Malignant Trophoblastic Neoplasm Research Articles

Cervical choriocarcinoma in a post-menopause woman: Case report and review of literature

Background: Cervical choriocarcinoma is a malignant trophoblastic neoplasm that arises from pluripotent gonadal germ cells. Various manifestations are expected including vaginal bleeding and symptoms related to metastasis. Here, we report a case of primary choriocarcinoma in a post-menopausal woman. Case presentation: A 67-year-old woman presented with vaginal bleeding and lower abdominal pain. Ultrasound and laboratory results were normal except for a β-hCG titer of 14850 IU/L. Hysteroscopy revealed a polyp in the posterior wall of the cervix. hysterectomy and bilateral salpingo-oophorectomy were performed due to suspected choriocarcinoma. The β-hCG titer decreased immediately after surgery. However, the β-hCG titer increased again one month after surgery and treatment was continued with weekly methotrexate administration. Conclusion: Manifestations such as vaginal bleeding is very important in post-menopausal women. Although there are no specific guidelines for the treatment of choriocarcinoma in these patients, hysterectomy following chemotherapy based on response to treatment and β-hCG titration is favorable.

Uterine Epithelioid Trophoblastic Tumor

A woman in her early 60s presented with postmenopausal bleeding. Pelvic ultrasound examination identified a large uterine mass. The patient underwent total hysterectomy to remove this uterine mass. Which of the following is a malignant trophoblastic neoplasm that can develop many years after pregnancy?a.Placental site noduleb.Exaggerated implantation sitec.Epithelioid trophoblastic tumord.Endometrial stromal sarcoma Answer: c. Epithelioid trophoblastic tumor Epithelioid trophoblastic tumor is a rare malignant neoplasm of chorionic-type intermediate trophoblast.1WHO Classification of Tumors5th ed. Female Genital Tumors. Vol 4. International Agency for Research on Cancer, Lyon2020Google Scholar Epithelioid trophoblastic tumor is generally not associated with specific symptoms, but vaginal bleeding or menometrorrhagia is often noted, as is low elevation of serum β-human chorionic gonadotropin.1WHO Classification of Tumors5th ed. Female Genital Tumors. Vol 4. International Agency for Research on Cancer, Lyon2020Google Scholar Epithelioid trophoblastic tumor can develop within a year of and up to 2 decades after an antecedent gestation and thus can be seen in postmenopausal patients. Epithelioid trophoblastic tumor forms a solid to cystic mass most commonly in the cervix or lower uterine segment with varying amounts of necrosis and hemorrhage. On microscopic examination, the tumor shows infiltrative mononuclear epithelioid cytologically atypical intermediate trophoblastic cells, often forming nests with hyalinization or necrosis centrally.2Fadare O. Parkash V. Carcangiu M.L. Hui P. Epithelioid trophoblastic tumor: clinicopathological features with an emphasis on uterine cervical involvement.Mod Pathol. 2006; 19: 75-82Crossref PubMed Scopus (76) Google Scholar

