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Seminar on gestational trophoblastic disease (gtd) (f inal)
 

Seminar on gestational trophoblastic disease (gtd) (f inal)

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SEMINAR PRESENTED BY DR MONIKA MOURYA AT NSCBMCH JABALPUR

SEMINAR PRESENTED BY DR MONIKA MOURYA AT NSCBMCH JABALPUR

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  • trophoblastic embolization (villi come out of placenta and locate in brain or lungs to block blood flow)
  • Triploid : has three set of chromsomes
  • Scattered: some parts of them are
  • This method does not answer the question of whether the mole is invasive ,or its potential malignancy
  • This method does not answer the question of whether the mole is invasive ,or its potential malignancy
  • Polyhy’dramnios
  • Oral contraceptives may interfere with the accurate measurement of hCG

Seminar on gestational trophoblastic disease (gtd) (f inal) Seminar on gestational trophoblastic disease (gtd) (f inal) Presentation Transcript

  • SEMINAR ON CHORIOCARCINOMA DEPARTMENT OF OBS & GYNAE N.S.C.B. MEDICAL COLLEGE, JABALPUR (M.P.) Speaker Dr. Monika Mourya
  • TYPES OF GTD
    • Benign
    • Hydatidiform mole/molar pregnancy (complete or incomplete)
    • Malignant
    • Invasive mole
    • Choriocarcinoma (chorioepithelioma)
    • Placental site trophoblastic tumor
  • Pathologic and clinical classifications for gestational trophoblastic disease PATHOLOGIC CLASSIFICATION CLINICAL CLASSIFICATION Hydatidiform mole *complete *incomplete Benign gestational trophoblastic disease Invasive mole Malignant trophoblastic disease Nonmetastatic Placental site trophoblastic tumor Metastatic Choriocarcinoma High risk Low risk
    • Risk factor for malignant change
    • Pre-evacuation uterine size larger than expected for gestational duration
    • Bilateral ovarian enlargement (> 9 cm theca lutein cysts)
    • Age greater than 40 years
    • Very high hCG levels(>100,000 m IU/ml)
    • Medical complications of molar pregnancy such as toxemia, hyperthyroidism and trophoblastic embolization (villi come out of placenta )
    • repeat hydatidiform mole
  • COMMON SITES FOR METASTATIC GESTATIONAL TROPHOBLASTIC TUMORS Site Per cent Lung 60-95 Vagina 40-50 Vulva/cervix 10-15 Brain 5-15 Liver 5-15 Kidney 0-5 Spleen 0-5 Gastrointestinal 0-5
  • HYDATIDIFORM MOLE (MOLAR PREGNANCY)
  • DEFINITION AND ETIOLOGY
    • Molar pregnancy is characterized histologically by abnormalities of the chorionic villi consisting of varying degree of trophoblastic proliferation and edema of villous stroma.
    • The etiology of hydatidiform mole remains unclear, but it appears to be due to abnormal gametogenesis and fertilization.
    • 2 types of H-mole
    • Complete Mole :
    • In a ‘ complete mole ’ the mass of tissue is completely made up of abnormal cells
    • There is no fetus and nothing can be found at the time of the first scan.
    • Partial Mole :
    • In a ‘ partial mole ’, the mass may contain both these abnormal cells and often a fetus that has severe defects.
    • In this case the fetus will be consumed ( destroyed) by the growing abnormal mass very quickly.
    Complete Mole Partial Mole
    • CYTOGENETICS
    • Complete molar pregnancy Chromosomes are paternal , diploid
    • 46,XX in 90% cases
    • 46,XY in a small part
    • Partial molar pregnancy Chromosomes are paternal and maternal, triploid.
