RESUMO
BACKGROUND: Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. OBJECTIVE: This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. STUDY DESIGN: This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January 2022. RESULTS: Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day 8. CONCLUSION: Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.
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Doença Trofoblástica Gestacional , Mola Hidatiforme , Neoplasias Uterinas , Recém-Nascido , Criança , Gravidez , Humanos , Feminino , Lactente , Estudos Retrospectivos , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/patologia , Estudos de Coortes , Mola Hidatiforme/epidemiologia , Mola Hidatiforme/patologia , Gravidez Múltipla , Doença Trofoblástica Gestacional/patologia , Gonadotropina Coriônica Humana Subunidade beta , Feto/patologia , Gonadotropina CoriônicaRESUMO
Gestational trophoblastic diseases derived from the chorionic-type intermediate trophoblast include benign placental site nodule (PSN) and malignant epithelioid trophoblastic tumor (ETT). Among PSNs, the World Health Organization classification introduced a new entity named atypical placental site nodule (APSN), corresponding to an ETT precursor, for which diagnostic criteria remain unclear, leading to a risk of overdiagnosis and difficulties in patient management. We retrospectively studied 8 PSNs, 7 APSNs, and 8 ETTs to better characterize this new entity and performed immunohistochemical analysis (p63, human placental lactogen, Cyclin E, and Ki67), transcriptional analysis using the NanoString method to quantify the expression of 760 genes involved in the main tumorigenesis pathways, and RNA sequencing to identify fusion transcripts. The immunohistochemical analysis did not reveal any significant difference in Cyclin E expression among the 3 groups (P = .476), whereas the Ki67 index was significantly (P < .001) higher in ETT samples than in APSN and PSN samples. None of the APSN samples harbored the LPCAT1::TERT fusion transcripts, in contrast to 1 of 6 ETT samples, as previously described in 2 of 3 ETT samples. The transcriptomic analysis allowed robust clustering of ETTs distinct from the APSN/PSN group but failed to differentiate APSNs from PSNs. Indeed, only 7 genes were differentially expressed between PSN and APSN samples; CCL19 upregulation and EPCAM downregulation were the most distinguishing features of APSNs. In contrast, 80 genes differentiated ETTs from APSNs, establishing a molecular signature for ETT. Gene set analysis identified significant enrichments in the DNA damage repair, immortality and stemness, and cell cycle signaling pathways when comparing ETTs and APSNs. These results suggested that APSN might not represent a distinct entity but rather a transitional stage between PSN and ETT. RNA sequencing and the transcriptional signature of ETT described herein could serve as triage for APSN from curettage or biopsy material, enabling the identification of cases that need further clinical investigations.
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Doença Trofoblástica Gestacional , Tumor Trofoblástico de Localização Placentária , Neoplasias Uterinas , Feminino , Humanos , Gravidez , Tumor Trofoblástico de Localização Placentária/química , Tumor Trofoblástico de Localização Placentária/metabolismo , Tumor Trofoblástico de Localização Placentária/patologia , Ciclina E , Placenta/patologia , Antígeno Ki-67 , Estudos Retrospectivos , Neoplasias Uterinas/diagnóstico , Doença Trofoblástica Gestacional/genética , Doença Trofoblástica Gestacional/patologiaRESUMO
Congenital combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare autosomal recessive disease resulting in hemorrhagic symptoms usually associated with developmental disorders and bone abnormalities. Pathogenic variants in two genes encoding enzymes of the vitamin K cycle, GGCX and VKORC1, can lead to this disorder. We present the case of a male fetus with a brachytelephalangic chondrodysplasia punctata (CDP), absence of nasal bone, growth restriction, and bilateral ventriculomegaly at 18 weeks of gestation. Pathological examination showed a Binder phenotype, hypoplastic distal phalanges, stippled epiphyses, and brain abnormalities suggestive of a brain hemorrhage. Two GGCX pathogenic variants inherited respectively from the mother and the father were identified. To our knowledge, this is the first prenatal description of VKCFD. Even if it remains a rare etiology, which is mostly described in children or adult patients, VKCFD should be considered in fetuses with CDP.
