Long-term survival after choriocarcinoma transmitted by liver graft: A successful report in pediatric transplantation.

BACKGROUND: LT is the standard of care for many pediatric liver disorders. Although long-term outcomes have improved, some rare complications such as transmission of occult donor tumors have been reported. CASE REPORT: An adolescent diagnosed with tyrosinemia was submitted to LT from a previous healthy donor due to HCC. Almost 8 months after LT, the patient presented a nodular hepatic lesion. Clinically, he had mild weight loss, lower limb edema, and gynecomastia. Thorax CT found lesions in the left lung parenchyma, which showed no increased uptake in PET SCAN. Liver biopsy revealed a carcinoma with desmoplastic stroma. ISS was withdrawn, and palliative chemotherapy was started for presumptive HCC relapse. AFP remained normal, but HCG had reached unexpected values of 1984 IU/L. As we requested detailed information about the other organ recipients from the same donor, we found that one of them passed away due to disseminated tumor. Five months after the beginning of chemotherapy, the patient underwent resection of liver segments V and VI. Histological examination confirmed liver metastatic choriocarcinoma. At the time of writing, with 11 years of follow-up, the patient had sustained remission with no signs of relapse. DISCUSSION: This case reports a diagnostic challenge in an adolescent with a particular unique background and a very rare pattern of tumor transmission. The authors aim to highlight the risk of cancer-bearing organs reveled post-LT and to testimony the experience of the successful outcome after a choriocarcinoma transmitted by liver graft.

Short tandem repeat analysis to identify the causative pregnancy of high-risk gestational trophoblastic neoplasia: Molar versus nonmolar pregnancy and its relation to the outcome.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) include a group of malignant neoplasms that originate from the trophoblasts of placental tissue in molar or nonmolar pregnancy. Currently, it is unclear whether the prognosis of high-risk GTN or gestational choriocarcinoma succeeding molar pregnancy or that following a nonmolar one is better. Comparison of the genetic short tandem repeat (STR) patterns of the DNA extracted from the tumor, patient, and her partner allows the genetic origins of the choriocarcinoma to be distinguished - whether it is gestational or non-gestational and whether it is derived from a molar or nonmolar pregnancy in the event it is gestational. This study aimed to investigate the causative pregnancy of patients with high-risk GTN, especially those with poor outcomes, and assess the impact of the causative pregnancy on patient outcome. METHODS: We evaluated 24 patients who were diagnosed with high-risk GTN between January 2000 and October 2019, including 15 cases of pathologically proven gestational choriocarcinomas and the causative pregnancy was investigated by STR analysis in which tumor DNA could be extracted. RESULTS: In high-risk GTN without history of anteceding molar pregnancies, nonmolar pregnancy was the causative pregnancy, which was confirmed in three cases. Molar pregnancy appeared be the causative pregnancy of high-risk GTN in patients with a history of antecedent molar pregnancies either with or without interruption by subsequent nonmolar pregnancies prior to developing high-risk GTN. High-risk GTN in most of the evaluated deceased cases (three of four) was due to nonmolar pregnancy, while all but one case with molar pregnancy as the causative pregnancy survived. DISCUSSION: STR analysis can distinguish the causative pregnancy of high-risk GTN, and nonmolar pregnancy as the causative pregnancy might have negative effects on the outcome of the disease.

Donor Choriocarcinoma Transmission From Solid Organ Transplantation: A Case Report.

Transplantation of any organ has some inherent risk of disease transmission, such as infection and malignancy. The present study aims to describe 2 cases of choriocarcinoma transmission after kidney and liver transplantation originating from the same patient. The donor was a 17-year-old woman who died of cerebral hemorrhage. Both organ recipients died of metastatic choriocarcinoma few months after the transplantation, within days after starting chemotherapy. Retrospective hCG (human chorionic gonadotropin hormone) analysis in donor's blood stored at the time of donation had a result of 9324 mIU/mL. Despite its rarity, clinicians should be aware of the risk of transplant-related choriocarcinoma from female donors in childbearing age. In some cases, hCG dosage should be performed before donation.

Transmission of a TP53 germline mutation from unaffected male carrier associated with pediatric glioblastoma in his child and gestational choriocarcinoma in his female partner.

