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.

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.

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)

[Clinical and radiological features of gestational trophoblastic tumors]. / Tumeurs trophoblastiques gestationnelles: aspects cliniques et radiologiques.

Gestational trophoblastic disease incorporates a group of diseases which differ from each other by their regressive evolution, their evolution to metastasis and to recurrence. It is a severe disease that affects women of childbearing age. Gestational trophoblastic tumors (GTT) are the malignant forms of gestational trophoblastic diseases. They are always a result of pregnancy, more often molar pregnancy (hydatidiform mole). The most common type of gestational trophoblastic tumors (GTT) is the invasive mole because, in most cases, the diagnosis is made when cancer is still confined to the uterus. Choriocarcinoma is a more rare type of tumor, often developing distant metastases. When there is a progression to a trophoblastic tumor, the assessment of locoregional extension and distant metastases is essential to establish an appropriate treatment protocol. We here report three clinical cases of GTT by describing their clinical presentations and the use of imaging techniques in the diagnosis and management of these disorders.

Mola invasiva / Invasive mole

La mola invasiva es poco frecuente y se caracteriza por la excesiva proliferación trofoblástica y penetración del trofoblasto dentro del miometrio, pero sin tendencia hacia la diseminación metastásica. El objetivo del trabajo es presentar un caso diagnosticado de neoplasia trofoblástica gestacional, tipo mola invasiva. Se realizaron estudios complementarios como: ecografía transabdominal, determinaciones de la fracción beta de la gonadotropina coriónica humana y una biopsia endometrial por legrado uterino. El resultado fue embarazo molar. Al ingreso le fue administrado metotrexato sistémico 25 mg intramuscular y ácido folínico un ámpula intramuscular de 15 mg diariamente, ambos durante cinco días. Posteriormente, a los 20 días se realizó histerectomía total abdominal sin anexectomía. La evolución clínica fue por consulta externa. Además, se realizó: radiografía de tórax, ultrasonografía de pelvis, dosificación de gonadotropina coriónica humana en su fracción beta, hemograma completo, tiempo de coagulación, sangramiento y transaminasa glutámico pirúvica evolutivas. En el manejo de la mola invasiva el tratamiento médico combinado con el quirúrgico fue efectivo y bien tolerado por la paciente(AU)

Invasive mole is an infrequent condition characterized by excessive trophoblastic proliferation and trophoblast penetration into the myometrium, without a tendency to metastatic dissemination. The purpose of the study is to present a case diagnosed with gestational trophoblastic neoplasia of the invasive mole type. The following complementary tests were performed: transabdominal echography, human chorionic gonadotropin beta subunit determinations, and endometrial biopsy by uterine curettage. The result was molar pregnancy. Upon admission the patient was administered systemic methotrexate 25 mg intramuscularly, as well as an intramuscular ampoule of folinic acid 15 mg daily, both during five days. Total abdominal hysterectomy without anexectomy was performed 20 days later. Clinical evolution was followed up on an outpatient basis. The following tests were also performed: chest radiography, pelvic ultrasonography, human chorionic gonadotropin beta dosage, complete blood count, clotting time, bleeding and evolutive glutamic-pyruvic transaminase. During management of the invasive mole, the combination of clinical and surgical treatments proved effective and was well assimilated by the patient(AU)

Multicenter analysis of gestational trophoblastic neoplasia in Turkey.

BACKGROUND: To evaluate the incidence, diagnosis and management of GTN among 28 centers in Turkey. MATERIALS AND METHODS: A retrospective study was designed to include GTN patients attending 28 centers in the 10-year period between January 2003 and May 2013. Demographical characteristics of the patients, histopathological diagnosis, the International Federation of Gynecology and Obstetrics (FIGO) anatomical and prognostic scores, use of single-agent and multi-agent chemotherapy, surgical interventions and prognosis were evaluated. RESULTS: From 2003-2013, there were 1,173,235 deliveries and 456 GTN cases at the 28 centers. The incidence was calculated to be 0.38 per 1,000 deliveries. According to the evaluated data of 364 patients, the median age at diagnosis was 31 years (range, 15-59 years). A histopathological diagnosis was present for 45.1% of the patients, and invasive mole, choriocarcinoma and PSTTs were diagnosed in 22.3% (n=81), 18.1% (n=66) and 4.7% (n=17) of the patients, respectively. Regarding final prognosis, 352 (96.7%) of the patients had remission, and 7 (1.9%) had persistence, whereas the disease was mortal for 5 (1.4%) of the patients. CONCLUSIONS: Because of the differences between countries, it is important to provide national registration systems and special clinics for the accurate diagnosis and treatment of GTN.

Rare Presentation of Chorioadenoma Destruens as Acute Haemoperitoneum Mimicking Ruptured Ectopic Pregnancy.

