Diagnosis Of Gestational Trophoblastic Disease Research Articles

Ultrasound screening for gestational trophoblastic disease

The Editorial1 and the article by Johns et al.2 on the screening for gestational trophoblastic disease emphasize the important role of ultrasound but do not sufficiently highlight the issue of the non-screening of unwanted pregnancies. The advent of ultrasound has indeed changed the clinical presentation of this disease entity as diagnosis is now being made very early in pregnancy. However, a significant number of pregnancies are not scanned, do not have serum beta human chorionic gonadotropin (hCG) evaluated and products of conception histologically examined. Currently in the UK, most pregnancies that carry to term or end in failure will undergo at least one ultrasound evaluation. However, most pregnancies that are terminated in the absence of fetal malformation do not undergo ultrasound screening. Furthermore, the products of conception from these terminations are rarely subjected to histological evaluation3. In the UK about 20% of all pregnancies are terminated representing a significant number of pregnancies in which the diagnosis of gestational trophoblastic disease may be missed as there is no ultrasound evaluation of the pregnancy and the products of conception are not subjected to histological analysis. The Royal College of Obstetricians and Gynaecologists does not consider ultrasound evaluation of all pregnancies prior to termination as essential, and therefore, such pregnancies are not being screened for gestational trophoblastic disease4. The increased index of suspicion for the presence of gestational trophoblastic disease, which would follow from suspicious findings on ultrasound screening of unwanted pregnancies, is hence not there. Therefore, there is no impetus for further evaluation of the pregnancies by serum beta hCG. This scenario increases the likelihood that the diagnosis of gestational trophoblastic disease will be missed where the pregnancy is unwanted. The recommendations of Johns et al.2 in their paper should be extended to all pregnancies as it would help clinicians to offer all pregnant patients the proper counseling, irrespective of the outcome of the pregnancy, and to offer the appropriate methods of management of their pregnancies. U. I. Esen*, * South Tyneside Foundation Trust, Obstetrics Gynaecology, South Shields, Tyne & Wear, UK

Management and outcome of healthy women with a persistently elevated serum β-hCG

5086 Background: Elevated serum beta human chronic gonadotrophin (β-hCG) not due to pregnancy can occur as a consequence of (1) gestational trophoblastic disease (GTD) (2) non-gestational trophoblastic tumours, (3) false positive, often associated with heterophilic antibodies, (4) during the menopause, and (5) it may represent a high normal level. The accurate differentiation between these causes is vital to avoid potentially inappropriate investigations and therapies which may induce infertility or other serious adverse events. Here we report the United Kingdom experience of patients with an elevated β-hCG where the cause was initially uncertain and provide a clinical algorithm for the management of such cases. Method: The Charing Cross and Sheffield GTD database was screened between 1981–2004 to identify patients referred with an elevated β-hCG in the absence of a previous diagnosis of GTD and who were not pregnant. Results: Between 1981–2004 fourteen women were referred with persistently raised serum β...

The diagnosis of gestational trophoblastic disease in early pregnancy: implications for screening, counseling and management

The diagnosis of gestational trophoblastic disease in early pregnancy: implications for screening, counseling and management

Trophoblastic diseases and pregnancy

Gestational trophoblastic disease (GTD) is a term commonly applied to a spectrum of interrelated disorders originating from the placental trophoblast. These include complete, partial and invasive moles, placental site trophoblastic tumours and choriocarcinomas. Modern genetic and molecular biology techniques enable rapid and accurate diagnosis and have contributed to a better understanding of the pathophysiology of GTD. As a result most women can be treated before they develop severe complications. This review addresses the perinatal diagnosis of GTD and focuses on the roles of ultrasound and Doppler examination in prenatal diagnosis and the importance of histopathology in the postnatal diagnosis of GTD.

