Gestational Gestational Trophoblastic DiseaseTrophoblastic Disease

Definitions Definitions • Gestational Trophoblastic Neoplasia Gestational Trophoblastic Neoplasia

(GTN) (GTN) chorioadenoma destruens, chorioadenoma destruens, metastasizing mole, choriocarcinoma.metastasizing mole, choriocarcinoma.– Non-metastatic gestational trophoblastic Non-metastatic gestational trophoblastic

neoplasia: process is confined to the uterusneoplasia: process is confined to the uterus– Metastatic gestational trophoblastic Metastatic gestational trophoblastic

neoplasia: metastases are demonstrated in neoplasia: metastases are demonstrated in the lung/vagina and/or in brain, liver, the lung/vagina and/or in brain, liver, kidney or elsewherekidney or elsewhere

• Hydatidiform mole: Gestational Hydatidiform mole: Gestational Trophoblastic Disease (GTD).Trophoblastic Disease (GTD).

Classification Classification

• Hydatidiform moleHydatidiform mole– Complete moleComplete mole– Partial molePartial mole

• Invasive moleInvasive mole

• Placental-site trophoblastic tumorPlacental-site trophoblastic tumor

• Choriocarcinoma Choriocarcinoma

Complete Hydatidiform MoleComplete Hydatidiform Mole

• PathologyPathology– Identifiable embryonic/fetal tissue Identifiable embryonic/fetal tissue ΘΘ– Chorionic villi: generalized hydatidiform Chorionic villi: generalized hydatidiform

swelling, diffuse trophoblastic swelling, diffuse trophoblastic hyperplasiahyperplasia

• Chromosomes: 46XX karyotype, Chromosomes: 46XX karyotype, molar chromosomes molar chromosomes paternal origin paternal origin

Partial Hydatidiform MolePartial Hydatidiform Mole

• Pathology:Pathology:– Chorionic villi with focal hydatidiform Chorionic villi with focal hydatidiform

swelling and cavitationswelling and cavitation– Villous scallopingVillous scalloping– Focal trophoblastic hyperplasiaFocal trophoblastic hyperplasia– Prominent stromal trophoblastic Prominent stromal trophoblastic

inclusionsinclusions– Identifiable embryonic or fetal tissueIdentifiable embryonic or fetal tissue

• Chromosomes: triploid karyotype Chromosomes: triploid karyotype (69 chromosomes)(69 chromosomes)

Clinical FeaturesClinical Features• Complete Hydatidiform MoleComplete Hydatidiform Mole

– Vaginal bleedingVaginal bleeding– Excessive uterine sizeExcessive uterine size– ToxemiaToxemia– Hyperemesis gravidarumHyperemesis gravidarum– Hyperthyroidism Hyperthyroidism – Trophoblastic embolizationTrophoblastic embolization– Theca lutein ovarian cystTheca lutein ovarian cyst

• Partial Hydatidiform Mole: signs & Partial Hydatidiform Mole: signs & symptoms of incomplete / missed symptoms of incomplete / missed abortionabortion

• USG : vesicular sonographic pattern USG : vesicular sonographic pattern “snowstorm” pattern“snowstorm” pattern

DiagnosisDiagnosis

Follow-upFollow-up• Human Chorionic GonadotropinHuman Chorionic Gonadotropin

Contraception Contraception • IUD IUD normal hCG level normal hCG level

• First choice:First choice:– Hormonal contraceptionHormonal contraception– Barrier methodsBarrier methods

Malignant Gestational Malignant Gestational Trophoblastic NeoplasiaTrophoblastic Neoplasia

• Nonmetastatic DiseaseNonmetastatic Disease

• Metastatic DiseaseMetastatic Disease

Nonmetastatic DiseaseNonmetastatic Disease

• Signs & symptoms:Signs & symptoms:– Irregular vaginal bleedingIrregular vaginal bleeding– Theca lutein cystsTheca lutein cysts– Uterine subinvolution or asymmetric Uterine subinvolution or asymmetric

enlargementenlargement– Persistently elevated serum hCG levelsPersistently elevated serum hCG levels

• Histology: anaplastic Histology: anaplastic syncytiotrophoblast & syncytiotrophoblast & cytotrophoblast w/o chorionic villous cytotrophoblast w/o chorionic villous structurestructure

Placental-site Trophoblastic Placental-site Trophoblastic TumorTumor

• Consist of: intermediate trophoblast & Consist of: intermediate trophoblast & a few syncytial elementsa few syncytial elements

• Produce small amount of hCG & Produce small amount of hCG & human placental lactogenhuman placental lactogen

• Tend to remain confined to the uterusTend to remain confined to the uterus

• Metastasizing late Metastasizing late

• Insensitive to chemtotherapyInsensitive to chemtotherapy

Metastatic DiseaseMetastatic Disease

Sites of metastatic spread:Sites of metastatic spread:

• Pulmonary: Pulmonary: – Signs: chest pain, cough, hemoptysis,d Signs: chest pain, cough, hemoptysis,d

yspnea, asymptomatic lesionyspnea, asymptomatic lesion– Radiographic patterns: an alveolar or Radiographic patterns: an alveolar or

“snowstrom” pattern; discrete, rounded “snowstrom” pattern; discrete, rounded densities; pleural effusion; an embolic densities; pleural effusion; an embolic pattern caused by pulmonary arterial pattern caused by pulmonary arterial occlusionocclusion

