在SMARCB1/ ini1缺陷和tp53突变的低分化脊索瘤中,原转移性CXCR4和组蛋白甲基转移酶EZH2上调

Albina Joldoshova, S. Elzamly, Robert Brown, J. Buryanek
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引用次数: 1

摘要

背景:脊索瘤是一种罕见的肿瘤,最常见于骶尾骨区脊索残余。通常,这些肿瘤是局部侵袭性和复发性的,它们有5-43%的转移能力。一种被称为低分化脊索瘤的新发现的侵袭性变异与常规脊索瘤不同,它不具有常规脊索瘤的高分化组织学外观,也表现出SMARCB1/INI1的缺失。在这里,我们描述了一例低分化脊索瘤,伴有SMARCB1/INI1缺失,并发TP53突变和Rb1缺失。方法:患者为中年男性,既往有骶尾椎脊索瘤切除术史,发现肝脏、肺和肾上腺有新的病变。结果:肝脏病变活检显示恶性上皮样细胞片,胞浆呈空泡状,坏死区域,高倍镜下可见5个有丝分裂。未见实质细胞学特征或基质物质。在回顾了广泛的免疫组织化学标记后,转移性肿瘤的起源无法确定;肿瘤仅呈Cam5.2、EMA和CD56阳性。由于患者既往病史,我们进行了Brachyury检查,结果为阳性。基因组检测显示SMARCB1突变、TP53突变和RB1缺失。进行了其他标记,肿瘤显示Ki-67增殖指数约为80%,p53蛋白突变,INI1缺失,组蛋白甲基转移酶EZH2和趋化因子受体CXCR4强烈表达。结论:低分化脊索瘤是一种高度侵袭性的脊索瘤,报道病例很少。这例SMARCB1/ ni缺陷、低分化脊索瘤也同时出现TP53突变和RB1缺失,导致恶性转化,转移前CXCR4和组蛋白甲基转移酶EZH2均上调,导致侵袭性行为和转移。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prometastatic CXCR4 and Histone Methyltransferase EZH2 Are Upregulated in SMARCB1/INI1-Deficient and TP53-Mutated Poorly Differentiated Chordoma
Background: Chordoma is a rare tumor most commonly arising in the sacrococcygeal region from notochord remnants. Usually, these tumors are locally invasive and recurrent, and they have a 5–43% ability to metastasize. A newly-described aggressive variant called poorly differentiated chordoma is different from conventional chordoma in that it does not have the well-differentiated histologic appearance of conventional chordoma and also exhibits the loss of SMARCB1/INI1. Herein, we describe a case of poorly differentiated chordoma with SMARCB1/INI1 loss, a concurrent TP53 mutation, and Rb1 loss. Methods: The patient is a middle-aged man with a history of previously resected sacrococcygeal chordoma, who was found to have new hepatic, lung, and adrenal lesions. Results: Biopsy of the liver lesion showed sheets of malignant epithelioid cells with vacuolated cytoplasm, areas of necrosis, and up to five mitoses in one high-power field. No physaliferous cytologic features or matrix material was seen. After reviewing an extensive panel of immunohistochemical markers, the origin of the metastatic tumor could not be determined; the tumor was only positive for Cam5.2, EMA, and CD56. Brachyury was performed due to the patient’s previous history and was positive. Genomic testing showed a SMARCB1 mutation, TP53 mutation, and RB1 loss. Additional markers were performed, and the tumor showed a Ki-67 proliferation index of approximately 80%, mutant p53 protein, loss of INI1, and strong expression of both the histone methyl transferase EZH2 and the chemokine receptor CXCR4. Conclusions: Poorly differentiated chordoma is a highly aggressive variant of chordoma with few cases reported. This case of SMARCB1/INI-deficient, poorly differentiated chordoma also showed a concurrent TP53 mutation and loss of RB1, which resulted in malignant transformation with upregulation of both prometastatic CXCR4 and the histone methyltransferase EZH2, causing aggressive behavior and metastasis.
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