Gestational Trophoblastic Disease GTD By Dr Dalya Muthefer

Gestational Trophoblastic Disease GTD By Dr. Dalya Muthefer

Gestational Trophoblastic Disease GTD Is defined as a spectrum of disorder resulting from an abnormal placental ( trophoblast ) growth and invasion, it is ranged from the benign condition ( hydatiform mole ) to the malignant ( gestational trophoblastic neoplasia GTN ). These disease retain certain characteristic of the normal placenta such as invasive tendencies and the ability to make h. CG hormone.

Clinical classification : Benign = 80% (HM) • Partial HM. • Complete HM. Malignant=20% (GTN) include Persistant or invasive mole =12 -15% of cases. Choriocarcenoma=5 -8% of cases. Placental site trophoblastic tumor (rare).

Epidemiology Less than 1 in 1000 pregnancies in most of the world, 2 in 1000 in Asia. Risk of recurrence is 1 % (previous one mole). 25% (previous two moles).

Risk factors Extremes of maternal age < 15 years or > 40 years of age. Patients with previous history of molar pregnancy. Possible other factors: deficiency of animal fat and carotene , history of prior spontaneous abortion. The incidence is in excess in maternal blood group A, and deficit in group O. Low socioeconomic state. Using of oral contraceptive pills

Hydatidiform mole (HM) Complete mole Partial mole

Comparison of Complete and partial moles Feature Complete Mole Partial Mole Age Greater risk (5 -103) Not age related Karyotype 90% XX, 10% XY All chromosomes paternally derived XXX or XXY 1 Chromosome set maternal: 2 chromosome sets paternal Fetus Absent Present h. CG Often > 100. 000 m. IU/m. L Rarely elevated above normal levels for pregnancy Primary Symptom Bleeding Secondary Symptoms Large uterine size for gestational age Hyperemesis Theca Lutein cysts Preeclampsia Hyperthyroidism Un common Risk of persistence (GTN) 4% 20%

Partial mole Complete mole

Management of HM : In general , the more active trophoblastic appearance the greater the risk of malignancy. Patients with hydatidiform mole are curative over 80% by treatment of evacuation. (suction curettage) About 90% of cases , the trophoblastic tissue die out completely. About 10% of cases the trophoblastic tissue does not die out completely and may persist or recur as invasive mole or choriocarcinoma.

The follow-up after moler evacuation : �The follow - up after evacuation is key necessary to ensure early recognition of persistent trophoblastic tissue and the development of GTN, this includes : �Clinically ( uterine involution , ovarian cyst regression and cessation of bleeding ) �Serial quantitative measurement of serum h. CG level 48 hours after evacuation of the mole then at weekly intervals till the h. CG become normal for three consecutive reading. Then monthly for 6 months then yearly. �To achieve effective follow - up , the pregnancy should be avoided to avoid the overlap of raising HCG level due to recent pregnancy , the use of mechanical or oral contraceptive pills until the h. CG levels returns to normal after the evacuation of the mole.

Indication of chemotherapy after the evacuation of the hydatidiform mole : Serum h. CG >20000 i. u/L , at any time after evacuation of mole. Raised h. CG at 4 to 6 weeks after evacuation of mole. Evidence of metastases , hepatic , brain and pulmonary. Persistent uterine hemorrhage after evacuation of mole with raised h. CG levels.

Early diagnosis of persistent trophoblastic disease ensures a good prognosis and an effective system of follow-up. A rising or persistently elevated serum h. CG concentration is diagnostic of GTN after a new pregnancy is ruled out. Approximately 75 percent of these cases represent invasive mole , and 25 percent are choriocarcinomas ; placental site trophoblast tumors are rare.

High-risk postmolar trophoblastic tumor: 1. 2. 3. 4. 5. 6. 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 h. CG levels(>100, 000 m IU/ml). Medical complications of molar pregnancy such as toxemia , hyperthyrodism and trophoblastic embolization (villi come out of placenta ). Repeated hydatidiform mole.

