Trophoblastic Lesions Research Articles

Risk Factors Related to Gestational Trophoblastic Disease

Background: Gestational trophoblastic diseases (GTD) consist of a group of neoplastic disorders arising from placental trophoblastic tissue after normal or abnormal fertilization. The WHO classification of GTD includes hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumor, and miscellaneous and unclassified trophoblastic lesions. This study aimed to analyze the risk factors related to the gestational trophoblastic disease. Material Methods: This prospective study was conducted at the Department of Obstetrics Gynecology in Uttara Adhunik Medical College Hospital, Dhaka, Bangladesh for 1 year; from April 2020 to March 2021. A total of 100 subjects were included in this study. Informed written consent was taken from the study subjects. Data was collected using a pre-formed data sheet. Data processing and analysis were done by using SPSS version 17. The test statistics used to analyze the data were descriptive statistics, the McNemar Chi-square test, and Repeated Measure ANOVA statistics. All patients underwent necessary investigations. All information was kept confidential and used only for this study purpose. The ethical Clearance Certificate was obtained from Bangladesh Medical College. Results: The majority of the patients were more than of 38 years age (53, 53.0%). Out of these patients, 50 (50.0%) were para one, while 40 (40.0%) were para more than four, most of the patients (63, 63.9%) were illiterate and 5 (5.0%) were graduates, most of the subjects (73, 73.0%) belonged to the low socioeconomic group. The most common presenting symptom was bleeding per vagina (35, 35.0%) followed by pain in the lower abdomen (24, 24.0%), the passage of moles (16, 16.0%), hyperemesis gravidarum (14, 14.0%) and dyspnea in 11 (11.0%) subjects. Conclusion: The disease was common in extremes of ages, low para, and grand multiparous women. The hydatidiform mole was the commonest type of trophoblastic disease in these patients. The most common presenting complaint was bleeding per vagina followed by pain in the lower abdomen. The hydatidiform mole was diagnosed in 65 (65.0%) patients, the invasive mole in 28 subjects (28.0%), and choriocarcinoma in 7 (7.0%) patients. No patient had a placental site trophoblastic tumor.

Molecular Analyses of Chorionic-Type Intermediate Trophoblastic Lesions: Atypical Placental Site Nodules are Closer to Placental Site Nodules Than Epithelioid Trophoblastic Tumors

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.

Histomorphological Analysis of Gestational Trophoblastic Disease Spectrum with Clinicopathological Correlation at a Teaching Hospital

Introduction: Clinically, all trophoblastic lesions are frequently combined under a broad spectrum of gestational trophoblastic diseases (GTDs) without the use of specific pathological terms. However, studies now demonstrate that various forms of GTDs demonstrate differences in etiology, histogenesis, morphology, and clinical behavior. Thus, the need for diagnostic histopathology of these lesions to distinguish gestational trophoblastic neoplasms from nonneoplastic lesions and molar pregnancies and also for early anticipation for early anticipation, risk category stratification, prognostication, management, and prediction of persistent GTD. Our study aimed to study the histomorphological patterns of various types of GTD with light microscopy and the pattern of occurrence of GTDs in relation to age, parity, and gestation. Materials and Methods: The present study was conducted in the department of pathology, from January 2020 to April 2022. All GTDs confirmed by histopathological examination by hematoxylin- and eosin-stained slides were included. Results: The spectrum of GTDs found in this study was seventy cases of hydatidiform mole (92.10%), three cases of exaggerated placental site (EPS) reaction (3.94%), and two cases of choriocarcinoma (2.63%) and one case (1.31%) of placental site trophoblastic tumor (PSTT). The most common presenting symptom was vaginal bleeding (93.42%). Conclusion: Hydatidiform mole forms the most common type of GTD with an incidence of complete moles more than partial moles. Histomorphological examination and analysis are helpful for confirmatory diagnosis. The most common clinical presentation of GTD was vaginal bleeding followed by amenorrhea. Emphasis on detailed descriptive morphological assessment can help in the histological distinction of benign lesions such as EPS reaction and placental site nodule and avert such cases from being erroneously diagnosed as neoplastic. The Ki-67 proliferation index helped in distinguishing the EPS reaction from neoplastic lesions such as PSTT which requires surgical intervention and chemotherapy.

LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth.

Gestational trophoblastic disease (GTD) is a heterogeneous group of lesions arising from placental tissue. Epithelioid trophoblastic tumor (ETT), derived from chorionic-type trophoblast, is the rarest form of GTD with only approximately 130 cases described in the literature. Due to its morphologic mimicry of epithelioid smooth muscle tumors and carcinoma, ETT can be misdiagnosed. To date, molecular characterization of ETTs is lacking. Furthermore, ETT is difficult to treat when disease spreads beyond the uterus. Here using RNA-Seq analysis in a cohort of ETTs and other gestational trophoblastic lesions we describe the discovery of LPCAT1-TERT fusion transcripts that occur in ETTs and coincide with underlying genomic deletions. Through cell-growth assays we demonstrate that LPCAT1-TERT fusion proteins can positively modulate cell proliferation and therefore may represent future treatment targets. Furthermore, we demonstrate that TERT upregulation appears to be a characteristic of ETTs, even in the absence of LPCAT1-TERT fusions, and that it appears linked to copy number gains of chromosome 5. No evidence of TERT upregulation was identified in other trophoblastic lesions tested, including placental site trophoblastic tumors and placental site nodules, which are thought to be the benign chorionic-type trophoblast counterpart to ETT. These findings indicate that LPCAT1-TERT fusions and copy-number driven TERT activation may represent novel markers for ETT, with the potential to improve the diagnosis, treatment, and outcome for women with this rare form of GTD.

Exaggerated Placental Site as a Cause of Hysterectomy for Massive Bleeding After First Trimester Voluntary Abortion.

Placental implantation anomalies in first-trimester abortions may determine severe bleeding leading to hysterectomy. There are very few cases of urgent hysterectomy post-abortion reported in the literature, related to placenta accreta spectrum, but in any of them is considered association with benign trophoblastic lesions. We report the case of a woman, who underwent surgical voluntary abortion by vacuum aspiration during first trimester, without any apparent surgical complications. Immediately, after this procedure, the patient had massive vaginal bleeding; an emergency hysterectomy was performed. Histological examination showed an exaggerated placental site (EPS). Morphological findings describe a trophoblastic tumor-like lesion, which differs from placenta accreta and often considered an asymptomatic occasional feature. Proliferative index, evaluated by double immunostain for CK8-18 and Ki-67, was unremarkable (<1%). Only a single report in the literature describes a case of symptomatic EPS 65 after first-trimester abortion. Major attention should be paid to trophoblastic pathology in order to understand a possible relationship with uterine bleeding and to find a clinical, ultrasound or chemical indicator.

Pathology of gestational trophoblastic disease (GTD)

Gestational trophoblastic disease (GTD) is subclassified into hydatidiform mole (HM), gestational trophoblastic tumours (GTT) and non-neoplastic trophoblastic lesions. HM, partial and complete, originate from villous trophoblast and are considered as preneoplastic conditions. The risk for the development of persistent GTD, mostly as invasive HM, ranges from 0.5% to 20%, which depends on the type of molar pregnancy. The risk of development of trophoblastic tumour after PHM is <0.5% and 2%-3% after CHM. GTT represent a spectrum of neoplasms that originates from the intermediate, largely extravillous, trophoblast and these include choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), epithelioid trophoblastic tumour (ETT) and mixed trophoblastic tumour. Among tumour like conditions, exaggerated placental site reaction (EPSR) and placental site nodule (PSN) (s)/plaque (s) are included. The morphological appearances of HM can be mimicked by abnormal (non-molar) villous lesions, and similarly, GTT can be mimicked both by non-malignant tumour-like conditions and non-gestational tumours with trophoblastic differentiation, which add to the diagnostic dilemma of these rare conditions. GTT have a favourable prognosis and better response to specific chemotherapeutic regimens when compared with non-gestational malignant genital tract neoplasms. The correct diagnosis and classification of these rare conditions are therefore important. This article focusses on the morphological appearances, immunocytochemistry as an aid in the diagnosis and the changes in current WHO classification of GTDs (WHO 2020).

