Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours.

BACKGROUND: Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. METHODS: The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. RESULTS: Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). CONCLUSION: PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

Dedifferentiated endometrioid adenocarcinoma with trophoblastic components and elevated serum alfa-fetoprotein: A case report and literature review.

RATIONALE: Dedifferentiated endometrioid adenocarcinoma (DEAC) consisted of a combination of undifferentiated and differentiated carcinoma is more aggressive than other conventional endometrioid adenocarcinomas. PATIENT CONCERNS: A 33-year-old woman with atypical vaginal bleeding was refereed to our hospital. She had an endometrial biopsy in a local clinic which showed differentiated endometrioid carcinoma with trophoblastic components. High levels of ß-Human chorionic gonadotropin (ß-hCG) and alfa-fetoprotein (AFP) were detected in the patient's serum. INTERVENTIONS: The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, total omentectomy and systemic pelvic lymphadenectomy in our center. DIAGNOSIS: Pathological investigation indicated that the tumor had well differentiated and undifferentiated adenocarcinoma as well as trophoblastic components. OUTCOMES: Serum ß-hCG and AFP dropped significantly after operation. But three weeks later, the patient had developed pulmonary metastases and elevation of serum ß-hCG. She died of the disease five months after surgery. LESSONS: DEAC with trophoblastic differentiation seems to follow an aggressive course with early metastasis and poor clinical prognosis. However, due to small number of cases, further studies are necessary.

Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

BACKGROUND: Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+ß-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay. METHODS: We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function. RESULTS: We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels. CONCLUSION: The Elecsys hCG+ß-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice.

Comparison of two assays measuring human chorionic gonadotrophin serum concentrations in pregnancy termination and trophoblastic or non-trophoblastic tumours.

BACKGROUND: Differences in human chorionic gonadotrophin (hCG) results provided by the commercial immunoassays reflect the heterogeneity of antibodies and the use of suboptimal standards. As a consequence, the principal forms of hCG and metabolites are differentially detected and the hCG tests are not suited for the same clinical applications. Conflicting results are available in the literature regarding which hCG variants are recognized by the Roche Elecsys hCG + ß test. The aim of our study was to compare the hCG concentrations provided by the Siemens Immulite 2000 test and the Roche test as well as to assess the concordance between both assays. METHODS: In this purpose, 152 samples obtained from women and 44 samples from men were analysed by both tests during the follow-up of pregnancy termination, gestational trophoblastic disease and malignancies. The intermediate precision of the Roche test was also investigated on a pool with a low hCG concentration. RESULTS AND CONCLUSIONS: The hCG concentrations measured with the Roche test were slightly lower compared with the Siemens assay; mean biases of -34.2% and -8% were respectively obtained for hCG values ≤100 UI/L and higher than 100 UI/L. The overall agreement between both assays was 96.1% for women and 97.7% for men. By using an upper reference limit of 3.2 UI/L for women and 1.6 UI/L for men, the Roche test demonstrated a respective concordance of 98.7% and 100%. This test also yielded an excellent precision with a coefficient of variation of 2.8% at a mean hCG concentration of 7 UI/L.

Pulmonary mass diagnosed as extrauterine epithelioid trophoblastic tumor.

Pulmonary extrauterine epithelioid trophoblastic tumors (ETTs) are extremely rare. A 26-year-old nonsmoking woman with a history of a suspected subclinical miscarriage presented with a large mass in the right lower lobe that was confirmed to be a pulmonary extrauterine ETT using immunohistochemical stains. When a nonsmoking fertile woman presents with a pulmonary mass and an elevated serum ß-human chorionic gonadotrophin in the absence of gynecologic disease, pulmonary extrauterine ETT should be considered.

Clinical features of early-stage nonhydropic mole for diagnosis of persistent trophoblastic disease.