Using short tandem repeat analysis for choriocarcinoma diagnosis: a case series

BackgroundChoriocarcinoma is a highly aggressive, malignant trophoblastic neoplasm that can be gestational or non-gestational in origin. Accurate discrimination between these two subtypes, the causative pregnancy type, and the pregnancy-to-treatment interval for gestational choriocarcinoma are vital for clinical management.MethodsFifteen choriocarcinomas were genotyped using multiplex fluorescent polymerase chain reaction amplification of 15 short tandem repeat (STR) loci and the amelogenin locus (XY determination). Genotype patterns at each locus from tumoral and maternal tissues were compared, and any prior or concurrent mole/placenta was also compared when available. According to STR results showing the presence or absence of the paternal chromosomal complement, the gestational or non-gestational origin of the tumor and the nature of the causative pregnancy was identified.ResultsFourteen tumors were gestational. Of these, seven were androgenetic/homozygous XX, and two were androgenetic/heterozygous XX, indicating that the causative pregnancies were molar pregnancies. Among the nine molar pregnancies, five were of the occult type. A menopausal patient developed a tumor from a mole that occurred seven years ago, identified by the genetically identical allele from the tumor and prior mole. One tumor originating from a previous mole was interrupted by term delivery. Two tumors found eight weeks postpartum were identified as originating from a prior occult mole. A pelvic choriocarcinoma was separated from a genetically distinct third trimester intrauterine placenta. Five gestational tumors were biparental: 2 XX, 3 XY. Of three ovarian tumors, two were confirmed gestational (1 androgenetic/homozygous XX; 1 biparental XY), and one was an ovarian tumor (XX) with a complete match of the genotype for all 15 loci, therefore ascertaining its non-gestational origin.ConclusionGestational choriocarcinoma can originate in an androgenetic or biparental manner. The majority are androgenetic/homozygous XX, while a large number of them might be occult molar pregnancies. The origin of ectopic androgenetic choriocarcinoma with concurrent intrauterine placenta might be from either dispermic twin gestation (mole and coexistent nonmolar fetus) or an antecedent molar pregnancy. Choriocarcinoma shortly postpartum might not be associated with the last placenta. STR analysis can be useful in distinguishing gestational choriocarcinoma from non-gestational, as well as the causative pregnancy, and serve as a helpful examination tool for guiding clinical management.

Infantile and Maternal Choriocarcinoma: A Case Report and Review of Literature

Background: Choriocarcinoma is a rare highly malignant trophoblastic neoplasm. It can be preceded by any form of gestation including a complete or a partial mole, miscarriage and normal pregnancy. Simultaneous intraplacental choriocarcinoma involving both mother and infant is extremely rare. Hepatomegaly, anemia, elevated sHCG is the diagnostic triad. Here we report a 6 weeks old Afghan girl infant with intraplacental choriocarcinoma presented by severe anemia and widespread multiple metastatic lesions in liver, lung and brain with an elevated level of sHCG . According to rarity of the disease, rapid progression and the high mortality rate with delay in diagnosis and intervation , choriocarcinoma should be one of the differential diagnosis in severe infantile and maternal anemia without any antecedent reason. According to highly vascular and friable nature of tumor, biopsy can be dangerous for diagnosis. As choriocarcinoma secrets sHCG, measurement of serum sHCG is the most common method used to diagnose choriocarcinoma

A population-based study of rare malignant trophoblastic neoplasms: Epithelioid trophoblastic tumor and placental site trophoblastic tumor

A population-based study of rare malignant trophoblastic neoplasms: Epithelioid trophoblastic tumor and placental site trophoblastic tumor

Transfusion materno-fœtale et diagnostic de choriocarcinome gestationnel

Choriocarcinoma is a rare but agressive malignant trophoblastic neoplasm. Fetomaternal transfusion can be the first sign of choriocarcinoma. We describe two cases of gestational choriocarinoma whose first manifestation was a fetomaternal transfusion. Fetomaternal transfusion is a rare demonstration of choriocarcinoma but its diagnosis must lead to a placenta examination with specific research of choriocarcinoma. The more the therapeutic care is precise, the better is the forecast.

Foetal defence against cancer: a hypothesis

Foetal defence against cancer: a hypothesis

Massive Fetomaternal Hemorrhage Caused by an Intraplacental Choriocarcinoma: A Case Report

Background. Intraplacental choriocarcinoma is a rare but highly malignant trophoblastic neoplasm. When found near term the risk of maternal metastasis is high because of the late diagnosis. Case. We describe a case of an intraplacental choriocarcinoma diagnosed postpartum after a near-term delivery of a severely anemic infant. A fetomaternal hemorrhage resulted in a hemoglobin concentration in the infant of only 2,1 g/dL. Neither mother nor child showed signs of metastatic disease. The macroscopic examination showed a hydropic placenta weighing more than 1 kilogram. Microscopy showed an intraplacental choriocarcinoma 3 cm in diameter. The tumor had infiltrated the maternal basal plate. Conclusion. Fetomaternal bleeding is a rare form of presentation of choriocarcinoma but its presence should always warrant detailed examination of placenta, mother, and infant.

