Types Of Gestational Trophoblastic Neoplasia Research Articles

Epithelioid Trophoblastic Tumor—A Challenge to Manage due to Its Rare Existence: A Case Report with Review of Literature

AbstractEpithelioid trophoblastic tumor (ETT) is the rarest type of gestational trophoblastic neoplasia. It has variable presentations and is an aggressive tumor. Because of its rarity, it is difficult to establish an appropriate diagnosis, management, and follow-up. A woman of age 45 years postmenopausal status with an antecedent term pregnancy 13 years back was diagnosed to have ETT in the hysterectomy specimen. She had come with urinary retention as the tumor was infiltrating the bladder. Beta-human chorionic gonadotropin levels were normal. Immunohistochemistry confirmed the diagnosis. Though metastatic workup was normal, adjuvant multiagent chemotherapy was given as the bladder flap margin was not free of tumor cells and antecedent pregnancy was > 4 years. Every new case of ETT needs to be reported to bring about more awareness of the unusual presentations, and it may help come to a consensus for appropriate management.

Misdiagnosis of epithelioid trophoblastic tumors: a case report and literature review

Background: The most common clinical types of gestational trophoblastic neoplasia are invasive hydatidiform mole and choriocarcinoma, which can be diagnosed without pathology, and be cured by chemotherapy. Epithelial trophoblastic tumor, a rare type of gestational trophoblastic neoplasia, does not exhibit precise clinical manifestations upon auxiliary examinations. Therefore, since epithelial trophoblastic tumors are prone to misdiagnoses and missed diagnoses, their diagnosis have to be confirmed through pathology and immunohistochemistry. Case: We describe a case of a 37-year-old woman that had been misdiagnosed at a local hospital after she had presented with irregular vaginal bleeding and elevated human chorionic gonadotropin. The initial diagnosis was ectopic pregnancy and she was subjected to left salpingectomy, however, after treatment, there was no significant drop in human chorionic gonadotropin. Later, she was diagnosed with gestational trophoblastic neoplasia and was treated with multiple chemotherapy and hysterectomy. However, after treatment, her human chorionic gonadotropin was found to repeatedly fluctuate. Eventually, pathological examination of a resected lung lesion confirmed the presence of epithelial trophoblastic tumors. Conclusions: Epithelial trophoblastic tumor is an intermediate trophoblastic tumor that is not sensitive to conventional chemotherapy. Surgical resection is the recommended therapeutic option. Gestational trophoblastic neoplasia patients presenting with persistently low levels of human chorionic gonadotropin and resistance to conventional chemotherapy should, therefore, be considered for early surgical resection, or tissue biopsy to pathologically confirm the diagnosis and inform treatment options.

Gestational trophoblastic neoplasia with extrauterine metastasis but lacked uterine primary lesions: a single center experience and literature review.

BackgroundTo investigate the clinicopathological characteristics, diagnoses, treatments, and outcomes of a special type of gestational trophoblastic neoplasia (GTN) which only has extrauterine metastases without uterine primary lesions.MethodsThe medical records and pathological sections of the patients who were pathologically diagnosed as GTN, only had extrauterine metastatic lesions but lacked uterine primary lesions, in Women’s Hospital of Zhejiang University School of Medicine from February 2014 to March 2021 were collected and reviewed.ResultsThirteen patients with pathologically confirmed GTN presenting with extrauterine metastases from a missing primary site were included in the past 7 years. The median age was 31.2 years old. 76.9% of patients had a non-hydatidiform pregnancy last time. The intervals between the antecedent pregnancy were > 12 months in 61.5% of patients. Pretreatment serum human chorionic gonadotropin(hCG) levels ranged from 118.7 to 807,270 IU/L. Six patients were misdiagnosed as ectopic pregnancy at initial diagnosis, and 4 as primary tumors at metastatic sites. All of them were diagnosed definitely by surgical pathology including 8 choriocarcinomas (CC), 4 epithelioid trophoblastic tumors (ETTs), and 1 mixed GTN (CC mixed with ETT). All patients achieved complete remission (CR) after treatments. Three patients relapsed; no patient died by the end of follow-up.ConclusionGTN presenting with extrauterine metastases from a missing primary site is easily misdiagnosed. Detection of serum hCG in these patients can reduce misdiagnosis. Chemotherapy combined with individualized surgery should be considered for these special GTN patients. Immune checkpoint inhibitors might be potential remedial measures for refractory and recurrent patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-022-09620-2.

