Metastatic Gestational Trophoblastic Neoplasms Research Articles

ODP390 Metastatic Gestational Trophoblastic Neoplasia Masquerading as Thyroid Storm in a Girl with Molar Pregnancy and Hyperthyroidism

Abstract The Case Patient is a 16-year-old female with molar pregnancy, admitted for D&C, referred for hyperthyroidism, concern for thyroid storm. A month prior, she presented with heavy vaginal bleeding, morning sickness. Ultrasound showed blighted ovum. HCG was significantly elevated, 668,123 mIU/mL. TSH was low at 0. 01 mIU/L, Free T4 elevated 2.3 ng/dL. No family history of thyroid dysfunction. She was for was noted to have respiratory distress, hypoxia, and tachycardia in the 120s post-operatively. LFTs normal, no fever, jaundice or CNS manifestations. Chest CT showed bilateral lower lobe localized pulmonary edema concerning for trophoblastic fluid embolism vs thyroid storm. BWPS = 40. She was placed on PTU, beta blockade, Lugol's iodine, and hydrocortisone. Repeat chest CT showed diffuse pulmonary nodules consistent with gestational trophoblastic neoplasm (GTN). No other metastasis on further imaging (chest, abdomen, pelvis, brain). Clinical status improved, FT4 normalized 5 days after starting treatment. TRAbs negative. She was discharged on Methimazole and Atenolol, which were eventually discontinued. HCG levels significantly decreased after D&C but remained detectable on follow-up. Endocervix/uterine curettage showed intraplacental choriocarcinoma arising within a complete hydatidiform mole. She is followed by Oncology and currently undergoing chemotherapy. Discussion HCG-mediated hyperthyroidism include gestational transient thyrotoxicosis, hyperemesis gravidarum, and trophoblastic hyperthyroidism (TH). Due to significant homology between TSH and the beta-subunit of HCG, HCG can cause hyperthyroidism. 2-60% of women with trophoblastic disease may have symptomatic hyperthyroidism at time of diagnosis which can be severe. Patients with GTN (choriocarcinoma in our case) have a higher likelihood of TH, as HCG exceeds 100,000 mIU/mL. Choriocarcinoma is the most aggressive type of GTN characterized by vascular invasion and widespread metastases, of which the most common sites are vagina and lungs. Patients with pulmonary metastasis my present with respiratory distress, chest pain, cough or hemoptysis. Our patient was initially thought to have impending thyroid storm mainly from findings of pulmonary edema, respiratory distress, tachycardia, and precipitant history (D&C), and was managed as such while further workup was being undertaken. Realization that the initial chest CT findings of pulmonary edema were actually related to multiple pulmonary nodules and GTN made thyroid storm less likely. Hyperthyroidism typically resolves with decreasing HCG levels in TH. Indeed, our patient no longer needed ATD once her HCG levels subsided s/p D&C. Conclusion One of the most common sites of metastasis in GTN is the lungs. An acute presentation of respiratory distress and pulmonary findings on chest imaging upon simultaneous discovery of TH may complicate management as thyroid storm needs to be considered. Although a higher index of suspicion for metastatic GTN should be made in this situation, a conservative management approach of treating for possible impending thyroid storm until definitive diagnosis has been established is prudent. Presentation: No date and time listed

Laparoscopic hysterectomy as a treatment modality for gestational trophoblastic neoplasia: A report of two cases

Introduction. Measuring the serum levels of human chorionic gonadotropin beta isoform (?-hCG) remains a crucial marker for diagnosing gestational trophoblastic neoplasms (GTNs). Choriocarcinoma is commonly diagnosed due to extremely high levels of ?-hCG, but the presence of distant metastasis is not uncommon. Placental site trophoblastic tumors and epithelioid trophoblastic tumors remain an enigma because the levels of ?-hCG are usually low. Case report. The first case report describes a 44-year-old woman, P2G3, admitted to the Clinic under the suspicion of molar pregnancy. She had vaginal bleeding with variable intensity, and her ?-hCG was 1,837,787 mIU/mL. After two explorative curettages, the level of ?-hCG declined, and a partial hydatidiform mole (HM) was diagnosed histopathologically. The patient was admitted to the Clinic on two occasions due to the increasing values of ?-hCG. Since ?-hCG failed to drop after two explorative curettages, a hysteroscopic biopsy, and one chemotherapy cycle, along with the suspicious ultrasonographic feature of metastatic GTN, and the fact that the patient has refused further chemotherapy, a total laparoscopic hysterectomy was performed. Choriocarcinoma was diagnosed after a histopathological exam was done. The second patient, a 50-year-old woman, P2G4, was admitted to the Clinic under the ultrasonographic suspicion of molar pregnancy. She was complaining of pelvic discomfort and frequent urination. Initial levels of ?-hCG were 128,359 mIU/mL. Instrumental revision of the uterine cavity was performed, and partial HM was diagnosed histo-pathologically. Because of the increasing levels of ?-hCG, ultrasonographical suspicion of the development of GTN in the uterine corpus, in accordance with the patient?s age and the fact that she has regular menstrual cycles, total laparoscopic hysterectomy was performed, and a histopathological exam made the diagnosis of the placental site trophoblastic tumor. Conclusion. Laparoscopic hysterectomy could be a treatment of choice for the chemotherapy-resistant GTNs but also for choriocarcinoma in patients who have finished their reproductive activity and refuse to be treated with chemotherapeutics.

