T and N categories per AJCC 8th-edition classification are predictive of local recurrence, metastasis and DSS outcomes for eyelid sebaceous carcinoma. Surgeons should perform strict surveillance testing for nodal and systemic metastases in patients with T2c or worse T category and/or N1 disease at presentation.

Neoadjuvant vismodegib for locally advanced (T4) periocular BCC enabled an eye-sparing surgery in all patients in our cohort. Prolonged treatment was well tolerated by most patients. Over half of patients achieved a complete response with no residual microscopic disease. Careful long-term follow-up is needed to confirm long-term disease-free survival.

onjunctival 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][2][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.In recent years, immune checkpoint inhibitors, a new class of drugs, have been successfully used to treat metastatic cutaneous melanoma. Immune checkpoint inhibitors prevent cancer cells from activating mechanisms that enable the cells to evade the host's immune system. Immune checkpoint inhibitors, by blocking receptors on the surface of activated T lymphocytes, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), facilitate the recognition of cancer cells by lymphocytes and a consequent effective immune response. Ipilimumab (a CTLA-4 inhibitor), pembrolizumab (a PD-1 inhibitor), and nivolumab (a PD-1 inhibitor) are approved by the US Food and Drug Administration for the IMPORTANCE Conjunctival melanoma has the potential for regional lymphatic and distant metastasis. There is an urgent need for effective treatment for patients with metastatic or locally advanced conjunctival melanoma.OBJECTIVE To describe the use of immune checkpoint inhibitors for the treatment of conjunctival melanoma in 5 adult patients. DESIGN, SETTING, AND PARTICIPANTSA retrospective review was conducted of the medical records of 5 patients with conjunctival melanoma who were treated with immune checkpoint inhibitors from March 6, 2013, to July 7, 2017. MAIN OUTCOMES AND MEASURESResponse to treatment and disease-free survival. RESULTSOf the 5 patients (4 women and 1 man) with metastatic conjunctival melanoma, 4 were treated with a programmed cell death 1 (PD-1) inhibitor, nivolumab, and had a complete response to treatment with no evidence of disease at 1, 7, 9, and 36 months after completing treatment. One patient with metastatic conjunctival melanoma was treated with another PD-1 inhibitor, pembrolizumab, and had stable metastases during the first 6 months of treatment. Later disease progression resulted in treatment cessation after 11 months and switching to another therapy. Two patients treated with nivolumab developed autoimmune colitis that necessitated stopping the immunotherapy; these patients subsequently were managed with systemic corticosteroids or infliximab.CONCLUSIONS AND RELEVANCE This case ...

Purpose: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies. Experimental Design: We present next-generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from eight OA sebaceous carcinomas from 29 patients. Results: We delineate two potentially distinct moleculargenetic subtypes of OA sebaceous carcinoma. The first is defined by somatic mutations impacting TP53 and/or RB1 [20/29 (70%) patients, including 10 patients whose primary tumors contained coexisting TP53 and RB1 mutations] with frequent concomitant mutations affecting NOTCH genes. These tumors arise in older patients and show frequent local recurrence. The second subtype [9/29 (31%) patients] lacks mutations affecting TP53, RB1, or NOTCH family members, but in 44% (4/9) of these tumors, RNA sequencing and in situ hybridization studies confirm transcriptionally active high-risk human papillomavirus. These tumors arise in younger patients and have not shown local recurrence. Conclusions: Together, our findings establish a potential molecular-genetic framework by which to understand the development and progression of OA sebaceous carcinoma and provide key molecular-genetic insights to direct the design of novel therapeutic interventions.

TED-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy with anti-cytotoxic T-lymphocyte antigen-4 or anti-PD-1 inhibitors. To the best of their knowledge, this is the first reported case of TED as a result of programmed cell death protein 1 inhibitor monotherapy. All 3 patients were treated with systemic steroids and responded quickly while continuing treatment with immune checkpoint inhibitors for their cancer. With increasing use of this class of drugs, clinicians should be familiar with the clinical manifestations and treatments for this adverse reaction.