Gestational Trophoblastic Disease: Current Evaluation and Management.

This review summarizes the current evaluation and management of gestational trophoblastic disease, including evacuation of hydatidiform moles, surveillance after evacuation of hydatidiform mole and the diagnosis and management of gestational trophoblastic neoplasia. Most women with gestational trophoblastic disease can be successfully managed with preservation of reproductive function. It is important to manage molar pregnancies properly to minimize acute complications and to identify gestational trophoblastic neoplasia promptly. Current International Federation of Gynecology and Obstetrics guidelines for making the diagnosis and staging of gestational trophoblastic neoplasia allow uniformity for reporting results of treatment. It is important to individualize treatment based on their risk factors, using less toxic therapy for patients with low-risk disease and aggressive multiagent therapy for patients with high-risk disease. Patients with gestational trophoblastic neoplasia should be managed in consultation with an individual experienced in the complex, multimodality treatment of these patients.

Management and prognostic analysis of patients with gestational trophoblastic neoplasia (GTN) in FIGO stage IV and its special type.

GTN is a group malignant diseases from placental trophoblastic cells. There are very few cases of GTN with FIGO (International Federation of Gynecology and Obstetrics) stage IV all over the world, and the special types (patients with metastatic lesions and with no evidence of GTN neither in genitalia nor in lungs) have rarely been reported. It is necessary to conduct large retrospective studies aimed at exploring the diagnosis, treatment and outcomes of this disease. In this retrospective study, 716 patients with GTN were treated at Zhejiang University School of Medicine Women's Hospital between January 1999 and September 2019; 26 patients were diagnosed as stage IV GTN; Among the 26 stage IV GTN patients, 5 were defined as the special types. The 5-year OS rate of the total 26 FIGO stage IV GTN patients was 69.0%. There was no significant difference of survival rate between stage IV GTN and its special type. And no significant differences in blood type, antecedent pregnancy type, the interval from last known pregnancy, pretreatment serum HCG (human chorionic gonadotropin) level, maximum diameter of tumors, FIGO score, underwent surgery or not and pathological pattern by the outcomes. Age, number of tumor lesions, primary chemotherapy regimen was EMA-CO or EP-EMA protocol and chemoresponse affected the prognosis significantly. Only number of tumor lesions > 8 was independent prognostic factors associated with poorer OS.

Atypical Placental Site Nodule Arising in a Postcesarean Section Scar: Case Report and Review of the Literature.

The distinction between benign and malignant trophoblastic lesions often presents a diagnostic challenge, even in entities with defined morphologic and immunohistochemical criteria. Lesions arising from chorionic-type intermediate trophoblast, namely placental site nodule (PSN) and epithelioid trophoblastic tumor (ETT), can be distinguished by existing criteria. However, a putative intermediate lesion termed "atypical placental site nodule" (APSN) has been described in the literature but is not well-classified. We present a case of APSN, along with a brief literature review, and we propose more definitive morphologic and immunohistochemical criteria for this entity, in order to facilitate easier diagnosis and gather more information regarding outcomes.

False diagnosis of and needless therapy for presumed gestational trophoblastic disease in women with an unusual site of residual pregnancy.

OBJECTIVE: This study aimed to determine the diagnostic value of magnetic resonance imaging (MRI), hysteroscopy, and laparoscopy to avoid unnecessary treatment when patients present with clinical manifestations that are close to those of gestational trophoblastic neoplasia (GTN). METHODS: Three patients who were falsely diagnosed with presumed GTN and received needless chemotherapy in our hospital from July 2011 to March 2012 were studied. We also reviewed data of patients with similar clinical features who were diagnosed as having residual pregnancy in recent years. Clinical manifestations were evaluated. RESULTS: All three patients had persistently high serum ß-human chorionic gonadotrophin levels and a mass with abundant blood supply in the uterus after termination of pregnancy. The patients were diagnosed with GTN and underwent chemotherapy. They responded poorly to chemotherapy and underwent surgery. The pathological diagnosis in all patients was residual pregnancy. In recent years, no patients were misdiagnosed because pelvic MRI, hysteroscopy, or laparoscopy was used when residual pregnancy could not be excluded. CONCLUSION: Gynecologists should diagnose carefully when patients present with clinical manifestations that are close to those of GTN to avoid unnecessary treatment. MRI, hysteroscopy, and laparoscopy could be important examinations for excluding residual pregnancy.

Classification systems in Gestational trophoblastic neoplasia - Sentiment or evidenced based?

