Trophoblastic Disease Research Articles

The impact of the distance traveled between residence and gestational trophoblastic neoplasia reference center and clinical outcomes in Brazilian women

ObjectiveTo relate the distance traveled from the patient's residence to the gestational trophoblastic neoplasia (GTN) reference center (RC) and the occurrence of unfavorable clinical outcomes, as well as to estimate the possible association between this distance and the risk of metastatic disease at presentation, the need for multiagent chemotherapy to achieve remission and loss to follow-up before remission. Study designRetrospective historical cohort study of patients with GTN followed at 8 Brazilian GTN-RC, from January 1st, 2000 - December 31st, 2017. ResultsEvaluating 1055 cases of GTN, and using a receiver operating characteristic curve, we found a distance of 56 km (km) from the residence to the GTN-RC (sensitivity = 0.57, specificity = 0.61) best predicted the occurrence of at least one of the following outcomes: occurrence of metastatic disease, need for multiagent chemotherapy to achieve remission, or loss to follow-up during chemotherapy. Multivariate logistic regression adjusted by age, ethnicity, marital status and the reference center location showed that when the distance between residence and GTN-RC was ≥56 km, there was an increase in the occurrence of metastatic disease (relative risk - RR:3.27; 95%CI:2.20–4.85), need for multiagent chemotherapy (RR:1.36; 95%CI:1.05–1.76), loss to follow-up during chemotherapy (RR:4.52; 95CI:1.93–10.63), occurrence of chemoresistance (RR:4.61; 95%CI:3.07–6.93), relapse (RR:10.27; 95%CI:3.08–34.28) and death due to GTN (RR:3.62; 95%CI:1.51–8.67). ConclusionsThe distance between the patient's residence and the GTN-RC is a risk factor for unfavorable outcomes, including death from this disease. It is crucial to guarantee these patients get prompt access to the GTN-RC and receive follow-up support.

Post-Molar Gestational Trophoblastic Neoplasia After Ectopic Molar Pregnancy in Broad Ligament: A Rare Case Report

Post-Molar Gestational Trophoblastic Neoplasia After Ectopic Molar Pregnancy in Broad Ligament: A Rare Case Report

Geographical Health District and Distance Traveled Influence on Clinical Status at Admission of Patients with Gestational Trophoblastic Disease.

To assess the potential relationship of clinical status upon admission and distance traveled from geographical health district in women with gestational trophoblastic disease (GTD). This is a cross-sectional study including women with GTD from the 17 health districts from the São Paulo state (I-XVII), Brazil, referred to the Botucatu Trophoblastic Disease Center (specialized center, district VI), between 1990 and 2018. At admission, hydatidiform mole was assessed according to the risk score system of Berkowitz et al. Gestational trophoblastic neoplasia was evaluated using the International Federation of Gynecology and Obstetrics / World Health Organization (FIGO/WHO) staging/risk score. Data on demographics, clinical status and distance traveled were collected. Multiple regression analyses were performed. This study included 366 women (335 hydatidiform mole, 31 gestational trophoblastic neoplasia). The clinical status at admission and distance traveled significantly differed between the specialized center district and other districts. Patients referred from health districts IX (β = 2.38 [0.87-3.88], p = 0.002) and XVI (β = 0.78 [0.02-1.55], p = 0.045) had higher hydatidiform mole scores than those from the specialized center district. Gestational trophoblastic neoplasia patients from district XVI showed a 3.32 increase in FIGO risk scores compared with those from the specialized center area (β = 3.32, 95% CI = 0.78-5.87, p = 0.010). Distance traveled by patients from districts IX (200km) and XVI (203.5km) was significantly longer than that traveled by patients from the specialized center district (76km). Patients from health districts outside the specialized center area had higher risk scores for both hydatidiform mole and gestational trophoblastic neoplasia at admission. Long distances (>80 km) seemed to adversely influence gestational trophoblastic disease clinical status at admission, indicating barriers to accessing specialized centers.