    • 69,XXY 80%
    • 69,XXX or 69,XYY 10-20%
  • COMPARATIVE PATHOLOGIC FEATURES OF COMPLETE AND PARTIAL HYDATIDIFORM MOLE Feature Complete Mole Partial Mole Karyotype Usually diploid 46XX Usually triploidy 69XXX most common. Villi All villi hydropin; no normal adjacent villi Normal adjacent villi may be present vessels present they contain no fetal blood cells blood cells Fetal tissue None present Usually present Trophoblast Hyperplasia usually present to variable degrees Hyperplasia mild and focal Uterine size More than date Less than date Theca Lutein cyst 30-60% common Uncommon b HCG High more than 50 thousand Less than 50 thousand Risk of persistent GTN 20% <5% Classical clinical symptoms Common Uncommon
  • Signs and Symptoms of complete Hydatidiform Mole
      • Vaginal bleeding
      • Hyperemesis ( severe vomit)
      • Size inconsistent with gestational age( with no fetal heart beating and fetal movement)
      • Preeclampsia
      • Theca lutein ovarian cysts
      • Signs and Symptoms of Partial Hydatidiform Mole
      • Vaginal bleeding
      • Absence of fetal heart tones
      • Uterine enlargement and preeclampsia is reported in only 3% of patients.
      • Theca lutein cysts, hyperemesis is rare.
  • Complete hydatidiform mole demonstrating enlarged villi of various size
  • Partial hydartidiform mole
  • Here is a partial mole in a case of triploidy. Note the scattered grape-like masses with intervening normal-appearing placental tissue.
    • INCIDENCE
    • 1 out of 1500-2000 pregnancies in the U.S. and Europe
    • 1 out of 500-600 (another report 1%) pregnancies in some Asian countries.
    • Complete > incomplete
    • 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
    • There is an increased risk of molar pregnancy for women over the age 40.
    • Approximately 10-17% of hydatidiform moles will result in invasive mole
    • Approximately 2-3% of hydatidiform moles progress to choriocarcinoma ( most of them are curable)
  • CLINICAL RISK FACTORS FOR MOLAR PREGNANCY Age (extremes of reproductive years) <15 >40 Reproductive history prior hydatidiform mole prior spontaneous abortion Diet Vitamin A deficiency Birthplace Outside North America( occasionally has this disease)
  • Hydatidiform mole: specimen from suction curettage
  • A large amount of villi in the uterus.
    • The microscopic appearance of hydatidiform mole:
      • Hyperplasia of trophobasitc cells
      • Hydropic swelling of all villi
      • Vessles are usually absent
  • Transvaginal sonogram demonstrating the “ snow storm ” appearance.
  • Color Dopplor facilitates visualization of the enlarged spiral arteriesclose proximity to the “ snow storm ” appearance
    • Sign and symptoms of H. Mole
    • Symptoms
    • Vaginal bleeding -most presenting symptom
    • Lower abdominal pain
    • Constitutional symptoms – hyperemisis gravidarum
    • Trophoblastic embolization – respiratory distress.
    • 2% of patient with complete mole diagnosed in patient with excessive uterine size and markedly elevated HCG level. This patient may develop chest pain, dysnea, tachypnea, tachycardia, severe respiratory distress during and after molar evacuation.
    • Expulsion of grape like vesicles per vaginum is diagnostic of vesicular mole.
    • Signs
    • Pre-eclampsia 27% of patient with complete mole associated with hypertension, proteinuria, hyperreflexia, (eclamptic convulsion rarely occur).
    • Hyperthyroidism – 7% of patient with complete molar gestation- patient develop tachycardia, tremor, worm skin diagnosis confirmed by increase level of T3 and T4.
    • Theca lutein ovarian cyst
  • 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.
    • Per abdomen findings
    • Size of uterus more than that expected for period of amenorrhoea 50% of cases.
    • Feel of uterus is firm and elastic
    • Fetal parts not felt nor any fetal movements, absence of fetal heart sound.
    • Vaginal Examination :
    • Internal ballottement can be elicited.
    • Unilateral/ bilateral enlargement (theca lutein cyst) of ovary may be palpable in 25-50% of cases.
