Prognostication of uveal melanoma is simple and highly predictive using The Cancer Genome Atlas (TCGA) classification: A review

Purpose: The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI's Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus (vs.) TCGA. Methods: Review of published reports on AJCC and TCGA classification for UM was performed. Outcomes based on AJCC 7th and 8th editions were assessed. For TCGA, UM was classified based on chromosomes 3 and 8 findings including disomy 3 (D3), monosomy 3 (M3), disomy 8 (D8), 8q gain (8qG), or 8q gain multiple (8qGm) and combined into four classes including Class A (D3/D8), Class B (D3/8qG), Class C (M3/8qG), and Class D (M3/8qGm). Outcomes of metastasis and death were explored and a comparison (AJCC vs. TCGA) was performed. Results: In the NCI CCG study, there were 80 eyes with UM sampled by enucleation (n = 77), resection (n = 2), or orbitotomy (n = 1) and analysis revealed four distinct genetic classes. Metastasis and death outcomes were subsequently evaluated per class in the WEH study. The WEH study reviewed 658 eyes with UM, sampled by FNAB, and found Class A (n = 342, 52%), B (n = 91, 14%), C (n = 118, 18%), and D (n = 107, 16%). Comparison by increasing class (A vs. B vs. C vs. D) revealed older mean patient age (P < 0.001), worse entering visual acuity (P < 0.001), greater distance from the optic disc (P < 0.001), larger tumor diameter (P < 0.001), and greater tumor thickness (P < 0.001). Regarding outcomes, more advanced TCGA class demonstrated increased 5-year risk for metastasis (4% vs. 20% vs. 33% vs. 63%,P < 0.001) with corresponding increasing hazard ratio (HR) (1.0 vs. 4.1, 10.1, 30.0,P= 0.01 for B vs. A andP < 0.001 for C vs. A and D vs. A) as well as increased 5-year estimated risk for death (1% vs. 0% vs. 9% vs. 23%,P < 0.001) with corresponding increasing HR (1 vs. NA vs. 3.1 vs. 13.7,P= 0.11 for C vs. A andP < 0.001 for D vs. A). Comparison of AJCC to TCGA classification revealed TCGA was superior in prediction of metastasis and death from UM. Conclusion: TCGA classification for UM is simple, accurate, and highly predictive of melanoma-related metastasis and death, more so than the AJCC classification.

Melanocytoma of the optic disk: A review

Melanocytoma is a deeply pigmented variant of melanocytic nevus that classically occurs in the optic disk, sometimes with contiguous involvement of the adjacent retina or choroid. Historically, this tumor was often confused with malignant melanoma both clinically and histopathologically. Today, however, it is generally recognized by its typical clinical features that differ from most melanomas and erroneous enucleation is rarely done. Histopathologically, melanocytoma is composed of intensely pigmented round to oval nevus cells with benign features. Although traditionally believed to be a relatively stationary lesion, it is now known to exhibit minor enlargement in 10--15% of cases and can cause minor visual loss by a variety of mechanisms. In rare instance, it can induce severe visual loss due to spontaneous necrosis of the lesion or compressive optic neuropathy. More importantly, it can exhibit malignant transformation into melanoma in 1--2% of cases. Ophthalmologists should be familiar with melanocytoma of the optic disk and affected patients should be followed periodically.

Tumors of the conjunctiva and cornea

Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Melanocytic lesions include nevus, racial melanosis, primary acquired melanosis, melanoma, and other ocular surface conditions like ocular melanocytosis and secondary pigmentary deposition. The most frequent nonmelanocytic neoplastic lesions include squamous cell carcinoma and lymphoma, both of which have typical features appreciated on clinical examination. The caruncle displays a slightly different array of tumors compared to those elsewhere on the conjunctiva, as nevus and papilloma are most common, but oncocytoma and sebaceous gland hyperplasia, adenoma, and carcinoma can be found. In this report, we provide clinical description and illustration of the many conjunctival and corneal tumors and we discuss tumor management.

