Quiescent Gestational Trophoblastic Disease Research Articles

Spontaneous regression of quiescent gestational trophoblastic disease after pregnancy: a case report

BackgroundA persistent low-level elevation of serum human chorionic gonadotropin (hCG) without clinical or radiological evidence of pregnancy or tumors was recently defined as quiescent gestational trophoblastic disease (Q-GTD). Whether patients with Q-GTD should be treated or allowed to become pregnant remains unclear. We herein report a rare case of Q-GTD in which the hCG level spontaneously returned to normal after a successful pregnancy.Case presentationThe patient was a 37-year-old primigravida who presented with a persistent low-level elevation of hCG after uterine evacuation of a hydatidiform mole. There was no evidence of neoplasia in the uterus or distant metastasis. The low-level elevation of hCG persisted for at least 2 years but never exceeded 200 mIU/mL. The patient had a successful pregnancy at the age of 40 years.ConclusionsInterestingly, her hCG level subsequently normalized without chemotherapy. The present case may imply the safety and therapeutic effect of pregnancy in women with Q-GTD.

What are the diagnostic considerations in a menopausal woman with a positive hCG test result?

EVIDENCE-BASED ANSWER The most common causes of elevated human chorionic gonadotropin (hCG) in a menopausal woman are a false-positive test (42%), quiescent gestational trophoblastic disease (GTD; 41%), low level pituitary production (10%), and malignancy (7.6%). After repeating the test in blood and urine, active malignancy and quiescent GTD should be ruled out by obtaining hyperglycosylated hCG and hCG free β-subunit. A physiologic pituitary source of hCG is likely in women with persistent low levels of hCG (<25–32 mIU/mL). This finding can be confirmed by the normalization of hCG levels after the administration of combined oral contraceptives for 2 or more weeks (SOR: C, case series of disease-oriented evidence).

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

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. 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. 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). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

Management of Chemoresistant and Quiescent Gestational Trophoblastic Disease

Gestational trophoblastic neoplasia (GTN) is highly chemosensitive and has a high cure rate. Since the introduction of chemotherapy, reliable measurement of human chorionic gonadotropin (hCG) levels, and individualised risk-based therapy into the management of GTN, almost all low-risk and more than 80 % of high-risk GTN cases are curable. However, approximately 25 % of high-risk GTN developed resistance to chemotherapy or relapsed after completion of initial therapy, which often necessitate salvage combination chemotherapy. On the other end of the spectrum, a proportion of patients with gestational trophoblastic disease (GTD) have persistently low levels of hCG, without clinical or radiological evidence of disease, a condition called quiescent GTD. Recently, measurement of hyperglycosylated hCG has been proposed for the management of patients with quiescent GTD. Although representing a small proportion of GTD cases, the management of patients with chemoresistant and quiescent GTD often poses challenges to medical practitioners.

Persistent low hCG levels beyond pregnancy: report of two cases and review of the literature

Unexpected finding or persistence of low human chorionic gonadotropin (hCG) levels is not a rare situation. It requires a clinico-biological approach in order to avoid misunderstandings that could lead to inappropriate diagnostic or therapeutic attitudes. Beyond pregnancy, persistent low levels of hCG may be associated with various benign and malignant conditions, i.e. quiescent gestational trophoblastic disease (QTD), raised pituitary hCG or false positive elevation caused by circulating heterophile antibodies. We report the cases of two non-pregnant patients with low serum hCG. In the first case, hCG levels raised during several years following a spontaneous abortion. The likelihood of heterophilic antibodies interference was ruled out and extensive clinical investigation excluded the presence of a tumour. The diagnosis was QTD. In the second case, elevated hCG came to light as an incidental finding in a women with chronic renal failure and led the clinicians to question the laboratory. The cause was probably an increase in pituitary hCG consecutive to terminal renal failure. These cases illustrate the importance of understanding the biology of the hCG and the causes of its persistent low elevation, which are reviewed in this article. It is essential to demonstrate clinically the presence of a tumour in order to avoid unnecessary and ineffective chemotherapy and/or hysterectomy.

