Primary paediatric intracranial epithelioid haemangioendothelioma.
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Biomarkers, Tumor↗
Biomedical subjects
F J Paradinas
Publications and source records attributed to F J Paradinas.
The diagnosis of hydatidiform mole in early tubal ectopic pregnancy.
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Choriocarcinoma↗
Pseudo-partial moles: placental stem vessel hydrops and the association with Beckwith-Wiedemann syndrome and complete moles.
AIMS: To describe the clinical and histological features of a series of cases of placentas originally diagnosed as partial moles in which the final diagnosis was that of placental stem villous hydrops, mesenchymal dysplasia or Beckwith-Wiedemann syndrome. METHODS AND RESULTS: We searched a computerized database containing cases of suspected or proven trophoblastic disease examined at the Trophoblastic Disease Unit at Charing Cross Hospital, London, to identify cases in which stem vessel hydrops was present without other histological features of partial mole. For each case, histological sections were examined and the histological features present recorded. There were 15 cases identified. Placental weight was above the 95th centile of the normal for gestation in all cases in which this information was documented. In an additional five cases the placenta was described as 'large'. All cases had marked stem vessel hydropic change with cyst formation and in the majority of cases some terminal villous hydrops was also present. In 13 of the 15 cases there was marked aneurysmal dilatation of stem villous vessels. Nine had focal chorioangiomatoid change and in four of these extramedullary haematopoiesis was focally present in these areas. No excessive trophoblast proliferation was noted in any case and no trophoblastic inclusions typical of partial mole were identified. CONCLUSIONS: This study has identified cases of stem villous hydrops, mesenchymal dysplasia or Beckwith-Wiedemann spectrum in pregnancies initially diagnosed as partial hydatidiform mole in the second half of pregnancy and has highlighted the need for detailed pathological examination and clinicopathological correlation in all such cases.
Adolescent↗
Expression of ZO-1 and occludin in normal human placenta and in hydatidiform moles.
Zonula occludens-1 (ZO-1) and occludin are key molecules in cell-cell contacts. They are tight junction constituents and therefore play a pivotal role in tissue differentiation and organogenesis. In the present report we have investigated the expression of ZO-1 and occludin in normal human placentae and in hydatidiform moles using immunohistochemical and Western blot analyses. In normal placentae, ZO-1 and occludin were mainly localized in the apical part of the syncytium, in cell-cell contacts between syncytium and villous cytotrophoblastic cells as well as between the latter. Extravillous cytotrophoblast of cell islands and cell columns was positive for ZO-1 and occludin in the cell layers proximally located to the villous stroma whereas the cytotrophoblastic cells, distally located from the villous stroma, were totally negative. Furthermore, fetal vessels showed a positive staining pattern for ZO-1 throughout gestation, whereas a positive reaction for occludin was produced mainly at term. A striking result was the altered expression of ZO-1 and occludin in partial and complete moles. In 11 moles, these two molecules were not expressed at all, while in the other nine, their expression was only cytoplasmic in syncytium and villous cytotrophoblastic cells. These findings suggest that ZO-1 and occludin participate in normal placental development, maintaining the organization and functions of different tissue components. The down-regulation and/or dysregulation of these two molecules may be related to phenotypic changes associated with epithelial cell transformation of the chorionic villi in partial and complete moles.
Blotting, Western↗
Choriocarcinoma and partial hydatidiform moles.
BACKGROUND: Partial hydatidiform moles (PMs) rarely require chemotherapy and have never previously been proven to transform into choriocarcinoma, the most malignant form of gestational trophoblastic disease (GTD). Consequently, some have questioned whether women with PMs need human chorionic gonadotropin (hCG) follow-up. Here, we investigate whether PMs can transform into choriocarcinomas. METHODS: Patients with a PM who developed a subsequent choriocarcinoma were identified from our GTD database. The histology of both PM and ensuing choriocarcinoma was reviewed and flow cytometry used to verify the triploid status of the PMs. To determine whether the choriocarcinoma arose from the PM, DNA from the PM and choriocarcinoma in each patient was compared using microsatellite polymorphisms. FINDINGS: Of the 3000 patients with PM, 15 required chemotherapy for persisting GTD. This was identified as choriocarcinoma in three cases. In one patient, the local pathologist could not differentiate between a PM or a hydropic abortion and neither central histological review nor hCG follow-up were obtained. This patient nearly died before the diagnosis of choriocarcinoma was made. Fortunately, the local pathologists correctly diagnosed PM in the two other patients who were then registered for hCG follow-up. Some months later, the hCG was rising and repeat uterine evacuation revealed choriocarcinoma. The PM was confirmed to be triploid in all three cases and genetic analysis showed that the subsequent choriocarcinomas contained identical single maternal and two paternal alleles at several independent loci. INTERPRETATION: Our results show that PMs can transform into choriocarcinoma. All patients with suspected PM should be reviewed centrally and, if confirmed, need hCG follow-up.
