Iris Melanoma Outcomes Based on the American Joint Committee on Cancer Classification (Eighth Edition) in 432 Patients.

PURPOSE: The American Joint Committee on Cancer (AJCC) classification was updated to the eighth edition in January 2017, providing staging for iris melanoma. This study evaluated outcomes of iris melanoma per the AJCC classification, eighth edition. DESIGN: Retrospective case series. PARTICIPANTS: Four hundred thirty-two patients with iris melanoma. METHODS: Management including tumor resection, plaque radiotherapy, or enucleation. MAIN OUTCOME MEASURES: Local tumor recurrence, melanoma-related systemic metastasis, and melanoma-related death. RESULTS: Of 432 patients with iris melanoma, AJCC classification was category T1 (n = 324 [75%]), T2 (n = 83 [19%]), T3 (n = 2 [<1%]), and T4 (n = 23 [5%]). There was no difference in age, race, gender, eye, or iris color among T categories. Overall, Kaplan-Meier analysis of outcomes (at 5 and 10 years) revealed visual acuity reduction by 3 lines or more (42% and 54%, respectively), secondary glaucoma (29% and 33%, respectively), local recurrence (8% and 17%, respectively), secondary enucleation (12% and 19%, respectively), lymph node metastasis (1% and 1%, respectively), melanoma-related systemic metastasis (5% and 10%, respectively), and melanoma-related death (3% and 4%, respectively). Compared with T1 category, the hazard ratio (HR) for local recurrence in nonenucleated eyes was 1.31 for T2, not evaluable (NE) for T3 (because of small cohort), and 6.61 for T4; the HR for metastasis was 3.41 for T2, NE for T3 (because of small cohort), and 25.6 for T4; the HR for death was 7.51 for T2, NE for T3 (because of small cohort), and 26.5 for T4; and the odds ratio for enucleation was 1.23 for T2, 3.63 for T3, and 4.72 for T4. Features predictive of melanoma-related metastasis (multivariate analysis) included secondary glaucoma (P < 0.001; HR, 4.51), T2 category (vs. T1; P = 0.01; HR, 4.09), and T4 category (vs. T1; P < 0.001; HR, 30.8). Features predictive of melanoma-related death (multivariate analysis) included older age (P = 0.008; HR, 2.16 per 10-year increase), T2 category (vs. T1; P = 0.005; HR, 8.07), and T4 category (vs. T1; P < 0.001; HR, 20.3). CONCLUSIONS: The AJCC eighth edition classification provides prognostic stratification of iris melanoma. By multivariate analysis, the ratio for melanoma-related metastasis was 4 times greater in category T2 and 31 times greater in T4 compared with T1. The ratio for melanoma-related death was 8 times greater in category T2 and 20 times greater in T4 compared with T1. The cohort size for T3 was too small to provide useful information.

New insights into oculodermal nevogenesis and proposal for a new iris nevus classification.

BACKGROUND/AIMS: To gain more knowledge about presence and dermatological associations of iris nevi as well as possible pathways involved in the formation of iris nevi. METHODS: We conducted a prospective, interdisciplinary observational study. Presence, morphology, topography of iris and cutaneous nevi as well as factors indicating sun-exposure were noted. RESULTS: A total of 632 participants including 360 (57%) women were examined. Of those, 26 subjects revealed 27 iris nevi. According to the current classification, all iris nevi were judged as solitary with the majority of them (n=20; 74%) located in the lower quadrants. In six (22.2%) cases we noted a peculiar 'incomplete sectoral pattern'; these nevi were located close to the pupil, were larger and had a more elongated, triangular shape compared with those located distant from the pupil, which appeared smaller and more roundish. Notably, five of these six peculiar (incomplete sectoral) iris nevi were located on the upper half of the iris. CONCLUSIONS: Based on our findings we propose classifying iris nevi into sectoral, incomplete sectoral and solitary subtypes. Additionally, we set up a hypothetic concept of oculodermal nevogenesis suggesting a time-dependent embryogenic alteration affecting the normal melanocyte location, migration and maturation along peripheral nerve sheets. Our new concept explains well the morphology and extension of benign melanocytic proliferations in the ocular region as well as their relation to uveal melanoma.

