{"title":"SMARCA4突变的食管癌:对这一罕见病例的综述。","authors":"Jing Xu, Zhikai Chi","doi":"10.21037/tgh-23-84","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Esophageal carcinoma with switch/sucrose nonfermenting (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (<i>SMARCA4</i>) mutation is a rare variant of malignant esophageal epithelial neoplasm, which is characterized by the loss of SMARCA4/BRG1 protein on immunohistochemistry or alterations in the <i>SMARCA4</i> gene on sequencing. Only a few case series and case reports of esophageal carcinoma with <i>SMARCA4</i> mutations have been published in the English literature; the rarity of the disease poses significant diagnostic challenges for surgical pathologists and could potentially lead to delayed or suboptimal patient care. Herein, we reviewed the available literature on esophageal carcinoma with <i>SMARCA4</i> mutations to discuss its epidemiology, clinical presentation, pathological and molecular features, diagnostic challenges, treatment, and prognosis.</p><p><strong>Methods: </strong>The PubMed, Scopus, Ovid, and Google Scholar databases were extensively reviewed. The references included in the articles were cross-examined to identify any missing articles. We searched for all published literature on esophageal carcinoma with <i>SMARCA4</i> mutations from inception of the databases to date.</p><p><strong>Key content and findings: </strong>Esophageal carcinoma with <i>SMARCA4</i> mutations is most common in middle-aged and older men. Barrett esophagus and gastroesophageal reflux disease (GERD) are the most associated risk factors. Dysphagia was the most common initial clinical presentation. Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Microscopically, the tumor cells exhibited epithelioid features mixed with variable components of rhabdoid and glandular differentiation. The tumor cells showed variable immunoreactivity for cytokeratin and sometimes weakly expressed neuroendocrine or B-lymphocyte markers (Pax5), which are potential diagnostic pitfalls. Melanoma marker tests showed negative results. The SMARCB1/INI1 protein remains intact, and a definitive diagnosis necessitates the presence of either SMARCA4/BRG1 protein loss or <i>SMARCA4</i> gene mutations. Esophageal carcinoma with <i>SMARCA4</i> mutations shows overly aggressive behavior and presents with advanced stages of disease; most patients succumb to the disease within 1 year of initial diagnosis.</p><p><strong>Conclusions: </strong>Esophageal carcinoma with <i>SMARCA4</i> mutation is an overly aggressive disease, and further research on the affected molecular pathway may help improve its prognosis.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"24"},"PeriodicalIF":3.8000,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074479/pdf/","citationCount":"0","resultStr":"{\"title\":\"Esophageal carcinoma with <i>SMARCA4</i> mutation: a narrative review for this rare entity.\",\"authors\":\"Jing Xu, Zhikai Chi\",\"doi\":\"10.21037/tgh-23-84\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Esophageal carcinoma with switch/sucrose nonfermenting (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (<i>SMARCA4</i>) mutation is a rare variant of malignant esophageal epithelial neoplasm, which is characterized by the loss of SMARCA4/BRG1 protein on immunohistochemistry or alterations in the <i>SMARCA4</i> gene on sequencing. Only a few case series and case reports of esophageal carcinoma with <i>SMARCA4</i> mutations have been published in the English literature; the rarity of the disease poses significant diagnostic challenges for surgical pathologists and could potentially lead to delayed or suboptimal patient care. Herein, we reviewed the available literature on esophageal carcinoma with <i>SMARCA4</i> mutations to discuss its epidemiology, clinical presentation, pathological and molecular features, diagnostic challenges, treatment, and prognosis.</p><p><strong>Methods: </strong>The PubMed, Scopus, Ovid, and Google Scholar databases were extensively reviewed. The references included in the articles were cross-examined to identify any missing articles. We searched for all published literature on esophageal carcinoma with <i>SMARCA4</i> mutations from inception of the databases to date.</p><p><strong>Key content and findings: </strong>Esophageal carcinoma with <i>SMARCA4</i> mutations is most common in middle-aged and older men. Barrett esophagus and gastroesophageal reflux disease (GERD) are the most associated risk factors. Dysphagia was the most common initial clinical presentation. Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Microscopically, the tumor cells exhibited epithelioid features mixed with variable components of rhabdoid and glandular differentiation. The tumor cells showed variable immunoreactivity for cytokeratin and sometimes weakly expressed neuroendocrine or B-lymphocyte markers (Pax5), which are potential diagnostic pitfalls. Melanoma marker tests showed negative results. The SMARCB1/INI1 protein remains intact, and a definitive diagnosis necessitates the presence of either SMARCA4/BRG1 protein loss or <i>SMARCA4</i> gene mutations. Esophageal carcinoma with <i>SMARCA4</i> mutations shows overly aggressive behavior and presents with advanced stages of disease; most patients succumb to the disease within 1 year of initial diagnosis.</p><p><strong>Conclusions: </strong>Esophageal carcinoma with <i>SMARCA4</i> mutation is an overly aggressive disease, and further research on the affected molecular pathway may help improve its prognosis.</p>\",\"PeriodicalId\":94362,\"journal\":{\"name\":\"Translational gastroenterology and hepatology\",\"volume\":\"9 \",\"pages\":\"24\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-03-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074479/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational gastroenterology and hepatology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.21037/tgh-23-84\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational gastroenterology and hepatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21037/tgh-23-84","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景和目的:食管癌伴有开关/蔗糖不发酵(SWI/SNF)相关、基质相关、肌动蛋白依赖的染色质调节因子A亚家族成员4(SMARCA4)突变是恶性食管上皮肿瘤的一种罕见变异,其特征是免疫组化显示SMARCA4/BRG1蛋白缺失或测序显示SMARCA4基因发生改变。英文文献中仅发表了几例SMARCA4基因突变食管癌的系列病例和病例报告;这种疾病的罕见性给外科病理学家的诊断带来了巨大挑战,并可能导致患者治疗的延误或不理想。在此,我们回顾了关于SMARCA4突变食管癌的现有文献,讨论了其流行病学、临床表现、病理和分子特征、诊断挑战、治疗和预后:广泛查阅了 PubMed、Scopus、Ovid 和 Google Scholar 数据库。方法:我们广泛查阅了 PubM、Scopus、Ovid 和 Google Scholar 数据库,并交叉检查了文章中的参考文献,以确定是否有遗漏的文章。我们检索了从数据库建立至今所有关于SMARCA4突变食管癌的已发表文献:SMARCA4突变的食管癌最常见于中老年男性。巴雷特食管和胃食管反流病(GERD)是最相关的风险因素。吞咽困难是最常见的初始临床表现。食管胃十二指肠镜检查(EGD)是首选的诊断方式。显微镜下,肿瘤细胞表现为上皮样特征,并混有横纹肌样和腺体分化的不同成分。肿瘤细胞对细胞角蛋白有不同的免疫反应,有时还弱表达神经内分泌或 B 淋巴细胞标记物(Pax5),这些都是潜在的诊断陷阱。黑色素瘤标记物检测结果为阴性。SMARCB1/INI1蛋白保持完整,要明确诊断,必须存在SMARCA4/BRG1蛋白缺失或SMARCA4基因突变。SMARCA4基因突变的食管癌表现出过度的侵袭性,并出现晚期病变;大多数患者在最初诊断后一年内死亡:结论:SMARCA4基因突变的食管癌是一种侵袭性很强的疾病,进一步研究受影响的分子通路可能有助于改善其预后。
Esophageal carcinoma with SMARCA4 mutation: a narrative review for this rare entity.
Background and objective: Esophageal carcinoma with switch/sucrose nonfermenting (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutation is a rare variant of malignant esophageal epithelial neoplasm, which is characterized by the loss of SMARCA4/BRG1 protein on immunohistochemistry or alterations in the SMARCA4 gene on sequencing. Only a few case series and case reports of esophageal carcinoma with SMARCA4 mutations have been published in the English literature; the rarity of the disease poses significant diagnostic challenges for surgical pathologists and could potentially lead to delayed or suboptimal patient care. Herein, we reviewed the available literature on esophageal carcinoma with SMARCA4 mutations to discuss its epidemiology, clinical presentation, pathological and molecular features, diagnostic challenges, treatment, and prognosis.
Methods: The PubMed, Scopus, Ovid, and Google Scholar databases were extensively reviewed. The references included in the articles were cross-examined to identify any missing articles. We searched for all published literature on esophageal carcinoma with SMARCA4 mutations from inception of the databases to date.
Key content and findings: Esophageal carcinoma with SMARCA4 mutations is most common in middle-aged and older men. Barrett esophagus and gastroesophageal reflux disease (GERD) are the most associated risk factors. Dysphagia was the most common initial clinical presentation. Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Microscopically, the tumor cells exhibited epithelioid features mixed with variable components of rhabdoid and glandular differentiation. The tumor cells showed variable immunoreactivity for cytokeratin and sometimes weakly expressed neuroendocrine or B-lymphocyte markers (Pax5), which are potential diagnostic pitfalls. Melanoma marker tests showed negative results. The SMARCB1/INI1 protein remains intact, and a definitive diagnosis necessitates the presence of either SMARCA4/BRG1 protein loss or SMARCA4 gene mutations. Esophageal carcinoma with SMARCA4 mutations shows overly aggressive behavior and presents with advanced stages of disease; most patients succumb to the disease within 1 year of initial diagnosis.
Conclusions: Esophageal carcinoma with SMARCA4 mutation is an overly aggressive disease, and further research on the affected molecular pathway may help improve its prognosis.