Persistent Gestational Trophoblastic Disease Research Articles

Triplet Pregnancy With a Complete Hydatidiform Mole Co-Existing With Two Fetuses [15K

INTRODUCTION: Triplet pregnancies with a hydatidiform mole and two co-existing fetuses (HMTCF) are rare, mostly resulting from infertility treatments. METHODS: This is a case of a 30 year old Caucasian G1P0 with infertility who underwent successful in vitro fertilization with a three-embryo transfer resulting in a triplet gestation of a HMTCF. RESULTS: The patient experienced preterm labor with bleeding and subsequent delivery of live twins at 26 weeks via cesarean. Her Beta HCG levels dropped appropriately and she had a normal postpartum course. CONCLUSION: The outcomes vary amongst reported cases: 32% terminated electively or due to maternal complications; 9% had spontaneous abortions; and 59% delivered vaginally or by cesarean delivery, for whom the average gestational age at delivery was 29±5 weeks. Of the pregnancies that were allowed to continue, 60% resulted in one or more live twin births. Antepartum complications included vaginal bleeding (55%), pre-eclampsia (23%), hyperemesis gravidarum (14%), hyperthyroidism (9%), and persistent gestational trophoblastic disease (41%). Patients with HMTCF should be counseled about the risks of such a pregnancy.

Invasive Complete Hydatidiform Moles: Analysis of a Case Series With Genotyping.

Complete hydatidiform moles (CHM) are purely androgenetic conceptions, with most (∼85%) arising from fertilization of an egg lacking maternal DNA by a single sperm that duplicates (homozygous/monospermic 46,XX) and a small subset arising via fertilization by 2 sperms (heterozygous/dispermic 46,XY or 46,XX). It remains controversial if heterozygous/dispermic CHMs have a significantly greater risk of persistent gestational trophoblastic disease. Analysis of zygosity of CHMs with and without invasion at presentation, including invasive CHMs with concurrent atypical trophoblastic proliferations concerning for or consistent with choriocarcinoma, has not been specifically addressed. In a prospective series of 1024 products of conception specimens subjected to immunohistochemical analysis of p57 expression and molecular genotyping with short tandem-repeat markers, 288 CHMs were diagnosed, of which 126 were genotyped, including 16 invasive CHMs. Zygosity was compared between those with and without invasion. Of the 16 study cases, 12 (75%) were homozygous/monospermic XX and 4 (25%) were heterozygous/dispermic (3 XY and 1 XX). Of the 110 genotyped noninvasive CHMs, 96 (87%) were homozygous/monospermic XX and 14 (13%) were heterozygous/dispermic (12 XY, 2 XX). Comparison of the zygosity results for the invasive CHMs (study group) with the noninvasive CHMs in the database did not demonstrate a statistically significant difference (P=0.24, Fisher exact test). In addition, of the 3 cases associated with metastatic gestational trophoblastic disease (pulmonary nodules) at presentation, 2 were homozygous/monospermic XX, indicating that this form is not without risk of significant gestational trophoblastic disease. Thus, the current study has demonstrated a higher frequency of heterozygous/dispermic CHMs among invasive cases compared with those lacking invasion, but does not support the use of zygosity data for risk assessment of CHMs. A persistent, unresolved diagnostic challenge identified in some invasive CHMs is interpretation of accompanying florid atypical trophoblastic proliferations which raise concern for choriocarcinoma. Future studies should address the need for reproducible diagnostic criteria and molecular biomarkers for distinguishing florid hyperplastic from malignant neoplastic trophoblastic proliferations.

Twin pregnancy with both complete hydatiform mole and coexistent alive fetus: Case report

Abstract Twin pregnancy consisting of a complete hydatidiform mole coexisting with a live fetus is a rare condition with an incidence of 1 in 22 000 to 1 in 100 000 pregnancies. Clinical information is limited and management is difficult due to the risk of pregnancy complications such as fetal death, vaginal bleeding, preeclampsia, hyperthyroidism, and the risk of persistent gestational trophoblastic disease. Thus, the report described about the change of size and implantation site of the molar mass coexisting with a live fetus is rare especially about sonographic findings such as echo patterns. Recently we experienced a case of complete hydatidiform mole with a healthy infant delivered at term.

