Role of hysteroscopy in diagnosis and management of trophoblastic disease

To confirm complete removal of trophoblastic tissues, hysteroscopy was performed in 21 patients after evacuation of hydatidiform mole with an interval of a week. In 15 of these cases, hysteroscopy employed within a week after evacuation of the mole revealed a residue of mole or necrotic decidua. Although complete removal was confirmed in 14 cases on the second hysteroscopy, re-curettage was necessary in 6 patients because necrotic tissues were still found in the uterine cavity. Possible diagnosis of invasive mole was made in 2 cases within 2 weeks after evacuation of the mole by hysteroscopic findings. Hysteroscopy was also performed in 27 patients who were suspected of having a trophoblastic disease from the clinical signs and urinary hCG titer. Hysteroscopic findings which suggested trophoblastic diseases were summarized in the following four categories; 1) the existence of vesicles, 2) buldging or 3) recess of the uterine wall with bleeding or dilated blood vessels and 4) hematoma of the uterine wall. In 9 of the 21 cases with choriocarcinoma, invasive mole or persistent trophoblastic disease, one or two of the above mentioned findings were noted. Moreover, it was possible to differentiate syncytial endometritis from trophoblastic disease from the hysteroscopic findings. Therefore, hysteroscopy seems to be a useful aid not only in confirming complete evacuation of hydatidiform mole but also in the diagnosis and management of malignant sequela.     

短串联重复序列STR分析在葡萄胎诊断中的作用研究

目的:探讨短串联重复序列(short tandem repeat,STR)基因多态性检测在葡萄胎鉴别诊断中的临床应用价值。方法:收集乌鲁木齐市妇幼保健院病理科2000年至2015年间临床及病理形态学上明确诊断完全性葡萄胎(CHM)、部分性葡萄胎(PHM)和水肿性流产各40例、20例和20例。组织标本经STR基因多态性检测,STR检测包括7个多态性位点(D7S820、D13S317、D16S59、TPOX、TH01、CSF1PO、VWA),分析其在葡萄胎鉴别诊断中的作用。结果:(1)组织病理学结果:水肿性流产可见局灶绒毛组织水肿,无明显的滋养叶细胞增生;PHM可见部分区域绒毛组织水肿及滋养细胞包涵体形成,滋养叶细胞轻到中度增生;CHM可见绒毛间质明显水肿,明显的水池形成及滋养细胞明显增生。(2)STR结果显示:病理学诊断为水肿性流产的病例中每个STR位点均含有父源和母源性各1个等位基因(18/18),2例检测失败。病理诊断为PHM的病例中,单卵单精型部分性葡萄胎(MPM)和单卵双精型部分性葡萄胎(DPM)分别为2(2/19)例和14例(14/19),还有3例为均含有父源和母源性各1个等位基因3(3/19),另有1例检测失败。病理诊断为CHM的病例中,单精纯合型完全性葡萄胎(MCM)和双精杂合型完全性葡萄胎(DCM)分别为25例(25/35)和10例(10/35),另有5例检测失败。结论:组织病理对于PHM的诊断准确性不高,7个STR位点多态性分析在CHM、PHM和水肿性流产的鉴别诊断中具有重要作用。     

Routine histopathologic analysis of product of conception following first-trimester spontaneous miscarriages

AIM: To evaluate the histopathologic findings relating to tissue samples collected at surgical uterine evacuation in first-trimester spontaneous miscarriages. METHODS: In this retrospective study, histopathologic diagnosis of the tissue samples obtained via surgical uterine evacuation in patients who were admitted to the Early Pregnancy Clinic in a 12-month period with the diagnosis of incomplete miscarriage (n = 970), missed miscarriage (n = 406) and anembryonic miscarriage (n = 230) in the first trimester was recorded and compared with the presurgery diagnosis. RESULTS: Uterine evacuation was performed in cases of incomplete miscarriage (n = 970, 60.4%), missed miscarriage (n = 406, 25.2%) and anembryonic miscarriage (n = 230, 14.3%). Histopathologic examination revealed the product of conception in 1119 patients (69.7%), while partial hydatidiform mole was diagnosed in 33 patients (2.1%). Complete hydatidiform mole was detected in only seven cases (0.43%). Exaggerated placental site and placental site trophoblastic nodule was detected in two cases (0.12%). Decidual tissue without chorionic villi was reported in 272 patients (16.9%), raising the suspicion of presence of other pathology. CONCLUSIONS: By routine histopathologic assessment of products of first-trimester spontaneous miscarriages, important pathologies such as molar pregnancy and placental trophoblastic disease can be diagnosed. Histopathological assessment has great value in the identification of an ectopic pregnancy or infection when compared with clinical and laboratory findings.     

