Updates in the Diagnosis of Gestational Trophoblast Disease

GTD (Gestational Trophoblastic Disease) is a pathology that encompasses benign and malignant clinical forms, affects women of childbearing age, has a variable incidence and is more frequent in developing or underdeveloped countries, colliding with the economic barrier. The frequent absence of clear protocols and guidelines for the correct diagnosis of the pathology results in inadequate classification, imprecise treatment and failed post-therapeutic observation, increasing the risk of relapses, morbidity and mortality. The present study aims to point out updated national and international practice protocols of diagnosis of GTD, through an integrative review. Seven articles were selected and it was observed that the main international reference centers are agreed with the management suggested by the IFGO (International Federation of Gynecology and Obstetrics), being the conduct in the Hydatidiform Mole (HM): evacuation by suction and curettage under ultrasound guidance, followed by hCG monitoring every 1 - 2 weeks until normalized (usually one month for Partial Hydatidiform Mole six months for Complete Hydatidiform Mole and one year for Gestational Trophoblastic Neoplasia). Unfortunately, regarding the diagnosis of MH, the guidelines of some countries show the absence or difficulty of access to the karyotype test and ploid p57 or pelvic ultrasound accompanying the uterine curettage, contrary to what is proposed by the IFGO guideline. Establishing and complying with consistent guidelines can improve patient care, with early diagnosis of the pathology and its complications, reducing the rate of recurrence, morbidity and mortality, especially in less developed countries.

Management of Gestational Trophoblast Disease: A Review Integrative National and International Guidelines

GTD (Gestational Trophoblastic Disease) is a pathology that encompasses benign and malignant clinical forms, affects women of childbearing age, has a variable incidence and is more frequent in developing or underdeveloped countries, colliding with the economic barrier. The frequent absence of clear protocols and guidelines for the correct diagnosis and treatment of the aforementioned pathology results in inadequate risk classification, imprecise treatment and failed post-therapeutic observation, increasing the risk of relapses, morbidity and mortality. The present study aims to compare the different national and international guidelines in the management of GTD, through an integrative review. Nine articles were selected and it was observed that the main international reference centers are agreed with the management suggested by the IFGO (International Federation of Gynecology and Obstetrics), being the conduct in the Hydatidiform Mole (HM): evacuation by suction and curettage under ultrasound guidance, followed by hCG monitoring every 1 - 2 weeks until normalized;in low-risk GTN (Gestational Trophoblastic Neoplasm): chemotherapy with methotrexate or actinomycin D, in high-risk: EMA/CO protocol, in ultra-high-risk EMA/PE, methotrexate with radiotherapy for brain metastases. All medical societies recommend the registration of these patients in GTD screening centers, endorse the use of the IFGO scoring system (2000) and recommend the surgical management of placental site trophoblastic or epithelioid tumors, as chemotherapy is less effective in these cases. The controversies are in the proper follow-up after the treatment of HM, use of ultrasound to evacuate the uterus, administration of anti-D immunoglobulin, time of oxytocin infusion and rescue regimens that can be used in cases of resistant or recurrent GTN. Establishing and complying with consistent guidelines can improve patient care, with early diagnosis of the pathology and its complications, reducing the rate of recurrence, morbidity and mortality, especially in less developed countries.

Expression of epidermal growth factor and its receptor in gestational trophoblastic diseases

Objective: To determine whether epidermal growth factor (EGF) and its receptor have any possible correlation with etiology of gestational trophoblastic diseases. Methods: Avidin-biotin immunoperoxidase techniques with polyclonal antibodies against EGF, EGFR were used to examine 53 cases of GTD, including complete hydatidiform mole(16),invasive mole(20),gestational choriocarcinoma(17).Results:EGF was mainly localized on syncytiotrophoblasts (ST), and was found less on cytotrophoblasts. Cytologic localization of EGFR showed the similar results. The positive rate of EGF and EGFR were 0.625, 0.813 in hydatidiform mole, 0.405, 0.450 in invasive mole and 0.118, 0.235 in gestational choriocarcinoma. There was significant difference of EGF or EGFR among hydatidiform mole group and other groups, respectively (P<0.05). Conclusion:The cellular levels of EGF and EGFR decreased gradually in the development of GTD. It implied that the autocrine and paracrine mechanism may play an important role on the proliferation and differentiation of trophoblast cells and the disorder of the system may lead to GTD malignant transformation.