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Carbono-Carbono Ligases , Condrodisplasia Punctata , Fatores de Coagulação Sanguínea , Carbono-Carbono Ligases/genética , Condrodisplasia Punctata/diagnóstico , Condrodisplasia Punctata/genética , Feminino , Feto , Humanos , Masculino , Gravidez , Vitamina K , Vitamina K 1 , Vitamina K Epóxido Redutases/genéticaRESUMO
Placental mesenchymal dysplasia (PMD) and complete hydatidiform mole (CHM) with a coexisting fetus are 2 rare placental abnormalities characterized by lacunar placenta and presence of an embryo on ultrasound examination. We report the case of a 34-yr-old woman referred at 32.6 weeks of gestation because of a multicystic placenta. A caesarean section was performed at 39.1 weeks of gestation giving birth to a 2905 g normal female infant. Pathological examination revealed macroscopic and microscopic morphological, and immunohistological features of PMD in the main placenta, and features of CHM in a separate placental mass. Fluorescent in situ hybridization and molecular genotyping analyses showed diandric diploidy in the CHM component and androgenetic/biparental mosaicism in the PMD component, confirming the association of PMD and CHM with a live infant. There was no progression to gestational trophoblastic neoplasia during follow-up for the mother, or any sign of Beckwith-Wiedemann syndrome or hepatic tumor in the child.
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Mola Hidatiforme , Doenças Placentárias , Neoplasias Uterinas , Cesárea , Criança , Feminino , Feto/patologia , Genótipo , Humanos , Mola Hidatiforme/patologia , Hiperplasia/patologia , Hibridização in Situ Fluorescente , Placenta/patologia , Doenças Placentárias/patologia , Gravidez , Neoplasias Uterinas/patologiaRESUMO
Whole-exome and targeted sequencing of 13 individuals from 10 unrelated families with overlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allowing delineation of an autosomal-recessive multi-system syndrome, which we suggest to name Alkuraya-Kucinskas syndrome (MIM 617822). Shared phenotypic features representing the cardinal characteristics of this syndrome combine brain atrophy with clubfoot and arthrogryposis. Affected individuals present with cerebral parenchymal underdevelopment, ranging from major cerebral parenchymal thinning with lissencephalic aspect to moderate parenchymal rarefaction, severe to mild ventriculomegaly, cerebellar hypoplasia with brainstem dysgenesis, and cardiac and ophthalmologic anomalies, such as microphthalmia and cataract. Severe loss-of-function cases were incompatible with life, whereas those individuals with milder missense variants presented with severe global developmental delay, syndactyly of 2nd and 3rd toes, and severe muscle hypotonia resulting in incapacity to stand without support. Consistent with a causative role for KIAA1109 loss-of-function/hypomorphic variants in this syndrome, knockdowns of the zebrafish orthologous gene resulted in embryos with hydrocephaly and abnormally curved notochords and overall body shape, whereas published knockouts of the fruit fly and mouse orthologous genes resulted in lethality or severe neurological defects reminiscent of the probands' features.
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Artrogripose/genética , Encéfalo/embriologia , Mutação/genética , Proteínas/genética , Adolescente , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Feminino , Técnicas de Silenciamento de Genes , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Linhagem , Peixe-Zebra , Proteínas de Peixe-Zebra/genéticaRESUMO
OBJECTIVE: Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens. METHODS: We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma. RESULTS: We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN áµ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis. CONCLUSION: HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.
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Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/genética , Antígenos HLA-G/genética , Mola Hidatiforme/tratamento farmacológico , Mola Hidatiforme/genética , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/genética , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Coriocarcinoma/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Antígenos HLA-G/metabolismo , Humanos , Mola Hidatiforme/metabolismo , Imuno-Histoquímica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Transcriptoma , Adulto JovemRESUMO
OBJECTIVES: To evaluate the frequency of placental pathological lesions in Beckwith-Wiedemann syndrome (BWS), an overgrowth disorder that exhibits etiologic molecular heterogeneity and variable phenotypic expression. MATERIALS AND METHODS: The study included 60 BWS patients with a proven molecular diagnosis and a placental pathological examination. Placentomegaly, placental mesenchymal dysplasia (PMD), chorangioma/chorangiomatosis, and extravillous trophoblastic (EVT) cytomegaly were evaluated and their frequencies in the different molecular subgroups were compared. Immunohistochemistry and fluorescent in situ hybridization (FISH) were performed on EVT cytomegaly. RESULTS: Placentomegaly was found in 70.9% of cases, PMD in 21.7%, chorangioma/chorangiomatosis in 23.3%, and EVT cytomegaly in 21.7%; there was no significant intergroup difference. EVT cytomegaly showed loss of p57 expression, increased Ki67 proliferating index, and polyploidy on FISH analysis. CONCLUSIONS: There was no genotype/epigenotype-phenotype correlation concerning placental lesions in BWS. Diffuse EVT cytomegaly with polyploidy may represent a placental finding suggestive of BWS.