Partial moles: from postnatal to prenatal diagnosis.

The partial hydatidiform mole is a histopathologic entity characterized by focal trophoblastic hyperplasia with villous hydrops together with identifiable fetal tissue which was first described by Szulman and Surti in 1978. Since then major advances in molecular biology have shown that more than 90 per cent of partial moles are secondary to diandric triploidy and that this condition accounts for most cases of persistent trophoblastic disease after partial mole. Case series describing the prenatal diagnosis of triploid partial mole were reviewed and outcomes were analysed for all pregnancies, and compared to those of non-molar triploidy using the chi-square test. In more than 90 per cent of both types of triploidy, the fetus shows growth restriction and multiple structural anomalies. Oligohydramnios and abnormal placental Doppler indices are common in both types. In triploid partial mole, 82.1 per cent of fetuses present with symmetrical growth restriction, the maternal serum human chorionic gonadotropin (MShCG) level is increased in 80.8 per cent of the cases and 41.9 per cent of the women are at risk of pre-eclampsia. The triploid partial mole is a lethal fetal condition which is linked with gestational trophoblastic disorders. The typical placental molar features are not always pathognomonic of triploid partial mole and are less likely to be apparent on ultrasound in early pregnancy. The perinatal diagnosis of this condition relies upon mainly on MShCG level and cytogenetic results which have to be correlated with the histopathologic diagnosis. Women with this pregnancy complication should be offered immediate termination and a specific follow-up.     

The risk of persistent trophoblastic disease after hydatidiform mole classified by morphology and ploidy

OBJECTIVE: Hydatidiform mole can be classified by histopathologic characteristics and by genetic constitutions and most complete moles are diploid, whereas most partial moles are triploid. We investigated the concordance between these two classifications, characterized moles with conflicting classifications, and compared the ability of the two classifications to discriminate between patients with and without a substantial risk of persistent trophoblastic disease. METHODS: 294 cases of consecutively collected hydropic placentas clinically suspected of hydatidiform mole made the basis of this retrospective study. We determined the ploidy and reviewed the original histopathologic material in all cases. Data on possible chemotherapy were collected for each patient. RESULTS: 270 of the conceptuses were histopathologically classified as hydatidiform mole. Among the 24 conceptuses classified as non-molar miscarriage, 20 were triploids, 2 were diploid androgenetic and 2 were diploid biparental. In 23% of the conceptuses, the histopathologic and genetic classifications were conflicting. 5% of the patients with hydropic placentas classified as partial mole encountered persistent trophoblastic disease; however, the genome was diploid in all these moles. None of 131 patients with a triploid hydropic gestation encountered persistent trophoblastic disease. CONCLUSION: As full concordance between the histopathologic and the genetic classifications was not found, we believe that features beyond the genetic constitution influence the development of morphologic features in hydatidiform moles. We recommend that gestations suspected of hydatidiform mole are subjected to histopathologic examination. If hydatidiform change and trophoblastic hyperplasia are identified, the ploidy should be used to identify patients with a high risk of persistent trophoblastic disease.     

NLRP7基因在葡萄胎发生中的作用

葡萄胎（HM）是异常人类妊娠,以绒毛滋养细胞增生、间质水肿,同时缺乏胚胎发育或者异常的胚胎发育为特征,是一种滋养细胞疾病（GTD）。超声的广泛使用使早期诊断和处理葡萄胎成为可能,但其确诊依据仍是组织学诊断;葡萄胎治疗有一定难度,且葡萄胎特别是复发性葡萄胎的预后不理想。葡萄胎的发生机制尚不明确,细胞遗传学研究发现葡萄胎组织染色体核型异常和基因印迹错误。最近对葡萄胎患者基因方面的研究发现,NLRP7基因与复发性葡萄胎存在相关性。就葡萄胎及其与NLRP7基因的研究进展综述。     

Worldwide controversies in gestational trophoblastic neoplasms.

