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Gestational Trophoblastic disease


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Lecture for undergraduate medical student

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Gestational Trophoblastic disease

  1. 1. Gestational Trophoblastic Disease (GTD) • Dr. Swati Singh • Department of Obs and Gyn • UDUTH
  2. 2. Molar Pregnancy
  3. 3. It is a spectrum of trophoblastic diseases that includes: Complete molar pregnancy Partial molar pregnancies Invasive mole Choriocarcinoma Placental site trophoblastic tumour The last 2 may follow abortion, ectopic or normal pregnancy. Definitions Gestational Trophoblastic Disease (GTD)
  4. 4. Chorio carcinoma I-Pathologic Classification II-Clinical Classification βhCG based: WHO, FIGO, ACOG 2004 & RCOG 2010 Benign G.T.D. G.T. Neoplasia Malignant G.T.D. Partial mole Complete mole Invasive mole MetastaticNon metastatic Low risk High risk Gestational Trophoblastic Disease (GTD) Placental site trophoblastic tumour Classifications
  5. 5. - Hydatidiform Mole (H. MOLE) = Vesicular Mole
  6. 6. Hydatidiform Moles (H.M.) Hydatidiform moles are abnormal pregnancies characterized histologically by : Trophoblastic proliferation (Both syncitiotrophoblast & cytotrophoblast) Edema of the villous stroma (Hydropic) . Based on the degree and extent of these tissue changes, hydatidiform moles are categorized as either Complete hydatidiform mole. Partial hydatidiform mole.
  7. 7. Feature Partial mole Complete mole Karyotype Most commonly 69, XXX or - XXY Most commonly 46, XX or -,XY Pathology Fetus Often present Absent Amnion, fetal RBC Usually present Absent Villous edema Variable, focal Diffuse Trophoblastic proliferation Focal, slight-moderate Diffuse, slight-severe Clinical presentation Diagnosis Missed abortion Molar gestation Uterine size Small for dates 50% large for dates Theca lutein cysts Rare 25-30% Medical complications Rare 10-25% Postmolar CTN 2.5-7.5% 6.8-20% Features Of Partial And Complete Hydatidiform Moles
  8. 8. Epidemiology& Risk Factors Incidence:USA 1/1000 South East 1/500 (Hospital) and in Nigeria 1/379. Risk Factors: Age: <20y (2fold) , > 40y(10 fold) & >50y (50% V.mole) Prior Molar Pregnancy Second molar: 1% - Third molar : 20%! Diet:↑ in low fat Vit. A or carotene diet (complete mole) Contraception :COC double the incidence Previous spontaneous abortion: double the incidence Repetitive H. moles in women with different partners
  9. 9. Partial moles have been linked to: Higher educational levels Smoking Irregular menstrual cycles Only male infants are among the prior live births Epidemiology & Risk Factors
  10. 10. Homozygous 90% Pathogenesis of complete H. Mole Karyotype
  11. 11. Pathogenesis of complete H. Mole Heterozygous 10% Karyotype
  12. 12. Pathogenesis of Partial H. Mole Karyotype
  13. 13. Complete H. Mole Microscopically Enlarged, edematous villi and abnormal trophoblastic proliferation that diffusely involve the entire villi No fetal tissue, RBCs or amnion are produced Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions “ like bunch of grapes" No fetal or embryonic tissue are produced Uterine enlargement in excess of gestational age . Theca-lutein cyst associated in 30%
  14. 14. Complete hydatidiform mole: Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions the name hydatidiform mole stems from this "bunch of grapes"
  15. 15. Partial H. Mole Microscopically: The enlarged, edematous villi and abnormal trophoblastic proliferation are slight and focal and did not involve the entire villi. There is a scalloping of chorionic villi Fetal or embryonic or fetal RBCs Macroscopically: The molar pattern did not involve the entire placenta. Uterine enlargement in excess of gestational age is uncommon. Theca-lutein cysts are rare Fetal or embryonic tissue or amnion
  16. 16. Partial Hydatiform Mole Vesicles Maternal side
  17. 17. Partial H. mole.
