Clinical features and demographic characteristics of gestational trophoblastic neoplasia: Single center experience and the SEER database.

The aim of this study was to analyze the clinical features and demographic characteristics of gestational trophoblastic neoplasia (GTN) patients, specifically choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumor (ETT). We utilized data from a local hospital and the SEER database, as well as survival outcomes of CC in SEER database. Additionally, we used multiple risk factors to create a prognostic nomogram model for CC patients. The study included GTN patients from the SEER database between 1975 and 2016 as well as those from the First Affiliated Hospital of Xi 'an Jiaotong University between January 2005 and May 2022. Related factors of patients were compared using the chi-square (χ2) or Fisher's exact test. For assessing overall survival we employed the Kaplan-Meier method and log-rank test. To construct the nomogram, we used Cox regression. Statistically significant differences were found between CC and PSTT/ETT patients in terms of surgery in local hospital, as well as age and year of diagnosis in the SEER database. Moreover, significant differences were observed between low and high (HR) /ultra-high risk (UHR) groups regarding FIGO stage, surgery and chief complaint at the local hospital, and FIGO stage, surgery and unemployment in the SEER database. The Cox regression analysis confirmed that age, race, surgery, marital status, FIGO stage, and unemployment were correlated with CC prognosis. Furthermore, the analysis showed that patients aged 40 years or older and those with FIGO Ⅲ/Ⅳ were independent prognostic factors of CC. The study indicates that atypical symptoms or signs may be the main reasons for HR /UHR patients to seek medical treatment. Therefore, providing multidisciplinary care is recommended for CC patients experiencing psychological distress due to unfavorable marital status or unemployment.

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.

Application of Current Pathologic Criteria for Atypical Placental Site Nodule Suggests That Refined Criteria Are Needed.

Atypical placental site nodules (APSNs) are histologically intermediate between placental site nodules (PSNs) and epithelioid trophoblastic tumors (ETTs). Little data exists to characterize these lesions and the risk of transformation from PSN to ETT. Recent World Health Organization (WHO) criteria for distinction of APSN are vague and not objectively defined. We identified cases signed out as PSN (n=33) and APSN (n=11) and aimed to characterize, statistically compare, and assess the risk of transformation in PSNs using data including size, location, mitotic rate, Ki-67 proliferation index, trophoblastic cells per high-power field, presence of severe cytologic atypia, beta-human chorionic gonadotropin levels, time since last pregnancy, presence of calcification, necrosis, or apoptosis, and follow-up results. All cases were confirmed to be positive for p63, and a Ki-67/AE1/AE3 dual stain was used to evaluate the Ki-67 proliferation index in the trophoblastic cells. In our cohort, slight changes in the interpretation of WHO criteria for PSN and APSN led to marked differences in the proportion of PSNs flagged as "atypical." There was no statistically significant difference in the persistence of APSN versus non-APSN. None of the PSNs transformed to ETT. Current criteria for distinction between PSN and APSN are largely subjective. More objective, clearly defined, and clinically meaningful criteria are needed to distinguish between PSN and APSN, thus aiding in assessing the rare risk of transformation to ETT.

Placental Site Trophoblastic Tumor in Mediastinal Recurrence of Mixed Germ Cell Tumor of the Testis: Report of a Case and Review of the Literature.

We present a rare case of a 42-year-old man diagnosed with a placental site trophoblastic tumor in combination with teratoma in a mediastinal recurrence of a testicular germ cell tumor post-orchiectomy and chemotherapy. To the best of our knowledge, this is the eighth case of placental site trophoblastic tumor in a male reported so far in the English literature. The purpose of this case report is to add data to the existing literature, review the literature, discuss the differential diagnoses with emphasis on morphologic and immunohistochemical differences between trophoblastic tumors, and highlight the management implications of a correct diagnosis.

Outcomes and prognostic factors of placental-site trophoblastic tumor: a retrospective study of 58 cases.