Adult↗
Amniotic tissue in complete hydatidiform moles can be androgenetic.
The purpose of this study was to determine whether amniotic tissue found associated with cases of complete hydatidiform mole (CM) was genetically identical to the CM, and therefore part of the molar pregnancy, or genetically dissimilar to the CM, suggesting derivation from a twin pregnancy. DNA was prepared from formalin-fixed, paraffin-embedded blocks of tissue containing both CM and amnion. Maternal DNA was prepared from decidual tissue in the same blocks, or from a maternal blood sample. Fluorescent microsatellite genotyping was carried out to determine the origin of both the CM and the amniotic tissue. In one of six cases examined, the amniotic tissue was genetically different from the CM and was therefore likely to be derived from a twin pregnancy. In the five remaining cases, the amniotic tissue was genetically identical to the CM and was likely to be derived from the same conceptus. It is concluded that androgenetic CM can support the development of amniotic tissue and that some early embryonic development may occur in CM. The presence of amnion, or other fetal tissues, associated with molar tissue should not therefore always be considered indicative of a diagnosis of partial mole (PM).
Alleles↗
Repetitive complete hydatidiform mole can be biparental in origin and either male or female.
Complete hydatidiform mole (CHM) is an abnormality in pregnancy due to a diploid conception which is generally androgenetic in origin, i. e. all 46 chromosomes are paternally derived. We have examined the genetic origin of repetitive hydatidiform moles in a patient having three CHM by two different partners, and no normal pregnancies. Using fluorescent microsatellite genotyping, we have shown all three CHM to be biparental, rather than androgenetic, in origin. Examination of informative markers for each homologous pair of chromosomes, in two of the CHM, failed to reveal any evidence of unipaternal disomy, suggesting that the molar phenotype might result from disruption of normal imprinting patterns due to a defect in the maternal genome. It has been suggested that intracytoplasmic sperm injection (ICSI), followed by selection of male embryos, can prevent repetitive CHM; but examination of sex chromosome-specific sequences in the three CHM described here, showed that, while two were female, the first CHM was male. Selection of male embryos is therefore unlikely to prevent repetitive CHM in this patient. Our results suggest that the genetic origin of repetitive CHM should be determined prior to in-vitro fertilization (IVF) and that current strategies for the prevention of repetitive CHM may not be appropriate where the CHM are of biparental origin.
Adult↗
Anti-neutrophil cytoplasmic antibody-positive crescentic nephritis occurring together with renal cell carcinoma.
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Aged↗
Expression pattern alterations of syndecans and glypican-1 in normal and pathological trophoblast.
Syndecans (syn-1, -2, -3, -4) and glypican-1 are proteoglycans expressed during development in association with changes in tissue organization and differentiation. They participate in the modulation of growth factor actions and in cell-cell and cell-matrix adhesion. The expression of syn-1, -2, -3, -4, and glypican-1 has been studied in normal human placenta and in gestational trophoblastic disease such as hydatidiform mole, invasive mole, and choriocarcinoma, using immunohistochemistry and western blots. Syndecan-3 was not expressed in normal or pathological tissues. During normal gestation, the other proteoglycans showed a specific staining pattern, which for some was modified during pregnancy. For instance, syn-1 was only expressed in syncytiotrophoblast; syn-4 was mainly localized in the villous and extravillous cytotrophoblast in the first trimester, whereas at term it was expressed in the syncytiotrophoblast. The most striking results are the altered expression patterns of syndecans and glypican-1 in pathological tissues. These proteoglycans showed a progressive decrease of immunostaining related to the increase of severity of trophoblastic disease, in particular in invasive mole and choriocarcinoma. In addition, dysregulation in the localization of the expression patterns was observed for syn-2 and -4. Because changes in syndecan expression enable cells to become more or less responsive to their micro-environment, the down-regulation and/or dysregulation of syndecans in relation to the degree of severity of trophoblastic diseases provides new insights into the progression of these pathologies.
Blotting, Western↗
Recent advances in gestational trophoblastic disease.