OBJECTIVES: To characterize the clinical features of "nonhydropic" hydatidiform mole and to investigate regression of serum human chorionic gonadotropin (hCG) as an aid in detecting persistent trophoblastic disease after nonhydropic hydatidiform mole. METHODS: Our study included women with histologically diagnosed nonhydropic molar pregnancies. Women did not exhibit macroscopic or characteristic ultrasonographic appearances specific to hydatidiform mole. Regression of serum hCG levels was compared with abortions of nonmolar pregnancies, which were histologically confirmed. RESULTS: Among 34 nonhydropic molar pregnancies, 32 complete hydatidiform moles were analyzed, excluding two partial hydatidiform moles. Compared with nonmolar aborted pregnancies, pre-evacuation hCG levels were significantly higher in the 32 complete hydatidiform moles. The 32 molar pregnancies progressed to 24 cases of spontaneous remission and eight cases of persistent trophoblastic disease. Among patients with spontaneous remission, the time at which serum hCG levels became undetectable and the onset of first postabortion menstruation were similar to those in patients who had nonmolar abortions. In all patients who experienced regression, serum hCG was undetectable after the third postabortion menstruation. In all patients with persistent trophoblastic disease, serum hCG levels exceeded 25 milli-international units/mL 4 weeks after evacuation. CONCLUSION: Without histological confirmation, it is difficult to diagnose nonhydropic molar pregnancy based solely on clinical presentation. Follow-up studies of serum hCG levels 4 weeks after abortion and after the third postabortion menstruation may aid in detecting impending persistent trophoblastic disease. LEVEL OF EVIDENCE: II.

May platelet count be a predictor of low-risk persistent gestational trophoblastic disease?

PURPOSE: The aim of this paper was to determine whether platelet count could be used as an early marker to predict low-risk persistent trophoblastic disease (PTD) from complete hydatidiform mole (CHM). METHODS: This study included 27 PTD, 30 CHM, and 30 healthy pregnant women. All patients were evaluated with respect to age, gestational age, parity, BMI, and platelet count. All women had low-risk disease using FIGO and WHO scoring systems. RESULTS: There were no significant differences in terms of age, gestational age, parity, BMI between the groups (P > 0.05, for all). Platelet levels were lower in patients with low-risk PTD compared with CHM and healthy pregnant group (P = 0.001 and P < 0.0001, respectively). Platelet levels were also found to be lower in patients with CHM than in healthy pregnancies (P = 0.006). There was a negative relationship between platelet count and low-risk PTD (r = 0.47, P < 0.0001) in the study. The receiver operating characteristic curve analysis revealed a high diagnostic value for platelet count with respect to low-risk PTD with an area under curve of 0.80 (95% confidence interval = 0.89-0.90), sensitivity = 77% and specificity = 75%. CONCLUSION: Platelet count was significantly decreased in low-risk PTD compared with CHM and healthy pregnant controls. Platelet count can be used as a reliable marker for the early detection of low-risk PTD.

Pre-evacuation hCG glycoforms in uneventful complete hydatidiform mole and persistent trophoblastic disease.

OBJECTIVE: To investigate whether the glycoform distribution patterns of human chorionic gonadotropin (hCG) obtained by chromatofocusing in pre-evacuation serum are different for patients who will eventually develop into persistent trophoblastic disease in case of complete hydatidiform mole pregnancy as compared to those patients for whom trophoblastic tissue will regress uneventfully. METHODS: Pre-evacuation blood samples were collected from women with complete hydatidiform mole with uneventful spontaneous regression after molar evacuation (n=32), from women with complete hydatidiform mole who developed persistent trophoblastic disease after evacuation of their mole (n=28) and, as a control group, from women during the first trimester of normal pregnancy (n=22). The serum specimens were subjected to chromatofocusing, and hCG was determined in the fractions collected in the pH range 7.0-3.0. RESULTS: Receiver operating characteristics (ROC) analysis revealed that 36% of complete hydatidiform mole patients with post-molar persistent trophoblastic disease development had different hCG glycoform profiles at 97% specificity (pH interval 6.3-5.1, hCG cutoff 9.9%). There was a significant difference between complete hydatidiform mole with and without persistent trophoblastic disease for the cumulative percent amounts of hCG in the pH interval 6.3-5.1 (p<0.0003). CONCLUSION: In 36% of the patients with complete hydatidiform mole with subsequent development of persistent trophoblastic disease, typical glycoform profiles for hCG are observed in pre-evacuation serum samples. This result suggests that hCG glycoform profiles are of potential use in the prediction of persistent trophoblastic disease.

Extrauterine epithelioid trophoblastic tumors presenting as primary lung carcinomas: morphologic and immunohistochemical features to resolve a diagnostic dilemma.

