Invasive and metastatic hydatidiform moles in Slovakia in 1993‒2022.

OBJECTIVE: A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes. BACKROUND: Invasive and metastatic mole is a highly curable type of gestational trophoblastic neoplasia. Both invasive and metastatic HM may be cured by hysterectomy without adjuvant chemotherapy. METHODS: Nineteen cases of histopathologically confirmed HM (10 invasive and 9 metastatic) were treated in SR from 1993 to 2022. Patients were divided into two groups according to treatment modality (hysterectomy only ‒ 8; hysterectomy and chemotherapy ‒ 11). The parameters included in the analysis were patient age, antecedent pregnancy, human chorionic gonadotropin level, tumor size and time to remission. RESULTS: The incidence of invasive and metastatic HM in the SR was 1:121,253 pregnancies, or 1:86,589 live births. The overall cure rate was 100%, without recurrence. Hysterectomy was performed as first-line therapy in 14 patients, with a cure rate of 57.1%. 4 out of 8 patients (50%) with metastatic moles, who underwent first-line hysterectomy, were cured without chemotherapy. There was no statistically significant difference between the two groups in all selected parameters. CONCLUSION: First-line hysterectomy may lead to remission without adjuvant chemotherapy or reduce the number of chemotherapies in invasive and metastatic HM (Tab. 4, Fig. 2, Ref. 21).

Cornual invasive hydatidiform mole: a rare case report and literature review.

BACKGROUND: The cornual pregnancy is a rare condition of ectopic pregnancies. Invasive hydatidiform mole is a rare form of gestational trophoblastic diseases. Cornual invasive hydatidiform mole is extremely rare. CASE PRESENTATION: A 17-year-old girl presented to the gynecology department with irregular vaginal bleeding. This patient was diagnosed with cornual invasive hydatidiform mole. Mono-chemotherapy was admitted firstly and with poor efficacy. The patient was cured by a combination of chemotherapy and resection of the uterine mass. CONCLUSION: Cases with cornual invasive hydatidiform mole are extremely rare conditions. Unlike common site of invasive hydatidiform mole, mono-chemotherapy may be insufficient for cornual invasive hydatidiform mole. Chemotherapy in combination with other treatments may be needed in this rare condition.

Combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios for early prediction of postmolar gestational trophoblastic neoplasia.

PURPOSE: To investigate factors predicting postmolar gestational trophoblastic neoplasia (GTN) by combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios. METHODS: This retrospective study enrolled patients with histopathologically proven molar pregnancy. Patients lost to follow-up before remission or developing postmolar GTN were excluded. Demographic and clinical characteristics and hCG data obtained before and after molar evacuation were collected. Area under the receiver operating characteristic curve (AUC) analysis was used to identify the hCG and hCG ratio cutoff values that predict postmolar GTN. Multivariate analysis was employed to identify independent predictors of GTN. RESULTS: There were 113 complete moles, 11 partial moles, and 52 unspecified moles included in the final analysis. Of the 176 cases, 90 achieved remission and 86 developed post-molar GTN. The incidence of postmolar GTN was 48.9%, with a median time to GTN development of 5 weeks. Univariate analysis showed age, molar evacuation performed elsewhere, pre-evacuation hCG, hCG at 2nd week post-evacuation, and ratio of hCG at 2nd week post-evacuation to post-evacuation hCG significantly predict GTN. Multivariate analysis revealed an hCG value ≥ 1400 IU/L at 2nd week post-evacuation (AUC: 0.92, aOR: 6.51, 95% CI 1.28-33.16; p = 0.024) and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 (AUC: 0.88, aOR: 12.27, 95% CI 2.15-70.13; p = 0.005) to independently predict GTN. CONCLUSIONS: An hCG value ≥ 1400 IU/L at 2nd week post-evacuation and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 independently and reliably predict postmolar GTN.

Invasive mole with lung metastasis after an abdominal complete hydatidiform mole treatment.

A 27-year-old woman, gravida 1, para 0, was transferred to our hospital with acute abdominal pain. Her serum human chorionic gonadotropin level was 60 231 mIU/mL. Transabdominal ultrasound revealed an echo-free space, and emergency laparoscopy-assisted surgery was performed with a preoperative diagnosis of ruptured ectopic pregnancy. The pelvic cavity was filled with clots, and the peritoneal surface of the uterine fundus was swollen and showed continuous bleeding. The lesion was located on peritoneum and not connected with the uterine cavity. Histological examination of the conceptus showed features of a complete hydatidiform mole. After a mild decrease, hCG levels adversely increased 3 weeks later with multiple lung nodules. With a diagnosis of invasive moles, the patient was administered chemotherapy. This case demonstrates that it is important to recognize the potential of ectopic hydatidiform moles through abdominal pregnancy. This is the first report of an invasive abdominal hydatidiform mole, and hCG monitoring seemed to be essential for gestational trophoblastic neoplasia detection.

Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease.

Hydatidiform moles are classified at the genetic level as androgenetic complete mole and diandric-monogynic partial mole. Conflicting data exist whether heterozygous complete moles are more aggressive clinically than homozygous complete moles. We investigated clinical outcome in a large cohort of hydatidiform moles in Chinese patients with an emphasis on genotypical correlation with post-molar gestational trophoblastic disease. Consecutive products of conceptions undergoing DNA genotyping and p57 immunohistochemistry to rule out molar gestations were included from a 5-year period at Beijing Obstetrics and Gynecology Hospital. Patient demographics and clinical follow-up information were obtained. Post-molar gestational trophoblastic disease or gestational trophoblastic neoplasia was determined by the 2002 WHO/FIGO criteria. A total of 1245 products of conceptions were classified based on genotyping results into 219 complete moles, 250 partial moles, and 776 non-molar gestations. Among 219 complete moles, 186 were homozygous/monospermic and 33 were heterozygous/dispermic. Among 250 partial moles, 246 were triploid dispermic, 2 were triploid monospermic, and 2 were tetraploid heterozygous partial moles. Among 776 non-molar gestations, 644 were diploid without chromosomal aneuploidies detectable by STR genotyping and 132 had various genetic abnormalities including 122 cases of various trisomies, 2 triploid digynic-monoandric non-molar gestations, 7 cases of possible chromosomal monosomy or uniparental disomy. Successful follow-up was achieved in 165 complete moles: post-molar gestational trophoblastic disease developed in 11.6% (16/138 cases) of homozygous complete moles and 37.0% (10/27 cases) of heterozygous complete moles. The difference between the two groups was highly significant (p = 0.0009, chi-square). None of the 218 partial moles and 367 non-molar gestations developed post-molar gestational trophoblastic disease. In conclusion, heterozygous/dispermic complete moles are clinically more aggressive with a significantly higher risk for development of post-molar gestational trophoblastic disease compared with homozygous/monospermic complete moles. Therefore, precise genotyping classification of complete moles is important for clinical prognosis and patient management.

The potential value of red blood cell distribution width in patients with invasive hydatidiform mole.

BACKGROUND: Red blood cell distribution width (RDW) has attracted increasing attention in cancer. The aim of this study was to assess the changes of RDW in patients with invasive hydatidiform mole and analyze the relationship between RDW and invasive hydatidiform mole. METHODS: A retrospective analysis was performed on 102 patients diagnosed as invasive hydatidiform mole in the First Affiliated Hospital of Guangxi Medical University from January 2009 to March 2018. A total of 120 healthy subjects were used as a control group. The Mann-Whitney U test was used for comparison between the invasive hydatidiform mole and control groups. Comparison of RDW with other blood parameters was performed using Spearman's. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) were also determined. RESULTS: The RDW, platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and absolute lymphocyte count were significantly elevated in the invasive hydatidiform mole group compared with control group. The hemoglobin (Hb) concentration, mean red blood cell volume (MCV) and platelet count (PLT) were significantly lower in invasive hydatidiform mole group than control group. Grade III and above invasive hydatidiform mole patients had higher levels of RDW than grade I and II patients. Correlation analysis showed that RDW was negatively correlated with Hb, MCV, NLR, and neutrophil count, but positively correlated with PDW and different stages of invasive hydatidiform mole. The ROC curve showed that the AUC of the RDW was 0.660 (95% CI 0.581-0.740; P < 0.01). CONCLUSION: This study reveals the potential value of RDW in invasive hydatidiform mole.

