Synovial sarcoma (SS) is an aggressive tumor that most often affects the deep soft tissues in young adults. Intrathoracic SS is rare and is associated with poor outcome, highlighting the urgent need for a novel therapeutic strategy. In the process of clinical sequencing, we identified two patients with intrathoracic SS harboring the BRAF V600E mutation. The patients were women aged 32 and 23 years, and both presented with SS18-SSX2-positive monophasic SS in the thoracic cavity. BRAF V600E mutations were detected by next generation sequencing, and validated immunohistochemically by diffuse intense positivity to BRAF V600E mutation-specific antibodies. The phosphorylated ERK (pERK) immunohistochemistry result was also positive. One patient received a combination therapy of dabrafenib and trametinib, which led to tumor shrinkage. However, the tumor growth progressed 7.5 months later with an additional NRAS Q61K mutation. Immunohistochemical screening of 67 archival SS tumor samples failed to identify additional samples with BRAF V600E mutation. However, 32% of BRAF V600E-negative cases was positive for pERK, and one of the six tumors showing the highest pERK expression harbored an FGFR2-activating mutation. This is the first report of targetable BRAF mutation in a small subset of SS. Our study suggests involvement of the mitogen-activated protein kinase pathway and the potential clinical implication of BRAF mutation screening in SS.

中文翻译：

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BRAF V600E 突变是一小部分滑膜肉瘤的潜在治疗靶点。

滑膜肉瘤 (SS) 是一种侵袭性肿瘤，最常影响年轻人的深层软组织。胸腔内 SS 很少见且预后不良，这突出表明迫切需要一种新的治疗策略。在临床测序过程中，我们确定了两名胸腔内 SS 患者携带 BRAF V600E 突变。患者年龄分别为 32 岁和 23 岁，均表现为胸腔 SS18-SSX2 阳性单相 SS。通过下一代测序检测到 BRAF V600E 突变，并通过对 BRAF V600E 突变特异性抗体的弥散强阳性进行免疫组织化学验证。磷酸化ERK（pERK）免疫组化结果也呈阳性。一名患者接受了达拉非尼和曲美替尼的联合治疗，导致肿瘤缩小。然而，7.5 个月后肿瘤生长进展，并伴有额外的 NRAS Q61K 突变。对 67 个存档 SS 肿瘤样本进行免疫组织化学筛查未能识别出具有 BRAF V600E 突变的其他样本。然而，32% 的 BRAF V600E 阴性病例呈 pERK 阳性，pERK 表达最高的 6 个肿瘤之一带有 FGFR2 激活突变。这是 SS 的一小部分中可靶向 BRAF 突变的第一份报告。我们的研究表明丝裂原活化蛋白激酶途径的参与以及 SS 中 BRAF 突变筛查的潜在临床意义。32% 的 BRAF V600E 阴性病例呈 pERK 阳性，pERK 表达最高的 6 个肿瘤之一带有 FGFR2 激活突变。这是 SS 的一小部分中可靶向 BRAF 突变的第一份报告。我们的研究表明丝裂原活化蛋白激酶途径的参与以及 SS 中 BRAF 突变筛查的潜在临床意义。32% 的 BRAF V600E 阴性病例呈 pERK 阳性，pERK 表达最高的 6 个肿瘤之一带有 FGFR2 激活突变。这是 SS 的一小部分中可靶向 BRAF 突变的第一份报告。我们的研究表明丝裂原活化蛋白激酶途径的参与以及 SS 中 BRAF 突变筛查的潜在临床意义。