Hyperglycosylated hCG, a review

Hyperglycosylated hCG (hCG-H) is a glycoprotein with the same polypeptide structure as hCG, and much larger N- and O-linked oligosaccharides. The oligosaccharides increase the molecular weight of hCG from 36,000 – 37,000 u to 40,000 – 41,000 u, depending on the extent of hyperglycosylation. hCG-H has triantennary N-linked oligosaccharides and double molecular size O-linked oligosaccharides (hexasaccharide compared with predominantly trisaccharide structures). hCG is produced by syncytiotrophoblast cells while hCG-H is made by extravillous cytotrophoblast cells. hCG-H promotes trophoblast invasion during choriocarcinoma, growth of cytotrophoblast cells and placental implantation in pregnancy. hCG-H is an independent molecule to hCG with totally separate biological functions. hCG has numerous functions during pregnancy, it promotes progesterone production, promotes angiogenesis in uterine vasculature, immuno-suppresses the invading placental tissue, promotes the growth of the uterus in line with the growth of the fetus during pregnancy, promotes the differentiation of growing cytotrophoblast cells, promotes the quiescence of contractions in the uterine myometrium during the course of pregnancy, and also has function in growth and development of fetal organs. Monoclonal antibody B152 uniquely binds hCG-H. Using this monoclonal antibody in immunometric assays permits detection of pregnancy. It also permits management of gestational trophoblastic diseases and detection of quiescent gestational trophoblastic disease. This same test can be used to differentiate of aggressive and minimally-aggressive gestational trophoblastic disease, and discrimination of patients that respond to chemotherapy and who are chemorefractory. The hCG-H test can be used to screen for Down syndrome pregnancies and predict patients likely to generate hypertensive disorder in pregnancy. It also can be used to differentiate pregnancies that will miscarry and pregnancies that will go to term.

USA hCG reference service, 10-year report

Introduction The USA hCG Reference Service has been dealing with cases of persistent low levels of hCG and gestational trophoblastic diseases for 10 years. Here we present the complete experience. Methods Total hCG in serum and urine was measured using the Siemen's Immulite 1000 assay. Hyperglycosylated hCG, nicked hCG, free ß-subunit and ß-core fragment were measured using microtiterplate assays with antibodies B152, B151, FBT11 and B210, respectively. Results The USA hCG Reference Service has identified 83 cases of false-positive hCG, 71 cases of aggressive gestational trophoblastic disease (GTD), 52 cases of minimally invasive GTD, 168 cases of quiescent GTD and 22 cases of placenta site trophoblastic tumor (PSTT). In addition, 103 cases of pituitary hCG have been identified, 60 cases of nontrophoblastic tumor, 4 cases of inherited hCG and 2 cases of Munchausen's syndrome. This is 565 cases total. Multiple new methods are described and tested for diagnosing all of these disorders. Conclusions The USA hCG Reference Service experience shows new methods for detecting multiple hCG-related disorders and recommends new approaches for detecting these hCG-related disorders.

Hyperglycosylated hCG in the Management of Quiescent and Chemorefractory Gestational Trophoblastic Diseases

Abstract Introduction The literature shows that hyperglycosylated hCG is the invasion stimulus in malignant gestational trophoblastic diseases. The USA hCG Reference Service has characterized 2 gestational trophoblastic disease conditions marked by low proportion of hyperglycosylated hCG. These are quiescent gestational trophoblastic disease, defined as inactive or benign invasive disease, and minimally invasive gestational trophoblastic disease, defined as slow growing or chemorefractory disease with hCG increasing very slowly (doubling rate 2–6 weeks). Here we examine the USA hCG Reference Service experience with both diseases. Methods Patient were referred to the USA hCG Reference Service, 133 cases shown to have quiescent gestational trophoblastic disease, 35 cases with aggressive and 30 with minimally invasive gestational trophoblastic disease. Results Quiescent or inactive gestational trophoblastic disease was demonstrated in 133 women. In 127 of these cases, no hyperglycosylated hCG was detected, and in 6 cases 4–27% hyperglycosylated hCG was detected. This is quiescent or inactive disease. Only 1 of 35 cases with aggressive gestational trophoblastic disease (>40% hyperglycosylated hCG) was chemorefractory. In contrast, 30 of 30 minimally invasive cases ( 3000 IU/L before commencing chemotherapy. This was successful in 10 of 10 minimally invasive cases. Discussion Measurement of hyperglycosylated hCG or invasiveness is a critical step in management of invasive gestational trophoblastic disease. Quiescent of inactive gestational trophoblastic disease requires no therapy. Minimally invasive disease in chemorefractory. The USA hCG Reference Service experience suggests waiting until hCG exceeds 3000 IU/L before commencing any chemotherapy.