Malignant transformation of choroidal nevus according to race in 3334 consecutive patients

Purpose: To evaluate choroidal nevus demographics, clinical features, imaging features, and the rate of transformation into melanoma by race. Methods: In this observational case series, There were 3334 participants (3806 choroidal nevi) at a single tertiary-referral center evaluated between January 2, 2007, and August 7, 2017. Retrospective chart and multimodal imaging review was performed. Patient demographics, tumor features, and outcomes were compared between different races using Chi-squared test, Fisher's exact test, t-test, and analysis of variance. The main outcome measure was clinical features of choroidal nevus and the rate of transformation into melanoma by race. Results: Of the 3334 patients, there were Caucasian (n = 3167, 95%) and non-Caucasian (n = 167, 5%). The non-Caucasian races included African-American (n = 27, <1%), Hispanic (n = 38, <1%), Asian (n = 15, <1%), Asian Indian (n = 2, <1%), Middle Eastern (n = 4, <1%), and unknown (n = 83, 3%). By comparison (Caucasian versus vs. non-Caucasian), there were differences in the mean age at presentation (61 vs. 56 years,P < 0.0001), female sex (63% vs. 52%,P < 0.01), dysplastic nevus syndrome (<1% vs. 1%,P < 0.01), and previous cutaneous melanoma (5% vs. 1%,P= 0.03). A comparison of tumor features revealed differences in presence of symptoms (12% vs. 20%,P < 0.01) and ?3 nevi per eye (3% vs. <1%,P= 0.04). A comparison of imaging features showed no differences. A comparison of outcome of nevus transformation into melanoma revealed no difference (2% vs. 3%,P= 0.29). However, of those nevi exhibiting growth to melanoma, ultrasonographic hollowness was less frequent in Caucasians (29% vs. 67%,P= 0.04). Conclusion: In this analysis of 3334 patients with choroidal nevus, we found differences in the mean age of presentation, sex, dysplastic nevus syndrome, previous cutaneous melanoma, presence of symptoms, and multiplicity of nevus per eye by race. However, there was no difference in the rate of transformation into melanoma by race.

Coats disease in 351 eyes: Analysis of features and outcomes over 45 years (by decade) at a single center

Purpose: To assess features and outcomes of Coats disease over 5-decades. Methods: Retrospective review of Coats disease patients at a single center. Features and outcomes were compared based on decade of presentation. Results: There were 351 patients with Coats disease. The presenting median age (6 years), male sex (84%), and unilaterality (100%) did not change per decade. Coats disease classification did not change per decade with Stage 1 (1%), Stage 2 (21%), Stage 3 (68%), Stage 4 (6%), and Stage 5 (1%). Clinical features that changed per decade (1970s vs. 1980s vs. 1990s vs. 2000s vs. 2010s) included 1980s features of more eyes with exudation in all 4 quadrants (22% vs. 58% vs. 44% vs. 33% vs. 27, P = 0.01) and total exudative retinal detachment (33% vs. 53% vs. 39% vs. 27% vs. 21%, P < 0.001). Imaging features that changed per decade included 2010s greater fluorescein angiographic extent of retinal non-perfusion in mean clock hours (4 vs. 4 vs. 3 vs. 5 vs. 6, P = 0.003), and 1980s greater mean height of retinal detachment ultrasonographically (5 vs. 12 vs. 5 vs. 5 vs. 4 mm, P < 0.001). Treatment features that changed per decade included 1980s greater primary enucleation (11% vs. 16% vs. 3% vs. 4% vs. 1%, P = 0.001), and 2010s greater use of laser photocoagulation (55% vs. 33% vs. 38% vs. 40% vs. 72%, P < 0.001), sub-Tenon corticosteroid (0% vs. 4% vs. 5% vs. 8% vs. 29%, P < 0.001), and intravitreal anti-VEGF) (0% vs. 4% vs. 2% vs. 13% vs. 18%, P = 0.003). Outcomes that changed per decade included 2010s findings of more complete resolution of subretinal fluid (64% vs. 59% vs. 38% vs. 58% vs. 72%, P = 0.01) and less need for primary/secondary enucleation (17% vs. 27% vs. 14% vs. 13% vs. 6%, P = 0.04). Conclusion: Eyes with Coats disease in the 1980s demonstrated more advanced findings, often requiring enucleation. Over the decades, greater use of laser photocoagulation and injections has led to improved disease resolution with greater globe salvage.