Role of Hysterectomy in Management of Gestational Trophoblastic Disease

To evaluate incidence, indications, and outcome of hysterectomy in women presenting with gestational trophoblastic disease. A prospective observational study using a standardized protocol for registration, assessment, and treatment of gestational trophoblastic disease. A total of 5976 consecutive new patients registered between January 1986 and December 2000 with a diagnosis of gestational trophoblastic disease. The setting was a supraregional tertiary referral center for gestational trophoblastic disease. Between January 1 1986 and December 31 2000, 5976 new patients with a diagnosis of gestational trophoblastic disease were registered at Weston Park Hospital, Sheffield. Of these patients, 301 required chemotherapy. Forty patients underwent hysterectomy. The average pretreatment risk score in women who had hysterectomy was 7.4. The mean time interval between diagnosis of molar disease and hysterectomy was 17 months. Indications for hysterectomy included uncontrollable vaginal or intraabdominal bleeding, localized chemo-resistant disease, and placental site trophoblastic tumor. In this group, 31 of 40 women had chemotherapy and 14 patients needed more than one regimen. These women were also more likely to have atypical histology (3 invasive moles, 6 placental site trophoblastic tumours, 13 choriocarcinomas, and 2 dimorphic tumours). There were 10 deaths in all registered patients with molar disease and 4 of these were in the hysterectomy group. Hysterectomy was performed in 1 in 150 northern UK women with gestational trophoblastic disease. Patients needing hysterectomy represent an increased-risk group as indicated by their high pretreatment risk scores, atypical histology, frequent use of salvage chemotherapy, and higher mortality.

Cytokeratin 20 as a biomarker of gestational trophoblastic disease: diagnostic and prognostic significance.

This study was designed to examine whether cytokeratin 20 (CK20) is expressed in molar pregnancies and may therefore be used in the diagnosis of gestational trophoblastic disease (GTD). The potential of CK20 expression in predicting the evolution and the prognosis of the different subtypes of GTD was also assessed. A total of 48 samples were studied for CK20 expression by RT-PCR methodology. Among these, 24 samples were obtained by curettage of the uterine cavity of patients diagnosed with hydatidiform mole (14 complete moles and 10 partial moles), 4 samples were obtained from choriocarcinoma cell lines (2 JAR and 2 JEG), and 20 samples were of normal trophoblast (control group) obtained from patients that underwent elective termination of pregnancy. Expression of CK20 was identified in all the samples of complete mole (CM), all choriocarcinoma cell lines, and 50% of the patients with partial mole (PM). None of the preparations of normal trophoblastic tissue from the control group expressed the CK20. A significant difference (P < 0.00001) was found in CK20 expression between samples of patients with GTD and control samples. Comparison between CK20 expression in CMs and PMs revealed a significantly more frequent expression of CK20 in CMs (P = 0.006). More than 50% of the patients with PMs that were positive for CK20 had an invasive evolution. In our opinion, CK20 may assist in distinguishing between molar and normal trophoblastic tissue and may be considered a marker of GTD. In cases in which pathological classification of different subtypes of GTD is in doubt, CK20-positive expression is suggestive for a CM whereas CK20-negative is more indicative for PM.

How would you make the diagnosis of gestational trophoblastic disease and how would you manage it?*1

How would you make the diagnosis of gestational trophoblastic disease and how would you manage it?*1

Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy.

Tubal ectopic hydatidiform moles are rare lesions, and only 40 cases have been reported in the world literature. We investigated the apparently high incidence of tubal ectopic hydatidiform moles in women referred for treatment to a Supraregional Trophoblastic Tumour Screening and Treatment Centre between 1986 and 1996. Of 4261 women referred during the study period, 25 (0.6%) had a suspected tubal ectopic hydatidiform mole and paraffin-embedded tissue was available in 20 (80%) of these. Each case was reviewed by two pathologists and DNA flow cytometric analysis was undertaken when the histological diagnosis was initially deemed equivocal or suggestive of hydatidiform mole. On review, 17 cases (85%) showed no evidence of hydatidiform mole (circumferential trophoblastic proliferation, hydrops, scalloped villi, and stromal karyorrhexis). Of these, 11 cases (65%) showed features of early placentation and six (35%) showed hydropic abortion. DNA flow cytometry was performed in 14 (82%) of these cases and revealed a diploid population in each case. Three cases of molar pregnancy (15%) were identified. Each of these cases had the histological features of an early complete hydatidiform mole. Sufficient tissue was available for DNA flow cytometric analysis in two of these cases and confirmed the presence of diploidy in each. Our results show that tubal ectopic hydatidiform mole is a rare entity and demonstrate that it is over-diagnosed. Polar trophoblastic proliferation and hydropic villi are features of early placentation and of hydropic abortion. Sheets of extravillous trophoblast may be particularly prominent in tubal ectopic gestation. In the absence of circumferential trophoblastic proliferation combined with hydropic change a diagnosis of gestational trophoblastic disease should be avoided.