Hyperglycosylated hCG in the management of quiescent and chemorefractory gestational trophoblastic diseases

Introduction The literature shows that hyperglycosylated hCG is the invasion stimulus in malignant gestational trophoblastic diseases. The USA hCG Reference Service has characterized 2 gestational trophoblastic disease conditions marked by low proportion of hyperglycosylated hCG. These are quiescent gestational trophoblastic disease, defined as inactive or benign invasive disease, and minimally invasive gestational trophoblastic disease, defined as slow growing or chemorefractory disease with hCG increasing very slowly (doubling rate 2–6 weeks). Here we examine the USA hCG Reference Service experience with both diseases. Methods Patient were referred to the USA hCG Reference Service, 133 cases shown to have quiescent gestational trophoblastic disease, 35 cases with aggressive and 30 with minimally invasive gestational trophoblastic disease. Results Quiescent or inactive gestational trophoblastic disease was demonstrated in 133 women. In 127 of these cases, no hyperglycosylated hCG was detected, and in 6 cases 4–27% hyperglycosylated hCG was detected. This is quiescent or inactive disease. Only 1 of 35 cases with aggressive gestational trophoblastic disease (> 40% hyperglycosylated hCG) was chemorefractory. In contrast, 30 of 30 minimally invasive cases (< 40% hyperglycosylated hCG) were chemorefractory. In chemorefractory cases hyperglycosylated hCG ranged from < 1% to 39% of total hCG. The USA hCG Reference Service showed that proportions hyperglycosylated hCG significantly increases as total hCG rises. They recommended in minimally invasive cases to wait to hCG was > 3000 IU/L before commencing chemotherapy. This was successful in 10 of 10 minimally invasive cases. Discussion Measurement of hyperglycosylated hCG or invasiveness is a critical step in management of invasive gestational trophoblastic disease. Quiescent of inactive gestational trophoblastic disease requires no therapy. Minimally invasive disease in chemorefractory. The USA hCG Reference Service experience suggests waiting until hCG exceeds 3000 IU/L before commencing any chemotherapy.

Persistent Low Levels of β-hCG in a Patient With Recurrent Pregnancy Loss

A subset of women with persistent low levels of beta-hCG have undergone potentially harmful treatments despite no evidence of pregnancy or gestational trophoblastic neoplasia. A 37-year-old woman with a history of recurrent pregnancy loss presented with persistent low levels of beta-hCG. She was treated for ectopic pregnancy and retained products and was later suspected of having a malignancy. However, further evaluation of her human chorionic gonadotropin led to a diagnosis of quiescent gestational trophoblastic disease. A diagnosis of quiescent gestational trophoblastic disease should be considered in all patients who present with persistent low levels of beta-hCG, including those with recurrent pregnancy loss.

New discoveries on the biology and detection of human chorionic gonadotropin.

Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG.For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis.While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy.New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic disease, diagnosing placental site trophoblastic tumor, managing testicular germ cell malignancies, and monitoring other human malignancies. There are very few molecules with such wide and varying functions as regular hCG and its variants, and very few tests with such a wide spectrum of clinical applications as total hCG.