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by germline alterations in the tumor suppressor gene TP53 LFS is associated with numerous malignancies including astrocytoma. Sanger sequencing and chromosomal microarray studies of blood and tumor tissue from a 4-yr-old boy with glioblastoma demonstrated a germline TP53 mutation with loss of heterozygosity for the short arm of Chromosome 17 as the second inactivating event in the tumor. There was no family history of LFS, but the child's mother had recently died from metastatic choriocarcinoma after antecedent normal term delivery of a then 6-mo-old daughter. The choriocarcinoma contained the same TP53 mutation detected in the proband and the 6-mo-old daughter was confirmed to be a carrier. Unexpectedly, the germline TP53 mutation was found to be inherited from the unaffected father. We report here the second genetically confirmed case of TP53-mutated choriocarcinoma in the partner of an LFS patient. Based on this case and recent literature, female partners of LFS patients may have increased risk of choriocarcinoma due to transmission of germline TP53 mutation from male carriers. Although the Toronto protocol has established an effective approach to detect tumors and improve survival in children and adults with LFS, there is a need to expand the current criteria to include surveillance of female partners of LFS patients for choriocarcinoma and other gestational trophoblastic disease. Recognition of this unique mode of transmission of TP53 mutations should be considered in genetic counseling for cancer risk assessment and family planning.

Primary intestinal choriocarcinoma in a patient with long-standing Crohn's disease.

Extra-gonadal choriocarcinoma is an extremely rare highly malignant neoplasm with a poor prognosis. In the gastrointestinal tract it usually arises in stomach, esophagous, bowel intestine and colon. Only few cases are pure and not associated with a classic adenocarcinoma. The correlation of Crohn's disease with choriocarcinoma is not reported. We describe a case of 47-year old man with primary choriocarcinoma of the colon in a previously documented Crohn's disease.

Malignancy risk scoring of hydatidiform moles.

BACKGROUND: Several risk factors leading to malignant transformation of hydatidiform moles have been described previously. Many studies showed that prophylactic chemotherapy for high risk hydatidiform moles could significantly decrease the incidence of malignancy. Thus, it is essential to discover a breakthrough to determine patients with high risk malignancy so that prophylactic chemotherapy can be started as soon as possible. OBJECTIVES: Development of a scoring system of risk factors as a predictor of hydatidiform mole malignant transformation. MATERIALS AND METHODS: This research is a case control study with hydatidiform mole and choriocarcinoma patients as subjects. Multiple logistic regression was used to analyze the data. Odds ratios (OR), attributable at risk (AR : OR-1) and risk index (ARxß) were calculated for develoipment of a scoring system of malignancy risk. The optimal cut-off point was determined using receiver operating characteristic (ROC) curve. RESULTS: This study analyzed 34 choriocarcinoma cases and 68 benign hydatidiform mole cases. Four factors significantly increased the risk of malignancy, namely age≥35 years old (OR:4.41, 95%CI:1.07- 16.09, risk index 5); gestational age≥12 weeks (OR:11.7, 95%CI:1.8-72.4, risk index 26); uterine size greater than the gestational age (OR:10.2, 95%CI:2.8-36.6, risk index 21); and histopathological grade II-III (OR:3.4, 95%CI:1.1-10.6, risk index 3). The lowest and the highest scores for the risk factors were zero and 55, respectively. The best cut-off point to decide high risk malignancy patients was ≥31. CONCLUSIONS: Malignant transformation of hydatidiform moles can be predicted using the risk scoring by analyzing the above four parameters. Score≥31 implies high risk patients so that prophylactic chemotherapy can be promptly administered for prevention.

Organ transplantation from donors (cadaveric or living) with a history of malignancy: review of the literature.

The evolution of organ transplantation has resulted in extended lifespan as well as better life quality of patients with end-stage diseases, which in turn causes an increased demand for organs. The persistent organ shortage requires a careful reconsideration of potential donors (living or cadaveric) that have current or historical malignancies. Donors with low-grade skin tumors, carcinomas in situ of the uterine cervix, and primary central nervous system (CNS) tumors can be considered as potential donors for recipients dying on wait list longing for organ transplantation. Recently, transplant centers have turned to other types of malignancies including low grade renal cell carcinoma, prostate, ureteral, endometrial and breast cancer, and favorable outcomes have been shown in such innovations. When considering donors with a history of malignancy, general biologic behavior of the tumor type, histology and stage at the time of diagnosis, and the length of disease-free interval should be considered (Transplantation 2002;74(12):1657-1663). With the review of literatures, we illustrate the organ utilization from donors with malignancies all around the world since earlier times and give some suggestions for decision making under the circumstance of whether to choose those marginal donors or not on the basis of reviewed literatures.

