Iris melanoma: Review of clinical features, risks, management, and outcomes.

Primary uveal melanoma is rare and affects approximately 8,000 persons per year worldwide. This malignancy can involve the iris, ciliary body, and choroid. Of these three structures, the iris is the least commonly affected site, representing only 4% of all uveal melanomas. Iris melanoma can arise from iris melanocytic nevus, iris melanocytosis, or de novo. In a longitudinal study of 1,611 patients with iris nevus, transformation into melanoma, using Kaplan-Meier estimates, was found in 2.6% by five years and in 4.1% by 10 years. The factors that predicted growth of iris melanocytic nevus into melanoma are denoted by a letter (ABCDEF) guide: A for age ≤40 years old at presentation (hazard ratio [HR] = 3, P = .01), B for blood (hyphema) (HR = 9, P < .0004), C for clock hour of tumor inferiorly (tumor location) (HR = 9, P = .03), D for diffuse flat tumor configuration (HR = 14, P = .02), E for ectropion uveae (HR = 4, P = .002), and F for feathery ill-defined margins (HR = 3, P = .02). At diagnosis, iris melanoma has a mean cross-sectional diameter of 5.5 mm and thickness of 2.1 mm, often with tumor seeding (28%) and secondary glaucoma (35%). We provide a comprehensive review of iris nevus and melanoma to explore relevant demographic and clinical data, risk factors for tumor growth, management, and prognosis, with the hope that clinicians will be more comfortable in understanding this rare malignant condition.

Iris melanocytic tumours in New Zealand/Aotearoa: presentation, management and outcome in a high UV exposure environment.

BACKGROUND/OBJECTIVES: Iris melanoma, a rare intraocular malignancy, represents the smallest subgroup of uveal melanoma. This first, comprehensive study of iris melanocytic lesions in the high ultraviolet environment in New Zealand/ Aotearoa (NZ) examines diagnosis, management and outcomes. SUBJECTS/METHODS: Retrospective study of iris melanocytic tumours referred to tertiary referral centres in Auckland, NZ, over 20 years (1999-2018). Data analysed include demographics, tumour characteristics, histology, genetic analyses, treatment modalities, recurrence, metastasis, 5-year and overall survival. RESULTS: Cohort (N = 51) was predominantly NZ European (98.0%) with no indigenous Maori, or Pasifika. Median age at presentation was 58 years. Tumours involved a median of two clock hours of iris. The posterior tumour margin extended to the anterior chamber angle in 22 patients (45.8%). Management included initial observation 54.9%, iridectomy/excision biopsy 29.4%, irido-cyclectomy 7.8%, plaque radiotherapy 7.8%, proton beam radiotherapy 7.8%, and ultimately enucleation 17.6%. Histology was performed in 19 cases (37%) with 16 confirmed melanomas (84%). Mean follow-up 4.2 years with median visual acuity of 6/7.5 two years post intervention. Melanoma-related metastasis and mortality occurred in two cases with five-year melanoma-related mortality of 2.0%. CONCLUSION: In a climate with high ultraviolet exposure iris melanocytic tumours occurred almost exclusively in NZ Europeans, however, the majority of cases were category T1, possibly reflecting early diagnosis in the NZ health system. Nonetheless, >50% underwent surgery or radiotherapy, often utilising more than one modality. A high index of suspicion and early referral of iris melanocytic lesions should be considered in regions with high UV exposure.

No differences in the long-term prognosis of iris and choroidal melanomas when adjusting for tumor thickness and diameter.

