In the name of GOD

Gestational Trophoblastic Neoplasms (GTN) Dr. Yousefi. Z

GTN is divided into three histologic categories :  hydatidiform mole,  invasive mole (chorioadenoma destruens)  choriocarinoma.  Partial hydatidiform moles  Placental site trophoblastic tumors (PSTT)

All derived from the human placental trophoblast and the paternal genome

Human chorionic gonadotropin (hCG) is secreted by these neoplasms and serves as a sensitive tumor marker that correlates well with the clinical course for all GTNs except PSTT.

The initial histologic features of any lesion identified as GTN are less important than the clinical data and hCG level.

Complete Hydatidiform Mole Macroscopically : Edema and swelling of virtually Villi without identifiable fetal parts or amniotic membranes Microscopically: The chorionic villi are hydropic with marked interstitial edema. fetal vessels are absent Proliferation of cytotrophoblast and syncytiotrophoblast

Complete moles: completely paternal chromosomal composition. most are 46,XX An empty egg by a haploid sperm followed by reduplication Empty ovum + 23  23  endoreduplication 46xx Homozy yous

Clinical finding : 1-One third to one half of uterine enlargement 2-Vaginal bleeding 3-Theca lute in cysts 20% 5-pregnancy – induced hypertension 4-pulmonary decompensation 6-hyperthyroidism 7-snowstorm (ultrasonography)

Partial mole partial moles often are associated with identifiable fetal parts or amniotic membranes one haploid maternal and two haploid paternal sets of chromosomes diagnosis : until after evacuation of the pregnancy

complete moles : 10% to 30% incidence of malignant partial mole : fewer than 5% of the patients

Invasive mole with invasion into the myometrium without intervening endometrial stroma uterine perforation and hemorrhage

choriocarcinoma choriocarcinoma rapidly invades the myometrium and uterine vessels, and systemic metastasis no chorionic villi are identified hematogenous embolization (affinity of trophoblast cell for blood vessel) Most cases have no tissue for pathologic study, hCG level has raise

50% of cases are preceded by hydatidform mole Gestational choriocarcinoma has been observed several years after last known pregnancy. Spontaneous regression of the primary uterine site

Placental site trophoblastic tumor Locally invasive neoplasms derived from intermediate cells of the placenta HPL from cytotrophoblast cell small amounts of hCG rare systemic metastasis significantly more resistant to standard chemotherapy than other forms of GTN hysterectomy is the initial therapy of choice

Risk factors for hydatidiform mole 1-prevous molar pregnancies 2-maternal age advanced maternal age, younger women or adolescents Animal fat Deficiency of folat –caroten and protein Low socioeconomic state

Management GTD complete physical and pelvic examinations complete blood count determination blood chemistry levels, including renal-liver baseline serum hCG level chest radiograph pelvic ultrasonography

Evacuation: suction dilation and curettage hysterectomy followed closely after hysterectomy incidence of malignant sequelae: after 20% after suction D&C to less than 5% after hysterectomy

Follow-up B-hCG levels every 1 to 2 weeks Until hCG level is undetectable After the first normal level for 2 to 4 weeks Every then 1 to 2 months for 6 months Oral contraceptives

Hydatidiform mole (compiete or parial ) Evacuation by suction D&C (hysterectomy only sterllization desired ) Monitor serum B-hCG weekly Good contraception

hCG returns to negative hCG levels q month X 6 May again attempt pregnancy if desired hCG plateaus or rises Exclude new pregnancy Stage and treat with chemotherapy Algorithm for diagnosis and treatment of a patient with hydatidiform mole

Hysterectomy only if sterillzation desired After completion of 6 months of hCG normal level pregnancy if desired False – positive hCG Test Results

The heterogeneity of hCG and the variability between different hCG assays may in False – positive test results. Presence of heterophilic antibodies

After evacuation of hydatidiform mole (9% to 36%) of patients requiring therapy Pattern of hCG regression If hCG level plateau or raise for 3 or more consecutive weekly levels appearance of metastatsis

higher frequency of post molar malignant GTN 1-Trophoblastic proliferation 2-Uterine enlargement 3- Theca lute in cysts 4- Respiratory distress syndrome after molar evacuation 5- post evacuation uterine hemorrhage