Atypical postcesarean epithelioid trophoblastic lesion with cyst formation: A rare case report with review of literature

Atypical postcesarean epithelioid trophoblastic lesion with cyst formation: A rare case report with review of literature

Objective Histologic Characterization of Trophoblastic Proliferations

Abstract Introduction/Objective Placental site nodules (PSNs) are rare intermediate trophoblastic lesions characterized by hyalinized cellular aggregates that are small, well-circumscribed, non-necrotic, and paucicellular. PSNs are generally incidental in gynecologic specimens. ETTs are malignant proliferations of intermediate trophoblasts and are generally larger, with nuclear atypia, and higher mitotic rate. Atypical placental site nodules (APSNs) are histologically intermediate between PSN and ETT and not well characterized in the literature to date. There exists room for more objective characterization of PSN and APSN. We use objective measurements to characterize trophoblastic proliferations based on size, location, mitotic rate, number of trophoblasts per high-power field (t-HPF), ki-67 index, beta-hCG, time since last pregnancy, presence of calcification or necrosis, and clinical follow-up. Methods The surgical pathology database of a single large academic institution was searched for cases of “placental site nodule,” “atypical placental site nodule,” “epithelioid trophoblastic tumor,” and “placental site trophoblastic tumor”. Clinical and morphologic data were recorded for each case. Ki-67/cytokeratin AE1/AE3 dual immunohistochemical stains were performed to assess the proliferative index of the trophoblastic cells. Results 70 cases of trophoblastic lesions (53 PSN, 4 APSN, 5 ETT, 8 PSTT) were identified. Results include: PSNs were on average 3.2 mm, 56.5 t-HPF, and 2.6% ki-67. APSNs 4.3 mm, 97.8 t-HPF, and 6.4% ki-67. ETTs 16.5 mm, 161.8 t-HPF, and 12.2% ki-67. Conclusion Objective measurements of trophoblastic lesions, as well as correlation with clinical data, may be useful for more accurate classification of these lesions, especially by those who encounter them rarely. To date, the clinical risk, optimal management, and risk for progression of APSNs are not well characterized and thus are worthy of additional study and description. For example, in our data, 14 cases originally signed out at PSN were at least 4 mm, which may re-classify them as APSN.

Placental examination in nonmacerated stillbirth versus neonatal mortality.

To retrospectively statistically compare clinical and placental phenotypes of nonmacerated fetuses and live-born perinatal deaths in 3rd trimester pregnancies. Twenty-five clinical and 47 placental phenotypes were statistically compared among 93 cases of nonmacerated (intrapartum, or recent antepartum death) 3rd trimester fetal deaths (Group 1), 118 3rd trimester neonatal deaths (Group 2) and 4285 cases without perinatal mortality (Group 3). Sixteen clinical and placental phenotypes were statistically significantly different between Group 3 and the two groups of perinatal deaths, which included eight placental phenotypes of fetal vascular malperfusion and eight other placental phenotypes of various etiology (amnion nodosum, 2-vessel umbilical cord, villous edema, increased extracellular matrix of chorionic villi, erythroblasts in fetal blood and trophoblastic lesions of shallow placentation). Statistically significant differences between Groups 1 and 2 were scant (oligohydramnios, fetal malformations, cesarean sections, hypercoiled umbilical cord and amnion nodosum being more common in the latter, and retroplacental hematoma more common in the former). Placental examination in neonatal mortality shows thrombotic pathology related to umbilical cord compromise and features of shallow placental implantation that are similar to those in nonmacerated stillbirth; however, the features of placental abruption were more common in recent antepartum death, as were the features related to neonatal congenital malformations in neonatal deaths.