The impact of previous cesarean section (C/S) on the risk for post-molar gestational trophoblastic neoplasia (GTN)

ObjectiveTo investigate the relationship between previous cesarean section (C/S) and risk for post-molar gestational trophoblastic neoplasia (GTN). MethodsData from patients who were treated for hydatidiform moles between 1995 and 2016 were retrospectively reviewed. Patient age, gravidity, parity, abortion history, gestational age, pretreatment beta-human chorionic gonadotropin (HCG), previous molar pregnancy, clinical symptoms, enlarged uterus, theca lutein cyst, type of GTN, World Health Organization risk score, chemotherapy, and mode of delivery were recorded. Hazard ratios (HR) and 95% confidence intervals (CI) for variables associated with the occurrence of post-molar GTN and invasive mole were estimated by univariate and multivariate Cox proportional hazards models. ResultsFrom 1995 to 2016, 182 patients were diagnosed with molar pregnancy and underwent treatment. Patients with previous C/S (C/S group) had higher age (37.0 vs 32.8. p = 0.004), gravidity (3.1 vs 2.0, p < 0.001), and parity (1.6 vs 0.9, p < 0.001) than patients without previous C/S (non-C/S group). Post-molar GTN (43.5 vs 26.5%, p < 0.001), invasive mole (21.7 vs 3.7%, p < 0.001), hysterectomy (28.3 vs 6.6%, p < 0.001), and chemotherapy (45.7 vs 28.7%, p = 0.03) were more frequent in the C/S group. In multivariate analysis, independent risk factors for post-molar GTN were previous C/S (HR 5.1, 95% CI 2.1–12.7), abortion history (HR 6.3, 95% CI 2.5–15.6), and pretreatment β-hCG (HR 1.3, 95% CI 1.1–1.6). ConclusionsIn this study, C/S was a strong risk factor for occurrence of post-molar GTN and invasive mole. Aggressive treatment, such as multi-agent chemotherapy or hysterectomy, can be considered for hydatidiform moles in patients with a C/S history.

Clinical characteristics and outcomes of extrauterine epithelioid trophoblastic tumors.

Epithelioid trophoblastic tumor (ETT) derived from intermediate trophoblasts is one type of gestational trophoblastic neoplasia (GTN), and it accounts for less than 2% of all gestational trophoblastic diseases (GTD). Extrauterine ETT is extremely rare, and there is currently no consistent strategy for its treatment and management. Therefore, the aim of the study is to analyze and summarize the clinicopathologic features of extrauterine ETT with or without metastasis. The Web of Knowledge, Google Scholar, EMbase, congress of library, and PubMed were searched for extrauterine ETT without primary uterine lesions. All available data were extracted from published case reports or serial case reports, and then, the clinical and pathological characteristics were analyzed. Twenty-two clinical studies consisting of 27 patients diagnosed with extrauterine ETT, according to the given inclusion and exclusion criteria, were included in the study. A total of 27 cases of extrauterine ETT were identified. Of these cases, four (14.81%) were located in the lungs, three (11.11%) in the ovaries, two (7.41%) in the vagina, and eight (29.63%) patients had other primary lesions. The patients originated from different continents, with 59% located in Asia and 26% in North America. Among 23 patients, the antecedent pregnancy prior to the diagnosis was full-term in 12 cases, abortion in 6 cases, hydatidiform mole in 3 cases, and invasive mole in 1 case. From the available antecedent information on pregnancy, the median interval from pregnancy to diagnosis of extrauterine ETT was 4years. Additionally, the median gravidity and para of the patients was three times and two times, respectively. The median hCG titer was 14,374mIU/mL in 5 patients, and the mean β-HCG titer was 3,724,805mIU/mL in 14 patients. For all patients, the disease was confined to extrauterine ETT at diagnosis. From the available information, 20 cases were successfully treated by extraction of local lesions, and 12 cases received chemotherapy. Diagnosis was confirmed by histological tests. The Ki-67 staining ranged from 8.7 to 80%, and tumors were positive for hCG, PLAP, EMA, and p63. In this study, we observed that abnormal levels of serum hCG titers and the local presentation of lesions with varying intervals after antecedent term pregnancy were the most common presenting features of extrauterine ETT. In addition, we found that the extraction of extrauterine lesions was needed for the treatment of extrauterine ETT. Of course, the follow-up was also important.