Mola completa coexistente con feto vivo normal: caso clínico y revisión de la literatura

The coexistence of a complete mole and live term fetus is a rare entity seldom reported in the literature. Primary non-invasive diagnosis is usually achieved through ultrasound examination and definitive diagnosis can be achieved when molar tissue samples are available for histopathological examination. Patients with a complete mole have a 12-20% risk of developing persistent gestational trophoblastic disease, hence the importance of close follow-up. We report the early diagnosis of a complete mole coexisting with a normal fetus and also provide a review of the literature on the topic.

Gestational trophoblastic disease in the western region of Saudi Arabia (single-institute experience)

ObjectiveTo estimate the prevalence of gestational trophoblastic disease (GTD) in the western region of Saudi Arabia, and to evaluate the success of treatment and the effect of age and risk group on survival. MethodsBetween January 2001 and December 2010, all patients treated for GTD were identified from the King Abdulaziz University Hospital database. Patients with persistent disease were evaluated according to their clinical treatment outcomes. ResultsIn total, 122 cases of GTD were identified in the database. Of these, 77 (63%) cases were diagnosed and received initial treatment at the study centre, resulting in an incidence of 1.26 cases per 1000 deliveries. The mean (±standard deviation) age of the study participants was 31.52±10.8 years, mean gestational age at diagnosis was 12.42±3.2 weeks, and mean follow-up for each patient was 24 months. There were 20 cases (26%) of persistent GTD after treatment. The majority of patients with low-risk disease were treated with single-agent methotrexate, with an overall success rate of 83%. The overall 5-year survival rate for all patients was 98%. Using the Wilcoxon (Gehan) test, risk group and age (cut-off 40 years) were not found to be significantly associated with survival (p=0.69). ConclusionsThis single-institute study reports the first survival data for GTD for Saudi Arabia. However, the overall incidence of GTD in Saudi Arabia will be defined by establishment of a GTD registry.

Utility of fluorescence in situ hybridization for ploidy and p57 immunostaining in discriminating hydatidiform moles

Discrimination between complete moles (CMs), partial moles (PMs), and hydropic abortions (HAs) is important as the risk of persistent gestational trophoblastic disease (GTD) differs for each condition. We evaluated whether ancillary fluorescence in situ hybridization (FISH) with a set of chromosome enumeration probes (CEP) for chromosomes X, Y, and 17 and p57 immunostaining could improve the clinical diagnosis. Forty-one products of conception (POC) were reclassified according to clinical performance, morphology, p57 immunostaining results, and FISH results. The accuracy of histological examination alone was 85% for the original diagnosis. FISH analysis showed diploidy in 19 of 20 CMs and triploidy in 4 of 6 PMs. The concordance rate was 92.5% on using the CEP probes. p57 Staining was negative in all CMs and positive in all PMs and HAs. Chromosomal abnormality was detected in 3 cases of HA by using FISH. In conclusion, combined p57 immunostaining and FISH with a set of 3 CEP probes for chromosomes X, Y, and 17 could be useful in the classification of hydatidiform moles.

Classification and Morphology of Gestational Trophoblastic Disease

Gestational trophoblastic disease (GTD) is a clinically and morphologically very heterogeneous group of interrelated lesions, characterised by abnormal growth of the different types of trophoblastic cells, sometimes associated with villous dysmaturity. The management and follow up of the patients and risk calculation for persistent GTD is mainly based on histopathologic diagnosis. The morphologic and differential diagnostic criteria of the villous forms of GTD (complete, partial and invasive hydatidiform moles) are summarised in the paper as well as ancillary techniques for correct diagnoses. Exaggerated placental sites (EPS) and placental site nodules (PSN) represent benign lesions, derived from the intermediate trophoblast and their characteristics are given. The concept of atypical PSN as a recently defined lesion is discussed. Gestational choriocarcinoma (CC), placental site trophoblastic tumor (PSTT) and the epitheloid trophoblastic tumor (ETT) represent tumorous forms of GTD, also termed as gestational trophoblastic tumors (GTT). Their morphologic criteria and clues for differential diagnosis are given, including the discussion about the transition from one lesion into another.

