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Gestational Trophoblastic Disease (GTD). Department of Obs. & Gyn., First Hospital of Xi ’ an Jiaotong University Gao Shang Feng. Introduction. What is GTD ? It is a rare kind of disease in which abnormal trophoblastic proliferation occurs.

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gestational trophoblastic disease gtd

Gestational Trophoblastic Disease (GTD)

Department of Obs.& Gyn., First Hospital of Xi’an Jiaotong University

Gao Shang Feng


What is GTD ?

  • It is a rare kind of disease in which abnormal trophoblastic proliferation occurs.
  • It is too among the rare human malignancies that can be cured even in the presence of widespread metastases.
Which does it include?
  • It includes a spectrum of interrelated tumors, including
  • hydatidiform mole (HM)
  • invasive mole (IM)
  • Choriocarcinoma (CH)
  • Placental-site trophoblastic tumor (PSTT, borderline, very rare)
relationship of hm im ch
Relationship of HM. IM. CH

hydatidiform therapeutic or

molespontaneous abortion

term pregnancy


invasion mole choriocarcinoma.

What is GTT (Gestational trophoblastic tumor)?

GTT is all GTD except hydatidiform mole.

They has its unique pathologic characteristics and biological behavior.

Even the most malignant case can be cured by chemotherapy.

hydatidiform mole8
Hydatidiform mole

It is a neoplastic proliferation of the trophoblast in which the terminal villi are transformed into vesicles filled with clear viscid material.

It is usually benign but has malignant potentiality.
  • Incidence:
  • south east Asia is 1/500-600
  • the US and Europe:1/500-2000
  • China:1/1238

It is divided into two classification

  • complete hydatidiform mole
  • partial hydatidiform mole
complete hydatidiform mole chm
complete hydatidiform mole(CHM):
  • the entire uterus filled with abnormal vesicles, no signs of fetus.
partial hydatidiform mole
partial hydatidiform mole
  • partial hydatidiform mole with evidence of a conceptus.

Though it is not known a number of associated factors have been noted:

  • the absence of fetal circulation;
  • dietary protein deficiency
  • viral infection;
  • age:>45 years women are 10 times more likely to develop HM than those younger
abnormal fertilization process:
  • the fertilization of a normal ovum with a duplicated haploid sperm:46XX
  • the fertilization of an empty egg by two sperms(dispermy):46XY

complete hydatidiform moles

  • Cytogenetic studies have demonstrated that complete hydatidiform moles usually have a 46xx karyotype, and the molar chromosomes are entirely of paternal origin.
  • Complete moles appear to arise from an ovum that has been fertilized by a haploid sperm, which then duplicates its own chromosomes, and the ovum nucleus may be either absent or inactivated
Although most complete moles have a 46xx chromosomal pattern, approximately 10% have a 46xy karyotype.
  • Chromosomes in a 46xy complete mole also appear to be entirely of paternal origin, but in this circumstance, an apparently empty egg is fertilized by two sperm.

partial hydatidiform mole

  • partial moles usually have a triploid karyotype (69 chromosomes ), with the extra haploid set of chromosomes derived from the father.
  • When a fetus is present in conjunction with a partial mole, it usually exhibits the stigmata of triploidy, including growth retardation and multiple congenital malformations.
complete hydatidiform mole
complete hydatidiform mole


Complete moles lack identifiable embryonic or fetal tissues, and the chorionic villi exhibit generalized hydatidiform swelling and diffuse trophoblastic hyperplasia.


we see a mass of vesicles, vary in size, grape-like with stems, blood and clot filling the inter-vesicle space

partial hydatidiform mole21
partial hydatidiform mole

It are characterized by the following pathologic features :

  • Chorionic villi if varying size with focal hydatidiform swelling and cavitation.
  • It contain identifiable embryonic or fetal tissues.

we see a mass of vesicles, vary in size, grape-like and identifiable embryonic or fetal tissues.


