Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma.

PURPOSE: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). DESIGN: Prospective, multicenter study. PARTICIPANTS: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. TESTING: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. MAIN OUTCOME MEASURES: Patients were managed for their primary tumor and monitored for metastasis. RESULTS: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. CONCLUSIONS: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.

Intraocular extension of conjunctival invasive squamous cell carcinoma after pterygium surgery and cataract extraction.

OBJECTIVES: Conjunctival squamous dysplasia can often be confused with pterygium and pinguecula. Incomplete excision of dysplastic tissue can lead to recurrence and rarely intraocular invasion. This study describes two cases in which invasive squamous cell carcinoma (SCC) of the conjunctiva was originally partially resected as pterygium and eventually required enucleation for intraocular invasion. METHODS: In this clinicopathologic small case series, two cases of intraocular SCC managed at a single tertiary ocular oncology institution are described. Clinical features, pathologic characteristics, and relevant imaging are described. RESULTS: In both cases, incomplete excision of conjunctival SCC was followed by rapid regrowth of the conjunctival lesion and signs of intraocular inflammation. An intraocular mass within the substance of the ciliary body was identified using ultrasound biomicroscopy in both the cases. Enucleation was performed. Pathologic features were typical to SCC. CONCLUSIONS: Intraocular spread on conjunctival SCC occurs only rarely but tends to follow recurrence of the conjunctival lesion after attempted excision. Modes of invasion may include direct invasion through sclera, along the tract of the anterior ciliary vessels, or inoculation through intraocular surgery incision.

Clinical and ultrasound biomicroscopy features associated with growth in iris melanocytic lesions.

PURPOSE: To determine the clinical and ultrasound biomicroscopy (UBM) features associated with growth in iris melanocytic lesions. STUDY DESIGN: Retrospective case series analysis. METHODS: We included all iris melanocytic lesions that were monitored between January 2005 and November 2009. At the end of the analysis, 44 eyes of 44 patients were included in the final analysis. The clinical features analyzed were: iris color, largest base diameter, radial location of the lesion epicenter, circumferential location of the lesion epicenter, lesion configuration, lesion pigmentation, intrinsic vascularity within the lesion, presence of associated pigmentation, the impact on the pupil, presence of iris atrophy, and lesion-induced localized cataracts. The UBM features included lesion thickness, presence of corneal touch, presence of surface plaque, internal structure, and internal reflectivity. Regression analysis was performed to define the features associated with growth. RESULTS: Twenty-three percent of the lesions showed documented growth. Mean follow-up was 21.4 months (range: 10-48). Clinical features associated with growth were a large basal diameter at baseline (P = .004) and inferior location (P = .004). UBM features associated with growth were: a greater baseline thickness (P = .01), presence of corneal touch (P = .007), an irregular internal structure (P = .0001), and the presence of dots and linear streaks (P < .0001). Clinical features that were not associated with growth were the radial location of the lesion in the iris (P > .999), lesion configuration (P > .999), lesion pigmentation (P > .999), the presence of pigment dispersion (P = .70), iris freckles (P = .15), corectopia (P > .999), ectropion (P > .999), and intrinsic vascularity (P = .70). UBM features not associated with growth were the presence of a surface plaque (P = .07) and the internal reflectivity (P = .77). CONCLUSION: Substantial growth in iris melanocytic lesions is associated with original larger basal diameter and inferior lesion location. On UBM growth is associated with greater original thickness, presence of corneal touch, and an irregular internal structure. Presence of these features could modify the frequency of observation of those lesions.

Ultrasound biomicroscopic imaging of iris melanoma: a clinicopathologic study.

PURPOSE: To demonstrate the correlation of ultrasound biomicroscopy (UBM) features of iris melanoma with histopathology. DESIGN: Retrospective analysis of medical records. METHODS: The medical records of patients that underwent surgery for iris melanoma at the Princess Margaret Hospital, University of Toronto, from June 1990 to October 1998 were reviewed. The clinical features, as well as the UBM findings prior to surgical intervention, were evaluated. The anatomic features noted on UBM were correlated with histopathologic features seen in the surgical specimens. RESULTS: Fourteen cases met the inclusion criteria and were included in the final analysis. The ultrasound acoustic characteristics showed a broad spectrum of findings among iris melanomas. Tumor acoustic parameters correlated well with histologic features, including tumor vascularity, surface plaque, extrascleral extension, ciliary body involvement, and integrity of iris pigment epithelium. CONCLUSIONS: UBM is a useful imaging technique for the in vivo assessment of primary iris melanoma and can provide detailed imaging of the tumor's interface with the angle structures. The preoperative assessment of these tumors by UBM may aid the surgeon in choosing the most appropriate technique to ensure total removal.

Management of iris melanomas with 125Iodine plaque radiotherapy.

PURPOSE: To report the experience of the Princess Margaret Hospital/University Health Network with the treatment of iris melanoma (IM) with (125)Iodine plaque brachytherapy. DESIGN: Retrospective noncomparative case series. METHODS: All cases of IM submitted to (125)Iodine plaque radiotherapy were included. Patients' demographic, clinical, management, and follow-up data were reviewed. Outcome measures included rates of tumor control, eye preservation, systemic metastases, and brachytherapy-related complications. RESULTS: Fourteen IMs were included in the study. All patients had blue/green irises. Mean largest basal dimension and thickness were 7.1 +/- 2.1 mm (range, 4.0 to 11.5 mm) and 2.2 +/- 0.8 mm (range, 1.0 to 3.5 mm), respectively. Ten patients (71%) had seeding and 2 (14%) had glaucoma at presentation. Median follow-up was 26.6 +/- 19.5 months (range, 6 to 72 months). Tumor control was achieved in 100% of the cases and no eye was enucleated because of radiation-induced complications. At last visit, all patients were alive and free of metastasis. Final visual acuity was the same as or better than before treatment in 9 patients (75%). Cataract was the most common complication (8; 75%), followed by persistent glaucoma (2; 17%) and anterior uveitis (1; 8%). No other significant complication was seen during the follow-up period. CONCLUSIONS: Plaque radiotherapy is a safe and effective conservative treatment option for IM, although cataract is a common, yet treatable, complication. This treatment scheme circumvents an intraocular procedure and may avoid the dissemination of malignant cells, and provides a margin of safety in the treatment of clinically undetectable disease.