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

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250518
Author(s):  
Gavin R. Oliver ◽  
Sofia Marcano-Bonilla ◽  
Jonathan Quist ◽  
Ezequiel J. Tolosa ◽  
Eriko Iguchi ◽  
...  
Keyword(s):  
Cell Growth ◽  
Copy Number ◽  
Placental Tissue ◽  
Gestational Trophoblastic Disease ◽  
Genomic Deletions ◽  
Smooth Muscle Tumors ◽  
Epithelioid Trophoblastic Tumor ◽  
Trophoblastic Tumors ◽  
Placental Site ◽  
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.

scholarly journals Fertility and pregnancy outcome in gestational trophoblastic disease

2021 ◽  
Vol 31 (3) ◽  
pp. 399-411
Author(s):  
Ulrika Joneborg ◽  
Leonoor Coopmans ◽  
Nienke van Trommel ◽  
Michael Seckl ◽  
Christianne A R Lok
Keyword(s):  
Pregnancy Outcome ◽  
Single Agent ◽  
Gestational Trophoblastic Disease ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Gestational Trophoblastic Neoplasia ◽  
Trophoblastic Tumor ◽  
Epithelioid Trophoblastic Tumor ◽  
Placental Site ◽  
Multi Agent

The aim of this review is to provide an overview of existing literature and current knowledge on fertility rates and reproductive outcomes after gestational trophoblastic disease. A systematic literature search was performed to retrieve all available studies on fertility rates and reproductive outcomes after hydatidiform mole pregnancy, low-risk gestational trophoblastic neoplasia, high- and ultra-high-risk gestational trophoblastic neoplasia, and the rare placental site trophoblastic tumor and epithelioid trophoblastic tumor forms of gestational trophoblastic neoplasia. The effects of single-agent chemotherapy, multi-agent including high-dose chemotherapy, and immunotherapy on fertility, pregnancy wish, and pregnancy outcomes were evaluated and summarized. After treatment for gestational trophoblastic neoplasia, most, but not all, women want to achieve another pregnancy. Age and extent of therapy determine if there is a risk of loss of fertility. Single-agent treatment does not affect fertility and subsequent pregnancy outcome. Miscarriage occurs more often in women who conceive within 6 months of follow-up after chemotherapy. Multi-agent chemotherapy hastens the natural menopause by three years and commonly induces a temporary amenorrhea, but in young women rarely causes permanent ovarian failure or infertility. Subsequent pregnancies have a high chance of ending with live healthy babies. In contrast, high-dose chemotherapy typically induces permanent amenorrhea, and no pregnancies have been reported after high-dose chemotherapy for gestational trophoblastic neoplasia. Immunotherapy is promising and may give better outcomes than multiple schedules of chemotherapy or even high-dose chemotherapy. The first pregnancy after immunotherapy has recently been described. Data on fertility-sparing treatment in placental site trophoblastic tumor and epithelioid trophoblastic tumor are still scarce, and this option should be offered with caution. In general, patients with gestational trophoblastic neoplasia may be reassured about their future fertility and pregnancy outcome. Detailed registration of high-risk gestational trophoblastic neoplasia is still indispensable to obtain more complete data to better inform patients in the future.

Epithelioid trophoblastic tumor: a case report

2006 ◽  
Vol 16 (3) ◽  
pp. 1473-1476 ◽  
Author(s):  
C. Lo ◽  
I. Low ◽  
A. L. Tan ◽  
J. Baranyai
Keyword(s):  
Gestational Trophoblastic Disease ◽  
Human Chorionic Gonadotrophin ◽  
Trophoblastic Disease ◽  
Trophoblastic Tumor ◽  
Uncomplicated Pregnancy ◽  
Epithelioid Trophoblastic Tumor ◽  
Trophoblastic Tumors ◽  
Clinicopathologic Findings ◽  
Tumor Like Lesions ◽  
Distinguishing Features

Epithelioid trophoblastic tumor is a rare and distinctive pathologic entity within the complex family of gestational trophoblastic disease. We describe a case of epithelioid trophoblastic tumor occurring in a 34-year-old woman, who presented with a large uterine tumor 3 years following an uncomplicated pregnancy. The clinicopathologic findings in this case are typical of this unusual entity and consistent with current literature, with the exception of negative beta-human chorionic gonadotrophin levels. The distinguishing features from other intermediate trophoblastic tumors and tumor-like lesions are discussed.

scholarly journals Gestational Trophoblastic Tumors: A Timely Review of Diagnostic Pathology

2018 ◽  
Vol 143 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Pei Hui
Keyword(s):  
Modern Medicine ◽  
Trophoblastic Tumor ◽  
Gestational Choriocarcinoma ◽  
Timely Review ◽  
Epithelioid Trophoblastic Tumor ◽  
Trophoblastic Tumors ◽  
Placental Site ◽  
Surveillance Programs ◽  
Placental Site Nodule ◽  
High Index Of Suspicion