Establishment of a choriocarcinoma model from immortalized normal extravillous trophoblast cells transduced with HRASV12.

Gestational choriocarcinoma is a malignant trophoblastic tumor. The development of novel molecular-targeted therapies is needed to reduce the toxicity of current multiagent chemotherapy and to treat successfully the chemoresistant cases. The molecular mechanisms underlying choriocarcinoma tumorigenesis remain uncharacterized, however, and appropriate choriocarcinoma animal models have not yet been developed. In this study, we established a choriocarcinoma model by inoculating mice with induced-choriocarcinoma cell-1 (iC³-1) cells, generated from HTR8/SVneo human trophoblastic cells retrovirally transduced with activated H-RAS (HRASV12). The iC³-1 cells exhibited constitutive activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways and developed into lethal tumors in all inoculated mice. Histopathological analysis revealed that the tumors consisted of two distinct types of cells, reminiscent of syncytiotrophoblasts and cytotrophoblasts, as seen in the human choriocarcinoma. The tumors expressed HLA-G and cytokeratin (trophoblast markers) and hCG (a choriocarcinoma marker). Comparative analysis of gene expression profiles between iC³-1 cells and parental HTR8/SVneo cells revealed that iC³-1 cells expressed matrix metalloproteinases, epithelial-mesenchymal transition-related genes, and SOX3 at higher levels than parental trophoblastic cells. Administration of SOX3-specific short-hairpin RNA decreased SOX3 expression and attenuated the tumorigenic activity of iC³-1 cells, suggesting that SOX3 overexpression might be critically involved in the pathogenesis of choriocarcinoma. Our murine model represents a potent new tool for studying the pathogenesis and treatment of choriocarcinoma.

What do women with gestational trophoblastic disease understand about the condition?

INTRODUCTION: Little is known about patients' understanding of the causes, treatments, and implications of gestational trophoblastic disease (GTD). Clinical observation suggests that such health literacy is limited. We report on the perceptions of causes and treatment of GTD and its impact on fertility and reproductive outcomes. METHODS: Cross-sectional analysis of 176 Australian women previously diagnosed with GTD (no longer receiving follow-up/treatment) recruited from a state-wide registry. Participants comprised 149 (85%) women with GTD who did not require chemotherapy and 27 (15%) women who required chemotherapy for malignancy or persistent molar disease. Data were collected from medical records and via self-report questionnaire. RESULTS: Participants were 94 women (53%) with partial mole, 75 (43%) with complete mole, 4 (2%) with choriocarcinoma, and 3 (2%) with hydatidiform mole not otherwise specified. Mean (SD) age at diagnosis and time since diagnosis were 32.1 (6.3) and 4.7 (3.3) years, respectively. Chance/bad luck was the most endorsed cause (n = 146, 83%); 23 (13%) thought GTD was hereditary and 10 (6%) identified a chromosomal etiology. Between 24% and 32% were unsure of the role of alcohol/drugs, venereal diseases, smoking, pollution, contraceptives, and lowered immunity. Surgical/medical procedure (n = 127, 72%) and healthy diet (n = 53, 30%) were the most endorsed treatments. Between 18% and 23% were unsure of the treatment effectiveness of diet, vitamins, exercise, complementary therapy, and contraception. All women treated with chemotherapy understood the rationale thereof; 23 (85%) perceived chemotherapy to be successful, and 19 (70%) could name the agent. Few women perceived a negative impact on their fertility (n = 28, 16%); 52 (30%) were reluctant to conceive again and 100 (57%) questioned their ability to have healthy children. After diagnosis, 111 (63%) had at least 1 live birth. CONCLUSIONS: Notwithstanding limitations, this study is the largest of its type to date. These descriptive data enhance our understanding of patients' experience on GTD, highlight the scope of GTD health literacy, and may be useful for clinicians to adjust the content of their patient education.

Choriocarcinoma in an AIDS patient--relapsing but not fatal.

