Complete Hydatidiform Mole at Menopause: A Case Report from Panzi Hospital, Bukavu, Democratic Republic of Congo

Gestational trophoblastic disease is an abnormal proliferation of trophoblastic tissue during pregnancy. It occurs in women of childbearing age, although a few cases have also been observed in post-menopausal women, although it is extremely rare in the latter. Here we describe a rare case of complete hydatidiform mole in a 56-year-old female patient who presented with genital bleeding combined with nausea and vomiting and a gravid uterus 16 cm in height. The ultrasound findings and the increase in serum β-HCG to 182566.00 mIU/ml suggested a diagnosis of complete hydatidiform mole. Given the post-menopausal state and the future risk of post-molar gestational trophoblastic neoplasia, we opted for total hysterectomy without preservation of the adnexa via a transabdominal approach, followed by antimitotic treatment with methotrexate. The uterus measured 18.45 cm × 11.18 cm with intra cavitary vesicles. Microscopic examination showed chorionic villi of variable size and shape, most of which were dilated and oedematous, associated with trophoblastic cell proliferation and haemorrhage suggestive of complete benign hydatidiform mole. Follow-up showed a consistent decrease in serum β-HCG levels and no evidence of residual disease. A suspicion of gestational trophoblastic disease should be borne in mind when evaluating a patient with peri- or post-menopausal bleeding to avoid delay in diagnosis and treatment.

Single Nucleotide Polymorphism-Based Chromosomal Microarray Evaluation of Hydatidiform Moles: A US National Reference Laboratory Experience

Objectives: This retrospective study evaluated 1) benefits of single nucleotide polymorphism (SNP)-based chromosomal microarrays (CMAs) in the diagnosis of complete hydatidiform mole (CHM) and partial HM (PHM) in products of conception (POC) and amniotic fluid (AF) specimens, and 2) frequency of whole-genome uniparental disomy (wgUPD) and triploidy in POC and AF specimens received at a US national reference laboratory. Methods: We reviewed consecutive 2138 POC and 3230 AF specimens and identified the cases with wgUPD and triploidy which are associated with molar pregnancy. Results: Of 2138 consecutive POC specimens tested, SNP-based CMA detected wgUPD in 10 (0.47%) and triploidy in 84 (3.93%). Of the 10 wgUPD cases, 9 (90%) were confirmed as CHM. Of 3230 consecutive AF specimens, the array detected wgUPD in 1 case (0.03%) and triploidy in 11 (0.34%). Conclusions: SNP-based microarray allows detection of wgUPD in POC and AF specimens at a US national reference laboratory. Correctly diagnosing HM and differentiating CHM from PHM are important for clinical management. The effective SNP-based CMA detection of wgUPD in CHM may enable physicians to monitor patients at risk for gestational trophoblastic disease and neoplasm. Conventional chromosome analysis of POC has a high failure rate, cannot be performed on formalin-fixed paraffin embedded samples, and cannot detect wgUPD. Further multi-institutional collaborative assessmen on accuracy, cost-effectiveness, and adequate access to SNP-based CMA, may lead this testing platform to be considered as the first-tier analysis tool for POC specimens, including those showing PHM or CHM.

Hydatidiform mole in a scar on the uterus:A case report

BACKGROUND Cesarean scar molar pregnancy is extremely rare,but the incidence has been rising due to the continuous increase in the rate of cesarean section.The presence of a hydatidiform mole in the scar left on the uterus by the procedure may lead to severe complications.We performed a literature review and found only seven reported cases of cesarean scar molar pregnancy.Accurate diagnosis and appropriate treatment are extremely important for the patients’prognosis.CASE SUMMARY A 35-year-old woman,gravida 4,para 1,complained of vaginal bleeding lasting more than 1 mo and amenorrhea lasting more than 2 mo.The patient’s serum human chorionic gonadotropin was 4287800 IU/L.Ultrasound showed a 11.5 cm×7.5 cm mass at the anterior lower wall of the uterus.The patient underwent suction evacuation,and partial grape-like tissue mixed with blood clots was removed.Uterine arterial embolization was performed to control intraoperative and postoperative bleeding.Histological examination confirmed the presence of a hydatidiform mole in uterine scar.After surgery,there was still a mass with heterogeneous intensity near the isthmus of the uterus on magnetic resonance imaging.The patient then underwent chemotherapy.During the 6-mo follow-up period,the mass disappeared and the serum human chorionic gonadotropin level gradually decreased to normal level.CONCLUSION We report a case of cesarean scar molar pregnancy successfully cured by comprehensive treatment.We found that cesarean scar molar pregnancy was subject to intraoperative bleeding,and uterine arterial embolization before surgery may be helpful.

