双胎妊娠完全性葡萄胎与胎儿共存伴肺转移一例.pdf

本文为回顾性研究，遵守 赫尔辛基宣言，并经甘肃省妇幼保健院伦理委员会批准，免除受试者知情同意，批准文号：2018院伦审研第（15）号。患者女，25岁，妊娠12周发现宫内单活胎合并部分性葡萄胎；孕 18 周出现血压升高（最高 157/98 mmHg，1 mmHg=0.133 kPa）、甲状腺功能亢进（促甲状腺刺激激素0.005 mIU/L；总三碘甲状腺原氨酸3.78 nmol/L；总甲状腺素 263 nmol/L）、中度贫血（血红蛋白 88 g/L）、心力衰竭（N-末端脑钠肽前体3 500 pg/mL），以及咳嗽、咳痰并痰中带血。血绒毛膜促性腺激素（human chorionic gonadotropin,HCG）水平上升显著：13 535 mIU/mL（孕5周）、107 874 mIU/mL（孕12周）、200 000 mIU/mL（孕18周）。孕16周盆腔MRI检查示：（1）宫腔偏右侧占位，大图1女，25岁，CHMCF伴肺转移。1A：孕16周轴位T1WI平扫病灶呈稍低、等及稍高信号；1B：孕16周轴位T2WI病灶呈稍高并稍低信号；1C：孕16周轴位T2WI压脂病灶呈稍高、高信号；1D：孕16周DWI示病灶扩散不受限；1E：孕18周轴位T2WI示病灶局部与子宫右侧壁分界欠清；1F：孕18周胸部CT轴位示双肺多发实性结节；1G：组织病理（HE 100）示凝血块中见滋养细胞及蜕膜组织；1H：免疫组化示，P57（-），Ki-67（增值指数70%）。CHMCF：双胎妊娠完全性葡萄胎与胎儿共存；DWI：扩散加权成像；CT：计算机断层扫描。Fig.1Female,25 years old,CHMCF with pulmonary metastases.1A:The 16th week of gestation,the axial T1WI shows slightly lower,equal and slightly higher signals.1B:The 16th week of gestation,the axial T2WI shows slightly higher and slightly lower signal;1C:The 16th week of gestation,the axial T2WI shows slightly higher and higher signal intensity.1D:The 16th week of gestation,the DWI shows unrestricted diffusion of the lesion;1E:The 18th week of gestation,the axial T2WI shows unclear boundary between the lesion and the right uterine wall.1F:The 18th week of gestation,the axial chest CT shows multiple solid nodules in both lungs.1G:Histopathological findings(HE 100),trophoblast cells and decidua tissue are found in the clot.1H:Immunohistochemistry,P57(-),Ki-67(value-added index 70%).CHMCF:complete hydatidiform mole and coexisting fetus;DWI:diffusion-weighted imaging;CT:computed tomography.