PURPOSE: Our goal was to assess the outcomes and explore the prognostic factors for patients with placental-site trophoblastic tumor (PSTT) through this retrospective analysis. METHODS: 2043 patients with gestational trophoblastic neoplasia (GTN) were registered at two tertiary hospitals between January 2003 and March 2021, of whom 58 (2.8%) were diagnosed with PSTT. We retrospectively analyzed the clinico-pathological characteristics, treatments, outcomes and prognostic factors. RESULTS: Only 4 patients died and 5 patients experienced a recurrence. Patients (n = 49) with stage I disease had a favorable prognosis, surgery with (n = 21) or without (n = 28) chemotherapy made no significant difference in overall survival (OS) (p = 0.251) or disease-free survival (DFS) (p = 0.425). 3 patients with stage I had fertility preserving surgery and successful pregnancy was achieved in 2 of them. The outcome of patients with advanced disease was poor. Univariate analysis revealed serum ß-hCG levels at diagnosis, FIGO stage IV and metastatic disease were significant predictors of both overall survival and disease-free survival. However, multivariate analysis indicated stage IV was the only significant independent predictor of adverse OS, while metastatic disease was the only significant independent predictor of adverse DFS. CONCLUSION: Surgery alone is sufficient for patients with stage I disease without high-risk factors. The prognosis of patients with advanced stage disease remains poor. Stage IV and metastatic disease were the most critical risk factors.

A first stage placental site trophoblastic tumor: a case report and review of literature.

Placental site trophoblastic tumor (PSTT) is a very rare form of gestational trophoblastic disease (GTD) that occurs mainly in women who have a history of termination of pregnancy. It has different characteristics from other gestational trophoblastic tumors: it grows slowly, secretes low levels of beta-human chorionic gonadotropin (ß-hCG), with low metastatic potential. We report a case of PSTT of a 32-year-old patient. Seven months after delivery, the patient presented at our Center with persistence of menorrhagia for at least 1 month. A slightly high level of beta-human chorionic gonadotropin (ß-hCG) was observed. TVUS and MRI, an operative hysteroscopy and a laparoscopy were performed. The histological and immunohistochemical findings demonstrated PSTT. Diagnosis of juvenile cystic adenomyoma (JCA) was also added. A total body CT scan was negative for metastases. A total hysterectomy with salpingectomy was performed. We performed a search of relevant studies about PSTT of the last years. A systematic search of Pubmed databases was conducted. Appropriate search terms were constructed by reviewing abstracts, titles and keywords relating to PSTT known to the authors. All articles known to the authors useful to the review were included, comparing with our clinical case. Stages and treatment are related to survival rates, with long term survival expected for stage I low-risk disease after hysterectomy. Our case is a stage I disease with good prognostic factors (patient's age and absence of metastases) and, as described in the literature, a total hysterectomy with salpingectomy was performed.

A Review of Current Management of Placental Site Trophoblastic Tumor and Epithelioid Trophoblastic Tumor.

IMPORTANCE: Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) are rare forms of gestational trophoblastic neoplasia (GTN). These tumors differ from choriocarcinoma as they are monophasic, have slower growth rates, have lower ß-hCG concentrations, and are more chemoresistant. Placental site trophoblastic tumor and ETT can be misdiagnosed, leading to inappropriate management.. OBJECTIVE: The aim of this study was to review the pathogenesis, presentation, pathologic findings, and treatment for PSTT and ETT. EVIDENCE ACQUISITION: A comprehensive literature review was performed identifying relevant research and review articles. Relevant textbook chapters and guidelines were also reviewed. RESULTS: Placental site trophoblastic tumor and ETT can present months to years after any antecedent pregnancy event with abnormal uterine bleeding and an elevated ß-hCG. Tumors are typically confined to the uterus and secrete lower levels of ß-hCG compared with other GTNs. The International Federation of Gynecology and Obstetrics prognostic scoring system does not correlate well with prognosis. These lesions can be misdiagnosed as smooth muscle tumors, metastatic melanoma, and cervical squamous cell carcinoma. However, they can be distinguished by their unique histologic and immunophenotypic features. CONCLUSIONS: Surgery is the mainstay of treatment for early-stage PSTT and ETT. For patients with advanced disease or for those with poor prognostic indicators, such as an antecedent pregnancy interval of greater than 48 months, a multimodal treatment paradigm of surgery and chemotherapy using a high-risk GTN platinum-etoposide containing regimen is recommended. RELEVANCE: Placental site trophoblastic tumor and ETT should be considered in the differential diagnosis in a reproductive age patient presenting with abnormal uterine bleeding and an elevated ß-hCG after any antecedent pregnancy event.