OBJECTIVE: To assess the long-term prognosis for patients with iris melanomas and compare it with the prognosis for small choroidal melanomas. DESIGN: Retrospective observational case series. METHODS: All patients treated for iris melanomas at a single referral institution between January 1st 1986 and January 1st 2016 were included. Patients treated for small choroidal melanomas during the same period were included for comparison. The cumulative incidence of melanoma-related mortality was calculated. Patient and tumor characteristics and size-adjusted hazard ratio (HR) for melanoma-related mortality were compared between iris and small choroidal melanomas. RESULTS: Forty-five iris melanomas and 268 small choroidal melanomas were included. Twenty-four iris melanomas (53%) had been treated with local resection, 12 (27%) with Ruthenium-106 brachytherapy, 7 (16%) with enucleation and 2 (4%) with proton beam irradiation. Twenty-one (68%), 7 (16%) and 2 (4%) of the iris melanomas were of the spindle, mixed and epithelioid cell types, respectively. Twenty-three patients had deceased before the end of follow-up. Median follow-up for the 22 survivors was 13.3 years (SD 9.4). Patients with iris melanomas were more often asymptomatic at presentation and had a trend towards significantly lower age (59 versus 63 years, Student's T-tests p = 0.057). Further, iris melanomas had significantly smaller basal diameter (5.8 versus 8.0 mm, p < 0.0001) and tumor volume (79 mm3 versus 93 mm mm3, p < 0.0001) but greater thickness (3.0 versus 2.5 mm, p < 0.0001). The cumulative incidence of iris melanoma-related mortality was 5% at 5 years after diagnosis, and 8% at 10, 15 and 20 years. The incidence was not significantly different to small choroidal melanomas (Wilcoxon p = 0.46). In multivariate Cox regression with tumor diameter and thickness as covariates, patients with choroidal melanomas did not have increased HR for melanoma-related mortality (HR 2.2, 95% CI 0.5-9.6, p = 0.29). Similarly, there were no significant survival differences in matched subgroups (Wilcoxon p = 0.82). CONCLUSIONS: There are no survival differences between iris and choroidal melanomas when adjusting for tumor size. The reason for the relatively favorable prognosis of iris melanomas compared to melanomas of the choroid and ciliary body is likely that they are diagnosed at a smaller size.

Iris metastasis as the initial presentation of metastatic esophageal cancer diagnosed by fine needle aspiration biopsy: A case report.

RATIONALE: Metastasis of neoplasms to the eye is quite uncommon. In this case report, we describe a patient where primary esophageal cancer was diagnosed by fine needle aspiration biopsy (FNAB) of an iris tumor. PATIENT CONCERNS: A 70-year-old male complained of redness and discomfort in the right eye. DIAGNOSIS AND INTERVENTIONS: The patient's right eye was diagnosed as idiopathic uveitis, and a topical steroid was administered. As vitreous opacities were observed even after topical therapy, oral prednisolone was administered. On slit-lamp examination of the right eye, an iris mass with neovascularization was seen in the anterior chamber. A metastatic tumor was suspected, and FNAB was performed. Histology revealed squamous cell carcinoma. Systemic workup revealed esophageal cancer with several metastases. Best-corrected visual acuity decreased to 20/400, and intraocular pressure was 40 mmHg in the right eye. Two iris tumors with neovascularization were present extending into the anterior chamber with posterior iris synechiae and 360 degree peripheral anterior synechiae. Intraocular pressure in the right eye was medically managed with hypotensive eye drops and oral acetazolamide. Iris metastases were treated with 40 Gray of radiation therapy and concurrent chemotherapy. OUTCOMES: The tumor regressed, but intraocular pressure was refractory to treatment because of 360 degree goniosynechial closure. The right eye lost light perception six months after treatment commenced, and the patient died 9 months after the onset of therapy due to multiple systemic metastases. LESSONS: This is a rare case of masquerade syndrome without systemic symptoms in which FNAB of an iris tumor led to a diagnosis of metastatic esophageal squamous cell carcinoma. Although the patient lost his sight due to uncontrollable ocular hypertension, systemic chemotherapy, and radiation therapy were initially effective in the treatment of the metastatic iris tumor. As the prognosis of patients with metastatic iris tumors is poor, it is important for ophthalmologists to consider such diagnoses and conduct systemic investigations when necessary.

Iris lymphoma-a systematic guide for diagnosis and treatment.

Iris lymphomas are rare malignant neoplasms arising either as primary tumors in the iris or as secondary tumors involving the iris. We summarize previously published data and make recommendations for work-up strategies for cases of suspected iris lymphoma. Our objective is to provide a structured overview of the typical clinical symptoms and signs, the pathologic, ophthalmic, as well as hematologic work-up for diagnosis, treatment, and follow-up of iris lymphomas and offer a flowchart on how to diagnose and treat these tumors.