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Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/patologia , Placenta/patologia , Adulto , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: Recently reported expression of programmed cell death 1 ligand 1 (PD-L1) in gestational trophoblastic diseases (GTDs) suggests that the immune tolerance of pregnancy might be hijacked during neoplastic process. We assessed PD-L1 protein expression in premalignant and malignant GTD lesions and analyzed associations with disease severity and chemotherapy outcomes. METHODS: We included 83 GTD whole-tissue sections from 76 patients in different treatment settings. PD-L1 protein expression was assessed with immunohistochemistry in each trophoblast subtype with the Allred total score (ATS), which combines intensity and proportion expression on a 0- to 8-point scale. Peritumoral immune infiltrate was scored on hematoxylin-eosin-safran-stained slides. RESULTS: PD-L1 expression was ubiquitous and strong in all GTD trophoblast subtypes. For invasive moles, ATS scores were maximal at 8 in 100%, 100%, and 75% of syncytiotrophoblast, villous cytotrophoblast, and extravillous cytotrophoblast specimens, respectively. For choriocarcinomas, ATS was 8 in 80% of specimens. Immune infiltrates were moderate to severe in 61%, 100%, and 100% of peritumoral zones of choriocarcinoma, epithelioid trophoblastic tumor, and invasive moles, respectively. Because of the homogeneous pathological findings, no significant differences in PD-L1 expression profiles or peritumoral immune infiltrates were found regarding FIGO (International Federation of Gynecology Obstetrics) prognostic score, fatal outcome, or chemosensitivity. CONCLUSIONS: We confirm that PD-L1 is constitutively expressed in all GTD premalignant and malignant trophoblast subtypes, independently from FIGO score, chemoresistance, or fatal outcomes, thereby suggesting a crucial role for PD-L1 in the development and tolerance of GTD. Assessment of anti-PD-L1 drug in GTD patients has been activated.
Assuntos
Antígeno B7-H1/biossíntese , Doença Trofoblástica Gestacional/imunologia , Lesões Pré-Cancerosas/imunologia , Trofoblastos/imunologia , Adulto , Antígeno B7-H1/imunologia , Estudos de Casos e Controles , Feminino , Doença Trofoblástica Gestacional/patologia , Humanos , Lesões Pré-Cancerosas/patologia , Gravidez , Prognóstico , Trofoblastos/patologiaRESUMO
We report a case of an unusual chorangioma in a 26-year-old gravida 2, para 1 female. The clinical course was complicated by premature birth at 34 weeks' gestation. The baby presented with congenital cardiac and renal malformations. The tumor was 11 cm in size, separated from the main placental mass and exhibited atypical histologic characteristics such as fibromatous areas, high cellularity, nuclear atypia and high mitotic index. These histologic features must not be interpreted as malignancy.
Assuntos
Síndrome CHARGE/etiologia , Hamartoma/patologia , Doenças Placentárias/patologia , Adulto , Diagnóstico Diferencial , Feminino , Hamartoma/diagnóstico , Cardiopatias Congênitas/etiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Rim/anormalidades , Trabalho de Parto Prematuro/etiologia , Doenças Placentárias/diagnóstico , Gravidez , Sarcoma/diagnósticoRESUMO
Gestational trophoblastic disease encompresses a group of interrelated diseases, following a pregnancy after a variable period of time. Hydatiform mole corresponds to premalignant disorders composed of villi with excess of paternal genetic material, with a malignant potential more important for complete mole than partial mole. Gestational trophoblastic neoplasia includes invasive mole, choriocarcinoma, placental site trophoblatic tumor and epithelioid trophoblastic tumor. Their histological diagnosis may be problematic on curettage material and needs to be correlated to serum hCG level and radiological findings. The use of chemotherapy has dramatically improved the prognosis of these lesions. All patients with this rare disease need to be registered in the national service for gestational trophoblastic disease (http://www.mole-chorio.com), which coordinates their management at the national level.