Clinical survey of 3680 iris tumors based on patient age at presentation.

OBJECTIVE: To report the spectrum of iris lesions based on patient age at presentation. DESIGN: Retrospective, nonrandomized, single-center case series. PARTICIPANTS: We included 3680 iris tumors in 3451 patients. METHODS: Chart review. MAIN OUTCOME MEASURES: Diagnostic category based on age. RESULTS: The mean age at presentation was 48 years and there were 449 (12%) tumors in children (≤20 years), 788 (21%) in young adults (21-40 years), 1308 (36%) in mid adults (41-60 years), and 1135 (31%) in senior adults (>60 years). Of 3680 tumors, the diagnostic category was cystic (n = 768; 21%) or solid (n = 2912; 79%). The cystic tumors originated from iris pigment epithelium (IPE; n = 672; 18%) or iris stroma (n = 96; 3%). The solid tumors included melanocytic (n = 2510; 68%) and nonmelanocytic (n = 402; 11%). The melanocytic tumors comprised nevus (n = 1503; 60%), melanocytoma (n = 68; 3%), melanoma (n = 645; 26%), and melanocytosis (n = 64; 3%). Of 2510 melanocytic tumors, the first and second most common diagnoses by age (children, young adult, mid adult, senior adult) were nevus (53%, 57%, 63%, and 63%, respectively) and melanoma (17%, 27%, 26%, and 27%, respectively). The nonmelanocytic tumors included categories of choristomatous (n = 4; <1%), vascular (n = 57; 2%), fibrous (n = 2; <1%), neural (n = 3; <1%), myogenic (n = 2;, <1%), epithelial (n = 35; 1%), xanthomatous (n = 8; <1%), metastasis (n = 67; 2%), lymphoid (n = 12; <1%), leukemic (n = 2; <1%), secondary (n = 12; <1%), and nonneoplastic simulators (n = 198; 5%). The median age (in years) at diagnosis included cystic (39), melanocytic (52), choristomatous (0.7), vascular (56), fibrous (53), neural (8), myogenic (42), epithelial (63), xanthomatous (1.9), metastasis (60), lymphoid (57), leukemic (25.5), secondary (59), and nonneoplastic simulators (49). Overall, the 3 most common specific diagnoses (children, young adult, mid adult, senior adult) were nevus (25%, 36%, 47%, and 47%, respectively), IPE cyst (28%, 30%, 15%, and 14%, respectively), and melanoma (8%, 16%, 20%, and 19%, respectively). CONCLUSIONS: In an ocular oncology practice, the spectrum of iris tumors includes cystic (21%) and solid (79%) tumors. The solid tumors were melanocytic (68%) or nonmelanocytic (11%). At all ages, the most common specific diagnoses were nevus (42%), IPE cyst (19%), and melanoma (17%).

Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study.

OBJECTIVE: To collaborate with multiple centers to identify representative epidemiological, clinical, and pathologic characteristics of melanoma of the iris. This international, multicenter, Internet-assisted study in ophthalmic oncology demonstrates the collaboration among eye cancer specialists to stage and describe the clinical and pathologic characteristics of biopsy-proven melanoma of the iris. METHODS: A computer program was created to allow for Internet-assisted multicenter, privacy-protected, online data entry. Eight eye cancer centers in 6 countries performed retrospective chart reviews. Statistical analysis included patient and tumor characteristics, ocular and angle abnormalities, management, histopathology, and outcomes. RESULTS: A total of 131 patients with iris melanoma (mean age, 64 years [range, 20-100 years]) were found to have blue-gray (62.2%), green-hazel (29.1%), or brown (8.7%) irides. Iris melanoma color was brown (65.6%), amelanotic (9.9%), and multicolored (6.9%). A mean of 2.5 clock hours of iris was visibly involved with melanoma, typically centered at the 6-o'clock meridian. Presentations included iritis, glaucoma, hyphema, and sector cataract. High-frequency ultrasonography revealed a largest mean tumor diameter of 4.9 mm, a mean maximum tumor thickness of 1.9 mm, angle blunting (52%), iris root disinsertion (9%), and posterior iris pigment epithelium displacement (9%). Using the American Joint Commission on Cancer-International Union Against Cancer classification, we identified 56% of tumors as T1, 34% of tumors as T2, 2% of tumors as T3, and 1% of tumors as T4. Histopathologic grades were G1-spindle (54%), G2-mixed (28%), G3-epithelioid (5%), and undetermined (13%) cell types. Primary treatment involved radiation (26%) and surgery (64%). Kaplan-Meier analysis found a 10.7% risk of metastatic melanoma at 5 years. CONCLUSIONS: Iris melanomas were most likely to be brown and found in the inferior quadrants of patients with light irides. Typically small and unifocal, melanomas are commonly associated with angle blunting and spindle cell histopathology. This multicenter, Internet-based, international study successfully pooled data and extracted information on biopsy-proven melanoma of the iris.

