Non-gestational choriocarcinoma: unraveling the similarities and distinctions from its gestational counterpart.

Choriocarcinoma is a highly vascular and invasive tumor of anaplastic trophoblast, predominantly made up of cytotrophoblasts and syncytiotrophoblasts without villi. Based on its origin, choriocarcinoma can be either gestational or non-gestational. Non-gestational choriocarcinoma can be of germ cell origin, or can be seen in association with a somatic high-grade malignancy. It is difficult to differentiate gestational from non-gestational choriocarcinoma, especially in the reproductive age group. It is important to distinguish between the two, for accurate staging and prognostication, deciding the primary treatment modality, (ie, surgery or chemotherapy), and tailoring follow-up timeframes after diagnosis. An extensive literature search was performed regarding all cases of non-gestational choriocarcinoma, published before March 2023. A note was made of whether the origin of choriocarcinoma was ascertained and how gestational choriocarcinoma was differentiated from non-gestational choriocarcinoma. The keywords used for literature search were "non-gestational choriocarcinoma", "primary choriocarcinoma", "ovarian choriocarcinoma", "ovarian germ cell tumors", or "choriocarcinomatous differentiation". This review aims to summarize the similarities and differences in the epidemiology, pathogenesis, clinical presentation, and management guidelines between gestational and non-gestational choriocarcinoma, which can form an important educational resource for clinicians and laboratory physicians dealing with such cases.

Frequent EGFR expression/EGFR amplification and lack of activating mutation in testicular choriocarcinoma.

Choriocarcinoma (CC) is the rarest but most aggressive histological component of adult testicular germ cell tumor (TGCT). Although we previously reported a putative role of epidermal growth factor receptor (EGFR) alterations in the progression of CC, little is known about the kinase-activating mutation status of EGFR, which predicts the response to EGFR-tyrosine kinase inhibitors. In this study, we clinicopathologically reviewed a total of 12 cases of mixed TGCTs with CC components. Immunohistochemistry, fluorescence in situ hybridization, and direct sequencing was performed to investigate EGFR expression, EGFR copy number alterations, and functional mutation of EGFR in these CC components, respectively. Four (33%) of 12 cases exhibited predominant CC components (>50%), and all these patients died due to disease within 62 months. Overexpression of EGFR, higher copy number of EGFR, and amplification of EGFR was observed in 12 (100%), 10 (83%), and 9 (75%) of 12 CC components, respectively. None of the cases showed any mutational events in exons 18 to 24, which encode the tyrosine kinase domain of EGFR. These results confirm an important role of EGFR in the tumor aggressiveness of testicular CCs and may suggest its possible innate resistance against conventional anti-EGFR therapies.

Primary non-gestational uterine choriocarcinoma mimicking leiomyoma.

Uterine choriocarcinoma is a trophoblastic neoplasm that is most commonly gestational but can also be non-gestational in origin. However, primary non-gestational uterine choriocarcinoma is very rare, with only few cases having been reported. We report a case of a premenopausal woman who had initially been diagnosed with myoma delivery but who was discovered to have primary non-gestational uterine choriocarcinoma. This 46-year-old woman had no history of pregnancy. She was referred to our hospital for treatment of the myoma delivery. After tumor removal, histological examination led to the diagnosis of choriocarcinoma. The serum human chorionic gonadotropin level (207,300 mIU/mL) prior to surgery was abnormally high, and because the computed tomography scans additionally revealed lung metastasis, the patient was diagnosed with FIGO stage III choriocarcinoma. Due to the lack of pregnancy history and abstinence from sexual intercourse for >1 year, we performed short tandem repeat analysis, and diagnosed the patient with non-gestational choriocarcinoma. Despite treatments using multiple anticancer agents after the surgery, the patient died 1 year after starting the treatments. On this occasion, we report a very rare case of a premenopausal woman who was diagnosed with primary non-gestational uterine choriocarcinoma mimicking leiomayoma.

A Transplantable Syngeneic Allograft Mouse Model for Nongestational Choriocarcinoma of the Ovary.

Nongestational choriocarcinoma is a rare malignancy in humans with poor prognosis. Naturally occurring choriocarcinoma is also rare in laboratory mice, and no genetic mouse model accurately recapitulates the features of this cancer. Here we report development of a genetically engineered mouse (GEM) model with alterations in Brca2, Trp53, and RB that develops ovarian tumors. Most of the ovarian tumors displayed histological characteristics of nongestational choriocarcinoma of the ovary (NGCO) (47%) with abundant syncytiotrophoblasts and cytotrophoblasts, positive immunolabeling for human chorionic gonadotropin, and positive periodic acid-Schiff reaction. The rest of the ovarian tumors were serous epithelial ovarian carcinoma (SEOC) (26%) or mixed tumors consisting of NGCO and SEOC (26%). We further established syngeneic orthotopic mouse models for NGCO by in vivo passaging of GEM tumors. These metastatic models provide a platform for evaluating new treatment strategies in preclinical studies aimed at improving outcomes in choriocarcinoma patients.