The classification system for Gestational trophoblastic neoplasia (GTN) has proved a controversial topic for over 100years. Numerous systems simultaneously existed in different countries, with three main rival classifications gaining popularity, namely histological, anatomical and clinical prognostic systems. Until 2000, prior to the combination of the FIGO and WHO classifications, there was no worldwide consensus on the optimal classification system, largely due to a lack of high quality data proving the merit of one system over another. Remarkably, a validated, prospectively tested classification system is yet to be conducted. Over time, increasing criticisms have emerged regarding the currently adopted combined FIGO/WHO classification system, and its ability to identify patients most likely to develop primary chemotherapy resistance or disease relapse. This is particularly pertinent for patients with low-risk disease, whereby one in three patients are resistant to first line therapy, rising to four out of five women who score 5 or 6. This review aims to examine the historical basis of the GTN classification systems and critically appraise the evidence on which they were based. This culminates in a critique of the current FIGO/WHO prognostic system and discussion surrounding clinical preference versus evidence based practice.

Dutch Risk Classification and FIGO 2000 for Gestational Trophoblastic Neoplasia Compared.

OBJECTIVE: Over the years, there has been a wide variety of classification systems in use worldwide to stratify patients between single-agent versus multi-agent chemotherapy, hindering comparison of international research results. The study presents a retrospective comparison of the International Federation of Gynecology and Obstetrics 2000 and Dutch risk classification system for gestational trophoblastic neoplasia. METHODS AND MATERIALS: All patients diagnosed with gestational trophoblastic neoplasia between January 2003 and December 2012 at the trophoblastic disease centre in London were retrospectively scored according to the Dutch classification system (N = 813). RESULTS: An extensive overlap between both scoring systems was seen, even though items and relative value of items were quite distinct. The Dutch system seems to be simpler and easier to apply in all situation; a degree of overtreatment can however be presumed with the use of either system. CONCLUSIONS: Although it is likely that outcome is indeed affected by the individual factors used in both systems, many factors relate to tumor bulk and may not be independently prognostic. We therefore believe that further refinement of the classification systems and their underlying prognostic items plus any new items that seem promising would be useful.

Gestational trophoblastic diseases - clinical guidelines for diagnosis, treatment, follow-up, and counselling.

Hydatidiform mole is treated with surgical uterine evacuation with suction and blunt curettage (D). Medical uterine evacuation should not be used (C). On clinical suspicion of hydatidiform mole, one representative sample of the evacuated tissue is fixed for histopathologic investigation and one is forwarded unfixed for genetic analysis (D). Serum hCG is measured on suspicion of hydatidiform mole. At the time of the uterine evacuation, the initial hCG is measured (A). After a hydatidiform mole that is both triploid and partial, serum hCG is measured weekly until there are two consecutive undetectable values (< 1 or < 2), after which the patient can be discharged from follow-up (C). After a diploid hydatidiform mole, a complete mole, or a hydatidiform mole without valid ploidy determination, serum hCG is measured weekly until the value is undetectable (< 1 or < 2). If serum hCG is undetectable within 56 days after evacuation, the patient can be discharged from follow-up after an additional four monthly measurements. If serum hCG is first normalised after 56 days, the patient is follow-up with monthly serum hCG measurement for six months. Safe contraception should be used during the follow-up period (A). If hCG stagnates (less than 10% fall over three measurements), increases, or if hCG can be demonstrated for longer than 6 months, the patient by definition has persistent trophoblastic disease (PTD). A chest X-ray should be taken and a gynaecologic ultrasound scanning performed. The patient is referred to oncologic treatment (A). Uterine re-evacuation as a treatment for PTD can, in general, not be recommended because the rate of remission is low, and there is the risk of perforation of the uterus (C). In all following pregnancies, the woman is offered an early ultrasound scan, e.g. in gestational week eight (D). Eight weeks after termination of all future pregnancies, serum hCG is measured (D). In PTD and invasive hydatidiform mole, the primary treatment is MTX, either orally every third week or IV every week (B). In MTX-resistant PTD, IV act D is added (or replaces the MTX) (B). Third line chemotherapy is BEP or EP, alternatively EMA-CO (B). Choriocarcinoma is primarily treated with chemotherapy. Hysterectomy and/or resection of metastases are possible treatments (A). Placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) are primarily treated with hysterectomy. In the case of disseminated disease, chemotherapy is considered (A). The risk of reoccurrence after trophoblastic disease treated with chemotherapy is approximately 3%. Most reoccurrences are seen within 12 months, and for this reason monitoring of hCG is recommended for one year, the first third months once or twice a month, thereafter every second to third month. Patients with PSTT and ETT are monitored with measurement of hCG throughout their lifetimes (C). In genetically verified twin pregnancy with hydatidiform mole and a living foetus, the pregnancy can continue if serum hCG is monitored and ultrasound scans regularly performed, and possible obstetric complications dealt with (C). In the case of recurrent hydatidiform mole and/or familial hydatidiform mole, patients should be referred to genetic workup and counselling (C). Women with a hereditary disposition to hydatidiform mole because of a mutation in NLRP7 should be informed of the possibility of becoming pregnant via egg donation (C).