    • Presence of vesicles in vaginal discharge is pathognomic of H mole.
    • If the cervical os is open instead of membranes, blood clot or vesicles may be felt.
    • Investigations
    • ABO/RH, CBC
    • Hepatic, renal thyroid function test.
    • Ultrasound – is the criterion standard for identifying both complete and partial molar pregnancies. The classic image is of a “Snowstorm” pattern.
    • Quantitative estimation of HCG – rapidly increase value of serum HCG (HCG more than 1 l00,000 m/IU/ml) are usual with molar pregnancies. Normal pregnancy value below 60,000m/IU/ml.
  • A sonographic findings of a molar pregnancy. The characteristic “ snowstorm ” pattern is evident.
  • Transvaginal sonogram demonstrating the “ snow storm ” appearance.
    • The most common symptom of a mole is vaginal bleeding during the first trimester
    • however very often no signs of a problem appear and the mole can only be diagnosed by use of ultrasound scanning. (rutting check)
    • Occasionally, a uterus that is too large for the stage of the pregnancy can be an indication.
    DIAGNOSIS
      • DIFFERENTIAL DIAGNOSIS
      • Abortion
      • Multiple pregnancy
      • Polyhydroamnios
      • Fibroid or ovarian tumour with pregnancy.
      • COMPLICATIONS
      • Immediate
      • Haemorrhage and shock
      • Sepsis
      • Perforation of uterus
      • Pre-eclampsia
      • Acute pulmonary insufficiency
      • Co-agulation failure
      • Late
      • Choriocarcinoma – following H mole ranges between 2-10%.
  • TREATMENT
    • Suction dilation and curettage :t o remove benign hydatidiform moles
    • When the diagnosis of hydatidiform mole is established, the molar pregnancy should be evacuated.
    • An oxytocic agent should be infused intravenously after the start of evacuation & continued for several hours to enhance uterine contractility
    • Hysterectomy (Removal of the uterus) : used rarely to treat hydatidiform moles if future pregnancy is no longer desired.
    • Chemotherapy with a single-agent drug
    • 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 )
    • Follow-up Protocols
    • History and clinical examination
    • Patients with hydatidiform mole are curative over 80% by treatment of evacuation.
    • The follow-up after evacuation is key necessary
    • Enquire about
    • uterine involution, ovarian cyst regression malignant deposit in ant vaginal wall, cessation of bleeding, persistent cough, breathlessness or haemoptysis
    • Investigation : Detection of HCG in urine or serum, chest X-ray before t/t and after evacuation to exclude metastases, there after it should be done at 3 rd , 6 th & 12 th month.
    • Contraception should be practiced during this follow up period combined oral pills and barrier method of contraception used, IUCD is contraindication b/c of its frequent association of irregular bleeding surgical sterlization is another alternative when she has completed her family.
  • Invasive mole
  • DEFINITION
    • 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.
  • Invasive mole: the tissue invades into the myometrial layer. No obvious borderline, with obvious bleeding.
  • 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.
  • Doppler image of invasive mole
  • CHORIOCARCINOMA
  • DEFINITION
    • This is extremely malignant form of trophoblastic tumour may be considered a carcinoma of chorionic epithelium, although an its growth and metastasis behave like sarcoma
    • Characterized by abnormal trophoblastic hyperplasia and anaplasia , absence of chorionic villi
  • Gross specimen of choriocarcinoma
  • Microscopic image of choriocarcinoma absence of chorionic villi
    • Incidence :
    • Occur in about 4% of patient after evacuation of complete mole, but seems more after when GTT develop after non molar pregnancy.
    • Patient develops choriocarcinoma – 50% after H. mole 15% after term pregnancy 25% after abortion or ectopic pregnancy.