Ovarian nongestational choriocarcinoma and associated adenocarcinoma with the same germ cell origin determined by a molecular genetic approach: A case report.

Ovarian non-gestational choriocarcinomas co-existing with adenocarcinoma are extremely rare and have been reported as epithelial ovarian carcinomas of a "non-germ cell origin" with "choriocarcinomatous differentiation". Although the cellular origin of non-gestational choriocarcinoma may be post-meiotic ovarian germ cells or the dedifferentiation of epithelial ovarian carcinoma, detailed genetic evidence has not yet been obtained to support this. We herein present a case of ovarian non-gestational choriocarcinoma co-existing with adenocarcinoma in a 29-year-old woman. The tumor rapidly increased in size and lung metastases appeared soon after parturition. We genetically demonstrated that the cellular origin of ovarian non-gestational choriocarcinoma was a post-meiotic germ cell derivation using a short tandem repeat analysis. The co-existing adenocarcinoma component was also shown to be of the same germ cell origin. These tumors showed the same homozygous pattern. A molecular genetic approach may be important for understanding the clinicopathological features of such tumors.

Brain metastases in gestational trophoblast neoplasia: an update on incidence, management and outcome.

OBJECTIVE: To update the demographic data, treatment details and outcomes for GTN patients with brain metastases managed with the modern treatment protocols at the UK centre for gestational trophoblast neoplasia at Charing Cross Hospital in London. METHODS: The hospital database and pharmacy records were reviewed to identify GTN patients treated with brain metastases. Data was assembled on the specific GTN diagnosis, staging, prognostic scores, chemotherapy regimens, additional interventions and outcomes. RESULTS: During the 22 year study period, 27 GTN patients with brain metastases were treated. One case clearly resulted from a prior molar pregnancy, 3 were of uncertain aetiology and 23 cases had no prior molar pregnancy. The standard chemotherapy regimens were EMA-CO or EMA-EP given with an enhanced CNS methotrexate dose combined with intrathecal methotrexate. Five patients required emergency neurosurgery and routine radiotherapy was not employed. Twenty three (85%) patients are long term survivors and four patients died. Of the patients who died, all four had chemotherapy refractive disease and two had extended intervals of 18 and 30 years from their antecedent pregnancy. CONCLUSION: The incidence of brain metastases in postmolar pregnancy GTN is extremely low. Patients with non-molar choriocarcinoma have an approximate 20% risk of CNS disease and should have routine CNS imaging. Treatment with CNS doses of EMA-CO or EMA-EP appears curative for most patients.

Laparoscopic Fertility-preserving Treatment of a Pure Nongestational Choriocarcinoma of the Ovary: Case Report and Review of Current Literature.

This case report demonstrates the feasibility of laparoscopic and fertility-preserving approach in nongestational choriocarcinoma of the ovary (NGCO). Pure NGCO is a rare malignant condition. In the last decade, only 14 cases have been reported in the literature. The use of laparoscopy and fertility-preserving procedures in nonepithelial ovarian malignancies is extremely controversial. A 23-year-old woman underwent emergency laparoscopy due to acute abdominal pain associated with an 8-cm large adnexal mass. The initial procedure consisted only of a left oophoroplasty, and histology revealed a tumor of high malignant potential compatible with a primary NGCO. Approximately 3 weeks after initial surgery, she was submitted to a laparoscopic staging surgery, including left adnexectomy, omentectomy, peritoneal biopsies, and retroperitoneal lymphadenectomy. Final pathology confirmed an International Federation of Gynecology and Obstetrics stage IIB NGCO. Before initiation of adjuvant chemotherapy based on 3 courses of bleomycin, etoposide, and cisplatin, the patient received goserelin for ovarian suppression. Nine months after therapy, the patient presented no signs of recurrence and reassumed normal menstruation cycles with normal levels of gonadotropins and tumor markers. The current report brings new insights into the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO.

The encouraging prognosis of nongestational ovarian choriocarcinoma with lung metastases.