Context.— Gestational trophoblastic tumors include 3 distinct entities: gestational choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Accurate diagnosis is important for clinical management of the patient. Objective.— To review clinical features and pathologic diagnosis of gestational trophoblastic tumors. Data Sources.— Literature and personal experience are the sources for this study. Conclusions.— Trophoblastic tumors are rare encounters in modern medicine, as a result of clinical practice of molar surveillance programs and early chemotherapeutic intervention for persistent gestational trophoblastic neoplasia. Diagnostic recognition of these tumors requires a high index of suspicion, awareness of their histologic characteristics, and appropriate application of immunohistochemical and molecular biomarkers. Recent attention has been given to a few precursor lesions of gestational trophoblastic tumors, including early/in situ choriocarcinoma and atypical placental site nodule.

scholarly journals Epithelioid trophoblastic tumor coexisting with choriocarcinoma around an abdominal wall cesarean scar: a case report and review of the literature

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunfeng Yang ◽  
Jianqi Li ◽  
Yuanyuan Zhang ◽  
Hanzhen Xiong ◽  
Xiujie Sheng
Keyword(s):  
Abdominal Wall ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Unknown Origin ◽  
Exploratory Laparotomy ◽  
Cesarean Scar ◽  
Trophoblastic Tumor ◽  
Epithelioid Trophoblastic Tumor ◽  
Trophoblastic Tumors ◽  
Wall Lesion

Abstract Background Mixed gestational trophoblastic neoplasms are extremely rare and comprise a group of fetal trophoblastic tumors including choriocarcinomas, epithelioid trophoblastic tumors, and placental site trophoblastic tumors. We present a case of a patient with extrauterine mixed gestational trophoblastic neoplasm adjacent to the abdominal wall cesarean scar. On the basis of a literature review, this type of case has never been reported before due to the unique lesion location and low incidence. Case presentation Our patient was a 39-year-old Chinese woman who had a history of two cesarean sections and one miscarriage. She had a recurrent anterior abdominal wall mass around her cesarean scar, and the mass was initially suspected of being choriocarcinoma of unknown origin. The patient had concomitant negative or mildly increased serum β-human chorionic gonadotropin at follow-up and no abnormal vaginal bleeding or abdominal pain. However, she underwent local excision twice and had two courses of chemotherapy with an etoposide and cisplatin regimen. She finally opted for exploratory laparotomy with abdominal wall lesion removal, subtotal hysterectomy, bilateral salpingectomy, and left ovarian cyst resection, which showed the abdominal wall lesion, whose components were revealed by microscopy and immunohistochemical staining to be approximately 90% epithelioid trophoblastic tumors and 10% choriocarcinomas from a solely extrauterine mixed gestational trophoblastic neoplasm around an abdominal wall cesarean scar. Conclusions It is worth noting whether epithelioid trophoblastic tumor exists in the setting of persistent positive low-level β-human chorionic gonadotropin. More studies are required to provide mechanistic insights into these mixed gestational trophoblastic neoplasms.

scholarly journals “It’s not lupus”. A placental site trophoblastic tumor presenting as a lupus-like paraneoplastic syndrome. A grand round case

Lupus ◽  
2021 ◽  
pp. 096120332098176
Author(s):  
Sarah J van der Lely ◽  
Jeffrey Boorsma ◽  
Marc Hilhorst ◽  
Jesper Kers ◽  
Joris Roelofs ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Gestational Trophoblastic Disease ◽  
Grand Round ◽  
Placental Site Trophoblastic Tumor ◽  
Trophoblastic Tumor ◽  
Anchoring Bias ◽  
Placental Site ◽  
History Of

Introduction: Placental site trophoblastic tumor (PSTT) is a rare subtype of gestational trophoblastic disease. Association of PSTT and nephrotic syndrome is exceedingly rare and has been described in 8 cases thus far. In all cases hysterectomy was performed within months after onset of symptoms, leading to immediate remission of nephrotic syndrome, except for one patient who died of complications of PSTT. Case: We describe the history of a woman in which PSTT was discovered years after onset of nephrotic syndrome. Kidney biopsy revealed lupus-like mesangiocapillary nephritis and over time the patient developed additional symptoms mimicking systemic lupus erythematosus (SLE). Discussion: We provide an overview of the literature on this clinical entity and elaborate on its pathophysiology. In addition, we reflect on the phenomenon of anchoring bias, that led physicians to assume the patient had SLE without questioning this diagnosis in the light of the unexplained finding of increased tumor markers.

scholarly journals A Rare Gestational Trophoblastic Disease: Placental Site Trophoblastic Tumor

