Home > Cancer Types > Gynecological > Gestational Trophoblastic Tumor

Gestational Trophoblastic Tumor

Gestational trophoblastic tumours (GTT) are a rare group of diseases in which the tissues formed in the uterus following conception grow abnormally to form a tumour. Most GTTs are benign (not cancer) and do not spread, but some types can become malignant (cancer) and spread to nearby tissues or distant parts of the body. There are three main types of gestational trophoblastic tumours: (i) hydatidiform mole (aslo known as molar pregnancy) - this is where the sperm and egg have joined but the tissues formed develop into a cyst; and (ii) choriocarcinoma - this can begin from a hydatidiform mole or from tissue that remains in the uterus following the delivery of a baby; (iii) placental-site trophoblastic disease - this is very rare and starts in the area of the uterus where the placenta was attached.

Found this page useful?

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications

Information Patients and the Public (7 links)


Information for Health Professionals / Researchers (9 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Kang HL, Zhao Q, Yang SL, Duan W
Efficacy of Combination Therapy with Actinomycin D and Methotrexate in the Treatment of Low-Risk Gestational Trophoblastic Neoplasia.
Chemotherapy. 2019; 64(1):42-47 [PubMed] Related Publications
OBJECTIVES: We aimed to identify an optimal regimen for low-risk gestational trophoblastic neoplasia (LR-GTN) providing reduction in dosage and toxicity/side effects, enhancement of therapeutic efficacy, and a shorter treatment duration.
METHODS: A total of 149 LR-GTN patients were enrolled in the affiliated Beijing Maternity Hospital of Capital Medical University from January 2014 to January 2017 and randomly divided into 3 groups with 50 cases in the methotrexate (MTX) group, 49 in actinomycin D (ACT-D) group, and 50 in ACT-D+MTX group. Follow-up recorded symptoms, physical and bimanual gynecological examinations, routine blood test, serum β-HCG level, liver and renal functions, electrolytes, electrocardiogram before each treatment course, and pelvic and abdominal B-mode ultrasound or pelvic/abdominal/chest computed tomography.
RESULTS: Serum complete remission (SCR) was 96.0, 87.8, and 83.7% for the ACT-D+MTX, ACT-D, and MTX groups, respectively, with SCR being highest in the ACT-D+MTX group, statistically higher than in the MTX group. Vomiting was the only side effect differing significantly by chemotherapy regimen, with a distinctly higher incidence in the ACT-D+MTX group compared with the MTX group (p = 0.028). The reduction rate of serum β-HCG in the ACT-D+MTX group was significantly greater than in the other 2 groups.
CONCLUSION: Combined ACT-D+MTX chemotherapy achieved overall better efficacy and showed less toxicity than ACT-D or MTX alone, and thus can be prioritized for the treatment of LR-GTN.
Related: Dactinomycin Methotrexate

Gadducci A, Carinelli S, Guerrieri ME, Aletti GD
Placental site trophoblastic tumor and epithelioid trophoblastic tumor: Clinical and pathological features, prognostic variables and treatment strategy.
Gynecol Oncol. 2019; 153(3):684-693 [PubMed] Related Publications
Placental site trophoblastic tumor [PSTT] and epithelioid trophoblastic tumor [ETT] are the rarest gestational trophoblastic neoplasias, developing from intermediate trophoblast of the implantation site and chorion leave, respectively. PSTT and ETT share some clinical-pathological features, such as slow growth rates, early stage at presentation, relatively low βhCG levels and poor response to chemotherapy. The mortality rate ranges from 6.5% to 27% for PSTT and from 10% to 24.2% for ETT. Advanced stage, long interval between antecedent pregnancy and diagnosis, and presence of clear cells are the independent prognostic variables for PSTT, and they may be similar for ETT. Hysterectomy can represent the only therapy for early disease, whereas adjuvant chemotherapy should be reserved to patients with poor risk factors, such as an interval from the antecedent pregnancy >4 years, deep myometrial invasion or serosal involvement. Few cases of fertility-sparing treatment in young women have been reported. An individualized multidisciplinary approach, including chemotherapy and debulking surgery with abdominal and/or extra-abdominal procedures, is warranted for advanced disease. EP/EMA and TP/TE are the preferred regimens in this setting. Immunohistochemistry has sometimes shown expression of EGFR, VEGF, MAPK, PDGF-R and PD-L1, and therefore investigational studies on biological agents targeting these molecules are strongly warranted for chemotherapy resistant-disease.

Sarmadi S, Izadi-Mood N, Sanii S, Motevalli D
Inter-observer variability in the histologic criteria of diagnosis of hydatidiform moles.
Malays J Pathol. 2019; 41(1):15-24 [PubMed] Related Publications
INTRODUCTION: In the event of encountering hydropic villi in products of conception specimens, pathologists will have to distinguish complete and partial hydatidiform mole (CHM & PHM) from hydropic abortion (HA). The histological diagnostic criteria are subjective and demonstrate considerable inter-observer variability.
MATERIALS AND METHODS: This study evaluated the inter-observer variability in diagnosis of CHM, PHM and HA according to defined histologic criteria. Ninety abortus conception specimens were reviewed. Representative haematoxylin and eosin-stained slides were assigned independently to two pathologists who were asked to make a diagnosis of CHM, PHM or HA, and provide a report of the identified diagnostic histological criteria. Kappa value was calculated for the inter-observer agreement.
RESULTS: There was a total of 36.7% disagreement between two pathologists (K = 0.403, Strength of Agreement = moderate), of which 24.4% and 12.2%, were differentiating PHM from CHM and PHM from HA, respectively. Among defined diagnostic histological criteria, the highest rate of agreement was observed in the identification of cistern formation and hydropic changes (K = 0.746 and 0.686 respectively, Strength of Agreement = substantial).
CONCLUSION: There was moderate to substantial agreement rate between two pathologists in identification of two essential histologic criteria for diagnosis of molar pregnancies i.e. "hydropic change" and "trophoblastic proliferation".

