Advances in conjunctival melanoma: clinical features, diagnostic modalities, staging, genetic markers, and management.

Conjunctival melanoma, a rare malignancy of the ocular surface, is increasing in incidence. When small, straightforward excision with "no touch" surgery and cryotherapy at an experienced centre can provide excellent outcomes. When advanced, management is more complex and highly individualized. The risk of metastatic disease from conjunctival melanoma is as high as 30% and depends on tumour origin, American Joint Committee on Cancer (AJCC) classification, biomarkers, and perhaps most important, management technique. Metastatic disease can result in melanoma-associated death. Therefore, early detection and prompt directed treatment at an experienced centre are important for protection from metastasis. In this review, we provide an update on conjunctival melanoma clinical features, diagnostic modalities, AJCC staging, genetic markers, and the most critical, controlled management with minimization of tumour seeding. We detail the new era of characterization of conjunctival melanoma with molecular biomarkers that predict melanoma prognosis. This could lead to precision medicine with targeted approaches to specific mutations that improve patient survival. As we work together, the field of conjunctival melanoma is moving forward.

Conditional survival of uveal melanoma using The Cancer Genome Atlas (TCGA) classification (Simplified Version) in 1001 cases.

PURPOSE: To understand conditional prognostic value of the Cancer Genome Atlas (TCGA) for uveal melanoma metastasis based on event-free survival at 1, 2, 3, 4, and 5 years. METHODS: A retrospective study of eyes with uveal melanoma categorized according to TCGA and studied for nonconditional and conditional risks for metastasis at 5 and 10 years. RESULTS: Of 1001 eyes with uveal melanoma, the nonconditional (standard, at presentation) 5-year/10-year metastatic rate was 18%/25%. The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed 10%/18% and the conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed 9%. The TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), and D (n = 114, 11%). The non-conditional 5-year/10-year metastatic rate revealed Group A (4%/6%), Group B (12%/20%), Group C (23%/49%), and Group D (60%/68%). The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed Group A (2%/5%), Group B (8%/18%), Group C (21%/40%), and Group D (38%/50%). The conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed Group A (2%), Group B (10%), Group C (33%), and Group D (20%). The peak incidence of metastasis for Groups A and B occurred during years 5-6, C during years 4-6, and D during years 1-2. CONCLUSION: Survival outcomes for uveal melanoma as non-conditional (at presentation) and conditional (event-free survival during follow-up) reveal reduction in metastatic rate over time. For those with 5-year metastasis-free survival, the 10-year conditional risk for metastasis was 9%.

Ocular Surface Squamous Neoplasia Managed With Primary Interferon α2b: A Comparative Analysis of 212 Tumors in Smokers Versus Nonsmokers.

PURPOSE: To explore clinical features and outcomes of ocular surface squamous neoplasia (OSSN) treated with primary interferon (IFN)-α2b, based on patient cigarette smoking status. METHODS: Retrospective nonrandomized, interventional cohort study on 212 consecutive tumors in 194 patients, all of whom were treated with topical and/or injection IFNα2b. RESULTS: There were 88 tumors in 76 patients with current or past smoking history (smokers) and 124 tumors in 118 nonsmoking patients (nonsmokers). A comparison (smokers vs. nonsmokers) revealed smokers with more frequent bilateral disease (16% vs. 3%, P = 0.003), more frequent involvement of inferior forniceal (34% vs. 21%, P = 0.03) and inferior tarsal conjunctiva (38% vs. 24%, P = 0.04), greater mean number of clock hour involvement (4.1 vs. 3.5 clock hours, P = 0.04), and greater dome growth pattern (30% vs. 15%, P = 0.01). There was no difference regarding method of IFNα2b administration as topical (61% vs. 71%, P = 0.14), injection (10% vs. 6%, P = 0.32), or combination topical/injection (28% vs. 23%, P = 0.33). A comparison revealed smokers with more frequent recurrence after initial response (23% vs. 13%, P = 0.04). There was no difference regarding initial tumor response or time to response, treatment side effects, or systemic outcomes. CONCLUSIONS: Regarding ocular surface squamous neoplasia, smokers more often display bilateral, dome-shaped tumors with inferior forniceal or tarsal involvement, and greater extent than nonsmokers. After treatment with topical and/or injection IFNα2b, control is equivalent, but smokers show greater recurrence.

Conjunctival Melanoma: Outcomes based on the American Joint Committee on Cancer Clinical Classification (8th Edition) of 425 Patients at a Single Ocular Oncology Center.

