Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

Purpose To evaluate the outcomes among patients with adenoid cystic carcinoma of the lacrimal gland treated at various stages of their disease at a tertiary care cancer center. Methods A retrospective case series of 20 patients with adenoid cystic carcinoma of the lacrimal gland treated at a single institution between 1952 and 2002. Clinical records were available for all 20 patients; histologic sections from 12 of the 20 patients were available for review. Disease-free survival was measured from the completion of treatment; overall survival was measured from the date of initial diagnosis. Results The study included 6 men and 14 women. The mean age at diagnosis was 39.5 years. The median follow-up time was 34 months (range, 6 to 264 months). The local/regional treatment modalities included exenteration with bone removal and radiation therapy (RT) in 5 patients, exenteration with RT (no bone removal) in 8 patients, exenteration (no RT or bone removal) in 1 patient, exenteration with bone removal (no RT) in 1 patient, local resection with RT in 3 patients, and local resection without RT in 2 patients. Overall, 16 patients had RT as part of their treatment regimen. Seven patients (35%) had local recurrence. Sixteen patients (80%) had distant metastasis during the study period. At the time of this report, 13 (65%) of the patients had died of disease. The median disease-free survival for the entire group was 18 months. Eight patients had a predominantly basaloid histologic pattern. Ten patients had verifiable histologic evidence of perineural invasion. Conclusions This study underscores the generally grave prognosis for patients with adenoid cystic carcinoma of the lacrimal gland and the difficulty in making any conclusive recommendations for local therapy for this disease.

Conjunctival melanoma is a rare tumor with the potential to invade the eye, eyelid, and orbit and spread to regional lymphatics and distant sites, including the lungs, skin, liver, and brain. It was previously reported to have local recurrence rates of 36% to 45% at 5 years and 31% to 59% at 10 years.¹ Lymph node involvement was found in 19% of patients with conjunctival melanoma and systemic metastases were found in 19% of patients within 10 years after initial diagnosis.^1,2 Melanoma-related death was reported in 9% to 18% of patients at 5 years.^1-3 The mainstay of treatment for local control is surgical excision with margins clear of tumor; locally advanced disease may necessitate an orbital exenteration. Adjuvant treatments include topical chemotherapy and radiotherapy and are aimed at improving local control. Historically, treatment options for metastatic conjunctival melanoma have been limited.