Form Of Gestational Trophoblastic Disease Research Articles

Clinical complications related to the benign form of gestational trophoblastic disease

A Doença Trofoblástica Gestacional (DTG) inclui doenças benignas como mola hidatiforme ou malignas como coriocarcinoma, tumor trofoblástico do sítio placentário, tumor trofoblástico epitelióide e mola invasora. A mola hidatiforme (MH) é classificada, segundo a morfologia, genética e histopatologia, em mola hidatiforme completa (MHC) e mola hidatiforme parcial (MHP). O seguinte estudo tem comoobjetivos conhecer as principais complicações clínicas associadas à DTG e relatar os principais métodos diagnósticos, além da abordagem terapêutica após gravidez molar.Trata-se de um estudo de revisão integrativa de literatura nas línguas portuguesa e inglesa, nas seguintes bases de dados: Medline, Pubmed, SciELO, Lilacs, Bireme e Clinicalkey.Em particular, a MHC tem caráter diploide, resultante da duplicação do material genético haploide de um único espermatozóide, enquanto, o MHP é triploide e ocorre após a fertilização de um óvulo normal por dois espermatozoides ou por um espermatozoide diploide. A MH é conceituada como uma gravidez fora do padrão de normalidade devido aos variados graus de proliferação do trofoblasto e edema das vilosidades associado à ausência ou anormalidades no embrião ou feto.Faz-se presente uma série de complicações clínicas graves que chegam a acometer 25% das pacientes com MH em fase avançada, fazendo parte desta: o hipertireoidismo, cistos ovarianos, hemorragia, mola invasora, complicações cardiopulmonares e pré-eclâmpsia. É fundamental alertar a importância da dosagem do beta-hCG para se obter um diagnóstico precoce e assim deve ser realizado em todas as gestantes com sangramento vaginal, a fim de identificar o desenvolvimento normal da gravidez ou intercorrências que necessitem de intervenção.

Post molar choriocarcinoma with solitary renal metastasis in the absence of primary uterine tumor: a case report and review of the literature

BackgroundChoriocarcinoma is a rare and highly malignant form of gestational trophoblastic disease that may develop following pregnancy, abortion, or a hydatiform mole. Renal metastatic involvement by post molar choriocarcinoma is even rarer. In this case report, we describe a unique case of post molar choriocarcinoma with a solitary renal metastasis in the absence of a primary uterine tumor and metastases in other sites, which presented with urological symptoms and spontaneous renal hemorrhage.Case presentationA 41-year-old Persian woman with history of complete hydatiform mole presented with severe flank pain, nausea, vomiting, gross hematuria, and vaginal bleeding. Laboratory tests demonstrated a serum beta human chorionic gonadotropin hormone level of 60,000 mIU/mL. Imaging studies showed a lesion at the lower pole of the left kidney with active bleeding surrounded by hematoma, as well as an empty uterine cavity. Additionally, bilateral pleural effusion was detected without any lesion within the lungs. Subsequently, the patient underwent laparotomy, partial nephrectomy, and left para-ovarian cystectomy. Endometrial curettage was also carried out. The histopathology report revealed choriocarcinoma renal metastasis with high expression of beta human chorionic gonadotropin, cytokeratin 7, and Ki 67. Moreover, there were no malignant cells in the endometrial curettage specimens, and a corpus luteum cyst was found within the para-ovarian cyst. Further investigations revealed that the pleural effusion was free of malignant cells, and there was no evidence of metastatic lesions in the brain. As a result, the patient was referred to the oncology department to receive chemotherapy, and the beta human chorionic gonadotropin levels dropped to 5 mIU/mL after receiving courses of a standard regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine/oncovin over 3 weeks. Finally, monthly measurements of beta human chorionic gonadotropin levels for 6 months indicated that levels have constantly remained within normal ranges, showing no evidence of recurrence or new metastasis.ConclusionsUrological symptoms such as hematuria or spontaneous renal hemorrhage might be the only presentation of post molar choriocarcinoma with renal involvement. Thus, it can be beneficial to measure serum beta human chorionic gonadotropin levels among females of childbearing age who present with unexplained urological symptoms, especially if there is a history of prior hydatiform mole.