Our objective was to describe the clinicopathologic features of epithelioid trophoblastic tumors (ETTs) in a series of patients who presented with elevated beta-human chorionic gonadotrophin (hCG) levels and extrauterine lesions resembling primary lung carcinomas. Clinical and pathologic materials were reviewed and Shih and Kurman's diagnostic criteria were applied. Three parous women (38, 49, and 34 y of age) with elevated beta-hCG levels had nondiagnostic gynecologic evaluations, including negative dilation and curettage specimens. Imaging revealed isolated pulmonary lesions, 2 to 8.5 cm in size, resembling primary lung carcinomas. Two patients received multiagent chemotherapy consisting of etoposide, methotrexate, dactinomycin, alternating with cisplatin and etoposide, and all underwent pulmonary resection. Histologically, the cytologic features, epithelioid growth pattern, and hyaline-like material simulated the appearance of nonsmall cell lung carcinoma, but overall, the histologic features along with the immunophenotype supported classification as ETT. Follow-up hysterectomy specimens were histologically normal. All 3 patients are alive and well. The rarity of ETT and its resemblance to squamous and pleomorphic carcinomas of lung have led to diagnostic difficulties. When reproductive-age women present with elevated beta-hCG levels, a pulmonary lesion, and no apparent intrauterine disease, primary pulmonary ETT should be considered. Correlating clinical indices with specific morphologic and immunohistochemical features can ensure diagnostic accuracy and appropriate treatment for favorable outcomes.

External validation of serum hCG cutoff levels for prediction of resistance to single-agent chemotherapy in patients with persistent trophoblastic disease.

Van Trommel et al have previously shown that serum human chorionic gonadotropin (hCG) cutoff levels can provide early prediction of resistance to first-line methotrexate (MTX) in patients with persistent trophoblastic disease (PTD). In this study, we validate this approach of prediction of resistance to single-agent chemotherapy in an independent and larger cohort of PTD patients using a different hCG assay. Receiver operating characteristics (ROC) curves were constructed to determine hCG cutoff levels and sensitivity between patients cured on single-agent chemotherapy (control group) and patients requiring change to combination chemotherapy (study group). Receiver operating characteristics analysis identified an hCG cutoff value of 737 IU l(-1) that enabled us to predict the subsequent development of single-agent chemotherapy resistance in 52% of patients before their fourth MTX course at 97.5% specificity. This would have enabled an earlier switch to combination chemotherapy reducing the MTX exposure by an average of 2.5 courses. The present findings confirm that serum hCG cutoff levels predict resistance to single-agent therapy earlier than traditional methods. Change to combination chemotherapy should be considered for patients whose serum hCG levels exceed these hCG cutoff values. For patients not exceeding the hCG cutoff levels, static or rising hCG levels should still be included in the criteria for change of chemotherapy.

Management and outcome of healthy women with a persistently elevated beta-hCG.

PURPOSE: Raised serum beta human chorionic gonadotrophin (beta-hCG) not due to pregnancy can occur as a consequence of (1) gestational trophoblastic neoplasia (GTN), (2) non-gestational trophoblastic tumours, (3) a false-positive beta-hCG, (4) the menopause or (5) a high normal level. Accurate differentiation between these causes is vital to avoid potentially inappropriate investigations and therapies, which may induce infertility or other serious adverse events. Here we report the United Kingdom experience of patients with an elevated beta-hCG of initial uncertain cause and provide a clinical algorithm for the management of such cases. METHOD: The Charing Cross and Weston Park Hospital GTN databases were screened to identify patients referred with an elevated beta-hCG who were not pregnant and had no previous diagnosis of GTN. RESULTS: Between 1981 and 2004 fourteen women presented with persistently raised serum beta-hCG resulting in diagnostic problems. False-positive beta-hCG was excluded in all. Three patients developed gestational choriocarcinoma after 9-29 months. However, in 11 women no cause for the persistently elevated beta-hCG was found. One of these achieved chemotherapy-induced normalisation of serum beta-hCG, but the remaining 10 underwent surgery and/or chemotherapy without benefit. Thus, 71% (10/14) of patients remain well with unexplained elevated beta-hCG levels. CONCLUSION: Elevated serum and urinary beta-hCG levels in healthy women should be investigated systematically to exclude an underlying malignant process and to avoid inappropriate surgical and medical intervention. Long-term follow-up is required as tumours may not become apparent for many months or years.

Recurrent gestational trophoblastic disease after hCG normalization following hydatidiform mole in The Netherlands.