A Rare Presentation of Gestational Trophoblastic Neoplasia

A Rare Presentation of Gestational Trophoblastic Neoplasia

Persistent cornual pregnancy mimicking uterine arteriovenous malformation: a case report

BackgroundUterine arteriovenous malformation(AVM) refers to the abnormal direct traffic between uterine arteries and veins, which can be characterized by the imaging examination, showing increased uterine vascularity and arteriovenous shunting. However, similar imaging manifestations can also be seen in a variety of conditions including retained production of conception, gestational trophoblastic disease, placental polyp, and vascular neoplasm.Case presentationHere we present a case of a 42-year-old woman who was suspected of suffering uterine AVM indicated by Doppler sonography and magnetic resonance imaging but was finally diagnosed with a persistent ectopic pregnancy located on the right uterine corner by pathology after laparoscopy. She recovered well after surgery.ConclusionUterine AVM is a rare and serious condition. In general, it presents special radiological manifestations. However, when complicated with other diseases it can also be distorting. Standardized diagnosis and management are important.

“More than a song and dance”: Exploration of patient perspectives and educational quality of gynecologic cancer content on TikTok

ObjectiveTo investigate themes, quality, and reliability of gynecologic cancer-related content on the social media application TikTok. MethodsTikTok was systematically searched for the 100 most popular posts for ovarian cancer (OC), endometrial cancer (EC), cervical cancer (CC), vulvar cancer (VC), and gestational trophoblastic disease (GTD) in August 2022. Data was collected for demographics, tone, and themes. Educational videos were rated for quality and reliability utilizing the modified DISCERN scale. Relationships between content demographics, disease sites, and themes were assessed. ResultsAs of August 2022, the top five hashtags for each gynecologic cancer on TikTok had 466.7 million views. 430 of the top 500 posts were eligible for inclusion (OC: n = 86, CC: n = 93, EC: n = 98, GTD: n = 63, VC: n = 90). The majority of creators (n = 323, 75.1%) were White, 33 (7.7%) were Black, 20 (4.6%) were Asian/Pacific Islander (API), 10 (2.3%) were South Asian, 20 (4.7%) were Hispanic/Latino/a, 24 (5.5%) were unable to determine. Eleven central themes were identified, with significant differences when analyzed by disease site and race. The median DISCERN score for all posts was 1.0, indicating poor educational quality and reliability. When compared by race, South Asian/API posters received the highest scores (3, IQR 2.5) versus Black (2: IQR 3), Hispanic/Latino/a (2: IQR 0), and White posters (1, IQR 2) (p = 0.0013). Conclusion(s)Gynecologic cancer-related content on TikTok is of poor educational quality, and racial disparities in gynecologic cancer extend to social media. Opportunities exist to create more diverse content to support racial and cultural experiences in gynecologic cancer treatment.

A Rare Case of Placental Site Trophoblastic Tumor

Placental site trophoblastic tumor (PSTT) is a rare entity of malignant gestational trophoblastic neoplasia (GTN) with an incidence of 0.23 to 3% of all gestational trophoblastic diseases (GTD). They originate from intermediate trophoblastic cells of the placenta. They are slow-growing tumors and less chemo sensitive. Per vaginal bleeding following a miscarriage is not uncommon, however malignant variants of gestational trophoblastic neoplasia also could be a possibility. We are reporting a 24-year-old who was an otherwise healthy female who presented with persistent per vaginal bleeding following the first-trimester miscarriage in her second pregnancy. Initial histology of suction evacuation for her miscarriage has shown a partial mole. Since she continues to have per vaginal bleeding even a month later, repeat evacuation was done and beta hCG was high (2132mIU/ml), she was treated with a methotrexate regime. During follow up there was a slow rising of beta hCG level and hysterectomy was carried out due to the suspicions of invasive mole or PSTT. Histology confirmed a placental site trophoblastic tumor and her recovery and follow-up were uneventful.

