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GESTATIONAL
TROPHOBLASTIC
DISEASE
GESTATIONAL TROPHOBLASTIC
DISEASE
Gestational → pregnancy
Tropho → nutrition
Blast → bud/early developmental cell
GTD → begins in the layer of cell called trophoblast
that normally surrounds an embryo.
The term gestational trophoblastic disease refers to
pregnancy-related trophoblastic proliferative
abnormalities.
INTRODUCTION
GTD:
• Abnormal growth of cells inside a women’s
uterus.
• Dont develop from cells of uterus.
• Starts in the cells that would normally develop
into placenta.
• Most GTD’s are benign, some are cancerous.
GTD
• BENIGN
• Hydatidiform mole
• MALIGNANT
• Invasive mole
• Choricocarcinoma
• Placental site trophoblastic
tumor
• Epithelioid trophoblastic
tumor
Relationship of HM. IM. CH
hydatidiform therapeutic or
mole spontaneous abortion
term pregnancy
ectopic
invasion mole choriocarcinoma.
HYDATIFORM MOLE
It is a neoplastic proliferation of the trophoblast in which
the terminal villi are transformed into vesicles filled with
clear viscid material.
BENIGN
Empty egg
↓
fertilizes by paternal X’s only
↓
46 XX (diploidy)
Fetus absent
20% → malignancy
No chemo,serum beta hCG
(-ve) f/u 1 year on OCPs.
INCOMPLETE MOLE
Normal egg
↓
Maternal & paternal X’s
↓
69XXY(triploidy)
Fetus non viable
10% → malignancy
No chemo,serum beta hCG(-ve)
f/u 1 year on OCPs.
COMPLETE MOLE
COMPLETEHYDATIDIFORM MOLE
• The entire uterus
filled with
abnormal vesicles,
no signs of fetus
PARTIAL HYDATIDIFORM
MOLE
Partial
hydatidiform
mole with
evidence of a
conceptus.
MALIGNANT
NON METASTASIS GOOD PROGNOSIS POORPROGNOSIS
↓ ↓ ↓
Uterus only pelvis/lungs brain/liver
100% cure > 95% cure 65% cure
SINGLE AGENT CHEMOTHERAPY MULTIPLE AGENT
1Y,F/U ON OCS AFER β hCG(-ve) CHEMOTHERAPY
5 Y F/U ON OCS AFTER
βhCG (-ve)
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
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
Epidemiology
• The antecedent pregnancy is :
Hydatidiform mole in about 57% of
cases.
Normal pregnancy in about 26% of
cases.
Abortion and ectopic pregnancy in
about 17% of cases.
Pathological features
Site: In the uterus 90% of
cases; 10 % of cases in the
ovaries ,vagina, vulva, lung,
liver, and brain.
Pathological features
• Macroscopically:
Uterus: It may be localized in the form of
hemorrhagic polyp or multiple hemorrhagic
,necrotic masses in the cavity.
 Some times it is present in the uterine
wall (intramural) and the cavity is empty.
Pathological features
Ovaries : May show stormal
lutein hyperplasia, and theca-
lutein cysts. And may be site of
secondaries.
Pathological features
• Microscopically:
Malignant hyperplasia of both
cytotrophoblasts,and syncytiotrophoblasts.
Extensive hemorrhage.
Absence of villi.
Destruction of the surrounding myomatrum.
Spread
• Blood : The main method of spread ,and occurs
to;
Genital : Vagina, vulva, and ovary.
Extra genital : Lung, liver, brain, and bones
especially skull and spine.
The lung is the commonest site for secondaries
and haemoptysis may be the presenting
symptom.
Causes of death
• Vaginal bleeding.
• Haemoptysis.
• Intraperitoneal hemorrhage.
• Peritonitis.
• Metastasis to the vaital organs e.g,brain.
• Pulmonary complications.
RISK FACTORS
i) Women age being under 20 years ,above 35
years of age.
ii) Previous GRD
iii) Being asia/ asian ethinicity
iv) Abo blood groups of parents appear to be a
factor-choriocarcinoma
v) Women with blood group A is higher risk
than o
• Persistent GTD should be
considered in any woman
developing:
acute respiratory or neurological
symptoms after any pregnancy.
CLINICAL FEATURES
Clinical features
The clinical classification of gestational
trophoblastic disease:
I. Non-metastatic.
II. Metastatic:
A. Low risk: All patient of documented
metastatic disease who do not have “high-
risk factors”.
B.High risk:
1. B-hCG level higher than
100.000miu/ml.
2. Associated pregnancy episode
more than 4 months before the
diagnosis.
ENLARGED UTERUS
DIAGNOSIS
i) Vomiting too much( hyperemesis)
ii) Vaginal bleeding
iii) Enlarged uterus before expected dates
iv) Hypertension
v) ↑ serum βhCG
vi) Pelvic discomfort
vii) Blood tests
viii)Ultrasound
ix) Proteinuria(2+)
PERSISTENT TROPOBLASTIC
DISEASE
• Gtd that is not cured by initial surgery.