Guo Z, Sui L, Qi J, et al.
miR-196b inhibits cell migration and invasion through targeting MAP3K1 in hydatidiform mole.
Biomed Pharmacother. 2019; 113:108760 [PubMed] Related Publications
MicroRNAs (miRNAs) are a class of small non-coding RNAs that are closely associated with carcinogenesis. Accumulating data indicate that miR-196b participates in the development of various types of cancers. However, the role of miR-196b in the formation of hydatidiform mole (HM) is still unclear. Our previous studies have demonstrated that miR-196b levels were decreased in JAR and BeWo cells and in HM tissue samples, as demonstrated by RT-PCR analysis. Furthermore, we discovered that overexpression of miR-196b in JAR and BeWo cells inhibited cellular proliferation, migration and invasion, as shown by Cell counting kit-8 (CCK-8) and transwell assays, respectively. Subsequently, we explored the interaction of miR-196b with its target gene in human choriocarcinoma cell lines. MAP3K1 is a target gene predicted by bioinformatic analysis that was previously shown to exhibit reduced expression levels following treatment with miR-196b in JAR and BeWo cells. We demonstrated that MAP3K1 was a direct target of miR-196b using the dual-luciferase reporter assay in Hela cells. In summary, the present study demonstrated that miR-196b suppressed proliferation, migration and invasion of human choriocarcinoma cells by inhibiting its transcriptional target MAP3K1. miR-196b and MAP3K1 may be considered potential targets for the clinical treatment of HM.
Related: MicroRNAs

Mora PAR, Sun SY, Velarde GC, et al.
Can carboplatin or etoposide replace actinomycin-d for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia?
Gynecol Oncol. 2019; 153(2):277-285 [PubMed] Related Publications
OBJECTIVE: To evaluate the impact of periodic shortage of actinomycin-d (Act-d) in the treatment of Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN) after methotrexate and folinic acid rescue (MTX/FA) resistance, treated alternately with carboplatin or etoposide as a second-line regimen.
METHODS: Retrospective cohort that included patients with failure of first-line MTX/FA regimen for low-risk GTN treated at Rio de Janeiro Federal University, Universidade Federal de São Paulo and Irmandade da Santa Casa de Misericórdia de Porto Alegre, from January/2010- December/2017.
RESULTS: From 356 patients with low-risk GTN treated with MTX/FA, 75 (21.1%) developed resistance, of which 40 (53.3%) received Act-d, 23 (30.7%) carboplatin and 7 (9.3%) etoposide. Although patients treated with single-agent chemotherapy as a second-line regimen had comparable clinical and primary treatment characteristics, those treated with Act-d (80%, p = 0.033) or etoposide (71.4%, p = 0.025) had higher remission rates when compared with carboplatin (47.8%). Only 29% of patients treated with carboplatin received the chemotherapy cycles without delay compared to Act-d (98%, p < 0.001) or etoposide (85%, p = 0.009). Patients treated with carboplatin had significantly more hematological toxicity, notably anemia (30.4%, p = 0.008), lymphopenia (47.7%, p < 0.001) and thrombocytopenia (43.4%, p < 0.001), as well as a higher occurrence of febrile neutropenia (14.4%, p = 0.044) and vomiting (60%, p < 0.001) than those receiving Act-d (5%, none, 2.5%, none, 10%, respectively).
CONCLUSION: Carboplatin did not have a satisfactory clinical response rate, likely due to severe hematological toxicity, which postponed chemotherapy. Our results reinforce the preference for Act-d as a second-line agent in patients with low-risk GTN after MTX/FA resistance.
Related: Carboplatin Dactinomycin Etoposide Methotrexate

Dubruc E, Allias F, Morel AP, et al.
Gestational trophoblastic neoplasms (GTNs) do not display epithelial-to-mesenchymal transition (EMT) features.
Virchows Arch. 2019; 475(1):121-125 [PubMed] Related Publications
Although epithelial-to-mesenchymal transition (EMT) has been described in the development of complete hydatidiform moles and the invasion of the maternal decidua by trophoblasts during normal human placentation, its implication in gestational trophoblastic neoplasm (GTN) without villi is totally unknown. We studied the immunoexpression of EMT transcription factors (TWIST1, ZEB1, ZEB2), E-cadherin, and vimentin in 18 trophoblastic tumors and pseudo-tumors. Weak nuclear TWIST1 immunostaining was seen in 5% to 10% of all trophoblastic cells, without ZEB1 and ZEB2 nuclear staining. Trophoblastic cells did not express vimentin, and the expression of E-cadherin was maintained in all cases, indicating the absence of EMT features in GTN.

