Invasive and metastatic hydatidiform moles in Slovakia in 1993‒2022.

OBJECTIVE: A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes. BACKROUND: Invasive and metastatic mole is a highly curable type of gestational trophoblastic neoplasia. Both invasive and metastatic HM may be cured by hysterectomy without adjuvant chemotherapy. METHODS: Nineteen cases of histopathologically confirmed HM (10 invasive and 9 metastatic) were treated in SR from 1993 to 2022. Patients were divided into two groups according to treatment modality (hysterectomy only ‒ 8; hysterectomy and chemotherapy ‒ 11). The parameters included in the analysis were patient age, antecedent pregnancy, human chorionic gonadotropin level, tumor size and time to remission. RESULTS: The incidence of invasive and metastatic HM in the SR was 1:121,253 pregnancies, or 1:86,589 live births. The overall cure rate was 100%, without recurrence. Hysterectomy was performed as first-line therapy in 14 patients, with a cure rate of 57.1%. 4 out of 8 patients (50%) with metastatic moles, who underwent first-line hysterectomy, were cured without chemotherapy. There was no statistically significant difference between the two groups in all selected parameters. CONCLUSION: First-line hysterectomy may lead to remission without adjuvant chemotherapy or reduce the number of chemotherapies in invasive and metastatic HM (Tab. 4, Fig. 2, Ref. 21).

Cornual invasive hydatidiform mole: a rare case report and literature review.

BACKGROUND: The cornual pregnancy is a rare condition of ectopic pregnancies. Invasive hydatidiform mole is a rare form of gestational trophoblastic diseases. Cornual invasive hydatidiform mole is extremely rare. CASE PRESENTATION: A 17-year-old girl presented to the gynecology department with irregular vaginal bleeding. This patient was diagnosed with cornual invasive hydatidiform mole. Mono-chemotherapy was admitted firstly and with poor efficacy. The patient was cured by a combination of chemotherapy and resection of the uterine mass. CONCLUSION: Cases with cornual invasive hydatidiform mole are extremely rare conditions. Unlike common site of invasive hydatidiform mole, mono-chemotherapy may be insufficient for cornual invasive hydatidiform mole. Chemotherapy in combination with other treatments may be needed in this rare condition.

Clinical evaluation of hysterectomy for the treatment of invasive mole in Southern Vietnam.

OBJECTIVE: This study aimed to determine the rate of salvage chemotherapy and review associated factors in invasive mole patients treated by primary or delayed hysterectomy. PATIENTS AND METHODS: This study was carried out at the Tu Du Hospital, where a total of 189 patients were diagnosed with invasive mole based on histologic examination by hysterectomy between 01/2016 to 12/2020. We used the life table method to estimate the cumulative rate. We applied the Cox proportional hazard model to determine the factors associated with the need for salvage chemotherapy. RESULTS: At 12-month follow-up, 47 patients had required salvage chemotherapy. The incidence was 24.87% (95% CI: 18.88-31.66). Applying the multivariate model, prophylactic chemotherapy (HR = 2.75, 95% Cl: 1.20-6.30) and two weeks postoperative hCG value greater than 1,900 mIU/mL (HR = 4.30, 95% Cl: 2.08-8.87) increased the risk of requiring salvage chemotherapy. Postoperative chemotherapy decreased the risk of requiring salvage chemotherapy (HR = 0.43, 95% Cl: 0.22-0.83). CONCLUSIONS: Hysterectomy can be considered safe and effective in treating invasive mole patients. Although patients were treated by hysterectomy, 24.87% of patients needed salvage chemotherapy to achieve remission. This study affirms the malignant nature of invasive mole, a subtype of gestational trophoblastic neoplasia (GTN). It is not purely a local invasion of molar villi. Postoperative chemotherapy plays an essential role in reducing the risk of requiring salvage chemotherapy.

Combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios for early prediction of postmolar gestational trophoblastic neoplasia.