Efficacy analysis of single-agent carboplatin AUC4 2-weekly as second-line therapy for methotrexate-resistant (MTX-R) low risk gestational trophoblastic neoplasia (GTN)

BackgroundApproximately one-third of patients with low-risk Gestational Trophoblastic Neoplasia (WHO 0–6) develop methotrexate-resistance (MTX-R). In the UK, subsequent treatment with either actinomycin-D (ActD) or multi-agent combination chemotherapy has depended on whether the hCG was above or below an hCG threshold. To reduce exposure to combination chemotherapy (CC), over the years the UK service has raised this threshold as well as using single-agent carboplatin AUC6 3-weekly at MTX-R instead of CC. Updated results for carboplatin demonstrate an 86% complete hCG response (hCG CR) but associated with haematological dose-limiting toxicity. MethodsIn 2017, single-agent carboplatin became the national standard second-line treatment following MTX-R at hCG of >3000 IU/L. Carboplatin was changed to two-weekly AUC4 scheduling and continued until normal hCG plus 3 consolidation cycles. For patients failing to respond, CC (Etoposide-Actinomycin-D or EMA-CO) was introduced. Results22 evaluable patients with a median hCG at MTX-R of 10,147 IU/L (IQR 5527–19,639) received carboplatin AUC4 2-weekly (median no. of cycles = 6, IQR 2–8). Of these, 36% achieved a hCG CR. All 14 non-CR patients were cured with subsequent CC; 11 and 2 patients with 3rd line and 4th line CC respectively and 1 patient following 5th line CC and hysterectomy. Overall survival remains 100%. ConclusionCarboplatin is not sufficiently active in the second-line treatment of low-risk MTX-resistant GTN. New strategies are required to increase hCG CR and spare more toxic CC regimens.

Partial Molar Pregnancy within the Fallopian Tube: A Rare and Challenging Entity

There have been a small number of ectopic molar pregnancies reported with estimates being around 1.5 in every 1,000,000 pregnancies. Ectopic pregnancy and molar pregnancy are not rare events with their incidence being 20 in every 1000 and 1 in every 500 to 1000 pregnancies respectively but their combination that is ectopic molar pregnancy is a rare entity so often not considered as a diagnostic possibility. Among ectopic pregnancies, fallopian tubes are the most common site (98% cases). Only 0.7 % of GTD (Gestational trophoblastic diseases) occur in Fallopian tube. Hydatidiform mole is the most common and a pre malignant form of GTD that occurs due to derranged fetal and placental development. Hydatidiform mole, a type of Gestational Trophoblastic disease, is an abnormal form of pregnancy/gestation which results from abnormal fertilization. Hydatidiform mole can either be a partial mole or complete mole. We report a case of a 30-year-old female with ruptured ectopic pregnancy, who initially presented with stable clinical status.

Measurement of Human Chorionic Gonadotrophin in Women with Gestational Trophoblastic Disease

Objectives: The objective of this study was to collect information on human chorionic gonadotrophin (hCG) laboratory testing and reporting in women with gestational trophoblastic disease (GTD), to assess the associated challenges, and to offer perspectives on hCG testing harmonisation. Design: Information was collected from laboratories by electronic survey (SurveyMonkey) using a questionnaire designed by members of the European Organisation for the Treatment of Trophoblastic Disease (EOTTD) hCG working party. Participants: The questionnaire was distributed by the EOTTD board to member laboratories and their associated scientists who work within the GTD field. Setting: The questionnaire was distributed and accessed via an online platform. Methods: The questionnaire consisted of 5 main sections. These included methods used for hCG testing, quality procedures, reporting of results, laboratory operational aspects, and non-GTD testing capability. In addition to reporting these survey results, examples of case scenarios which illustrate the difficulties faced by laboratories providing hCG measurement for GTD patient management were described. The benefits and challenges of using centralised versus non-centralised hCG testing were discussed alongside the utilisation of regression curves for management of GTD patients. Results: Information from the survey was collated and presented for each section and showed huge variability in responses across laboratories even for those using the same hCG testing platforms. An educational example was presented, highlighting the consequence of using inappropriate hCG assays on clinical patient management (Educational Example A), along with an example of biotin interference (Educational Example B) and an example of high-dose hook effect (Educational Example C), demonstrating the importance of knowing the limitations of hCG tests. The merits of centralised versus non-centralised hCG testing and use of hCG regression curves to aid patient management were discussed. Limitations: To ensure the survey was completed by laboratories providing hCG testing for GTD management, the questionnaire was distributed by the EOTTD board. It was assumed the EOTTD board held the correct laboratory contact, and that the questionnaire was completed by a scientist with in-depth knowledge of laboratory procedures. Conclusions: The hCG survey highlighted a lack of harmonisation of hCG testing across laboratories. Healthcare professionals involved in the management of women with GTD should be aware of this limitation. Further work is needed to ensure an appropriate, quality-assured laboratory service is available for hCG monitoring in women with GTD.