OBJECTIVES: To determine the risk for recurrent trophoblastic disease after spontaneous normalization of human chorionic gonadotropin (hCG) levels in patients with hydatidiform mole and to determine the risk for tumor relapse after apparent remission following chemotherapy in patients with low- and high-risk persistent trophoblastic disease. METHODS: From 1994 until 2004, 355 patients with hydatidiform mole were registered at the Dutch Central Registry of Hydatidiform Mole and were monitored by sequential hCG assays in serum at the department of Chemical Endocrinology of the Radboud University Nijmegen Medical Centre. HCG regression curves were analyzed together with clinical information collected from the Hydatidiform Mole Database. RESULTS: Among the 355 registered hydatidiform mole patients, 265 patients attained spontaneous normalization following evacuation. Of the 265 patients, one patient (0.38%) subsequently required chemotherapeutic treatment for recurrent trophoblastic disease (95% confidence interval 0.0% to 2.1%). HCG levels did not decline to normal (<2.0 ng/ml) spontaneously in 90 patients; those patients were subsequently treated. Relapse rates were 8.1% (6/74) and 6.3% (1/16) for the low- and high-risk category respectively. CONCLUSION: Our analysis indicates that relapse risk in hydatidiform mole patients with spontaneous normalization is extremely low (one in 265 patients) after two normal hCG levels (<2.0 ng/ml) are achieved. Our results support the suggestion that two subsequent normal hCG levels may be sufficient to ensure sustained remission after hydatidiform mole evacuation. In contrary, in order to assure sustained remission, the relapse rates after chemotherapy in the current study emphasize the need for surveillance of trophoblastic tumor patients even after complete remission has apparently been achieved.

Serous carcinoma of the endometrium with choriocarcinomatous differentiation: a case report and review of the literature indicate the existence of 2 prognostically relevant tumor types.

Nongestational choriocarcinomas rarely occur outside the gonads or teratomas. We report a serous carcinoma of the endometrium with a choriocarcinomatous component and review of the literature. A 61-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy for a serous carcinoma with choriocarcinomatous component. Immunohistochemistry showed a strong p53 staining of the serous component and the cytotrophoblastic cells of the choriocarcinomatous component; the syncytiotrophoblast was negative. The initial serum human chorionic gonadotropin (hCG) was 225,000 IU/L. Postoperatively, the patient developed diffuse pulmonary metastatic disease. Despite chemotherapy, the patient died 2 months after initial diagnosis. Abstracting the data from the reported cases and from the literature, it can be assumed that 2 different tumor types exist. The first one is morphologically and clinically more related to the gestational choriocarcinoma with strongly elevated serum hCG levels, early onset of (distant) metastatic disease, and consecutively rapid and often fatal clinical course. The second type presents as an endometrial carcinoma with single syncytiotrophoblast-like cells, associated with low serum hCG, no distant metastatic disease, and, consequently, a better prognosis. The prognostically relevant component for long-time survival in the latter variant is the nontrophoblastic component.

Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment.

Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant (n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 +/- 125 pmol/l in the first trimester of pregnancy (n = 13), 2,483 +/- 302 pmol/l in the third trimester of pregnancy (n = 7), and <2 pmol/l on day 15 postpartum (n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 +/- 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 +/- 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels (r(2) = 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN.

[Syndrome of persistent low levels of human chorionic gonadotrophin (hCG)]. / Syndrom perzistujících nízkých hladin humánních choriových gonadotropinu (hCG) etiologie, klasifikace, diagnostika, postupy.

OBJECTIVE: To analyze the syndrome of persistent low levels of hCG in terms of its etiology, classification, diagnosis, and management. DESIGN: Retrospective analysis. SETTING: Center for Trophoblastic Disease in Czech Republic, Institute for Care of Mother and Child, Prague, Institute of Postgraduate medical education, IPVZ, Prague METHODS: An analysis of the syndrome of persistent low levels of hCG recorded in CTN in 29 women in the years 1979-2005 by the immunoluminesence method which can quantitatively assess variable levels of hCG in blood and urine. A comparison was made of our findings with results of a similar studies having been done in England and USA. RESULTS: Persistent low levels of hCG (PLL) can be differentiated according to cause. 1. PLL-F False positive, also known as Phantom hCG, often caused by heterogenous antibodies. 2. PLL-H Of hypophysial origin, mainly in perimenopause and menopause. 3. PLL-Q Quiescent with trophoblastic disease in history, of trophoblastic origin. 4. PLL-U Undetermined, in history without trophoblastic disease, but in the past with physiological or pathological pregnancy. Assuming also to be of trophoblastic origin. All types of PLL lead in practice to the wrong diagnosis of trophoblastic disease and to a high percentage (40-80%) of needless chemotherapy and operations. In no case of PLL did chemotherapy or operations have an effect on PLL and thus are contraindicated. PLL-Q and PLL-U require continuous clinical and laboratory monitoring and repeated examinations with sophisticated visualization methods. The percentage of developing malignant trophoblastic tumors after PLL-Q and PLL-U is unclear. Extreme incidence was established in 7-25%. PLL-Q and PLL-U are considered as a marker of persistent trophoblastic invasion. Its detection by visualization methods in any organ localization before it turns into a limited solid tumor is excluded by it microscopic dissociative structure. CONCLUSION: The syndrome of persistent low levels of hCG (PLL) lately affects all gynecological and obstetrical workplaces. According to cause it can be divided into: 1. PLL false positive, 2. PLL of hypophysial origin, 3.PLL quiescent with trophoblastic disease in the history, 4. PLL undetermined, in history without trophoblastic disease. In the last two items mentioned above we assume to be of trophoblastic origin. Their morphological base is persistent trophoblastic invasion. The syndrome of PLL often leads to the wrong diagnosis of trophoblastic disease and to needless chemotherapy and operations. In this work was described the diagnosis of PLL, its classification, cause, and management. The percentage of PLL turned into malignant trophoblastic disease is unknown and ranges from 7-25% and requires monitoring in an accredited, national center for trophoblastic disease.