Coats disease: An overview of classification, management and outcomes

Coats disease is an idiopathic retinal vascular disorder with retinal telangiectasia with intraretinal and/or subretinal exudation without appreciable retinal or vitreal traction. The condition is sporadic with no associated systemic abnormalities. Unilateral involvement in young males is the typical presentation with most cases being diagnosed in the first and second decade of life. Younger the patient, more severe is the presentation and poorer the visual outcome. The management varies with the stage of the disease. Over the years, we have shifted from enucleation to a more conservative approach for the treatment of Coats disease with laser photocoagulation, cryotherapy and surgery for retinal detachment achieving good outcomes. The anti-VEGF agents have come into the scene as important form of adjuvant treatment along with the traditional management options. This article describes the clinical features, underlying pathology, classification and staging, the complications and the management of Coats disease and gives an overview of the changing trends in treatment and outcomes spanning across five decades.

Intraocular medulloepithelioma – A review of clinical features, DICER 1 mutation, and management

Intraocular medulloepithelioma is a nonhereditary neoplasm of childhood arising from primitive medullary epithelium. It most often involves the ciliary body. Most patients present between 2 and 10 years of age with loss of vision, pain, leucocoria, or conjunctival congestion. The mass appears as a grey-white ciliary body lesion with intratumoral cysts. Presence of a neoplastic cyclitic membrane with extension to retrolental region is characteristic. Secondary manifestations like cataract and neovascular glaucoma may be present in up to 50% and 60% patients, respectively. These could be the first signs for which, unfortunately, about 50% patients undergo surgery before recognition of the hidden tumor. Systemic correlation with pleuropulmonary blastoma (DICER1 gene) has been documented in 5% cases. Histopathology shows primitive neuroepithelial cells arranged as cords closely resembling the primitive retina. Histopathologically, the tumor is classified as teratoid (containing heteroplastic elements) and nonteratoid (containing medullary epithelial elements), each of which are further subclassified as benign or malignant. Retinoblastoma-like and sarcoma-like areas may be seen within the tissue. The treatment modality depends on tumor size and extent of invasion. For small localized tumors (?3-4 clock hours), conservative treatments with cryotherapy, plaque radiotherapy, or partial lamellar sclerouvectomy (PLSU) have been used. Plaque brachytherapy is generally preferred for best tumor control. Advanced and extensive tumors require enucleation. Rare use of intra-arterial and intravitreal chemotherapy has been employed. Systemic prognosis is favorable, but those with extraocular extension and orbital involvement show risk for local recurrence and metastatic disease, which can lead to death.

Comparison of posterior lamellar resection versus lumpectomy for initial management of localized tarsal conjunctival sebaceous carcinoma in 54 cases

Purpose: Comparison of outcomes of localized eyelid sebaceous carcinoma (American Joint Committee on Cancer (AJCC) 8th edition categories T1, T2, T3) following initial management with posterior lamellar resection (PLR) versus (vs) lumpectomy (nonposterior lamellar resection, non-PLR). Methods: This was a retrospective, comparative, interventional case series. Of 54 patients, 26 were managed by PLR and 28 by nonPLR. The main outcome measures were vision loss, orbital exenteration, lymph node metastasis, and remote metastasis were the main outcome measures. Results: A comparison of PLR vs nonPLR revealed no difference in mean age at presentation (70 vs 72 years), race (Caucasian 100% vs nonCaucasian 93%), gender (female 54% vs male 71%), entering mean visual acuity (20/30 vs 20/50), or corneal involvement (23% vs 11%). There was significant difference in clinical features with PLR demonstrating greater mean basal diameter (21 mm vs 12 mm, P = 0.004), and positive margins were seen more frequently in PLR (69% vs 46%). There was significantly less number of surgical procedures in PLR to achieve complete tumor control (1.7 vs 2.5, P = 0.001). Outcomes at mean 55 months follow-up revealed significantly better control with PLR (vs nonPLR) with fewer orbital exenterations (15% vs 43%, P = 0.038), fewer lymph node, and systemic metastases (0% vs 39%, P < 0.001). There was no significant difference in final mean visual acuity (20/60 vs 20/200). Conclusion: For eyelid sebaceous carcinoma, the initial management is critical to the patient's outcome. PLR demonstrates superior outcomes with regard to preservation of visual acuity and avoidance of exenterations, lymph node metastases, and systemic metastases compared to patients managed with other techniques.