2016 ◽  
Author(s):  
Senem Yaman Tunç ◽  
Elif Ağaçayak ◽  
Mehmet Sait İçen ◽  
Serdar Başaranoğlu ◽  
Mehmet Sıddık Evsen ◽  
...  
Keyword(s):  
Uterine Cavity ◽  
Total Abdominal Hysterectomy ◽  
Abdominal Hysterectomy ◽  
Gestational Trophoblastic Disease ◽  
Placental Site Trophoblastic Tumor ◽  
Trophoblastic Tumor ◽  
Trophoblastic Cells ◽  
Placental Site ◽  
Gestational Trophoblastic Diseases ◽  
Abnormal Vaginal Bleeding

<p>Placental site trophoblastic tumor (PSTT) is a highly rare form of gestational trophoblastic diseases that arise from intermediate trophoblastic cells. By presenting this case, we aimed to review the treatment and diagnosis, approach to PSTT.<br />A 31-year-old (G2P1A1L1) patient had abnormal vaginal bleeding. Serum ß-HCG was 5.82 mIU/ml and the transvaginal USG detected a polypoid mass in uterine cavity. Probe curettage was performed. Histopathologic specimens were confirmed as PSTT. No metastasis was detected. A total abdominal hysterectomy was performed.<br />PSTT is a rare tumor. In contrast to other trophoblastic tumors, PSTT produces a small amount of ß-HCG and it is relatively insensitive to chemotherapy. Adjuvant chemotherapy is suggested to follow surgical treatment in the cases with metastasis.</p>

scholarly journals The role of surgery in the management of women with gestational trophoblastic disease

2017 ◽  
Vol 44 (1) ◽  
pp. 94-101 ◽  
Author(s):  
LANA DE LOURDES AGUIAR LIMA ◽  
LÍLIAN PADRON ◽  
RAPHAEL CÂMARA ◽  
SUE YAZAKI SUN ◽  
JORGE REZENDE FILHO ◽  
...  
Keyword(s):  
Placental Tissue ◽  
High Sensitivity ◽  
Gestational Trophoblastic Disease ◽  
Human Chorionic Gonadotrophin ◽  
Gestational Trophoblastic Neoplasia ◽  
Chemotherapy Treatment ◽  
Invasion And Metastasis ◽  
Surgical Interventions ◽  
Trophoblastic Disease

ABSTRACT The Gestational Trophoblastic Disease includes an interrelated group of diseases originating from placental tissue, with distinct behaviors concerning local invasion and metastasis. The high sensitivity of the serial dosages of human chorionic gonadotrophin, combined with advances in chemotherapy treatment, have made gestational trophoblastic neoplasia curable, most often through chemotherapy. However, surgery remains of major importance in the management of patients with gestational trophoblastic disease, improving their prognosis. Surgery is necessary in the control of the disease's complications, such as hemorrhage, and in cases of resistant/relapsed neoplasia. This review discusses the indications and the role of surgical interventions in the management of women with molar pregnancy and gestational trophoblastic neoplasia.

Epithelioid Trophoblastic Tumor: Review of a Rare Neoplasm of the Chorionic-Type Intermediate Trophoblast

2006 ◽  
Vol 130 (12) ◽  
pp. 1875-1877
Author(s):  
Kimberly H. Allison ◽  
Jason E. Love ◽  
Rochelle L. Garcia
Keyword(s):  
Gestational Trophoblastic Disease ◽  
Reproductive Age ◽  
Placental Lactogen ◽  
Variable Expression ◽  
Trophoblastic Tumor ◽  
Trophoblastic Cells ◽  
Epithelioid Trophoblastic Tumor ◽  
Positive Immunostaining ◽  
Nodular Growth ◽  
Type Intermediate

Abstract We present a brief review of epithelioid trophoblastic tumor, a rare trophoblastic neoplasm derived from chorionic-type intermediate trophoblastic cells that typically presents in reproductive-age women between 1 and 18 years following a previous gestation. Histologic features include a nodular growth pattern of monomorphic, epithelioid cells within a hyaline matrix. Areas of necrosis and mitotic activity (0–9 mitoses per 10 high-power fields) are additional features of this neoplasm. Positive immunostaining for p63 and cytokeratin, frequent location in the lower uterine segment and endocervix, as well as the epithelioid appearance can lead to confusion with squamous cell carcinoma. Inhibin-α is typically expressed, as well as focal, more variable expression of other trophoblastic markers including β-human chorionic gonadotropin, human placental lactogen, placental alkaline phosphate, and Mel-CAM (CD148). The clinical behavior of this rare form of gestational trophoblastic disease is difficult to predict. Although most cases follow a benign course following resection, there is a potential for metastatic disease.

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