Early identification of resistance to first-line single-agent methotrexate in patients with persistent trophoblastic disease.

PURPOSE: A generally accepted definition for resistance to first-line single-agent chemotherapy for persistent trophoblastic disease (PTD) is lacking. In the present study, a normogram for serum human chorionic gonadotropin (hCG) from patients with normalization of serum hCG after first-line single-agent chemotherapy for PTD was constructed to identify patients resistant to this chemotherapy. PATIENTS AND METHODS: Between 1987 and 2004, data from 2,132 patients were registered at the Dutch Central Registry for Hydatidiform Moles. A normal serum hCG regression corridor was constructed for 79 patients with low-risk PTD who were cured by single-agent methotrexate (MTX) chemotherapy (control group). Another group of 29 patients with low-risk PTD needed additional alternative therapies (dactinomycin and multiagent chemotherapy) for failure of serum hCG to normalize with single-agent chemotherapy (study group). RESULTS: Serum hCG measurement preceding the fourth and sixth single-agent chemotherapy course proved to have excellent diagnostic accuracy for identifying resistance to single-agent chemotherapy, with an area under the curve (AUC) for receiver operating characteristic curve analysis of 0.949 and 0.975, respectively. At 97.5% specificity, serum hCG measurements after 7 weeks showed 50% sensitivity. CONCLUSION: In the largest study to date, we describe the regression of serum hCG levels in patients with low-risk PTD successfully treated with MTX. At high specificity, hCG levels in the first few courses of MTX can identify half the number of patients who are extremely likely to need alternative chemotherapy to cure their disease and for whom further treatment with single-agent chemotherapy will be ineffective.

[Difficulties and biases of interpretation in cases of the trophoblast disease]. / Trudnosti i greshki pri interpretatsiia na sluchai s trofoblastna bolest.

The trophoblastic disease (TD) is an unifying term for the nosologicunits: Mola hydatidosa, Mola hydatidosa invasivum, Chorionepithelioma. This kind of trophoblast pathology has geographic differences in the expression but the its overall incidence is not high. The clinicians often fail to consider the possibility of trophoblastic disease due to its low incidence rate. The forms of TD have clinical manifestations that are not specific. There are principles, which taken into account, could help the clinicians put the right diagnosis. Two cases of the clinical practice are reviewed in maintenance of this opinion.

Human chorionic gonadotropin in cancer.

Human chorionic gonadotropin (hCG) is mainly used for detection and monitoring of pregnancy and pregnancy-related disorders but it is also an extremely sensitive and specific marker for trophoblastic tumors of placental and germ cell origin. Thus treatment of relapsing choriocarcinomas and testicular germ cell tumors is often initiated on the basis of rising hCG levels even in the absence of clinical or histological evidence of a relapse. While these tumors mostly produce the intact heterodimeric hormone consisting of an alpha (hCGalpha), and a beta subunit (hCGbeta), many nontrophoblastic tumors produce only hCGbeta This is usually a sign of aggressive disease and elevated serum levels of hCGbeta are strongly associated with poor prognosis. Elevated serum levels are observed in 45-60% of patients with biliary and pancreatic cancer and in 10-30% of most other cancers. Methods that detect hCG and hCGbeta together are mainly used for measurement of hCG-like immunoreactivity in serum. However, the reference range for hCG is 5-8 fold higher than that for hCGbeta and thus moderately elevated levels can be identified only with a specific and sensitive hCGbeta assay.