Gestational trophoblastic neoplasia (GTN) Invasive mole Choriocarcinoma Placental site trophoblastic tumor

Gestational trophoblastic neoplasia (GTN) v GTN defines a heterogeneous group of lesions that represent an aberrant fertilization event. v The pathogenesis is unique because the maternal tumor arises from fetal tissue. v It is the most curable gynecologic malignancy. v Malignant trophoblastic disease can exist in: Ø Invasive mole ( = non – metastatic form). Ø Choriocarcinoma = metastatic form (Both are treated with chemotherapy and follow up by serum BHCG). Ø Placental site trophoblastic tumor (PSTT).

Invasive mole �The diagnosis of invasive moles or “chorioadenoma destruens” is applied to the moles characterized by : Ø Abnormal peneterativeness Ø Extensive local invasion Ø Excessive trophoblastic proliferation Ø With preserved villous pattern. � The proliferative villi may invade the myomatrum , paramatrum , broad ligament , or the vaginal wall , although there is rarely evidence of metastasis. �The morbidity and mortality (10%) of this disease results from the penetration of the tumor through the myomatrum and to the pelvic vessels with the resultant hemorrhage

Clinical Manifestation �irregular vaginal bleeding. �uterine subinvolution. �theca lutein cyst does not disappear after emptying uterus. �abdominal pain. �metastatic focus manifestation. Diagnosis �history and clinical manifestation. �successive measurement of HCG. �ultrasound examination. �X-ray and CT. �histologic diagnosis obtained after hysterectomy.

Invasive hydatidiform mole infiltrating the myometrium

Choriocarcinoma(metastatic GTN) �Choriocarcinoma subdivide into: Ø good-prognosis (low risk). Ø Poor- Prognosis (High risk). Epidemiology �The incidence of choriocarcinoma in the West: 1 : 10000 and 1 : 70000 pregnancies; and , in Asia 1: 6000 pregnancies. �The antecedent pregnancy is : Ø Hydatidiform mole in about 5 o% of cases. Ø Normal pregnancy in about 25% of cases. Ø Abortion and ectopic pregnancy in about 25 % of cases. �Choriocarcinoma is more likely to occur after complete mole.

Pathological features �Site : In the uterus 90 % of cases; 10 % of cases in the , vagina, lung, liver, and brain. �Macroscopically: Ø Uterus : It may be localized in the form of hemorrhagic polyp or multiple hemorrhagic , necrotic masses in the cavity. Ø Some times it is present in the uterine wall ( intramural ) and the cavity is empty. �Microscopically: Ø Malignant hyperplasia of both cytotrophoblasts , and syncytiotrophoblasts. Ø Extensive hemorrhage. Ø Absence of villi. Ø Destruction of the surrounding myomatrum.

Spread �Direct : Through the myomatrum and may end in uterine perforation , internal hemorrhage, and peritonitis. �Blood : The main method of spread , and occurs to; Ø Genital : Vagina ( 30% ). Ø Extra genital : Lung ( 80% ) , ( the commonest site liver , brain (10%) and bones especially skull and spine. (10%).

Causes of death in choriocarcinoma : Vaginal bleeding. Haemoptysis. Intraperitoneal hemorrhage. Peritonitis. Metastasis to the vaital organs e. g , brain. Pulmonary complications.

Clinical feathers Symptoms : Ø Recent history of expulsion of vesicular mole , or abortion , or full term pregnancy. Ø Persistent vaginal bleeding is the commonest presentation. Ø Haemoptysis. Ø Abdominal pain. Ø Palpable abdominal mass ( enlarge uterus or parauterine metastasis ). Ø neurological symptoms. Signs: Ø Marked deterioration of the general condition. Ø An abdominal swelling may be felt. Ø The uterus symmetrically enlarged. Ø Hemorrhagic secondaries may be seen in the vagina.