Placental Site Trophoblastic Tumor – A Rare Gestational Trophoblastic Disease: A Case Report and Review of Literature

Abstract Placental site trophoblastic tumor (PSTT) represents a rare form of gestational trophoblastic disease. It occurs commonly in females with a history of miscarriage, termination of pregnancy, or any other ongoing pathological pregnancy. We report this rare case in a 23-year-old female, who previously had a history of recurrent miscarriages. In this case, we emphasize on clinical and histopathological features for better understanding and awareness of such rare entities.

Hydatidiform Mole-Between Chromosomal Abnormality, Uniparental Disomy and Monogenic Variants: A Narrative Review.

A hydatidiform mole (HM) or molar pregnancy is the most common benign form of gestational trophoblastic disease characterized by a proliferation of the trophoblastic epithelium and villous edema. Hydatidiform moles are classified into two forms: complete and partial hydatidiform moles. These two types of HM present morphologic, histopathologic and cytogenetic differences. Usually, hydatidiform moles are a unique event, but some women present a recurrent form of complete hydatidiform moles that can be sporadic or familial. The appearance of hydatidiform moles is correlated with some genetic events (like uniparental disomy, triploidy or diandry) specific to meiosis and is the first step of embryo development. The familial forms are determined by variants in some genes, with NLRP7 and KHDC3L being the most important ones. The identification of different types of hydatidiform moles and their subsequent mechanisms is important to calculate the recurrence risk and estimate the method of progression to a malign form. This review synthesizes the heterogeneous mechanisms and their implications in genetic counseling.

Clinical characteristics and management outcomes of patients with hydatidiform mole in a national referral hospital in Kenya: A retrospective study

Background: Hydatidiform mole is a benign form of gestational trophoblastic disease with potential for malignant transformation. It is characterized by abnormal trophoblastic proliferation with placental villi vascular welling with or without embryo formation.
 Objective: To determine patient clinical characteristics and management outcomes of hydatidiform mole diagnosed at Kenyatta National Hospital, Nairobi, Kenya.
 Methods: A descriptive retrospective study design was employed. The medical records of patients admitted with a clinical diagnosis of hydatidiform mole at the Kenyatta National Hospital between January 2013 and December 2017 were retrieved. Data were collected using an abstraction tool, entered, and analyzed using the Statistical Package for Social Sciences (SPSS) version 22 (IBM, Armonk, NY, USA). Categorical data were summarized into frequencies and proportions and continuous data into means, standard deviations, medians, and interquartile ranges.
 Results: During the study period, 137 records of patients admitted and managed for hydatidiform mole were retrieved. Most, 110 (80%) and 97 (71%) patients were 20-34 years old and multiparous, respectively. The mean gestational age at presentation was 17 weeks (SD 7.4), and bleeding was the most common symptom in 105 (77%) patients. Only 46 (34%) patients had documented histological confirmation of the hydatidiform mole. None of the patients completed six months of follow-up; hence, there was no documentation of treatment outcomes.
 Conclusion: In this study, the clinical presentation of the hydatidiform mole was relatively uniform, but the approach to definitive diagnosis, management, and follow-up was suboptimal and inadequately documented. Hence, management outcomes cannot be objectively determined.

Tru-cut placental site trophoblastic tumor biopsy: A novel way for diagnosis. Case report

