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Gestational trophoblastic disease



Gestational Trophoblastic Disease -

Gestational Trophoblastic Disease -

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Gestational Trophoblastic Disease -

  1. 1. Gestational Trophoblastic Disease (GTD)
  2. 3. Types of GTD <ul><li>Benign </li></ul><ul><li>Hydatidiform mole/molar pregnancy (complete or incomplete) </li></ul><ul><li>malignant </li></ul><ul><li>Invasive mole </li></ul><ul><li>Choriocarcinoma (chorioepithelioma) </li></ul><ul><li>Placental site trophoblastic tumor </li></ul>
  3. 4. <ul><li>The term Gestational Trophoblastic Tumors has been applied the latter three conditions </li></ul><ul><li>Arise from the trophoblastic elements </li></ul><ul><li>Retain the invasive tendencies of the normal placenta or metastasis </li></ul><ul><li>Keep secretion of the human chorionic gonadotropin (hCG) </li></ul>Types of GTD
  4. 5. Pathologic and clinical classifications for gestational trophoblastic disease Low risk High risk Choriocarcinoma Metastatic Placental site trophoblastic tumor Nonmetastatic Malignant trophoblastic disease Invasive mole Benign gestational trophoblastic disease Hydatidiform mole *complete *incomplete CLINICAL CLASSIFICATION PATHOLOGIC CLASSIFICATION
  5. 6. Hydatidiform Mole (molar pregnancy)
  6. 7. Definition and Etiology <ul><li>Hydatidiform mole is a pregnancy characterized by vesicular swelling of placental villi and usually the absence of an intact fetus. </li></ul><ul><li>The etiology of hydatidiform mole remains unclear, but it appears to be due to abnormal gametogenesis and fertilization </li></ul>
  7. 8. <ul><li>In a ‘ complete mole ’ the mass of tissue is completely made up of abnormal cells </li></ul><ul><li>There is no fetus and nothing can be found at the time of the first scan. </li></ul>Definition and Etiology
  8. 9. <ul><li>In a ‘ partial mole ’, the mass may contain both these abnormal cells and often a fetus that has severe defects. </li></ul><ul><li>In this case the fetus will be consumed ( destroyed) by the growing abnormal mass very quickly. (shrink) </li></ul>Definition and Etiology
  9. 10. Incidence <ul><li>1 out of 1500-2000 pregnancies in the U.S. and Europe </li></ul><ul><li>1 out of 500-600 (another report 1%) pregnancies in some Asian countries. </li></ul><ul><li>Complete > incomplete </li></ul>
  10. 11. <ul><li>Repeat hydatidiform moles occure in 0.5-2.6% of patients, and these patiens have a subsequent greater risk of developing invasive mole or choriocarcinoma </li></ul><ul><li>There is an increased risk of molar pregnancy for women over the age 40 </li></ul>Incidence
  11. 12. <ul><li>Approximately 10-17% of hydatidiform moles will result in invasive mole </li></ul><ul><li>Approximately 2-3% of hydatidiform moles progress to choriocarcinoma ( most of them are curable) </li></ul>Incidence Not definitely benign disease , has a tight relationship with GTT
  12. 13. Clinical risk factors for molar pregnancy Outside North America( occasionally has this disease) Birthplace Vitamin A deficiency Diet prior spontaneous abortion prior hydatidiform mole Reproductive history >40 <15 Age (extremes of reproductive years)
  13. 14. Cytogenetics <ul><li>Complete molar pregnancy Chromosomes are paternal , diploid </li></ul><ul><li>46,XX in 90% cases </li></ul><ul><li>46,XY in a small part </li></ul><ul><li>Partial molar pregnancy Chromosomes are paternal and maternal, triploid. </li></ul><ul><li>69,XXY 80% </li></ul><ul><li>69,XXX or 69,XYY 10-20% </li></ul>Wrong life message , so can not develop normally
  14. 15. Comparative Pathologic Features of Complete and Partial Hydatidiform Mole Hyperplasia mild and focal Hyperplasia usually present to variable degrees Trophoblast Usually present None present Fetal tissue blood cells present they contain no fetal blood cells vessels Normal adjacent villi may be present All villi hydropin; no normal adjacent villi Villi Usually triploidy 69XXX most common. Usually diploid 46XX Karyotype Partial Mole Complete Mole Feature
  15. 16. Complete hydatidiform mole demonstrating enlarged villi of various size
  16. 17. Hydatidiform mole: specimen from suction curettage
  17. 18. A large amount of villi in the uterus.