Molecular Genetic Analyses of Choriocarcinoma

Background Choriocarcinoma is a highly malignant trophoblastic neoplasm. Most of them are gestational in origin, while non-gestational ones are exceedingly rare. The genetic origin, immunogenicity, sensitivity to chemotherapy and prognosis of these two kinds of conditions are quite different, so identification of these two kinds of choriocarcinoma is of great importance. The objective of this study is to distinguish choriocarcinoma as gestational or non-gestational and identify the causative pregnancy of gestational choriocarcinoma through molecular genetic analysis. Methods Twelve patients with choriocarcinoma, who had experienced surgery prior to chemotherapy, were enrolled in this study. DNA was prepared from blood samples from the patient and her partner using standard techniques. In order to prepare DNA from choriocarcinoma tissue, areas of choriocarcinoma were firstly microdissected from haematoxylin and eosin-stained sections. PCR amplification and fluorescent microsatellite genotyping were performed using DNA from the couples and captured tissue. The genetic contributions to the choriocarcinoma were determined by comparing the genotypes of the choriocarcinoma and that of the couples. Results Four of twelve cases had only a maternal contribution, indicating a non-gestational origin. The remaining eight cases were all gestational in origin and the causative pregnancies were identified as AnCHM (androgenetic complete hydatidiform mole) in six and normal pregnancies in two respectively. Conclusion Microsatellite polymorphism analysis is a molecular approach for distinguishing the non-gestational choriocarcinoma from the gestational one, and can also be used to identify the causative pregnancy of gestational choriocarcinoma. Antecedent pregnancy prior to choriocarcinoma is not always its causative pregnancy. Therefore, it is reasonable to identify the causative pregnancy by its genetic origin, instead of clinical impression.

Genetic Origin of Malignant Trophoblastic Neoplasms Analyzed by Sequence Tag Site Polymorphic Markers

Objective. To study the causative conception of malignant gestational trophoblastic neoplasms (GTNs), we analyzed malignant GTNs by microsatellite PCR markers.Method. DNAs extracted from 12 malignant GTNs were subjected to PCR for five different chromosomal locations.Result. Of the 7 cases after a complete mole (CM), 5 were derived from androgenesis, but the remaining 2 were from normal fertilization. Of the 5 cases after nonmolar pregnancies, 2 placental site trophoblastic tumors had alleles from both parents. Of the other 3 choriocarcinomas, 1 was from normal fertilization after spontaneous abortion but 2 originated from androgenesis, suggesting that 1 was from a CM prior to the antecedent abortion, transforming after a long interval.Conclusion. By combining the previous cases with these, our analysis of 39 cases demonstrated that trophoblastic neoplasms can arise from at least three different modes of origin (androgenesis, normal fertilization, and parthenogenesis), and antecedent pregnancy is not always identical to the causative conception. Placental site trophoblastic tumors might have different machinery for carcinogenesis because of the predominance of paternal and maternal contributions. In addition, a long dormancy of trophoblasts before malignant transformation, especially for those originating from normal fertilization, was also suggested.

Expression of CDKI P27 Kip1 in malignant and non-malignant trophoblastic cells

Summary The cyclin-dependent kinase inhibitors (CDKIs) inhibit the kinase activities of the cyclin and CDK complexes and block transitions of the cell cycle. As a negative regulator of the cell cycle, CDKI P27 kip1 regulates the decision of cell cycle to enter into S-phase or arrested in G1-phase by blocking G1 cyclin dependent kinase activities. Evidence suggests that P27 kip1 may be involved in tumorigenesis and acts as a tumor suppressor gene. In this study, the expression of P27 kip1 in complete hydatidiform mole (CHM), invasive mole (IM) and choriocarcinoma (CC) was investigated as well as in normal chorionic villi by immunohistochemistry. Decreased expression of P27 kip1 was observed in malignant trophoblastic neoplasms with a positive rate of 21.43%, which is less than that in normal chorionic villi (80%) and in CHM (73.33%) (P kip1 in those CHMs with large uterus size for gestational date was lower than that in those with a normal or small uterus for date (42.86% vs 100%). (P kip1 may be involved in the tumorigenesis of gestational trophoblastic neoplasm as a negative regulator of cell cycle, and the expression level of P27 kip1 in trophoblastic cells may be a prognostic factor for CHM.