Effect of actinomycin D on ovarian reserve in low-risk gestational trophoblastic neoplasia

ObjectiveThis study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after chemotherapy.MethodsThis study recruited premenopausal women aged...

Perioperative Considerations for Hysterectomy in Second-Trimester Molar Pregnancy.

Second-trimester complete molar pregnancies are rare. Due to a later presentation, means to reduce surgical and long-term morbidity from hemorrhage, hyperthyroidism, and gestational trophoblastic neoplasia risk should be considered. A 48-year-old woman presented at 17 6/7 weeks of gestation with vaginal bleeding, with a human chorionic gonadotropin (hCG) level of 483,906 milli-international units/mL, biochemical hyperthyroidism, and ultrasonographic suspicion for complete molar pregnancy. The patient received preoperative uterine artery embolization and antithyroid medication before undergoing total abdominal hysterectomy. Her thyroid function and hCG level normalized by 1 week and 69 days postoperatively, respectively. Uterine artery embolization and hysterectomy may reduce surgical blood loss and lower the risk of malignancy for patients at high risk for gestational trophoblastic neoplasia. Preoperative treatment of hyperthyroidism with gestational trophoblastic disease can reduce morbidity from thyrotoxicosis.

HYPERTHYROIDISM SECONDARY TO GESTATIONAL TROPHOBLASTIC DISEASE : A LITERATURE REVIEW

Gestational trophoblastic disease (GTD) is a rare form of pregnancy-related cancer that is effectively treatable. GTD is accompanied by the potentially fatal complication of hyperthyroidism. We created a review consisting of five case reports. This case report was conducted on women who became pregnant when they were >35 years old. They showed consistent laboratory results, in which there was an increase in hCG levels. TSH and thyroid stimulating antibodies cannot account for the hyperthyroidism associated with GTD. The source of the thyroid stimulating agent is trophoblastic tissue. The thyrotropic effects of ?-hCG mediate GTD hyperthyroidism. Other research examined the prevalence of hyperthyroidism in women with normal pregnancy, hydatidiform mole, and choriocarcinoma who had ?-hCG serum levels below 100,000 IU/ml. Early prenatal screening may significantly reduce hyperthyroidism rates. Thyroid hormone synthesis inhibitors treat hyperthyroidism in pregnancy. Thioamides, propylthiouracil (PTU), and methimazole (MMI) are the most prevalent U.S. antithyroid medications (ATD). Plasmaphoresis may be an option for people who are resistant to therapy or need emergency surgery. GTD can cause fatal hyperthyroidism. Anti-thyroid medicines can handle most GTD hyperthyroidism. Surgery may be a possibility for patients refractory to medical treatment.

Gestational trophoblastic neoplasia of intermediate trophoblasts: Epithelioid trophoblastic tumor and placental site trophoblastic tumor, a study of morphologic, immunohistochemical, and next generation sequencing.

Gestational trophoblastic tumors are very rare neoplasms. We determined the distinctive morphological, immunohistochemical, and clinical features of placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT) in our cohort. Nine cases of PSTT and four cases of ETT were retrieved from the archives. Histomorphologic, immunohistochemical, and clinical features were noted. A molecular study was performed on one PSTT and one ETT case using next-generation sequencing. While the nodular pattern, geographic necrosis, and extracellular eosinophilic globules were peculiar to ETTs, vessel wall affinity, marked pleomorphism, intranuclear pseudoinclusion, spindle tumor cell, and vacuolar degeneration were more specific for PSTTs in our series. An immunohistochemical panel of p63, hPL, and CD146 were helpful for the exact typing of the tumor. p63 positivity supports the ETT and diffuse staining of hPL and CD146 supports the PSTT diagnosis. Three of the patients with metastatic disease (lung and brain metastasis) except one have a high mitotic count (12 and 8) and a long interval between (8 and 10 years) antecedent pregnancy and diagnosis. While KIT and TP53 mutations were observed only in PSTT, amino acid changes in KDR, APC, and SMAD4 genes were detected both in the ETT and PSTT cases. In the prediction of metastasis, the long intervals between antecedent pregnancy and diagnosis, deep myometrial invasion, mitotic count, and Ki67 proliferation index were involved rather than other histomorphological parameters, but none of the parameters is an absolute predictor of the metastasis.