PURPOSE: The aim of this study was to evaluate outcomes of conjunctiva melanoma based on the American Joint Committee on Cancer Classification (AJCC) 8th edition. DESIGN: Retrospective interventional case series. METHODS: Outcomes analysis of 425 patients. RESULTS: In this analysis of 425 patients with conjunctival melanoma, there were 266 (63%) patients classified as T1, 75 (18%) as T2, 84 (20%) as T3, and 0 (0%) as T4. A comparison (T1 vs T2 vs T3) revealed that history of primary acquired melanosis was more common in T2 (81% vs 96% vs 81%; P = 0.01) and conjunctival nevus more common in T1 (20% vs 9% vs 11%; P = 0.03). Of 381 patients with follow-up (mean of 57.6 months), comparison revealed higher T category with increasing local recurrence/new tumor (30% vs 43% vs 49%; P = 0.004), increasing exenteration (3% vs 9% vs 28%; P < 0.001), increasing melanoma-related locoregional lymph node metastasis (2% vs 7% vs 12%; P = 0.001), increasing melanoma-related systemic metastasis (9% vs 25% vs 23%; P < 0.001), and increasing melanoma-related death (4% vs 12% vs 18%; P < 0.001). A comparison at 10 years revealed visual acuity loss of >3 lines (32% vs 42% vs 63%; P < 0.001), melanoma recurrence/new tumor (47% vs 70% vs 74%; P < 0.001), exenteration (4% vs 24% vs 46%; P < 0.001), melanoma-related locoregional lymph node metastasis (3% vs 13% vs 25%; P < 0.001), melanoma-related systemic metastasis (13% vs 45% vs 40%; P < 0.001), and melanoma-related death (8% vs 22% vs 37%; P < 0.001). CONCLUSIONS: Based on the AJCC 8th edition of conjunctival melanoma, the 10-year risk per T category significantly increased for visual acuity loss of >3 lines, recurrence/new tumor, exenteration, locoregional and systemic melanoma-related metastasis, and melanoma-related death.

Conjunctival Tumors: Review of Clinical Features, Risks, Biomarkers, and Outcomes--The 2017 J. Donald M. Gass Lecture.

Conjunctival tumors encompass a broad range of diagnoses. The 3 most important malignant tumors include ocular surface squamous neoplasia (OSSN) (14%), melanoma (12%), and lymphoma (7%). Conjunctival malignancies are rarely found in children. Regarding OSSN, pre-disposing conditions include chronic solar radiation, immune deficiency (HIV), organ transplant, autoimmune conditions, xeroderma pigmentosum, and chronic exposure to cigarette smoke. OSSN is managed surgically or with topical/injection immunotherapy or chemotherapy. Metastasis occurs in <1%. Regarding melanoma, predisposing conditions include primary acquired melanosis (PAM), chronic nevus, and chronic solar radiation. Treatment of PAM or nevus can prevent melanoma. Melanoma management involves surgical resection with clean margins and avoidance of direct tumor manipulation ("no touch" technique). The first surgery is most important, to minimize tumor seeding. Biomarkers including BRAF, TERT, and PTEN provide information regarding risk for metastasis and allow for targeted antibiomarker therapies. Ten-year risk for melanoma metastasis is 25%. Tumors >2 mm thickness or those located in fornix, caruncle, or orbit are at highest risk for metastasis. Regarding lymphoma, predisposing conditions include benign reactive lymphoid hyperplasia, immune deficiency (HIV), immune dysfunction, and chronic inflammation/infection (Helicobacter pylori, Chlamydia psittaci). The 4 most important subtypes include extranodal marginal zone lymphoma (ENMZL), follicular lymphoma, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma. Treatment includes surgical resection, cryotherapy, radiotherapy, systemic chemotherapy, or targeted anti-B-cell therapy (rituximab). Lymphoma-related survival (5-year) depends on subtype and ranges from 97% (ENMZL) to 9% (MCL). Recognizing conjunctival tumors and understanding predisposing factors, biomarkers, and treatment strategies are vital to patient outcomes.

Sebaceous Carcinoma of the Ocular Region: The 2014 Professor Winifred Mao Lecture.

Sebaceous carcinoma is a malignancy arising in the periocular region that can lead to blindness and tumor-related metastases. This study is a review of published literature and personal experience. This malignancy can arise from the sebaceous units in the tarsus (meibomian glands), in association with the cilia (Zeis glands), in the brow, and in the caruncle. There is a tendency for diffuse intraepithelial growth (pagetoid spread) that can be clinically invisible. Detection before lymph node metastasis is critical. This malignancy often masquerades as chronic unilateral conjunctivitis or blepharitis, typically in older patients. Management includes a 2-step approach with step 1 focused on eyelid and conjunctival map biopsies to determine the full extent of solid deep tumor and pagetoid spread. After complete review of all biopsies, step 2 is performed using local resection for all deep tumor, cryotherapy to pagetoid disease, and reconstruction. In most cases, the posterior lamella of eyelid is sacrificed with tumor removal, whereas the anterior lamella of the eyelid can be saved. After removal and cryotherapy, immediate reconstruction, using clean instruments, with buccal membrane graft for the posterior lamella and skin flap for the anterior lamella, is developed. For persistent or recurrent pagetoid disease, cryotherapy, topical mitomycin C, or plaque radiotherapy is provided. Exenteration is sometimes necessary. Sebaceous carcinoma, if detected early, can be managed with carefully planned map biopsy to determine tumor extent, followed by local resection, cryotherapy, and eyelid reconstruction. Orbital exenteration is occasionally necessary.