EXPRESSION OF P53 PROTEIN AND PROLIFERATING CELL NUCLEAR ANTIGEN IN HUMAN GESTATION TROPHOBLASTIC DISEASE

To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.

Gestational Trophoblastic Neoplasia: Clinical and Therapeutic Profile in Madagascar

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. This includes complete and partial hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). The aim of this study was to report the epidemiological, clinical and therapeutic profile of gestational trophoblastic neoplasia (GTN) over period of ten years in the department of Oncology Radiotherapy at the University Hospital Joseph Ravoahangy Andrianavalona (HJRA) Antananarivo Madagascar. Medical records of women diagnosed with GTD in the department of Oncology Radiotherapy at HJRA from January 1st, 2007 to September 2017 were retrospectively reviewed. Only patients with the FIGO diagnosis GTN were included, while those with the histological diagnosis of hydatidiform mole (HM), also sometimes classified as GTD, were not included in this study. Also excluded were all cases with incomplete or missing data. Twenty four patients were included. Median age of patients at the time of diagnosis was 37 years (range 18 - 60). Most patients developed GTN following molar pregnancy (75%), had disease duration from antecedent pregnancy of less than 6 months (58.20%), and had the pre-treatment hCG level more than 10,000 IU/L (58.27%). At diagnosis, 14 patients (58.33%) had localized disease (M0). Most common metastatic sites at initial diagnosis were the liver and brain (20.83%). After a median follow-up from initial diagnosis of six months (range 1 - 24), 58.33% were lost to follow up. This represented an increase in the percentage of patients lost to follow up prior to completion of therapy, when compared with our previous results for an earlier time period. GTN in Malagasy woman displays an aggressive clinic profile. Finding ways to increase treatment compliance provides the best way to minimize recurrences of this potentially deadly disease.

The Clinical Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection Treatments in 43 Women with a History of Gestational Trophoblastic Disease

Background:To analyze the clinical outcomes of in vitro fertilization(IVF)/intracytoplasmic sperm injection treatments in women with a history of gestational trophoblastic disease(GTD).Methods:This retrospective study included 43 patients with a history of GTD as the study group and 43 matched patients as the control group.The patients in the study group were divided into two groups according to the therapy received.Patients in Subgroup A(n=32)underwent uterine curettage treatment only.Patients in Subgroup B(n=11)underwent uterine curettage combined with chemotherapy.The characteristics of ovarian stimulation and outcomes of embryos and pregnancy were compared.Results:In the first cycle,there was a higher number of retrieved oocytes and normal fertilized oocytes in the control group than those in the study group(9.2 vs.6.2 and 6.0 vs.4.0,respectively;P<0.05);however,a similar mature oocyte rate(83.5%vs.85.0%),normal fertilization rate(84.5%vs.80.1%),number of good-quality embryos(1 vs.2),and viable embryos(2 vs.2)were found between the two groups(P>0.05).There was no difference in the outcomes between Subgroup A and Subgroup B.There was a significant difference in thickness of the endometrium between the control group and study group(10.9 mm vs.9.2 mm,respectively;P<0.05).The biochemical pregnancy rate and ongoing pregnancy rate in the control group were significantly higher than those in the study group(51.4%vs.31.7%and 37.8%vs.18.3%,respectively;P<0.05).In the study group,28(93.3%)patients had intrauterine adhesion(IUA)and 23(76.7%)patients used an intrauterine device(IUD),which were both significantly higher than those in control group(P<0.05).In addition,the rate of IUA in second-look hysteroscopy was lower than that in the first surgery in the study group(P<0.05).Conclusions:Patients with a history of GTD can present with a similar normal fertilization rate and number of viable embryos.However,patients with a history of GTD may have a thinner endometrium and lower ongoing pregnancy rate.Hysteroscopy before frozen embryo transfer and usage of an IUD can improve the occurrence of IUA.