Coexisting Epithelioid Trophoblastic Tumor and Placental Site Trophoblastic Tumor During Asymptomatic Relapse: A Case Report and Literature Review.

Gestational trophoblastic neoplasms are a group of trophoblastic tumors that include choriocarcinoma (CC), epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs). Mixed gestational trophoblastic neoplasms include combinations of CCs with ETTs and/or PSTTs; combinations of ETTs and PSTTs have also been described. This report describes the case of a 49-yr-old female with mixed ETT and PSTT discovered due to menstrual delay and a positive beta-human chorionic gonadotropin in serum 11 yr after normal pregnancy; it is an asymptomatic recurrence of the neoplasm after 2 yr. Moreover, only the ETT recurred without evidence of PSTT by biopsy and without any increase in human chorionic gonadotropin levels, even though human chorionic gonadotropin was positive in the first onset of the disease. We also reviewed published English literature, which revealed that there are only 36 cases of mixed trophoblastic tumors to date, of which pure mixed ETT and PSTT were reported only in four cases including our case. The most common combination is CC admixed with an ETT (52%), followed by CC with PSTT in 30.5%. CC admixed with an ETT and/or PSTT account for 83% of the cases, of which pure mixed ETT and PSTT were reported only in 4 cases (11%). The rarity of this condition entails reporting of all cases to facilitate future research and clinical management.

Gestational trophoblastic neoplasia: Novelties and challenges.

Gestational trophoblastic diseases are a group of pregnancy-related disorders, originated from trophoblast cells. They include benign and aggressive tumors, such as the invasive mole, the choriocarcinoma, the placental site trophoblastic tumor (PSTT), and the epithelioid trophoblastic tumor (ETT). These malignancies are characterized as gestational trophoblastic neoplasm (GTN), rarer, although more dangerous. The diagnosis of GTN is made in most cases by monitoring serum chorionic gonadotropin (hCG) with histological confirmation. The use of specific tissue biomarkers has been increasingly employed as a differential diagnosis, leading to more accurate results and different therapy protocols and prognosis for each GTN. The treatment is based on the International Federation of Gynecology and Obstetrics anatomical staging system and the World Health Organization prognostic score system. If an accurate diagnosis is made and the guidelines followed, the cure for choriocarcinoma and invasive mole cases can reach 98%, whereas PSTT and ETT still present mild success rates. The improved knowledge about GTN and its peculiarities allows physicians to efficiently achieve the differential diagnosis and choose the best available therapy protocol, thus increasing the overall survival of affected women. Nevertheless, obtaining epidemiological data and improving knowledge through basic and translational research are essential to answer open questions on GTN physiopathology, their causes, and cellular behavior.

"It's not lupus". A placental site trophoblastic tumor presenting as a lupus-like paraneoplastic syndrome. A grand round case.

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.

Placental site trophoblastic tumour and epithelioid trophoblastic tumour.

Placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) are the rarest subtypes of gestational trophoblastic disease (GTD). Their diagnosis is complicated and lacks specific and sensitive tumour markers. They are slow-growing tumours and can occur months to years after any type of antecedent pregnancy. The primary treatment for localised disease is hysterectomy. However, extra-uterine invasion and/or metastasis occur in about one-third of cases and still cause death in a small number. Most patients are young; hence, fertility preservation is a consideration. The major obstacle for prognosis is chemotherapy resistance. The current understanding of these tumours remains elusive and no randomized controlled trials have been done. Even those centres treating a large number of patients with GTD will infrequently manage PSTT/ETT. In this review, we assess progress in the understanding of the disease and discuss four main clinical challenges - establishing conformity of practice, devising a risk-adapted approach to clinical management, establishing long-term follow-up data and evaluating therapies for poor prognosis and multi drug-resistant patients.