The distinctive role of systemic immune-inflammatory parameters in gestational trophoblastic diseases

The distinctive role of systemic immune-inflammatory parameters in gestational trophoblastic diseases

Immunohistochemical expression of BCL-2 in hydatidiform moles: a tissue microarray study.

Hydatidiform moles (HM) are members of gestational trophoblastic diseases (GTD) and, in some cases, might progress to gestational trophoblastic neoplasia (GTN). HMs are either partial (PHM) or complete (CHM). Some HMs are challenging in arriving at a precise histopathological diagnosis. This study aims to investigate the expression of BCL-2 by immunohistochemistry (IHC) in HMs as well as in normal trophoblastic tissues "products of conception (POC) and placentas" using Tissue MicroArray (TMA) technique. TMAs were constructed using the archival material of 237 HMs (95 PHM and 142 CHM) and 202 control normal trophoblastic tissues; POC and unremarkable placentas. Sections were immunohistochemically stained using antibodies against BCL-2. The staining was assessed semi-quantatively (intensity and percentage of the positive cells) in different cellular components (trophoblasts and stromal cells). BCL-2 showed cytoplasmic expression in more than 95% of trophoblasts of PHM, CHM and controls. The staining showed a significant reduction of the intensity from controls (73.7%), PHMs (76.3%) to CHM (26.9%). There was a statistically significant difference between PHM and CHM in the intensity (p-value 0.0005) and the overall scores (p-value 0.0005), but not the percentage score (p-value > 0.05). No significant difference was observed in the positivity of the villous stromal cells between the different groups. All cellular components were visible using the TMA model of two spots/case (3 mm diameter, each) in more than 90% of cases. Decreased BCL-2 expression in CHM compared to PHM and normal trophoblasts indicates increased apoptosis and uncontrolled trophoblastic proliferation. Construction of TMA in duplicates using cores of 3 mm diameter can overcome tissue heterogeneity of complex lesions.

Evaluation of change in RECIST tumor size and survival in patients with rare cancers treated with checkpoint inhibitor therapy (SWOG S1609).

2504 Background: RECIST has been used for over twenty years to evaluate changes in tumor burden. At each scan, the sum of maximum diameters of “target” lesions are measured. Changes in the sum are categorized into an “objective status” at each scan, including complete and partial response and stable and progressive disease. Prior research among patients treated with chemotherapy did not find a threshold effect corresponding to the RECIST categories; instead a linear association was observed. Herein we use a unique clinical trial resource, a basket trial of patients with rare cancer treated with combination anti-CTLA-4 and anti-PD-1 therapy, to evaluate the association between quantitative change in RECIST tumor burden and survival among patients treated with checkpoint inhibitor therapy. Methods: The study population was 796 patients enrolled on the S1609 DART (Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors) trial, a basket immunotherapy trial evaluating ipilimumab plus nivolumab across solid rare tumor subtypes. The analysis population was 720 patients; patients not eligible (n=50; mostly due to non-rare diagnosis), THOSE who did not receive protocol therapy (n=22), OR WHOSE DISEASE WAS NOT evaluated by RECIST (n=4; gestational trophoblastic disease evaluated by -hCG) were excluded. All patients had RECIST-measurable disease at study entry. Associations between overall and progression-free survival (OS and PFS) and change in tumor burden between baseline and the first scan were evaluated using log-rank tests and Cox regression models stratified by basket. Landmark analyses (at day 65) controlled for lead-time bias. Linear regression models and R2 were estimated for median and 2-year estimates across tumor change intervals. Results: The median age of the cohort was 61, 52% werethe distribution of percent change in tumor burden at the first scan. The linear correlation between median and 6-month PFS and change in tumor burden had R2 = 0.92 and 0.74.; median and 1-year OS had R2 = 0.79 and 0.79. Martingale residuals for both PFS and OS showed linear trends up to tumor increase of +50% with no thresholds at definitions of partial response or stable disease. Conclusions: This is the first evaluation of the association between numeric changes in RECIST tumor burden among patients receiving checkpoint therapy. Our results suggest that similar to results among patients who received chemotherapy there is a linear correlation with PFS and OS. As a consequence, the thresholds for RECIST categories do not correspond to thresholds in patient outcomes. [Table: see text]

Reconsideration of the Diagnostic Criteria for an Atypical Placental Site Nodule Comparing Typical Placental Site Nodule of the Uterus: A Report of Two Cases.