  • trophoblastic proliferation.
  • hydropic degeneration of the stroma.
  • absence of blood vessels or extreme scantiness of blood vessels.



partial hydatidiform mole

complete hydatidiform mole

trophoblastic proliferation is considered the most important single criteria.
  • Ovaries respond to hCG stimulation ,30-50% theca-lutein cysts develop, bilateral
clinical course
Clinical course

It has eight of symptoms and physical signs.


because it is a pregnancy.

  • vaginal bleeding

after a period of amenorrhea (average 12 weeks) may continue intermittently for several weeks---profuse bleeding---anemia and infection.

  • abdominal cramps
abnormally enlarged and soft uterus

in about half the cases, the uterus growth is rapid, it is larger than the dates suggest.

ovarian cyst torsion

when we do pelvic examination adnexal masses may be found. it is theca lutein cyst in about one third of the cases

severe and early –onset PIH (Pregnancy Induced Hypertension syndrome)
  • hyperthyroidism

plasma thyroxin concentration elevates

  • exaggerated early pregnancy symptoms

nausea, vomit etc



  • abnormal bleeding after amenorrhea
  • inappropriately enlarged uterus;
  • absence of fetal heart sounds or could not feel fetal parts by palpation between 16-20th week
  • hyperemesis gravidarum
  • bilateral ovarian cysts
serum hCG monitor

an unusually high titer of chorionic gonadotropin, especially after the one-hundredth day of pregnancy, help to confirm the diagnosis of HM.


It is a reliable and sensitive technique for the diagnosis of complete molar pregnancy. Because the chorionic villi exhibit diffuse hydatidiform swelling. Complete moles produce a characteristic vesicular sonographic pattern, usually referred to as a “snowstorm” pattern.

Ultrasonography may also contribute to the diagnosis of partial molar pregnancy by demonstrating focal cystic spaces in the placental tissues and an increase in the transverse diameter of the gestational sac.
differential diagnosis
Differential diagnosis
  • abortion;
  • multiple pregnancy;
  • polyhydramnios
  • the uterus should be evacuated as soon as possible after the diagnosis is made.(by suction curettage)
  • suction;
  • oxytocin administration:we can use blood transfusion or/and fluid is used to decrease the size of the uterus;
tissue sent for histology: it should be routine practice with all cases of incomplete miscarriage;
  • acute pulmonary complications
total abdominal


in older multiparas

hysterectomy may

be indicated.

management of theca-lutein cysts

these tumors should not be excised because they regress after the trophoblastic tissue has been removed.


HM don’t need usually chemotherapy because HM is benign disease.

follow up examinations
㈧Follow-up examinations
  • follow up mode in the 2

years after discharge

  • on each follow-up

check, the following

should be addressed


abnormal vaginal bleeding,

cough, hemoptysis

signs of metastasis

  • pelvic examination
  • hCG evaluation
  • B-ultrasound
  • chest X-ray film
contraceptive method

required for 1-2 years

  • condom is recommended.
  • IUD (intrauterine device)and pills are contraindicated for their potentiality of causing abnormal vaginal bleeding.
ask question
Ask question
  • What is the etiology of GTD?
  • What is the classification of HM?
  • What is the main pathologic changes of HM?
  • What is the clinical course of HM?
  • How Follow-up examinations is we?
About 80% of the cases of HM have a benign course. one-half of patients become pregnant subsequently. about 16% of HM become invasion moles and some 2.5% progress intochoriocarcinoma
  • Invasion Mole arises from HM
  • it has malignant potentialities, invades the myometrium and penetrates the uterine wall, extends into the broad ligament or peritoneal cavity.
in half or more of all cases invasive mole metastasizes through the peripheral circulation to distant sites, mostly to the lung.
pathologic findings49
Pathologic findings
  • excessive trophoblastic proliferation and invasiveness
  • the degree of anaplasia is variable: completely benign---highly malignant
differentiation between invasive mole and choriocarcinoma lies in whether the villous pattern is preserved:
  • if we see villi, it must be invasion mole;
  • if we can’t see villi, it is choriocarcinoma.
clinical course51
Clinical course
  • Symptoms caused by primary lesions

vaginal bleeding

pelvic examination reveals delayed involution of the uterus, persisting cyst .

abdominal pain

intra-abdominal hemorrhage, penetration of the uterus .