Choriocarcinoma is associated with high mortality in immunocompromised patients, in contrast to a good prognosis in immunocompetent individuals. Respiratory failure due to metatstatic choriocarcinoma is associated with high mortality in any patient. We report a case of a woman with AIDS that survived metastatic choriocarcinoma and respiratory failure. We also observed that in contrast to some in vitro studies, the markedly elevated levels of beta-subunit of human chorionic gonadotropin in this patient did not have any apparent inhibitory effect on viral replication.

[Successful treatment of locally invasive, nonmetastatic choriocarcinoma after ectopic pregnancy by monochemotherapy].

A case of choriocarcinoma in 33-year old woman after ectopic pregnancy has been reported. CT-scan established an invasion of the vagina, posterior wall of the bladder and rectum. The patient's leading symptoms were: severe genital bleeding,haematuria, acute postbleeding anaemia, haemorrhagical shock. After treatment with Metothrexate and symptomatic therapy the patient achieved complete clinical remission and she is free of disease 18 months after the onset of the therapy.

Gestational choriocarcinoma arising from a cornual ectopic pregnancy: a case report and review of the literature.

INTRODUCTION: Gestational choriocarcinoma associated with ectopic pregnancy is an extremely rare event. We report a case of a choriocarcinoma arising from a cornual pregnancy. CASE: The patient is a 35-year-old G8 P2052 who was referred to our department due to failure of treatment for a suspected ectopic pregnancy. The patient had initially been treated with methotrexate injection but her beta-hCG levels reached a plateau 3 weeks later and, despite another two methotrexate injections, started to rise. The patient underwent dilation and curettage that did not reveal any trophoblastic tissue. A diagnostic hysteroscopy that followed demonstrated occluded ostia of the left tube. The patient subsequently underwent diagnostic laparoscopy that revealed a mass in the left cornua, which was removed with wedge-wide resection. Histologic evaluation revealed choriocaricnoma. DISCUSSION: Appropriate monitoring of beta-hCG titers following conservative management of suspected ectopic pregnancy is important, not only to diagnose persistent ectopic gestation, but also to rule out the presence of malignant trophoblastic disease, albeit the latter is a rare diagnosis.

Postpartum choriocarcinoma presentation, management and survival.

OBJECTIVE: To determine the clinical presentation and outcome of postpartum choriocarcinoma. STUDY DESIGN: Case note review of patients with choriocarcinoma treated at the Sheffield Trophoblastic Disease Centre. RESULTS: Thirty-five patients were identified between 1977 and 2005. Mean age was 27 years (range, 21-37). Thirty-three patients complained of persistent postpartum hemorrhage, and in 3 cases there were other symptoms. Two patients presented with nongynecologic symptoms. Mean time until diagnosis was 7 weeks postpartum (range, 0-60), with a mean delay from onset of symptoms to treatment of 7 weeks (maximum, 19). Twenty patients had metastatic disease, but this did not correlate with delay in diagnosis. The mean International Federation of Gynecology and Obstetrics score was 10. Multidrug regimens were used in most patients; however, 8 low-risk patients had a complete response with methotrexate alone. The mean survival was 7.8 years (range, 1-21). Two patients died from disease. CONCLUSION: Postpartum choriocarcinoma presents mainly with vaginal bleeding, and there is often a delay in diagnosis despite being under the care of gynecologists. In the small numbers that present with nongynecologic symptoms there is a rapid awareness of the possibility of gestational trophoblastic neoplasia; nevertheless, the outcome may be fatal, especially in the presence of symptomatic brain metastases.

Hemorragia digestiva e invaginación intestinal por coriocarcinoma intestinal / Gastrointestinal bleeding and intestinal invagination due to intestinal choriocarcinoma

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Trends in gestational choriocarcinoma: a 27-year perspective.