Placental site nodules (PSNs) are non-neoplastic remnants of chorionic-type intermediate trophoblastic cells from a previous gestation that form a well-defined single nodule or multiple nodules in the uterine and extrauterine sites. As the cases of PSNs transformed into gestational trophoblastic tumors were described in the literature, "atypical placental site nodules" (APSNs) have been considered as putative transitional lesions between PSNs and gestational trophoblastic tumors. Although histologic criteria and cutoff point of Ki-67 proliferation index for differentiating an APSN from a typical PSN have not been clearly defined, nodules larger than 5 mm with increased cellularity, a corded or nested appearance, marked nuclear atypia, increased mitotic activity, and an increased Ki-67 proliferation index (>5% or >8%) of intermediate trophoblastic cells seem to be accepted as diagnostic criteria for APSNs. However, some of the criteria, including lesion size and histologic features of the trophoblastic cells in the nodule are not only subjective but have features inherent of the intermediate trophoblastic cells of the fetal membrane and a typical PSN. We thought that it is not reasonable to consider them as diagnostic features of APSNs, if not associated with cellular proliferation. We present 2 cases of incidentally identified PSNs that were larger than 10 mm in size with a corded or nested arrangement of trophoblastic cells, which could have been categorized as APSNs according to the currently proposed criteria to discuss whether the currently proposed diagnostic criteria for APSNs are appropriate.

Symptoms of anxiety and depression in women with gestational trophoblastic disease compared to women who had a miscarriage: a cross-sectional study

This study was conducted between March 2020 and February 2021 to analyze anxiety and depression symptoms in 64 women with gestational trophoblastic disease (GTD) and 99 women who had miscarried. The Hospital Anxiety and Depression Scale (HADS) was applied by telephone three months after pregnancy loss. Multivariate analysis was performed using hierarchical logistic regression to evaluate associations between variables. Probable anxiety (HADS-A ≥ 8) and depression (HADS-D ≥ 8) were found in 53.1% and 43.8% of the GTD group and 49.5% and 39.4% of the miscarriage group, with no difference between the groups. Severe symptoms of anxiety (HADS-A 15-21) and depression (HADS-D 15-21) were found, respectively, in 12.5% and 4.7% of the GTD group and in 9.1% and 4.0% of the miscarriage group, also with no difference between the groups. Lack of partner support proved a risk factor for anxiety and depression, while poor education increased the risk of depression symptoms 3.43-fold following pregnancy loss. In conclusion, three months after pregnancy loss the frequency of anxiety and depression symptoms was similarly high in both groups, with poor education and lack of partner support being significant risk factors for the subsequent development of psychiatric morbidity.

Hydatidiform Mole Types and Age Demographics in Sindh Province, Pakistan

Hydatidiform mole can be classified as partial and complete depending on the clinical and histopathological features. There is regional variation in incidence of hydatidiform mole with more cases seen in Asia, Africa and other developing countries. This cross-sectional descriptive study was done at the department of histopathology in Diagnostic and research laboratory Hyderabad Sindh. A total of 261 cases were added in the study including 251 cases of suction and evacuation and 10 cases of hysterectomy. The mean age was 27.16±6.66 with age range of 17-60 years. In our study out of 260 samples, 155(59.6%) were of complete mole while 105(40.4%) were of partial mole. The incidence of mole was highest in the age group 26-30 years. The prevalence of hydatidiform mole was notably higher in comparison to numerous other studies. In conclusion, it is recommended that all abortion specimens undergo evaluation to prevent misdiagnosis of gestational trophoblastic disease and to ensure appropriate treatment and follow-up, thereby minimizing the risk of complications. Keywords: Hydatidiform mole. Complete mole. Partial mole. Molar pregnancy.