本文刊登于《中国实用妇科与产科杂志》2022,38(5):529-533
DOI:10.19538/j.fk2022050112
【引用本文】中国优生科学协会生殖道疾病诊治分会,中国医师协会微无创医学专业委员会妇科肿瘤学组.子宫内膜息肉恶变诊治专家指导意见(2022年版)[J].中国实用妇科与产科杂志,2022,38(5):529-533.
作者:中国优生科学协会生殖道疾病诊治分会中国医师协会微无创医学专业委员会妇科肿瘤学组
基 金 项 目 :国 家 自 然 科 学 基 金(81471419,81972448,82172626);天津市重大疾病防治科技重大专项(18ZXDBSY00200);天津市科技计划(18ZXDBSY00220);天津市卫生健康科技项目(ZD20020);天津市医学重点学科(专科)建设项目(TJSYXZDXK021)
通讯作者:薛凤霞,天津医科大学总医院妇产科 天津市女性生 殖 健 康 与 优 生 重 点 实 验 室 ,天 津 300052,电 子 信 箱 :xuefengxia@tmu.edu.cn;张师前,山东大学齐鲁医院,山东济南250012,电子信箱:r370112@126.com;段华,首都医科大学附属北京妇产医院/北京妇幼保健院妇科微创中心,北京 100006,电子信箱:duanhua@ccmu.edu.cn
执笔专家:张颖(首都医科大学附属北京妇产医院/北京妇幼保健院妇科微创中心);王颖梅(天津医科大学总医院)
参与讨论专家(按姓氏笔画排序):王颖梅(天津医科大学总医院);闫晔(天津医科大学总医院);段华(首都医科大学附属北京妇产医院/北京妇幼保健院妇科微创中心);张师前(山东大学齐鲁医院);张颖(首都医科大学附属北京妇产医院/北京妇幼保健院妇科微创中心);薛凤霞(天津医科大学总医院)1 子宫内膜息肉恶变的高危因素
2 子宫内膜息肉恶变的病理诊断及类型
2.1 子宫内膜息肉的病理诊断标准 内膜息肉恶变源于息肉本身的子宫内膜,在息肉表面腺体增生过程中,逐渐发展成癌前病变,最后发生癌变。病理学检查是诊断内膜息肉恶变的金标准。病理诊断内膜息肉恶变需满足以下条件[20-21]:(1)必须看到完整的子宫内膜息肉形态。(2)恶变仅局限于息肉内或息肉表面被覆内膜。(3)子宫内膜息肉根蒂部及息肉周围内膜无恶变。从病理学上,内膜息肉恶变需与子宫内膜癌及癌前病变呈息肉样生长进行鉴别。前者是指恶变起源于息肉内或息肉表面腺体,与息肉周围的内膜并无相关性;而后者是指子宫内膜癌或癌前病变呈息肉样生长,病变与周围子宫内膜无明确界限,且息肉组织中无良性息肉成分。
2.2 子宫内膜息肉恶变的病理类型 内膜息肉恶变发生于内膜腺体,癌变的组织学类型可为子宫内膜样腺癌、浆液性腺癌、透明细胞癌或黏液性癌,并以子宫内膜样腺癌最为常见。生育年龄女性内膜息肉恶变多为子宫内膜样腺癌,而>65岁的绝经后患者以子宫内膜浆液性腺癌最常见,这些特点与子宫内膜癌在人群中的病理类型分布情况相同[22]。随着子宫内膜癌癌症基因组图谱(TCGA)分子分型的研究及应用进展,内膜息肉恶变患者可参考子宫内膜癌分子分型,包括POLE超突变、MSI高突变、低拷贝和高拷贝4种类型,以指导治疗和评估预后。
3 子宫内膜息肉恶变诊断及评估
3.3.5 肿瘤标志物 尚无敏感特异的肿瘤标志物可用于诊断内膜息肉恶变。对于合并有子宫外病变的内膜息肉恶变患者尤其是浆乳癌患者,癌抗原 125(CA125)可升高[33],有助于监测临床治疗效果,但 CA125 的敏感度及特异度均不高。附睾蛋白4(HE4)的价值也尚需深入研究。
4 子宫内膜息肉恶变的治疗