Gestational Trophoblastic Disease Diagnosis and Treatment:An Analysis of 56 Cases

Objective To investigate the diagnosis and treatment of gestational trophoblastic disease （GTD）. Methods A retrospective review was conducted on 56 patients with GTD who under- went treatment in Ruijin hospital from January 2007 to December 2012. Their infor- mation of diagnosis, treatments, follow-up and efficacy were collected and analyzed Results Misdiagnosis rate was 41.1% （23/56）for the first time. Of 56 patients, 31 had direct curettage, 19 had curettage after trichosanthis （TCS） treatment, 3 had curettage after intervention treatment and 3 did not have curettage. Twenty patients with gesta- tional trophoblastic neoplasia （GTN） took fluorouracil＋vincristine＋dactinomycin （VCR ＋KSM＋5-FU） chemotherapy, but 2 of them changed to etoposide＋methotrexate＋acti- nomycetes streptozotocin-D＋cyclophosphamide＋vincristine （EMA-CO） chemo- therapy due to drug resistance. Three patients＂ with GTN took EMA-CO chemotherapy. Two patients with placental site trophoblastic tumor （PSTT） required surgeries, one took hysterectomy, another got mass and adnexectomy. Apart from 1 case who gave up treatment and was dead, all the other women went into remission from their diseases. Conclusion The diagnosis of trophoblastic disease rely on a comprehensive analysis. A reasonable choice of TCS or intervention can be effective and safe in treating GTD. Most patients with GTN could get complete remission by selecting the appropriate chemotherapy and surgery.

Immunobiology and immunotherapy of gestational trophoblastic disease

Gestational trophoblastic diseases are a heterogeneous group of pregnancy related tumors that show extensive metastatic spread but are readily responsive to chemotherapy.This one of a kind treatability of gestational trophoblastic tumors may to some extent be inferable from a host immunologic reaction to the paternal antigens that are expressed on the trophoblastic cells.In this review,we evaluate the current cognizance of immunobiology of gestational trophoblastic diseases and also establish the immunologic behaviour of gestational trophoblastic diseases which should be researched further in order to gain a better understanding of the aetiology of these neoplasias.This will further help structuring immunotherapeutic methodologies for their 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.

Invasive Mole of the Uterus: A Case Report

Invasive mole is a rare subgroup of gestational trophoblastic disease characterized by the invasion of molar tissue into the myometrium or uterine vasculature. In this paper, we report the third case of invasive mole described in the Malagasy literature. A 33-year-old woman was referred to the Soavinandriana Hospital, her complaint was persistent vaginal bleeding during 2 months, occurring at 3 months of pregnancy with biological anemia without hemodynamic repercussions. The human chorionic gonadotropin (HCG) level was 385,931 mIU/ml. A haemostasis hysterectomy was performed. Histological examination showed an enlarged uterus and endometrial cavity containing edematous chorionic villi with trophoblastic proliferation invading the myometrium. The diagnosis was an invasive mole, stage I, FIGO score 6. Chemotherapy was prescribed but was not honored. After 45 days of follow-up, the serum βHCG level decreased to 1803 mIU/ml, without clinical symptoms. The patient then lost sight. Persistent vaginal bleeding after pregnancy may be the only clinical symptom of an invasive mole and should raise suspicion. Histological examination establishes the diagnosis. As this is an unusual cause of vaginal bleeding, our case should remind physicians that when faced with this symptom, the possibility of an invasive mole should be considered in order to make an early diagnosis for less aggressive treatment.