Background: A Placental Site Trophoblastic Tumor (PSTT) is a rare form of gestational trophoblastic disease and usually manifests itself with abnormal uterine bleeding and elevated β-hCG serum levels even months or years after any antecedent pregnancy event. Typically, tumors are confined into the uterus and secrete lower levels of β-hCG compared with other Gestational Trophoblastic Neoplasia (GTN). They can be detected sonographically like heterogeneous solid mass in the uterine cavity with minimal to high vascularization, but sometimes they develop into myometrium without endometrial involvement. To the best of our knowledge, uterine biopsy is the only way to make a reliable diagnosis, but for these reasons sometimes Dilation and Curettage (D&C) or hysteroscopy are not exhaustive. Their final diagnosis is histopathological and often very difficult due to their rarity, thus many times they directly present metastasis symptoms (mainly pulmonary) or paraneoplastic syndromes. Case presentation: A 37-year-old woman with the purpose of a second pregnancy, after seven weeks of amenorrhea, complained irregular bleeding and metrorrhagia. The patient underwent transvaginal ultrasound (US) and a lesion of 50 mm was found in myometrium, its echostructure was inhomogeneous and richly vascularised (CS4) with rear acoustic reinforcement. It was associated with slightly elevated serum levels of β-hCG. The patient performed a hysteroscopy with simultaneous tru-cut biopsy of the lesion under US guidance and a placental site trophoblastic tumor was diagnosed by histological examination. Conclusion: In this paper we suggest a novel method to perform the PSTT diagnosis. A tru-cut core biopsy allows a deep and precise biopsy with less invasivity and low risk of bleeding or uterine damage. Our case study shows that the employment of this novel technique can help in the diagnosis through a targeted sampling of the myometrium even in those cases in which the endometrial cavity is not involved.

Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus in a retrospective cohort of 141 patients

Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January2022. Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day8. Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.

Synchronous placental site trophoblastic tumor and choriocarcinoma

Link of Video Abstract: https://youtu.be/bx7KdiTKiOQ Introduction: Gestational trophoblastic neoplasia (GTN) comprises a series of malignancies characterized by abnormal proliferation of fetal trophoblastic tissue. GTN lesions refer to a class of malignant lesions that have distinct histopathologic features, including invasive hydatidiform moles, choriocarcinomas, placental site trophoblastic tumors (PSTT), and epithelioid trophoblastic tumor (ETT). Most often, they occur coexist separately, but there are also cases of mixed GTN with a combination of histologic PSTT, ETT, or choriocarcinoma. PSTT is a rare form of gestational trophoblastic disease (GTD). The percent incidence of this disease is 0.23% of total GTD and 1-2% of total GTN. The incidence rate of choriocarcinoma is also limited. Data collection on the incidence of mixed GTN has been more challenging due to the rarity of this disease. Case Description: We report a case of a 26-year-old female patient with choriocarcinoma and PSTT. The patient’s beta-human chorionic gonadotropin (β-hCG) levels remained elevated despite treatment with single-agent chemotherapeutic regimen. She underwent a series of chemotherapy treatments and two surgeries were required. The histological examination of the uterine tumor revealed a choriocarcinoma whilst the hysterectomy thereafter showed a PSTT. After the hysterectomy the β-hCG level continued to rise. Due to chemotherapy resistance, EMACO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) was changed to EP-EMA (Etoposide, cisplatin, etoposide, methotrexate, actinomycin-D). After two administrations of EP-EMA, β-hCG levels normalized. Conclusion: This is a rare case of mixed GTN of choriocarcinoma and PSTT. Mixed GTN should be considered when chemotherapy is not effective in the treatment of GTN. These cases need to be reported to improve the diagnosis and management of patients.

A case of non-mosaic 47, XXX presenting as placental site trophoblastic, tumor secondary to partial mola

Background: Placental trophoblastic tumor is a very rare form of gestational trophoblastic disease (GTD). There are some case reports in which some tumors have been associated with Trisomy X. Objective: is to inform and suggest a possible management for similar cases in a future. Material and methods: A systematic search was carried out in the bibliography and subsequent surgery. Case: Patient with karyotype 47, XXX and ETG. The associated phenotype consisted of a prominent forehead, epicanthal fold in both eyes, micrognathia with dental crowding. The biomarkers CKAE1/AE3, Ki75 were positive. The pathology report suggests an incomplete atypical mole. The final diagnosis was trophoblastic tumor of the placental site. Conclusion: We recommend hysterectomy with preservation of the ovaries if they are not involved.