Genetically identified complete hydatidiform mole coexisting with a normal fetus following IVF-ET

A complete hydatidiform mole coexisting with a fetus following in vitro fertilization and embryo transfer (IVF-ET) is a rare event. The diagnosis is often not easy because of the morphological similarity to a partial mole, but important to the treatment. We present a recent case in which STR polymorphism analysis clearly revealed a different genetic origin for the fetal and molar parts. STR polymorphisms on 15 variable number tandem repeat loci and a gender-determination locus, which were detected by polymerase chain reaction, indicating that the cord/placenta and molar tissue were parental and androgenous, respectively. During follow-up, the patient developed persistent gestational trophoblastic tumor (GTT) which was successfully treated with chemotherapy. In this case, STR polymorphism analysis exactly diagnosed a twin pregnancy consisting of a complete hydatidiform mole and a fetus.

Termination of a partial hydatidiform mole and coexisting fetus: A case report

BACKGROUND We describe the treatment strategy for a patient who was found to have a partial hydatidiform mole and coexisting fetus(PHMCF)during the second trimester.The patient was a 38-year-old Chinese woman who had become pregnant following in vitro fertilization and embryo transplantation.We wanted to determine the safest therapeutic strategy to terminate the PHMCF during the second trimester.CASE SUMMARY In this case,we present a patient who was found to have a PHMCF complicated with serious continuous vaginal bleeding and pre-eclampsia during the second trimester.After careful evaluation,the pregnancy was considered to be unsustainable and was terminated via caesarean section(CS).An infant with weak vital signs and a partially cystic placenta measuring 110 mm×95 mm×35 mm were delivered by CS.The patient was discharged after 4 d.The serum levels ofβ-human chorionic gonadotropin decreased to within a normal range 5 wk after the operation,and no evidence of persistent trophoblastic disease or lung metastases was noticed at the 6-mo follow-up.CONCLUSION CS termination of PHMCF during the second trimester may be a relatively safe therapeutic strategy.

Preliminary Study on c-Ha-ras Oncogene Mutations in Hydatidiform Mole Tissues

ve To study the presence of c-Ha-ras oncogene mutations in hydatidiform mole (HM) tissues and to further explore its relationship with mole's malignancy

Low and Maternal-specific Expression of p57^(KIP2) in Hydatidiform Mole and Its Clinical Implication

Summary: In situ hybridization was applied to locate and detect the expression of p57 KIP2 in hydatidiform mole (5 cases of partial hydatidiform mole and 18 cases of complete hydatidiform mole) and normal villi (23 cases). The positive signals of p57 KIP2 expression were analyzed by HPIAS-1000 Image-Analysis System. p57 KIP2 was highly expressed in normal villi but showed distinct low expression in hydatidiform mole (P<0.01). Furthermore, the locus of low expression of p57 KIP2 accorded with the place where lesion of trophoblast occurred. Detection of p57 KIP2 made it possible to study the genetics of hydatidiform mole at the transcriptional level. Low expression of p57 KIP2 could be a molecular marker in hydatidiform mole and a target for therapy.

Study on neoplasia of hydatidiform mole by detecting telomerase reverse transcriptase mRNA expression in peripheral blood mononuclear cells