Lapatinib Inhibits Amphiregulin-induced BeWo Choriocarcinoma Cell Proliferation by Reducing ERK1/2 and AKT Signaling Pathways.

Human choriocarcinoma is the most aggressive type of gestational trophoblastic neoplasia. The expression of epidermal growth factor receptor (EGFR) in choriocarcinomas is significantly higher than those of trophoblastic cells in healthy placentas. Lapatinib is a potent EGFR and human epidermal growth factor receptor 2 (HER2) inhibitor that inhibits cell proliferation and induces apoptosis in various human cancer cells. Amphiregulin (AREG) is the most abundant EGFR ligand in amniotic fluid during human pregnancy. To explore the role of AREG in human choriocarcinoma cell proliferation. The effect of lapatinib and AREG on cell proliferation was examined by the MTT assay. Western blots were used to investigate EGFR and HER2 expression, and the activation of caspase-3, extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) signaling pathways. Treatment with lapatinib reduced BeWo cell proliferation by inducing apoptosis. Moreover, AREG treatment stimulated BeWo cell proliferation by activating ERK1/2 and PI3K/AKT signaling pathways, which was blocked by lapatinib. Targeting EGFR/HER2 might be a useful therapeutic strategy for human choriocarcinoma.

The Controversy of Hydatidiform Mole Treatment In Women age ≥ 40 year-old

&lt;p&gt;Background: Hydatidiform mole or commonly known as molar pregnancy is one of the gestational trophoblastic disease (GTD) caused by an abnormal trophoblast proliferation. About 50% of gestational trophoblast neoplasm (GTN) arises from molar pregnancy. Higher risk of GTN was found in older patient, especially women age ≥40 years old. Management of hydatidiform mole is often faced come challenges, especially in developing country like Indonesia. Although, suction curettage is the most recommended treatment for the evacuation of molar pregnancy, hysterectomy is considerable for women who have completed childbirth and do not wish to preserve their fertility.&lt;br /&gt;Case: Here we present case of 48 years old women with hydatidiform mole. Considering the age of the patient and the completion of her childbearing, we decided to do a laparotomy total abdominal hysterectomy for the evacuation of the mole instead of suction curettage. Turned out that this patient had an invasive mole, one of the types of gestational trophoblastic neoplasia.&lt;br /&gt;Conclusion: Although suction curettage is the most frequent technique for molar evacuation, hysterectomy is a reasonable option as primary treatment to be performed in older patients and for those who do not wish to preserve their fertility. The other important points such as socio-economic status, education level, and geographical issues should be considered also on managing older patients with hydatidiform mole in developing countries&lt;/p&gt;

Comment on "Retained Placenta Accreta Mimicking Choriocarcinoma".

