An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO) overexpression, loss of phosphatase and tensin homologue (PTEN) expression, and overexpression of the Wnt–β-catenin pathway. Current work in immunotherapy continues to identify various tumor resistance mechanisms; future work is needed to develop adjuvant treatments that target those mechanisms, in order to improve the efficacy of immunotherapy and to expand its scope.

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.

We describe the case of a 69-year-old woman who presented with a decline in vision in the left eye and was found to have a choroidal lesion with clinical and echographic features concerning for primary uveal melanoma. Systemic imaging identified numerous metastases to the liver, kidneys, paratracheal lymph nodes, lung, and brain. The hepatic lesion was biopsied, and genetic analysis identified a Val600Glu (c.1799T&#x3e;A) <i>BRAF</i> mutation, consistent with a cutaneous primary malignancy, although no primary tumor was identified. This case highlights that metastasis to the choroid is a rare presentation of nonuveal melanoma that can mimic primary uveal melanoma. Genetic analysis of tumor tissue can identify the origin of the melanoma and guide treatment options. Systemic imaging should be performed prior to intervention for choroidal neoplasms.

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A 55-year-old woman presented with a 3-month history of right groin swelling, discomfort and impaired mobility. On examination, a palpable mass was noted both to the right of midline in the lower abdomen and in the right groin. MRI of the pelvis showed two masses involving the anterior abdominal wall and right groin, as well as lymph node involvement. CT imaging revealed multiple bilateral pulmonary metastases. Pathology demonstrated a myxohayline stroma morphology. Tumour was also notable for NR4A3 gene region rearrangement and mutation in KIT exon 11 at position c.1669 T>G. Based on these findings, she was diagnosed with extraskeletal myxoid chondrosarcoma (EMC). The patient has been on imatinib, a tyrosine kinase inhibitor with activity against KIT, for 3 years with stable disease. Metastatic EMC is generally treated with surgical resection and perioperative radiation therapy with adjuvant chemotherapy and is associated with poor prognosis.