Elucidating the multiple genetic alterations involved in the malignant transformation of a <scp> <i>KRAS</i> </scp> mutant neurenteric cyst. A case report
Elucidating the multiple genetic alterations involved in the malignant transformation of a <scp> <i>KRAS</i> </scp> mutant neurenteric cyst. A case report
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阐明<scp> <i>KRAS</i> </scp>突变神经肠囊肿恶性转化中涉及的多种遗传改变。
DOI：
10.1111/neup.12822
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发表时间：
2022
期刊：
影响因子：
2.3
通讯作者：
Fujii Yukihiko
中科院分区：
文献类型：
--
作者：
Saito Shoji;Natsumeda Manabu;Sainouchi Makoto;Takino Toru;Shibuya Kohei;On Jotaro;Kanemaru Yu;Ogura Ryosuke;Okada Masayasu;Oishi Makoto;Shimada Yoshifumi;Wakai Toshifumi;Okuda Shujiro;Ajioka Yoichi;Kakita Akiyoshi;Fujii Yukihiko
神经性囊肿(NC)表现为良性的组织病理学，很少表现为恶变。我们在此描述一例表现为恶变的NC。女性，65岁，因延髓背侧表面囊性肿块压迫而出现步态障碍。进行了两次部分切除，使她的症状得到改善。第二次手术两年后，灌注Gd的T1加权磁共振成像显示左侧脑室三角区有一个侵袭性病变，并有对比增强，为此进行了部分切除和放射治疗。然而，观察到了大规模的再生，患者在第三次手术11个月后最终死于疾病。第一次和第二次手术标本的组织病理学分析发现，囊壁内表面排列着假复层立方上皮细胞，没有类似胃肠道粘膜的核或细胞异型性。根据这些发现，该病变被诊断为NC。第三例手术标本显示明显的恶性上皮细胞特征，细胞核延长，深染，有丝分裂，小的坏死灶，无图案或片状排列。根据这些发现，该病变被诊断为NC伴恶变。下一代测序显示所有样本中都存在KRASp.G12D突变。此外，第三例手术标本存在以下12个新基因的改变：ARID1Aoss、BAP1p.F170L、CDKN1Boss、CDKN2Aoss、CDKN2Boss、FLCNoss、PTCH1 Loss、PTENloses、PTPRDoss、SUFU Loss、TP53 Loss和TSC1 Lost。上述结果提示，KRAS突变与NC的发生发展有关，额外的基因改变有助于NC的恶性转化。
Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65‐year‐old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium‐perfused T1‐weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet‐like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next‐generation sequencing revealedKRASp.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12de novogene alterations:ARID1Aloss,BAP1p.F170L,CDKN1Bloss,CDKN2Aloss,CDKN2Bloss,FLCNloss,PTCH1loss,PTENloss,PTPRDloss,SUFUloss,TP53loss, andTSC1loss. The aforementioned results suggest thatKRASmutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.