MOLAR ECTOPIC PREGNANCY;

Ectopic molar pregnancy is a rare occurrence. Clinical diagnosis of a molar pregnancy is difficult but histopathology is thegold standard for diagnosis. The management of ectopic molar pregnancies consists of surgically removing the conceptus, follow up &chemotherapy, if required. We are reporting a case report of a 35-year-old married, nulliparous woman, admitted in emergency with a 6-week history of amenorrhea, severe abdominal pain & an episode of fainting at home. Per abdominal examination revealed tendernessover the right iliac fossa, with guarding & rigidity. Diagnosis of ruptured ectopic pregnancy was made.Emergency laparotomy was done.Histopathological examination, showed tubal ectopic pregnancy with partial hydatidiform mole & a separate corpus luteal cyst.She wasfollowed up with serial beta hCG which became normal within 1 month. Although ectopic molar pregnancy is a rare entity but all ectopicpregnancies should be examined histologically to rule out presence of gestational trophoblastic disease to plan follow-up accordingly inorder to avoid persistent gestational trophoblastic disease which has a chance of malignant conversion.The prognosis of ectopic molarpregnancies is the same as for other forms of gestational trophoblastic disease.

Ki-67 Expression in Hydatidiform Moles and Hydropic Abortions

BackgroundDifferential diagnosis of hydatidiform moles from non-molar specimens as well as their sub-classification such as complete and partial hydatidiform moles are important for clinical management and accurate risk assessment for persistent gestational trophoblastic disease, but diagnosis based solely on histomorphology suffers from poor interobserver and intraobserver reproducibility.ObjectivesThis study was undertaken to determine whether the expression of Ki-67 protein could differentiate these entities.Materials and MethodsWe performed Ki-67 immunohistochemical staining in 19 molar (8 partial and 11 complete moles) and 10 non-molar (hydropic abortions) formalin-fixed, paraffin-embedded tissue samples. Ploidy analysis using flow cytometry had confirmed diploidy in hydropic abortions and complete moles and triploidy in partial moles.ResultsKi-67 immunoreactivity was assessed in villous cytotrophoblasts, syncytiotrophoblasts and stromal cells. Positive cells were found to be restricted mostly to the villous cytotrophoblasts, while syncytiotrophoblasts showed an absence of immunostaining for Ki-67, and occasional weak nuclear staining was seen in the stromal cells. There was a significant difference in Ki-67 immunoreactivity of cytotrophoblastic cells between hydropic abortions and complete moles (P < 0.001), hydropic abortions and partial moles (P = 0.002) and also between complete and partial moles (P < 0.001). On the other hand, there is significant overlap in the Ki-67 immunoreactivity between complete and partial moles (++ staining category) and between partial moles and hydropic abortions (+ staining category).ConclusionsDespite the significant differences , Ki-67 immunostaining could not be helpful in distinguishing molar placentas from hydropic abortions as well as partial from complete hydatidiform moles, because there are considerable overlaps between results in different categories.

Detection of Sugar Chain Expression in Hydatidiform Mole Using Lectin Histochemistry

BackgroundHydatidiform moles carry a significant risk for developing persistent gestational trophoblastic disease. Lectins are useful tools to identify cellular glycosylation pattern and changes in glycosylation that occur during growth, development, differentiation and also, during disease states.ObjectivesConsidering the changes in glycosylation that occur during cell proliferation, differentiation and transformation, the aim of the present study was to evaluate the sugar chain expression in hydatidiform mole by using HRP-conjugated lectins.Materials and MethodsLectin histochemistry with a panel of HRP-conjugated lectins comprising SBA, PNA, VVA, UEA-1, LTA, GS-І (B4) and WGA were performed in 20 molar (partial & complete moles) formalin-fixed, paraffin-embedded tissue samples.ResultsThe partial and complete moles generally showed similar reactivity with all used lectins. None of lectins reacted with villous cytotrophoblasts, whereas 4 of 7 lectins comprising WGA, LTA, UEA-І and PNA (after pretreatment with neuraminidase) showed a moderate to strong reactivity with villous syncytiotrophoblasts in both partial and complete hydatidiform moles. The villous stroma reacted with all used lectins except VVA.ConclusionsOur histochemical findings showed a relatively heavy glycosylation of syncytiotrophoblasts of both partial and complete molar tissues, which was prominent in apical portion. This may play a role in their capacity to increase trophoblastic proliferation.

