Hydatidiform mole-2023.pdf

1 GESTATIONAL TROPHOBLASTIC DISEASES Learning Objectives: By the end of this lecture, the student needs to: - Identify the definition of gestational trophoblastic diseases. -...

1 GESTATIONAL TROPHOBLASTIC DISEASES Learning Objectives: By the end of this lecture, the student needs to: - Identify the definition of gestational trophoblastic diseases. - Outline the classification. - Itemize each type of gestational trophoblastic tumors. In regard to hydatidiform mole, the student needs to: - Describe the definition. - Outline the epidemiology & risk factors. - Interpret the genetic and pathological features. - Recognize the clinical presentation & differential diagnosis. - Label investigations & management. - List complications & follow-up. - State prognosis. GESTATIONAL TROPHOBLASTIC DISEASES (GTD): Gestational trophoblastic diseases (GTD) include several disease processes that arise from the cells of conception. The World Health Organization (WHO) divides GTD into: I. Premalignant:. Hydatidiform mole: a. Complete mole. b. Partial mole. II. Malignant (gestational trophoblastic neoplasia (GTN)): 1. Invasive mole (chorioadenoma destruens). 2. Choriocarcinoma: a. Non-metastatic. b. Metastatic: I. Good-prognosis. II. Poor-prognosis. 3. Placental-site trophoblastic tumor/epitheloid trophoblastic tumors.  2 HYDATIDIFORM MOLE Definition: Hydatidiform mole is a neoplasm of the trophoblast that involves both epithelial layers: cytotrophoblast and sycytiotrophoblast and composed of products of conception that lack an intact fetus and show gross cyst-like swelling of the chorionic villi due to accumulation of fluid. There is disintegration and loss of blood vessels in the villous core. Etiology: Normal trophoblast behaves like malignant growth invading maternal tissue locally and fragments of it enters the blood stream to lodge in the lungs, this is normally controlled by maternal immunological factors that limit the local uterine invasion and destroy the extrauterine deposits. It is thought that trophoblastic tumors can result from a defective maternal immune response to the invasion by the trophoblast due to breakdown of normal host resistance. In consequence, the primitive vasculature within each villus does not form properly, with the result that embryo starves, dies and absorbed, the villi become distended with nutrients that will provide the trophoblast with excessive growth stimulus so it continues to thrive and, in certain circumstances invades maternal tissue. The increased syncytiotrophoblast activity leads to an increased production of human chorionic gonadotrophin (hCG), chorionic thyrotrophin and progesterone. Epidemiology: The incidence rate varies worldwide between 1-3 in1000-2000 pregnancies in North America and 1 in 200-300 live births in Asia. Partial moles are more common than complete moles, ratio of 60:40. Majority of moles abort spontaneously during first trimester. Risk Factors: 1. Race: H. mole is more common in Asian women than western. 2. Maternal age: Incidence is more under the age of 15 years and rise sharply after 45 especially after 50 years. It appears that GTD may result from defective fertilization, a process that is more common in both younger and older individuals. The risk of partial mole remains relatively unchanged across the age groups. 3. Previous molar pregnancy: The chance of recurrence only 2% following one mole, and increases with 2 or more molar pregnancies. 4. Nutritional and socioeconomic factors: The incidence of complete mole has been noted to be higher in geographic areas where people consume less carotene, animal fat and folic acid. 5. Underlying genetic disorder: as it is occasionally found in family clusters. Genetic features of H. mole: 1. Complete mole: Karyotype usually 46XX, where haplotype sperm (23X) fertilize an empty anucleate oocyte lacking maternal DNA, the sperm duplicates its DNA to form 46XX complement. 5- 10% formed by process of dispermy: two spermatozoa, one 23X, the other 23Y fertilize an empty egg with no nuclear material give 46XY. Less than 1% may have biparental karyotype due to autosomal recessive disease causing recurrent complete mole. 2. Partial mole: Triploid karyotype 69XXX or 69XXY. Most common mechanism is fertilization of normal egg by 2 sperms with 2 of chromosomes being of paternal origin. Not all triploid concepts lead to partial mole but in these circumstances the double contribution is from the maternal side and no placental changes seen.  3 Pathological features: 1. Complete mole: Clinical picture: numerous edematous vesicles like a bunch of small clear grapes (hydatidiform) which is seen in the second trimester and most cases are diagnosed earlier. The fetus cannot be identified and no membrane present. Microscopy: large edematous villi, avascular with variable degree of trophoblastic hyperplasia. 