• Mole grown from the surface layer of uterus
into the muscular layer below(myometrium)
• Can spread withi n the body like a malignant
cancer
• Treatment → chemotherapy
Treatment
• Prophylaxis: After care of vesicular
mole;
 D&C after one week of the
evacuation.
 Monitored for the signs and symptoms of
trophoblastic neoplassmic by:.
I. serial hCG.
II. Diagnostic D&C is done if :
 The hCG levels remains high.
 The hCG levels rises after gets negative.
 Uterine sub involution.
 Persistence of theca lutein cysts in the
ovaries.
 Every case of secondary postpartum
haemorrhage.
 Every case of post abortive bleeding.
Active treatment
I. Non metastatic GTD:
o Methotrexate (antimetabolite) +folinic
acid.
o The cytotoxic therapy is controlled by
doing CBC,platelet count and LFT.
o After the the hCG level gets normal
;stop the therapy and follow-up by
weekly estimation of hCG levels.
Active treatment
• Women scoring: Non metastatic
GTD,and(low risk) GTD receive
intramuscular methotrexate on
alternate days, followed by six rest
days, with each course consisting of
four injections
Activetreatment
o Physical examination, chest x-ray,
and LFT.
o Total abdominal hysterectomy ,if the
patient does not desire to maintain
child-bearing, in the middle of the
first treatment course .
II.Low metastatic GTD:
o Methotraxate , or Actinomycin D
,if there is resistance ,change to
triple chemotherapy.
III.High risk metastatic GTD :
o Triple chemotherapy :
Methotraxate,
Actinomycin D, and
Cytoxan.
Follow-up
• After successful therapy ,the hCG levels
are obtained :
every 2weeks for 3 months,
 every month for 3months,
every 2months for 6 months then every
sixes months indefinitely.
Follow-up
• If at any time hCG levels rises, repeat
the evaluation , staging ,and
chemotherapy.
• Physical examination, and chest x-ray
follow-up at 6 weeks, then every
3months for one year, then every 6
months for one year.
Future pregnancy
• If a further molar pregnancy does occur,
in 68–80% of cases it will be of the
same histological type
• Women who undergo chemotherapy
are advised not to conceive for one
year after completion of treatment
INVASIVE MOLE
• Hydatidiform mole : grown into →muscular layer
of uterus .
• Develop from both complete (common)& partialmoles.
• Develop in a little less than 1 out of 5 women who had a
complete mole removed.
• Risk:Women> 40 years ,has had GTD in the past.
• Sometimes go away on their own,bt most often more treatment
is needed.
• A tumor/mole that grows completely through the wall of uterus
may result in bleeding into abdominal/pelvic cavity;this can be
life threatening.
CHORIOCARCINOMA
• Malignant form of GTD.
• Develops from: complete(common)&partial moles,
normal pregnancy, miscarriage.
• Rarely can develop that are not related to
pregnancy(areas other than uterus)
• Develop in ovaries ,testicles, chest or abdomen.
• These cases :it is mixed with other types of cancer
→mixed germ cell tumor.
PLACENTAL SITE
TROPHOBLASTIC TUMOR
• Very rare form of GTD
• Develops: placenta attaches the lining of uterus.
• Develops after:normal pregnancy/abortion but may
develop after a complete/partial mole.
• Most of them don’t spread to other parts of body.
• Tendency to grow(invade) the muscular layer of uterus.
• Insensitive to chemo drugs,surgery is aimed at completely
removing the disease.
TREATMENT
i)Evacuation of pregnancy : relief of symptoms
prevent complication
Suction curettage is prefered method of evacuation.
ii) Hysterectomy : if no other pregnancy is wished
by the patient.
iii)Chemotherapy drugs : methotrexate (IV) systemic.
iv) Advised not to get pregnant for 1 year after
completion of treatment.
MOLAR PREGNANCY
QUESTIONS
• History
• Exam
• Sonography
• Pre-operative working
• Histology benign
• Histology malignancy
DIAGNOSIS,MAGNT:
• Bleeding ,nausea& vomiting
→vesicles
• Fundus> before date
→no Fetal heart tone
• Snowstorm fetus absent
→honey coomb,fetus present
• hCG tilter serum,chest x ray
→suction empty the uterus
• Complete &incomplete H.moles
→hCG tilter
• Good&poor prognosis
→single& multiplechemotherapy
PROGNOSIS & STAGING
• Women with a hydatidiform mole have an
excellent prognosis.
• Choriocarcinoma →→ highly malignant tumor life
threatening.
Patient compliants ????
Vaginal bleeding…passage of
grapes(villi ie vesicles)
• Hyperemesis
• No fetal sounds(tone)
• Uterus extends to her
umbilicus before
dates(20wks)
• proteinuria,(2+)
• Hypertension(140/90)
GTD Types, Risks, and Treatment</b

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GTD Types, Risks, and Treatment</b

  • 2. GESTATIONAL TROPHOBLASTIC DISEASE Gestational → pregnancy Tropho → nutrition Blast → bud/early developmental cell GTD → begins in the layer of cell called trophoblast that normally surrounds an embryo. The term gestational trophoblastic disease refers to pregnancy-related trophoblastic proliferative abnormalities.