PURPOSE: To investigate factors predicting postmolar gestational trophoblastic neoplasia (GTN) by combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios. METHODS: This retrospective study enrolled patients with histopathologically proven molar pregnancy. Patients lost to follow-up before remission or developing postmolar GTN were excluded. Demographic and clinical characteristics and hCG data obtained before and after molar evacuation were collected. Area under the receiver operating characteristic curve (AUC) analysis was used to identify the hCG and hCG ratio cutoff values that predict postmolar GTN. Multivariate analysis was employed to identify independent predictors of GTN. RESULTS: There were 113 complete moles, 11 partial moles, and 52 unspecified moles included in the final analysis. Of the 176 cases, 90 achieved remission and 86 developed post-molar GTN. The incidence of postmolar GTN was 48.9%, with a median time to GTN development of 5 weeks. Univariate analysis showed age, molar evacuation performed elsewhere, pre-evacuation hCG, hCG at 2nd week post-evacuation, and ratio of hCG at 2nd week post-evacuation to post-evacuation hCG significantly predict GTN. Multivariate analysis revealed an hCG value ≥ 1400 IU/L at 2nd week post-evacuation (AUC: 0.92, aOR: 6.51, 95% CI 1.28-33.16; p = 0.024) and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 (AUC: 0.88, aOR: 12.27, 95% CI 2.15-70.13; p = 0.005) to independently predict GTN. CONCLUSIONS: An hCG value ≥ 1400 IU/L at 2nd week post-evacuation and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 independently and reliably predict postmolar GTN.

5-Fluorouracil and actinomycin D lead to erythema multiforme drug eruption in chemotherapy of invasive mole: Case report and literature review.

RATIONALE: 5-Fluorouracil (5-FU) and actinomycin D (ActD) are often used in chemotherapy for various cancers. Side effects are more common in bone marrow suppression, liver function impairment, and gastrointestinal responses. Skin effects are rare and easy to be ignored by doctors and patients, which can lead to life-threatening consequence. PATIENT CONCERNS: We reported a 45-year-old woman patient developed skin erythema and fingernail belt in chemotherapy of 5-FU and ActD. DIAGNOSIS: Erythema multiforme drug eruption. INTERVENTIONS: Laboratory tests including blood and urine routine, liver and kidney function, electrolytes and coagulation function and close observation. OUTCOMES: The rash was gone and the nail change returned. LESSONS: Delays in diagnosis or treatment may lead to serious consequence. We should pay attention to the dosage of 5-FU and ActD, monitor adverse reactions strictly, to reduce occurrence of skin malignant events.

O papel da ultrassonografia na doença trofoblástica gestacional / The role of ultrasonography in gestational trophoblastic disease

A doença trofoblástica gestacional (DTG) agrupa um conjunto de anomalias do desenvolvimento trofoblástico, que incluem formas clínicas benignas como a mola hidatiforme completa e parcial, o nódulo do sítio placentário atípico e o sítio trofoblástico exagerado, e malignas, caracterizando a neoplasia trofoblástica gestacional (NTG). De modo geral, seu diagnóstico precoce antecipa complicações clínicas que podem estar associadas a near miss obstétrico. Diante da suspeição clínica, é a ultrassonografia (US) precoce o exame de escolha pa ra o diagnóstico, associado à dosagem sérica de gonadotrofina coriônica humana, capaz de minimizar a ocorrência de complicações clínicas associadas à gravidez molar. Nos casos de NTG, é a US também de grande valia para estadiamento, avaliação de prognóstico e acompanhamento da mulher tratada para DTG. Este estudo faz uma revisão sobre o papel da US na DTG, sendo importante para familiarizar os tocoginecologistas com essa doença e salientar o papel da US consoante as melhores práticas clínicas.(AU)

Gestational trophoblastic disease (GTD) includes a set of trophoblastic developmental anomalies, which include benign forms such as complete and partial hydatidiform mole, atypical placental site nodule and exaggerated trophoblastic site, and malignant forms, characterizing gestational trophoblastic neoplasia (GTN). In general, its early diagnosis anticipates clinical complications that could be associated with obstetric near miss. In view of clinical suspicion, early ultrasonography (US) and serum levels of human chorionic gonadotropin are the best diagnostic screening techniques, able to minimizing the occurrence of medical complications associated with molar pregnancy. In cases of GTN, US is also of great value for staging, assessment of prognosis and follow-up of women treated for GTN. This study reviews the role of US in GTD, being important to familiarize tocogynecologists with this disease and highlight the role of US according to best clinical practices to minimize the morbidity of these patients and maximize the remission rates of this disease.(AU)

Life-threatening rupture of interstitial ectopic pregnancy: a rare presentation of metastatic invasive mole.

