UNASSIGNED: Epithelioid endothelial tumor (ETT) is an extremely rare tumor that typically occurs in women of reproductive age. The diagnosis tends to be delayed because it often necessitates a total hysterectomy. Therefore, it is important to understand ETT macroscopic and imaging findings. Here, we report a case of ETT with detailed macroscopic and imaging findings.
UNASSIGNED: A 39-year-old woman with positive pregnancy test results was admitted to a nearby hospital. No gestational sac was found in the uterus, and magnetic resonance imaging (MRI) revealed a cystic mass of approximately 7 cm that extended continuously from the anterior wall of the lower uterine segment into the pelvic cavity. She underwent laparoscopic and hysteroscopic surgeries for a ruptured cervical pregnancy. Pathology of the specimens obtained from this surgery did not allow for the diagnosis of ETT. Two months after the surgery, as the serum human chorionic gonadotropin β subunit (β-HCG) level did not decrease, she was diagnosed with low-grade gestational trophoblastic neoplasia, leading to the administration of chemotherapy. After three regimens of chemotherapy over 9 months, her β-HCG level decreased but did not reach normal levels. Ultimately, a total hysterectomy was performed. The pathological diagnosis was mixed ETT and choriocarcinoma. A literature review revealed several cases similar to ours.
UNASSIGNED: ETT in the lower uterus often perforates the myometrium and forms cystic lesions in the retroperitoneal space or subserosa. The MRI and laparoscopic/hysteroscopic findings in this case may have contributed to the early diagnosis of ETT.

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection rather than additional salvage chemotherapy or high-dose intense chemotherapy might provide a superior clinical outcome and enhance cure rate.

BACKGROUND: Epithelioid Trophoblastic Tumor (ETT) and Placental Site Trophoblastic Tumor (PSTT) are two of the rarest GTNs that share certain features at diagnosis and management. Atypical Placental Site Nodule (APSN) is a relatively new entity considered as a premalignant lesion.
OBJECTIVE: The aim of this review was to summarize the main characteristics of each of these entities, their diagnostic features, and their treatment\'s standard of care including fertility-sparing treatments.
RESULTS: This study provides a thorough review of ETT, PSTT, and APSN.
CONCLUSIONS: The reader will gain an insight view of these rare tumors arising from the intermediate trophoblast.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Gestational trophoblastic neoplasia (GTN) is a group of rare tumors characterized by abnormal trophoblastic proliferation following pregnancy including invasive moles, choriocarcinomas, and intermediate trophoblastic tumors (ITT). Although the treatment and follow-up of GTN has been heterogeneous, globally the emergence of expert networks has helped to harmonize its management.
We provide an overview of the current knowledge, diagnosis, and management strategies in GTN and discuss innovative therapeutic options under investigation. While chemotherapy has been the historical backbone of GTN treatment, promising drugs such as immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway and anti-angiogenic tyrosine kinase inhibitors are currently being investigated remodeling the therapeutical landscape of trophoblastic tumors.
Chemotherapy regimens for GTN have potential long-term effects on fertility and quality of life, making innovative and less toxic therapeutic approaches necessary. Immune checkpoint inhibitors have shown promise in reversing immune tolerance in GTN and have been evaluated in several trials. However, immunotherapy is associated with rare but life-threatening adverse events and evidence of immune-related infertility in mice, highlighting the need for further research and careful consideration of its use. Innovative biomarkers could help personalize GTN treatments and reduce chemotherapy burden in some patients.

Epithelioid trophoblastic tumor (ETT) is a rare malignancy arising from neoplastic proliferation of chorionic-type intermediate trophoblasts. ETT poses significant challenges to clinicians in the diagnosis and treatment and can hence lead to a poor prognosis. We report a unique case of metastatic ETT in a HIV-positive patient.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is the rarest type of gestational trophoblastic tumor (GTT). It has been reported that more than 50% of ETTs arise in the uterine cervix or the lower uterine segment. Here, we report a case of ETT within the lower uterine segment and cervical canal and discuss its manifestations, possible causes, and related influencing factors.
METHODS: A 35-year-old woman (gravida 7, miscarriage 3, induction 2 with 1 being twins, para 2 of cesarean section, live 2), who had amenorrhea for 9 mo after breastfeeding for 22 mo after the last cesarean section, was diagnosed with ETT. The lesion was present in the lower uterine segment and endocervical canal with severe involvement of the anterior wall of the lower uterine segment and the front wall of the lower uterine segment where the cesarean incisions were made. Laboratory tests showed slight elevation of serum beta-human chorionic gonadotropin. Intraoperative exploration showed the presence of a normal-sized uterus body with an enlarged tumor in the lower uterine segment. The surface of the lower uterine segment was light blue, the entire lesion was approximately about 8 cm × 8 cm × 9 cm, with compression and displacement of the surrounding tissue. Histological examination diagnosed ETT. Immunohistochemical analysis showed positive expression of p63, with a Ki-67 proliferation index of 40%.
CONCLUSIONS: A search of the PubMed database using the search terms \"cesarean section\" and \"epithelioid trophoblastic tumor\" retrieved nine articles, including 13 cases of ETT and ETT-related lesions, all 13 cases had a history of cesarean section, and the lesions were all located at the cesarean section incision on the anterior wall of the lower uterine segment. The present case is the 14th reported case of ETT after cesarean section. Therefore, we deduced that cesarean section trauma had an important effect on the occurrence of ETT at this site.