Expressions of proliferation markers (Ki-67, proliferating cell nuclear antigen, and silver-staining nucleolar organizer regions) and of p53 tumor protein in gestational trophoblastic disease

Objective: This study was undertaken to determine whether the expressions of 3 proliferation markers (Ki-67, proliferating cell nuclear antigen, and silver-staining nucleolar organizer regions) and of p53 tumor protein could differentiate spontaneous abortions from gestational trophoblastic diseases and also discriminate among gestational trophoblastic disease subgroups. Study Design: Twenty-two partial hydatidiform moles, 17 complete hydatidiform moles, 6 invasive hydatidiform moles, and 20 nonhydropic spontaneous abortions (control group) were evaluated by means of immunohistochemical techniques with antibodies to Ki-67, proliferating cell nuclear antigen, and p53. One-step silver staining was used to detect silver-staining nucleolar organizer regions. Results: The expressions of Ki-67, proliferating cell nuclear antigen, silver-staining nucleolar organizer regions, and p53 were significantly higher in the gestational trophoblastic disease group than in the control group. The results of linear discriminant analysis showed that silver-staining nucleolar organizer region count had the highest sensitivity and specificity (93.3% and 100%, respectively) for distinguishing gestational trophoblastic disease from spontaneous abortion. Sensitivity and specificity for discriminating gestational trophoblastic disease from spontaneous abortion increased to 100% when all four markers were used together. Proliferating cell nuclear antigen was found to be the best discriminating variable for differentiating among gestational trophoblastic disease subgroups. Conclusion: Our findings suggest that expressions of Ki-67, proliferating cell nuclear antigen, silver-staining nucleolar organizer regions, and p53 may aid in the diagnosis of gestational trophoblastic diseases. These fairly rapid, simple, and economic techniques could serve as a useful adjunct to conventional methods in the diagnosis of gestational trophoblastic diseases. (Am J Obstet Gynecol 2001;184:567-74.)

A large yolk sac may be important in the early diagnosis of gestational trophoblastic disease: a case report

A large yolk sac in a deformed shape gestational sac was detected by ultrasonography in an 8 week pregnant woman. The disappearance of the yolk sac and the gestational sac, enlargement of the uterine cavity and a heterogeneous appearance similar to early gestational trophoblastic disease were recognized when ultrasonographic examination was performed 2 weeks later. After uterine evacuation, partial hydatidiform mole was diagnosed by histopathological evaluation of the curettage material. In our study, the role of the large yolk sac in predicting trophoblastic disease is discussed.

Color doppler ultrasonography in the earlier differentiation of benign molehydatidiforms from malignant gestational trophoblastic disease

To find out the effectiveness of color Doppler ultrasonography of the uterine arteries in the differentiation of benign molehydatidiforms from malignant gestational trophoblastic disease. Prospective study was performed in 32 women who were referred to the Oncology Department with the diagnosis of gestational trophoblastic disease. Uterine artery Doppler studies were made and resistance index for both uterine arteries were calculated. In the follow-up, twelve of these patients required chemotherapy (first group) and 20 of them were treated with only suction curettage (second group). Non parametric Mann Whitney U test was used for the statistical analysis. Median of the lowest uterine artery resistance index were 0.29 for the first group and 0.46 for the second group. Resistance index were significantly lower in the first group (alpha<0.001). Color Doppler study of the uterine arteries is helpful in the differentiation of benign molehydatiforms from malignant gestational trophoblastic disease.

Agent orange and the risk of gestational trophoblastic disease in Vietnam.

There have been claims of an increased risk for gestational trophoblastic disease (i.e., hydatidiform mole and choriocarcinoma) in Vietnam since the period of Agent Orange sprayings. In 1990, we conducted a case-control study in Ho Chi Minh City to investigate risk factors for gestational trophoblastic disease in Vietnam. Eighty-seven married women, all of whom had a recent pathologic diagnosis of gestational trophoblastic disease, identified in the Obstetrical and Gynecological Hospital, were included in the study. Eighty-seven married women who were admitted mainly in the surgery departments of the same hospital were the controls, and they were matched to cases for age and area of residence. Odds ratios (ORs), adjusted for matching variables and other potential confounders, were estimated with unconditional logistic regression. A statistically significant trend in risk was observed with previous live births (p = .01). Cases were found to eat less meat per wk (OR = 0.4, 95% confidence interval [95% CI] = 0.2-0.9 for > or = five meat dishes) and to own fewer consumer goods than controls. An increase in risk was associated with the breeding of pigs (OR = 5.7, 95% CI = 1.2-27.6 for raising three or more pigs). A cumulative Agent Orange exposure index was constructed, using the patient's complete residence history. No significant difference was found between cases and controls for this index (OR = 0.7, 95% CI = 0.2-1.8 for high-exposure category), nor was such a difference noted for the agricultural use of pesticides.