Metastatic DiseaseMetastatic DiseaseSites of metastatic spread:Sites of metastatic spread:• Vaginal: highly vascular, appear Vaginal: highly vascular, appear

reddened or violaceousreddened or violaceous• Hepatic: epigastric or right upper Hepatic: epigastric or right upper

quadrant pain quadrant pain Glisson’s capsule; Glisson’s capsule; hepatic lesions: hemorrhagic & friable hepatic lesions: hemorrhagic & friable & may rupture & may rupture exsanguinating exsanguinating intraperitoneal bleedingintraperitoneal bleeding

• Central Nervous System: brain Central Nervous System: brain metastasis was preceded by metastasis was preceded by pulmonary &/or vaginal involvement; pulmonary &/or vaginal involvement; acute focal neurologic deficits.acute focal neurologic deficits.

Metastatic DiseaseMetastatic Disease

Diagnostic evaluation:Diagnostic evaluation:

• Pretreatment evaluation:Pretreatment evaluation:1.1. A complete hystory & physical A complete hystory & physical

examinationexamination

2.2. Measurement of the serum hCG valueMeasurement of the serum hCG value

3.3. Hepatic, thyroid, & renal function testsHepatic, thyroid, & renal function tests

4.4. Determination of baseline peripheral Determination of baseline peripheral MBC & platelet countsMBC & platelet counts

Metastatic DiseaseMetastatic Disease

Diagnostic evaluation:Diagnostic evaluation:

• Metastatic work-up:Metastatic work-up:1.1. A chest radiographA chest radiograph

2.2. USG / CT scan of the abdomen & pelvisUSG / CT scan of the abdomen & pelvis

3.3. Measurement of CSF hCG levelMeasurement of CSF hCG level

4.4. Angiography of abdominal & pelvic Angiography of abdominal & pelvic organsorgans

FIGO StagingFIGO Staging• Stage I: Gestational trophoblastic Stage I: Gestational trophoblastic

tumors strictly confined to the uterine tumors strictly confined to the uterine corpuscorpus

• Stage II: Gestational trophoblastic Stage II: Gestational trophoblastic tumors extending to the adnexa or to tumors extending to the adnexa or to the vagina, but limited to the genital the vagina, but limited to the genital structuresstructures

• Stage III: Gestational trophoblastic Stage III: Gestational trophoblastic tumors extending to the lungs, w/ or tumors extending to the lungs, w/ or w/o genital tract involvementw/o genital tract involvement

• Stage IV: all other metastatic sites.Stage IV: all other metastatic sites.

FIGO (WHO) Risk Factor Scoring w/ FIGO FIGO (WHO) Risk Factor Scoring w/ FIGO StagingStaging

00 11 22 44

AgeAge < 40< 40 4040

Antecedent Antecedent pregnancypregnancy

HydatidiforHydatidiform m

MoleMole

AbortioAbortion n

Term Term

Interval months Interval months from Index from Index PregnancyPregnancy

< 4< 4 4 – 6 4 – 6 7 – 12 7 – 12 > 12> 12

Pretreatment hCG Pretreatment hCG Milli IU/MIMilli IU/MI

< 10< 1033 101033-10-1044 >10>1044--101055

>10>1055

Largest tumor size Largest tumor size including uterusincluding uterus

3 – 4 3 – 4 cmcm

5 cm5 cm

Site of metastases Site of metastases including uterusincluding uterus

SpleenSpleenkidneykidney

GI tractGI tract BrainBrainliverliver

Number of Number of metastases metastases identifiedidentified

1 – 4 1 – 4 5 – 8 5 – 8 >8>8

Previous failed Previous failed chemotherapychemotherapy

Single Single drugdrug

2 or 2 or more more drugsdrugs

Management of Gestational Management of Gestational Trophoblastic DiseaseTrophoblastic Disease

Figure 2: Management of Trophoblastic Figure 2: Management of Trophoblastic NeoplasiaNeoplasia

Figure 3: Management of Trophoblastic Figure 3: Management of Trophoblastic

NeoplasiaNeoplasia

Management of Trophoblastic Management of Trophoblastic Disease Disease

Subsequent pregnanciesSubsequent pregnancies•Pregnancies after Hydatidiform Mole: Pregnancies after Hydatidiform Mole: patients with a complete molar patients with a complete molar pregnancy are at no increased risk of pregnancy are at no increased risk of obstetric complications.obstetric complications.

•For any subsequent pregnancy, these For any subsequent pregnancy, these things are recommended:things are recommended:

– A pelvic USG during the 1A pelvic USG during the 1stst trimester trimester– A thorough histologic review of the A thorough histologic review of the

placenta or products of conceptionplacenta or products of conception– An hCG measurement 6 weeks after An hCG measurement 6 weeks after

completion of the pregnancy to exclude completion of the pregnancy to exclude occult trophoblastic neoplasiaoccult trophoblastic neoplasia

Subsequent pregnanciesSubsequent pregnancies

Pregnancies after Persistent GTNPregnancies after Persistent GTN

• Patients w/ GTN who are treated Patients w/ GTN who are treated successfully w/ chemotherapy can successfully w/ chemotherapy can expect normal reproduction.expect normal reproduction.

• Frequency of congenital Frequency of congenital melformations was not increased, melformations was not increased, although chemotherapeutic agents although chemotherapeutic agents have teratogenic & mutagenic have teratogenic & mutagenic potential. potential.