Hysteroscopic management of molar pregnancy: A series of 36 cases.

Background: Hydatidiform Mole (HM) is the most common form of gestational trophoblastic disease. Dilatation and curettage is the classical treatment of this affection. Hysteroscopic resection (HsR) is an alternative for the treatment of intra-uterine pathology. Objective: To describe the feasibility of HsR for the management of HM. Result: Case series of patients who had a complete or partial HM confirmed by histological examination of the trophoblastic tissue resected by operative hysteroscopy between 2007 and 2019. After approval of our ethics committee, we evaluated 36 patients who underwent hysteroscopic resection for molar pregnancy. Histological analysis showed partial HM in 28 patients (77.8%) and complete HM in 8 (22.2%). Main surgical complications were uterine perforation in one patient and glycine resorption in 10 patients with two cases of hyponatremia corrected by standard treatment. We performed an ultrasound control 1 month after the intervention in 19 patients (52.8%) as they had slow decrease of HCG or bleeding complaints and found retained product of conception (RPOC) in six patients (16.7%). Conclusion: This first report on a small number of patients demonstrate that hysteroscopic resection is a feasible procedure for the management of molar pregnancy. Direct visualization of the procedure helps the surgeon to control the resection. Further studies are mandatory to compare this technique with D&C in term of RPOC and fertility outcomes as it remains the standard treatment.

A Rare Case of Choriocarcinomatous Pulmonary Embolism revealed by Ischemic Strokes

Choriocarcinoma is a malignant tumor with high metastatic potential belonging to the spectrum of gestational trophoblastic tumors, which can be of germ cell origin (nongestational) or gestational. Choriocarcinomatous pulmonary embolism represents a rare and aggressive extra-gonadal form of gestational trophoblastic disease, most often occurring after a normal or pathological pregnancy. The presentation is similar to that of cruoric embolism, but it is characterized by local invasion and significant hematogenous dissemination leading to distant metastases. Increased Human chorionic gonadotropin hormone (hCG) levels are suggestive of the diagnosis. We report a case of choriocarcinomatous pulmonary embolism involving the inferior lobar artery of the left lung in a 44-year-old female patient admitted for multiple ischemic strokes. The diagnosis of choriocarcinoma was done on CT scan in the presence of high levels of Human chorionic gonadotropin hormone (hCG) contrasting with negative pelvic imaging and a history of previous spontaneous abortion. The outcome was favourable after chemotherapy which was an additional argument in favor of the diagnosis of choriocarcinoma.

Does COVID-19 Affect the Course of Trophoblastic Gestational Disease in Partial Hydatidiform Moles; Is It A Viral or A Pandemic?

Objective: Hydatiform mole (HM) is a non-malignant form of gestational trophoblastic disease (GTD) characterized by failure of normal fetal development and overgrowth of trophoblasts. With this retrospective cohort study, we planned to determine the incidence of PHM, etiology and progression rates to Gestational trophoblastic neoplasia (GTN) during the COVID-19 epidemic. Materials and Method: This retrospective cohort study was conducted in Ankara Etlik Zübeyde Hanım Women’s Health Training and Research Hospital Early Pregnancy Assessment Unit between March 2016 and February 2022. Patients who underwent therapeutic curettage (T/C) with the diagnosis of missed abortion, intrauterine exitus (IUEX), molar pregnancy or incomplete abortion after single spontaneous pregnancy were included in the study. The study group consisted of 138 patients who were diagnosed with partial hydatiform mole as a result of pathological examination in this process. There were 135 patients in the control group. Results: The number of patients who applied during the pandemic period and were diagnosed with PHM was 62 (44.92%). The mean age of the patients in the study group was 31.97±8.26 years. The mean body mass index of these patients was 26.38±5.13 m2/kg. The mean paternal age in the study group was 34.95±8.32 years, and it was higher than the paternal age of the patients in the control group (p=0.028). While the incidence of PHM was 1.22/1000 births in our hospital in 2019, this figure was calculated as 3.79/1000 births in 2020. The incidence of progression to GTN at 4 years before the pandemic was 0.02/1000 births; In 2020-2021, this rate was calculated as 0.25/1000 births. Conclusion: During the pandemic period, along with the increase in the incidence of PHM compared to the pre-pandemic period, an increase in the incidence of progression to GTN disease was detected.