Persistent Low Concentration of Human Chorionic Gonadotropin in a Nonpregnant Woman

A 48-year-old woman presented for radio-iodine ablation therapy 3 months after undergoing a complete thyroidectomy performed for compressive goiter symptoms. The patient’s medical history included stage-3 follicular variant papillary thyroid cancer with no nodal involvement and no metastatic disease. A 6.5-cm papillary carcinoma had been identified and removed surgically. Despite this surgical treatment, 3 foci were detected by 125I uptake testing, a finding that prompted the use of therapeutic ablation. Because the patient reported 5 months of amenorrhea, a quantitative serum human chorionic gonadotropin (hCG) test (hCG+β assay, Roche Diagnostics) was performed to rule out pregnancy. The result was 7.0 IU/L (reference interval: <5.0) and the administration of 100 mCi I131 was cancelled owing to concern for a potential pregnancy. A repeat hCG test performed 4 days later was 7.0 IU/L. Follicle stimulating hormone (FSH) was determined to be 110 IU/L [reference intervals: 1.9–11.6 (follicular phase), 1.4–9.6 (luteal phase), and 21.5–131 IU/L (postmenopausal)]. hCG is produced by the trophoblastic tissue of the placenta and hence is a reliable marker for pregnancy. hCG also has clinical utility as a tumor marker because of its production by trophoblastic and nontrophoblastic neoplasms. Finally, hCG is also produced by the gonadotropic cells of the pituitary during the menopause (1)(2). As demonstrated by this patient, a persistent low concentration of hCG is particularly perplexing. Such cases have 3 potential etiologies: (a) false-positive hCG due to interfering antibodies, (b) quiescent gestational trophoblastic disease, and (c) pituitary hCG. ### false-positive hCG due to interfering antibodies There are several reports of falsely increased hCG due to endogenously produced interfering antibodies (3). Interfering antibodies can be of 2 types: human antianimal antibodies (HAAA) or heterophile antibodies. HAAAs are directed toward a specific antigen and may be produced after treatment with therapeutic antibodies or exposure to animal antigens (4). Heterophile antibodies display …

Placental site trophoblastic tumor

Placental site trophoblastic tumor (PSTT) is a rare neoplasm that rises from intermediate trophoblasts and commonly presents with low and variable concentration of HCG immunoactivity in serum, which can be difficult to differentiate from early stage choriocarcinoma/gestational trophoblastic neoplasm (GTN) or quiescent gestational trophoblastic disease. PSTT can occur after a normal pregnancy, spontaneous abortion, termination of pregnancy, ectopic or molar pregnancy. There is a wide clinical spectrum of presentation and behavior ranging from a benign condition to an aggressive disease with fatal outcome. Nontrophoblastic malignancies such as germ cell tumors or other tumors secreting low HCG must also be considered in the differential diagnosis. Because treatments for these conditions are different, a means of differentiating PSTT from other diagnoses is important. Surgery is the cornerstone of treatment. Chemotherapeutic regimen should be EMA/CO for first line chemotherapy; EMA/EP should be used in EMA/CO refractory cases. This article reviews the literatures on this rare but fatal disease.

Gestational trophoblastic diseases: 2. Hyperglycosylated hCG as a reliable marker of active neoplasia