Assuntos
Doença Trofoblástica Gestacional , Biomarcadores Tumorais/sangue , Gonadotropina Coriônica , Inibidor de Quinase Dependente de Ciclina p21/análise , Diagnóstico Diferencial , Feminino , Doença Trofoblástica Gestacional/sangue , Doença Trofoblástica Gestacional/classificação , Doença Trofoblástica Gestacional/diagnóstico , Doença Trofoblástica Gestacional/epidemiologia , Doença Trofoblástica Gestacional/patologia , Doença Trofoblástica Gestacional/terapia , Humanos , Imunofenotipagem , Incidência , Antígeno Ki-67/análise , Invasividade Neoplásica , Gravidez , Prognóstico , Neoplasias Uterinas/sangue , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
Hydatidiform moles are rare and thus most pathologists and geneticists have little experience with their diagnosis. It is important to promptly and correctly identify hydatidiform moles given that they are premalignant disorders associated with a risk of persistent gestational trophoblastic disease and gestational trophoblastic neoplasia. Improvement in diagnosis can be achieved with uniformization of diagnostic criteria and establishment of algorithms. To this aim, the Pathology and Genetics Working Party of the European Organisation for Treatment of Trophoblastic Diseases has developed guidelines that describe the pathological criteria and ancillary techniques that can be used in the differential diagnosis of hydatidiform moles. These guidelines are based on the best available evidence in the literature, professional experience and consensus of the experts' group involved in its development.
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Doença Trofoblástica Gestacional , Mola Hidatiforme , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/genética , Doença Trofoblástica Gestacional/diagnóstico , Doença Trofoblástica Gestacional/genética , Diagnóstico Diferencial , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologiaRESUMO
Ovarian sex cord-stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as FOXL2 variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz-Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli-Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the DICER1 variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature.
RESUMO
INTRODUCTION: SARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. Diffuse placental damage of this kind is rare, but can sometimes lead to obstetric complications, such as intrauterine fetal death (IUFD). The objectives of this study were to identify possible predictors of severe placental lesions. METHODS: We retrospectively studied 96 placentas from SARS-Cov-2 positive pregnant women who gave birth between March 2020 and March 2022. Cases with and without severe placental lesions were compared in terms of clinical and laboratory findings. RESULTS: Twelve of the 96 patients had severe placental lesions. There was no significant association with diabetes, obesity or severe clinical maternal disease. In contrast, presence of severe placental lesions was significantly associated with neonatal intensive care, cesarean section, prematurity, IUFD, intrauterine growth restriction (IUGR), gestational age, maternal hypofibrinogenemia and thrombocytopenia. No cases of severe placental lesions were observed in vaccinated patients or in those with the Omicron variant. DISCUSSION: In these patients, severe placental lesions due to SARS-Cov-2 were significantly associated with the presence of coagulation abnormalities (hypofibrinogenemia and thrombocytopenia), IUGR and gestational age. These results support laboratory and ultrasound monitoring of these parameters in pregnant women with SARS-Cov-2 infection, especially during the second trimester, to predict potential negative fetal outcomes.
Assuntos
Afibrinogenemia , COVID-19 , Complicações Infecciosas na Gravidez , Recém-Nascido , Feminino , Gravidez , Humanos , Placenta/patologia , COVID-19/complicações , COVID-19/patologia , SARS-CoV-2 , Gestantes , Cesárea/efeitos adversos , Estudos Retrospectivos , Afibrinogenemia/complicações , Afibrinogenemia/patologia , Natimorto , Morte Fetal/etiologia , Complicações Infecciosas na Gravidez/patologia , Retardo do Crescimento Fetal/patologiaRESUMO
Hydatidiform moles (HMs) are divided into two types: partial hydatidiform mole (PHM) which is most often diandric monogynic triploid and complete hydatidiform mole (CHM) which is most often diploid androgenetic. Morphological features and p57 immunostaining are routinely used to distinguish both entities. Genetic analyses are required in challenging cases to determine the parental origin of the genome and ploidy. Some gestations cannot be accurately classified however. We report a case with atypical pathologic and genetic findings that correspond neither to CHM nor to PHM. Two populations of villi with divergent and discordant p57 expression were observed: morphologically normal p57 + villi and molar-like p57 discordant villi with p57 + stromal cells and p57 - cytotrophoblasts. Genotyping of DNA extracted from microdissected villi demonstrated that the conceptus was an androgenetic/biparental mosaic, originating from a zygote with triple paternal contribution, and that only the p57 - cytotrophoblasts were purely androgenetic, increasing the risk of neoplastic transformation.