OBJECTIVE: To study nongestational ovarian choriocarcinoma (NGOC) with lung metastases: its early diagnosis, optimal therapeutic method, and prognosis. STUDY DESIGN: Twelve cases of NGOC with lung metastases treated in Peking Union Medical College Hospital from 1982-2011 were analyzed retrospectively. The 12 cases included 9 pure NGOCs and 3 mixed with other germ cell tumors (mature teratoma, endodermal sinus tumor and embryonal carcinoma components, and dysgerminoma, respectively). Chemotherapy was given in all 12 cases, mainly including EMA/CO, BEP, and RESULTS: The median age for the cases was 23.9 years. Abdominal pain was the most common symptom (7/12). Follow-up was available for 11 cases, ranging from 17-174 months (median, 86.6 months). Of those, only 1 patient died of the disease, at 42 months from the disease onset. The other patient for whom follow-up was not available gave up treatment due to chemoresistance and disease progression. An overall sustained remission had been achieved in 10 cases (83.3%). CONCLUSION: Surgery combined with the appropriate chemotherapy regimen can improve therapeutic efficacy and survival in the treatment of NGOC with lung metastasis, even in recurrent or chemorefractory cases. Commencement of EMA/CO chemotherapy, which seems to be associated with better prognosis, should be considered as a good choice of treatment. Conservative surgery is acceptable for young patients desiring to preserve fertility.

Uterine endometrial carcinoma with trophoblastic differentiation: a case report with literature review.

Choriocarcinoma is categorized as either gestational or nongestational depending on its origin. Nongestational choriocarcinoma originated in the trophoblastic differentiation is a rare but an aggressive tumor. This article reports a nongestational case of a uterine endometrial carcinoma with trophoblastic differentiation. A 54-year-old woman with a history of atypical genital bleeding that underwent semi-radical hysterectomy, bilateral salpingo-oophrectomy, and pelvic lymph nodes dissection. Pathological investigation showed that the tumor had endometrioid adenocarcinoma and choriocarcinomatous components. Although a series of multimodality treatments including craniotomy were performed, she died of aggressive lung and brain metastases one year after the primary surgery.

Nongestational ovarian choriocarcinoma with bilateral teratoma: A rare case report and literature review.

INTRODUCTION: Trophoblastic neoplasms are often associated with pregnancy, and nongestational trophoblastic neoplasms are extremely rare. Nongestational ovarian choriocarcinoma (NGCO) is a highly aggressive germ cell-derived tumor frequently presenting with early hematogenous metastasis. PATIENT CONCERNS: Herein, we report a case of a 28-year-old unmarried woman with regular menstruation who experienced vaginal bleeding 1 week after her last menstrual cycle. Doppler ultrasound revealed bilateral adnexal masses and elevated serum human chorionic gonadotropin (hCG) levels. The patient was initially misdiagnosed as presenting an ectopic pregnancy. DIAGNOSIS: The final pathology confirmed an International Federation of Gynecology and Obstetrics stage IA NGCO with bilateral mature teratoma of the ovary. This is an extraordinary instance of ovarian choriocarcinoma which emerged without any prior gestation, and the patient's lack of a history of pregnancy made the diagnosis ignored. INTERVENTIONS: After initial surgery and 1 cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, a laparoscopic fertility-preserving comprehensive staging surgery was performed. Two cycles of chemotherapy with BEP were administered as supplemental therapy postsurgery, and leuprorelin was administered to protect ovarian function. OUTCOMES: Menstruation resumed 4 months after chemotherapy completion, and tumor indicators were within the normal range. No signs of recurrence were observed at the 36-month follow-up. CONCLUSION: NGCO should be considered if a female patient exhibits irregular vaginal bleeding and masses in the adnexal area. The present case and our literature review also highlighted that fertility-sparing surgery and multidrug chemotherapy are effective methods for treating NGCO.

Challenges in the diagnosis and treatment of pure non-gestational uterine choriocarcinoma in a child: a case report.

BACKGROUND: Diagnosing non-gestational uterine choriocarcinoma in children is challenging because of its rarity and nonspecific imaging findings. Herein, we report a case of non-gestational uterine choriocarcinoma in a child, which was unexpectedly found during exploratory laparotomy and confirmed by histopathological findings. However, the tumor did not respond to chemotherapy. CASE PRESENTATION: A 4-year-old Indonesian female patient was brought into the emergency unit with chief complaint of vaginal bleeding. She had suffered from vaginal spotting 4 months before being admitted to the hospital. Physical examination revealed a distended abdomen in the left lumbar region and a palpable fixed mass with a smooth surface. Abdominal computed tomography scans revealed a large mass (10 × 6 × 12 cm) with fluid density and calcification. Thus, we suspected left ovarian teratoma. The patient's luteinizing hormone, follicle-stimulating hormone, and lactate dehydrogenase levels were 25.2 mIU/ml, 0.1 mIU/ml, and 406 U/l, respectively. According to the clinical and radiological findings, we decided to perform an exploratory laparotomy and found a tumor originating from the uterus, not the ovarium. We did not observe liver nodules and any enlargement of abdominal lymph nodes. Subsequently, we performed hysterectomy. The histopathological findings supported the diagnosis of choriocarcinoma. The patient was discharged uneventfully on postoperative day 5. Thereafter, the patient underwent nine cycles of chemotherapy, including carboplatin (600 mg/m2 IV), etoposide (120 mg/m2 IV), and bleomycin (15 mg/m2 IV). However, on the basis of the clinical findings of a palpable mass and partial intestinal obstruction, the tumor relapsed soon after the ninth cycle of chemotherapy. Currently, the patient is undergoing chemotherapy again. CONCLUSIONS: Although pure non-gestational uterine choriocarcinoma is rare, it should be considered as one of the differential diagnoses for intraabdominal tumors in a child, so as to better guide and counsel families regarding the surgical plan and prognosis, respectively. In the present case, the patient's response to chemotherapy was poor, implying that the treatment of non-gestational choriocarcinoma is still challenging, particularly in the pediatric population.