收稿日期：2022-06-15 接受日期：2023-05-22基金项目：甘肃省卫生健康行业科研计划项目（编号：GSWSKY2021-059）82磁共振成像 2023年6月第14卷第6期 Chin J Magn Reson Imaging,Jun,2023,Vol.14,No.6http:/病例报告Case Report小约为16.1 cm7.2 cm17.7 cm，病灶呈“蜂窝状”改变，T1加权像（T1-weighted image,T1WI）为稍低、等及稍高信号，T2加权像（T2-weighted image,T2WI）为稍高及稍低信号，扩散加权成像（diffusion-weighted imaging,DWI）序列呈等及稍低信号，子宫蜕膜层及结合带清晰、连续，子宫肌壁内未见明确异常信号灶；（2）宫腔单胎、头位，胎儿位于宫腔左侧，以上考虑为双胎妊娠完全性葡萄胎与胎儿共存（图 1A1D）。18周复查盆腔MRI示：盆腔偏右侧占位较前范围增大（18.5 cm9.2 cm21.7 cm），病灶局部与子宫右侧壁分界欠清，考虑完全性葡萄胎进展（图1E）。头颅MRI未见异常。给予诊断性抗感染治疗后咳嗽、咳痰改善不明显，经患者及家属同意后行胸部计算机断层扫描（computed tomography,CT）检查示双肺多发实性结节，多考虑转移瘤（图1F）。患者与家属商议后要求终止妊娠，给予降压、治疗甲亢、纠正低蛋白血症、贫血及心衰等对症支持治疗后引产，可见患者排出胎儿及大量“葡萄串”样组织，随后在超声监视下清理残留“葡萄串”样组织。大体示：宫腔内排出物为灰白、灰褐色水泡样物及凝血块组织一堆，体积21 cm17 cm6 cm。病理示：凝血块中见滋养细胞及蜕膜组织（图1G）。免疫组化示：P57（-），Ki-67（增值指数70%），考虑为完全性葡萄胎（图1H）。患者清宫术后连续四次血HCG水平未见下降，且出现肺转移瘤，通过国际妇产科联合会（Federation of Gynecology and Obstetrics,FIGO）分期最终诊断为侵蚀性葡萄胎（期：3分）。给予放线菌素D单药1日方案连续化疗12次后，血HCG降至正常，超声示宫腔少量积液，双肺转移灶较前基本消失。至今共1年未见肿瘤复发转移征象。讨论葡萄胎是最常见的妊娠滋养细胞疾病，绝大多数是由空卵受精或双精子受精所致，分别称为完全性葡萄胎和部分性葡萄胎。两者均可发生于双胎妊娠，总发病率约为 1/（20 000100 000），且绝大多数为双胎妊娠完全性葡萄胎与胎儿共存（complete hydatidiform mole and coexisting fetus,CHMCF）。CHMCF的本质为异卵双胎，即一个受精卵发育为正常胎儿及胎盘组织，而异常受精卵则发育为完全性葡萄胎，病理上表现为高度增生的滋养细胞伴绒毛水肿，形似“葡萄串”样，无胎儿及胎盘成分1。CHMCF的临床表现有阴道流血、妊娠试验阳性、妊娠剧吐、子宫过度增大、甲亢、早发型子痫前期和因卵巢黄素化囊肿引起的腹胀。极少数可因肺部或脑部转移而出现咯血或癫痫发作2。LIN等3统计了1966至2015年于美国多个中心诊治的72例CHMCF患者，得出妊娠合并症的总发病率高达63%。本例患者在孕12周行常规超声检查时即提示妊娠合并葡萄胎可能，但患者除发现右侧卵巢生理性囊肿外无其他明显症状，至孕中期才逐渐出现血HCG的异常升高、高血压、甲亢，以及咳嗽、咳痰并痰中带血等并发症。有研究指出，异常高水平的HCG或HCG持续上升反映出滋养细胞高度增生，往往提示具有较大风险出现局部浸润和远处转移4。本例患者孕早期的HCG未见异常升高，孕中期的异常持续升高不同于正常妊娠，结合多发妊娠合并症，须高度怀疑侵袭性葡萄胎的发生。CHMCF的影像学检查包括超声和MRI，若怀疑出现远隔脏器转移，则需要相关专科检查。超声因其易操作性及无电离辐射，现已成为产前常规检查。但由于CHMCF组织成分较为复杂，不易与稽留流产、不全流产、妊娠合并宫腔积血等相鉴别5。有研究得出，超声对中孕期妊娠合并葡萄胎的诊断准确性仅为 60%70%，且对于侵蚀性葡萄胎的诊断敏感性较低。若孕妇同时合并有羊水过少、子宫肌瘤等特殊情况，诊断准确性则会更低6。随着MRI的飞速发展，其作为超声检查强有力的补充手段，在产前诊断中发挥着越来越重要的作用。IMAFUKU等7的研究指出，不同于超声的小视野MRI可显示胎儿及胎盘的全视野成像，且不用受近、远场的影响，可多方位观察胎儿、胎盘、葡萄胎组织与子宫肌层的关系。以下为妊娠滋养细胞疾病的MRI特征：（1）子宫及宫腔异常增大。