Chikvaidze N, Kintraia N, Muzashvili T, et al.
PHENOTYPIC CHARACTERISTICS OF CHORIONIC VILLI DURING GESTATIONAL TROPHOBLASTIC DISEASES.
Georgian Med News. 2019; (286):140-145 [PubMed] Related Publications
Differential diagnosis of gestational trophoblastic diseases (GTP) using standard micromorphological examination is complicated and less reliable. Therefore, the aim of our study was to investigate the immunohistochemical phenotype of chorionic villi during GTP, as well as in physiological cases. Study included five groups: I group - normal chorionic villi, II group - chorionic villi with hydropic changes, III group - Partial mole, IV group - Complete mole, V group - early Complete mole. Following markers were examined using standard immunohistochemistry: CK7, CK20, P63, PLAP, P57, CK5, CK8/18, CEA, CD34 Ki67, P53, E-cadherin, vimentin, β-catenin and inhibin. Study results showed that chorionic villi are characterized with marked phenotypic heterogeneity in normal tissue, as well as in cases of GTP, which can be used as an additional criterion for the differential diagnosis of GTP.

Li X, Xu Y, Liu Y, et al.
The management of hydatidiform mole with lung nodule: a retrospective analysis in 53 patients.
J Gynecol Oncol. 2019; 30(2):e16 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To investigate the significance of lung nodule in hydatidiform mole, we retrospectively compared the clinical outcomes of those patients treated with different strategies.
METHODS: The patients were divided into three groups: chemotherapy immediately once lung nodule was detected (group 1, n=17), delayed chemotherapy until human chorionic gonadotrophin (hCG) level met the diagnostic criteria for gestational trophoblastic neoplasia (GTN) (group 2, n=18), and hCG surveillance alone until hCG level was normalized spontaneously (group 3, n=18). The clinical parameters of these patients were collected and analyzed.
RESULTS: Totally 53 (4.0%) patients were included from 1,323 cases with molar pregnancy during past 16 years. Among them, the diameters of lung nodules were 0.3-2.5 cm. Chemotherapy cycles for achieving hCG normalization and the failure rate of first-line chemotherapy in group 1 were significantly increased than that in group 2 (5 vs. 3 cycles, p=0.000, 58.8% vs. 11.1%, p=0.005). The hCG level of all 18 cases in group 3 was normalized spontaneously within 6 months. Of those, lung nodules of 9 patients disappeared spontaneously, accounting for 25% (9/36) of patients who initially selected observation. The proportion of single nodule in group 3 was significantly higher than that in group 2 (10/18 vs. 2/18, p=0.012).
CONCLUSION: Our results suggest that lung nodule alone is not an adequate indication of chemotherapy in molar pregnancy. hCG surveillance is safe for patients with lung nodule, especially with single nodule, as long as their hCG levels do not meet International Federation of Gynecology and Obstetrics diagnostic criteria for GTN.

Fathaddin AA, Arafah MA
A malignant placental site trophoblastic tumor of the uterus with multiple metastases: A case report of a rare tumor showing an aggressive behavior.
Indian J Pathol Microbiol. 2019 Jan-Mar; 62(1):142-145 [PubMed] Related Publications
One of the very rare forms of gestational neoplastic diseases is the malignant placental site trophoblastic tumor. Due to its rarity, the data regarding its diagnosis and management are limited. The prognosis of this tumor is unpredictable with potential malignant behavior and metastasis. We report a case of malignant placental site trophoblastic tumor with multiple metastatic deposits in the ovaries, lungs, kidneys, adrenals, and pancreas. The patient was treated by surgery and an extensive subsequent chemotherapy. The disease progressed, and the patient died 17 months after diagnosis.

Kar A, Mishra C, Biswal P, et al.
Differential expression of cyclin E, p63, and Ki-67 in gestational trophoblastic disease and its role in diagnosis and management: A prospective case-control study.
Indian J Pathol Microbiol. 2019 Jan-Mar; 62(1):54-60 [PubMed] Related Publications
Background: Gestational trophoblastic disease (GTD) constitutes a spectrum of tumors and tumor-like conditions, characterized by proliferation of pregnancy-associated trophoblastic tissue of progressive malignant potential. It is very difficult to differentiate these complex groups of lesions basing on histomorphology alone. Immunohistochemistry (IHC) with cyclin E, P63, and Ki-67 has a definite role in the identification of different trophoblasts and entities of GTD and also in the determination of biological behavior.
Aims: The aim of this study is to find the differential expression of cyclin E, p63, and Ki-67 in normal placenta, hydropic abortus (HA), and various entities of GTD.
Design and Settings: A prospective case-control study conducted in a government medical college.
Methods: Total 96 cases, divided into Group A (48 histologically confirmed cases of GTD) and Group B (controls comprising 8 HA and 40 normal placentas of different trimesters), were studied. The histological samples were subjected to IHC using cyclin E, Ki-67, and p63.
Statistical Analysis: Results were analyzed using SPSS statistical method.
Results: Among the three immunomarkers used, Cyclin E and Ki-67 show statistically significant difference (P < 0.05) when compared between GTD and control groups, but it was insignificant for p63 (P = 0.369). Strong staining intensity of cyclin E and Ki-67 is seen in complete moles, choriocarcinoma, and placental site trophoblastic tumor.
Conclusion: This study was done to evaluate the role of cell cycle regulatory proteins such as cyclin E and p63 and proliferation marker Ki-67 in the detection of various trophoblasts and differential diagnosis of the lesions associated with them.
Related: MKI67 CCNE1 CKAP4

