PDF(Pubmed)
Abstract：
Malignant gastrointestinal neuroectodermal tumors (GNETs), also called clear-cell sarcoma-like tumors of the gastrointestinal tract, are rare and highly aggressive tumors originating in the gastrointestinal tract. These tumors are generally immunohistochemically positive for S-100 protein (S-100) and SRY-related HMG-box 10 (SOX10), and often contain EWSR1-ATF1 or EWSR1-CREB1. The histological features of GNETs overlap with those of clear-cell sarcoma of the tendons and aponeuroses. However, GNETs immunohistochemically lack melanocyte-specific markers and often demonstrate positivity for CD56, synaptophysin and neuron-specific enolase. The present case reports a woman with a history of desmoplastic malignant melanoma exhibiting a BRAF mutation, which later transformed into a GNET of the small intestine with both a BRAF mutation and two subtypes of EWSR1-ATF1 fusion genes. Tumor cells were revealed to be weakly immunoreactive or negative for S-100 and SOX10, lacked markers of melanocytic differentiation and were focally positive for CD56. Combination therapy with dabrafenib mesylate and trametinib dimethyl sulfoxide proved to be temporarily effective against this tumor. The present case is relatively unique as, to the best of our knowledge, there is no case of GNET with a history of melanoma. Furthermore, there is no report of GNET exhibiting both a BRAF mutation and an EWSR1-ATF1 fusion gene. Further accumulation of similar cases is necessary to elucidate the pathological significance of this GNET having a BRAF mutation.
摘要：
恶性胃肠神经外胚层肿瘤(GNETs),也被称为胃肠道的透明细胞肉瘤样肿瘤，是起源于胃肠道的罕见且高度侵袭性的肿瘤。这些肿瘤的S-100蛋白（S-100）和SRY相关的HMG-box10（SOX10）通常免疫组织化学阳性，并且通常含有EWSR1-ATF1或EWSR1-CREB1。GNETs的组织学特征与肌腱和腱膜的透明细胞肉瘤的组织学特征重叠。然而,GNETs在免疫组织化学上缺乏黑素细胞特异性标记，并且通常显示出CD56，突触素和神经元特异性烯醇化酶的阳性。本病例报道一名女性，有增生性恶性黑色素瘤病史，表现出BRAF突变，后来转化为具有BRAF突变和EWSR1-ATF1融合基因的两种亚型的小肠GNET。发现肿瘤细胞对S-100和SOX10的免疫反应性弱或阴性，缺乏黑素细胞分化的标志物，并且对CD56呈局部阳性。甲磺酸达布拉非尼和曲美替尼二甲基亚砜的联合治疗被证明对这种肿瘤暂时有效。目前的情况相对独特，因为，据我们所知,无黑色素瘤病史的GNET病例。此外，没有GNET同时显示BRAF突变和EWSR1-ATF1融合基因的报道。类似病例的进一步积累对于阐明具有BRAF突变的GNET的病理学意义是必要的。