Complete hydatidiform mole with coexisting twin fetus: usefulness of MRI in management planning.

Complete hydatidiform mole with coexistent twin fetus is a rare condition. Only one out of a total reported 16 cases before the 1980s was diagnosed antenatally; hence, there was really no need to take a clinical decision. The number of cases of CHMCTF has since gone up dramatically with the availability of advanced ultrasound and emerging IVF techniques including newer ovulation drugs [1]. The optimal management is a challenge that remains a clinical dilemma. The present viewpoint is tilted toward expectant management with strict surveillance to prevent/treat complications early, so as to be able to deliver a normal baby in many of these patients. No difference in the risk of developing persistent gestational trophoblastic disease (PGTD) and gestational trophoblastic neoplasia (GTN) in patients undergoing termination of pregnancy as well as patients allowed to continue pregnancy has permitted the clinician to delay intervention till after delivery, while successfully managing the complications associated with trophoblastic disease. The role of MRI in addition to ultrasound in correctly distinguishing this condition from the partial hydatidiform mole is discussed, thus assisting in the management plan.

Characterization of Androgenetic/Biparental Mosaic/Chimeric Conceptions, Including Those With a Molar Component

Recent studies have demonstrated the value of ancillary techniques, including p57 immunohistochemistry and short tandem repeat genotyping, for distinguishing hydatidiform moles (HM) from nonmolar specimens and for subtyping HMs as complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM). With rare exceptions, CHMs are p57-negative and androgenetic diploid; partial hydatidiform moles are p57-positive and diandric triploid; and nonmolar specimens are p57-positive and biparental diploid. Androgenetic/biparental mosaic/chimeric conceptions can have morphologic features that overlap with HMs but are genetically distinct. This study characterizes 11 androgenetic/biparental mosaic/chimeric conceptions identified in a series of 473 products of conception specimens subjected to p57 immunohistochemistry and short tandem repeat genotyping. Fluorescence in situ hybridization was performed on 10 to assess ploidy. All cases were characterized by hydropically enlarged, variably sized and shaped villi. In 5 cases, the villi lacked trophoblastic hyperplasia, whereas in 6 there was a focal to extensive villous component with trophoblastic hyperplasia and features of CHM. The villi lacking trophoblastic hyperplasia were characterized by discordant p57 expression within individual villi (p57-positive cytotrophoblast and p57-negative stromal cells), whereas the villous components having trophoblastic hyperplasia were uniformly p57-negative in both cell types. Short tandem repeat genotyping of at least 2 villous areas in each case demonstrated an excess of paternal alleles in all regions, with variable paternal:maternal allele ratios (usually >2:1); pure androgenetic diploidy was identified in those cases with a sufficiently sized villous component having trophoblastic hyperplasia and features of CHM. Fluorescence in situ hybridization demonstrated uniform diploidy in 7 cases, including 4 of 5 tested cases with trophoblastic hyperplasia and 3 of 5 cases without trophoblastic hyperplasia. Two cases without trophoblastic hyperplasia had uniformly diploid villous stromal cells but 1 had triploid and 1 had tetraploid cytotrophoblast; 1 case with trophoblastic hyperplasia had uniformly diploid villous stromal cells but a mixture of diploid, triploid, and tetraploid cytotrophoblast. In 3 cases with a CHM component, persistent gestational trophoblastic disease developed. These results indicate that androgenetic/biparental mosaic/chimeric conceptions are most often an admixture of androgenetic diploid (p57-negative) and biparental diploid (p57-positive) cell lines but some have localized hyperdiploid components. Recognition of their distinctive p57 expression patterns and genotyping results can prevent misclassification as typical CHMs, PHMs, or nonmolar specimens. The presence of androgenetic cell lines, particularly in those with a purely androgenetic CHM component, warrants follow-up because of some risk of persistent gestational trophoblastic disease.