Vascular tumors of the iris in 45 patients: the 2009 Helen Keller Lecture.

OBJECTIVE: To report on a series of vascular tumors of the iris. DESIGN: Noncomparative case series. A retrospective medical record review of all patients with an iris vascular tumor was performed to identify the clinical features and develop a simple classification of these lesions. Included were demographics, clinical features, systemic associations, complications, management, and histopathology. RESULTS: There were 54 eyes in 45 patients with an iris vascular tumor. These were categorized as racemose hemangioma (41 eyes: 29 simple and 12 complex), cavernous hemangioma (3 eyes: 2 localized and 1 systemic), capillary hemangioma (1 eye, localized), varix (3 eyes, localized), and microhemangiomatosis (6 eyes, localized). The hemangiomas occurred in adults at a median age of 55 years, whereas capillary hemangioma occurred in infancy and cavernous hemangioma with systemic involvement occurred in a child. Of the 41 eyes with iris racemose hemangioma, none showed systemic involvement. Of all 54 eyes, transient hyphema was the main complication, found at some point in 30% or more of each affected eye except for iris capillary and racemose hemangioma. Surgical resection was necessary in 1 cavernous hemangioma and 1 varix. The remainder were managed with observation. CONCLUSIONS: There are now well-documented examples of iris racemose hemangioma, cavernous hemangioma, capillary hemangioma, varix, and microhemangiomatosis. Transient hyphema is the main complication. Observation is usually advised. Most are solitary lesions confined to the iris and some (cavernous hemangioma and microhemangiomatosis) can have important systemic associations.

Biomicroscopy and fluorescein angiography of pigmented iris tumors. A retrospective study on 44 cases.

The classification of pigmented iris tumors is a difficult clinical problem. Based on the retrospective observation of colour photographs and iris angiograms of 44 pigmented iris tumors observed over 19 years, the authors present an original grading scheme with scores depending on both the biomicroscopical and the fluoroiridographic patterns of the tumors. The biomicroscopical parameters considered were: thickening of the iris in the area of tumor, pupillary distortion and/or ectropion uveae and uneven pigment density. The fluoroiridographic parameters were: early visibility of the anomalous tumoral network, hyperfluorescence inside or around the tumor, and dye leakage at sites remote from the mass. Based on the score of each tumor, the 44 cases were divided into 3 groups with the different degrees of malignancy confirmed by either histological examination or by follow-up behaviour. The authors suggest that routine use of biomicroscopic-fluoroiridographic classification of pigmented iris tumors would be useful.

[Ophthalmologic differentiation of various forms of neurofibromatosis]. / Ophthalmologische Differenzierung von Neurofibromatoseformen.

Neurofibromatosis (NF) is one of the most frequent autosomal-dominant hereditary disorders. The molecular-genetic differentiation of NF 1 and NF 2 has important implications for the ophthalmologist. Among 80 patients with NF 1, Lisch nodules were diagnosed in 83% as typical criteria for the disease. In 6 patients who did not meet the NIH criteria for NF 1 and NF 2, the ophthalmological investigation showed no cataracts or Lisch nodules; thus, the ophthalmological examination can help to confirm a subtype of NF. In 8 out of 22 NF 2 patients a juvenile posterior subcapsular cataract was diagnosed. Our examination demonstrates that the diagnostic value of lens opacities in NF 2 patients--especially for early detection of the disease--must be clarified, especially with regard to the fact that there were no patients with incipient cataract and no neuroradiological criteria for the disease.