An invasive mole is an uncommon type of gestational trophoblastic disease, and if considering its implantation in an interstitial extrauterine location, we are facing a rarer condition.There are 14 cases described of interstitial ectopic gestational trophoblastic disease. As far as we know, we present the third case of invasive mole within interstitial location, in this case with pulmonary metastases.The diagnosis of an interstitial implantation is challenging. Our patient was initially diagnosed with an intrauterine hydatidiform molar pregnancy, and a uterine aspiration was performed. Two weeks later, she presented with haemodynamical instability due to a severe haemoperitoneum. A laparotomy was immediately performed and revealed a ruptured interstitial pregnancy with molar vesicle extrusion. Besides its rarity, we highlight the clinical presentation with hypovolaemic shock due to rupture of ectopic pregnancy in a young nulliparous woman, which required an emergent surgical approach with lifesaving purpose while preserving future fertility.

Mola hidatiforme completa invasiva: una causa poco común de hipertiroidismo / Invasive complete hydatidiform mole: a rare cause of hyperthyroidism

Hydatidiform mole (HM) is a form of gestational trophoblastic disease, which can be classified as complete or partial and is characterized by high levels of human chorionic gonadotropin (HCG). Hyperthyroidism results from the effect of β-hCG on TSH receptors. Clinical case: A 53-year-old multiparous woman, with no relevant history, was admitted to the Gynaecology Emergency Department with a clinic presentation of hypogastralgia and hyperemesis gravidarum with 1 month of evolution and symptoms of hyperthyroidism. The investigation showed a distended uterus with echogenic material with a thickness of 81 mm at filled by uterine cavity. β-hCG> 10000mIU / mL. She was admitted for suction curettage, and the resulting sample was compatible with HM. The additional analytical study showed primary hyperthyroidism and negative thyroid autoimmunity. Thyroid ultrasound was unaltered. The patient started therapy with metibasol and propanolol, showing clinical and analytical improvement. She also underwent, total abdominal hysterectomy and bilateral annexectomy with general anaesthesia, without complications. Chest x-ray without changes. Through histological analysis it was determined that the diagnosis was that of an invasive complete HM. Sixteen weeks after surgery, she presented β-hCG <2mIU / mL and normal thyroid function. The patient is still being monitored in the Gynaecology outpatient consultation. Thyroid function should be included in the laboratory analysis of HM. Removing the source of β-hCG allows the resolution of hyperthyroidism. However, due to the risk of thyroid storm, it is crucial to control the thyroid function before performing the surgical procedure. Given the possibility of persistence of trophoblastic tissue, it is essential to maintain regular follow-up with β-hCG assays. (AU)

Gut Microbial Diversity in Female Patients With Invasive Mole and Choriocarcinoma and Its Differences Versus Healthy Controls.

Objective: To investigate variation in gut microbiome in female patients with invasive mole (IM) and choriocarcinoma (CC) and compare it with healthy controls. Methods: Fecal microbiome of 12 female patients with IM, 9 female patients with CC, and 24 healthy females were analyzed based on 16s rDNA sequencing. Alpha (α) diversity was evaluated using Shannon diversity index and Pielou evenness index, while beta (ß) diversity was assessed using principle coordinate analysis (PCoA) of unweighted Unifrac distances. The potential functional changes of microbiomes were predicted using Tax4Fun. The relative abundance of microbial taxa was compared using Welch's t test. The role of varied gut microbiota was analyzed via receiver operating characteristic (ROC) curve. Results: The α diversity and ß diversity were significantly different between IM patients and controls, but not between CC patients and controls. In addition, the abundance of cancer-related genes was significantly increased in IM and CC patients. Notably, a total of 19 families and 39 genera were found to have significant differences in bacterial abundance. ROC analysis indicated that Prevotella_7 may be a potential biomarker among IM, CC, and controls. Conclusion: Our study demonstrated that the diversity and composition of gut microbiota among IM patients, CC patients, and healthy females were significantly different, which provides rationale for using gut microbiota as diagnostic markers and treatment targets, as well as for further study of gut microbiota in gestational trophoblastic neoplasia (GTN).