Li JW, Hu CC, Shi HY, Wu RJ
Extrauterine epithelioid trophoblastic tumors presenting as lung mass: A case report and literature review.
Medicine (Baltimore). 2019; 98(5):e14010 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Extrauterine epithelioid trophoblastic tumors (ETT) is a rare variant of gestational trophoblastic neoplasms. Here we aim to learn more clinical and pathological characteristics of ETT patient with an isolated pulmonary mass without uterine lesions, through a rare case of extra-uterine ETT and 7 cases published in English periodicals literature.
PATIENT CONCERNS: A 31-year-old Chinese woman, presented with low-level elevation of serum human chorionic gonadotropin (HCG) for more than 2 years without abnormal symptoms. Dilation and curettage (D&C) was performed and histopathology revealed a secretory phase of endometrium. Chest computed tomography (CT) scan showed a 0.8 cm nodular lesion in the upper left lobe. Then a thoracotomy with left upper lobe segmentectomy was performed.
DIAGNOSIS: After pathological and immunohistochemistry diagnosis, the case was confirmed as ETT (III).
INTERVENTIONS: According to FIGO guideline, the patient took 3 cycles of multivalent chemotherapy consisting of cisplatin and etoposide, alternating with etoposid, methotrexate dactinomycin (EP-EMA).
OUTCOMES: The patient had no obvious signs of recurrence after 13 months of follow-up.
LESSONS: When a fertile age woman persistently shows abnormal low-level escalation of HCG, ETT should be taken into consideration, especially lung X-ray or CT showing lesions without apparent abnormality of the uterus.

Earp KE, Hancock BW, Short D, et al.
Do we need post-pregnancy screening with human chorionic gonadotrophin after previous hydatidiform mole to identify patients with recurrent gestational trophoblastic disease?
Eur J Obstet Gynecol Reprod Biol. 2019; 234:117-119 [PubMed] Related Publications
OBJECTIVE: To determine whether post-pregnancy human chorionic gonadotrophin screening after previous hydatidiform mole identifies patients with recurrent gestational trophoblastic disease.
STUDY DESIGN: A retrospective evaluation of 9315 patients who underwent post-pregnancy screening from 2000 to 2009, as part of the National Gestational Trophoblastic Disease Service in the UK.
RESULTS: Patients with previous hydatidiform mole, who had human chorionic gonadotrophin screening after one or more subsequent pregnancies, were identified (n = 9315). Of these, 8630 patients had an initial hydatidiform mole that did not require chemotherapy. In 12,329 subsequent pregnancy events, screening with human chorionic gonadotrophin identified 3 cases of gestational trophoblastic neoplasm. The remaining 685 patients developed gestational trophoblastic neoplasm, following their initial hydatidiform mole and required chemotherapy. In this group there were 1012 further pregnancy events, human chorionic gonadotrophin screening identified 3 patients with gestational trophoblastic neoplasm. The overall recurrence rate was 6 in 13,341 events (risk 1: 2227). The rate was 3 in 12,329 (risk 1:4110) for HM that did not require chemotherapy and 3 in 1012 (1:337) for previously treated gestational trophoblastic neoplasm. All 6 patients with recurrent disease were successfully treated with chemotherapy.
CONCLUSION: Routine post-pregnancy human chorionic gonadotrophin screening may be safely discontinued in patients with one previous uncomplicated hydatidiform mole.

Zhao P, Lu Y, Huang W, et al.
Total hysterectomy versus uterine evacuation for preventing post-molar gestational trophoblastic neoplasia in patients who are at least 40 years old: a systematic review and meta-analysis.
BMC Cancer. 2019; 19(1):13 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The clinical value of total hysterectomy for patients with hydatidiform mole (HM) being at least 40 years old remains highly controversial. Since the practice of hysterectomy has been applied globally for decades, there is an urgent need to perform a systematic review to assess its risks and benefits.
METHODS: Six electronic databases, including four English databases and one Chinese database, were searched from the inception of each database till October 6th 2017. Studies were included if they: 1) were human studies, 2) explicitly indicated exposure to hysterectomy, 3) explicitly indicated control to uterine evacuation, 4) explicitly indicated the participants were older patients with HM being at least 40 years in age, 5) compared the outcome of interest as the incidence of post-molar GTN. Two authors independently conducted the literature search, study selection, data extraction. Pooled odds ratios were analyzed using Review Manager 5.3.
RESULTS: The overall pooled effect size of total hysterectomy had a significant advantage in preventing post-molar gestational trophoblastic neoplasia over uterine evacuation with an OR of 0.19 (95% CI, 0.08-0.48; P = 0.0004) and a low heterogeneity (I
CONCLUSIONS: Total hysterectomy, as compared to uterine evacuation, is a better therapeutic method for patients with HM being at least 40 years old unless fertility is still desired.

