, for which an objective reproducible scoring system has been developed. Mapping and clinical staging of conjunctival disease has improved. Adjunctive radiotherapy and topical chemotherapy have made tumour control more successful, with reduced morbidity. Genetic analyses have identified BRAF and other mutations, which may predict responsiveness to new chemotherapeutic agents, for example Vemurafenib, should metastatic disease develop. Multicentre studies are under way to enhance survival prediction by integrating clinical stage of disease with histological grade of malignancy and genetic abnormalities. Such improved prognostication would not only be more relevant to individual patients, but would also provide greater opportunities for basic science research.

Figure 1

Conjunctival diagram for tumour mapping displaying the conjunctiva as a flat surface. The conjunctiva is divided into quadrants. The centre of the conjunctiva is the centre of the cornea. The limbus, bulbar conjunctiva, fornix, tarsal conjunctiva, eyelid margin, and skin are progressively more peripheral. Courtesy of Bertil Damato.

Figure 2

Clinical appearance of conjunctival melanosis: (a) freckle, (b) racial, (c) melanocytic intra-epithelial neoplasia (C-MIN) (d) invasive melanoma, and (e) pigmented squamous cell carcinoma.

Figure 3

Histology micrographs of conjunctival melanosis (haematoxylin and eosin): (a) freckle/racial, (b) C-MIN=1, (c) C-MIN⩾5, (d) naevus, and (e) melanoma.

Figure 4

Scoring system of C-MIN. The maximum score is 10. From Damato and Coupland, Expert Rev Anticancer Ther 2009. Published with permission from the authors.

Figure 5

C-MIN of the upper lid (a), and bulbar and forniceal conjunctiva (b). (c) Racial/complexion melanosis.

Figure 6

Histological micrographs demonstrating invasive C-MIN. Epithelioid cells are present, some of which are arranged in nests. The tumour cells invade the substantia propria. Haematoxylin and eosin (a and b). The neoplastic cells are positive for melan-A (c and d). Courtesy of Sarah E Coupland.

Figure 7

Surgical technique for excision of conjunctival tumours. Copied with permission from Damato and Coupland. Expert Rev. Anticancer Ther 2009.

Figure 8

Examples of CoMs treated with radiotherapy: (a1) right CoM: involving the nasal bulbar conjunctiva, caruncle, and fornices, (b1) complete resolution of the tumour after excision, proton beam radiotherapy, and topical chemotherapy, (a2) right nasal bulbar CoM, (b2) same patient in (a2) after excision, ruthenium brachytherapy and topical mitomycin C.