Invasive mole presenting as a heavily bleeding vaginal lesion 3 weeks after uterine evacuation.

Gestational trophoblastic disease occurs in 1-3:1000 gestations worldwide. Up to one-fifth of complete hydatidiform moles undergo malignant transformation, with 2%-4% manifesting as metastatic disease. Of these, a third present with vaginal metastases, which can cause bleeding and discharge. We describe the case of a 49-year-old primiparous woman presenting with syncope and intense bleeding from an anterior vaginal lesion, 3 weeks after uterine evacuation for a presumed spontaneous abortion. A vaginal metastatic nodule was suspected; haemostasis was achieved with vaginal packing, precluding the need for surgical intervention. The patient was ultimately diagnosed with invasive mole with vaginal and lung metastases (stage III high-risk gestational trophoblastic neoplasia (GTN)) and started on multiple-agent chemotherapy. Two months later the lesion had regressed completely, and remission was reached 2 weeks later. Clinicians should consider the possibility of metastatic GTN with vaginal involvement whenever heavy vaginal bleeding follows a recent history of failed pregnancy.

A Case of Rapid Transformation from Hydatidiform Mole to Invasive Mole: The Importance of ß-hCG (Human Chorionic Gonadotropin) Serum Levels in Follow-Up Evaluation.

BACKGROUND Gestational trophoblastic disease (GTD) is a spectrum of disorders consisting of premalignant (ie, complete [CHM] and partial hydatidiform moles [PHM]) and malignant conditions (ie, invasive moles, choriocarcinoma, placental site trophoblastic tumors, and epithelioid trophoblastic tumor). If GTD persists after initial treatment and has persistent elevated beta human chorionic gonadotropin (ß-hCG), it is referred to as post-molar gestational trophoblastic neoplasia (pGTN). To date, there is no detailed information regarding how fast invasive moles can develop from CHM. However, the risk of developing any pGTN from CHM is rare within 1 month and is greatest in the first 12 months after evacuation, with most cases presenting within 6 months. CASE REPORT We present a case of a 46-year-old primigravida woman with rapid transformation of an invasive mole. In the beginning, the patient had a chief concern of a uterus size greater than the gestational dates. Laboratory evaluation showed high ß-hCG serum level (>300 000 mIU/mL), and ultrasonography evaluation revealed a hydatidiform mole. Suction evacuation and curettage procedures were then performed. Pathology evaluation afterwards revealed a complete hydatidiform mole without any sign of malignancy. Twenty-two days afterwards, the patient came to the emergency room with vaginal bleeding. ß-hCG serum level was high (53 969 mIU/mL), and ultrasonography examination showed the presence of fluid filling the uterine cavity. The patient was then diagnosed with GTN, and hysterectomy was chosen as the treatment of choice. After the surgery, her ß-hCG serum level gradually reverted back to normal. CONCLUSIONS Invasive moles can develop less than 1 month after suction evacuation and curettage procedure for CHM. Serial ß-hCG serum level evaluation according to the guideline should be performed to prevent late diagnosis, which could lead to the development of metastasis and worsen the prognosis.

An invasive mole with pulmonary metastases in a 55-year-old postmenopausal Syrian woman: a case report and review of the literature.