OBJECTIVE: To evaluate trends in incidence and survival rates for gestational choriocarcinoma with the use of population-based data. METHODS: Overall and 5-year average age-adjusted incidence rates were computed with the Surveillance, Epidemiology, and End Results program public-use database. Differences by age at diagnosis, race, stage, registry, and over calendar time were compared by Poisson regression, and survival censored for deaths other than choriocarcinoma by log-rank tests and Cox's proportional hazard ratios. RESULTS: Between 1973 and 1999, 450 cases were recorded. The annualized age-adjusted incidence rate for choriocarcinoma was 0.133 per 100,000 woman-years and decreased by 49.7% (2.8% per year). By race (whites, blacks, and others), incidence rates declined by 62.3%, 27.2%, and 54.3%, respectively. In the Poisson model evaluating incidence rates, age, race, registry, and stage were significant main effects. Compared with whites, the relative risk was higher for blacks (2.14, 95% confidence interval [CI] 1.60, 2.86) and others (2.30, 95% CI 1.67, 3.18). Rates were highest in Utah and lowest in Iowa. By age at diagnosis, rates were higher in 20-39-year-olds. The 5-year relative survival rate was 89.5%. Censored survival was significantly lower among blacks (whites 92.4%, blacks 84.9%, others 87.1%, P = .045), for advanced disease (localized 94.5%, regional 92.9%, distant 87.1%, P = .02), and with increasing age at diagnosis (P = .017). Age and calendar time significantly influenced censored survival independent of stage and registry. CONCLUSION: Gestational choriocarcinoma incidence rates have declined and survivals have improved, but blacks continue to have higher incidence and lower survival rates.

Ethnic differences at risk for gestational trophoblastic disease in New Mexico: A 25-year population-based study.

OBJECTIVE: The purpose of this study was to compare gestational trophoblastic disease incidence rates with the use of population-based data. STUDY DESIGN: All incident cases between 1973 and 1997 and live birth, pregnancy, and women at risk were tabulated with the use of data that were derived from the New Mexico Tumor Registry and Vital Records and Health Statistics Annual Reports. Statistical methods included trends analyses, odds ratios, and Poisson regression. RESULTS: Of 939 total cases, 312 non-Hispanic white women, 399 Hispanic white women, 201 American Indian women, and 27 other women were affected. Age-adjusted incidence rates were significantly higher for American Indian women (11.16%) compared with non-Hispanic (3.57%) or Hispanic white women (5.32%); the probability value was <.001. When live birth (1:438 women) and pregnancy (1:486 women) denominators were considered, American Indian women alone were at increased risk, and the ratio increased by 56% over 25 years. American Indian women were also at increased risk for partial mole (relative risk, 4.03; 95% CI, 2.57-6.31), invasive mole (relative risk, 26.7; 95% CI, 7.81-93.14), and choriocarcinoma (relative risk, 6.29; 95% CI, 1.81-22.66) variants. CONCLUSION: American Indians are at increased risk relative to the other predominant ethnic groups in New Mexico. Age-adjusted standardization provided a reproducible measurement that may be applicable across other registries.

Transmission of donor cancer into cardiothoracic transplant recipients.

BACKGROUND: The demand for transplantable organs exceeds donor supply. Patients with central nervous system (CNS) or other tumors are controversial donors, and the donor cancer transmission rates in cardiothoracic transplant recipients have not been determined. The Israel Penn International Transplant Tumor Registry (IPITTR) was queried to define the risk of donor cancer transmission in cardiothoracic transplant recipients. METHODS: All heart, lung, or heart-lung recipients of organs from donors with a history of malignancy were reviewed. Donor and recipient demographics, histologic findings, and recurrence were reviewed. RESULTS: Twenty-two patients received 17 hearts, 3 lungs, and 2 heart-lung transplants from donors with known CNS or other malignancies. No malignancy transmissions were noted with astrocytomas (n = 3) or glioblastomas (n = 1), except a medulloblastoma that recurred at 6 months. The transmission rate for CNS tumors was 17% (1 of 6), and 1- and 3-year survivals were 67% and 50%, respectively. The most common non-CNS donor cancer was renal cell carcinoma (n = 5). Two renal cell cancer transmissions occurred, both when vascular extension was present. The most aggressive tumor transmission was choriocarcinoma (n = 2) and melanoma (n = 2). Two of 3 choriocarcinomas metastasized with 67% mortality, and both melanomas were transmitted and resulted in death. Other donor cancers included angiosarcoma (n = 2), cervical (n = 1), lung (n = 1), prostate (n = 1), and a liver adenocarcinoma. The transmission rate for all non-CNS groups was 56% (9 of 16) with a 2-year survival of 40%. CONCLUSIONS: The IPITTR experience indicates that tumor transmission is high (10 of 22, 45%) in cardiothoracic transplant recipients. Similar to intra-abdominal organ recipients in the IPITTR, (1) renal cell carcinomas without capsular invasion appear safe with no transmission, (2) vascular invasion in renal cell carcinoma appears to result in early tumor transmission, and (3) melanoma and choriocarcinoma have high rates of transmission with early and almost universal death.