Nickkho-Amiry M, Horne G, Akhtar M, et al.
Hydatidiform molar pregnancy following assisted reproduction.
J Assist Reprod Genet. 2019; 36(4):667-671 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
INTRODUCTION: The use of assisted reproduction techniques (ART) is increasing; however, reports of molar pregnancy following ART remain scarce. Currently, the Human Fertility and Embryology Authority (HFEA) collates data on the molar pregnancies that have resulted through the use of ART. Recently, they have indicated that they will no longer collect these data.
AIM: This paper aimed to examine the incidence of molar pregnancy amongst patients undergoing assisted reproduction.
METHODS: We contacted HFEA and placed a request under the Freedom of Information Act (2000) for the number of molar pregnancies that resulted from fresh/frozen embryo transfer since HFEA started collecting data in 1991 to February 2018. We also asked how many patients who had suffered a molar pregnancy went on to have a normal pregnancy and how many had subsequent molar pregnancies, in subsequent treatment cycles.
RESULTS: Between 68 and 76 molar pregnancies occurred within this period using ART (n = 274,655). The incidence of molar pregnancy using fresh intracytoplasmic sperm injection (ICSI) (1/4302) and fresh in vitro fertilisation (IVF) (1/4333) was similar. The risk of recurrence of molar pregnancy following a previous molar was higher following ART compared to spontaneous conceptions.
CONCLUSION: The use of ICSI should be protective against triploidy; however, the retrospective data suggests that molar pregnancy is not eliminated with the use of ART. It is pertinent to continue to record this data, through the gestational trophoblastic disease centres, in order to ensure no further increase in incidence, appropriate follow-up, and transparency in communication.

Baumgarten J, Happel C, Becker S, et al.
HCG-induced hyperthyroidism in a 51-year-old patient with hydatidiform mole.
Nuklearmedizin. 2018; 57(6):N57 [PubMed] Related Publications

Missaoui N, Landolsi H, Mestiri S, et al.
Immunohistochemical analysis of c-erbB-2, Bcl-2, p53, p21
Pathol Res Pract. 2019; 215(3):446-452 [PubMed] Related Publications
Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21
Related: CDKN1A MKI67 TP53 CKAP4

Gresnigt TM, Sikkema JM
Urine pregnancy test (UPT) hCG negative molar pregnancy: a short report from Masanga/Sierra Leone.
Trop Doct. 2019; 49(2):129-132 [PubMed] Related Publications
In Masanga, Sierra Leone, a multigravid woman presented with a urine pregnancy test negative molar pregnancy. This can be explained by the 'hook-effect'. In resource-poor settings where quantitative serum hCG cannot be determined, it is of paramount importance to remain vigilant of the diagnosis of molar pregnancy. Clinical judgement and sonography remain key in diagnosing molar pregnancy in district hospitals in low- and middle-income countries (LMICs), especially since their occurrence is much more common in these countries.

Ronnett BM
Hydatidiform Moles: Ancillary Techniques to Refine Diagnosis.
Arch Pathol Lab Med. 2018; 142(12):1485-1502 [PubMed] Related Publications

Gao T, Sun M, Yao L, Jiang W
False diagnosis of and needless therapy for presumed gestational trophoblastic disease in women with an unusual site of residual pregnancy.
J Int Med Res. 2019; 47(2):673-681 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
OBJECTIVE: This study aimed to determine the diagnostic value of magnetic resonance imaging (MRI), hysteroscopy, and laparoscopy to avoid unnecessary treatment when patients present with clinical manifestations that are close to those of gestational trophoblastic neoplasia (GTN).
METHODS: Three patients who were falsely diagnosed with presumed GTN and received needless chemotherapy in our hospital from July 2011 to March 2012 were studied. We also reviewed data of patients with similar clinical features who were diagnosed as having residual pregnancy in recent years. Clinical manifestations were evaluated.
RESULTS: All three patients had persistently high serum β-human chorionic gonadotrophin levels and a mass with abundant blood supply in the uterus after termination of pregnancy. The patients were diagnosed with GTN and underwent chemotherapy. They responded poorly to chemotherapy and underwent surgery. The pathological diagnosis in all patients was residual pregnancy. In recent years, no patients were misdiagnosed because pelvic MRI, hysteroscopy, or laparoscopy was used when residual pregnancy could not be excluded.
CONCLUSION: Gynecologists should diagnose carefully when patients present with clinical manifestations that are close to those of GTN to avoid unnecessary treatment. MRI, hysteroscopy, and laparoscopy could be important examinations for excluding residual pregnancy.

Nguyen NMP, Ge ZJ, Reddy R, et al.
Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles.
Am J Hum Genet. 2018; 103(5):740-751 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1