Persistent GTD irregular vaginal bleeding Theca lute in cysts Uterine sub involution Persistently elevated serum hCG level

Clinical classification of malignant gestational trophoblastic neoplasia Nonmetastatic GTN A. Not defined in terms of good versus poor prognosis Metastatic GTN Good prognosis (i.e., absence of high-risk factors ) Pretreatment serum B-hCG level < 40,000 mIU/ml Less than 4-month duration of symptoms attributable to disease No evidence of brain or liver metastasis No significant prior chemotherapy No antecedent term pregnancy

Poor pregnosis (i.e., any single high-risk factor ) pretreatment serum B-hCG level >40,000 Iu/ml more than 4-month duration of symptoms attributable to disease brain or liver metastasis or both failed prior chemotherapy antecedent term pregnancy

Malignant GTN distant metastases Gastrointestinal urologic hemorrhage Hemoptysis Neurological symptoms due to cerebral hemorrhage Clinical hyperthyroidism

Four principal pulmunary radiologic patterns snowstorm pattern (Alveolar pattern ) Discrete rounded densities Plural effusion Embolic pattern

Management : Physical and pelvic examinations Baseline hCG level Chest radiograph Pelvic ultrasonography

CT of brain, chest, and abdomen –pelvis Exclude an uterine pregnancy

Stage I Stage II Stage III Stage IV Strictly confined to uterine corpus Extends outside the uterus, but limited to genital structures Extends to the lungs with or without genital tract involvement All other metastatic sites Sub stages assigned for each stage as follows : A: no risk factors present B: One risk factor C: Both risk factors Risk factors used to assign substages : 1- pretherapy serum hCG> 100,000 mIU/ml 2- Duration of disease > 6 months

Who Orgnaization prognostic scoring system for gestational trophoblastic neoplasia Prognostic factor0124 Age<39>39_- Antecedent pregnancyHydatidiformAbortion, ectipicTerm pregnancy- Interval (months)< >12 hCG level (IU/liter)< >10 ABO blood groups (female/male) O/ABA/OAB Largest tumor (cm)<33-5>5_ Site of metastasis_Spleen, kidneyGastrointestinal tract, liverBrain Number of metastases_1-34-8>8 Prior chemotherapy__Single drugMultiple druge The total score is obtained by adding the individual scores for each prognostic factor. Total score : 8, high risk. Interval :between antecedent pregnancy and start of chemotherapy.

WHO Scoring system Score : <4,low risk 5-7 mid risk >8, high risk Chemotherapy alone is successful in curing 85% of patients with non metastatic and good- prognosis

Hysterectomy rarely is indicated as Initial therapy for women with malignant GTN

Persistence of a lung nodule after hCG normalization Should not necessarily surgery

Whole-brain and whole-liver irradiation in conjunction with chemotherapy

protocol for treatment of GTD Stage I single agent chemotherapy Resistant combination chemotherapy or hysterectomy with adjuvant chemotherapy Stage II,III low risk single agent chemotherapy high risk combination chemotherapy Resistant second line chemotherapy Stage IV combination chemotherapy radiotherapy Resistant second line chemotherapy

liver 2,000 rd therapy prevent hepatic hemorrhage selective occlusion of the hepatic artery

Response during therapy Weekly intervals during therapy After remission hCG levels in the normal level Every 1 month First year of surveillance.

Follow up Molar pregnancy 6 month GTN 1year Met static GTN Except lung 2 year

Recurrence rates after therapy for GTN have been 3% to 2.6%

Late complication Slight increase in the incidence of spontaneous abortion Repeat molar 1% ovarian failure as a result of prolonged multi drug chemotherapy

Low incidence of congenital malformations The incidence of placenta accreta particular, appears to be increased After first pregnancy We should be a chest radiography. Serum BhCG after 6-8 weeks of post partum Placenta should be undergo pathology