Integrin αvβ3, expression on the endometrium in infertile women

Choriocarcinoma is a highly malignant trophoblastic neoplasm. Most of them are gestational in origin, while non-gestational ones are exceedingly rare. The genetic origin, immunogenicity, sensitivity to chemotherapy and prognosis of these two kinds of conditions are quite different, so identification of these two kinds of choriocarcinoma is of great importance. The objective of this study is to distinguish choriocarcinoma as gestational or non-gestational and identify the causative pregnancy of gestational choriocarcinoma through molecular genetic analysis.Twelve patients with choriocarcinoma, who had experienced surgery prior to chemotherapy, were enrolled in this study. DNA was prepared from blood samples from the patient and her partner using standard techniques. In order to prepare DNA from choriocarcinoma tissue, areas of choriocarcinoma were firstly microdissected from haematoxylin and eosin-stained sections. PCR amplification and fluorescent microsatellite genotyping were performed using DNA from the couples and captured tissue. The genetic contributions to the choriocarcinoma were determined by comparing the genotypes of the choriocarcinoma and that of the couples.Four of twelve cases had only a maternal contribution, indicating a non-gestational origin. The remaining eight cases were all gestational in origin and the causative pregnancies were identified as AnCHM (androgenetic complete hydatidiform mole) in six and normal pregnancies in two respectively.Microsatellite polymorphism analysis is a molecular approach for distinguishing the non-gestational choriocarcinoma from the gestational one, and can also be used to identify the causative pregnancy of gestational choriocarcinoma. Antecedent pregnancy prior to choriocarcinoma is not always its causative pregnancy. Therefore, it is reasonable to identify the causative pregnancy by its genetic origin, instead of clinical impression.

Malignant trophoblastic neoplasms with different modes of origin

The genetic origin of 24 trophoblastic neoplasms was determined using PCR polymorphisms. Based on pregnancy history, these tumors included nine postmolar trophoblastic tumors, 12 tumors preceded by live birth or abortion, and three nongestational tumors. Androgenetic origin was defined in eight post-molar trophoblastic tumors, and the remaining one might have arisen from a normal fertilization. Six tumors retained genetic features carried by the homozygous complete mole. Two tumors showed PCR polymorphism compatible with that of the heterozygous complete mole. All 12 tumors in the second class had alleles of both paternal and maternal contribution. However, discordance of sex between the antecedent pregnancy product and the tumor was recognized in three choriocarcinomas. The absence of paternal contribution suggested a parthenogenetic origin of three nongestational choriocarcinomas. The findings that PCR polymorphisms were either homozygous in certain loci or heterozygous in others may mean that the tumor was derived from a germ cell after meiosis I. As a result, at least three subtypes with different modes of origin were demonstrated in the 24 trophoblastic tumors. These findings underscore the importance of precise genetic marker analyses in a large series to clearly identify clinical and biologic characteristics of each subset of tumors.

Genetic origin of malignant trophoblastic neoplasms

The genetic origin of three trophoblastic neoplasms [two choriocarcinomas and a placental site trophoblast tumor (PSTT)] was determined by analysis of the restriction fragment length polymorphism (RFLP) pattern. One choriocarcinoma, which was believed not illogically to have developed from an antecedent complete mole, contained both paternal and material RFLP alleles and thus was probably the product of a normal fertilization. The other choriocarcinoma was not of gestational origin but had RFLPs homozygous at some loci and heterozygous at others, compatible with the parthenogenic origin of this tumor from a germ cell after meiosis I. The PSTT required amplification of DNA sequences by polymerase chain reaction (PCR) because of the small amount of tumor material available. This tumor contained RFLP alleles from both parents and appeared to have resulted from a previous unrecognized (and abnormal) pregnancy.