BACKGROUND: Invasive mole is a subtype of gestational trophoblastic neoplasms (GTNs) that usually develops from the malignant transformation of trophoblastic tissue after molar evacuation. Invasive moles mostly occur in women of reproductive age, while they are extremely rare in postmenopausal women. CASE PRESENTATION: We present the case of a 55-year-old postmenopausal Syrian woman who was admitted to the emergency department at our hospital due to massive vaginal bleeding for 10 days accompanied by constant abdominal pain with diarrhea and vomiting. Following clinical, laboratory and radiological examination, total hysterectomy with bilateral salpingo-oophorectomy was performed. Histologic examination of the resected specimens revealed the diagnosis of an invasive mole with pulmonary metastases that were diagnosed by chest computed tomography (CT). Following surgical resection, the patient was scheduled for combination chemotherapy. However, 2 weeks later the patient was readmitted to the emergency department due to severe hemoptysis and dyspnea, and later that day the patient died in spite of resuscitation efforts. CONCLUSION: Although invasive moles in postmenopausal women have been reported previously, we believe our case is the first reported from Syria. Our case highlights the difficulties in diagnosing invasive moles in the absence of significant history of gestational trophoblastic diseases. The present study further reviews the diagnostic methods, histological characteristics and treatment recommendations.

Invasive mole with lung metastasis after an abdominal complete hydatidiform mole treatment.

A 27-year-old woman, gravida 1, para 0, was transferred to our hospital with acute abdominal pain. Her serum human chorionic gonadotropin level was 60 231 mIU/mL. Transabdominal ultrasound revealed an echo-free space, and emergency laparoscopy-assisted surgery was performed with a preoperative diagnosis of ruptured ectopic pregnancy. The pelvic cavity was filled with clots, and the peritoneal surface of the uterine fundus was swollen and showed continuous bleeding. The lesion was located on peritoneum and not connected with the uterine cavity. Histological examination of the conceptus showed features of a complete hydatidiform mole. After a mild decrease, hCG levels adversely increased 3 weeks later with multiple lung nodules. With a diagnosis of invasive moles, the patient was administered chemotherapy. This case demonstrates that it is important to recognize the potential of ectopic hydatidiform moles through abdominal pregnancy. This is the first report of an invasive abdominal hydatidiform mole, and hCG monitoring seemed to be essential for gestational trophoblastic neoplasia detection.

Manejo clínico de la neoplasia trofoblástica gestacional: presentación de un caso / Clinical management of gestational trophoblastic neoplasia: presentation of a case

La enfermedad trofoblástica gestacional es una entidad poco frecuente que se produce por una proliferación anormal de la placenta. Engloba un diverso espectro de entidades histológicas, que conllevan a su vez diversas implicaciones clínicas. Unas son de carácter benigno (mola parcial y mola completa, placentomegalia, nódulo del sitio placentario) y otras de carácter maligno, estas últimas reciben en común la denominación de Neoplasia Tofoblástica Gestacional (NTG) y tienen un alto potencial de metastatización. Forman parte de las NTG: la mola invasiva, el tumor trofoblástico del sitio placentario, el tumor trofoblástico epitelioide y el coriocarcinoma gestacional. Lo más común es que la NTG debute tras la aparición de una gestación molar, pero también es posible que ocurra tras otro tipo de evento obstétrico como una gestación a término, o una gestación ectópica. Es pues de vital importancia realizar un correcto seguimiento tras evacuar una gestación molar, realizando una monitorización de los valores séricos de la BhcG y sospechando una enfermedad trofoblástica persistente ante los supuestos que posteriormente describiremos.La principal herramienta terapéutica para la NTG es el uso de la quimioterapia, aunque también se puede optar por la cirugía endeterminados casos. Habrá que valorar de modo individualizado en función de la histología, score pronóstico y deseos genésicos futuros de la paciente. Afortunadamente, la tasa de supervivencia y de curación de la NTG con un tratamiento y seguimiento adecuado es muy elevada. (AU)

Gestational trophoblastic disease is a rare entity that is caused by an abnormal proliferation of the placenta. It encompasses adiverse spectrum of histological entities, which carry various clinical implications. Some of them are benign (partial mole and complete mole, placentomegaly, placental site nodule) and others of a malignant nature, which are known as Gestational TrophoblasticNeoplasia (GTN) and have a high potential for metastasization. Are part of the GTN: invasive mole, trophoblastic tumor of theplacental site, trophoblastic tumor epithelioid and gestational choriocarcinoma. The most common is that NTG debuts after theappearance of a molar gestation, but it also may occur after another type of obstetric event such as a term gestation, or an ectopicgestation. It is therefore of vital importance to carry out a correct follow-up after evacuating a molar gestation, monitoring the serumvalues of BhcG and suspecting a persistent trophoblastic disease in the event that we will later describe. The main therapeutic toolfor NTG is the use of chemotherapy, although surgery can also be chosen in certain cases. It will be necessary to assess individuallyaccording to histology, prognostic score and future genetic desires of the patient. Fortunately, the survival and cure rate of NTG with proper treatment and follow-up is very high. (AU)