（2）宫腔内见“蜂窝”状囊泡影，T1WI以低信号为主，T2WI以高信号为主，囊泡分布均匀，中间可见低信号分隔，包膜完整；胎盘血肿或宫腔积血在T1WI上则表现为高信号；T2WI及T2WI压脂序列能够帮助提示病变的肌层浸润情况。本组病例前次盆腔MRI显示子宫蜕膜层连续，两周后MRI复查，子宫蜕膜层局部欠连续，预示着葡萄胎进展为恶性的可能。（3）囊泡样结构在DWI上一般表现为扩散不受限；合并积血或血肿则表现为扩散受限。（4）增强扫描囊泡分隔可强化，囊腔无强化；若子宫肌层强化均匀，则良性可能性大；若病灶与子宫肌层分界不清，突入甚至穿透子宫肌层，则提示恶性可能。此外，通过增强扫描还能明确胚胎或胎盘的附着部位及血供情况。清宫后葡萄胎组织残留或进展为侵袭性葡萄胎，首先考虑附着部位的残留或侵犯。本病需与双胎妊娠部分性葡萄胎与胎儿共存（partial hydatidiform mole and coexisting fetus,PHMCF）相鉴别。尤其当存活胎儿与葡萄胎组织分界不清时，仅通过影像学检查较难区分，需依赖病理、免疫组化甚至细胞遗传学检查。所有CHMCF的葡萄胎和胎儿核型均为二倍体，且父系印记基因p57呈阴性，而PHMCF 90%以上的核型为三倍体，如果胎儿同时存在，其核型一般也为三倍体，且p57蛋白呈阳性8。本例患者于孕12周常规产前检查时由超声发现活产妊娠合并葡萄胎，在临床较为罕见，但超声因其局限性导致诊断出现误差，进一步行MRI检查后纠正了诊断，且通过MRI的随诊，加之临床表现及胸部CT检查，最终诊断为侵袭性葡萄胎，使得患者得以早期治疗。综上所述，CHMCF 发病罕见且临床表现非特异性，加之正常胎儿会掩盖葡萄胎各种异常表现，使其早期的诊断受到极大挑战。超声因其视野较小，且83磁共振成像 2023年6月第14卷第6期 Chin J Magn Reson Imaging,Jun,2023,Vol.14,No.6http:/病例报告Case Report容易受操作者水平、孕妇肥胖、羊水过多、多胎、子宫肌瘤等影响，诊断准确性较低且不稳定。而MRI无上述困扰，多序列、功能成像及增强扫描不仅在诊断上占据优势，还能够显示出血、局部浸润、胚胎或胎盘的附着部位、子宫及病变的血供特点，可更准确地提示病变良恶性，从而指导临床制订治疗方案。作者利益冲突声明：全体作者均声明无利益冲突。作者贡献声明：徐生芳解读病例及相关图像，设计研究方案，对稿件重要内容进行规范及修改，获得了甘肃省卫生健康行业科研计划项目基金资助；梁莉起草并撰写稿件，分析解读图像并获取图像，参与稿件内容的撰写及修改；陈瑞蓉获取、分析并解释本病例的影像学图像及数据，参与稿件内容的撰写及修改；全体作者都同意发表最后的修改稿，同意对本研究的所有方面负责，确保本研究的准确性和诚信。参考文献References1王丽娟,林海雪,林仲秋.2020年RCOG妊娠滋养细胞疾病管理指南 解读J.中国实用妇科与产科杂志,2021,37(2):198-204.DOI:10.19538/j.fk2021020117.WANG L J,LIN H X,LIN Z Q.Interpretation of RCOG management guidelines for gestational trophoblastic diseases in 2020J.China Ind Econ,2021,37(2):198-204.DOI:10.19538/j.fk2021020117.2SILEO F G,GIULIANI G A,FACCHINETTI F,et al.Complete hydatidiform mole in higher-order multiple pregnanciesJ.Minerva Obstet Gynecol,2022,74(3):308-313.DOI:10.23736/S2724-606X.21.05031-4.3LIN L H,MAEST I,BRAGA A,et al.Multiple pregnancies with complete mole and coexisting normal fetus in North and South America:a 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