This article reviews worldwide controversies concerning gestational trophoblastic neoplasms (hydatidiform mole, invasive mole, and choriocarcinoma). The epidemiology, endocrinology, histopathologic grading, classification, diagnosis, treatment, management and follow-up (including chemotherapy, irradiation, and immunotherapy) of gestational trophoblastic neoplasms - particularly molar pregnancies - are discussed; and ways to help create a standardized classification system and provide optimal treatment for each type of patient are suggested.     

Utility of p57 protein(KIP2) in molar disease to determine its androgenetic origin

OBJECTIVE: To determine, qualitatively and semiquantitatively, the expression of p57 protein in different trophoblastic cell populations of hydatidiform mole and anembryonic pregnancy. STUDY DESIGN: We performed an observational study of the histopathologic and immunohistochemical findings of 48 cases of hydatidiform mole and 2 anembryonic pregnancies. The histologic samples stained with hematoxylin-eosin were reviewed blindly by 3 pathologists to establish a diagnosis and compare it to the previous one. Afterward, immunohistochemical staining was performed using a polyclonal antibody on paraffin-embedded, formalin-fixed tissue sections. The nuclear staining was assessed in 5 cell types: villous mesenchyme, cytotrophoblast, syncytiotrophoblast, intervillous trophoblast and decidua. RESULTS: The degree of agreement between the previous histologic diagnosis and the current one was excellent (kappa = 0.702). The sensitivity was 82.6% for complete and 84% for partial mole. On immunohistochemical analysis, the degree of agreement was low (kappa = 0.2). The sensitivity was 53.9% for complete mole and 59.1% for partial mole. The cell population with the least expression for p57 was the cytotrophoblast. The results for anembryonic pregnancies remained the same. CONCLUSION: Immunohistochemistry with p57 is a useful method to differentiate complete from partial mole, which is important to establish the prognosis of the patient.     

Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic Counselling

Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal hyperproliferation of trophoblastic cells, which derive from the trophectoderm, the outer layer of the blastocyst that would normally develop into the placenta during pregnancy. GTDs encompass hydatidiform mole (HM) (complete and partial), invasive mole, gestational choriocarcinoma, placental-site trophoblastic tumor, and epithelioid trophoblastic tumor. Of these, the most common is HM, and it is the only one that has been reported to recur in the same patients from independent pregnancies, which indicates the patients’ genetic predisposition. In addition, HM is the only GTD that segregates in families according to Mendel’s laws of heredity, which made it possible to use rare familial cases of recurrent HMs (RHMs) to identify two maternal-effect genes, NLRP7 and KHDC3L, responsible for this condition. Here, we recapitulate current knowledge about RHMs and conclude with the role and benefits of testing patients for mutations in the known genes.     

Ancillary Techniques to Refine Diagnosis of GTD

Gestational trophoblastic disease (GTD) consists of hyperplastic and neoplastic disorders of placental trophoblast; i.e., hydatidiform moles and gestational trophoblastic tumors, respectively. While the histological diagnosis of well-developed complete hydatidiform mole and gestational choriocarcinoma is generally accurate, significant diagnostic challenges persist in the routine evaluation of early complete hydatidiform mole, partial hydatidiform mole, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Recently, the applications of new immunohistochemical markers and molecular techniques have significantly enhanced the diagnostic accuracy of various GTDs. P57 immunohistochemistry is a highly useful marker in confirming complete hydatidiform mole, including its early forms. PCR-based short tandem repeat DNA genotyping has emerged as a powerful diagnostic measure to precisely classify both complete and partial hydatidiform moles. With highly desired sensitivity and specificity, these powerful ancillary studies should be advocated and integrated into the routine diagnostic algorithm of GTD.     

Familial recurrent hydatidiform mole: a review

This article reviews published data on familial recurrent hydatidiform mole with particular reference to the genetic basis of this condition, the likely outcome of subsequent pregnancies in affected women and the risk of persistent trophoblastic disease following molar pregnancies in these families. Familial recurrent hydatidiform mole is characterized by recurrent complete hydatidiform moles of biparental, rather than the more usual androgenetic, origin. Although the specific gene defect in these families has not been identified, genetic mapping has shown that in most families the gene responsible is located in a 1.1 Mb region on chromosome 19q13.4. Mutations in this gene result in dysregulation of imprinting in the female germ line with abnormal development of both embryonic and extraembryonic tissue. Subsequent pregnancies in women diagnosed with this condition are likely to be complete hydatidiform moles. In 152 pregnancies in affected women, 113 (74%) were complete hydatidiform moles, 26 (17%) were miscarriages, 6 (4%) were partial hydatidiform moles, and 7 (5%) were normal pregnancies. Molar pregnancies in women with familial recurrent hydatidiform mole have a risk of progressing to persistent trophoblastic disease similar to that of androgenetic complete hydatidiform mole.     