Advances in the last 20 years have led to a better understanding of the process of gestational trophoblastic disease (GTD), and consequently, to improved diagnosis, management, and prognosis. Patients with GTD should be registered at a trophoblastic disease center for follow-up, and those with persistent disease should receive chemotherapy, methotrexate, and folinic acid for low-risk disease, and EMACO (etoposide, actinomycin-D, methotrexate, vincristine, and cyclophosphamide) for high-risk disease, without loss of fertility. Most patients with relapsing or resistant disease can be treated effectively with surgery and/or cisplatin in EP/EMA (etoposide, platinum-etoposide, methotrexate, actinomycin-D) combination.
Female↗
Management of placental site trophoblastic tumors.
OBJECTIVE: To analyze the genetic background of tumors in patients with placental site trophoblastic tumors (PSTTs) and clinical outcome in patients treated for this rare variant of trophoblastic disease at a single center. STUDY DESIGN: Analysis of all patients with PSTTs treated at the Charing Cross Hospital between 1975 and 1995. RESULTS: We studied the molecular genetics of a group of PSTTs using polymerase chain reaction allelotyping and GeneScan software. We were able to show, in the seven cases in which detailed molecular analysis was successful, that four of these PSTTs were from diploid, bi-parental pregnancies and three were androgenetic tumors following monospermic complete hydatidiform moles. For patients with PSTT localized to the uterus, the treatment of choice is hysterectomy. The sensitivity of PSTT to current cytotoxic chemotherapy is variable. Several patients have been cured using the etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine schedule, but clinical impressions suggest that cisplatinum probably should be introduced into the chemotherapy schedule from the outset in a schedule such as etoposide, cisplatin/etoposide, methotrexate, actinomycin D. CONCLUSION: PSTT is a very rare variant of gestational trophoblastic tumor, and its biologic behavior is clearly heterogeneous. The treatment of choice for patients whose disease is limited to the uterus is hysterectomy; for patients with more extensive or metastatic disease, chemotherapy is indicated, but the clinical outcome is variable. A long interval from the antecedent pregnancy to clinical presentation is a major adverse prognostic variable, and the outcome in patients whose last known pregnancy was > 2 years prior to presentation with PSTT is poor.
Adult↗
The diagnosis and prognosis of molar pregnancy: the experience of the National Referral Centre in London.
Since 1973, hCG follow up and treatment of patients with hydatidiform moles in the UK has been centralised. Registrations of moles have increased from 475 to 1248 in 2 years but histological review shows that first trimester non-molar hydropic abortions (HAs) and complete moles (CMs) are often called partial moles (PMs) by pathologists. The introduction and widespread acceptance of the term PM in 1977, coincided with improvements in ultrasound which brought forward 6 weeks the average time of evacuation of CMs, when hydrops is not yet complete but partial and when vessels are present in most CMs, leading to erroneous diagnoses of PM. Many true PMs are dismissed as HAs and often, HAs are called PMs. Valid diagnostic criteria for younger CMs and for PMs have been available for over 10 years and when used, PM is overwhelmingly associated with triploidy. Reported diploid PMs are partly explained by misdiagnosed HAs, rare cases of Beckwith-Widemann syndrome, CMs with partially developed hydrops, twin pregnancies and rare androgenetic CMs with fetal red cells in villi. A rare mole with "normal" diploid biparental karyotype probably exists but morphologically resembles CM. CM and PM have widely different prognosis but the present diagnostic confusion means much of the published epidemiological, clinical and genetic information on PM based on suspect diagnostic criteria ia also suspect.
Female↗
Diploid hydatidiform moles with fetal red blood cells in molar villi. 1--Pathology, incidence, and prognosis.
It is believed that fetal development does not occur in complete mole (CM); when present, it is usually interpreted as proof of partial mole (PM), in most cases a triploid conception with a low incidence of persistent trophoblastic disease (PTD). However, histological examination of 3180 moles in 8 years showed 60 moles (1.8 per cent) with features of CM and either embryonic tissues or amnion in the sample. Flow cytometry (FC) in 40 showed diploid complement in all. In ten of the 40, there was evidence of a twin; in 17, there was only amnion, which could belong to a twin; in the remaining 13, there was no evidence of a twin and nucleated fetal red blood cells (FRCs) were seen within molar vessels in ten (0.3 per cent). Seven of the 40 patients (17.5 per cent) and one of the ten with FRCs in villi (10 per cent) developed PTD, an incidence comparable to that of CM. Genetic studies in seven of these tea are reported separately. Finding fetal tissues with a mole or FRCs in molar vessels is not enough to classify it as PM, since it can be a CM with a twin, fetal development CM, or possibly a third type of mole. These rare diploid moles with fetal tissues have histological appearances and prognosis similar to those of CM.
Adult↗
Diploid hydatidiform moles with fetal red blood cells in molar villi. 2--Genetics.