Gestational trophoblastic neoplasms (GTN) are proliferative degenerative disorders of placental elements and include complete or partial mole (90%), invasivemole (5-8%), choriocarcinoma (1-2%) and placental site tumor (1-2%). Chorioadenoma destruens is a trophoblastic tumor, characterized by myometrial invasion through direct extension or via venous channels. We present a case of invasive mole eroding uterus and uterine vasculature, causing sudden rupture of uterus with massive haemoperitoneum mimicking ectopic pregnancy. A 20 year old G1P0 at 6 weeks gestation presented in Casualty of Kasturba Hospital complaining of severe acute onset lower abdominal pain for one hour. Clinical examination revealed shock. Sonography suggested ectopic pregnancy and immediate exploratory laparotomy was decided. On laparotomy, 2000cc of haemoperitoneum was noted. Grape like vesicles protruding through fundal perforation with profuse active bleeding was seen. Bleeding persisted despite evacuation. Step wise uterine devascularisation failed to achieve haemostasis. Total abdominal hysterectomy was performed as a life saving measure.

Differential expression of E-cadherin, ß-catenin, and Lewis x between invasive hydatidiform moles and post-molar choriocarcinomas.

Trophoblast cell adhesion and migration are carefully coordinated during normal placental development. We have compared the expression of three adhesion molecules, E-cadherin, ß-catenin, and Lewis x, by immunohistochemistry during normal trophoblast differentiation, and in hydatidiform moles and choriocarcinomas. Both E-cadherin and ß-catenin were expressed in normal placenta cytotrophoblast, and this expression decreased with trophoblast maturation. E-cadherin was mainly localized along the contact between cytotrophoblast and syncytiotrophoblast, which indicates its role in the differentiation of the syncytial layer. Lewis x disappeared progressively during differentiation of normal villous vessels, and was expressed in molar pregnancies. Interestingly, whereas choriocarcinomas were not, or poorly, stained, invasive hydatidiform moles (invHMs) strongly expressed Lewis x in vascular structures. This observation correlated well with E-cadherin and ß-catenin expression and suggests that these three markers are associated with the invasive transformation. The presence of robust endothelial structures in invHMs could also explain their ability to maintain organized villous architecture (contrary to metastatic choriocarcinomas) during their invasion of extrauterine tissues such as the lung or the brain after dissemination through the blood flow. In our hands, Lewis x appeared to be a new, reliable marker that can be used to clearly distinguish invHMs from choriocarcinomas.

MRI of the placenta - a short review.

While ultrasound is still the gold standard method of placental investigation, magnetic resonance imaging (MRI) has certain benefits. In advanced gestational age, obese women, and posterior placental location, MRI is advantageous due to the larger field of view and its multiplanar capabilities. Some pathologies are seen more clearly in MRI, such as infarctions and placental invasive disorders. The future development is towards functional placental MRI. Placental MRI has become an important complementary method for evaluation of placental anatomy and pathologies contributing to fetal problems such as intrauterine growth restriction.

Contribution of referent pathologists to the quality of trophoblastic diseases diagnosis.

OBJECTIVE: To evaluate the contribution of referent pathologists (RPs) to the quality of diagnosis of trophoblastic diseases and to study the level of diagnostic agreement between the initial pathologists and the RPs. METHODS: This observational retrospective study was carried between 1 November 1999 and 11 January 2011 using the database of the French Trophoblastic Disease Reference Centre in Lyon. All files for hydatiform moles (HMs), trophoblastic tumours and non-molar pregnancies for which there was an initial suspicion of trophoblastic disease were included, whenever there was rereading of the slides by an RP. A total of 1851 HMs and 150 gestational trophoblastic tumours were analysed. RESULTS: When the initial pathologist diagnosed a complete mole, the RP confirmed the diagnosis in 96% of cases. When the initial pathologist diagnosed a partial mole, the RP confirmed the diagnosis in only 64% of cases. For trophoblastic tumours, when the initial pathologist diagnosed a choriocarcinoma, the RP confirmed the diagnosis in 86% of cases. When the initial anatomopathology suggested an invasive mole, the diagnosis was confirmed in 96% of cases. Finally, when the initial diagnosis was a placental site trophoblastic tumour or an epithelioid trophoblastic tumour, the RP confirmed the diagnosis in 60 and 100% of cases, respectively. CONCLUSION: A systematic policy of rereading of slides for all suspicious moles improves the quality of management of trophoblastic diseases at a national level.

Nephrotic syndrome associated with invasive mole: a case report.

Gestational trophoblastic disease describes a number of gynaecological tumours that originate in the trophoblast layer, including hydatidiform mole (complete or partial), placental site trophoblastic tumour, choriocarcinoma and gestational trophoblastic neoplasia (GTN). Invasive moles are responsible for most cases of localized GTN. Two cases of GTN previously reported in the literature exhibited membranous glomerulonephritis (MGN). However, histologic examinations in our case did not reveal evidence of MGN. Clinical features and pathologic findings were consistent with minimal change disease associated with an invasive mole. In the present case, we observed complete remission of nephrotic syndrome following removal of the invasive mole.

Gestational trophoblastic disease: experience at Nawabshah Hospital.