Atypical postcesarean epithelioid trophoblastic lesion with cyst formation: a case report and literature review.

We report an extremely rare case of atypical postcesarean epithelioid trophoblastic lesion with cyst formation. A 41-year-old Chinese woman presented with lower abdominal pain and menstrual disorder. Her serum human chorionic gonadotropin (hCG) was low (0.373 IU/L), and her urine hCG was negative. Ultrasound images showed a 3.7×2.8×2.5 cm(3) mass on the surface of the lower uterine segment, and a laparoscopy indicated a cystic mass in the serosal surface of the lower uterine segment. Histology indicated a cystic lesion consisting of epithelioid trophoblastic cells with an intermediate pattern between a classical placental site nodule and an epithelioid trophoblastic tumor; thus, the term atypical postcesarean epithelioid trophoblastic lesion with cyst formation was appropriate. As in atypical placental site nodule, serum hCG monitoring after treatment is necessary.

Diagnosis, classification and treatment of gestational trophoblastic neoplasia.

Gestational trophoblastic neoplasia (GTN) is the term to describe a set of malignant placental diseases, including invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Both invasive mole and choriocarcinoma respond well to chemotherapy, and cure rates are greater than 90%. Since the advent of chemotherapy, low-risk GTN has been treated with a single agent, usually methotrexate or actinomycin D. Cases of high-risk GTN, however, should be treated with multiagent chemotherapy, and the regimen usually selected is EMA-CO, which combines etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. This study reviews the literature about GTN to discuss current knowledge about its diagnosis and treatment.

[Belgian register and reference centers for gestational trophoblastic diseases]. / REGISTRE BELGE ET CENTRES DE RÉFÉRENCE POUR LES MALADIES TROPHOBLASTIQUES GESTATIONNELLES.

Gestational trophoblastic diseases include placental pathologies comprising fertilization abnormalities (hydatidiform moles) and malignant lesions (choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor). Due to their low incidence and heterogeneity, their diagnosis, management and treatment are not always optimal. Following the example of other European countries, a national registration system with two reference centers has been set up to guide physicians and patients and to propose individualized management. The centers offer their expertise through a systematic centralised pathology review by a panel of experts. HCG values are plotted in regression curves. In case of gestational trophoblastic neoplasia, an imaging work-up is proposed, from which the FIGO score and stage are derived and will guide the choice of treatment. Belgian centers offer a multidisciplinary approach, in partnership with the referent physician. More information for practitioners and patients is available on a web site: www.mole-chorio-bgog.eu, which also harbours a forum of discussion.

[Gestational trophoblastic disease]. / Les maladies trophoblastiques gestationnelles.

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.

Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

INTRODUCTION: Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. METHODS: Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. RESULTS: Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). DISCUSSION: Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia.

Gestational trophoblastic neoplasia (GTN) includes invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The overall cure rate in treating these tumors is currently >90%. Thorough evaluation and staging allow selection of appropriate therapy that maximizes chances for cure while minimizing toxicity. Nonmetastatic (stage I) and low-risk metastatic (stages II and III, score <7) GTN can be treated with single-agent chemotherapy resulting in a survival rate approaching 100%. High-risk GTN (stages II-IV, score ≥7) requires initial multiagent chemotherapy with or without adjuvant radiation and surgery to achieve a survival rate of 80-90%.

[Histopathology of gestational trophoblastic disease. An update]. / Gestationsbedingte Trophoblasterkrankungen. Aktuelle Aspekte.

