Extrauterine Epithelioid Trophoblastic Tumor (ETT) Arising from an Antecedent Undiagnosed Molar Pregnancy Presenting as an Adnexal mass: A Case Report

Introduction/Objective Epithelioid trophoblastic tumor (ETT) is an extremely rare neoplasm derived from chorionic type intermediate trophoblast. ETT usually follows an antecedent term pregnancy but can also follow spontaneous abortions or molar pregnancy. ETT most often arises from the endometrium, followed by the cervix. Extrauterine ETT are extremely rare, with few cases reported in literature. Methods/Case Report A 41-year-old woman with three term pregnancies presented with abdominal pain, ten years after her last pregnancy. Imaging findings of a 3.5 cm adnexal mass coupled with an elevated serum β-hCG (~ 900 mIU/ml), led to the suspicion of an ectopic pregnancy. Hysterectomy with salpingectomy revealed a 4.7 cm, tan- yellow, necrotic mass in the adnexal region abutting but distinct from the uterine serosa. Histologic evaluation showed a well- circumscribed tumor with pushing borders. The tumor cells were epithelioid with well-defined eosinophilic cytoplasm, monomorphic nuclei, frequent mitosis, and abundant geographic necrosis. The tumor cells were positive for β-hCG, GATA-3, PLAP and inhibin, with focal weak staining squamous markers p63 and p40. DNA fingerprinting analysis, performed to confirm the diagnosis of ETT, revealed a homozygous tumor with two copies of non-maternal genes indicating that the antecedent index gestation giving rise to the tumor was an undiagnosed hydatidiform mole. Following surgery, serum β-hCG levels were normal and the patient is currently on surveillance. Results (if a Case Study enter NA) NA Conclusion We present an extremely rare case of extrauterine ETT arising from a previously undetected molar pregnancy. The diagnosis should be suspected when a mass is observed at extrauterine sites with elevated β-hCG levels in patients with or without vaginal bleeding. Histologic differential of squamous cell carcinoma needs to be ruled out with immunostains. Due to its rarity and highly variable presentation, this entity remains a diagnostic challenge. DNA fingerprinting analysis demonstrating non-maternal genes can help confirm the diagnosis of ETT.

Uterine Epithelioid Trophoblastic Tumor in a 44-Year-Old Woman: A Diagnostic Dilemma

Background: Epithelioid trophoblastic tumor (ETT) is a rare and newly defined disease, which most commonly occurs in women of reproductive age and can be a sequela of any gestational event. ETT can be present in both intrauterine and extrauterine sites. Case report: A woman of reproductive age, without specific comorbidities and with a single pregnancy and natural childbirth eight years ago, was diagnosed initially with poorly differentiated pleomorphic leiomyosarcoma on the hemostatic uterine curettage. Conclusion: Our case highlights that ETT presents a diagnostic challenge due to its rarity and histologic resemblance to other pathologies. Misdiagnosis delays effective treatment and affects survival. To date, only 8 cases of ETT of the uterus without previous gestational event and normal human chorionic gonadotropin (β-HCG) levels in a 60-year literature survey have been reported.

LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth

Gestational trophoblastic disease (GTD) is a heterogeneous group of lesions arising from placental tissue. Epithelioid trophoblastic tumor (ETT), derived from chorionic-type trophoblast, is the rarest form of GTD with only approximately 130 cases described in the literature. Due to its morphologic mimicry of epithelioid smooth muscle tumors and carcinoma, ETT can be misdiagnosed. To date, molecular characterization of ETTs is lacking. Furthermore, ETT is difficult to treat when disease spreads beyond the uterus. Here using RNA-Seq analysis in a cohort of ETTs and other gestational trophoblastic lesions we describe the discovery of LPCAT1-TERT fusion transcripts that occur in ETTs and coincide with underlying genomic deletions. Through cell-growth assays we demonstrate that LPCAT1-TERT fusion proteins can positively modulate cell proliferation and therefore may represent future treatment targets. Furthermore, we demonstrate that TERT upregulation appears to be a characteristic of ETTs, even in the absence of LPCAT1-TERT fusions, and that it appears linked to copy number gains of chromosome 5. No evidence of TERT upregulation was identified in other trophoblastic lesions tested, including placental site trophoblastic tumors and placental site nodules, which are thought to be the benign chorionic-type trophoblast counterpart to ETT. These findings indicate that LPCAT1-TERT fusions and copy-number driven TERT activation may represent novel markers for ETT, with the potential to improve the diagnosis, treatment, and outcome for women with this rare form of GTD.