Assuntos
Mola Hidatiforme , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Neoplasias Uterinas/patologia , Mosaicismo , Diploide , Genótipo , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Imuno-Histoquímica , Mola Hidatiforme/genética , Mola Hidatiforme/metabolismoRESUMO
Twin pregnancy with both complete hydatiform mole and coexistent fetus is a rare situation and a challenging diagnosis. We report an unusual case of twin pregnancy with complete mole diagnosed after pathological examination of the placenta. A 30-year-old woman, 14 weeks gestation, presented with vaginal bleeding. The abdominal ultrasound examination revealed an heterogeneous aspect of inferior placenta, which was interpreted as a hematoma, and, a multilacunar placental aspect with an oligoamnios respectively at initial follow-up and 22 weeks gestation. The karyotype from chorionic villi was normal (46 XY). At 25 weeks, after a spontaneous abortion, she delivered a 950g newborn who died quickly. On placental gross examination two distinct but connected masses were identified: one exhibited a normal placental aspect and the other vesicular villi with necrotic and hemorrhagic fragments. On microscopic examination, the normal placenta showed well-developed chorionic villi and the multicystic placenta showed molar villi. Immunohistochemical study and fluorescence in situ hybridization confirmed a complete hydatiform mole. No persistent gestational trophoblastic neoplasia was observed during the follow-up.
Assuntos
Erros de Diagnóstico , Doenças em Gêmeos , Mola Hidatiforme/diagnóstico , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Placenta/patologia , Complicações Neoplásicas na Gravidez/diagnóstico , Gravidez de Gêmeos , Neoplasias Uterinas/diagnóstico , Adulto , Amostra da Vilosidade Coriônica , Diagnóstico Tardio , Reações Falso-Negativas , Evolução Fatal , Feminino , Hematoma/diagnóstico , Humanos , Mola Hidatiforme/complicações , Mola Hidatiforme/diagnóstico por imagem , Mola Hidatiforme/patologia , Hibridização in Situ Fluorescente , Recém-Nascido , Nascido Vivo , Masculino , Metrorragia/etiologia , Trabalho de Parto Prematuro/etiologia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/patologia , Ultrassonografia Pré-Natal , Neoplasias Uterinas/complicações , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologiaRESUMO
The prenatal examination of the placenta is often an afterthought to that of the fetus in ultrasonography. Not giving the placenta its due may however result in potentially serious placental pathologies remaining undiscovered, notably in the presence of anechoic zones. These latter have earned numerous names, including "placental lakes", "placental venous lakes", "placental lacunae" or "placental caverns" among others, but they have received little attention in the literature. We thus feel that it is essential to review the various pathologies that placental lakes may signal, since any one of them may greatly affect patient management. The difficulty resides in the diversity of these pathologies, sometimes oncological, other times fetal, and in the potential need for multidisciplinary surgery. Some of these causes of placental lakes may result in maternal or fetal complications and/or necessitate increased and casespecific surveillance. The diagnosis and treatment of such cases requires close collaboration between sonographers, obstetricians, geneticists and pathologists. The work we present here focuses on the different etiologies to consider in the presence of a lacunar placenta and the necessary diagnostic measures. Our objective is to propose a diagnostic flowchart to aid clinicians in this dense differential diagnosis.
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Doenças Placentárias/diagnóstico por imagem , Placenta/diagnóstico por imagem , Placentação , Ultrassonografia Pré-Natal , Cromossomos Humanos Par 16 , Feminino , Feto/anormalidades , Doença Trofoblástica Gestacional/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Humanos , Mola Hidatiforme/diagnóstico por imagem , Mosaicismo , Gravidez , Gravidez de Gêmeos , Trissomia , Neoplasias Uterinas/diagnóstico por imagemRESUMO
INTRODUCTION: Pregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific. METHOD: We collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples. RESULTS: We report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers' infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2. DISCUSSION: SARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.