Immunoexpression of P53 protein in trophoblastic diseases

Background and objective: Trophoblastic diseases constitute a spectrum of tumors and tumor- like conditions characterized by proliferation of pregnancy associated trophoblastic tissue of progressive malignant potential. This study aimed to assess the value of p53 protein immunoexpression in the diagnosis of hydatidiform molar pregnancy and the differential diagnosis of its subtypes (complete and partial) from abortions. Methods: A cross-sectional study of tissue sections from 68 formalin-fixed, paraffin- embedded specimens of products of conception, including 1st trimester abortion (n=15), partial hydatidiform mole PHM (n=24), complete hydatidiform CHM (n=24) and full term placenta (n=5), all were examined at the Histopathology Department of Maternity Teaching Hospital in Erbil, Iraq during the period of Jan.2013-Jun.2013. Immunohistochemistry was performed using p53 antibody and the standard streptavidin-biotin immunoperoxidase method. The labeling index (number of positive nuclei/total number of nuclei) for villous cytotrophoblasts, syncytiotrophoblasts and stromal cells were evaluated separately. Statistical analysis was carried out by one way ANOVA and Fisher’s exact tests, statistical significance was determined at P ≤0.05. Results: All villous trophoblastic lesions showed higher p53 immunoexpression in all villous components especially cytotrophoblasts, being the highest in complete hydatidiform mole (>50%) and partial hydatidiform mole (>20%). A statistically significant difference was found in immunoexpressins of p53 that was useful in separating abortion from complete hydatidiformmole, P <0.001, and partial hydatidiform mole, P <0.0002. It was also useful in separating between the complete hydatidiform mole and partial hydatidiform mole (P <0.001). Conclusion: p53 immunoexpression was valuable in differentiation between molar and non molar pregnancies and between subtypes of molar pregnancies.

Histomorphological Study of Gestational Trophoblastic Lesions in a Tertiary Medical Centre: A Prospective Study

Background: Gestational trophoblastic diseases(GTDs) consists of pregnancy related disorders ranging from benign Hydatidiform mole, Invasive mole to neoplastic conditions including Choriocarcinoma, Placental site trophoblastic tumor and Epitheloid trophoblastic tumor with varying potential for local invasion and metastasis. GTDs mimic growth pattern encountered in early normal placental development, nonmolar abortions and variety of nontrophoblastic lesions. Therefore an appreciation of different types of GTDs with its histomorphological manifestations are important for the confirmation of diagnosis. Thus the study was undertaken. Materials & methods: The material for the study comprised of products of conception specimens received in the Department of Pathology, J.J.M. Medical college, Davangere, India during the period of 2 years. Detailed gross examination was done before fixation and subsequent microscopic analysis was done. Results: 65 cases of GTDs were diagnosed in 495 cases of products of conception. 37 cases of complete mole, 27 cases of partial mole and one case of Invasive mole were diagnosed. Diffuse hydropic swelling of the villi, round smooth villous outline, circumferential trophoblastic proliferation and focal hydropic swelling of the villi, irregular scalloping outline of the enlarged villi, focal trophoblastic cell proliferation were characteristic features of complete & partial mole respectively. Histomorphological features were analysed in all the cases and compared with studies done by others. Conclusion: The classification and histomorphological analysis of GTDs are important elements for better understanding of the disease. Studies are needed to look for ancillary markers in distinguishing different types of GTDs and for predicting the prognosis. DOI: 10.21276/APALM.1193

FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling

Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in vivo. IHC studies showed increased nuclear expression of FBI-1, including hydatidiform moles, choriocarcinoma (CCA), and placental site trophoblastic tumor, in GTD. In JAR and JEG-3 CCA cells, ectopic FBI-1 expression opposed apoptosis through repression of proapoptotic genes (eg, BAK1, FAS, and CASP8). FBI-1 overexpression also promoted Akt activation, as indicated by Akt-pS473 phosphorylation. FBI-1 overexpression promoted mobility and invasiveness of JEG-3 and JAR, but not in the presence of the phosphoinositide 3-kinase inhibitor LY294002. These findings suggest that FBI-1 could promote cell migration and invasion via phosphoinositide 3-kinase/Akt signaling. In vivo, nude mice injected with CCA cells with stable FBI-1 knockdown demonstrated reduced tumor growth compared with that in control groups. These findings suggest that FBI-1 is clinically associated with the progression of, and may be a therapeutic target in, GTD, owing to its diverse oncogenic effects on dysregulated trophoblasts.

