Gestational trophoblastic disease

Jump to navigation Jump to search

Gestational trophoblastic disease

Patient Information

Overview

Causes

Classification

Hydatidiform Mole
Gestational trophoblastic neoplasia

Epidemiology

Risk factors

Clinical Features

Differential Diagnosis

Prognostic Factors and Survivorship

For patient information on Hydatiform mole, click here

For patient information on Choriocarcinoma, click here

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

WikiDoc Resources for Gestational trophoblastic disease

Articles

Most recent articles on Gestational trophoblastic disease

Most cited articles on Gestational trophoblastic disease

Review articles on Gestational trophoblastic disease

Articles on Gestational trophoblastic disease in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Gestational trophoblastic disease

Images of Gestational trophoblastic disease

Photos of Gestational trophoblastic disease

Podcasts & MP3s on Gestational trophoblastic disease

Videos on Gestational trophoblastic disease

Evidence Based Medicine

Cochrane Collaboration on Gestational trophoblastic disease

Bandolier on Gestational trophoblastic disease

TRIP on Gestational trophoblastic disease

Clinical Trials

Ongoing Trials on Gestational trophoblastic disease at Clinical Trials.gov

Trial results on Gestational trophoblastic disease

Clinical Trials on Gestational trophoblastic disease at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Gestational trophoblastic disease

NICE Guidance on Gestational trophoblastic disease

NHS PRODIGY Guidance

FDA on Gestational trophoblastic disease

CDC on Gestational trophoblastic disease

Books

Books on Gestational trophoblastic disease

News

Gestational trophoblastic disease in the news

Be alerted to news on Gestational trophoblastic disease

News trends on Gestational trophoblastic disease

Commentary

Blogs on Gestational trophoblastic disease

Definitions

Definitions of Gestational trophoblastic disease

Patient Resources / Community

Patient resources on Gestational trophoblastic disease

Discussion groups on Gestational trophoblastic disease

Patient Handouts on Gestational trophoblastic disease

Directions to Hospitals Treating Gestational trophoblastic disease

Risk calculators and risk factors for Gestational trophoblastic disease

Healthcare Provider Resources

Symptoms of Gestational trophoblastic disease

Causes & Risk Factors for Gestational trophoblastic disease

Diagnostic studies for Gestational trophoblastic disease

Treatment of Gestational trophoblastic disease

Continuing Medical Education (CME)

CME Programs on Gestational trophoblastic disease

International

Gestational trophoblastic disease en Espanol

Gestational trophoblastic disease en Francais

Business

Gestational trophoblastic disease in the Marketplace

Patents on Gestational trophoblastic disease

Experimental / Informatics

List of terms related to Gestational trophoblastic disease


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]

Overview

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.

Classification

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

Epidemiology

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]

Choriocarcinoma

  • 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
Management

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.

References

  1. Martin BH, Kim JH (January 1998). "Changes in gestational trophoblastic tumors over four decades. A Korean experience". J Reprod Med. 43 (1): 60–8. PMID 9475151.
  2. Steigrad SJ (December 2003). "Epidemiology of gestational trophoblastic diseases". Best Pract Res Clin Obstet Gynaecol. 17 (6): 837–47. PMID 14614884.
  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.
  4. Parazzini F, Mangili G, La Vecchia C, Negri E, Bocciolone L, Fasoli M (December 1991). "Risk factors for gestational trophoblastic disease: a separate analysis of complete and partial hydatidiform moles". Obstet Gynecol. 78 (6): 1039–45. PMID 1945204.
  5. Messerli ML, Lilienfeld AM, Parmley T, Woodruff JD, Rosenshein NB (October 1985). "Risk factors for gestational trophoblastic neoplasia". Am. J. Obstet. Gynecol. 153 (3): 294–300. PMID 2996354.
  6. Kumar N, Saxena YK, Rathi AK, Chitra R, Kumar P (October 2003). "Host and risk factors for gestational trophoblastic disease: a hospital-based analysis from India". Med. Sci. Monit. 9 (10): CR442–7. PMID 14523334.
  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.
  8. Seckl MJ, Sebire NJ, Berkowitz RS (August 2010). "Gestational trophoblastic disease". Lancet. 376 (9742): 717–29. doi:10.1016/S0140-6736(10)60280-2. PMID 20673583.
  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. "academic.oup.com".
  13. Joneborg U, Marions L (2014). "Current clinical features of complete and partial hydatidiform mole in Sweden". J Reprod Med. 59 (1–2): 51–5. PMID 24597287.
  14. Lambert M, Unger J, De Nayer P, Brohet C, Gangji D (1990). "Amiodarone-induced thyrotoxicosis suggestive of thyroid damage". J. Endocrinol. Invest. 13 (6): 527–30. PMID 2258582.
  15. Ahmadieh H, Salti I (2013). "Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment". Biomed Res Int. 2013: 725410. doi:10.1155/2013/725410. PMC 3824811. PMID 24282820.
  16. Vialettes B, Guillerand MA, Viens P, Stoppa AM, Baume D, Sauvan R, Pasquier J, San Marco M, Olive D, Maraninchi D (1993). "Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies". Acta Endocrinol. 129 (1): 31–8. PMID 8351956.
  17. Cohen JH, Ingbar SH, Braverman LE (1989). "Thyrotoxicosis due to ingestion of excess thyroid hormone". Endocr. Rev. 10 (2): 113–24. doi:10.1210/edrv-10-2-113. PMID 2666114.
  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.

Template:WikiDoc Sources