Dabi Y, Hajri T, Massardier J, et al.
Outcome of First-Line Hysterectomy for Gestational Trophoblastic Neoplasia in Patients No Longer Wishing to Conceive and Considered With Isolated Lung Metastases: A Series of 30 Patients.
Int J Gynecol Cancer. 2018; 28(9):1766-1771 [PubMed] Related Publications
OBJECTIVE: This study aimed to assess the outcome of first-line hysterectomy in patients diagnosed as having gestational trophoblastic neoplasia (GTN) whose postoperative imaging showed lung images considered as metastases.
METHODS: From 1999 to 2016, patients no longer wishing to conceive, treated by their initial physician by hysterectomy, and whose postoperative imaging workup showed lung images considered as metastasis were identified in the French Trophoblastic Disease Reference Center database. We sought to identify significant predictive factors of requiring salvage chemotherapy.
RESULTS: Thirty patients were identified with a maximum number of 2 visible lung nodules and a median largest size of 14 mm on chest x-ray. Nine of these patients had an International Federation of Gynecology and Obstetrics score of higher than 6, and there were no postterm GTN. Twenty-two patients (73.33%; 95% confidence interval, 54.11-87.72; P = 0.0053) normalized their human chorionic gonadotropin (hCG) without salvage chemotherapy, whereas 7 received 1 line of salvage monochemotherapy (8-day methotrexate) and 1 required 2 lines of monochemotherapy (5-day actinomycin D after failure of methotrexate). After a 12.45-month median follow-up (range, 3-48.4 months) since the first normalized hCG, none of these patients died. The median interval between successful hysterectomy and hCG normalization was 3.15 months (range, 1.6-8.7 months). Patients who required salvage chemotherapy had a median size of the largest lung metastasis on chest computed tomography of 4 mm larger than those cured by hysterectomy (P = 0.0455).
CONCLUSIONS: For GTN patients no longer wishing to conceive with lung metastases discovered postoperatively, treated by hysterectomy, and whose hCG is decreasing, it is reasonable to expect and to inform patients that approximately 27% will require salvage chemotherapy. However, in patients with lung metastases discovered preoperatively, evidence to recommend first-line hysterectomy is insufficient and these patients should receive first-line chemotherapy.
Related: Dactinomycin Methotrexate

Usui H, Qu J, Sato A, et al.
Gestational Trophoblastic Neoplasia From Genetically Confirmed Hydatidiform Moles: Prospective Observational Cohort Study.
Int J Gynecol Cancer. 2018; 28(9):1772-1780 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to evaluate the incidence and risk factors of gestational trophoblastic neoplasia (GTN) from hydatidiform moles (HMs) cytogenetically diagnosed in a prospective cohort setting.
METHODS: The prospective observational cohort study included cases of cytogenetically defined molar pregnancies, which were diagnosed by a multiplex short tandem repeat polymorphism analysis. Cases were classified as androgenetic complete HMs (CHMs), diandric monogynic triploid partial HMs (PHMs), or biparental abortion. Gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Incidences for each category, that is, CHM, PHMs, and biparental abortion, were calculated. Clinical variables (age, partner age, gravidity, parity, height, weight, BMI, and gestational age) and laboratory data (serum human chorionic gonadotropin [hCG], white blood cell count, hemoglobin, and platelet count) were compared between spontaneous remission cases and GTN cases in androgenetic CHMs.
RESULTS: Among 401 cases, 380 were classified as follows: 232 androgenetic CHMs, 60 diandric monogynic PHMs, and 88 biparental abortions. A total of 35 cases (15.1%) of CHMs, but only 1 case of PHM (1.7%) and no biparental abortions, exhibited progression to GTN. The hCG value before evacuation was significantly higher in GTN cases than in spontaneous remission cases (P = 0.001, Kruskal-Wallis test). Patient age was also significantly higher in GTN cases than in spontaneous remission cases (P = 0.002, Student t test).
CONCLUSIONS: Under the cohort cytogenetic diagnosis setting, the traditional risk factors for GTN after molar pregnancy, hCG value before evacuation and age, were confirmed in androgenetic CHMs. The risk of GTN was lower for PHMs than for CHMs. However, 1 patient with cytogenetic PHMs developed into GTN.
Related: Polymorphisms

Ngan HYS, Seckl MJ, Berkowitz RS, et al.
Update on the diagnosis and management of gestational trophoblastic disease.
Int J Gynaecol Obstet. 2018; 143 Suppl 2:79-85 [PubMed] Related Publications
Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low-risk GTN (FIGO Stages I-III: score <7) is treated with single-agent chemotherapy but may require additional agents; although scores 5-6 are associated with more drug resistance, overall survival approaches 100%. High-risk GTN (FIGO Stages II-III: score >7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

Pires KSN, Sun SY, Gonçalves CM, et al.
Versican silencing in BeWo cells and its implication in gestational trophoblastic diseases.
Histochem Cell Biol. 2019; 151(4):305-313 [PubMed] Related Publications
Versican is a proteoglycan known to interact with cells to influence their ability to proliferate, differentiate, migrate, invade and assemble extracellular matrix, with all of these cell functions present during placentation. In the placenta, cytotrophoblast cells have the ability to differentiate into the syncytiotrophoblast, a mechanism that is greatly increased in gestational trophoblastic diseases (GTD). Nevertheless, the molecular signaling underlying the increased syncytiotrophoblast differentiation are still being unveiled and may result in novel therapeutic targets for GTD. Versican expression was investigated to establish its differential expression among GTD (partial moles, complete moles, invasive moles and choriocarcinoma) and the possible functional outcomes from versican gene silencing. Tissue samples had their versican expression evaluated using immunohistochemistry and RT-PCR. BeWo cells were employed for versican silencing with siRNA and the efficiency was confirmed by RT-PCR, immunofluorescence and flow cytometry. Cell death and forskolin-induced syncytialization were analyzed by a morphological analysis and human chorionic gonadotropin (hCG) production using immunofluorescence. Versican V0 and V1 isoforms were mainly expressed in the syncytiotrophoblast and they were the most expressed in benign rather than in malignant tumors. BeWo cells also expressed V0 and V1 isoforms, but only in cells undergoing syncytial fusion. After versican silencing, cell death was greatly increased, whereas spontaneous and forskolin-induced syncytialization decreased as well as hCG production. Versican is differentially expressed in GTD and is important for hydatidiform moles pathophysiology, protecting trophoblast cells from death and playing a role in their differentiation and functionality.