  • SYMPTOMS AND SIGNS
    • Bleeding
    • Infection
    • Abdominal swelling
    • Vaginal mass
    • Lung symptoms
    • Symptoms from other metastasis
  • PATIENT MAY COMMONLY PRESENT WITH SIGN OF METASTASIS
    • Pulmonary metastasis
    • 80% of patient with metastatic GTT lung involvement patient present with chest pain, cough, hemoptysis, dyspnea.
    • Four principle pulmonary pattern
    • Alveolar or snow strom pattern.
    • Discrete rounded densities- cannon ball appearance
    • Embolic pattern caused by pulmonary arterial occlusion
    • Vaginal metastasis
    • occur in about 30%
    • Liver metastasis
    • Occur in about 10%
    • Central Nervous System
    • Involve brain in 10% cases
  • WHO Prognostic Scoring System 0-4 low risk, 5-7 intermediate risk, >8 high risk for death Score Prognostic factor 0 1 2 4 Age(years) ≤ 39 >39 — — Pregnancy history Hydatidiform mole Abortion, ectopic Term pregnancy — Interval (months) of treatment <4 4-6 7-12 >12 Initial hCG(mIU/ml) <10 3 10 3 -10 4 10 4 -10 5 >10 5 Largest tumor(cm) <3 3-5 >5 — Sites of metastasis Lung Spleen, kidney GI tract, liver Brain No. of metastasis — 1-4 4-8 8 Previous (treatment) — — Single drug 2 or more
  • FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR
    • Stage I : Disease confined to uterus
    • Ia : Confined to uterus with no risk factor
    • Ib : Confined to uterus with 1 risk factor
    • Ic : confined to uterus with 2 risk factor
    • Stage II : GTT extending outside uterus but limited to genital str. (adenexa vagina broad ligaments)
    • IIa : GTT involving genital tract with out risk factor
    • Iib : GTT involving genital tract with 1 risk factor
    • IIC : GTT involving genital tract with 2 risk factor
  • FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR
    • Stage III : GTT extending of lung with or without
    • Known genital tract involvement
    • IIIa : GTT extending to lung with no risk factor
    • IIIb : GTT extending to lung with 1 risk factor
    • IIIc : GTT extending to lung with 2 risk factor
    • Stage IV: All other metastatic sites
    • IVa : All metastatic sites other site with out risk factor
    • IVb : All metastatic sites other site with out 1 risk factor
    • IVc: All other metastatic sites site with out 2 risk factor
    • Risk Factor ; HCG > 100;000mIU/ml
    • Duration of ds longer then 6 months from formenation of antedent pregnancy.
  • Diagnostic Evaluation
    • All Patients with persistent GTT should undergo careful pretreatment evaluation including the following –
    • Complete history and physical examination .
    • Measurement of serum HCG value.
    • . Hepatic, thyroid and renal function test.
    • Determination of baseline peripheral WBC and platelet count.
    • Once the diagnosis established the further examination should be done to determine the extent of disease (Chest X- ray, CT scan of abdomen, pelvis and Head, MRI, USG)
  • Management
    • Preventive and Curative
    • a. Preventive – Prophylactic CT in at risk women following evacuation of molar pregnancy.
    • Risk Women –
    • Age of patient >35 years.
    • Level of HCG > 100,000 IU/ 24 Hours.
    • Histological diagnosed infiltrative mole.
    • Previous history of motor pregnancy.
    • Meticulous follow up following evacuation of H. mole of at least one years to detect early evidence of trophoblastic reactivation.
    • Single agent chemotherapy is highly effective in case of persistent trophoblastic disease.
    • Selective hysterectomy in H. mole in patients of age>35years.
  • Those who want to retain fertility
    • 1. Single agent CT is preferred treatment in patients with stage I disease who want to retain fertility.
    • When patients are resistant to single agent chemotherapy and desire to retain fertility combination chemotherapy should be administered.
    • Stage II & III – Vaginal and pelvic metastatics.
    • Vaginal – In low risk cases.
    • Single agent chemotherapy have 80% rate of remission.
