B Damato

Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing

Background:The absence of BRCA1-associated protein 1 (BAP1) expression in uveal melanoma (UM) is associated with metastatic progression and reduced survival. In this study, we examine nuclear BAP1 (nBAP1) protein expression in primary UMs (PUMs) that show both ‘typical’ and ‘atypical’ clinical courses according to their chromosome 3 status, and secondary hepatic metastatic UM (MUM), correlating the results with histological, clinical and survival data.Methods:Nuclear BAP1 expression was immunohistochemically assessed in tissue microarrays (TMAs) of: (a) 68 PUM patients, who had been treated surgically; and (b) 13 MUM patients, with 5 cases being paired with primary tumour tissue. All cases were fully annotated. The percentage of tumour cell nuclei staining positively for BAP1 was scored by independent observers.Results:Nuclear BAP1 protein expression was absent in 35 out of 68 (51%) PUM patients, correlating strongly with poor prognostic clinicopathological and genetic parameters and reduced survival (Log rank, P<0.001). Lack of nBAP1 expression importantly identified a subset of ‘atypical’ PUM patients with disomy of chromosome 3 but with unexpected metastatic relapse. Nuclear BAP1 expression was absent in 10 out of 13 (77%) MUM and expression was concordant in all paired PUM and MUM patients.Conclusions:Absent nBAP1 protein expression is an independent survival predictor for UM patients, easily examined using immunohistochemistry.

An audit of conjunctival melanoma treatment in Liverpool

PurposeTo evaluate treatment of conjunctival melanomas at the Ocular Oncology Service in Liverpool.MethodsWe included 40 patients initially treated at our centre for invasive conjunctival melanoma and 36 patients referred for salvage therapy after surgery elsewhere. Patients underwent local excision or radiotherapy. Adjunctive cryotherapy for invasive and intra-epithelial neoplasia was abandoned in favour of ruthenium brachytherapy and mitomycin C chemotherapy, respectively. Tumours were staged according to circumferential spread, basal diameter, and histological thickness.ResultsThe 40 previously-untreated tumours were confined to bulbar conjunctiva in 31 patients and involved extrabulbar conjunctiva in 9, affecting caruncle in 6 of these. All eyes were conserved, most retaining initial visual acuity. Invasive conjunctival recurrence, which occurred in six patients, was more likely with medial tumours (Log-rank, P=0.004) and if treatment did not include radiotherapy (Log-rank, P=0.03). Four patients died of metastases, all with caruncular involvement. Of the 36 patients referred for salvage therapy after previous surgery, 11 had no visible tumour, 9 had only intra-epithelial neoplasia, and 16 had invasive melanoma, which was recurrent in seven. After salvage therapy, five patients died, all of whom were referred with recurrent invasive tumour and only one of whom had caruncular involvement.ConclusionsExcision of invasive melanoma with adjunctive brachytherapy and topical chemotherapy achieved high rates of local tumour control with little ocular morbidity. Without caruncular involvement, disease-specific mortality was rare unless the patient was referred after a surgical procedure. Our results suggest that inadequate surgical intervention increases risks of local recurrence and metastatic death.

Conjunctival melanoma and melanocytic intra-epithelial neoplasia

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.

Differences in uveal melanomas between men and women from the British Isles

PurposeThe purpose of this study is to compare uveal melanomas (UMs) in men and women.MethodsThe Liverpool Ocular Oncology Centre (LOOC) database was reviewed. Patients treated for UM at the LOOC between 1993 and 2010 were selected. Differences between sexes were identified using the χ 2-test for categorical variables and the Mann–Whitney test for continuous variables.ResultsThe 3380 patients comprised 1685 women and 1695 men. The tumours were considered clinically to have arisen in choroid in 89.5%, ciliary body in 5.3%, and iris in 5.2%. Tumours in women were less likely to originate in choroid (87.2 vs91.7%; P<0.001) and showed more circumferential spread in ciliary body (P<0.001) and iris (P=0.003). Tumours in men were more likely to extend to within 3u2009mm of optic disc or fovea (46.3 vs39.0%, P<0.001), showing more extensive optic-disc involvement (P<0.001). The median largest basal tumour diameter was 12.2u2009mm in men and 11.9u2009mm in women (P=0.001). The tumour thickness had a median of 4.4u2009mm and 3.8u2009mm in men and women, respectively (P=0.015). The 180 ciliary body tumours occurred in 112 women and 68 men. In these, the prevalence of extraocular spread was higher in women (19.6 vs8.8%; P=0.052). The 175 iris melanomas were more common in women than men (103 vs72, respectively).ConclusionsIn men, UMs tend to be larger and more posterior than in women.

Primary B-cell lymphoma of the ciliary body with 360° ('ring'-like) growth pattern.

Sir, n nThere are few reports of anterior uveal non-Hodgkin lymphomas (NHL), which mainly involve the iris.1, 2, 3, 4, 5 Uveal lymphomas affecting almost exclusively the ciliary body (CB) are extremely rare. We describe a case of B-NHL with 360° infiltration of the CB without significant iris or choroidal involvement. To our knowledge, such a case of CB lymphoma with a ‘ring-like pattern mimicking a melanoma has not been described previously.

Prediction of metastasis

Purpose To describe the Liverpool approach to the prediction of metastasis from uveal melanoma.