  18. 19. <ul><li>The microscopic appearance of hydatidiform mole: </li></ul><ul><ul><li>Hyperplasia of trophobasitc cells </li></ul></ul><ul><ul><li>Hydropic swelling of all villi </li></ul></ul><ul><ul><li>Vessles are usually absent </li></ul></ul>
  19. 20. A sonographic findings of a molar pregnancy. The characteristic “snowstorm” pattern is evident.
  20. 21. Transvaginal sonogram demonstrating the “ snow storm” appearance.
  21. 22. Color Dopplor facilitates visualization of the enlarged spiral arteriesclose proximity to the “ snow storm” appearance
  22. 23. Color Doppler image of a hydatidiform mole and surrounding vessels. The uterine artery is easily identified from its anatomical location.
  23. 25. Dopplor waveform analysis demonstrates low vascular resistance(RI=0.29) in the spiral arteries, much lower than that obtained in normal early pregnancy
  24. 27. Partial hydartidiform mole
  25. 28. Microscopic image of partial molar pregnancy.
  26. 29. Here is a partial mole in a case of triploidy. Note the scattered grape-like masses with intervening normal-appearing placental tissue.
  27. 30. Large bilateral theca lutein cysts resembling ovarian germ cell tumors. With resolution of the human chorionic gonadotropin(HCG) stimulation, they return to normal-appearing ovaries.
  28. 31. Signs and Symptoms of Complete Hydatidiform Mole <ul><ul><li>Vaginal bleeding </li></ul></ul><ul><ul><li>Hyperemesis ( severe vomit) </li></ul></ul><ul><ul><li>Size inconsistent with gestational age( with no fetal heart beating and fetal movement) </li></ul></ul><ul><ul><li>Preeclampsia </li></ul></ul><ul><ul><li>Theca lutein ovarian cysts </li></ul></ul>
  29. 32. Signs and Symptoms of Partial Hydatidiform Mole <ul><ul><li>Vaginal bleeding </li></ul></ul><ul><ul><li>Absence of fetal heart tones </li></ul></ul><ul><ul><li>Uterine enlargement and preeclampsia is reported in only 3% of patients. </li></ul></ul><ul><ul><li>Theca lutein cysts, hyperemesis is rare. </li></ul></ul>
  30. 33. Diagnosis of hydatidiform mole <ul><li>Quantitative beta-HCG </li></ul><ul><li>Ultrasound is the criterion standard for identifying both complete and partial molar pregnancies. The classic image is of a “snowstorm” pattern </li></ul>
  31. 34. <ul><li>The most common symptom of a mole is vaginal bleeding during the first trimester </li></ul><ul><li>however very often no signs of a problem appear and the mole can only be diagnosed by use of ultrasound scanning. (rutting check) </li></ul><ul><li>Occasionally, a uterus that is too large for the stage of the pregnancy can be an indication. </li></ul><ul><li>NOTE: Vaginal bleeding does not always indicate a problem! </li></ul>Diagnosis
  32. 35. Differential diagnosis <ul><ul><li>Abortion </li></ul></ul><ul><ul><li>Multiple pregnancy </li></ul></ul><ul><ul><li>Polyhydramnios </li></ul></ul>
  33. 36. Treatment <ul><li>Suction dilation and curettage :to remove benign hydatidiform moles </li></ul><ul><li>When the diagnosis of hydatidiform mole is established, the molar pregnancy should be evacuated. </li></ul><ul><li>An oxytocic agent should be infused intravenously after the start of evacuation and continued for several hours to enhance uterine contractility </li></ul>
  34. 37. <ul><li>Removal of the uterus (hysterectomy) : used rarely to treat hydatidiform moles if future pregnancy is no longer desired. </li></ul>Treatment
  35. 38. <ul><li>Chemotherapy with a single-agent drug </li></ul><ul><li>Prophylactic (for prevention) chemotherapy at the time of or immediately following molar evacuation may be considered for the high-risk patients( to prevent spread of disease ) </li></ul>Treatment
  36. 39. High-risk postmolar trophoblastic tumor <ul><li>Pre-evacuation uterine size larger than expected for gestational duration </li></ul><ul><li>Bilateral ovarian enlargement (> 9 cm theca lutein cysts) </li></ul><ul><li>Age greater than 40 years </li></ul><ul><li>Very high hCG levels(>100,000 m IU/ml) </li></ul><ul><li>Medical complications of molar pregnancy such as toxemia, hyperthyrodism and trophoblastic embolization (villi come out of placenta ) </li></ul><ul><li>repeat hydatidiform mole </li></ul>
  37. 40. <ul><li>Patients with hudatidiform mole are curative over 80% by treatment of evacuation. </li></ul><ul><li>The follow-up after evacuation is key necessary </li></ul><ul><li>uterine involution, ovarian cyst regression and cessation of bleeding </li></ul>Follow-up
  38. 41. <ul><li>Quantitative serum hCG levels should be obtained every 1-2 weeks until negative for three consecutive determinations, </li></ul><ul><li>Followed by every 3 months for 1 years. </li></ul><ul><li>Contraception should be practiced during this follow-up period </li></ul>Follow-up
  39. 42. Invasive mole
  40. 43. Definition <ul><li>This term is applied to a molar pregnancy in which molar villi grow into the myometrium or its blood vessels, and may extend into the broad ligament and metastasize to the lungs, the vagina or the vulva. </li></ul>
  41. 44. Invasive mole: the tissue invades into the myometrial layer. No obvious borderline, with obvious bleeding.