Clinical Presentation and Management of Hydatidiform Mole in a Peripheral Tertiary Hospital

This study was conducted in Faridpur Medical College Hospital, Faridpur, from January 2008 to December 2008 among fifty patients, diagnosed as a case of molar pregnancy. Incidenc of molar pregnancy was 8.27 per thousand pregnancy. Sixty percent of the patients were multiparous and eighty percent of low socio economic status . B positive blood group was prevalent (36%) in this study.Sixty percent( 60%) of the patients presented with amenorrhoea and abnormal vaginal bleeding.. Most of the patients (72%) were treated with suction evacuation and curettage. Of them hemorrhage was the most common immediate complication (80%). Complication like shock and perforation during evacuation was 14% and 4% respectively. Three patient (6%) developed Persistent Gestational Trophoblastic Disease(GTD) and one (2%) patient developed choriocarcinoma with lung metastasis and died. Thirty two (64%) patients attended for regular follow up but ten patients (20%) had attended irregularly and eight patients (16%) had dropped out .This study shows that follow up for molar pregnancy cases is not satisfactory in a district medical college hospital.Further improvement can be done by increasing awareness of the patients. DOI: http://dx.doi.org/10.3329/bjog.v25i2.13741 Bangladesh J Obstet Gynaecol, 2010; Vol. 25(2) : 59-64

Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia.

Para-adnexal choriocarcinoma in a woman previously diagnosed with complete hydatidiform mole

Aim To understand the long-term sequelae of complete molar pregnancy and identify potential sites of choriocarcinoma. Methods Case report of a recent metastatic choriocarcinoma identified within para-adnexal tissue in a patient with persistently elevated serum beta-HCG, previously diagnosed with complete molar pregnancy on endometrial curettings. Review of current literature. Results The potential complications of complete molar pregnancy include persistent or metastatic gestational trophoblastic disease. Choriocarcinoma is a complication in 2–5% of cases and is typically identified intrauterine or as a distant metastasis. Rare sites of occurrences such as ovary and fallopian tube have been reported. Discussion Choriocarcinoma is an uncommon outcome in complete molar pregnancy. Careful examination of hysterectomy and salpingo-oopherectomy specimens is crucial to determine the cause of persistently elevated serum beta-HCG levels in women diagnosed and treated for complete molar pregnancy.

Diagnostic Utility of Microsatellite Genotyping for Molar Pregnancy Testing

Molecular genotyping by analysis of DNA microsatellites, also known as short tandem repeats (STRs), is an established method for diagnosing and classifying hydatidiform mole. Distinction of both complete hydatidiform mole and partial hydatidiform mole from nonmolar specimens is relevant for clinical management owing to differences in risk for persistent gestational trophoblastic disease. To determine the technical performance of microsatellite genotyping by using a commercially available multiplex assay, and to describe the application of additional methods to confirm other genetic abnormalities detected by the genotyping assay. Microsatellite genotyping data on 102 cases referred for molar pregnancy testing are presented. A separate panel of mini STR markers, flow cytometry, fluorescence in situ hybridization, and p57 immunohistochemistry were used to characterize cases with other incidental genetic abnormalities. Forty-eight cases were classified as hydatidiform mole (31, complete hydatidiform mole; 17, partial hydatidiform mole). Genotyping also revealed 11 cases of suspected trisomy and 1 case of androgenetic/biparental mosaicism. Trisomy for selected chromosomes (13, 16, 18, and 21) was confirmed in all cases by using a panel of mini STR markers. This series illustrates the utility of microsatellite genotyping as a stand-alone method for accurate classification of hydatidiform mole. Other genetic abnormalities may be detected by genotyping; confirmation of the suspected abnormality requires additional testing.