A promising therapeutic strategy for metastatic gestational trophoblastic disease: Engineered anticancer gene-expressing stem cells to selectively target choriocarcinoma.

Gestational trophoblastic disease (GTD) is an unusual disease occurring in pregnancy that originates from abnormal trophoblastic cells and comprises a group of diseases with different properties of invasion, metastasis and recurrence. The GTD group includes hydatidiform moles and gestational trophoblastic neoplasms (GTNs), with GTNs being divided into invasive moles, choriocarcinoma, placental site trophoblastic tumors and epithelioid trophoblastic tumors. The present review focuses on current effective treatments for GTD, including conventional and novel promising direct enzyme prodrug therapies (DEPTs). Conventional therapies, such as chemotherapy and hysterectomy, are currently used in a clinical setting; however, the use of diverse DEPTs, including antibody-DEPT and gene-DEPT is also being attempted to cure GTNs. In addition, gene delivery tools using genetically engineered neural stem cells (NSCs) are presently being examined for the treatment of GTNs. The tumor-tropism of NSCs by chemoattractant factors is a unique characteristic of these cells and can serve as a vehicle to deliver anticancer agents. Previous studies have demonstrated that injection with NSC-expressing suicide genes into xenograft animal models has a significant inhibitory effect on tumor growth. Stem cells can be genetically engineered to express anticancer genes, which migrate to the metastatic sites and selectively target cancer cells, and are considered to effectively target metastatic GTNs. However, the safety issue of stem cell therapy, such as tumorigenesis, remains a challenge. Novel therapies comprising a combination of conventional and novel promising treatments are anticipated to be definitive treatments for metastasized and/or recurrent patients with GTNs.

Unusual Presentation of Hypothyroidism in a Pregnant Woman, Mimicking Gestational Trophoblastic Neoplasm.

Hypothyroidism is a common health issue worldwide with varying clinical manifestations. We report a woman who experienced an incomplete abortion and undiagnosed hypothyroidism who was referred to the oncologist with the suspicion of metastatic gestational trophoblastic neoplasm (GTN). A 29-year-old woman with incomplete abortion was referred to an oncologist for possible GTN due to persistent active vaginal bleeding, an elevated beta human chorionic gonadotropin (hCG), abnormal cervical inspection exam, abnormal liver function tests, ovarian enlargement, ascites, and a pleural effusion. She was found to have hypothyroidism in further work-up. She was managed with thyroid hormone replacement therapy and her condition improved after 6 weeks. Complete resolution of the ovarian mass and pericardial and pleural effusion was achieved. This case describes an important experience; hypothyroidism should be considered in the differential diagnosis of any woman with an incomplete abortion presenting with an ovarian mass. Evaluation and correct diagnosis are important to prevent mismanagement.

Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia.

Metastatic gestational trophoblastic neoplasm presenting as spontaneous renal and cerebral hemorrhage with low titer of HCG: A case report of an unusual case

Gestational trophoblastic neoplasm includes tumor spectrum of four entities: hydatidiform mole (complete and partial), invasive mole, choriocarcinoma and placental site trophoblastic tumor. The hydatidiform mole is usually benign, but it is regarded as a pre-malignant disease. The other three conditions are malignant and are termed gestational trophoblastic tumor. Although most molar pregnancies behave in a benign fashion, metastatic tumors develop after complete molar pregnancy in 4% of patients. However, even when the disease is spread to many distal organs, it is highly curable with chemotherapy in most cases. We recently encountered an unusual case of metastatic gestational trophoblastic neoplasm following complete mole, presenting as spontaneous renal and cerebral hemorrhage with a fatal course.