Metastatic symptoms
    • cough, hemoptysis---positive X-ray signs
    • profuse vaginal bleeding---vaginal or cervical metastasis, we can see bluish nodule in vaginal
    • headache, nausea, vomit, paralysis or coma—it is caused by cerebral lesion.
  • history and clinical manifestation
  • hCG assay:
  • diagnosis suspected if hCG titers persist to be high 12 weeks after evacuation of a HM, or once regress to normal range but rise rapidly.
possible reasons : retained HM
  • pregnancy
  • huge theca-lutein cyst persist
  • when we remove these reasons we can diagnosis invasive mole
  • other measurement
  • B-ultrasound
  • X-ray
  • respond well to chemotherapeutic agents
  • main causes of death: hemorrhage, metastasis and infection

Identical to that for choriocarcinoma

  • It is highly malignant GTT
  • It may follow HM, invasion mole, abortion, normal pregnancy, ectopic pregnancy.
pathologic findings58
Pathologic findings
  • Gross inspection
    • irregular or circumscribed hemorrhagic growth in the uterine wall
    • ulcerating surface opens into the endometrial cavity (rarely embedded in myometrium)
    • penetration into broad ligament or the peritoneal cavity
    • dark red is filled metastatic nodules
Histologic findings
    • we see masses of anaplastic trophblastic cells in microscopy;
    • invasion into the uterine wall, destroying vessels, muscle tissue
    • prominent necrosis and hemorrhage
    • villi can not be recognized
    • spread through circulation
clinical manifestations
Clinical Manifestations
  • irregular bleeding after preceding gestation;
  • malignant tumor cells enter the circulation through the open blood vessels and are transported to lungs, brain or to other distant sites.
metastatic symptoms
  • pulmonary lesions
  • cerebral lesions
  • metastatic nodule in the vagina, vulva or cervix ,it is bluish nodule filled dark red blood.
  • Diagnosis must be suspected as a possible reason for continued (irregular) bleeding after any form of pregnancy.
  • we assay hCG , the time of hCG change into normal is different in various diseases.
hcg change
hCG change
  • HM:84-100 days
  • Artificial abortion:30 days
  • Spontaneous abortion:19 days
  • Normal delivery:12 days
  • Ectopic pregnancy:8-9 days

International staging of WHO may be summarized as follows:

Ⅰ: lesion localized in uterus, no metastasis;

Ⅱ: lesion extends beyond uterus, but still confined to internal genitalias;

Ⅲ: pulmonary lesion

Ⅳ: metastasis to other distant sites.

  • highly sensitive to chemotherapy, which is invariably the treatment choice.
  • surgery has little place (because of the high vascularity and the effectiveness of chemotherapy). it is indicated for tumor resistant to chemotherapy and single metastases persisting despite chemotherapy.

most often used drugs

  • methotrexate (MTX)
  • actinomycin D (Act-D)
  • 5-fluorouracil (5-Fu)
  • vincristine (VCR)
  • cyclophosphamide (CTX)
  • chlo-ranbucil, etc
  • low-risk patients are usually treated with a single agent
  • medium-risk patients are usually treated with EMA-CO regimen with 80-90% survival rate. (Etoposide, Methotrexate,Actinomycin,Cyclophosphamide,Vincristin)
  • toxic reaction: marrow depression ;
  • gastrointestinal ulceration;
  • change in liver and renal function
standard for discharge
Standard for discharge
  • three consecutive weekly assays for hCG are negative
  • two more courses for consolidation
  • all symptoms and signs disappear
  • unresponsive or drug fails to reach the tumor;
  • if the tumor can be eradicated by drug therapy, young women, there is no reason to remove the uterus;
  • the ovaries need not be removed.
follow up examinations71
Follow-up examinations
  • at 1-month interval for 1 year: at 3-month interval for 2 years
  • at 1-year interval for 3 years
  • at 2-year interval afterwards. pelvic examination

chest X-ray film


ask question72
Ask question :
  • What are the basic histologic and pathologic differences between invasive mole and choriocarcinoma?