Clinical characteristics and outcomes of extrauterine epithelioid trophoblastic tumors.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) derived from intermediate trophoblasts is one type of gestational trophoblastic neoplasia (GTN), and it accounts for less than 2% of all gestational trophoblastic diseases (GTD). Extrauterine ETT is extremely rare, and there is currently no consistent strategy for its treatment and management. Therefore, the aim of the study is to analyze and summarize the clinicopathologic features of extrauterine ETT with or without metastasis. METHOD: The Web of Knowledge, Google Scholar, EMbase, congress of library, and PubMed were searched for extrauterine ETT without primary uterine lesions. All available data were extracted from published case reports or serial case reports, and then, the clinical and pathological characteristics were analyzed. RESULTS: Twenty-two clinical studies consisting of 27 patients diagnosed with extrauterine ETT, according to the given inclusion and exclusion criteria, were included in the study. A total of 27 cases of extrauterine ETT were identified. Of these cases, four (14.81%) were located in the lungs, three (11.11%) in the ovaries, two (7.41%) in the vagina, and eight (29.63%) patients had other primary lesions. The patients originated from different continents, with 59% located in Asia and 26% in North America. Among 23 patients, the antecedent pregnancy prior to the diagnosis was full-term in 12 cases, abortion in 6 cases, hydatidiform mole in 3 cases, and invasive mole in 1 case. From the available antecedent information on pregnancy, the median interval from pregnancy to diagnosis of extrauterine ETT was 4 years. Additionally, the median gravidity and para of the patients was three times and two times, respectively. The median hCG titer was 14,374 mIU/mL in 5 patients, and the mean ß-HCG titer was 3,724,805 mIU/mL in 14 patients. For all patients, the disease was confined to extrauterine ETT at diagnosis. From the available information, 20 cases were successfully treated by extraction of local lesions, and 12 cases received chemotherapy. Diagnosis was confirmed by histological tests. The Ki-67 staining ranged from 8.7 to 80%, and tumors were positive for hCG, PLAP, EMA, and p63. CONCLUSION: In this study, we observed that abnormal levels of serum hCG titers and the local presentation of lesions with varying intervals after antecedent term pregnancy were the most common presenting features of extrauterine ETT. In addition, we found that the extraction of extrauterine lesions was needed for the treatment of extrauterine ETT. Of course, the follow-up was also important.

Histopathological and clinical features of molar pregnancy.

OBJECTIVE: To analyse own set of molar pregnancies and to develop clinically relevant procedures. TYPE OF STUDY: Review article with analysis of own data. SETTINGS: Department of Pathology 3rd Faculty of Medicine, Charles University, Faculty Hospital Královské Vinohrady, Prague; Department of Obstetrics and Gynecology 3rd Faculty of Medicine, Charles University, Faculty Hospital Královské Vinohrady, Prague. INTRODUCTION: The study monitors the decrease of laboratory values of beta-subunit of hCG gonadotropin (beta-hCG) after evacuation of partial and complete hydatidiform moles in a set of 45 partial and 46 complete moles. Two case reports of invasive moles. RESULTS: In cases of partial hydatidiform moles there was complete regression of beta-hCG in all cases, 89% regressed in six weeks, none of the women showed no subsequent elevation after reaching negativity. In cases of complete hydatidiform moles the decrease was less gradual, the negativity after six weeks was confirmed in 78%, three complete moles became malignant. CONCLUSION: The decrease of beta-hCG after molar pregnancy termination is variable. Even if in cases of complete hydatidiform moles the risk of malignization after reaching negativity is low, beta-hCG checks are recommended at monthly intervals for 6 months. Correct diagnosis of complete mole and its differentiation from partial mole can be achieved using immunohistochemistry - p57 antibody.

A metastatic invasive mole arising from iatrogenic uterus perforation.

BACKGROUND: Invasive mole derives from hydatidiform mole, but its pathogenesis remains unknown. Invasive mole arising from iatrogenic uterine perforation has not been reported yet. CASE PRESENTATION: A reproductive woman was admitted because she suffered form severe abdominal pain and acute intra-abdominal hemorrhage after suction evacuation due to misdiagnosis as inevitable abortion. The patient underwent hysteroscopy and laparoscopy, by which an iatrogenic uterine perforation and omentum and pelvic peritoneum metastases were confirmed. All lesions were removed and the final pathological diagnosis was metastatic invasive mole. The patient underwent post-operative chemotherapy with methotrexate and presented a good prognosis. CONCLUSION: Invasive mole arising form iatrogenic uterine perforation displays an unusual metastatic manner other than general invasive moles. The prevention of uterine perforation should be emphasized during suction evacuation for mole pregnancy.

Laparoscopic Management of an Invasive Mole Perforating the Uterus.