Objectives. To determine whether circulating hyperglycosylated human chorionic gonadotropin (hCG-H), a promoter of choriocarcinoma growth and tumorigenesis, is a reliable marker of active gestational trophoblastic neoplasia (GTN) or choriocarcinoma, and whether hCG-H can consistently discriminate quiescent gestational trophoblastic disease (GTD) from neoplasia. Methods. Patients were those referred to the USA hCG Reference Service for consultation. These included a total of 82 women with GTN, including 30 with histologic choriocarcinoma. They were compared with 26 patients with resolving hydatidiform mole and 69 with quiescent GTD (persistent positive low value of real hCG but no clinical evidence of disease). All were tested for total hCG and hCG-H. hCG-H was calculated as the percentage of total hCG (hCG-H(%)). Results. We compared the utility of total hCG and hCG-H(%) in detecting active GTN and quiescent GTD. There was no significant difference when measuring total hCG (includes regular and hyperglycosylated hCG), between women with quiescent GTD and self-resolving hydatidiform mole compared to choriocarcinoma/GTN cases ( P > 0.05 and P > 0.05). In contrast, hCG-H(%) was significantly higher in choriocarcinoma/GTN cases ( P < 0.000001, and P < 0.000001). The usefulness of hCG and hCG-H(%) testing was assessed for discriminating between the 69 quiescent GTD cases, which required no therapy, and choriocarcinoma/GTN which need treatment. While hCG would detect 62% and 24% of malignancies at a 5% false positive rate, hCG-H(%) would detect 100% and 84% of malignancies at this same false positive rate. Follow-up data were received and repeat consultations were performed in 23 cases in which active disease was subsequently demonstrated. In 12 of 23 cases, hCG-H(%) results were able to first identify active disease 0.5 to 11 months prior to rapidly rising hCG or detection of clinically active neoplasia. In the remaining 11 cases, hCG-H(%) active disease appeared at the same time as rising hCG or demonstrable clinical tumor. Discussion and conclusion. hCG-H(%) appears to reliably identify active trophoblastic malignancy. It is a 100% sensitive marker for discriminating quiescent GTD from active GTN/choriocarcinoma. It is also a marker for the early detection of new or recurrent GTN/choriocarcinoma. The data presented appear sufficient to encourage the adoption of hCG-H as a tumor marker in trophoblastic disease. Further studies are now urgently required to confirm and extend our findings.

Gestational trophoblastic diseases: 4. Presentation with persistent low positive human chorionic gonadotropin test results

Objectives. A high proportion of women with persistent low levels of hCG, in the absence of pregnancy or any evidence of tumor, have received chemotherapy and hysterectomy for assumed malignancy. Such chemotherapy and surgery were ineffective and unwarranted. This study identifies the causes of persistent low level of hCG and provides guidelines for the management of these patients, preventing unnecessary treatment in the future. Methods. The USA hCG Reference Service has consulted on 170 women with low levels of hCG persisting for 3 months or longer. Serum total hCG was measured in the Diagnostic Products Corporation (DPC) Immulite assay and hyperglycosylated hCG in the Nichols Advantage test. Results. Among these 170 patients, the average persistent hCG result was 102 ± 152 mIU/ml, with a range of 6.1–900 mIU/ml. Thirteen (7.6%) of the 170 patients had true malignancy, 5 had placental site trophoblastic tumor, 3 had other gestational trophoblastic neoplasms (GTN), and 5 had non-trophoblastic malignancies. The remaining 157 patients had false-positive hCG, quiescent gestational trophoblastic disease (quiescent GTD), or pituitary hCG (hCG of pituitary origin). Of 71 patients with false-positive hCG, 47 patients received chemotherapy and 9 had surgery that had no effect on the level of hCG. Five of these patients with false-positive hCG were being monitored for hydatidiform mole or GTN. The majority of these cases were first investigated following an incidental pregnancy test. Of 69 patients who had quiescent GTD, 41 received chemotherapy and 9 underwent hysterectomy. All these therapies were unnecessary and ineffective. While 21 patients with quiescent GTD followed incidental pregnancy tests, the majority were discovered while monitoring patients after treatment for hydatidiform mole or GTN/choriocarcinoma ( n = 48). Seventeen cases of pituitary hCG were found among those women who were peri- or post-menopause. Two patients also received chemotherapy for assumed malignancy which was not present. Conclusion. Clinicians frequently assume that an elevated hCG implies that a patient is pregnant or has GTD or recurrent GTN, even when apart from the pregnancy test, no clinical evidence was found to support such a diagnosis. In most of these cases of persistent low hCG etiologies, all therapies were found unnecessary and ineffective. Guidelines are proposed for managing these patients. It is essential to demonstrate a malignancy clinically and with readily available biochemical tests before initiating therapy. This applies whether the patient is identified by an incidental pregnancy test or is actively being monitored for gestational trophoblastic disease.