Pure nongestational choriocarcinoma of the ovary: a case report.

Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational choriocarcinoma of the ovary is extremely rare, and its diagnosis is very difficult during the reproductive years. We present a case of a 33-year-old woman diagnosed with pure nongestational ovarian choriocarcinoma. Following surgery, multiple courses of a chemotherapy regimen of etoposide, methotrexate, and actinomycin-D (EMA) were effective.

Usefulness of intraoperative imprint cytology in ovarian germ cell tumors.

OBJECTIVE: This study retrospectively investigated the usefulness of intraoperative diagnosis based on imprint cytology and frozen sections for ovarian germ cell tumor. STUDY DESIGN: Intraoperative studies were reviewed for 23 cases with ovarian germ cell tumor treatment for which both frozen sections and imprint cytology were available. Final histopathologic diagnoses were compared with those based on intraoperative examinations. RESULTS: Underlying pathologies included dysgerminoma (n = 6), yolk sac tumor (n = 1), non-gestational choriocarcinoma (n = 1), mature cystic teratoma with malignant transformation (n = 1), immature teratoma (n = 11), and mixed germ cell tumor (n = 3). Discrepancies between intraoperative imprint cytology and definitive histologic diagnosis were seen in 6 of the 23 cases. Accuracy was 54.5% (6/11) for immature teratoma and 91.7% (11/12) for other tumors. Cytologic examination facilitated accurate diagnosis in both of our cases, and intraoperative diagnosis by frozen section proved inaccurate. CONCLUSION: These results demonstrate that intraoperative assessment based on imprint cytology for immature teratoma has a relatively lower sensitivity, but an acceptable sensitivity for other germ cell tumors. Diagnostic approaches combining frozen sections and imprint cytology are advisable to improve the yield for intraoperative diagnosis.

Molecular genetic analysis of nongestational choriocarcinoma in a postmenopausal woman: a case report and literature review.

Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Most cases occur in association with preceding gestational events. However, on very rare occasions, nongestational choriocarcinoma arises from germ cell or trophoblastic differentiation in different types of carcinoma. This article reports the case of a 58-year-old woman with primary nongestational choriocarcinoma of the uterus that developed 19 years after her final pregnancy and 4 years after menopause. A total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination showed choriocarcinoma of the uterus without components of other germ cell tumors. Karyotype analysis of the tumor cells demonstrated XX. We confirmed its nongestational origin by DNA polymorphism analysis at 15 short tandem repeat loci. After surgery, the patient was given four courses of combination chemotherapy. She is still alive and there has been no evidence of recurrence 3 years after surgery.

Pathological complete response and two-year disease-free survival in a primary gastric choriocarcinoma patient with advanced liver metastases treated with germ cell tumor-based chemotherapy: a case report.

Choriocarcinoma is an early metastasizing and highly invasive tumor and characterized as a high-level human chorionic gonadotropin-secreting tumor. It normally arises in the gestational trophoblast, gonads and much less frequently in the stomach. Primary gastric choriocarcinoma appears to have a poor prognosis; especially with liver metastasis, the survival period is expected to be <1 month. This unfavorable clinical outcome is partly due to the lack of defined chemotherapy against primary gastric choriocarcinoma. We herein report a case of a 68-year-old male primary gastric choriocarcinoma patient with advanced liver metastases in which germ cell tumor-based chemotherapy achieved a pathological complete response and 2-year disease-free survival.

[Primary choriocarcinoma of the maxillary gingival]. / Choriocarcinome gingivo-mandibulaire primitif.

INTRODUCTION: Primary non-gestational extragonadal choriocarcinomas are uncommon and their head and neck localization more exceptional. OBSERVATION: We report on a primary choriocarcinoma case of the mandibular gingivae in a 26-year-old woman who presented with pulmonary and renal metastasis. Complete response (clinical, biological and radiological) was achieved with combined chemotherapy according to APE regimen associating actinomycin, cisplatin and etoposid. The patient was free of disease 4 years after therapy completion. DISCUSSION: Primary gingival mandibular choriocarcinoma is very rare. Clinical presentation is atypical; diagnosis is based on histopathological examination and positivity for HCG. Our case report showed high chemo-sensitivity and comparable outcome to the other localizations.