Hydatidiform Mole; Histological Types and Age Distribution in Basrah

Background Hydatidiform mole (HM) is a placental pathology, which is a form of gestational trophoblastic disease (GTD). HM is classified into complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM). The incidence of molar pregnancy varies according to the geographical area. It is found to be higher in developing countries. Age is a risk factor for developing HM. In this study, we aim to determine the frequency of hydatidiform mole among cases of early trimester evacuation specimens and its relation to patient's age at Basrah maternity and paediatric hospital and Al- Mosawi private hospital. Patients and Methods This was a descriptive retrospective study for a four-year period; all cases of early trimester evacuation specimens were from January 1, 2017, to December 31, 2020. All specimens were fixed in 10% formalin and dehydrated in graduated alcohol, (5) micron thickness sections were obtained, stained with hematoxylin and eosin and examined, and cases of CHM, PHM and RPOG were analyzed. Results A total of 216 evacuation specimens were examined, and the patients age ranged from 14–50 years. Among these, 78.2% of patients were between 20 and 30 years. The percentage of RPOC was 54.2%, while that of CHM was 19.4% and that of PHM was 26.4%. The maximum cases of complete and partial mole were in the 20–30 years age group. Conclusions The frequency of HM was high compared to many other studies.

A first stage placental site trophoblastic tumor: a case report and review of literature.

Placental site trophoblastic tumor (PSTT) is a very rare form of gestational trophoblastic disease (GTD) that occurs mainly in women who have a history of termination of pregnancy. It has different characteristics from other gestational trophoblastic tumors: it grows slowly, secretes low levels of beta-human chorionic gonadotropin (β-hCG), with low metastatic potential. We report a case of PSTT of a 32-year-old patient. Seven months after delivery, the patient presented at our Center with persistence of menorrhagia for at least 1 month. A slightly high level of beta-human chorionic gonadotropin (β-hCG) was observed. TVUS and MRI, an operative hysteroscopy and a laparoscopy were performed. The histological and immunohistochemical findings demonstrated PSTT. Diagnosis of juvenile cystic adenomyoma (JCA) was also added. A total body CT scan was negative for metastases. A total hysterectomy with salpingectomy was performed. We performed a search of relevant studies about PSTT of the last years. A systematic search of Pubmed databases was conducted. Appropriate search terms were constructed by reviewing abstracts, titles and keywords relating to PSTT known to the authors. All articles known to the authors useful to the review were included, comparing with our clinical case. Stages and treatment are related to survival rates, with long term survival expected for stage I low-risk disease after hysterectomy. Our case is a stage I disease with good prognostic factors (patient's age and absence of metastases) and, as described in the literature, a total hysterectomy with salpingectomy was performed.

The current state of pathology and immunohistochemistry in gestational trophoblastic disease therapeutic management: A tertiary center experience

Gestational trophoblastic disease (GTD) is derived from the abnormal development of trophoblastic tissue and covers a broad range of benign and malignant disorders. The histological diagnosis of GTD continues to be a challenge, even among expert pathologists. The present study evaluates the roles of pathology and immunohistochemistry in GTD diagnostic and therapeutic approaches. A retrospective study was conducted in Filantropia Clinical Hospital, Bucharest, Romania, involving cases of GTD between 2010 and 2020. We reported 19 clinically diagnosed and histologically confirmed cases of GTD, 15 moles (complete and partial), along with 4 cases of gestational trophoblastic neoplasia (GTN). The mean age of the patients studied was 31.3±7.5 years. The percentage of cases diagnosed after the sonographic evaluation was 94.7%. The rate of progression of GTD to GTN was 5.2%. Seven patients with low-risk GTD (risk score six or less) were treated with first-line chemotherapy (CT), and two cases required second-line CT. Twelve patients with highrisk GTD (risk score seven or more) were treated with first-line CT (n = 4), first-line CT followed by second-line CT (n = 4), first-line CT with adjuvant surgery (n = 3), and first-line surgery (one case). No causal relationship has been established between the forms of gestational trophoblastic disease regarding hCG level, the rate of normalization of hCG, and the rate of progression to GTN. After chemotherapy for GTD, only 42.1% of patients who wanted a future pregnancy could conceive. Underutilized in the current practice (5.2%), the immunohistochemical markers for trophoblasts and DNA genotyping are particularly useful tools in the fast and accurate diagnosis and prognosis of GTD.