2. Partial mole: Macroscopically and on ultrasound (U/S) scan during first trimester it resembles normal products of conception, as a result the diagnosis can be missed unless the products are sent for histopathology. The embryo is viable on early U/S but becomes non-viable at 10-12weeks. Some hydropic villi are seen, whereas other villi are normal, fetus with membranes may be present. When the fetus is present it often has the features of triploidy (IUGR, congenital malformations). Histological examination: Fetal erythrocytes and vessels in the villi are common finding and less trophoblastic hyperplasia (swelling of the villi). Clinical presentation: The majority of patients are diagnosed prior to 16 weeks as a result of first trimester bleeding or abnormal U/S. 1. Bleeding in early pregnancy after variable period of amenorrhea is most common clinical sign of mole which is variable from dark brown vaginal discharge to very severe life threatening one and may be associated with anemia over 50% of cases. 2. Passing molar tissue and vesicles with large amount of blood or dark fluid leak into the vagina. 3. Hyperemesis gravidarum: Excessive vomiting in about 25% of molar pregnancy due to extremely elevated human chorionic gonadotrophin (HCG) levels. 4. Uterine enlargement: Uterus larger than gestational age is a classical sign of complete mole due to excessive trophoblastic growth and retained blood. Similar frequency present with same size or smaller. Uterus described to be doughy, fetal parts not felt, fetal heart not heard. 5. Bilateral ovarian theca-lutein cysts: Clinical picture of large for date uterus may be exaggerated by presence of large theca-lutein cyst of the ovaries due to excessive HCG stimulation about 25% of cases; which usually regress spontaneously after mole evacuation. If they cause symptoms of marked pelvic pressure, then they can be decompressed by laparoscopic or ultrasonographically directed aspiration. Sometimes they may cause severe pain if they rupture or undergo torsion and may need surgical intervention. 6. Pre-eclampsia: In about 12-54% of patients: hypertension, proteinuria, edema with hyperreflexia and rarely convulsions. We should always suspect mole if pre-eclampsia develops early in pregnancy. 7. Hyperthyroidism: Tachycardia, tremor and warm skin in about 7% of cases due to the thyrotrophic effect of HCG, they resolve after mole evacuation. 8. Disseminated intravascular coagulopathy: Develop in long standing mole due to embolization of trophoblastic tissue to the lung leading to release of thromboplastin substances which stimulate fibrin and platelet deposition within the vascular tree and coagulation failure. Best corrected by fresh frozen plasma, platelet transfusion and rarely cryoprecipitate before mole evacuation. 9. On examination of the patient: Tachycardia, tachypnea, hypertension. In trophoblastic embolization: wheezing and rhonchi may be heard. 10. Pelvic examination: grape-like vesicles and blood clots. The clinical presentation of complete mole has changed considerably over the past few decades were excessive uterine size, anemia, hyperemesis, pre-eclampsia, theca lutin cysts, hyperthyroidism and metastatic disease are seen less far often due to early diagnosis.  4 Partial mole usually presents with signs and symptoms consistent with incomplete or missed abortion like vaginal bleeding and absence of fetal heart tones, 3% uterine enlargement and pre-eclampsia. Theca-lutein cysts, hyperemesis and hyperthyroidism are rare. Differential diagnosis: 1. Partial mole should be differentiated from hydropic degeneration in an abortus (missed miscarriage). 2. Degenerating fibroid. 3. Threatened miscarriage (early pregnancy bleeding). 4. Ectopic pregnancy. 5. Multiple pregnancy (excessive vomiting). 6. Hyperemesis gravidarum. 7. Pre-eclampsia. 8. Hyperthyroidism. 9. DIC. 10. Ovarian tumors and their complications. Diagnosis: 1. Ultrasonography: The classic image of snow-storm appearance with multiple highly reflective echos and areas of vacuolation within uterine cavity. Gestational sac with fetus may also present with large theca lutein cyst. U/S diagnosis of complete mole is usually reliable but partial mole is more difficult. 2. Quantitative beta-HCG: Levels more than 200 000 IU/ml are suggestive of molar pregnancy although partial moles are only infrequently above the range of normal pregnancy. Investigations: 1. CBP and clotting function: Platelet count, prothrombin time, partial thromboplastin time and fibrinogen level. 2. LFT & RFT. 3. TFT. 4. CXR. Treatment: Prior to evacuation, correct any metabolic upset, stabilize the patient. Correct anemia and coagulopathy. Treat pre-eclampsia, thyrotoxicosis, and dehydration. 