Assuntos
COVID-19/complicações , Doenças Placentárias/etiologia , Nascimento Prematuro/etiologia , Natimorto , Adulto , COVID-19/diagnóstico , COVID-19/patologia , Feminino , Morte Fetal/etiologia , França , Humanos , Recém-Nascido , Masculino , Morte Perinatal/etiologia , Placenta/patologia , Placenta/virologia , Doenças Placentárias/diagnóstico , Doenças Placentárias/patologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/patologia , Resultado da Gravidez , Nascimento Prematuro/patologia , Nascimento Prematuro/virologia , SARS-CoV-2/fisiologia , Trofoblastos/patologia , Trofoblastos/virologiaRESUMO
The human placenta shares properties with solid tumors, such as rapid growth, tissue invasion, cell migration, angiogenesis, and immune evasion. However, the mechanisms that drive the evolution from premalignant proliferative placental diseases-called hydatidiform moles-to their malignant counterparts, gestational choriocarcinoma, as well as the factors underlying the increased aggressiveness of choriocarcinoma arising after term delivery compared to those developing from hydatidiform moles, are unknown. Using a 730-gene panel covering 13 cancer-associated canonical pathways, we compared the transcriptomic profiles of complete moles to those of postmolar choriocarcinoma samples and those of postmolar to post-term delivery choriocarcinoma. We identified 33 genes differentially expressed between complete moles and postmolar choriocarcinoma, which revealed TGF-ß pathway dysregulation. We found the strong expression of SALL4, an upstream regulator of TGF-ß, in postmolar choriocarcinoma, compared to moles, in which its expression was almost null. Finally, there were no differentially expressed genes between postmolar and post-term delivery choriocarcinoma samples. To conclude, the TGF-ß pathway appears to be a crucial step in the progression of placental malignancies. Further studies should investigate the value of TGF- ß family members as biomarkers and new therapeutic targets.
RESUMO
NLRP7 is a maternal-effect gene that has a primary role in the oocyte. Its biallelic mutations are a major cause for recurrent diploid biparental hydatidiform moles (HMs). Here, we describe the full characterization of four HMs from a patient with a novel homozygous protein-truncating mutation in NLRP7. We found that some HMs have features of both complete and partial moles. Two HMs expressed p57 in the cytotrophoblast and stromal cells and exhibited divergent and discordant immunostaining. Microsatellite DNA-genotyping demonstrated that two HMs are diploid biparental and one is triploid digynic due to the failure of meiosis II. FISH analysis demonstrated triploidy in the cytotrophoblast and stromal cells in all villi. Our data highlight the atypical features of HM from patients with recessive NLRP7 mutations and the important relationship between NLRP7 defects in the oocyte and p57 expression that appear to be the main contributor to the molar phenotype regardless of the zygote genotype.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Mola Hidatiforme/metabolismo , Recidiva Local de Neoplasia/metabolismo , Neoplasias Uterinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Feminino , Genótipo , Doença Trofoblástica Gestacional , Humanos , Mola Hidatiforme/genética , Mutação/genética , Recidiva Local de Neoplasia/genética , Nevo Pigmentado/genética , Fenótipo , GravidezRESUMO
p57 immunostaining is performed on hydropic products of conception to diagnose hydatidiform moles (HMs), which can progress to gestational trophoblastic neoplasia. Partial hydatidiform mole (PHM) and hydropic abortion (HA) display positive staining in stromal and cytotrophoblastic cells, whereas complete hydatidiform mole (CHM) is characterized by loss of p57 expression in both cell types. In some cases, an aberrant pattern is observed, called discordant p57 expression, with positive cytotrophoblast staining and negative stromal staining, or vice versa. The aim of this study was to describe the clinical, biological, and pathological characteristics of p57-discordant villi (p57DV) and other associated populations in cases of divergent p57 expression and to compare the evolutions of p57DV-associated and classic CHMs. Seventy cases of p57DV diagnosed by referent pathologists were divided into two groups, G1: p57DV ± non-CHM component (n = 22) and G2: p57DV + CHM component (n = 48). p57DV morphology was similar in the two groups. Observation of more than two populations and hybrid villi on p57 immunostaining were significantly more frequent in G2. The clinical, ultrasound, and biological presentations of p57DV-associated and classic CHMs were similar. The initial pathological diagnosis was more frequently incorrect, missing the CHM component, for the p57DV-associated CHMs. Molecular genotyping was informative in seven cases and identified as androgenetic/biparental mosaicism in four cases. These results show that p57DV are a diagnostic challenge for pathologists and that most are associated with a CHM component. However, the clinical management of p57DV-associated CHMs should be the same as that of classic CHMs.