BACKGROUND: Gestational Trophoblastic Disease (GTD) is a heterogeneous group of diseases that includes partial and complete hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumour. The incidence of GTD varies in different parts of the world. The malignant potential of this disease is higher in South East Asia in comparison to western countries. Objectives of study were to determine the frequency, clinical presentation and management outcomes of GTD. This retrospective, descriptive case series was conducted in the Department of Obstetric and Gynaecology Nawabshah Medical College Hospital, from 1st Jan 2007 to 30th Dec 2007. METHODS: The case records of all the gestational trophoblastic cases during study period were analysed regarding their history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. RESULTS: There were a total of 1056 Obstetric admissions during the study period, which included 30 cases of trophoblastic disease with a frequency of GTD was 28 per 1000 live births. Of these 30 cases, 21 (70%) patients had hydatidiform mole, 7 (23.3%) patients had invasive disease and 2 (6.6%) patients had choriocarcinoma. Twenty three patients (76.6%) received chemotherapy while 25 (83.3%) patients had suction evacuation and 4 (13.3%) patients underwent hysterectomy. Among all patients, 29 (96.7%) fully recovered and 1 (3.3%) died because of extensive disease; metastasis extending up to brain. CONCLUSION: Frequency of GTD was higher compared to national and international studies. The disease was common in extremes of ages, low para and grand multiparous women. Hydatidiform mole was the commonest type of trophoblastic disease in these patients. Most common presenting complaint was bleeding per vagina followed by pain in lower abdomen.

Diagnostico clínico e histopatológico: embarazo molar: presentación de un caso clínico / Clinical and histopatológical diagnostics: molar pregnancy: presentation clinical of a case

La ETG es el término general utilizado para identificar distintos procesos donde existe una hiperplasia de diferentes tipos de epitelio trofoblástico, según la OMS puede clasificarse en 4 tipos: 1) Mola hidatiforme: completa o parcial, más común la primera en un 67 por ciento, 2) Mola invasora (corioadenoma destruens) 3) Coricarcinoma 4)Tumor trofoblástico del lecho placentario, su incidencia varia, pero en países desarrollados se estima sea 1.1/1000 embarazos, siendo esta mas alta en países subdesarrollados se presenta caso clìnico de una paciente la cual se le hace diagnóstico clínico e histopatológico y procedimientos para evacuación uterina por embarazo molar.

Gestational trophoblastic disease: experience at a tertiary care hospital of Sindh.

OBJECTIVE: To determine the frequency, clinical presentation and management outcomes of Gestational Trophoblastic Disease (GTD). STUDY DESIGN: Descriptive case series. PLACE AND DURATION: Department of Gynaecology and Obstetrics, Liaquat University of Medical and Health Sciences, Jamshoro, from March 2003 to March 2004. PATIENTS AND METHODS: The case records of all the gestational trophoblastic cases during study period were analyzed regarding their illness history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. RESULTS: There were a total of 1030 obstetric admissions during the study period, which included 23 cases of trophoblastic disease. Hence, frequency of GTD was 1 per 45 live births. Of these 23 cases, 19 (82.6%) patients had hydatidiform mole and 4 patients had malignant trophoblastic disease. Eight patients (34.7%) received chemotherapy while rest of the patients had suction evacuation and follow-up. Among all patients, 21 (91.3%) fully recovered and 2 (8.69%) died because of extensive disease; metastasis extending upto brain. CONCLUSION: Frequency of trophoblastic disease was high in this series compared to world and national literature. Therefore, emphasis should be on the early diagnosis of disease as proper management in the early stages strongly influences the outcome of disease. Suction evacuation and follow-up are ideal treatments for benign trophoblastic disease.

[Sensitivity, specificity, predictive positive and negative value of the main clinical signs and symptoms of hydatiform mole]. / Sensibilità, specificità, valore predittivo positivo e negativo dei principali segni clinici e sintomi della mola idatidea.

AIM: Especially in the first weeks of pregnancy, complete and partial hydatiform moles are not easily detected by sonography, symptoms and clinical signs. Due to the rarity of moles, it is possible that they may be confused with abortive pregnancies until the pathological examination. The aim of this study is to identify the sensitivity, specificity, predictive positive and negative value of the main symptoms and clinical signs of molar pregnancies. METHODS: Thirteen molar pregnancies have been detected after pathological examination from January 2003 to July 2005 in Perugia. Their main clinical signs and symptoms are compared with those recorded in 288 abortive pregnancies, 56 ectopic pregnancies and 27 Hyperemesis gravidarum, observed in the same period. RESULTS: Vaginal bleeding and pelvic pain are the most sensitive symptoms and have the highest predictive negative values. The size of the uterus greater for date is the most specific sign. Pelvic pain with hyperemesis, and uterus size greater for date have the highest predictive positive values, but the lowest sensitivity. CONCLUSIONS: A mole should be excluded in patients with hyperemesis and pelvic pain, and in patients with uterus size greater for date. In the first case, a hyperemesis gravidarum may be diagnosed and, in the second one, a twin pregnancy may be confirmed with a sonographic scan.