  18. 18. The classic features are Irregular vaginal bleeding Hyperemesis Excessive uterine enlargement & Early failed pregnancy. Breathlessness due to anaemia Abdominal pain Presentation Some women will present early with passage of molar tissue
  19. 19. Rarer presentations include: Hyperthyroidism Early onset pre-eclampsia Abdominal distension due to theca lutein cysts Very rarely Acute respiratory failure Neurological symptoms such as seizures (?metastatic disease).
  20. 20. Clinical Findings  Anemia  Breathlessness  Pseudo- Toxemia which consist of Systolic hypertension edema and proteinuria  The Uterus is doughy in consistence  Absence of fetal part  Enlarged Cystic Ovaries
  21. 21. Complete Molar Pregnancy
  22. 22. Complete hydatidiform mole. The classic "snowstorm" appearance is created by the multiple placental vesicles.
  23. 23. Complete H.Mole (High-resolution) U/S Complex intrauterine mass containing many small cysts. Complete H.Mole Associated theca-lutein cysts. U/S Power Doppler
  24. 24. In most patients with a partial mole, the clinical and U/S diagnosis is Usually missed or incomplete abortion. This emphasizes the need for a thorough histopathologic evaluation of all missed or incomplete abortions
  25. 25. Classically: A thickened, hydropic placenta with fetal or embryonic tissue Multiple soft markers, including:  Cystic spaces in the placenta and  Transverse to AP dimension a ratio of the gestation sac of > 1.5, is required for the reliable diagnosis of a partial molar pregnancy
  26. 26. Differential diagnosis • Multiple pregnancy. • Hydatidiform mole. • Threatened abortion. • Ectopic pregnancy.
  27. 27. Partial Molar Pregnancies
  28. 28. There are 2 important basic lines : 1-Evacuation of the mole 2-Regular follow-up to detect persistent trophoblastic disease If both basic lines are done appropriately, mortality rates can be reduced to zero. Management
  29. 29. For Partial mole: It depends on the fetal parts Small fetal parts :Suction curettage Large fetal parts: Medical (oxytocics) In partial mole the oxytocics is safe ,as the hazard to embolise and disseminate trophoblastic tissue is very low Also, the needing for chemotherapy is 0.1- 0.5%. Is That The Same For Partial Mole?
  30. 30. Post-evacuation Surveillance Why? To determine when pregnancy can be allowed To detect persistent trophoblastic disease (i.e. GTN)
  31. 31. The Post-evacuation Surveillance. How? A baseline serum β -hCG level is obtained within 48 hours after evacuation. Levels are monitored every 1 to 2 weeks while still elevated to detect persistent trophoblastic disease (GTN). These levels should progressively fall to an undetectable level (<5 mu/ml). If symptoms are persistent, more frequent β hCG estimation and U/S examination ± D&C are advised
  32. 32. What Is The Optimum Follow-up Period Following Normalization of β hCG? A. For 6 months from the date of uterine evacuation. B. For 6 months from normalization of the β hCG level. B C. For 12 months from the date of uterine evacuation. (For Nigeria)
  33. 33. Barrier methods until normal β hCG level. Once βhCG level have normalized:Combined oral contraceptive (COC ) pill may be used. If oral COC was started before the diagnosis of GTD ,COC can be continue as its potential to increase risk of GTN is very low IUCD should not be used until β hCG levels are normal to reduce uterine perforation. What Is Safe Contraception Following GTD?