[New treatment options for iridociliary tumors]. / Neue therapeutische Möglichkeiten bei iridoziliären Tumoren.

BACKGROUND: Benign iridal tumors rarely necessitate a therapeutic intervention. In contrast, malignant tumors of the iris can threaten the patient's life and eyesight and require early treatment to prevent the development of metastases. OBJECTIVE: Presentation of current treatment options for iridal tumors with special emphasis on iridal melanoma. METHODS: This article gives an overview of the current literature based on a PubMed search as well as own clinical experience. RESULTS: Treatment options for iridal and ciliary body melanomas comprise radiotherapeutic and surgical (eyeball-sparing and non-sparing) approaches. The eyeball-sparing surgical procedure of choice is block excision. While local tumor control rates and metastasis rates of block excision and radiotherapy are comparable, there are distinct differences especially between the spectra of complications. New treatment procedures include immunomodulatory approaches and targeted therapies. Using checkpoint inhibitors, no convincing enhancement of overall survival could be demonstrated for metastatic iridal melanoma, as is the case for cutaneous melanoma. In contrast, tumor vaccination with the help of tumor RNA-laden patient-derived dendritic cells seems to be a promising option for a subgroup of high-risk patients. Targeted therapies aiming to suppress the MAPK and PI3K/Akt pathways could not achieve any improvement in patient survival. CONCLUSION: For the primary treatment of iridal melanoma a surgical, eyeball-sparing approach and also when appropriate, radiotherapy can be recommended. In the future, eligible high-risk patients could profit from a tumor vaccination. To date, there is no effective systemic treatment for metastatic iridal melanoma.

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.

[Diagnosis and Therapy of Iris Lesions]. / Diagnostik und Therapie von Irisläsionen.

The most common iris lesions are iris nevi, iris melanomas and iris pigment epithelium cysts. However, there is an abundance of rare differential diagnoses that have to be considered, including other melanocytic and non-melanocytic lesions. Diagnostic tools include the slit lamp examination, gonioscopy, tonometry, transillumination, ultrasound biomicroscopy (UBM), optical coherence tomography, fluorescein angiography and standardized photography-assisted documentation. The timely identification of malignant lesions (i.e. iris melanoma) is paramount. To assess malignancy criteria of iris nevi, the ABCDEF rule (age young, blood, clock hour inferior, diffuse growth, ektropion uveae, feathery margins) can be applied. Statistically, up to 11% of iris nevi may develop into iris melanomas within 20 years. TNM Staging follows the 2010 AJCC cancer staging manual and helps determine the optimal treatment strategy. Treatment options include radiotherapy, such as plaque brachytherapy and proton beam radiation therapy, as well as surgical excision. Both the surgical and the radiotherapeutic approaches show comparable local tumor control rates. However, the spectrum of therapy-related side effects and complications may differ amongst treatment modalities. After initial treatment, patients should be followed up every 3 - 6 months. Tumor-related mortality ranges between 0 - 11% and is significantly lower than in other uveal melanomas. A prognostic value of common genetic alterations, which have been identified as significant prognostic factors in posterior uveal melanoma, could not be shown for iris melanoma.

Iris metastases from systemic cancer: a report of three cases / Metástase de íris de câncer sistêmico: relato de três casos

ABSTRACT Ocular metastasis is relatively uncommon, with a reported incidence of approximately 8%, according to the results of autopsy evaluation. The majority of ocular metastases are located within the choroid, while metastatic tumors affecting the iris are rare. Metastatic tumors may manifest as stromal nodules or ill-defined iris thickening, or they may present with nonspecific features such as pain, iridocyclitis, and hyphema. Here, we describe three patients with iris metastasis and discuss the diagnostic challenges and unusual findings associated with these cases.

RESUMO A maioria das metástases oculares do câncer sistêmico são encontrados na coroide. As metástases para a íris são incomuns, podendo se manifestar como nódulo estromal, espessamento de íris de limites mal definidos ou como uma iridociclite ou hifema. Relatamos 3 pacientes com lesão de íris e história pregressa de câncer sistêmico. Enfatizamos a dificuldade no diagnóstico e raridade dessas lesões comparando com relatos anteriores.

Iris metastases from systemic cancer: a report of three cases.

