1. Gestational Trophoblastic Disease (GTD)
Department of Obs.& Gyn., First Hospital of Xi’an Jiaotong University
Gao Shang Feng

2. Introduction 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.

3. 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)

4. Relationship of HM. IM. CH
hydatidiform therapeutic or
mole spontaneous abortion
term pregnancy
ectopic
invasion mole choriocarcinoma.

5. 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.

6. Hydatidiform mole

7. Hydatidiform mole

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

9. It is usually benign but has malignant potentiality.
Incidence:
south east Asia is 1/
the US and Europe:1/
China:1/1238

10. Classification It is divided into two classification
complete hydatidiform mole
partial hydatidiform mole

11. complete hydatidiform mole(CHM):
the entire uterus filled with abnormal vesicles, no signs of fetus.

12. partial hydatidiform mole
partial hydatidiform mole with evidence of a conceptus.

13. Etiology
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

14. 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

15. Chromosomes 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

16. 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.

17. . 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.

18. Pathologic findings

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

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

21. 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.

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

23. Microscopic trophoblastic proliferation.‘
Microscopic
trophoblastic proliferation.
hydropic degeneration of the stroma.
absence of blood vessels or extreme scantiness of blood vessels.

24. complete hydatidiform mole
Normal
trophoblastic
partial hydatidiform mole
complete hydatidiform mole

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

26. It has eight of symptoms and physical signs.
Clinical course
It has eight of symptoms and physical signs.

27. amenorrhea
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

28. abnormally enlarged and soft uterus
in about half the cases, the uterus growth is rapid, it is larger than the dates suggest.

29. 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

30. severe and early –onset PIH (Pregnancy Induced Hypertension syndrome)
hyperthyroidism
plasma thyroxin concentration elevates
exaggerated early pregnancy symptoms
nausea, vomit etc

31. Diagnosis suspicion: 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

32. 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.

33. Ultrasonography:
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.

34. 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.

35. Differential diagnosis
abortion;
multiple pregnancy;
polyhydramnios

36. Treatment
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 infusion.it is used to decrease the size of the uterus;

37. acute pulmonary complications
tissue sent for histology: it should be routine practice with all cases of incomplete miscarriage;
acute pulmonary complications

38. hysterectomy in older multiparas hysterectomy may be indicated.
total abdominal
hysterectomy
in older multiparas
hysterectomy may
be indicated.

39. management of theca-lutein cysts
these tumors should not be excised because they regress after the trophoblastic tissue has been removed.

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

41. ㈧Follow-up examinations
follow up mode in the 2
years after discharge
on each follow-up
check, the following
should be addressed

42. abnormal vaginal bleeding, cough, hemoptysis signs of metastasis
symptom
abnormal vaginal bleeding,
cough, hemoptysis
signs of metastasis
pelvic examination
hCG evaluation
B-ultrasound
chest X-ray film

43. required for 1-2 years condom is recommended.
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.

44. 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?

45. About 80% of the cases of HM have a benign course
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 into choriocarcinoma

46. Invasion Mole

47. Introduction 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.

48. in half or more of all cases invasive mole metastasizes through the peripheral circulation to distant sites, mostly to the lung.

49. Pathologic findings
excessive trophoblastic proliferation and invasiveness
the degree of anaplasia is variable: completely benign---highly malignant

50. 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.

51. 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 .

52. 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.

53. Diagnosis 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.

54. 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

55. Prophylaxis respond well to chemotherapeutic agents
main causes of death: hemorrhage, metastasis and infection

56. Identical to that for choriocarcinoma
Treatment:
Identical to that for choriocarcinoma

57. Choriocarcinoma
It is highly malignant GTT
It may follow HM, invasion mole, abortion, normal pregnancy, ectopic pregnancy.

58. 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 blood:.it is filled metastatic nodules

59. ulcerating surface opens into the endometrial cavity (rarely embedded in myometrium)

60. 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

61. 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.

62. metastatic symptoms
pulmonary lesions
cerebral lesions
metastatic nodule in the vagina, vulva or cervix ,it is bluish nodule filled dark red blood.

63. Diagnosis
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.

64. hCG change HM:84-100 days Artificial abortion:30 days
Spontaneous abortion:19 days
Normal delivery:12 days
Ectopic pregnancy:8-9 days

65. Staging 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.

66. Treatment
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.

67. Chemotherapy most often used drugs methotrexate (MTX)
actinomycin D (Act-D)
5-fluorouracil (5-Fu)
vincristine (VCR)
cyclophosphamide (CTX)
chlo-ranbucil, etc

68. principles
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

69. Standard for discharge
three consecutive weekly assays for hCG are negative
two more courses for consolidation
all symptoms and signs disappear

70. Operation
unresponsive or drug fails to reach the tumor;
if the tumor can be eradicated by drug therapy, esp.in young women, there is no reason to remove the uterus;
the ovaries need not be removed.

71. 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
hCG

72. Ask question :
What are the basic histologic and pathologic differences between invasive mole and choriocarcinoma?