Gestational Trophoblastic disease in New Zealand, 1980 — 1986

During the period 1980 to 1986, inclusive, 350 cases of gestational trophoblastic disease were recorded within New Zealand; of these cases nearly 70% were reported to a Register established to obtain epidemiological information. Clinical information obtained with the notifications revealed no difference in incidence of gestational trophoblastic disease among the 3 main ethnic groups which make up the New Zealand population; the uterine fundus was recorded as being large for dates in only 26%; the most common clinical presentation was as a threatened abortion; 7% of the cases were diagnosed at either routine ultrasound examination or at termination of pregnancy, there having been no suspicions prior to that procedure. A review of histological material obtained following notification suggested that the histological diagnosis of trophoblastic disease could not be substantiated in 14.7% of cases. During the period under review, therefore, there were 299 cases of trophoblastic disease (all but 2 of which were hydatidiform mole) and 447,667 pregnancies giving an incidence of 1 case of trophoblastic disease per 1,497 pregnancies.     

Recurrent complete hydatidiform mole: where we are,is there a safe gestational horizon? Opinion and mini-review

Benign hydatidiform mole, complete or partial, is the most common type of gestational trophoblastic disease (GTD) characterised by excessive trophoblastic proliferation and abnormal embryonic development. Although most complete hydatidiform moles (CHMs) are diploid androgenetic, a few cases of CHMs are biparental, characterised by recurrence and familial clustering. In these rare cases, mutations in NLRP7 or KHDC3L genes, associated with maternal imprinting defects, have been implicated. Current data regarding future pregnancy options in hydatidiform moles are discussed and our opinion is presented based on an incidence that took place in our hospital with a woman with consecutive molar pregnancies. In recurrent hydatidiform moles, DNA testing should be performed and when NLRP7 or KHDC3L mutation are detected, oocyte donation should be proposed as an option to maximise woman’s chances of having a normal pregnancy.     

Laparoscopic management of a cornual ectopic pregnancy associated with persistant gestational throphoblastic disease: a case report

A 30-year-old woman underwent laparoscopy for diagnosis and treatment of ectopic pregnancy. A dark-red bulging mass was observed in the right uterine horn. Laparoscopic hysterotomy was performed. The histological examination revealed a hydatidiform mole, which was confirmed by DNA ploidy analysis showing triploidy (69 XXY) as apartial hydatidiform mole after the cytogenetic examination. On the third postoperative day, the thoracic computed tomography scan revealed punctuate lesions. These lesions disappeared after single-agent chemotherapy with methothrexate. To the best of our knowledge, this is the first case of cornual persistent gestational trophoblastic neoplasia managed by laparoscopic surgery.     

Telomerase activity in complete hydatidiform mole.

OBJECTIVE: To investigate whether telomerase is activated in complete hydatidiform mole and whether it could predict the development of persistent gestational trophoblastic tumors (GTTs). STUDY DESIGN: For this prospective study, 21 patients with complete hydatidiform mole were recruited. Molar tissue was obtained for telomerase activity measurement using the telomeric repeat amplification protocol assay. Patients' clinical characteristics, telomerase activity and subsequent clinical outcome were analyzed. RESULTS: Telomerase activity was detected in 12 cases (57.1%) with varied intensity. Two of four patients who had telomerase activity, uterine size larger than expected and preevacuation serum beta-human chorionic gonadotropin (beta-hCG) levels > 10(6) mIU/mL developed persistent GTT. CONCLUSION: Telomerase activity is detectable in some complete hydatidiform moles and might be useful for predicting persistent GTT when combined with uterine size and preevacuation serum beta-hCG level.     

Twin pregnancy with a complete hydatidiform mole and co-existent live fetus: two case reports and review of the literature

Introduction  The aim of this study was to report the clinical features, management, and outcome of two cases of complete hydatidiform mole with a coexisting viable fetus and to review the literature. Case reports  In this article, we report on the well-documented follow-up of two cases of twin pregnancies with complete hydatidiform mole and a normal fetus. Genetic amniocentesis showed normal fetal karyotype in both of two cases. In the first case, a live male infant was delivered by a cesarean section because of severe maternal bleeding at 29 weeks of gestation. In the second case, termination of pregnancy was performed due to early onset of severe preeclampsia and vaginal hemorrhage. Conclusion  The chances of a live birth have been estimated between 30 and 35% and the risk of persistent trophoblastic disease is similar to singleton molar pregnancies in complete mole with coexisting fetus pregnancy. Therefore, in these pregnancies, expectant management instead of termination of pregnancy can be suggested.     