Gestational trophoblastic diseases derived from the chorionic-type intermediate trophoblast include benign placental site nodule (PSN) and malignant epithelioid trophoblastic tumor (ETT). Among PSNs, the World Health Organization classification introduced a new entity named atypical placental site nodule (APSN), corresponding to an ETT precursor, for which diagnostic criteria remain unclear, leading to a risk of overdiagnosis and difficulties in patient management. We retrospectively studied 8 PSNs, 7 APSNs, and 8 ETTs to better characterize this new entity and performed immunohistochemical analysis (p63, human placental lactogen, Cyclin E, and Ki67), transcriptional analysis using the NanoString method to quantify the expression of 760 genes involved in the main tumorigenesis pathways, and RNA sequencing to identify fusion transcripts. The immunohistochemical analysis did not reveal any significant difference in Cyclin E expression among the 3 groups (P = .476), whereas the Ki67 index was significantly (P < .001) higher in ETT samples than in APSN and PSN samples. None of the APSN samples harbored the LPCAT1::TERT fusion transcripts, in contrast to 1 of 6 ETT samples, as previously described in 2 of 3 ETT samples. The transcriptomic analysis allowed robust clustering of ETTs distinct from the APSN/PSN group but failed to differentiate APSNs from PSNs. Indeed, only 7 genes were differentially expressed between PSN and APSN samples; CCL19 upregulation and EPCAM downregulation were the most distinguishing features of APSNs. In contrast, 80 genes differentiated ETTs from APSNs, establishing a molecular signature for ETT. Gene set analysis identified significant enrichments in the DNA damage repair, immortality and stemness, and cell cycle signaling pathways when comparing ETTs and APSNs. These results suggested that APSN might not represent a distinct entity but rather a transitional stage between PSN and ETT. RNA sequencing and the transcriptional signature of ETT described herein could serve as triage for APSN from curettage or biopsy material, enabling the identification of cases that need further clinical investigations.

Gestational trophoblastic diseases (GTD) encompass a spectrum of rare pre-malignant and malignant entities originating from trophoblastic tissue. This updated review will highlight important radiological features, pathology and classification, and provide insight into the clinical management of these uncommon disorders. There is a wide geographic variation with the incidence of hydatidiform mole varying between 0.57 and 2 per 1000 pregnancies. The use of ultrasound (US) in the management of early pregnancy symptoms and complications has positively impacted the earlier detection of these diseases and resulted in diminished morbidity. Additional imaging modalities are reserved for problem solving or assessment of pulmonary manifestations of molar pregnancy. Having an awareness of their pleomorphic sonographic presentation and additional pathology that can mimic GTD is critical to avoiding pitfalls. Histologic and molecular analysis further aids in differential diagnosis. Gestational trophoblastic neoplasia (GTN) is inclusive of all malignant GTDs, and arises after 20% of molar pregnancies but can also be seen with non-molar gestations. Biochemical monitoring with human chorionic gonadotrophin is imperative for ongoing monitoring and surveillance and allows early detection of this entity. Doppler US is used for confirmation of diagnosis with magnetic resonance imaging (MRI) reserved for problem solving or assessment of myometrial invasion. This is of heightened relevance in patients undergoing surgical management. Cross sectional imaging is reserved for patients in the setting of GTN for the purposes of staging, prognostication and in the setting of recurrent disease. This may require a combination of computed tomography, MRI and positron emission tomography. Doppler US can provide insight into chemotherapeutic response/predict resistance in patients with GTN. As our understanding of these disorders evolves, there has been maturation in management options with a shift from traditional chemotherapy to innovative immunotherapy, particularly in the setting of resistant or high-risk disease.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is a special type of gestational trophoblastic tumor. However, its pathogenesis has been incompletely elucidated. ETT rarely occurs in the ovaries and fallopian tubes, unlike placental site trophoblastic tumor, requiring a histopathological biopsy and immunohistochemistry for further diagnosis.
METHODS: A 29-year-old woman with irregular vaginal bleeding and elevated serum chorionic gonadotropin (β-hCG) levels presented similar symptoms to ectopic pregnancy. Transvaginal ultrasound revealed abnormal echoes of the left adnexa. Postoperatively, the pathology of the left ovary and fallopian tube was reported as ETT. The patient was followed up with regular hCG measurements and ultrasounds. The blood hCG values showed an upward trend 3 mo after the operation and then chemotherapy was prescribed. The current health status is normal.
CONCLUSIONS: For women of childbearing age with elevated serum β-hCG levels, practitioners should consider ETT and be alert to the poor prognosis of the disease. After surgery, the patient\'s condition should be closely observed to prevent recurrence and metastasis. Postoperative chemotherapy is only helpful for treating the disease to a certain extent.