Hypered laparoscopic and endoscopic management of lower gastrointestinal bleeding from metastatic Jejunal and ileal choriocarcinoma of unknown primary.

IntroductionChoriocarcinoma is form of malignant neoplasm that arise from trophoblastic cells that occurs mostly in ovaries and testes and it can metastasis to lungs, liver or to gastrointestinal tract.Presentation of caseThis is 37 years old female presented as a case of lower gi bleeding and was diagnosed to have metastatic jejunal and ilium choriocarcinoma of unknown primary and underwent ileocecal resection first then followed up with small bowel resection around 60 cm from duodenojejunal junction with primary anastomosis. The patient was found to have liver and brain metastasis and received chemotherapy with full response.DiscussionChoriocarcinoma is the most aggressive form of gestational trophoblastic disease that metastasizes through the lymphatic and hematogenous routes, and when its metastasis to the small bowel it's considered the worst prognosis with high mortality rate. Treatment consists of surgery and combined chemotherapy which is what our patient responded with.ConclusionMetastatic choriocarcinoma with unknown primary can be treated surgically with chemotherapy.

Genetic Screening of Susceptible Women to Recurrent Molar Pregnancy for Prevention of Gestational Choriocarcinomas

Hydatidiform mole is an abnormal pregnancy characterized by hyper-proliferation of trophoblastic cells (both cytotrophoblast and syncytiotrophoblast). If the proliferation phenomenon not well controlled, e.g. due to poor medical health care system, mole can become invasive and lead to gestational choriocarcinomas. Gestational choriocarcinoma by strong metastatic potentiality, as one of the most aggressive, malignant form of gestational trophoblastic disease, could be spread through directly vascular and the middle layer of the uterine wall (Myometrium‎) and would involve distant sites such as the lungs, spleen, intestines, kidney, and liver. When a hydatidiform mole occurs once, it is known as sporadic hydatidiform mole; if it happens again, the condition is known as recurrent hydatidiform mole. In recurrent form, the gestational choriocarcinoma occurrence risk increased up to a 100-fold. Therefore, early onset identify of susceptible women to recurrent molar pregnancy is clinical importance because of the increased risk of developing neoplasia. Due to the role of maternal homozygous and compound heterozygous recessive gene, mutations have been reported in hydatidiform mole occurrence, women screening can be improved by molecular genotyping methods.

Placental Site Trophoblastic Tumor – A Systematic Review

Placental site trophoblastic tumor (PSTT), a rare form of gestational trophoblastic disease (GTD) has a wide clinical and biological spectrum with benign to malignant potential. PSTT can occur after any type of pregnancy and no specific risk factors have been established. Mitotic index is the most important prognostic factor in determining the outcome of disease. Though early and benign disease is cured with surgery, for advanced metastatic disease, chemotherapy plays an important role in management. However, chemotherapy resistance is a main obstacle in achieving adequate control in patients with advanced disease. This article reviews the literature on this rare disease and tries to provide a comprehensive view on its management.

Genotyping diagnosis of gestational trophoblastic disease: frontiers in precision medicine.