Gestational trophoblastic diseases: 3. Human chorionic gonadotropin-free β-subunit, a reliable marker of placental site trophoblastic tumors

Objectives. Placental site trophoblastic tumor (PSTT) commonly presents with low and variable concentration of hCG immunoreactivity in serum which can be difficult to differentiate from early stage choriocarcinoma/gestational trophoblastic neoplasm (GTN) or quiescent gestational trophoblastic disease (quiescent GTD). Nontrophoblastic malignancies such as germ cell tumors or other tumors secreting low hCG must also be considered in the differential diagnosis. Because treatments for these conditions are different, a means of differentiating PSTT from other diagnoses is important. We investigate the usefulness of hCG-free β-subunit to make this discrimination. Methods. Data collected on cases referred to the USA hCG Reference Service for consultation served as a basis for this retrospective analysis. There were 13 cases with histology proven PSTT and 12 with nontrophoblastic malignancy. hCG-free β-subunit was measured by immunoassay and reported as a proportion of total hCG (hCG-free β-subunit(%)). hCG-free β-subunit(%) results were determined for all histologically proven cases of PSTT and for the nontrophoblastic malignancies. Comparisons of hCG-free β-subunit(%) were made and compared with those of the 82 choriocarcinoma/GTN cases and 69 quiescent GTD cases. The accuracy of hCG-free β-subunit(%) to discriminate these malignancies was analyzed by investigating the areas under receiver-operating characteristics curve ± standard error. Results. hCG-free β-subunit(%) was the predominant hCG form in cases of PSTT (mean ± standard deviation, 60 ± 19%) and nontrophoblastic malignancies (91 ± 11%), thus discriminating these diagnoses from choriocarcinoma/GTN (9.3 ± 9.2%) and from quiescent GTD (5.4 ± 7.8%). The cutoff of >35% free β-subunit is proposed. At this cutoff, 100% detection at 0% false-positive is achieved. The accuracy of hCG-free β-subunit(%) for this discrimination is 100 ± 0%. At a proposed cutoff of >80%, the free β-subunit test will also distinguish PSTT from nontrophoblastic malignancy, with 77% detection at 23% false-positive or an accuracy of 92 ± 3.2%. Conclusion. Measurement of the proportion hCG-free β-subunit(%) was found to be useful in the diagnosis of PSTT using proposed cutoff values of >35% and >80%. While this finding needs to be confirmed by larger studies, it would be reasonable to measure hCG-free β-subunit(%) whenever the diagnosis of PSTT is considered.

Persistent low levels of human chorionic gonadotropin: A premalignant gestational trophoblastic disease

Objective: This study was undertaken to evaluate the significance of persistent low-level human chorionic gonadotropin (hCG) titers (usually <50 IU/L) in the absence of clinical evidence of pregnancy or gestational trophoblastic disease. Study Design: The USA hCG Reference Service consulted on 114 cases with persistent low levels of hCG; 51 had false-positive hCG results. The remaining 63 cases had real hCG results and are presented here. Results: Antecedent gestational events included hydatidiform mole (27), pregnancy (35), and gestational trophoblastic neoplasm (1). Forty of the 63 (64%) cases received therapy, including chemotherapy (38), hysterectomy (2), or both (10). Despite treatment, in all cases, low hCG titers persisted. After 1 to 4.5 years of low titers, four women had a sudden rapid increase in hCG levels, and malignant disease was confirmed or clearly suggested (gestational trophoblastic neoplasm [3] and placental site trophoblastic tumor [1]). Invasive trophoblast antigen (ITA) is a marker of invasive cytotrophoblast cells. ITA was measured in 38 of the cases with persistent low hCG, in all cases ITA accounted for less than 25% of the hCG concentration. It was also determined in the 4 cases indicated with malignant disease, accounting for more than 80% of the hCG. Conclusion: The presence of persistent low-level hCG titers defines a subset of women with preinvasive or quiescent gestational trophoblastic disease. ITA effectively detected the presence or absence of invasive cells in these cases. The recommended management of the quiescent disease is close surveillance without therapy until malignant disease detected. (Am J Obstet Gynecol 2003;188:1254-9.)