By setting up a real-time fluorescent quantitative RT-PCR assay to detect human telomerase reverse transcriptase （hTERT） mRNA in hydatidiform mole in peripheral blood mononuclear cells, to analyze the correlation between the expression level of hTERT mRNA and the prognosis of hydatidiform mole, and to evaluate the clinic value of quantitative determination of hTERT mRNA in the diagnosis of hydatidiform mole. Methods： A real-time fluorescent quantitative RT-PCR （FQ RT-PCR） assay based on TaqMan fluorescence methodology and the Light-Cycler system was used to quantify the full range of hTERT mRNA copy numbers in 30 samples of hydatidiform mole and the neoplasia of hydatidiform mole. The normalized hTERT （NhTERT） was standardized by quantifying the number of GAPDH transcripts as internal control and expressed as 100x （hTERT/GAPDH） ratio. Based on the prognosis of the hydatidiform mole, the patients were divided into two groups： the experimental group and the control group, to compare the telomerase reverse transcriptase mRNA expression in peripheral blood mononuclear cells. Results： hTERT mRNA was both expressed in the peripheral blood mononuclear cells and pathological tissues in the mole experimental group and the control group. In the mole experimental group, the values were 6.31±0.32 and 6.24±0.44, respectively, and there was no significant difference between them （P〉0.05）. But in the control group the values were 1.21±0.65 and 1.40±0.61, respectively, and there was no significant difference between them （P〉0.05） The values in experimental group was significantly higher than those in the control group （P〈0.01）. Conclusion： Quantitative determination of hTERT mRNA by FQ RT-PCR is a rapid and sensitive method, hTERT in peripheral blood mononuclear cells may have potential use as a biomarker for the early detection of the prognosis of the hydatidiform mole.

Detection of Homozygous Deletions and Mutations in the CDKN2A Gene in Hydatidiform Moles

OBJECTIVE To investigate homozygous deletions and mutations in the CDKN2A gene(p16 INK4a and p14 ARF gene)in hydatidiform moles. METHODS A total of 38 hydatidiform mole samples and 30 villi samples were examined for homozygous deletions in the CDKN2A gene by PCR and for mutations by DHPLC. RESULTS i)Among 38 hydatidiform mole samples, homozygous deletions in the p16 INK4a exon 1 were identified in 5 cases(13.2%),while no homozygous deletions were found in the p16I NK4aexon 1 of 30 early-pregnancy samples.The rates of those deletions in hydatidiform compared to early-pregnancy villi samples was statistically significant(P=0.036).ii)No homozygous deletions in the p14 ARF exon 1 or p16 INK4a exon 2 were found in any of the hydatidiform moles or early-preganancy samples.iii) In all hydatidiform moles and early-pregnancy villi samples,no mutations were detected by DHPLC. CONCLUSION We suggest there may be a close correlation between homozygous deletions in the CDKN2A gene and occurrence of hydatidiform moles variation in the CDKN2A gene is mainly caused by homozygous deletions,while mutations may be not a major cause.

The changes of clinical features of hydatidiform mole:analysis of 113 cases

Objective:To investigate the changes of the clinical features of hydatidiform mole.Methods:One hundred and thirteen cases of hydatidiform mole treated in Peking Union Medical College Hospital during 1989-2006 were reviewed retrospectively and a comparison was made to historic data(1948-1975)using χ2 test.Results:The median age was 28 years(ranges from 20 to 55 years).The median gestational age was 90.2 days.Vaginal bleeding remaines the most common presenting symptom,ocurring in 94 of 113 cases(83.2%).Fifty-two of 113 cases(46%)presented with excessive uterine size.Pregnancy induced hypertension syndome(PIH),hyperemsis,hemoptysis and theca lutein cysts occurred in 4 of 113(3.5%),12 of 113(10.6%),4 of 113(3.5%)and 19 of 113 cases(16.8%)respectively.Incidence of postmolar trophoblastic neoplasia was 21%(24 of 113).Campared to historic data,the incidence of vaginal bleeding and PIH were statistically lower(P<0.005).The incidence of postmolar gastational trophoblastic neoplasia(GTN)was increased moderately without statistical significance compared to historic data.Conclusions:Because of the wide use of ultrasonography and serum hCG test,the current patients with hydatidiform mole have been diagnosed earlier in gestation and the clinical features have changed.Patterns of medical practice should be changed accordingly.