Ocular metastasis is relatively uncommon, with a reported incidence of approximately 8%, according to the results of autopsy evaluation. The majority of ocular metastases are located within the choroid, while metastatic tumors affecting the iris are rare. Metastatic tumors may manifest as stromal nodules or ill-defined iris thickening, or they may present with nonspecific features such as pain, iridocyclitis, and hyphema. Here, we describe three patients with iris metastasis and discuss the diagnostic challenges and unusual findings associated with these cases.

Diffuse Anterior Retinoblastoma with Globe Salvage and Visual Preservation in 3 Consecutive Cases.

PURPOSE: Diffuse anterior retinoblastoma is an exquisitely rare variant of retinoblastoma in which the tumor resides in the anterior segment of the eye, without apparent retinal involvement. Previously published cases have been managed with enucleation. We describe globe salvage and visual preservation in 3 consecutive cases using chemotherapy and radiotherapy. DESIGN: Retrospective case series. PARTICIPANTS: Three children with diffuse anterior retinoblastoma. METHODS: Plaque radiotherapy plus intravenous chemotherapy. MAIN OUTCOME MEASURES: Globe and vision preservation. RESULTS: The mean patient age at presentation elsewhere was 5.7 years (median, 7; range, 3-7 years). There were 2 white female patients and 1 African American male patient. The initial observation by parents/caregiver was reduced vision (n = 1), red eye (n = 1), or cloudy eye (n = 1), and the initial finding by physician was iris tumor (n = 2) or hyphema (n = 1). Referring diagnosis was iris melanoma (n = 1), infectious endotheliitis (n = 1), and possible tumor (nonspecified) (n = 1). At our evaluation, visual acuity was 20/50 to 20/60 (n = 2) and fix no follow (n = 1). In all cases, the opposite eye was normal. Mean intraocular pressure was 20 mm Hg (median, 16; range, 15-30 mmHg). Our examination revealed solid iris tumor (n = 3), ciliary body involvement (n = 2), and anterior chamber seeding (n = 3). In no case was there choroidal or retinal tumor, vitreous seed or subretinal seed, or extrascleral extension. Clear corneal fine-needle aspiration biopsy confirmed the diagnosis as retinoblastoma in each case. Treatment included plaque radiotherapy (n = 3) plus additional systemic chemotherapy (n = 2). At mean follow-up of 35 months (median, 34; range, 20-51 months), there has been no recurrence, extrascleral extension, enucleation, metastasis, or death. In all 3 cases, cataract surgery was necessary at a mean interval of 16 months after complete and stable regression of retinoblastoma. CONCLUSIONS: The rare diffuse anterior form of retinoblastoma can be managed with globe-salvaging alternatives and with visual preservation in selected cases.

Sector iris hemangioma in association with diffuse choroidal hemangioma.

Two patients referred for iris lesions were found to have sector hemangioma of the iris stroma in contiguity with diffuse choroidal hemangioma. Neither patient had other manifestations of Sturge-Weber syndrome.

Melanoma of the eye: revealing hidden secrets, one at a time.

Melanoma of the eye can involve the uveal tract with iris, ciliary body, or choroid involvement or it can involve the conjunctiva, eyelid, or orbit. Uveal involvement with choroidal melanoma is the most common, found in light complexion Caucasians with an age-adjusted incidence of 4.3 per million persons. Early detection of uveal melanoma is critical. The ABCDEF guide helps to differentiate iris nevus from iris melanoma. The letters represent: A, age young (≤40 years); B, blood in anterior chamber; C, clock hour of mass inferiorly; D, diffuse configuration; E, ectropion; and F, feathery margins. The mnemonic of TFSOM-UHHD (To Find Small Ocular Melanoma-Using Helpful Hints Daily) helps to differentiate choroidal nevus from small melanoma and represents: T, thickness over 2 mm; F, fluid; S, symptoms; O, orange pigment; M, margin within 3 mm of the optic disc; UH, ultrasound hollow; H, halo absent; and D, drusen absent. Patients with 3 or more of these factors are likely to have melanoma. These key clinical features help to identify small melanoma at a time when therapy could be life-saving. Conjunctival melanoma usually arises from primary acquired melanosis, a flat pigmentation that can lead to melanoma. Wide excision using no touch strategy is important to tumor control. Ocular examination is advised annually for all persons for detection of refractive error, cataract, glaucoma, and other conditions, but also for the detection of asymptomatic malignancies like melanoma. One at a time, we have uncovered the secrets of ocular melanoma and we forge ahead with the goal to solve the riddle of this challenging disease.