  42. 45. Invasive hydatidiform mole infiltrating the myometrium
  43. 46. A case of invasive mole: inside the uterine cavity the typical “ snow storm” appearance can be detected, The location of blood flow suggest an invasive mole.
  44. 47. The same patient owing to the myometrial invasion. Reduced vascular resistance is detected in the uterine artery.
  45. 48. Transvaginal color Doppler scan of a patient with invasive mole Following uterine curettage, Persistent color signals within the myometeriun
  46. 49. Doppler image of invasive mole
  47. 50. Power Doppler easily detects a vascular echogenic nodule within the myometrium, suggesting invasive mole
  48. 51. Doppler image of invasive mole. Doppler waveform analysis depicts low vascular resistance (RI= 0.35)
  49. 52. Common Sites for Metastatic Gestational Trophoblastic Tumors 0-5 Gastrointestinal 0-5 Spleen 0-5 Kidney 5-15 Liver 5-15 Brain 10-15 Vulva/cervix 40-50 Vagina 60-95 Lung Per cent Site
  50. 53. Choriocarcinoma
  51. 54. Definition <ul><li>A malignant form of GTD which can develop from a hydatidiform mole or from placental trophoblast cells associated with a healthy fetus ,an abortion or an ectopic pregnancy. </li></ul>
  52. 55. <ul><li>Characterized by abnormal trophoblastic hyperplasia and anaplasia , absence of chorionic villi </li></ul>Definition
  53. 56. Gross specimen of choriocarcinoma
  54. 57. Microscopic image of choriocarcinoma absence of chorionic villi
  55. 58. Microscopic image of choriocarcinoma
  56. 59. Doppler image of choriocarcinoma
  57. 60. Doppler image of choriocarcinoma
  58. 61. Symptoms and signs <ul><li>Bleeding </li></ul><ul><li>Infection </li></ul><ul><li>Abdominal swelling </li></ul><ul><li>Vaginal mass </li></ul><ul><li>Lung symptoms </li></ul><ul><li>Symptoms from other metastases </li></ul>
  59. 62. WHO Prognostic Scoring System 0-4 low risk, 5-7 intermediate risk, >8 high risk for death 2 or more Single drug — — Previous (treatment) 8 4-8 1-4 — No. of metastasis Brain GI tract, liver Spleen, kidney Lung Sites of metastasis — >5 3-5 <3 Largest tumor(cm) >10 5 10 4 -10 5 10 3 -10 4 <10 3 Initial hCG(mIU/ml) >12 7-12 4-6 <4 Interval (months) of treatment — Term pregnancy Abortion, ectopic Hydatidiform mole Pregnancy history — — >39 ≤ 39 Age(years) 4 2 1 0 Prognostic factor Score
  60. 63. FIGO Staging System for Gestational Trophoblastic Tumors All other metastatic sites Ⅳ Extends to the lungs with or without genital tract Ⅲ Extends to the adnexae, outside the uterus, but limited to the genital structures Ⅱ Limited to uterine corpus Ⅰ Description Stage
  61. 64. <ul><li>Substages assigned for each stage as follows: </li></ul><ul><li>A: No risk factors present </li></ul><ul><li>B: One risk factor </li></ul><ul><li>C: Both risk factors </li></ul><ul><li>Risk factors used to assign substages: </li></ul><ul><li>1. Pretherapy serum hCG > 100,000 mlU/ml </li></ul><ul><li>2. Duration of disease >6 months </li></ul>FIGO Staging System for Gestational Trophoblastic Tumors
  62. 66. IIb IIa
  63. 67. IIIa<3cm or locate in half lung IIIb disease beyond IIIa
  64. 69. Diagnosis and evaluation <ul><li>Gestational trophoblastic tumor is diagnosed by rising hCG following evacuation of a molar pregnancy or any pregnancy event </li></ul><ul><li>Once the diagnosis established the further examinations should be done to determine the extent of disease ( X-ray, CT, MRI) </li></ul>
  65. 70. Treatment <ul><li>Nonmetastatic GTD </li></ul><ul><li>Low-Risk Metastatic GTD </li></ul><ul><li>High-Risk Metastatic GTD </li></ul>
