Case Presentation and Overview

W.V. is a 39‐year‐old Caucasian male who, on July 4, 2017, presented with right arm numbness while running a 10‐K race. Magnetic resonance imaging (MRI) of the brain revealed a 3‐cm, peripherally enhanced mass (Fig. 1), and computed tomography (CT) with contrast of the chest, abdomen, and pelvis revealed subcentimeter (2‐4 mm) pulmonary nodules with no other sites of disease. On July 7, 2017, he underwent craniotomy with resection of a parietal tumor. Frozen section was initially suspicious for primary glioma; however, final pathology showed metastatic melanoma that was positive for S100, MITF, and SOX10 by immunohistochemistry. There was no history of prior melanoma or nonmelanoma skin cancers, and no primary tumor was identified on a total body skin examination. In addition, a standard comprehensive examination for mucosal, ocular, and other occult sources was performed, and no definitive primary was identified. The tumor was positive for the BRAF V600E mutation by next‐generation sequencing. The patient subsequently underwent radiation to the postoperative bed, receiving 30 grays (Gy) in 5 fractions.

In August 2017, the patient began systemic therapy with ipilimumab 3 mg and nivolumab 1 mg/kg. He received 2 doses of therapy, which was then discontinued because of the development of colitis. After a 6‐week course of steroids, he was initiated on maintenance nivolumab at 480 mg intravenously every 4 weeks. He received 1 year of nivolumab without complication. CT scans of the body and MRI scans of the brain remained stable during this time. For surveillance and to monitor tumor response to treatment, CT scans were used rather than positron emission tomography (PET)/CT scans because the small pulmonary nodules were below the limits of PET detection and were better imaged by dedicated CT scans.

One month after the completion of nivolumab, CT scans showed enlargement of a left upper lobe pulmonary nodule, and the patient subsequently underwent video‐assisted thoracoscopic surgery wedge resection. Pathology showed metastatic melanoma 1 cm in size. It was noted on pathology that 15% of nucleated cells in the periphery and 5% of cells in the center were CD8‐positive lymphocytes. Although the significance of this observation is unclear, preliminary data demonstrate better outcomes for patients who have increased CD8 infiltration of their melanoma.1

After he underwent video‐assisted thoracoscopic surgery resection, the patient was followed with active surveillance. In August 2019, slow but steady growth was noted in the subcentimeter pulmonary nodules over an approximately 18‐month period. All nodules had grown by approximately 2 to 3 mm, with the largest measuring 1 cm. After discussion with the patient, he was started on encorafenib and binimetinib on October 1, 2019. At the time of publication, the patient was tolerating treatment without complications and has had a near complete response to treatment.

中文翻译：

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转移性黑色素瘤。

案例介绍和概述

WV是一位39岁的白人男性，他于2017年7月4日在参加10K比赛时表现出右臂麻木。脑部的磁共振成像（MRI）显示肿块3厘米，周围增大（图1），计算机断层扫描（CT）胸部，腹部和骨盆形成对比，发现肺下结节（2-4毫米）没有其他疾病的地方。2017年7月7日，他接受了开颅手术并切除了顶叶肿瘤。最初，冷冻切片可疑为原发性神经胶质瘤。然而，最终的病理结果显示，转移性黑色素瘤通过免疫组织化学对S100，MITF和SOX10呈阳性。没有既往的黑色素瘤或非黑色素瘤皮肤癌病史，在全身皮肤检查中未发现原发肿瘤。此外，对黏膜，眼，和其他隐匿来源，并没有确定的原发性。肿瘤是阳性的通过下一代测序对BRAF V600E进行突变。患者随后接受放射治疗，并分5次接受30灰度（Gy）治疗。

2017年8月，患者开始以3 mg ipilimumab和1 mg / kg nivolumab进行全身治疗。他接受了2剂治疗，但由于结肠炎的发展而被中止。服用了6周的类固醇激素后，他开始每4周静脉给予480 mg nivolumab维持治疗。他接受了1年的nivolumab治疗，无并发症。在这段时间内，身体的CT扫描和大脑的MRI扫描保持稳定。为了监视和监测肿瘤对治疗的反应，使用CT扫描而不是正电子发射断层扫描（PET）/ CT扫描，因为小的肺结节低于PET检测的极限，并且通过专用CT扫描可以更好地成像。

尼古鲁单抗治疗完成一个月后，CT扫描显示左上叶肺结节增大，随后患者接受了电视胸腔镜手术楔形切除术。病理显示转移性黑色素瘤大小为1厘米。病理学发现，外周有核细胞的15％和中心有细胞的5％是CD8阳性淋巴细胞。尽管这一观察的意义尚不清楚，但初步数据表明，黑色素瘤CD8浸润增加的患者预后较好。1个

在他进行了电视辅助的胸腔镜手术切除后，对该患者进行了主动监视。2019年8月，在大约18个月的时间内，厘米下肺结节出现缓慢但稳定的增长。所有结节已长约2至3毫米，最大结节为1厘米。与患者讨论后，他于2019年10月1日开始接受encorafenib和binimetinib治疗。在发表时，患者耐受治疗且无并发症，并且对治疗的反应几乎完全。