Placental site trophoblastic tumour: the rarest subtype of gestational trophoblastic disease.

Placental site trophoblastic tumour (PSTT) is a very rare form of gestational trophoblastic disease that grows slowly, secretes low levels of beta-subunit of human chorionic gonadotropin (ß-hCG), presents late-onset metastatic potential and is resistant to several chemotherapy regimens. Here, we report a case of PSTT in a 36-year-old woman who presented with amenorrhea and persistently elevated serum level of ß-hCG after a miscarriage. Transvaginal ultrasound revealed a hypovascular ill-defined solid lesion of the uterine fundus and MRI showed a tumour infiltrating the external myometrium with discrete early enhancement and signal restriction on diffusion-weighted imaging. PSTT was suspected, and after endometrial biopsy by hysteroscopy and posterior hysterectomy, microscopic examination allowed the final diagnosis. The level of ß-hCG dropped significantly in about a month after surgical treatment. Due to the rarity of PSTT, reporting new cases is crucial to improve the diagnosis and managing of these patients.

Placental site trophoblastic disease.

A case study of a 38-year-old woman with a diagnosis of placental site trophoblastic tumor is presented. The patient had a 22-month history of amenorrhea since her last pregnancy, and a dilation and curettage procedure was performed after a 3.1×2.4×2.8 cm endometrial echogenic lesion was visualized on a pelvic ultrasound. When the diagnosis of placental site trophoblastic tumor was made by histopathologic and immunohistochemical analysis, complementary examinations including including pelvic magnetic resonance imaging (MRI) and a chest computed tomography (CT) were done. There was no evidence of disease outside the uterus, and a laparoscopic hysterectomy with bilateral salpingectomy was performed. After a surveillance period of 12 months, no disease recurrence was identified. Best imaging studies, treatment options, and proper surveillance for these type of tumors are discussed alongside the case study.

A malignant placental site trophoblastic tumor of the uterus with multiple metastases: A case report of a rare tumor showing an aggressive behavior.

One of the very rare forms of gestational neoplastic diseases is the malignant placental site trophoblastic tumor. Due to its rarity, the data regarding its diagnosis and management are limited. The prognosis of this tumor is unpredictable with potential malignant behavior and metastasis. We report a case of malignant placental site trophoblastic tumor with multiple metastatic deposits in the ovaries, lungs, kidneys, adrenals, and pancreas. The patient was treated by surgery and an extensive subsequent chemotherapy. The disease progressed, and the patient died 17 months after diagnosis.

Gestational Trophoblastic Tumors: A Timely Review of Diagnostic Pathology.

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.

CARE-Placental site trophoblastic tumor presenting with thrombotic microangiopathy: A case report.

RATIONALE: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasm (GTN). PATIENT CONCERNS: A 28-year-old Chinese female with initial presentation of thrombotic microangiopathy (TMA) with symptoms of edema of the lower extremities and eyelid, thrombocytopenia and anemia. DIAGNOSES: The primary diagnosis was chronic glomerulonephritis according to the related laboratory tests and clinical symptoms. INTERVENTIONS: A total abdominal hysterectomy with a bilateral salpingectomy was performed. OUTCOMES: The PSTT patient was cured, which contributed to the symptom relief of TMA. LESSONS: This case report aims to elucidate the relationship between TMA and PSTT, so as to achieve timely diagnosis and treatment and reduce misdiagnosis.

[Squamous cell carcinoma in situ of the cervix and placental site nodule: Case report]. / Carcinoma escamocelular in situ del cérvix y nódulo del sitio placentario: reporte de caso.

An asymptomatic 24-year-old woman underwent a colposcopy, cervical biopsy, and subsequently, a conization for a cervical squamous cell carcinoma in situ with glandular extension. Simultaneously, an endometrial biopsy was carried out in which, incidentally, a placental site nodule was diagnosed, a rare non-neoplastic lesion originating in the intermediate trophoblast. Given the coexistence of these two entities, it was necessary to make a differential diagnosis between them and also with other pathologies of the trophoblast such as an exaggerated placental site, placental site trophoblastic tumor, and epithelioid trophoblastic tumor.