    • High risk patients managed with primary intensive combination chemotherapy.
  • Curative Management -
    • Chemotherapy.
    • Surgery.
    • Radiation.
    • Management of various stages-
    • Stage I:
    • Initial – single agent chemotherapy or hysterectomy with adjunctive chemotherapy .
    • Resistant – Combination chemotherapy Hysterectomy with adjunctive chemotherapy.
    • Local resection, pelvic infusion.
    • Stage II & III-
    • Low risk –
    • Initial - Single agent chemotherapy.
    • Resistant – Combination chemotherapy.
    • High Risk –
    • Initial – Combination chemotherapy.
    • Resistant – second line combination chemotherapy
    • Stage IV-
    • Initial - Combination Chemotherapy.
    • Brain – Whole heat irradiation (3000 CGY)
    • craniotomy to manage complications.
    • Liver – Resection to manage complications.
    • Resistant – second line combination chemotherapy
    • hepatic arterial infusion.
  • Adjuvant chemotherapy is adminstered for three resons
    • To reduce the likelihood of disseminating viable tumour cell at surgery.
    • To maintain cytotoxic level of chemotherapy in the blood stream and tissue in case viable tumour cells are disseminated at surgery .
    • To treat any occult metastasis that may already present at the time of surgery.
  • Follow up-
    • All patients with stage I through stage III disease should receive follow up with-
    • Weekly measurement of HCG level until they are normal for 3 consecutive weeks.
    • Monthly measurement of HCG value until level are normal for 12 consecutive months.
    • Effective contraception during the entire interval of hormonal follow up.
  • Chemotherapy
    • Single agent chemotherapy with either actinomycin D or methotrexate has achieved comparable and excellent remission rates in both non metastatic and low risk metastatic GTN.
    • single drug regimen in low rate case –
    Drug Dosage Route Days Methotrexate 1-15 mg/kg IM/IV 1,3,5,7. Folonic acid 1-015 mg/kg IM 2,4,6,8. Actinomycin D 12  g/kg IV 1-5 Cyclophosphamide 3mg/kg IV 1-5
  • EMA- CO protocol in poor prognosis metastatic disease
    • The course will restart after 7-14 days. If possible, Generally 2 additional courses are given after the hCG levels become normal.
    Days Drug Dose Day-1 Etoposide 100mg /m 2 in 200 ml saline infused over 30 minutes. Actinomycin D 0.5 mg IV bolus Methotrexate 100mg /m 2 bolus folllowed by 200mg /m2 IV infusion over 12 hours. Day -2 Etoposide 100mg /m 2 in 200 ml saline infused over 30 minutes. Actinomycin D 0.5 mg IV bolus Folinic acid 15mg IM every 12 hrs for 4 doses begnning 24 hours after starting methotrexate. Day-8 Cycolphosphamide 600mg/m 2 IV in saline over 30 min. Vincristine (oncovin) 1mg/m 2 bolus
  • PROGNOSIS
    • Cure rates should approach 100% in nonmetastatic and low-risk metastatic GTD
    • Intensive multimodality therapy has resulted in cure rates of 80-90% in patients with high-risk metastatic GTD
  • FOLLOW-UP AFTER SUCCESSFUL TREATMENT
    • 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
    • Contraception should be maintained for at least 1 year after the completion of chemotherapy. Condom is the choice.
  • Placenta Site Trophoblastic Tumor (PSTT)
    • Placenta Site Trophoblastic Tumor is an extremely rare tumor that arised from the placental implantation site
    • Tumor cells infiltrate the myometrium and grow between smooth-muscle cells
    DEFINITION
  •  
    • Serum hCG levels are relatively low compared to those seen with choriocarcinoma.
    • Several reports have noted a benign behavior of this disease. They are relatively chemotherapy-resistant, and deaths from metastasis have occurred.
    • Surgery has been the mainstay of treatment
    DIAGNOSIS AND TREATMENT
  •