We read the presented case of retained invasive placenta mimicked gestational choriocarcinoma (GCC) with an enthusiasm [1]. We thought if this is a case of GCC, which sign should be the leading sign. The clinical diagnosis of GCC is challenging in most of the cases. The predominant symptom is abnormal vaginal bleeding. Serum human chorionic gonadotropin beta (β-hCG) measurement and doppler ultrasonography examination are the leading diagnostic work-ups. Contrast-enhanced MRI is also useful for detecting an abundant blood flow in the tumor. In this case, authors did not consider to use MRI study. The authors demonstrated a serum β-hCG level of 203 IU/L, which is unlikely in cases with GCC. One should expect β-hCG measurements exceeding 100.000 IU/L in GCC [2]. This finding decrease its likelihood to be a GCC. Instead of a GCC, authors could compose their theory on the other types of gestational trophoblastic neoplasia, which are placental site trophoblastic tumor, epithelioid trophoblastic tumor, or placental site nodule. Additionally, although the authors demonstrated increased vascularity on doppler ultrasonography, the color flow pattern was seen just at the uteroplacental contiguity, not all around the mass. The presented case was a dichorionic diamniotic twin pregnancy in a nulliparous pregnant woman with 2 previous first trimester curettage operations. Authors said that the third stage of labor was complicated by retained placenta, and placentas were extracted manually and with banjo curettage under ultrasound guidance. It is possible that one of the placentas or a cotyledon was retained, was left in situ, and was not perceived during elimination process towards the placenta. In our opinion, considering the suggested findings, this case is a typical presentation of a case of morbidly adherent placenta. It would be improper to build up a theory upon findings which does not meet the GTN criteria exactly, and it would be improper to make a preliminary diagnosis of GCC in this unique case.

Vaginal carcinoma after hysterectomy for invasive hydatidiform mole: a diagnostic dilemma between epithelioid trophoblastic tumor and vaginal cancer

Vaginal cancer is an uncommon type of gynecologic malignancy. The occurrence of vaginal carcinoma after a hysterectomy in the absence of a prior cervical epithelial lesion is very uncommon, and that after a hysterectomy for hydatidiform mole is extremely rare. Hydatidiform mole is a well-recognized precursor lesion for several types of gestational trophoblastic neoplasia, including epithelioid trophoblastic tumor which has overlapping histologic features with epithelial carcinoma. Epithelioid trophoblastic tumor typically develops many years after a previous pregnancy and sometimes may not be associated with clinical elevation of serum hCG. In this report, a 51-year-old woman presented with a vaginal mass after a previous hysterectomy for an invasive complete hydatidiform mole 7 years before. The histomorphology of tumor in the vaginal biopsy raised a diagnostic dilemma between epithelioid trophoblastic tumor and poorly differentiated vaginal carcinoma. A panel of immunohistochemical stains, including p63, pl6 and CK5/6, helps confirm the diagnosis of squamous cell carcinoma of the vagina. A correct diagnosis is important as the treatment regimen is similar to that of locally advanced cervical cancer using chemoradiation therapy.

Placental site and epithelioid trophoblastic tumours: Diagnostic pitfalls

ObjectiveTo describe the clinical and histological pitfalls in the diagnosis of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT), two rare types of gestational trophoblastic neoplasia (GTN). MethodsThis retrospective, observational, study was carried out in the French Trophoblastic Disease Reference Centre, Lyon, between 2000 and 2011. Due to the many similarities in the diagnosis, treatment and prognosis of PSTT and ETT, these two types of tumour were investigated together. Twenty-two patients with PSTT or ETT were analysed. ResultsThe clinical presentation of these two types of tumour was irregular vaginal bleeding (55%) or amenorrhoea (27%), with a median plasma hCG level of 205IU/L. Seven of the 22 patients (32%) were initially misdiagnosed as an ectopic pregnancy. Median age at presentation was 35-years, with a median interval of 12months between the antecedent pregnancy and diagnosis of PSTT or ETT. The initial histological diagnosis was incorrect in 7/18 (39%) patients; there was a major disagreement with the referral pathologist in five of these seven patients (28%). ConclusionsPSTT and ETT are the most difficult types of GTN to diagnose clinically and histologically. An incorrect diagnosis can lead to significant therapeutic deviations from the recommended first-line treatment, namely hysterectomy. Clinical and histological expertise is essential to avoid the pitfalls in the diagnosis of PSTT and ETT.