STUDY OBJECTIVE: To show the possibility of conservative laparoscopic management in a case of invasive mole perforating the uterus. DESIGN: Video with explanations. SETTING: An invasive mole is a potentially life-threatening complication of gestational trophoblastic disease [1]. This is a case of a 24-year-old female presenting with abdominal pain and vaginal bleeding. There have been several previous reports of cases of uterine perforation by an invasive mole, all of which were managed with abdominal hysterectomy [2-7]. To our knowledge, this is the first report of an invasive mole perforation with active bleeding managed by laparoscopy without hysterectomy. INTERVENTIONS: Sonography revealed a large amount of fluid and a 3 × 3-cm heterogeneous lesion next to the posterior uterine wall. Her hemoglobin level dropped from 10.6 mg/dL to 8.6 mg/dL, and her ß-human chorionic gonadotropin level was 19,004 mIU/mL. On laparoscopy, ∼2500 mL of hemoperitoneum was found, along with an actively bleeding bulging mass in the posterior uterine wall. This mass was dissected, and hemostasis was secured with sutures and electrocoagulation. Pathology confirmed the diagnosis of a complete mole. After surgery, the patient was treated with 5 courses of a methotrexate-folinic acid regimen. Her recovery was uneventful. CONCLUSION: Uterine perforation by an invasive mole can be managed conservatively with laparoscopic surgery and postoperative chemotherapy. The transmural lesion will increase the risk of future uterine rupture during pregnancy in this patient.

[Effects of prophylactic chemotherapy on outcomes and prognosis of patients older than 40 years with invasive mole].

Objective: To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients. Methods: One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group, while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group). The general clinical data (including age, clinical stage, risk factor score), treatment, outcomes and relapse of patients were retrospectively compared between two groups. Results: (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old. Ratio of clinical stageⅠ-Ⅱ were 3/11 versus 29.8% (31/104), clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2% (73/104). Ratio of risk factor score 0-6 were 11/11 versus 84.6% (88/104), risk factor score >6 were 0 versus 15.4% (16/104). There were no significant statistical differences between two groups in age, clinical stage or risk factor score (all P>0.05). (2) Treatment: the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different (Z=3.071,P=0.002). There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of ß-hCG, consolidation chemotherapy courses, total therapeutic chemotherapy courses or ratio of hysterectomy (all P>0.05). (3) Outcomes and relapse: between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group, the complete remission rate were 11/11 versus 98.1%(102/104), the relapse rate were 0 versus 1.0%(1/102). There were no significant difference between the two groups in outcomes or relapse rate (P>0.05). Conclusions: Prophylactic chemotherapy does not substantially benefit the IM patients older than 40 years. Prophylactic chemotherapy may not significantly improve patients' prognosis, in which increased sample size is required in further study.

Spontaneous renal hemorrhage caused by invasive mole: a case report.

CASE: The authors report a case with spontaneous renal hemorrhage caused by invasive mole. The diagnosis was gestational trophoblastic disease (GTD), with metastasis to brain, kidneys, and lungs at Stage IV. The patient was given etoposide-methotrexate-actinomycin D plus cyclophosphamide-vincristine (EMACO) treatment regimen for 11 times including three times with consolidation chemotherapies. Laparoscopically-assisted vaginal hysterectomy (LAVH) + laparoscopic-assisted left renal excision + evacuation of the left perirenal hematoma were performed during the eighth chemotherapy. CONCLUSION: Post-operational pathological examination revealed trophoblasts within the lesions present in uterine fundus and the residue images of a few trophoblasts present in the left renal mass.

Ovarian hyperstimulation syndrome in a spontaneous pregnancy with invasive mole.

Spontaneous ovarian hyperstimulation syndrome (sOHSS) is an extremely rare event. Herein, we report a case of severe sOHSS with invasive mole in a 29-year-old woman. In this case the full-blown OHSS developed after evacuation when the serum ß-hCG value was declining. Also noticeable was a very high level of cancer antigen-125. Molecular biology study of the follicle-stimulating hormone (FSHR) gene did not detect exonic mutations, but revealed the presence of c.-29G>A (rs1394205) in the 5'-non-coding region of exon 1. The A307T and S680N polymorphisms of exon 10 of FSHR was Thr307 Asn680. Although sOHSS is a rare entity, clinicians must bear the differential diagnosis of sOHSS in mind if a patient presents with gross ascites and other symptoms of ovarian cancer, which also may be signs of OHSS. Whether the single nucleotide polymorphism rs1394205 affects the level of transcriptional activity of the FSHR gene needs to be studied in the future.

Invasive mole in a perimenopausal woman: a case report and systematic review.