  66. 71. Treatment of Nonmetastatic GTD <ul><li>Hysterectomy is advisable as initial treatment in patients with nonmetastatic GTD who no longer wish to preserve fertility </li></ul><ul><li>This choice can reduce the number of course and shorter duration of chemotherapy. </li></ul><ul><li>Adjusted single-agent chemotherapy at the time of operation is indicated to eradicate any occult metastases and reduce tumor dissemination. </li></ul>
  67. 72. <ul><li>Single-agent chemotherapy is the treatment of choice for patients wishing to preserve their fertility. </li></ul><ul><li>Methotrexate(MTX) and Actinomycin-D are generally chemotherapy agents </li></ul><ul><li>Treatment is continued until three consecutive normal hCG levels have been obtained and two courses have been given after the first normal hCG level. </li></ul>Treatment of Nonmetastatic GTD To prevent relapse or metastasis
  68. 73. <ul><li>Single-agent chemotherapy with MTX or actinomycin-D is the treatment for patients in this category </li></ul><ul><li>If resistance to sequential single-agent chemotherapy develops, combination chemotherapy would be taken </li></ul><ul><li>Approximately 10-15% of patients treated with single-agent chemotherapy will require combination chemotherapy with or without surgery to achieve remission </li></ul>Treatment of Low-Risk Metastatic GTD
  69. 74. <ul><li>Multiagent chemotherapy with or without adjuvant radiotherapy or surgery should be the initial treatment for patients with high-rist metastatic GTD </li></ul><ul><li>EMA-CO regimen formula is good choice for high-rist metastatic GTD </li></ul><ul><li>Adjusted surgeries such as removing foci of chemotherapy-resistant disease, controlling hemorrhage may be the one of treatment regimen </li></ul>Treatment of High-Risk Metastatic GTD
  70. 75. EMA-CO Chemotherapy for poor Prognostic Disease (Repeat every 15 days as toxicity permits) IV on day8 1mg/M 2 Oncovin (vincristine) IV on day8 600mg/M 2 Cyclophosphamide 15mg IM or p.o. q 12 hours×4 starting 24 hours after starting methotrexate Folinic acid IV daily×2 days 0.5mg Actinomycin D IV losding dose, then 200mg/M2 over 12 hours day 1 100mg/M 2 Methotrexate IV daily×2 days (over 30-45 minutes) 100mg/M 2 Etoposide(VP-16)
  71. 76. Prognosis <ul><li>Cure rates should approach 100% in nonmetastatic and low-risk metastatic GTD </li></ul><ul><li>Intensive multimodality therapy has resulted in cure rates of 80-90% in patients with high-risk metastatic GTD </li></ul>
  72. 77. Follow-up After Successful Treatment <ul><li>Quantitative serum hCG levels should be obtained monthly for 6 months, every two months for remainder of the first year, every 3 months during the second year </li></ul><ul><li>Contraception should be maintained for at least 1 year after the completion of chemotherapy. Condom is the choice. </li></ul>
  73. 78. Placenta Site Trophoblastic Tumor (PSTT)
  74. 79. <ul><li>Placenta Site Trophoblastic Tumor is an extremely rare tumor that arised from the placental implantation site </li></ul><ul><li>Tumor cells infiltrate the myometrium and grow between smooth-muscle cells </li></ul>Definition
  75. 81. <ul><li>Surum hCG levels are relatively low compared to those seen with choriocarcinoma. </li></ul><ul><li>Several reports have noted a benign behavior of this disease. They are relatively chemotherapy-resistant, and deaths from metastasis have occurred. </li></ul><ul><li>Surgery has been the mainstay of treatment </li></ul>Dignosis and treatment
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