Immunohistochemistry in the diagnosis of the gestational trophoblastic disease.

The gestational trophoblastic disease summarizes all types of hydatidiform moles, placental site trophoblastic tumor and choriocarcinoma. It is of clinical relevance to distinguish between complete hydatidiform mole and partial hydatidiform mole to predict prognosis of recurrency of molar pregnancy and the risk of the development of malign and metastatic gestational trophoblastic disease. Differential diagnosis of choriocarcinoma versus placental site trophoblastic tumor, carcinoma or sarcoma with low differentiation can cause problems in borderline-cases. The present study investigates the value of immunohistochemistry in the diagnosis of gestational trophoblastic disease. Nine cases of patients with complete hydatidiform mole, 20 cases of partial hydatidiform mole and seven cases of choriocarcinoma were analyzed for the immunohistochemical reaction with antibodies against human choriogonadotropin (hCG), human placental lactogen (hPL). placental alkaline phosphatase (PLAP), cytokeratine and vimentin. Complete hydatidiform mole shows strong expression of hCG and weak expression of PLAP. Weak hCG and strong PLAP expression is found in partial hydatidiform mole. Choriocarcinoma presents strong expression of hCG and weak expression of hPL and PLAP. All tissues show positive reaction with anticytokeratine and negative reaction with anti-vimentin. Our study proves immunohistochemistry as useful tool for differential diagnosis in borderline cases of gestational trophoblastic disease.

Serum interleukin-2 and soluble interleukin-2 receptor in gestational trophoblastic diseases.

To investigate serum interleukin-2 (IL-2) and soluble interleukin-2 receptor (SIL-2) levels in gestational trophoblastic diseases (GTD). Sixty-six patients with GTDs and 23 first-trimester healthy pregnant women (controls) participated in this study. According to the World Health Organization scoring system, GTDs were subgrouped into the following groups: 30 hydatidiform mole spontaneous regression (HMSR), 12 postmolar gestational trophoblastic tumors of high risk (PMHR), 14 low-risk choriocarcinomas, and ten high-risk choriocarcinomas. Before treatment, a blood sample from each case was assayed for beta-hCG by radioimmunoassay, IL-2 by IRMA, and SIL-2R by enzyme-linked immunosorbent assay. Follow-up beta-hCG assays were carried out at weekly intervals after treatment for 3 months, then monthly for 1 year. Serum IL-2 levels in all subgroups of GTD were significantly lower than that of controls. Meanwhile, there were concomitant significant elevations of serum SIL-2R, showing mean rises of 3.86-fold, 3.9-fold, twofold, and 6.1-fold for cases of HMSR, PMHR, low-risk choriocarcinoma, and high-risk carcinoma, respectively. All cases of high-risk choriocarcinoma revealed abnormally high SIL-2R values. There was a significant positive correlation between serum beta-hCG and SIL-2R concentrations. The possible causes of IL-2 decreases and SIL-2R increases may indicate a defective immune response in GTDs. The high correlation between SIL-2R level and tumor burden suggests the use of serum SIL-2R assay for disease monitoring: SIL-2R is indirect marker of tumor activity, and it is useful in the differential diagnosis of GTD because a normal value of serum SIL-2R excludes high-risk cases of choriocarcinoma.

Diagnosis of gestational trophoblastic disease by transvaginal color doppler

Diagnosis of gestational trophoblastic disease by transvaginal color doppler

Serum Cytokines in Gestational Trophoblastic Diseases

Interleukin 1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assayed by 125I immunoradiometric assay in sera of 42 cases of vesicular mole (VM), 24 cases of choriocarcinoma and 23 normal pregnant women at their first trimester (controls). According to pathologic diagnosis and serial serum hCG beta assays, the cases with VM and choriocarcinoma were subdivided into remission and progressive tumor groups. The progressive tumor groups--both VM and choriocarcinoma--showed marked elevations of serum IL-1 beta, IL-6 and TNF alpha. For choriocarcinoma in remission this elevation was considerably less pronounced. The VM cases in remission had only a slight increase of the mean serum IL-6 value and none of the cases had elevated IL-1 beta or TNF values. These results may indicate that serum IL-1 beta and TNF-alpha assays are valuable biomarkers in the differential diagnosis of gestational trophoblastic disease (GTD). Moreover, normal values of these cytokines may rule out high-risk GTD, whereas markedly elevated values may indicate poor prognosis.