Pregnancy outcomes after successful chemotherapy for choriocarcinoma and invasive mole: Long-term follow-up

In order to preserve the fertility of young patients with choriocarcinoma and invasive mole, chemotherapy alone was given without hysterectomy in 265 cases from 1959 through 1980. By the end of 1985, 205 patients had become pregnant after recovery, with a total of 355 pregnancies. Among these, 23 were terminated by induced abortions, 26 as miscarriages, two as ectopic gestations, two as intrauterine deaths, and three as stillbirths. Among 303 livebirths (including four sets of twins), six infants died neonatally, three of whom were found to have congenital anomalies incompatible with life, and two died during infancy. All the remaining 295 children had normal growth and development, the oldest now being 25 years of age. The rates of fetal wastage, malformations, twin pregnancies, and neonatal and infantile deaths did not deviate from the normal. Cytogenetic study of the peripheral lymphocytes of 94 of the children revealed no increase of chromosomal aberrations. The rates of recurrence of disease and of death caused by recurrence of disease in these were not increased in comparison with those in patients who underwent hysterectomy. These data indicate that treatment of malignant trophoblastic neoplasms with chemotherapy alone is compatible with the preservation of fertility in most women.

Re-evaluation of 5-fluorouracil as a single agent for gestational malignant trophoblastic neoplasms.

Large doses of 5-fluorouracil, administered by slow intravenous drip, have proven to be very effective in the treatment of malignant trophoblastic tumors. From 1964 through 1975, 5-fluorouracil was used as a single chemotherapeutic agent in 173 cases of invasive mole and 139 cases of choriocarcinoma. This series of patients was further divided into Group A (212 cases) in which 5-fluorouracil was used as initial therapy, and Group B (100 cases) in which 5-fluorouracil was given to those who developed resistance to 6-mercaptopurine and/or to methotrexate. The overall remission rate in Group A patients was 98.4% for invasive mole and 93.0% for choriocarcinoma. In Group B patients the corresponding remission rate was 93.6% and 71.7%, respectively, indicating that 5-fluorouracil is effective in patients who develop resistance to other antimetabolic agents. The rate of recurrence among 213 patients achieving complete remission during follow-up was 1.4% (3 cases). All of the remaining 210 patients had survived for more than 5 years up to the end of 1981, and 96 patients (45.7%) had survived for more than 10 years. In comparison with other antimetabolites, 5-fluorouracil has the advantages of being more effective and less toxic, and can be administered through multiple routes. Therefore, it has remained the agent of first choice in the chemotherapy of malignant trophoblastic neoplasms.

A proposal on the clinical staging of malignant trophoblastic neoplasms based on the study of process of development of the disease.

An agreement on the criteria of diagnosis of malignant trophoblastic neoplasms has been reached in recent years. Outstanding achievements have been made in the treatment causing a dramatic improvement in prognosis. However, there still lacks a satisfactory clinical staging which may be used to designate the extent and development of this group of tumors. Without a universally accepted method of staging, the clinical materials from various sources cannot be compared, the prognosis of patients cannot be correctly predicted, and the therapeutic results of different methods of treatment cannot be accurately evaluated. Therefore, in 1962, based on the careful analysis of a large series of cases, a preliminary proposal of clinical staging of malignant trophoblastic tumors was reported (1). Through years of trial in patients, it was found that this staging method is very practical for clinical use and correlates well with the prognosis of the disease (2). Recently, it has been re-evaluated on the basis of an intensive study of the process of development of the diseases in 870 patients. The results are reported below.KeywordsBrain MetastasisPulmonary MetastasisTumor EmbolusOvarian VeinChest FilmThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.