持续性单纯宫内无回声的临床结局分析

目的分析持续性单纯宫内无回声的临床结局。方法回顾性收集我院于2015年3月至2021年5月收治的持续性单纯宫内无回声患者共3759例,并收治1例因单纯宫内无回声于外院清宫后血β-HCG下降不良,进一步转诊至我院处理的患者,共计3760例,分析所有患者临床特点及特殊临床结局。结果3760例患者中,3745例患者的临床结局为稽留流产,15例患者的临床结局为非稽留流产。非稽留流产患者中,有11例患者术后第一天查血β-HCG下降>50%,其病理报告均提示为“葡萄胎”;有3例患者术后第一天查血β-HCG较前不降反升,幅度均<15%,其病理报告均为“蜕膜组织”,因病理报告时间具有延后性,故均及时行盆腔超声检查,提示为异位妊娠,并及时进行腹腔镜检术;1例外院转诊来院患者,术后第7天血β-HCG下降幅度较小,我院复查发现血β-HCG为8754mIU/mL,盆腔超声提示为间质部妊娠,并行腹腔镜检术+左侧间质部切开取胚术。结论临床工作中超声提示持续性单纯宫内无回声患者大部分表现为稽留流产,但仍有部分患者存在葡萄胎和异位妊娠的可能性,因此清宫前后均应密切监测血β-HCG,注重病理检查,必要时复查盆腔超声,谨防葡萄胎和异位妊娠,防止漏诊误诊。

宫角异位型侵袭性葡萄胎一例

本文报道了一例异位侵袭性葡萄胎患者的临床特征、诊断过程及治疗方案。其人绒毛膜促性腺激素(β-HCG)提示24335 m IU/mL、超声提示左侧附件区异常回声(不除外滋养细胞疾病)及病检示(宫内组织)分泌期样宫内膜,左输卵管及左宫角、左阔韧带病灶查见水肿的绒毛组织并伴有滋养叶细胞增生,多系葡萄胎;免疫组化提示p53(+)、p57(-)、HCG(+),人胎盘碱性磷酸酶(PLAP)(-)、Ki-67(高表达),组织学类型符合完全性葡萄胎,CD34及弹力纤维染色提示一处血管内查见绒毛组织,符合侵袭性葡萄胎改变,确诊为侵袭性葡萄胎。治疗上采用了以手术为主、辅助化疗的综合治疗策略。

Twin pregnancy and partial hydatidiform mole following in vitro fertilization and embryos transfer： a novel case of placental mosaicism

Twin pregnancy with mosaic partial hydatidiform mole （PHM） and survival of two healthy fetuses following in vitro fertilization and embryos transfer （IVF-ET） is a rare situation and is considered a challenge for management. A 32-year-old Chinese woman conceived twin pregnancy following IVF-ET. At 22 weeks＇ gestation, an additional intrauterine echogenic mass with features of PHM were shown by successive ultrasound examinations. At 35 weeks＇ gestation, two live male infants and two placentas were delivered by caesarean section （CS）. Histologic examination of the abnormal placenta confirmed mosaic PHM. Genetic study showed the abnormal placental mosaicism （expressed in molar-69XXY and normal vili-46XY）, co-existing with a hypospadia new-born （46XY） in one amniotic sac. However, the other one was normal. Serial serum β-hCG levels showed a declining trend and serum β-human chorionic gonadotropin （hCG） were undetectable at 6 months after delivery. The case demonstrated that it is possible to prolonged gestation by PHM under close surveillance during the entire pregnancy.

Analysis of Clinicopathologic Classification Features of Hydatidiform Mole Misdiagnosed as Missed Abortion Preoperatively

Objective:To analyze clinicopathologic classification features of the cases that were diagnosed as missed abortion preoperatively but turn out to be hydatidiform mole(HM)postoperatively.Methods:A retrospective analysis was conducted on the patients who had a missed abortion in our hospital from 2017 to 2018.Clinical and pathological characteristics of different types of HMs were observed.Diagnostic value of karyotype in HM was discussed based on the karyotype analysis of villi chromosome.Results:A total of 278(11.2%)HM patients were misdiagnosed as missed abortion.Naked-eye detection rate of HM was 26.61%,and sensitivity of transvaginal ultrasound on HM was 7.91%.One hundred and forty-seven(52.88%)HM cases could not be genotyped via pathological hematoxylin and eosin(HE)staining.70 HM patients underwent P57 immunohistochemistry,which had guiding significance to the classification.In addition,the karyotype diagnosis of the tissues from 15 cases basically matched their P57 classifications.Conclusions:P57 should be listed as a routine test in hydatidiform pathological examination at the same time of HE staining,and what’s more,P57 expression is consistent with genotyping,which should be recommended for the patients with HM if observed by naked eye.