P31.11: Complete hydatidiform mole and normal live birth: placental mosaicism or twin with CHM?

Introduction: survival of a normal fetus to term in the presence of hydatidiform mole remains an extremely uncommon occurrence. Prenatal diagnosis is possible by ultrasonography showing molar invasion of the normal placenta without clear margin. Antenatal detection of mole co existing with a viable fetus should warrant genetic analysis and search for gross malformation of the fetus. Case report: we report a rare case exhibiting molar pregnancy and a coexisting normal fetus. A 29 year, primigravida had an episode of vaginal bleeding at 18 weeks which suggested avascular lower placenta with multiple cystic area measuring 12 × 5 × 9 cm with normal fetus. She had two weekly growth scan and Doppler as diagnosis was not clear. It was thought to be multiple placental lakes. Growth and Doppler remains normal and had term SVD. Placenta was sent for histopathology which suggested normal placenta with an area of complete hydatidiform mole. It was difficult to differentiate from mosaic CHM, twin with normal co-twin and CHM. Discussion: coexistent live fetus and molar placenta has never been reported. Complications including pre-eclampsia, hyperthyroidism, vaginal bleeding, persistent gestational trophoblastic disease, preterm labour, miscarriage and anaemia increases. Several factors may influence the outcome in partial mole such as karyotype of the fetus, size of the molar placenta, the speed of molar degeneration and fetal anaemia.

LOW DOSES OF HIGH FREQUENCY LOW MAGNITUDE LOADING INCREASE MODULUS & MAINTAIN GAG IN CULTURED TENDONS

Objective: The purpose of this study was to evaluate the association of telomerase activity in complete hydatidiform moles with subsequent development of persistent gestational trophoblastic tumor. Study Design: By means of the standard telomerase repeat assay, we examined telomerase activity in 4 normal placentas, 31 complete hydatidiform moles (16 cases of uneventful regression, according to serum levels of β-human chorionic gonadotropin, after evacuation and 15 cases in which persistent gestational trophoblastic disease developed after evacuation), 7 invasive moles, and 5 choriocarcinoma tissue samples. Results: Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform moles in patients who eventually underwent chemotherapy for the treatment of persistent gestational trophoblastic tumors. All 9 patients with metastatic disease (International Federation of Gynecology and Obstetrics stage III) had telomerase activity in the initial molar tissue sample. In contrast, telomerase activity was evident in only 3 of 16 (12.5%) complete hydatidiform moles from patients with spontaneous remission after evacuation (P < .05). Telomerase activity was detected in all 7 invasive moles and all 5 choriocarcinoma tissue samples but was not detected in normal placentas. Conclusion: The presence of telomerase activity in complete hydatidiform moles is associated with the development of persistent gestational trophoblastic tumors, such as invasive moles and choriocarcinoma. (Am J Obstet Gynecol 1999;180:328-33.)

Severe Peritonitis Induced by Methotrexate During Treatment of Persistent Gestational Trophoblastic Disease

This letter reports a case of methotrexate-induced peritonitis in an extensively investigated patient.

Hydatidiform Mole with Coexistant Viable Fetus

Background: A hydatidiform mole with a coexistent viable fetus is a rare entity. Case: This article reports a case of a 30-year-old, gravida 4, para 2, who presented at 14 weeks' period of gestation with bleeding per vaginum. Ultrasonography revealed a twin pregnancy consisting of a hydatidiform mole and a coexistent fetus. After a detailed discussion with the patient and her mate, the pregnancy was terminated. Results: A pathologic examination was consistent with a complete mole coexistent with a normal fetus and placenta. Serial monitoring of the patient's serum β–human chorionic gonadotropin was performed until this parameter was negative. Results: On follow-up, the patient has been free of persistent gestational trophoblastic disease (GTD). Conclusions: A hydatidiform mole coexistent with a viable fetus is rare and has poor prognosis. Continuation of pregnancy in CMCF is controversial because of the risk of maternal complications and risk of persistent GTD. (J GYNECOL SURG 28:150)