OBJECTIVE: Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumors. We present a case of a perimenopausal woman with invasive mole. A systematic review was performed to identify reports on GTD in older women and to determine adequate treatment options. CASE: A 51-year-old perimenopausal woman was admitted to hospital with abdominal feeling of pressure and nausea. Diagnostic curettage revealed hydatidiform mole. She also presented symptomatic hyperthyroidism with hypertensive blood pressure and uneasiness. After treatment with beta blockers and carbimazole, the patient underwent abdominal hysterectomy and bilateral oophorosalpingectomy. Histopathological examination confirmed an invasive hydatidiform mole (IHM). Serum ß-hCG has decreased from initially 300,000-100 unit/L after 4 weeks. DATA SOURCES: A systematic review was performed to identify all prior cases of GTD in women over 50. We searched in Medline, The Cochrane Library and Embase, to identify any articles published in the English language after 1970 and before Oct 31, 2013 pertaining to GTD in older woman (50 years or older). TABULATION, INTEGRATION, AND RESULTS: Ten records were included in the systematic review, involving 203 cases of trophoblastic disease in older women. Although the diagnosis of GTD in older women is rare, it should be considered especially in patients with suspicious intrauterine findings in transvaginal ultrasound examinations. Different treatments were performed. In a limited number of reports, older women with GTD underwent initial hysterectomy. Benefits are avoidance of chemotherapy-induced toxicity and reduced risk of recurrence. Hysterectomy should be performed by an experienced surgeon. CONCLUSION: It is concluded that GTD is very rare in peri- or postmenopausal women. Treatment has to be individualized, and hysterectomy can be considered as an appropriate option.

[Value of laparoscopic surgery in the diagnosis of suspected gestational trophoblastic neoplasia cases with uterine mass].

OBJECTIVE: To evaluate the value of laparoscopic surgery in the diagnosis of suspected gestational trophoblastic neoplasia (GTN) cases with uterine mass. METHODS: The clinical characteristics of patients underwent laparoscopic surgery for a suspected diagnosis of GTN with uterine mass in Peking Union Medical College Hospital from November 2009 to November 2014 were retrospectively reviewed and analyzed. GTN and other pregnant-related disease were definitely diagnosed by pathological findings. The prognoses of the GTN cases were also investigated. RESULTS: Sixty-two patients with a suspected diagnosis of GTN with uterine mass were studied. Among them, 17 cases were definitely diagnosed as GTN, including 8 choriocarcinoma, 5 invasive mole and 4 placental site trophoblastic tumor (PSTT). The other 45 cases were diagnosed as benign pregnancy-related diseases, including 29 cornual pregnancy, 6 cesarean scar pregnancy, 5 placenta accreta, 4 intramural uterine pregnancy and 1 exaggerated placental site. There were no significantly differences between the two groups in average age, preoperative value or tendency of ß-hCG, and location or size of lesions (P>0.05). More GTN patients showed a history of hydatidiform mole [5/17 vs 4% (2/45) , P>0.05], and more patients with benign pregnancy-related disease showed a history of cesarean section [38% (17/45) vs 1/17, P>0.05]. No serious perioperative complication was found in these patients received laparoscopic surgery. All GTN patients achieved complete remission by chemotherapy later. Except for 1 case loss, no recurrence was found in 11 low-risk stage I cases with an average follow-up period of 11- 66 months, 1 high-risk stage I case with a follow-up period of 61 months and 4 cases PSTT with a follow-up period of 13-66 months. CONCLUSIONS: There were some atypical GTN cases with uterine mass, which were difficult to be differentiated from benign pregnancy-related diseases according to the clinical characteristics. Laparoscopic surgery with a pathologic diagnosis could be an essential way with efficiency and safety.

Decorin and biglycan immunolocalization in non-villous structures of healthy and pathological human placentas.

AIMS: Decorin and biglycan are members of the small leucine-rich proteoglycan family, and constituents of both the extracellular matrix (ECM) and the cell surface. They are recognized as important factors in the control of proliferation, migration and invasion in vivo and in vitro. In this study, the localization patterns of decorin and biglycan were determined in healthy placentas and in highly invasive placental pathologies. METHODS AND RESULTS: The study included immunolocalization of decorin and biglycan in samples of first-trimester and term placentas, placenta accreta, invasive mole, and choriocarcinoma. Extravillous cytotrophoblast (EVT) cells were positive for both proteoglycans in all pathologies and in first-trimester placentas, although not in term placentas. Biglycan was immunolocalized in the ECM of all healthy and pathological placentas, whereas decorin was observed only in term placenta ECM. CONCLUSIONS: The expression of both proteoglycans was cell-specific and gestation time-dependent in healthy placentas, and was associated with invasive EVT cells in pathological placentas. In view of the biological properties of these molecules, it is possible that the biglycan pattern found here is intrinsically implicated in the invasive activity of EVT cells in both healthy and disordered placentas.