Gestational Trophoblastic Disease

Definitions Gestational Trophoblastic Neoplasia (GTN)  chorioadenoma destruens, metastasizing mole, choriocarcinoma. Gestational Trophoblastic Neoplasia (GTN)  chorioadenoma destruens, metastasizing mole, choriocarcinoma. –Non-metastatic gestational trophoblastic neoplasia: process is confined to the uterus –Metastatic gestational trophoblastic neoplasia: metastases are demonstrated in the lung/vagina and/or in brain, liver, kidney or elsewhere Hydatidiform mole: Gestational Trophoblastic Disease (GTD). Hydatidiform mole: Gestational Trophoblastic Disease (GTD).

Classification Hydatidiform mole Hydatidiform mole –Complete mole –Partial mole Invasive mole Invasive mole Placental-site trophoblastic tumor Placental-site trophoblastic tumor Choriocarcinoma Choriocarcinoma

Complete Hydatidiform Mole Pathology Pathology –Identifiable embryonic/fetal tissue Θ –Chorionic villi: generalized hydatidiform swelling, diffuse trophoblastic hyperplasia Chromosomes: 46XX karyotype, molar chromosomes  paternal origin Chromosomes: 46XX karyotype, molar chromosomes  paternal origin

Partial Hydatidiform Mole Pathology: Pathology: –Chorionic villi with focal hydatidiform swelling and cavitation –Villous scalloping –Focal trophoblastic hyperplasia –Prominent stromal trophoblastic inclusions –Identifiable embryonic or fetal tissue Chromosomes: triploid karyotype (69 chromosomes) Chromosomes: triploid karyotype (69 chromosomes)

Clinical Features Complete Hydatidiform Mole Complete Hydatidiform Mole –Vaginal bleeding –Excessive uterine size –Toxemia –Hyperemesis gravidarum –Hyperthyroidism –Trophoblastic embolization –Theca lutein ovarian cyst Partial Hydatidiform Mole: signs & symptoms of incomplete / missed abortion Partial Hydatidiform Mole: signs & symptoms of incomplete / missed abortion

USG : vesicular sonographic pattern  “snowstorm” pattern USG : vesicular sonographic pattern  “snowstorm” pattern Diagnosis

Follow-up Human Chorionic Gonadotropin Human Chorionic Gonadotropin Contraception IUD  normal hCG level IUD  normal hCG level First choice: First choice: –Hormonal contraception –Barrier methods

Malignant Gestational Trophoblastic Neoplasia Nonmetastatic Disease Nonmetastatic Disease Metastatic Disease Metastatic Disease

Nonmetastatic Disease Signs & symptoms: Signs & symptoms: –Irregular vaginal bleeding –Theca lutein cysts –Uterine subinvolution or asymmetric enlargement –Persistently elevated serum hCG levels Histology: anaplastic syncytiotrophoblast & cytotrophoblast w/o chorionic villous structure Histology: anaplastic syncytiotrophoblast & cytotrophoblast w/o chorionic villous structure

Placental-site Trophoblastic Tumor Consist of: intermediate trophoblast & a few syncytial elements Consist of: intermediate trophoblast & a few syncytial elements Produce small amount of hCG & human placental lactogen Produce small amount of hCG & human placental lactogen Tend to remain confined to the uterus Tend to remain confined to the uterus Metastasizing late Metastasizing late Insensitive to chemtotherapy Insensitive to chemtotherapy

Metastatic Disease Sites of metastatic spread: Pulmonary: Pulmonary: –Signs: chest pain, cough, hemoptysis,d yspnea, asymptomatic lesion –Radiographic patterns: an alveolar or “snowstrom” pattern; discrete, rounded densities; pleural effusion; an embolic pattern caused by pulmonary arterial occlusion

Metastatic Disease Sites of metastatic spread: Vaginal: highly vascular, appear reddened or violaceous Vaginal: highly vascular, appear reddened or violaceous Hepatic: epigastric or right upper quadrant pain  Glisson’s capsule; hepatic lesions: hemorrhagic & friable & may rupture  exsanguinating intraperitoneal bleeding Hepatic: epigastric or right upper quadrant pain  Glisson’s capsule; hepatic lesions: hemorrhagic & friable & may rupture  exsanguinating intraperitoneal bleeding Central Nervous System: brain metastasis was preceded by pulmonary &/or vaginal involvement; acute focal neurologic deficits. Central Nervous System: brain metastasis was preceded by pulmonary &/or vaginal involvement; acute focal neurologic deficits.

Metastatic Disease Diagnostic evaluation: Pretreatment evaluation: Pretreatment evaluation: 1.A complete hystory & physical examination 2.Measurement of the serum hCG value 3.Hepatic, thyroid, & renal function tests 4.Determination of baseline peripheral MBC & platelet counts

Metastatic Disease Diagnostic evaluation: Metastatic work-up: Metastatic work-up: 1.A chest radiograph 2.USG / CT scan of the abdomen & pelvis 3.Measurement of CSF hCG level 4.Angiography of abdominal & pelvic organs

FIGO Staging Stage I: Gestational trophoblastic tumors strictly confined to the uterine corpus Stage I: Gestational trophoblastic tumors strictly confined to the uterine corpus Stage II: Gestational trophoblastic tumors extending to the adnexa or to the vagina, but limited to the genital structures Stage II: Gestational trophoblastic tumors extending to the adnexa or to the vagina, but limited to the genital structures Stage III: Gestational trophoblastic tumors extending to the lungs, w/ or w/o genital tract involvement Stage III: Gestational trophoblastic tumors extending to the lungs, w/ or w/o genital tract involvement Stage IV: all other metastatic sites. Stage IV: all other metastatic sites.

FIGO (WHO) Risk Factor Scoring w/ FIGO Staging 0124 Age < 40  40 Antecedent pregnancy Hydatidifor m MoleAbortionTerm Interval months from Index Pregnancy < 4 4 – 6 7 – 12 > 12 Pretreatment hCG Milli IU/MI < > >10 5 Largest tumor size including uterus 3 – 4 cm  5 cm Site of metastases including uterus Spleenkidney GI tract Brainliver Number of metastases identified 1 – 4 5 – 8 >8 Previous failed chemotherapy Single drug 2 or more drugs

Management of Gestational Trophoblastic Disease

Figure 2: Management of Trophoblastic Neoplasia

Figure 3: Management of Trophoblastic Neoplasia

Management of Trophoblastic Disease

Subsequent pregnancies Pregnancies after Hydatidiform Mole: patients with a complete molar pregnancy are at no increased risk of obstetric complications. Pregnancies after Hydatidiform Mole: patients with a complete molar pregnancy are at no increased risk of obstetric complications. For any subsequent pregnancy, these things are recommended: For any subsequent pregnancy, these things are recommended: –A pelvic USG during the 1 st trimester –A thorough histologic review of the placenta or products of conception –An hCG measurement 6 weeks after completion of the pregnancy to exclude occult trophoblastic neoplasia

Subsequent pregnancies Pregnancies after Persistent GTN Patients w/ GTN who are treated successfully w/ chemotherapy can expect normal reproduction. Patients w/ GTN who are treated successfully w/ chemotherapy can expect normal reproduction. Frequency of congenital melformations was not increased, although chemotherapeutic agents have teratogenic & mutagenic potential. Frequency of congenital melformations was not increased, although chemotherapeutic agents have teratogenic & mutagenic potential.