Gestational trophoblastic disease: An overview

Gestational trophoblastic disease (GTD) represents a group of tumours arising from the trophoblastic tissue of the placenta. It comprises a spectrum of clinical entities ranging from non invasive molar pregnancy, to metastatic gestational trophoblastic neoplasm, and can follow any type of pregnancy.

Patients with presenting unusual manifestations with gestational trophoblastic neoplasm: case series and review of literatures

Early recognition of gestational trophoblastic neoplasms (GTN) will maximize the chances of cure with chemotherapy but some patients present with many different symptoms months or even years after the causative pregnancy making diagnosis difficult. Clinicians should be aware of the possibility of GTN in any reproductive age woman with bizarre central nervous system symptoms, gastrointestinal symptoms or radiographic evidence of metastatic tumor of unknown primary origin. We reported two cases of metastatic gestational trophoblastic neoplasms with bizarre pulmonary symptoms, one patient with small bowel metastasis, and two patients with brain metastasis presenting with unusual manifestations.

Overt Hyperthyroidism Secondary to Metastatic Gestational Trophoblastic Neoplasm

Gestational trophoblastic disease is a rare cause of overt hyperthyroidism. Biochemical and clinical hyperthyroidism results from elevated levels of human chorionic gonadotropin, a hormone that is structurally similar to thyroid stimulating hormone. We report a case of a woman with gestational trophoblastic neoplasm with pulmonary metastases who presented with signs, symptoms, and biochemical evidence of hyperthyroidism. The hyperthyroidism improved dramatically with β-blocker therapy and combination chemotherapy.

Successful treatment of two patients with gestational trophoblastic neoplasm presenting with emergent neurologic symptoms

The objective of this study is to present the successful treatment of two young patients with gestational trophoblastic neoplasms (GTN) presenting with emergent neurologic symptoms without any gynecological problems. Case 1, a 22-year-old patient, was admitted to an infectious disease ward, with admitting diagnosis of encephalitis due to neurologic symptoms. Case 2, a 33-year-old patient, underwent craniotomy due to hemorrhagic brain tumor in the neurosurgery department. The diagnosis of GTN should be considered in any woman of reproductive age who has neurologic symptoms. It seems that multiagent chemotherapy in conjunction with whole-brain irradiation results in acceptable survival rate in brain metastatic GTN patients. Craniotomy is often necessary in fulminant cases.

Metastatic gestational trophoblastic neoplasm. A study of two cases in unusual clinical settings and review of the literature

Two cases of metastatic gestational trophoblastic neoplasms (MGTN) diagnosed by mediastinoscopic and gastroscopic biopsies, respectively, are presented. Both patients are young women who presented with hemorrhagic events involving the CNS in one case and the gastrointestinal tract in the other, with histories of recent pregnancies. Both cases belong to the group of high-risk MGTN because of the location of the metastatic lesions (CNS and liver) and because of the delayed onset of chemotherapy. One patient is in clinical remission, 3 years later, and the other succumbed to her disease. A review of the literature suggests that CNS involvement has a better prognosis than liver metastases. The patient diagnosed to have MGTN by a gastroscopic biopsy is the first reported, to the best of out knowledge. The outcome of MGTN, although greatly improved by chemotherapy, is still fatal in numerous cases in the high-risk group. Since an early diagnosis is critical for successful chemotherapy, it is advisable to perform HCG titers in the blood serum of young patients presenting with unexplained hemorrhagic events, especially in those with recent gestations.

METHOTREXATE WITH CITROVORUM FACTOR RESCUE FOR GESTATIONAL TROPHOBLASTIC NEOPLASMS

Thirty-five patients with nometastatic gestational trophoblastic neoplasms and 3 patients with metastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor rescue. The antecedent pregnancy was molar in all patients. The known histologic diagnosis in 34 patients was hydatdiform mole and choriocarcinoma in 3. Up to March 1977, the duration of remissions ranged from 1 to 21 months. Complete and sustained remission was achieved in 91% of patients with nonmetastatic disease and in 2 of the 3 patients with metastases, without evidence of marrow or hepatic and with substantially reduced epithelial toxicity. Response to treatment and the number of courses required to achieve remission were determined solely on the basis of the human chorionic gonadotropin response as measured by the beta subunit radioimmunoassay.