Diagnosis of gestational trophoblastic disease: value of endovaginal color flow Doppler sonography.

The early diagnosis of invasive trophoblastic disease is important in the successful treatment of this disease. Standard pulsed Doppler sonography and transabdominal color flow sonography have been used in the diagnosis of gestational trophoblastic disease, including the identification of invasive trophoblastic disease [1 , 2]. We report the early diagnosis of an invasive mole with endovaginal color flow sonography, which showed vascular invasion of the myometrium.

Diagnostic and therapeutic curettage in gestational trophoblastic disease

From June 1976 through June 1989, 37 nonconsecutive patients underwent uterine curettage during the course of their gestational trophoblastic disease. In 22 patients (59%) trophoblastic tissue was obtained. Three (8.1%) patients sustained a uterine perforation during the procedure. In six patients curettage was performed for bleeding. There were six patients curetted during assessment for metastatic trophoblastic disease. Twenty-eight patients underwent curettage for the presumed diagnosis of nonmetastatic gestational trophoblastic disease. In retrospect, four of these women (14.3%) had insufficient criteria for the diagnosis of gestational trophoblastic disease. Of the remaining 23 patients, four (17.4%) went into clinical remission without further treatment. Ten patients (43.5%) had a transitory decline in serum beta-human chorionic gonadotropin levels that subsequently rose or plateaued. Six patients (26.1%) showed no effect from the curettage on their serum beta-human chorionic gonadotropin trend during a short period of observation. Three patients (13.0%) with nonmetastatic gestational trophoblastic disease were not observed for a possible therapeutic effect after curettage. Thus, in only 4/20 (20%) women with nonmetastatic trophoblastic disease was a therapeutic effect from curettage shown.

Gestational trophoblastic disease in women aged 50 or more

Twenty cases of gestational trophoblastic disease in women aged 50 or more are reported. The lesions were 7 hydatidiform mole (35%), 8 invasive mole (40%), and 5 choriocarcinoma (25%). The most common presenting symptom was abnormal vaginal bleeding. Three choriocarcinoma patients were postmenopausal and all of them had choriocarcinoma. None of the patients with hydatidiform mole or invasive mole died of the disease, but 4 of 5 choriocarcinoma patients died of the disease. Because of the high rate (56.3%) of malignant sequelae after molar evacuation, a primary hysterectomy for the treatment of hydatidiform mole in this age group is recommended. It is important to maintain a high level of suspicion for the diagnosis of gestational trophoblastic disease in the elderly women.

Complete blood count parameters may have a role in diagnosis of gestational trophoblastic disease.

Objective:The goal of this study was to investigate whether gestational trophoblastic disease (GTD) and healthy pregnancy differ with respect to complete blood count parameters and these parameters can be used both to explain the pathophysiologic mechanisms and differentiate the two conditions from each other.Methods:The data obtained from 37 women with GTD and 61 healthy pregnancies (control group) regarding platelet (PLT), mean PLT volume (MPV) and PLT distribution width (PDW), and white blood cell (WBC) levels were evaluated. Patients with GTD were further subdivided into two groups composed of 20 partial mole (PM) and 17 complete mole (CM) cases.Results:PDW and WBC were lower in the GTD than the control. There were no differences for PLT and MPV. WBC was lower in PM and both WBC and PDW were lower in CM compared with control. ROC curve analysis revealed an area under curve (AUC) 75.5% for WBC and AUC 69.3% for PDW. A cut-off value was determined 8.19 for WBC with 81.0% sensitivity and 54.1% specificity. While, 15.85 were accepted for PDW, with 87.9% sensitivity and 44.4% specificity.Conclusion:Lower WBC in GTD may suggest that molar pregnancy requires a lower inflammatory reaction facilitating trophoblastic invasion. Lower PDW as an indicator of platelet activation in CM may suggest that CM requires less PLT activation than healthy pregnancy that needs stronger trophoblast invasion for normal placental development. Decreased PDW levels especially < 15.85 and WBC levels < 8.19 may alert clinicians for risk of GTD.