Gestational Trophoblastic Neoplasia: Challenges Dealt in the Diagnosis.

Exaggerated placental site (EPS) is defined as a non-neoplastic trophoblastic lesion where middle trophoblasts infiltrate exaggeratedly into endometrium and myometrium. It consists of cells showing the same immunophenotypical features as the intermediate trophoblasts in the normal placental implantation site and is observed as an exaggerated form of the normal physiological process [1]. Dr. Shaheen Anjum is Associate Professor in the Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College & Hospital; Dr. Kalpana Baghel is Assistant Professor in the Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College & Hospital; Dr. Nidhi Garg is Junior Resident in the Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College & Hospital; Dr. Nazoora Khan is Professor in the Department of Pathology Jawaharlal Nehru Medical College & Hospital.

Clinicopathology of gestational trophoblastic diseases with emphasis on intermediate trophoblastic tumors and tumor-like lesions

Clinicopathology of gestational trophoblastic diseases with emphasis on intermediate trophoblastic tumors and tumor-like lesions

A case report of complete mole with co-existent exaggerated placental site reaction and review of the literature.

Exaggerated placental site (EPS) is defined as a non-neoplastic trophoblastic lesion, which intermediate trophoblasts infiltrate exaggeratedly into endometrium and myometrium. These lesions may occur following normal pregnancy, ectopic pregnancy, abortus or molar pregnancy. Herein we share a case of EPS detected after evacuation due to molar pregnancy. We also review the related literature, where only a few reports exist describing the clinical course, histopathology and differential diagnosis of EPS.

Negative Pregnancy Test in Patients with Trophoblastic Diseases

Quantitative and qualitative human chorionic gonadotrophin (hCG) assays are widely used to detect pregnancy state and abnormal trophoblastic lesions. At least five different forms of hCG have been characterized and different trophoblastic diseases produce different forms of hCG in varying proportions. Because of the difference in antibody specificity in various commercial automated immunoassays of HCG, discordant results may be obtained by laboratories using different hCG assays, with a falsely low or negative result obtained if the assay does not recognize the hCG variants produced from the trophoblastic tissue. On the other hand, significantly elevated hCG concentration can paradoxically lead to false-negative results in two-site immunometric assay due to high-dose hook effect. Clinicians managing patients with trophoblastic lesions should be aware of these limitations of current hCG assays and clinical laboratories should have measures to avoid analytical false negative hCG results.

Ruptured cerebral aneurysm from choriocarcinoma

Gestational trophoblastic diseases include hydatidiform moles, invasive moles, choriocarcinoma, placental-site trophoblastic tumours and miscellaneous trophoblastic lesions. Choriocarcinoma is a rare disease that arises from the trophoblastic epithelium of the placenta at the beginning of pregnancy. Among the confirmed cases, 45% occur after molar pregnancy, 25% after normal pregnancy, 25% after an abortion and 5% after ectopic pregnancy. This tumour is usually diagnosed based on its histopathologic appearance and a high level of serum beta-human chorionic gonadotropin (β-HCG). Choriocarcinoma exhibits a good response to chemotherapy and radiation. However, it is also known for its tendency to spread rapidly to multiple organs, including the lungs, liver and brain. As one of the worst prognostic factors, brain metastasis complicates 3–28% of gestational choriocarcinoma cases. Increased β-HCG levels and a low serum cerebrospinal fluid β-HCG level can be strongly suggestive of intracranial choriocarcinoma, even in the absence of histopathologically proven disease. Reviewing the literature, there were 23 cases of intracerebral haemorrhage from an oncotic aneurysm as an initial presentation of choriocarcinoma. We report a further case of intracerebral haematoma secondary to oncotic aneurysm as the first presentation of metastatic choriocarcinoma with normal serum β-HCG.