Anatomy and pathology of tubal pregnancy

The prevalence of tubal pregnancy has increased markedly during the past decade. The reasons for this are obscure. A systematic gross and histopathologic study of 25 consecutive ectopic pregnancies has been performed using a clearing method not used previously for this purpose. In addition, the presence of the corpus luteum and its location in reference to the tubal pregnancy are documented. Results indicate that trophoblastic spread was predominantly intraluminal in 67% of cases. Intratubal hemorrhage, generally in parallel to trophoblastic spread, often led to marked tubal destruction. Histologic evidence of salpingitis was noted in only seven of 24 specimens (29%). The corpus luteum was contralateral to the ectopic pregnancy in five of 21 cases (23.8%). Clinical correlates and areas of future research are discussed. Results indicate that segmental resection of the tubal pregnancy is appropriate in selected cases.     

Immunohistochemical expression analysis of inhibin-alpha and -beta subunits in partial and complete moles, trophoblastic tumors, and endometrial decidua.

The expression of inhibin-alpha subunit has been described in normal placentas, hydatidiform moles, and trophoblastic tumors. We performed a double immunohistochemical expression analysis of inhibin-alpha and inhibin-beta subunits in a cytogenetically well characterized series of 21 complete and 22 partial hydatidiform moles, 2 placental site trophoblastic tumors, and one choriocarcinoma. Syncytiotrophoblastic cells were consistently inhibin-alpha and inhibin-beta positive in all hydatidiform moles and in the one choriocarcinoma. Cytotrophoblast was negative for both subunits in all trophoblastic lesions studied. While villous intermediate trophoblastic cells were consistently inhibin-alpha negative in all hydatidiform moles, focal inhibin-beta immunoreactivity was detected in villous intermediate trophoblast in approximately one third of complete and partial hydatidiform moles. Decidual stromal cells in 40 hydatidiform moles were inhibin-alpha and inhibin-beta positive in approximately one third of cases. Both placental site trophoblastic tumors were inhibin-alpha positive but inhibin-beta negative. Our findings indicate that inhibin-alpha and -beta subunits are consistently coexpressed in syncytiotrophoblast in complete and partial moles. Immunohistochemical detection of inhibin subunits may be useful in the differential diagnosis of trophoblastic lesions.     

Sensibilidad de la ecografía transvaginal en el diagnóstico de la mola hidatiforme de primer trimestre

Objective

To assess the accuracy of first trimester ultrasound to diagnose complete or partial hydatidiform moles.

Patients and methods

All cases of sonographically suspected and/or histologically proven complete or partial hydatidiform mole diagnosed in our center from January 1998 to December 2010 were analyzed. The sensitivity and positive predictive value of ultrasound in the detection of molar pregnancies were calculated.

Results

The study group included 59 patients. Of these, 49 were suspected of having hydatidiform mole by ultrasound, 39 of which were histologically confirmed (27 partial and 12 complete). In the remaining 10 cases, the histological diagnosis was pregnancy loss. During the same period, histopathology demonstrated molar pregnancy in a further 10 patients (nine partial and one complete) previously diagnosed as pregnancy loss by ultrasound. Therefore, the study included a total of 49 cases with a final diagnosis of hydatidiform mole (36 partial, 13 complete). The sensitivity and positive predictive value of ultrasound in first-trimester hydatidiform mole was 79.6% (39/49) and 79.6% (39/49) respectively. Of the 49 molar pregnancies, 10 (20.4%) were not identified correctly. The detection rate for complete mole (12/13, 92.3%) was slightly better than that for partial mole (27/36, 75%) but this difference was not significant (p=0.18).

Conclusion

The accuracy of first-trimester ultrasound in the diagnosis of hydatidiform mole is high. No significant differences were found between the diagnosis of partial and complete hydatidiform mole. In view of the significant number of molar pregnancies not diagnosed by ultrasound, we recommend histopathological evaluation of all cases of pregnancy loss.