术后辅助治疗依据有无影响预后的高危因素决定,高危因素包括:(1)局部浸润范围:伴有淋巴脉管间隙浸润(lymphovascular space invasion,LVSI)和子宫肌层浸润。尤其是浆液性腺癌伴有LVSI时,宫外转移发生率和肿瘤复发率显著升高[3 3]。(2)分子分型:高拷贝型。(3)子宫外转移。无上述高危因素、局限于息肉内的恶变患者,术后是否补充辅助治疗对预后无影响[36],推荐术后随访。术后补充辅助治疗的条件及辅助治疗方案的选择参照子宫内膜癌。
推荐意见:无生育要求的内膜息肉恶变患者,不建议采取仅切除恶变息肉的保守性手术治疗,推荐全子宫切除术,是否保留卵巢以及是否进行系统性全面分期,需结合龄、是否绝经、病理类型、有无肌层浸润、分子分型、基因检测等情况决定。术后病理提示存在不良预后高危因素的患者,依据子宫内膜癌指南补充辅助治疗。
4.2 有生育要求患者子宫内膜息肉恶变的治疗 年轻有生育需求且病变局限于息肉内者可行宫腔镜下恶变息肉切除术,术后辅以口服孕激素或宫内置入左炔诺孕酮宫内缓释系统,并规律随访,根据情况进行辅助生殖技术治疗。
4.2.1 保留生育功能治疗的指征 当内膜息肉发生癌前病变及早期癌变且病理类型为子宫内膜样腺癌、对于年轻有生育要求的患者均可保留子宫;其保留生育功能治疗指征参考子宫内膜不典型增生及早期子宫内膜癌,建议如下[37]:(1)年龄<40岁,有强烈的生育愿望。(2)组织学类型为高分化子宫内膜样腺癌。随着近年来子宫内膜癌分子分型的研究进展,对于有保留生育功能意愿的患者,有条件者建议行分子分型,排除高拷贝型子宫内膜癌、Lynch综征及BRCA基因突变。(3)癌变局限于息肉内,无肌层浸润。(4)影像学评估未见明显子宫外转移病灶。(5)病变雌、孕激素受体阳性。(6)血清 CA125正常。(7)无孕激素治疗及妊娠禁忌证,无其他生育障碍因素。(8)有较好的依从性及随访条件。
4.2.2 治疗原则与操作规范
4.2.2.1 手术方法 保留生育功能的手术是指切除恶变的内膜息肉而保留子宫。内膜息肉恶变保留生育功能的治疗不同于普通的内膜息肉切除,既要严格采用无瘤防御原则(minimallyinvasive procedures and tumor free strategy,MIPTFS)完整切除内膜息肉,又要在达到诊疗目的,并最大限度保护子宫内膜。推荐采用四步法[38],具体如下:(1)从息肉根蒂部完整切除内膜息肉。(2)息肉根蒂部周围0.2~0.5cm内膜活检。(3)切除息肉根蒂部下方深约0.3cm的子宫肌层组织。(4)宫腔其余部位子宫内膜多点活检。使用四步切除法获得的标本能有效地将内膜息肉恶变和子宫内膜癌累及息肉进行鉴别、明确恶变的息肉对子宫肌层有无浸润、同时明确恶变息肉是否同时合并其余部位子宫内膜病变,为制定手术方案提供依据。手术时控制膨宫压力小于平均动脉压。
4.2.2.2 宫腔镜器械选择 单极或双极等电切器械、非能量冷刀器械(如抓钳或剪刀)以及新近发展起来的微型电切镜系统和双极真空管激光均可使用,依据术者经验选择。宫腔镜组织切除回收系统因不能保持切除息肉的完整性,因而不建议使用。
4.2.3 术后药物治疗 术后高效孕激素治疗方案参考子宫内膜不典型增生及子宫内膜癌的治疗:醋酸甲地孕酮160~320mg每日 1 次或醋酸甲羟孕酮 250~500mg每日 1次,治疗时间至少6个月以上,每3个月宫腔镜及子宫内膜活检复查。如子宫内膜正常,建议借助辅助生殖技术尽早完成生育;暂无生育计划者,建议宫腔内放置左炔诺孕酮宫内缓释系统,仍应至少每6~12个月评估子宫内膜1次,以监测病变有无复发[37]。随访过程中如出现难以解释的异常子宫出血以及子宫内膜增厚,则需及时行子宫内膜评估。
5 子宫内膜息肉恶变的随访
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