The differential diagnosis of villous forms of gestational trophoblastic disease (GTD) includes hydropic abortion, complete and partial hytatidiform mole and placental mesenchymal dysplasia. In addition to histologic criteria, p57(KIP2) immunohistochemistry might be helpful. Choriocarcinoma represents the most immature form of GTD. This and downregulation of HSP-27 might contribute to the high chemosensitivity, compared to placental site (PSTT) and epitheloid trophoblastic tumor (ETT). Within the differential diagnosis of the non-villous forms of GTD an algorithmic approach of immunohistochemistry is very helpful. With an incidence of 1.6% of all abortions within the first trimester the exaggerated placental site reaction (EPS) is rare. There is no molecular indication that the EPS represents a precursor lesion of PSTT. The morphologic prediction of the behaviour of PSTT is not well established. Factors which might be associated with adverse outcome are age >35 years, interval since last pregnancy >2 years, growth outside the uterus, deep myometrial invasion, destructive growth, extensive coagulative necrosis, presence of cells with clear cytoplasm, high mitotic rate and a Ki-67 labeling index >50%. Recent molecular data suggest a neoplastic transformation of (cyto-) trophoblastic stem cells, within the pathogenesis of (non-villous) GTD. The detection of target molecules for a targeted therapy is currently irrelevant.

Methotrexate for 2000 FIGO low-risk gestational trophoblastic neoplasia patients: efficacy and toxicity.

OBJECTIVE: We sought to review efficacy and toxicity of an 8-day methotrexate (MTX) regimen in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) from the French Trophoblastic Disease Reference Center. STUDY DESIGN: Between 1999 and 2006, 142 low-risk GTNs were diagnosed according to International Federation of Gynecology and Obstetrics (FIGO) criteria for GTN and to the FIGO scoring system. We report their characteristics, remission/resistance/recurrence rates, and treatment toxicity. RESULTS: The 8-day MTX regimen achieved a 77.5% remission rate. All patients but 1 (99.9%) achieved remission and remained disease free until the time of analysis. Severe (grade 3 or 4) blood/bone marrow toxicity and metabolic/laboratory toxicity was noted in 4.2% of cases, of which 2 (1.4%) were grade 4. CONCLUSION: For patients with GTN diagnosed according to FIGO criteria and considered low risk according to the FIGO scoring system, an 8-day MTX regimen is an adequate treatment associating a high rate of remission to a low rate of toxicity.

Impact of the revised FIGO/WHO system on the management of patients with gestational trophoblastic neoplasia.

OBJECTIVE: To study the effect of a change in disease scoring systems on the management of patients with gestational trophoblastic neoplasia (GTN) in our supra-regional treatment centre. METHODS: We reviewed disease characteristics and treatment outcomes in 632 GTN patients managed at our centre from 1973 to 2006. Two disease scoring systems were used sequentially, the Sheffield modification of the Charing Cross Scoring System (SCCSS) before 2000, and the revised FIGO/modified WHO system (FIGO 2000) thereafter. RESULTS: Using the SCCSS 573 (90.7%) patients were classified as low risk (LR) and 59 (9.3%) as high risk (HR). With FIGO 2000, 587 (92.9%) were LR and 45 (7.1%) HR. For LR patients, the complete response (CR) to first line single agent chemotherapy was 77% before 2000 and 61.6% from 2000 to 2006. For HR patients, the CR rates with first line chemotherapy were 79.5% and 75% respectively. The higher threshold for assigning a patient as HR using FIGO 2000 had an impact on the success of treatment; only 7/19 patients (37%) who were scored 6 by FIGO 2000, and thus treated as LR with methotrexate/folinic acid, achieved a CR. CONCLUSION: In our experience, the revised FIGO/modified WHO scoring system has down scored some patients who would have been considered as high risk with the previous scoring system. A trend to lower CR with first line chemotherapy and an increase in the need for second line chemotherapy was seen.

Treatment of gestational trophoblastic neoplasia according to the FIGO 2000 staging and scoring system: a 20 years' experience.

OBJECTIVE: To reassess the efficacy of the Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system in comparison to the original World Health Organization (WHO) prognostic scoring system (1983) in a single-institute setting. DESIGN: Retrospective review of the medical records of 89 patients with gestational trophoblastic neoplasia. SETTING: Mackay Memorial Hospital, Taipei, a regional referral center for northern Taiwan, over a 20-year period. METHODS: All selected patients were classified retrospectively by the original WHO prognostic scoring system (1983) and the FIGO 2000 system. MAIN OUTCOME MEASURE: Efficacy as the correlation of risk categorization by percentage of patients between the original WHO scoring system (1983) and the FIGO 2000 system. RESULTS: The correlation was 97%. Only two patients were classified as middle risk group in the original WHO system (1983), but as high-risk group by the FIGO 2000 system. CONCLUSION: There was good correlation between the original WHO (1983) and FIGO 2000 systems. Treatment outcomes by FIGO 2000 system were somewhat better than by the original WHO classification.