Iris metastasis from systemic cancer in 104 patients: the 2014 Jerry A. Shields Lecture.

PURPOSE: To describe the clinical features, treatment, and outcome of patients with iris metastasis. METHODS: Retrospective case series of 160 tumors in 107 eyes of 104 patients with iris metastasis from systemic cancer. RESULTS: The median age at presentation with iris metastasis was 60 years. Iris metastasis was more common in whites (n = 93, 89%) and women (n = 65, 62%). The primary tumor was located in the breast (n = 34, 33%), lung (n = 28, 27%), skin (melanoma) (n = 13, 12%), kidney (n = 7, 7%), esophagus (n = 3, 3%), and others (n = 19, 19%). The main symptoms were pain (n = 33, 32%) or blurred vision (n = 31, 30%). The main findings were corectopia (n = 38, 37%) and secondary glaucoma (n = 38, 37%). The metastasis was unifocal (n = 84, 78%) or multifocal (n = 23, 21%) for a total of 160 tumors. The main tumor was centered at the iris root (n = 72, 69%), midzone (n = 22, 21%), or pupillary margin (n = 10, 10%), with median tumor diameter of 5 mm. Coexistent conjunctival or ciliary body/choroidal metastases were found in 39 patients. Management of iris metastasis included systemic chemotherapy (n = 18, 22%), external beam radiotherapy (n = 34, 41%), plaque radiotherapy (n = 20, 24%), surgical excision (n = 4, 5%), enucleation (n = 3, 4%), or observation (n = 4, 5%). Following treatment, tumor control without recurrence was achieved in 95% cases. In 98 cases with adequate follow-up information, death occurred in 85 (87%) at median 10 months (range, <1-239 months) from the date of iris metastasis. CONCLUSIONS: Metastatic tumors to the iris generally originate from primary malignancies in the breast, lung, or skin (melanoma). Despite successful ocular treatment, life prognosis is poor.

Intraocular mantle cell lymphoma of the iris.

PURPOSE: Non-Hodgkin lymphoma (NHL) is a neoplastic process of the lymphatic system in which tumors develop from lymphocytes. The absence of Reed-Sternberg cells differentiates NHL from Hodgkin lymphoma (HL). Mantle cell lymphoma is a mature B-cell NHL, typically with an aggressive course. Manifestations of intraocular mantle cell lymphoma include anterior uveitis, morphologic changes to the uvea, vitritis, intraocular masses, as well as subretinal or choroidal infiltrates. CASE REPORT: A 71-year-old white man with known mantle cell lymphoma presents with recent-onset blurred vision in the left eye resulting from an atypical anterior chamber cellular reaction. Iris examination reveals topographic and morphologic atypia suggestive of neoplasia. He subsequently developed posterior cervical lymph node involvement indicating recurrence of his mantle cell lymphoma. He was restarted on chemotherapy and radiation. The iris and anterior chamber reaction responded to systemic oncological therapy. CONCLUSIONS: Mantle cell lymphoma may present with ocular manifestations such as an anterior chamber cellular reaction and morphologic changes to the uvea. This case stresses the importance of seeking an etiology in any secondary or atypical uveitis.

[Pigmented ciliary body tumours: benign or malignant?]. / Tumor pigmentado del cuerpo ciliar: ¿benigno o maligno?

CASES REPORT: We report the cases of 2 women with a pigmented tumour in the ciliary body, one a melanocytoma and the other a melanoma, with different clinical manifestations. The first one presented with decreased visual acuity associated with recent growth of the tumour, as well as sectorial opacities of the lens and subluxation. The second one is asymptomatic and has been kept under observation for more than 30 years. DISCUSSION: Although the definitive diagnosis of a pigmented tumour of the ciliary body is only achieved by the histopathology study, the group of clinical features is a determining factor when a conservative treatment is indicated.