1. Suction evacuation: method of treatment of H. mole. Under general anesthesia dilate the cervix carefully to avoid damage to 12mm and introduce suction curettage with negative pressure 60-70mmHg, then after evacuation gentle curation to avoid Asherman syndrome. Uterotonic agents are continued postoperatively to reduce the likelihood of hemorrhage, ergometrine is preferred to oxytocin as it produces sustained rather than rhythmic contractions. Second uterine evacuation may be recommended in selected cases with retained tissue is seen in the uterine cavity on ultrasound after first evacuation. 2. Medical termination by prostaglandin or oxytocin induction is not recommended because of the increased risk of bleeding, malignant squeal and forcing trophoblastic tissue into the venous space of placental bed and dissemination into the lung. 3. Hysterectomy: Suitable in older patients who completed their families because the risk of postmolar trophoblastic disease increases with maternal age. Care must be taken to do little manipulation to avoid embolization of trophoblastic tissue. Rare cases hysterectomy required to control hemorrhage in emergency situations.  5 Complications: 1. Perforation of uterus during suction curettage due to large uterus. If perforation noted, complete the procedure under laparoscopic guidance. 2. Hemorrhage during evacuation. 3. Molar metastasis: Respiratory distress at time of surgery due to trophoblastic embolization to the lung leading to respiratory compromise and hypoxemia with pulmonary edema, the greatest risk factor is a uterus larger than gestational age; condition may be fatal in 5% of cases. 4. High-output heart failure caused by anemia or iatrogenic fluid overload. It should be aggressively treated with assisted ventilation and monitoring. 5. Choriocarcinoma: Malignant trophoblastic disease develops in 10-20%of molar pregnancy, quantitative HCG should be serially monitored for 1 year, after complete mole the risk 1:10, partial mole 1: 200, therefore careful follow up of HCG is essential. Follow-up: Close survey of HCG after evacuation to ensure early recognition of persistent trophoblastic disease (PTD), about 90% of trophoblastic tissue die out spontaneously after evacuation but 10% remain as PTD and require chemotherapy. HCG is produced predominantly by syncytiotrophoblast cells, it is expressed by all forms of pre- malignant and malignant GTD except few atypical cases of PSTT/ETT. After molar pregnancy HCG return to normal non-pregnant level by 4-6 weeks after evacuation, if failure to fall within 6-8 weeks to non-pregnant or rise at any time or plateau over a period of 3 weeks or more then refer to specialist for chemotherapy. Clinical factors that have been associated with risk of malignant disease are: advanced maternal age, high levels of HCG, eclampsia, hyperthyroidism and bilateral theca lutein cysts. Predicting who will develop PTD remains difficult, and treatment decisions should not be based on the presence of any or all these risk factors. Indications for chemotherapy: 1. High or static HCG levels after one or two uterine evacuations. 2. Persistent uterine bleeding with rising HCG values. 3. Pulmonary metastasis with static or rising HCG values. 4. Evidence of intracranial, hepatic or gastro-intestinal metastasis. 5. Histological diagnosis of choriocarcinoma or placental site trophoblastic tumor.. Radioimmunoassay of HCG normally cross-react with LH, so more specific assay is for beta subunit of HCG.. Serial quantitative beta-HCG levels should be determined.. The first level 48 hours after evacuation then every 2 weeks till the level within the reference range.. The level consistently drops and should never increase.. Once the level reached reference rate, check them each month for a year.. Any rise in level should prompt a chest radiograph, ultrasound and pelvic examination to detect early metastasis.. Patient with prior molar pregnancy have increased risk of a second mole in a future pregnancy. Evaluate all future pregnancies with ultrasonography. Contraception: The patient must avoid pregnancy for a year after evacuation to avoid any confusion about the development of malignant disease, they should be encouraged to use effective contraception during the entire interval of HCG follow up. If pregnancy occurs, the elevation in beta-HCG levels cannot be differentiated from the disease process. Combined oral contraception or barrier methods are best choices for contraception. Previously it was thought that oral contraception increases the risk of post molar trophoblastic disease, but they proved to be safe.  6 Progesterone only pills are liable to cause irregular bleeding and should not be used. Intrauterine contraceptive device is inadvisable, first because it may cause uterine bleeding raising the fear of choriocarcinoma and second is that if it was inserted before achieving normal HCG level; it may carry a high risk of perforation. If the patient completed her family; we should consider sterilization. Prognosis: Because of early diagnosis and appropriate treatment, the current mortality rate from H.mole is essentially zero. Approximately 10% of women with complete mole develop trophoblastic malignancy.