Investigations in recent decades have exploited tissue DNA genotyping as a powerful ancillary tool for the precision diagnosis and subclassification of gestational trophoblastic disease. As lesions of gestational origin, the inherited paternal genome, with or without copy number alterations, is the fundamental molecular basis for the diagnostic applications of DNA genotyping. Genotyping is now considered the gold standard in the confirmation and subtyping of sporadic hydatidiform moles. Although a precise diagnosis of partial mole requires DNA genotyping, prognostic stratification according to distinct genetic zygosity in complete moles has recently gained significant clinical relevance for patient care. Beyond hydatidiform moles, DNA genotyping has fundamental applications in the diagnosis or prognostic assessment of gestational trophoblastic tumors, in particular gestational choriocarcinoma. DNA genotyping provides a decisive tool in the separation of gestational trophoblastic neoplasia from non-gestational counterparts/mimics of either germ cell or somatic origin. The FIGO/WHO prognostic scoring scheme requires ascertaining the precise index gestational event and the time interval between the tumor and index gestation, where DNA genotyping can provide highly relevant information. With rapid acquisition of molecular diagnostic capabilities in the clinical practice, DNA genotyping has become closely integrated into the routine diagnostic workup of various forms of gestational trophoblastic disease.

Distinct microRNA profiles for complete hydatidiform moles at risk of malignant progression

MicroRNAs are small noncoding RNAs with important regulatory functions. Although well-studied in cancer, little is known about the role of microRNAs in premalignant disease. Complete hydatidiform moles are benign forms of gestational trophoblastic disease that progress to gestational trophoblastic neoplasia in up to 20% of cases; however, there is no well-established biomarker that can predict the development of gestational trophoblastic neoplasia. This study aimed to investigate possible differences in microRNA expression between complete moles progressing to gestational trophoblastic neoplasia and those regressing after surgical evacuation. Total RNA was extracted from fresh frozen tissues from 39 complete moles collected at the time of uterine evacuation in Brazil. In the study, 39 cases achieved human chorionic gonadotropin normalization without further therapy, and 9 cases developed gestational trophoblastic neoplasia requiring chemotherapy. Total RNA was also extracted from 2 choriocarcinoma cell lines, JEG-3 and JAR, and an immortalized normal placenta cell line, 3A-subE. MicroRNA expression in all samples was quantified using microRNA sequencing. Hits from the sequencing data were validated using a quantitative probe-based assay. Significantly altered microRNAs were then subjected to target prediction and gene ontology analyses to search for alterations in key signaling pathways. Expression of potential microRNA targets was assessed by quantitative real-time polymerase chain reaction and western blot. Finally, potential prognostic protein biomarkers were validated in an independent set of formalin-fixed paraffin-embedded patient samples from the United States (15 complete moles progressing to gestational trophoblastic neoplasia and 12 that spontaneously regressed) using quantitative immunohistochemistry. In total, 462 microRNAs were identified in all samples at a threshold of <1 tag per million. MicroRNA sequencing revealed a distinct set of microRNAs associated with gestational trophoblastic neoplasia. Gene ontology analysis of the most altered transcripts showed that the leading pathway was related to response to ischemia (P<.001). Here, 2 of the top 3 most significantly altered microRNAs were mir-181b-5p (1.65-fold; adjusted P=.014) and mir-181d-5p (1.85-fold; adjusted P=.014), both of which have been shown to regulate expression of BCL2. By quantitative real-time polymerase chain reaction, BCL2 messenger RNA expression was significantly lower in the complete moles progressing to gestational trophoblastic neoplasia than the regressing complete moles (-4.69-fold; P=.018). Reduced expression of BCL2 was confirmed in tissue samples by western blot. Immunohistochemistry in the independent patient samples revealed significantly lower cytoplasmic expression of BCL2 in the villous trophoblasts from cases destined for progression to gestational trophoblastic neoplasia compared with those that regressed, both with respect to staining intensity (optic density 0.110±0.102 vs 0.212±0.036; P<.001) and to the percentage of positive cells (16%±28% vs 49.4%±28.05%; P=.003). Complete moles progressing to gestational trophoblastic neoplasia are associated with a distinct microRNA profile. miR-181 family members and BCL2 may be prognostic biomarkers for predicting gestational trophoblastic neoplasia risk.