Imafuku H, Miyahara Y, Ebina Y, Yamada H
Ultrasound and MRI Findings of Twin Pregnancies with Complete Hydatidiform Mole and Coexisting Normal Fetus: Two Case Reports.
Kobe J Med Sci. 2018; 64(1):E1-E5 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
BACKGROUND: Both twin pregnancies with complete hydatidiform mole and coexisting normal fetus (CHMCF) and partial hydatidiform mole can be found in association with a live fetus and a placenta displaying a molar degeneration. Two cases of CHMCF using magnetic resonance imaging (MRI) for a diagnosis are reported.
CASE: In the first, CHMCF was suspected at 12 weeks of gestation. At 18 weeks of gestation, the existence of molar placenta and a sac separating from fetus and normal placenta was clearly depicted on MRI. At 19 weeks of gestations, she had termination of pregnancy because of a development of gestational trophoblastic neoplasia (GTN) and started chemotherapy. In the second case, CHMCF was suspected at 14 weeks of gestation. MRI demonstrated the existence of molar placenta and a sac separating from fetus and normal placenta. She chose induced abortion and there was no evidence of GTN during the 1 year-follow up period. Pathological examination in both cases was consistent with a complete hydration mole and a coexisting normal female fetus.
CONCLUSION: MRI was useful for an accurate diagnosis for CHMCF.

Li J, Li S, Yu H, et al.
A comprehensive analysis of gestational trophoblastic neoplasia trials posted at online clinical trial registries.
Eur J Obstet Gynecol Reprod Biol. 2018; 230:136-140 [PubMed] Related Publications
OBJECTIVE: We conducted a comprehensive analysis of gestational trophoblastic neoplasia (GTN) trials posted at online registries and aimed to provide useful information for future GTN trial designs.
STUDY DESIGN: We searched ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Portal (ICTRP) Search Portal, Australian New Zealand Clinical Trial Registry, ISRCTN Register, and Chinese Clinical Trial Register for all the clinical trials reporting GTN treatments. The general information of each trial was extracted.
RESULTS: Twenty trials meeting the inclusion criteria were included in the final analysis. In total, 6 trials were phase II trials, 2 were phase II/III trials, 7 were phase III trials, and 1 was a phase IV trial; and the phase type of 4 trials were not reported. The conditions included low-risk GTN (n = 15), high-risk GTN (n = 2), and mixed GTN (n = 3). Randomization was performed in 15 trials, and the remaining 5 trials were single-arm trials. The median enrollment size for randomized clinical trials (RCTs) and single-arm trials was 80 and 38, respectively. Among the RCTs, parallel assignment was used in 12 trials, crossover assignment was used in 1, and the intervention models of 2 were not reported. For masking, 15 trials were open-label, 2 were single-blinded, 2 were double-blinded, and the masking status of 1 was not reported. Ovarian functions and pregnancy outcome after chemotherapy were evaluated in only 2 trials. Regarding sponsorship, 2 trials had industry sponsorship.
CONCLUSION: Conducting RCTs for GTN is challenging, and international collaboration and smarter clinical trial designs are required for future GTN trials.

Mangili G, Cioffi R, Danese S, et al.
Does methotrexate (MTX) dosing in a 8-day MTX/FA regimen for the treatment of low-risk gestational trophoblastic neoplasia affect outcomes? The MITO-9 study.
Gynecol Oncol. 2018; 151(3):449-452 [PubMed] Related Publications
OBJECTIVE: To compare clinical outcomes of patients diagnosed with low-risk gestational trophoblastic neoplasia (GTN) receiving intramuscular methotrexate 50 mg total dose/day versus 1 mg/kg/day in a 8-day methotrexate/folinic acid (MTX/FA) regimen.
METHODS: This retrospective, multicenter study included 176 patients: 99 (56%) receiving methotrexate 50 mg total dose/day on days 1, 3, 5, 7 alternated with FA 7,5 mg on days 2, 4, 6, 8, every 14 days (group A); and 77 patients (44%), receiving methotrexate 1 mg/kg/day on days 1, 3, 5, 7 alternated with FA 7,5 mg on days 2, 4, 6, 8, every 14 days (group B). Patients' characteristics and outcomes were compared by univariate analysis.
RESULTS: Forty-five patients (25.6%) developed resistance to MTX and received a second-line treatment, 7 (4%) received a third-line treatment and 8 (4.5%) relapsed after initial remission. There was no difference between group A and B patients in the average number of chemotherapy cycles required to achieve remission (5.7 ± 2.6 vs 6.3 ± 2.3, p = 0.106). The 2 treatment groups showed comparable rates of MTX resistance (28.3% vs 22.1%, p = 0.387) and relapse (3% vs 6.5%, p = 0.300). There was no difference in the incidence of treatment toxicity of any CTCAE grade between group A and B patients (16.2% vs 15.2%, p = 0.999). Subgroup analysis stratifying patients by weight (<50 kg, ≥60 kg, ≥70 kg, ≥80 kg) confirmed these results.
CONCLUSION: The 2 MTX schedules showed comparable efficacy in the treatment of low-risk GTN with an acceptable rate of toxicity.
Related: Methotrexate