Investigations: Ø Serum h. CG. Ø CBC Ø L. F. T. Ø U/S for abdomen and pelvis. Ø Chest X-ray for pulmonary metastasis. Ø Liver scan Ø CT scan for the secondaries. Ø EEG.

Choriocarcinoma: Ultrasound reveals a hyperechoic mass showing hypervascularity on color Doppler.

Clinical classification of GTN q According to the FIGO system , patients who score 6 and below receive low-risk treatment while patients scoring 7 are given high-risk treatment (chemotherapy ) q According to the presence of metastasis 1) Non metastatic trophblastic disease(Disease is limited to the uterus) 2) Metastatic either : �Good Prognosis Metastatic Trophoblastic neoplasia �Poor Prognosis Metastatic Trophoblastic neoplasia q. Drug-resistant disease

The international federation of gynaecology and obstetrics(FIGO) prognostic scoring system employed for assessing the intensity of the initial chemotherapy treatment. Score 0 1 2 4 Age ( years ) < 40 ≥ 40 - - Antecedent pregnancy Mole Abortion Term - <4 4 -6 7 -13 ≥ 13 Months from index pregnancy Pre-treatment h. CG (IU/L) Largest tumour size < 1000 -100000 >100000 < 3 cm 3 - 5 cm ≥ 5 cm - Site of metastases Lung Number of metastases - Previous chemotherapy - Spleen, kidny gastrointestin Brain , liver al 1 -4 5 -8 >8 - Single agent Two or more drugs

Treatment of GTN : Chemotherapy (single agent , multi agent). Surgery. Radiotherapy.

Medical (chemotherapy) I. Non metastatic and good prognosis GTN we use the Single agent chemotherapy. Ø Methotrexate ( antimetabolite ) + folinic acid. Is the treatment of choice given on alternate days followed by six rest days. The cytotoxic therapy is controlled by doing CB , platelet count and LFT. Ø After the h. CG level gets normal ; stop therapy and follow - up by weekly estimation of h. CG levels. Physical examination, chest x-ray, and LFT. Ø Actinomycin D , if there is resistance. Ø Treatment is 100 % successful.

II. Poor Prognosis metastatic trophoblastic neoplasia and drug resistant tumor we use Multiple agent chemotherapy is recommended in this disease. �EMA - CO is considered the regimen of choice in most high–risk patients (Etoposide , Methotrexate, Actinomycin D , Cyclophosphamide, Vincristin ). �The overall survival rate for these patients is 80 – 85 %. �Patients with cerebral or hepatic metastases are treated concurrently with radiotherapy for the whole brain or liver (for hemostasis).

Surgery: Total abdominal hysterectomy may be done in patients not desirous of further reproduction , and in old age woman. Surgical excision of isolated metastases e. g. pulmonary if resistant to chemotherapy. operation is also important in controlling bleeding , infection, complication. in removing remained or drug-resistant foci. Irradiation Whole brain irradiation for cerebral metastases , and the whole organ irradiation for hepatic metastases

Follow-up After successful therapy , physical examination , and chest x-ray follow - up together with the h. CG levels are obtained for serial interval measurement. If at any time h. CG levels rises , repeat the evaluation , staging , and chemotherapy. Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment.

Placental Site Trophoblastic Tumor. Rare tumors (account for 0. 23% cases of GTD). It has a variety of clinical features and its course is unpredictable. Can appear shortly after termination of pregnancy or years later. Hysterectomy is considered optimal therapy and is usually adequate in most situations. It has normal HCG level but high human placental lactogen level so used as a tumor marker. It is chemoresistant and radioresistant.

Future Childbearing After treatment of GTN, molar pregnancies occur in only about 1 -2 % of subsequent pregnancies. These patients should be evaluated with a first trimester ultrasonography. Fertility rates and pregnancy outcomes are similar in patients treated for GTD compared with the general population. Standard chemotherapy protocols have minimal impact on the subsequent ability to reproduce. Patients treated with EMA/CO regimens have an increased rate of second malignancies, particularly hematologic.