  34. 34. Part II: Gestational Trophoblastic Neoplasia (GTN)
  35. 35. Nonmetastatic disease  Locally invasive GTT develops in about 15%  Patient usually present with  Irregular vaginal bleeding  Theca lutein cysts  Uterine subinvolution or asymptomatic enlargement  Persistently elevated serum hCG level  Persistent GTT After hydatiaiform mole
  36. 36. Invasive Mole Villus formation preserved Trophoblast cells invade myometrium and blood vessels Myometrium invaded Myometrium Villus
  37. 37. Invasive H. Mole Myometrial invasion Sometimes involving the peritoneum, parametrium, or vaginal vault. Originate almost always from H. mole Vesicles
  38. 38. Placental-site trophoblastic tumor  Uncommon but important variant of choriocarcinoma  Characteristic  Produce small amount of hCG and hPL  Remain confined to the uterus  Metastasizing late in their course  Relatively insensitive to chemotherapy
  39. 39. Gestational Choriocarcinoma Aneuploidy (not multiplication of 23 ) 1 in 30,000 pregnancies in western world 1 in 300 to 1000 in Nigeria 40% after molar pregnancy: Easily Diagnosed 60% non-molar pregnancy: Difficult Diagnosis The main presentations are often non-gynecologic including hemoptysis or pulmonary embolism, cerebral hemorrhage, gastrointestinal or urologic
  40. 40. Gestational Choriocarcinoma Sheets of anaplastic cytotrophoblast and syncytiotrophoblast cells with hemorrhage & necrosis. Myometrial & B. vessels invasion and early metastases No Villus formation Cytotrophoblast Syncytiotrophoblast
  41. 41. Metastatic disease  Metastatic GTT occur in about 4% after complete mole  Symptom of metastases may result from spontaneous bleeding at metastatic foci  The common site of metastases are  Lung(80%)  vagina(30%)  pelvis(20%)  liver(10%)  brain(10%)
  42. 42. GTN Vaginal Metastasis
  43. 43. Cranial MRI scan: Large metastasis on the left (black arrows) Brain MRI of a patient with a solitary brain metastasis in remission
  44. 44. Autopsy specimen Multiple hemorrhagic hepatic metastasis CT Scan: Liver metastsis
  45. 45. Disease confined to the uterusStage I GTN extends outside of the uterus but is limited to the genital structures (adnexa, vagina, broad ligament) Stage II GTN extends to the lungs, with or without known genital tract involvement Stage III All other metastatic sites (brain, liver) Stage IV FIGO Anatomic Staging Of GTN
  46. 46. Staging : FIGO  Risk factor affecting staging  hCG level > 100,000 mIU/ml  Duration of disease longer than 6 months from termination of pregnancy  Stage 1-4  Without risk factors a  1 risk factor b  With 2 risk factors c
  47. 47. 4210FIGO SCORING >40<40Age (years) --TermAbortionMoleAntecedent pregnancy ≥137to <134to <7<4Pregnancy to treatment Interval (months) > 100,00010,000-100,0001000-10,000<1000Pretreatment serum hCG (iu/l) --≥53 to<5< 3Largest tumour size, including uterus (cm) Liver & brain Gastro- intestinal Spleen & Kidney LungSite of metastases >85-81-4--Number of metastases ≥2 DrugsSingle drug----Previous failed chemotherapy FIGO Prognostic Scoring For GTN (2000( Total Score Survival : ≤ 6 = Low risk (100%) ≥7 = High risk. (95%)
  48. 48. Non metastatic GTD Metastatic Single agent Chemotherapy Methotrexate or Actinomycen D Multi-agent Chemotherapy Low Risk ( ≤ 6) High Risk (≥7) What Is The Optimum Treatment For GTN? GTN
  49. 49. What is the best methotrexate regimen? MTX:1mg/kg IM D:1, 3 ,5 ,7 alternating with Folinic acid 0.1mg/kg IM D 2 , 4 , 6 , 8 followed by 6 rest days Treatment is continued, until the hCG level has returned to normal and then for a further 6 consecutive weeks. As any chemotherapy treatment is reevaluated if FBC, liver or kidney FT are affected or at drug resistance
  50. 50. Chemotherapy  Combination chemotherapy  Triple therapy : MTX, Act-D, cyclophosphamide  EMA-CO : etoposide, MTX, Act-D, cyclophosphamide, vincristine  EMA-EP : etoposide and cisplatin on day 8  Duration of therapy Until 3 normal hCG level  After that, at least 2 additional course are administered
  51. 51. Follow Up  Stage 1-3 receive follow-up with  Weekly hCG level until normal for 3 wks  Monthly hCG level until normal for 12 months  Effective contraception during the entire interval of hormonal follow-up  Stage 4 receive follow-up with  Weekly hCG level until normal for 3 wks  Monthly hCG level until normal for 24 months
  52. 52. Stage Survival Percent % I 424/424 100 II 27/27 100 III 130/131 99 IV 14/18 78 What Is The Survival of GTN By FIGO Stage? Disaia &Creasman Clinical Gynecological Oncology 2007