The purpose of this study was to determine the genetic origin of a series of seven diploid hydatidiform moles with fetal red blood cells in the molar villi, normally a characteristic feature of triploid, partial hydatidiform moles. DNA was prepared from formalin-fixed, paraffin-embedded blocks of molar tissue and blood from the patient and her partner. The genetic origin of molar tissue was determined by comparing microsatellite polymorphisms in molar and parental tissue following polymerase chain reaction (PCR) amplification of DNA. In six cases, the hydatidiform mole was shown to be androgenetic in origin and therefore genetically to be a complete hydatidiform mole. In one case, the hydatidiform mole was of biparental origin, having both a maternal and a paternal contribution to the genome. We conclude that fetal red blood cells may be observed in the villi of complete hydatidiform moles. In cases where the degree of trophoblastic hyperplasia and ploidy is suggestive of a complete hydatidiform mole, the presence of fetal red blood cells alone should not be considered indicative of a diagnosis of partial hydatidiform mole.
DNA, Neoplasm↗
Chemotherapy for ovarian germ cell tumours.
59 patients were treated for newly diagnosed metastatic ovarian germ cell tumours with POMB/ACE chemotherapy (which contains cisplatinum, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). The median follow-up was 7.7 years. The 3 year survival is 87.8% (95% confidence interval 76.9-93.9%) and no relapses occurred more than 3 years after treatment. 4 (7%) patients had primary drug resistance to POMB/ACE and 4 (7%) have relapsed. One patient in complete remission developed secondary acute myeloid leukaemia after receiving a total of 1.3 g/m2 etoposide. 6 of 12 (50%) patients referred at relapse were salvaged by POMB/ACE. 14 of 33 (42%) women (> 18 years old) have had successful pregnancies after fertility conserving surgery and chemotherapy with no congenital abnormalities reported. The POMB/ACE regimen is as efficacious as other published regimens for ovarian germ cell tumours (OGCT) and balances a low incidence of life-threatening toxicity with a high success rate.
Adolescent↗
A clinical, histopathological and flow cytometric study of 149 complete moles, 146 partial moles and 107 non-molar hydropic abortions.
We have compared the clinical and histological features of 149 complete moles with 146 triploid partial moles and 107 diploid non-molar hydropic abortions initially registered as moles for human chorionic gonadotrophin (hCG) follow-up. Forty-one patients with complete moles, five with partial moles and one with hydropic abortion received chemotherapy for hCG elevations interpreted as persistent trophoblastic disease. Complete moles were aborted or were evacuated significantly earlier than partial moles (means of 12.1 and 15.4 weeks; P < 0.001) and hydropic abortions significantly earlier than complete moles (mean 10.7 weeks; P < 0.005). The means of the highest recorded hCG were higher in complete moles (184,056 i.v.) than in partial moles (66,259 i.v.) and hydropic abortion (7942 i.v.). When hCG became normal without chemotherapy, this occurred earlier in patients with hydropic abortion than in those with partial moles (means of 46.7 days and 62.8 days; P < 0.001) and earlier in partial moles than in complete moles (mean 78.3 days; P < 0.005). The incidence of partial moles was comparable throughout fertile years but rose to 1.9 times the average after 40 years. Complete moles were commoner between 14 and 25 years and after 35 years, reaching 4.8 times the average after 40 years. Hydropic abortions were rare before 25 years and increased with age to 12 times the average after 40 years. Stromal karyorrhexis and shape of villi, before they become hydropic, discriminate well between complete and partial mole. Hydrops increased and vascularity decreased with molar age and the presence of non-hydropic villi or vessels did not discriminate between partial mole and the younger complete moles evacuated nowadays.
Abortion, Spontaneous↗
A case of metastatic transitional cell carcinoma in the testis histologically mimicking intratubular germ cell neoplasia.
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Carcinoma, Transitional Cell↗
Placental site trophoblastic tumor: molecular analysis and clinical experience.
Placental site trophoblastic tumor is a very rare variant of gestational trophoblastic disease which differs histologically and immunocytochemically from gestational choriocarcinoma. The English language literature includes only 74 reported cases. Seventeen patients have been managed at Charing Cross Hospital with this diagnosis. The median follow-up is 4.6 years, and the 5-year overall survival is 80% (95% confidence interval, 55-93%). Multivariate regression analysis identified an interval of >2 years since the preceding pregnancy as an independent adverse prognostic factor. Genotypic analysis by PCR allelotyping has confirmed the gestational origin of all 11 tumors successfully studied. More detailed molecular analysis has identified the causative pregnancy for eight tumors. Five were diploid biparental tumors following term pregnancies, and three were androgenetic tumors following monospermic complete hydatidiform moles.
Adult↗