输卵管妊娠葡萄胎合并腹腔内出血一例

输卵管妊娠葡萄胎在临床上极为罕见,术前诊断大多存在困难,确诊主要依靠术后组织病理学诊断。报告1例38岁女性因右侧输卵管妊娠破裂致腹腔内出血急诊行腹腔镜右侧输卵管切除术,术后病理提示完全性葡萄胎的病例。该患者术后恢复良好,随访期间血清人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)下降满意,无阴道出血、咳嗽和咳血等相关病灶转移症状。输卵管妊娠葡萄胎多表现为急腹症,因此对于急腹症患者临床上应警惕葡萄胎的可能性,其治疗多以手术为主,必要时行化疗,术后需严密随访,注意病变侵蚀及恶变可能。

双胎之一完全性葡萄胎妊娠并发侵蚀性葡萄胎1例

目的探讨双胎之一完全性葡萄胎妊娠的发病机制、临床特点及诊疗方法。方法回顾性分析1例双胎之一完全性葡萄胎妊娠并发侵蚀性葡萄胎病例的诊疗经过及妊娠结局,并复习相关文献。结果孕妇促排卵治疗后自然妊娠,孕期超声考虑双胎妊娠合并葡萄胎,经剖宫产获得足月新生儿。结合其临床表现、影像学检查、组织病理学特征及免疫组化,最终确诊为双胎之一完全性葡萄胎。剖宫产后随访2个月,产妇确诊为侵蚀性葡萄胎(Ⅲ:2),给予MTX单药化疗7个疗程后临床痊愈。结论双胎妊娠合并葡萄胎的处理,应综合考虑,对于双胎之一完全性葡萄胎并发侵蚀性葡萄胎更应制定个体化的诊疗方案。

中期妊娠合并完全性葡萄胎继发远处转移1例并文献复习

目的探讨中期妊娠合并完全性葡萄胎(CHMCF)继发远处转移病例的临床特征和诊疗方法。方法回顾性分析2021年7月湖北省妇幼保健院收治的1例CHMCF患者的诊治经过及随访情况,结合文献复习探讨其诊治策略。结果本例患者因先兆流产收入院保胎治疗,彩超提示宫腔内除正常胎儿胎盘组织外另有一蜂窝样无回声区;行药物引产术,术后确诊CHMCF;随访期间血人绒毛膜促性腺激素(β-HCG)下降不佳,肺部出现微小转移灶,予以一周期甲氨蝶呤化疗后降至阴性,随访半年余未复发。结论CHMCF是一种高风险妊娠,超声结合血β-HCG的动态监测对CHMCF的早期识别具有重要意义,同时完善的遗传学筛查对其临床处置和预后具有指导意义。在临床处理上,应结合产前母体并发症有无、血β-HCG增长趋势及患者对继续妊娠风险的承受力制定个体化诊疗方案。此外,终止妊娠后的密切随访对于优化母胎结局亦至关重要。

CNV结合STR分型技术检测孕早期流产组织潜在葡萄胎效果及风险因素分析

目的:评估基因组拷贝数变异测序(CNV-seq)结合短串联重复序列(STR)多态性分析技术在检测孕早期(≤9周)流产物组织中潜在葡萄胎病例的应用效果.方法:收集2021年1月-2022年12月行孕早期流产组织CNV-seq结合STR多态性检测病例114例,其中部分新鲜绒毛组织进行CNV-seq结合STR多态性检测,部分组织行病理学检测.比较两种检测方法结果,并分析潜在葡萄胎病例的临床特征和影响因素.结果:CNV-seq结合STR多态性检测共检出染色体异常病例28例,阳性率为24.6%,其中单亲二倍体(UPD)8例,占阳性病例28.6%;病理学检出葡萄胎病例12例,阳性率为10.5%,其中完全性葡萄胎(CHM)10例,占阳性病例的83.3%.两种检测方法的结果一致率为89.5%,Kappa值为0.75,两种方法具较好一致性.潜在葡萄胎病例与非葡萄胎病例在年龄、孕次、流产次、β-hCG水平、超声表现等方面有差异,其中年龄、β-hCG水平和超声表现是潜在葡萄胎危险因素(均P<0.05).结论:CNV-seq结合STR多态性分析技术能有效检测孕早期流产物组织中潜在葡萄胎病例,有助于指导临床治疗和避免再次流产.