HSD3B1 Is a Specific Trophoblast-Associated Marker Not Expressed in a Wide Spectrum of Tumors

Hydroxyl-δ-5-steroid dehydrogenase (HSD3B1) is an enzyme that catalyzes the oxidative conversion of δ-5-3 β-hydroxyl steroids to the δ-4-3-keto configuration and is involved in steroid hormone synthesis. It has been shown to be expressed in normal trophoblastic tissue and benign and neoplastic trophoblastic lesions. HSD3B1 has not been detected in a large number of lung, breast, and uterine carcinomas; however, its expression has not been studied in a wide variety of other nontrophoblastic neoplasms. To test if HSD3B1 is highly specific for normal trophoblasts and trophoblast-associated lesions, we examined the expression of HSD3B1 in a wide spectrum of tumors. Tissue microarrays containing 473 carcinomas from the lung, breast, ovary, uterus, liver, pancreas, stomach, and colon; 32 ovarian granulose cell tumors; and 12 adrenocortical adenomas were studied by immunohistochemistry using a commercially available monoclonal antibody, HSD3B1. One tissue microarray containing normal tissues was also included. Positive staining of intermediate trophoblasts and syncytiotrophoblasts in normal placental tissue served as a positive control. Normal tissues and tumors from the various sites were all negative for HSD3B1 except for 2 adrenocortical adenomas with weak focal immunoreactivity. Our study further confirmed that HSD3B1 is a highly specific trophoblast-associated marker that can be used in the distinction of trophoblastic tumorlike lesions and tumors from nontrophoblastic lesions and tumors.

Atypical Epithelioid Trophoblastic Lesion With Cyst and Fistula Formation After a Cesarean Section

We report 2 unusual cases of gestational trophoblastic disease from chorionic-type intermediate trophoblastic cells after a Cesarean section. A 32-year-old woman presented with a 2-year history of vaginal bleeding, while a 41-year-old woman presented with a pelvic mass. Both patients had cystic lesions with a fistula formation beneath their Cesarean scars in the anterior uterine isthmus. Microscopically, both lesions were lined with multiple layers of intermediate trophoblastic cells without penetration into the surrounding myometrium, endometrium, or blood vessels. The trophoblastic cells were generally bland. However, a subset of trophoblastic cells showed large, hyperchromatic nuclei in some areas. The trophoblastic cells were p63 positive and human placental lactogen negative. The Ki67 indexes were 12.7% and 8.6%, respectively. We propose their description as atypical epithelioid trophoblastic lesions with cyst and fistula formation after a Cesarean section.

Recent advances in diagnostics of trophoblastic disease

Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours, overwhelmingly affecting women of childbearing age. These tumours are rare, and they appear when trophoblastic cells start to grow out of control. In these conditions production of beta subunit of human chorionic gonadotropin (hCG) is evident. Hydatidiform moles, partial or complete, are in most cases benign featured by villous hydrps, scalloping effect, hyperplastic trophoblastic pseudoinclusions and syncytiotrophoblastic sprouts. Invasive mole is an aggressive trophoblastic lesion with myometrial and/or vascular invasion. Choriocarcinoma, placental site trophoblastic tumor and epitheloid trophoblastic tumor are clearly malignant tumors with proliferation of intermediate trophoblast, with metastatic potential. Tumor-like trophoblastic conditions are placental site nodul and exaggerated placental site which are proliferative lesions and reactive processes and are not considered as true tumor lesions. In all of these conditions vaginal bleeding is the most common symptom followed by elevation of serum beta hCG. GTD has to be confirmed histologically with extensive sampling of the material. Follow up is necessary in all women with GTD and it is rutinley done by measurement of serum levels of hCG. Since GTDs are proliferative conditions of different trophoblastic tissues, pathologists should be well histologicly educated about normal pregnancy stages and its abnormalities in order of adequate diagnosing these rare conditions.