Gestational trophoblastic disease

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Gestational trophoblastic disease

Patient Information




Hydatidiform Mole
Gestational trophoblastic neoplasia


Risk factors

Clinical Features

Differential Diagnosis

Prognostic Factors and Survivorship

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Gestational trophoblastic disease
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Micrograph of intermediate trophoblast, decidua and a hydatidiform mole (bottom of image). H&E stain.

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Synonyms and keywords: GTD, pregnancy-related tumors, trophoblastic diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]


Gestational trophoblastic disease (GTD) includes a spectrum of disease states affecting pregnant individuals and range from benign conditions such as complete and partial molar pregnancy, exaggerated placental site tumor (EPS), and placental-site nodule (PSN) to malignant disorders (gestational trophoblastic neoplasia) such as invasive mole, choriocarcinoma (CC), placenta-site trophoblastic tumor (PSTT), and epitheloid trophoblastic tumors (ETT). Hydatidiform moles are a benign entities which may be either complete or partial. These benign moles may occasionally transform into invasive moles, which are malignant and may even progress to choriocarcinoma. Gestational trophoblasts may invade uterine tissue. GTD may simulate pregnancy due to increased uterine size, however they contain abnormal fetal tissue and typically the uterus is inappropriately large for date. This tissue may grow at the same rate as a normal pregnancy, and produces beta human chorionic gonadotropin (beta-hCG), a hormone produced by the placenta, which is measured to monitor fetal well-being after implantation. While GTD overwhelmingly affects women of child-bearing age, it may rarely occur in postmenopausal women.


Gestational trophoblastic disease (GTD) may be classified as follows:


The reported incidence of GTD varies widely worldwide, from a low of 23 per 100,000 pregnancies (Paraguay) to a high of 1,299 per 100,000 pregnancies (Indonesia). However, at least part of this variability is caused by differences in diagnostic criteria and reporting. The reported incidence in the United States is about 110 to 120 per 100,000 pregnancies. The prevalence rates of both hydatidiform mole and choriocarcinoma have declined over the past three decades in all groups, which may be due to better awareness of the condition leading to risk factor avoidance, dietary improvement and decreased overall birth rate.[1]

Hydatidiform Mole

  • The worldwide prevalence of molar pregnancy varies according to geographic region, ranging from 1200 per 100,000 pregnancies in Indonesia, India, and Turkey to 100-200 per 100,000 pregnancies in Japan and China and 50 to 100 per 100,000 pregnancies in North America and Europe.[2]


  • The reported incidence of choriocarcinoma, the most aggressive form of GTD, in the United States is about 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is about 0.18 per 100,000 women between the ages of 15 years and 49 years.
  • The reported prevalence of choriocarcinoma varies widely according to the geographic region, and ranges from a low of 2 per 100,000 pregnancies in the United States to a high of 202 per 100,000 pregnancies in China.[3]

Risk Factors

Risk factors for gestational trophoblastic disease include the following:[4][5][6]

Clinical Features

Gestational trophoblastic disease (GTD) may present with the following clinical features:[7][8]

The following table outlines the variation in clinical presentations of molar pregnancy (complete, partial and invasive), choriocarcinoma, placental-site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT):[9][10][11][12][13]

Clinical Features Complete Hydatidiform Mole Partial Hydatidiform Mole Invasive Molar Pregnancy Choriocarcinoma Placental-site trophoblastic tumor (PSTT) and Epithelioid trophoblastic tumor (ETT)
Presenting Complaints
Neoplastic Conversion
  • High rate of progression (15-20%)
  • < 5 % progression rate
Beta Human Chorionic Gonadotropin (Beta-hCG) baseline levels
  • Extremely high levels ( > 100000 mIU/ml in half of the patients
  • Highly elevated ( > 100000 mIU/ml in one in ten patients)
  • High
  • High
  • Moderatley elevated (< 1000 mIU/ml in majority of patients)
History of Pregnancies
  • Not related
  • Not related
Metastatic Route

Differential Diagnosis

Gestational trophoblastic disease must be differentiated from other causes of hyperthyroidism such as Grave's disease and toxic nodular goiter. The following table differentiates these causes of hyperthyroidism:

Cause of thyrotoxicosis TSH receptor antibodies Thyroid US Color flow Doppler Radioactive iodine uptake/Scan Other features
Graves' disease + Hypoechoic pattern ? Diffuse uptake Ophthalmopathy, dermopathy, acropathy
Toxic nodular goiter - Multiple nodules - Hot nodules on thyroid scan -
Toxic adenoma - Single nodule - Hot nodule -
Subacute thyroiditis - Heterogeneous hypoechoic areas Reduced/absent flow ? Neck pain, fever, and
elevated inflammatory index
Painless thyroiditis - Hypoechoic pattern Reduced/absent flow ? -
Amiodarone induced thyroiditis-Type 1 - Diffuse or nodular goiter ?/Normal/? ? but higher than in Type 2 High urinary iodine
Amiodarone induced thyroiditis-Type 2 - Normal Absent ?/absent High urinary iodine
Central hyperthyroidism - Diffuse or nodular goiter Normal/? ? Inappropriately normal or high TSH
Trophoblastic disease - Diffuse or nodular goiter Normal/? ? -
Factitious thyrotoxicosis - Variable Reduced/absent flow ? Normal or decreased serum thyroglobulin
Struma ovarii - Variable Reduced/absent flow ? Increased abdominal RAIU
Disease Findings
Thyroiditis Direct chemical toxicity with inflammation Amiodarone, sunitinib, pazopanib, axitinib, and other tyrosine kinase inhibitors may also be associated with a destructive thyroiditis.[14][15]
Radiation thyroiditis Patients treated with radioiodine may develop thyroid pain and tenderness 5 to 10 days later, due to radiation-induced injury and necrosis of thyroid follicular cells and associated inflammation.
Drugs that interfere with the immune system Interferon-alfa is a well-known cause of thyroid abnormality. It mostly leads to the development of de novo antithyroid antibodies.[16]
Lithium Patients treated with lithium are at a high risk of developing painless thyroiditis and Graves' disease.
Palpation thyroiditis Manipulation of the thyroid gland during thyroid biopsy or neck surgery and vigorous palpation during the physical examination may cause transient hyperthyroidism.
Exogenous and ectopic hyperthyroidism Factitious ingestion of thyroid hormone The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[17]
Acute hyperthyroidism from a levothyroxine overdose The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[18]
Struma ovarii Functioning thyroid tissue is present in an ovarian neoplasm.
Functional thyroid cancer metastases Large bony metastases from widely metastatic follicular thyroid cancer cause symptomatic hyperthyroidism.
Hashitoxicosis It is an autoimmune thyroid disease that initially presents with hyperthyroidism and a high radioiodine uptake caused by TSH-receptor antibodies similar to Graves' disease. It is then followed by the development of hypothyroidism due to the infiltration of the thyroid gland with lymphocytes and the resultant autoimmune-mediated destruction of thyroid tissue, similar to chronic lymphocytic thyroiditis.[19]
Toxic adenoma and toxic multinodular goiter Toxic adenoma and toxic multinodular goiter are results of focal/diffuse hyperplasia of thyroid follicular cells independent of TSH regulation. Findings of single or multiple nodules are seen on physical examination or thyroid scan.[20]
Iodine-induced hyperthyroidism It is uncommon but can develop after an iodine load, such as administration of contrast agents used for angiography or computed tomography (CT), or iodine-rich drugs such as amiodarone.
Trophoblastic disease and germ cell tumors Thyroid-stimulating hormone and HCG have a common alpha-subunit and a beta-subunit with considerable homology. As a result, HCG has weak thyroid-stimulating activity and high titer HCG may mimic hyperthyroidism.[21]

Prognostic Factors and Survivorship

The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM staging system has limited prognostic value. The probability of cure depends on the following:

Selection of treatment depends on these factors plus the patient’s desire for future pregnancies. The beta-hCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.


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  3. Altieri A, Franceschi S, Ferlay J, Smith J, La Vecchia C (November 2003). "Epidemiology and aetiology of gestational trophoblastic diseases". Lancet Oncol. 4 (11): 670–8. PMID 14602247.
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  7. Sun SY, Melamed A, Goldstein DP, Bernstein MR, Horowitz NS, Moron AF, Maestá I, Braga A, Berkowitz RS (July 2015). "Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: does early diagnosis alter risk for gestational trophoblastic neoplasia?". Gynecol. Oncol. 138 (1): 46–9. doi:10.1016/j.ygyno.2015.05.002. PMID 25969351.
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  9. "Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole - American Journal of Obstetrics & Gynecology".
  10. Dhanda S, Ramani S, Thakur M (2014). "Gestational trophoblastic disease: a multimodality imaging approach with impact on diagnosis and management". Radiol Res Pract. 2014: 842751. doi:10.1155/2014/842751. PMC 4122023. PMID 25126425.
  11. Milenković V, Lazović B (2011). "[Gestational trophoblastic disease--literature review]". Med. Pregl. 64 (3–4): 188–93. PMID 21905598.
  12. "".
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  18. Jha S, Waghdhare S, Reddi R, Bhattacharya P (2012). "Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis". Thyroid. 22 (12): 1283–6. doi:10.1089/thy.2011.0353. PMID 23067331.
  19. Fatourechi V, McConahey WM, Woolner LB (1971). "Hyperthyroidism associated with histologic Hashimoto's thyroiditis". Mayo Clin. Proc. 46 (10): 682–9. PMID 5171000.
  20. Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G (1991). "High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland". J. Intern. Med. 229 (5): 415–20. PMID 2040867.
  21. Oosting SF, de Haas EC, Links TP, de Bruin D, Sluiter WJ, de Jong IJ, Hoekstra HJ, Sleijfer DT, Gietema JA (2010). "Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors". Ann. Oncol. 21 (1): 104–8. doi:10.1093/annonc/mdp265. PMID 19605510.

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