Pulmonary deportation of hydatidiform mole:a 12-year,single tertiary center experience in China

Background:Pulmonary deportation of hydatidiform mole is an exceedingly rare entity.The underlying mechanisms and proper management strategies remain unclear based on sporadic case reports over the past six decades.This study aimed to investigate the clinical features and rational treatment of patients with benign molar pregnancies with pulmonary deportation based on our experience.Methods:Medical records of 20 cases of hydatidiform mole with pulmonary deportation were retrospectively reviewed at Peking Union Medical College Hospital from November 2006 to May 2019.The detailed information of all patients was recorded and analyzed.Patients were divided into different groups according to their characteristics and Mann-Whitney U test was used to compare the duration to achieve a normal b-human chorionic gonadotrophin(b-hCG)level after the first evacuation among groups.Results:Initial pulmonary computed tomography scans showed suspected bilateral,left and right chest deportation of hydatidiform mole in 12,four,and four patients,respectively,with the maximum nodular diameter ranging from 0.6 to 1.2 cm.Ten patients achieved lesion resolution while the remaining ten patients achieved decreases in the size of their pulmonary lesions.The median duration to achieve a normal b-hCG level after the first evacuation was 15.5(13.0,21.9)weeks.There was no significant difference in the duration to achieve a normal b-hCG level after the first evacuation between two groups based on age(≥40 years vs.<40 years:15.8[12.2,21.5]weeks vs.15.5[12.9,23.0]weeks,Z=0.094,P=0.925),type of antecedent mole(partial mole vs.complete mole:15.2[12.5,27.4]weeks vs.15.9[12.9,21.5]weeks,Z=0.165,P=0.869),distribution of pulmonary nodules(bilateral lungs vs.unilateral lung:15.2[12.8,22.5]weeks vs.15.9[13.2,22.2]weeks,Z=0.386,P=0.700),maximum size of pulmonary nodules(>0.5 cm vs.0.5 cm:13.0[11.3,17.2]weeks vs.16.0[14.5,23.8]weeks,Z=1.815,P=0.070),and number of uterine evacuations(once vs.twice or three times:15.0[13.0,16.3]weeks vs.16.0[12.8,23.9]weeks,Z=0.832,P=0.405).The post-molar cohort was followed up for 17 to 139 months,and no gestational trophoblastic neoplasia was observed.Conclusions:No surgeries other than uterine evacuation and no chemotherapy regimens are recommended for such patients if they achieve satisfactory decreases in the level of hCG and gradual decrease or disappearance of pulmonary deportation nodules.Patients should be informed about the necessity of long-term follow-up.More collaborative international studies on this exceedingly rare condition may guide decisions regarding optimal management strategies.

超声诊断葡萄胎合并妊娠49例临床分析

目的:探讨葡萄胎合并妊娠的超声诊断价值及其预后。方法:回顾性分析2014年1月至2023年4月于四川大学华西第二医院超声诊断疑似葡萄胎合并妊娠的49例孕妇的临床资料,并根据病理检查结果分为葡萄胎组(20例)和良性病变组(25例),分析两组的超声检查和临床特征,并对不同医师超声图像的判读采用一致性检验。结果:①49例患者中31例孕妇选择终止妊娠,14例孕妇选择继续妊娠,4例失访。有明确病理诊断的45例患者,其中完全性葡萄胎4例,部分性葡萄胎16例;良性病变共25例,包括胎盘间叶发育不良5例、胎盘绒毛发育异常4例、胎盘粘连2例、胎盘梗死1例等。超声诊断葡萄胎合并妊娠的准确率44.4%(20/45)。②与良性病变组比较,葡萄胎组患者中占位的体积明显较大、占位中无回声的数量(一个切面>15个)明显较高、单个无回声的大小差异(≥80%)明显较低,差异均有统计学意义(P<0.05)。③2位超声医师对葡萄胎合并妊娠的超声图像进行判读,所有超声判读结果Kappa一致性系数均在0.75以上。结论:占位体积越大、占位中的无回声数量越多(一个切面>15个)、占位中无回声分布大小越一致越倾向诊断葡萄胎合并妊娠。胎盘间叶发育不良等良性疾病的超声表现易与葡萄胎混淆,应谨慎。虽然超声诊断的准确率不高,但及时发现异常便于临床管理。