The management of hydatidiform mole using prophylactic chemotherapy and hysterectomy for high-risk patients decreased the incidence of gestational trophoblastic neoplasia in Vietnam: a retrospective observational study.

The management of hydatidiform mole (HM) and the incidence of post-molar gestational trophoblastic neoplasia (GTN) in Vietnam has not been reported to date. This study aimed to study the incidence of HM and post-molar GTN and identify factors associated with post-molar GTN at a tertiary hospital in Vietnam. Five hundred and eighty-four patients who were treated for HM at Tu Du Hospital between January and December 2010 were included in this study. The mean age and gestational age at the first evacuation were 28.8 years old and 11.0 weeks, respectively. After the initial evacuation and pathological examination, 87 patients who were older than 40 or did not wish to have children underwent a hysterectomy, while the others underwent second curettage. All 472 patients who had human chorionic gonadotropin (hCG) ≥ 100,000 IU/L before treatment received one cycle of methotrexate with folinic acid as prophylactic chemotherapy. The incidence of HM was 11.1 per 1,000 deliveries; 47 patients (8.0%) developed post-molar GTN. Gestational week, hCG level at one week after the first evacuation, and pathological remnants were significantly associated with the development of post-molar GTN. The results of this study suggest that prophylactic chemotherapy and hysterectomy may be useful for high-risk HM patients to reduce post-molar GTN in settings in which the risk of post-molar GTN and loss to follow-up after HM are greater and hCG measurements and appropriate GTN treatments are unavailable. However, future studies on the long-term outcomes and side effects of prophylactic therapies on HM are required.

Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease.

Hydatidiform moles are classified at the genetic level as androgenetic complete mole and diandric-monogynic partial mole. Conflicting data exist whether heterozygous complete moles are more aggressive clinically than homozygous complete moles. We investigated clinical outcome in a large cohort of hydatidiform moles in Chinese patients with an emphasis on genotypical correlation with post-molar gestational trophoblastic disease. Consecutive products of conceptions undergoing DNA genotyping and p57 immunohistochemistry to rule out molar gestations were included from a 5-year period at Beijing Obstetrics and Gynecology Hospital. Patient demographics and clinical follow-up information were obtained. Post-molar gestational trophoblastic disease or gestational trophoblastic neoplasia was determined by the 2002 WHO/FIGO criteria. A total of 1245 products of conceptions were classified based on genotyping results into 219 complete moles, 250 partial moles, and 776 non-molar gestations. Among 219 complete moles, 186 were homozygous/monospermic and 33 were heterozygous/dispermic. Among 250 partial moles, 246 were triploid dispermic, 2 were triploid monospermic, and 2 were tetraploid heterozygous partial moles. Among 776 non-molar gestations, 644 were diploid without chromosomal aneuploidies detectable by STR genotyping and 132 had various genetic abnormalities including 122 cases of various trisomies, 2 triploid digynic-monoandric non-molar gestations, 7 cases of possible chromosomal monosomy or uniparental disomy. Successful follow-up was achieved in 165 complete moles: post-molar gestational trophoblastic disease developed in 11.6% (16/138 cases) of homozygous complete moles and 37.0% (10/27 cases) of heterozygous complete moles. The difference between the two groups was highly significant (p = 0.0009, chi-square). None of the 218 partial moles and 367 non-molar gestations developed post-molar gestational trophoblastic disease. In conclusion, heterozygous/dispermic complete moles are clinically more aggressive with a significantly higher risk for development of post-molar gestational trophoblastic disease compared with homozygous/monospermic complete moles. Therefore, precise genotyping classification of complete moles is important for clinical prognosis and patient management.