A Profile of Cases of Gestational Trophoblastic Neoplasia at a Large Tertiary Centre in Dubai

Objectives. To study (1) the prevalence of different types of gestational trophoblastic neoplasia (GTN) in the local and nonlocal population of women at Al Wasl Hospital, a tertiary level referral centre for northern Emirates, (2) the safety of cervical preparation before uterine evacuation, (3) the role of repeat uterine evacuation in curing these cases, and (4) the percentage of cases ultimately requiring chemotherapy. Material and Methods. Retrospective analysis of case records of 35 women with diagnosis of gestational trophoblastic neoplasia were managed in the Department of Obstetrics and Gynecology at Al Wasl Hospital, over a 2-year period between January 2007 to December 2008. Results. 35 cases of gestational trophoblastic neoplasia were seen in a 2-year period (January 2007 to December 2008) at Al Wasl Hospital, with 7000 deliveries per year, prevalence being 1 in 400 live births. 60% cases were local Arabs. Histopathology revealed complete mole in 13 cases, partial mole in 17 cases, hydropic degeneration of villi in 4 cases, and no identifiable tissue in 1 case. No cases of choriocarcinoma or placental site trophoblastic tumour were seen during the study period. 34% cases received cervical preparation with prostaglandins prior to surgical curettage. Complications were minor. 62% were cured by primary suction curettage, 12% after second (repeat) uterine evacuation, and 25% needed single drug chemotherapy. 8% cases defaulted after primary evacuation and were lost to followup. Conclusions. Prevalence of GTN in the local Arab population is similar to other Asian populations. The majority of cases are cured by simple suction uterine curettage. Cervical preparation with prostaglandins should be done in selected cases to avoid perforation during evacuation. Second (repeat) uterine evacuation can be curative in some cases with strict selection criteria and avoid the need for chemotherapy. Regional registry of cases is needed to estimate the true incidence of this disease.

Differentiating Squamous Cell Carcinoma of the Cervix and Epithelioid Trophoblastic Tumor

Epithelioid trophoblastic tumor (ETT) is a recently described subtype of gestational trophoblastic neoplasia (GTN). Its diagnosis requires a high level of suspicion because it is often mistaken for more common cervical or uterine corpus epithelial neoplasms. This is a 39-year-old woman who presented with a cervical mass and positive human chorionic gonadotropin and was diagnosed with both locally advanced squamous cell cervical carcinoma and nonmetastatic GTN. She was treated unsuccessfully with concurrent intravenous cisplatin plus pelvic radiation and single-agent intravenous methotrexate. A retrospective review of the cervical biopsy using immunohistochemistry as well as genotyping of the tumor changed the original diagnosis to ETT. It is known that ETT is relatively unresponsive to chemotherapy compared with most other types of GTN; therefore, surgery would have been the optimal treatment. She died despite multiple salvage chemotherapies. Malignant GTN is one of the most curable gynecologic malignancies; however, its correct diagnosis is critical for the appropriate treatment. It can be easily misdiagnosed as a carcinoma because of their morphologic similarity. Genetic fingerprinting and immunohistochemistry are potentially valuable tools to confirm the diagnosis of ETT.

Ovarian Involvement of Epithelioid Trophoblastic Tumor

Epithelioid trophoblastic tumor (ETT) is an uncommon type of gestational trophoblastic neoplasia originating from the chorionic-type intermediate trophoblast. To our knowledge, ovarian involvement of ETT with initial presentation as an ovarian tumor has not been reported. A 32-year-old woman presented with a 9-cm left ovarian mass. No clinical evidence of uterine involvement was identified at diagnosis or follow-up. The patient had a previous history of hydatidiform mole treated with suctional curettage 5 years before. Ovarian involvement of ETT can be challenging to pathologists and may be potentially confused with ovarian epithelial carcinoma, particularly of clear cell differentiation.

Clinical importance of the diagnosis of trophoblastic pseudotumors

Trophoblastic pseudotumor, a type of gestational trophoblastic neoplasia, is discussed in the context of a case report. The criteria for diagnosis, lack of placental villi, cytotrophoblast, extensive hemorrhage, and necrosis, can only be fulfilled on histopathologic study of a hysterectomy specimen. Clinical management should be based on the titer of the beta subunit of human chorionic gonadotropin, not on the type of gestational trophoblastic neoplasia.