Langhe R, Muresan BA, Akpan E, Abdul Wahab NA
Atypical presentation of molar pregnancy.
BMJ Case Rep. 2018; 2018 [PubMed] Related Publications
The classic features of molar pregnancy are irregular vaginal bleeding, hyperemesis, enlarged uterus for gestational age and early failed pregnancy. Less common presentations include hyperthyroidism, early onset pre-eclampsia or abdominal distension due to theca lutein cysts. Here, we present a case of molar pregnancy where a woman presented to the emergency department with symptoms of acute abdomen and was treated as ruptured ectopic pregnancy. The woman underwent laparoscopy and evacuation of retained products of conception. Histological examination of uterine curettage confirmed the diagnosis of a complete hydatidiform mole. The woman was discharged home in good general condition with a plan for serial beta-human chorionic gonadotropin (beta-hCG) follow-up. Complete follow-up includes use of contraception and follow-up after beta-hCG is negative for a year.

Victoria Diniz M, Sun SY, Barsottini C, et al.
Experience With the Use of an Online Community on Facebook for Brazilian Patients With Gestational Trophoblastic Disease: Netnography Study.
J Med Internet Res. 2018; 20(9):e10897 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
BACKGROUND: The term gestational trophoblastic disease (GTD) includes both complete and partial moles, which are uncommon nonviable pregnancies with the potential to evolve into a malignancy known as gestational trophoblastic neoplasia. While highly curable, the potential for malignancy associated with molar pregnancies worries the patients, leading them to seek information on the internet. A Facebook page headed by Brazilian specialized physicians in GTD was created in 2013 to provide online support for GTD patients.
OBJECTIVE: The objective of our study was to describe the netnography of Brazilian patients with GTD on Facebook (FBGTD) and to evaluate whether their experiences differed depending on whether they received care in a Brazilian gestational trophoblastic disease reference center (BRC) or elsewhere.
METHODS: This was a cross-sectional study using G Suite Google Platform. The members of FBGTD were invited to participate in a survey from March 6 to October 5, 2017, and a netnographic analysis of interactions among the members was performed.
RESULTS: The survey was answered by 356 Brazilian GTD patients: 176 reference center patients (RCP) treated at a BRC and 180 nonreference center patients (NRCP) treated elsewhere. On comparing the groups, we found that RCP felt safer and more confident at the time of diagnosis of GTD (P=.001). RCP were more likely to utilize FBGTD subsequent to a referral by health assistants (P<.001), whereas NRCP more commonly discovered FBGTD through Web searches (P<.001). NRCP had higher educational levels (P=.009) and were more commonly on FBGTD for ≥ 6 months (P=.03). NRCP were more likely to report that doctors did not adequately explain GTD at diagnosis (P=.007), had more doubts about GTD treatment (P=.01), and were less likely to use hormonal contraception (P<.001). Overall, 89% (317/356) patients accessed the internet preferentially from home and using mobile phones, and 98% (349/354) patients declared that they felt safe reading the recommendations posted by FBGTD physicians.
CONCLUSIONS: This netnographic analysis of GTD patients on FBGTD shows that an Web-based doctor-patient relationship can supplement the care for women with GTD. This resource is particularly valuable for women being cared for outside of established reference centers.

Gavanier D, Leport H, Massardier J, et al.
Gestational trophoblastic neoplasia with brain metastasis at initial presentation: a retrospective study.
Int J Clin Oncol. 2019; 24(2):153-160 [PubMed] Related Publications
OBJECTIVE: To evaluate the survival and functional outcome of patients with brain metastasis due to gestational trophoblastic neoplasia (GTN).
METHODS: A 17-year retrospective study based on case review of women with brain metastasis from GTN identified by the electronic databases held in the French Reference Centre.
PRIMARY OUTCOME MEASURE: 5-year overall survival calculated with the Kaplan-Meier method.
SECONDARY OUTCOME MEASURES: causes of death, prognostic factors and functional outcomes.
RESULTS: 21 patients had GTN brain metastasis and were treated with multidrug chemotherapy without concomitant whole-brain radiation therapy. Three patients died early (< 4 weeks) of cerebral hemorrhage, 3 died ≥ 1 months after treatment initiation and 15 were alive at the date of last contact. The overall survival rate at 5 years was 69.8% (95% CI 44.3-85.3). After excluding early deaths, the survival rate at 5 years was 81.5% (95% CI 52.3-93.7). No predictive factor of survival was identified. Although 11 of the 12 (92%) surviving patients contacted still reported sequelae, nine of them (75%) had resumed a normal life.
CONCLUSIONS: After excluding early deaths, this study implies a high survival rate in patients with brain metastasis from GTN. These results were achieved in the total absence of whole-brain radiotherapy and almost completely without the need for intrathecal methotrexate.

CancerIndex.org
Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.
About

[Home]    Page last updated: 02 September, 2019     © CancerIndex, Established 1996