  • 3. INTRODUCTION GTD: • Abnormal growth of cells inside a women’s uterus. • Dont develop from cells of uterus. • Starts in the cells that would normally develop into placenta. • Most GTD’s are benign, some are cancerous.
  • 4. GTD • BENIGN • Hydatidiform mole • MALIGNANT • Invasive mole • Choricocarcinoma • Placental site trophoblastic tumor • Epithelioid trophoblastic tumor
  • 5. Relationship of HM. IM. CH hydatidiform therapeutic or mole spontaneous abortion term pregnancy ectopic invasion mole choriocarcinoma.
  • 6. HYDATIFORM MOLE It is a neoplastic proliferation of the trophoblast in which the terminal villi are transformed into vesicles filled with clear viscid material.
  • 7. BENIGN Empty egg ↓ fertilizes by paternal X’s only ↓ 46 XX (diploidy) Fetus absent 20% → malignancy No chemo,serum beta hCG (-ve) f/u 1 year on OCPs. INCOMPLETE MOLE Normal egg ↓ Maternal & paternal X’s ↓ 69XXY(triploidy) Fetus non viable 10% → malignancy No chemo,serum beta hCG(-ve) f/u 1 year on OCPs. COMPLETE MOLE
  • 8. COMPLETEHYDATIDIFORM MOLE • The entire uterus filled with abnormal vesicles, no signs of fetus
  • 10. MALIGNANT NON METASTASIS GOOD PROGNOSIS POORPROGNOSIS ↓ ↓ ↓ Uterus only pelvis/lungs brain/liver 100% cure > 95% cure 65% cure SINGLE AGENT CHEMOTHERAPY MULTIPLE AGENT 1Y,F/U ON OCS AFER β hCG(-ve) CHEMOTHERAPY 5 Y F/U ON OCS AFTER βhCG (-ve)
  • 11. 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
  • 12. 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
  • 13. Epidemiology • The antecedent pregnancy is : Hydatidiform mole in about 57% of cases. Normal pregnancy in about 26% of cases. Abortion and ectopic pregnancy in about 17% of cases.
  • 14. Pathological features Site: In the uterus 90% of cases; 10 % of cases in the ovaries ,vagina, vulva, lung, liver, and brain.
  • 15. Pathological features • Macroscopically: Uterus: It may be localized in the form of hemorrhagic polyp or multiple hemorrhagic ,necrotic masses in the cavity.  Some times it is present in the uterine wall (intramural) and the cavity is empty.
  • 16. Pathological features Ovaries : May show stormal lutein hyperplasia, and theca- lutein cysts. And may be site of secondaries.
  • 17. Pathological features • Microscopically: Malignant hyperplasia of both cytotrophoblasts,and syncytiotrophoblasts. Extensive hemorrhage. Absence of villi. Destruction of the surrounding myomatrum.
  • 18. Spread • Blood : The main method of spread ,and occurs to; Genital : Vagina, vulva, and ovary. Extra genital : Lung, liver, brain, and bones especially skull and spine. The lung is the commonest site for secondaries and haemoptysis may be the presenting symptom.
  • 19. Causes of death • Vaginal bleeding. • Haemoptysis. • Intraperitoneal hemorrhage. • Peritonitis. • Metastasis to the vaital organs e.g,brain. • Pulmonary complications.
  • 20. RISK FACTORS i) Women age being under 20 years ,above 35 years of age. ii) Previous GRD iii) Being asia/ asian ethinicity iv) Abo blood groups of parents appear to be a factor-choriocarcinoma v) Women with blood group A is higher risk than o
  • 21. • Persistent GTD should be considered in any woman developing: acute respiratory or neurological symptoms after any pregnancy. CLINICAL FEATURES
  • 22. Clinical features The clinical classification of gestational trophoblastic disease: I. Non-metastatic. II. Metastatic: A. Low risk: All patient of documented metastatic disease who do not have “high- risk factors”.
  • 23. B.High risk: 1. B-hCG level higher than 100.000miu/ml. 2. Associated pregnancy episode more than 4 months before the diagnosis.
  • 25. DIAGNOSIS i) Vomiting too much( hyperemesis) ii) Vaginal bleeding iii) Enlarged uterus before expected dates iv) Hypertension v) ↑ serum βhCG vi) Pelvic discomfort vii) Blood tests viii)Ultrasound ix) Proteinuria(2+)
  • 26. PERSISTENT TROPOBLASTIC DISEASE • Gtd that is not cured by initial surgery. • Mole grown from the surface layer of uterus into the muscular layer below(myometrium) • Can spread withi n the body like a malignant cancer • Treatment → chemotherapy
  • 27. Treatment • Prophylaxis: After care of vesicular mole;  D&C after one week of the evacuation.  Monitored for the signs and symptoms of trophoblastic neoplassmic by:. I. serial hCG.
  • 28. II. Diagnostic D&C is done if :  The hCG levels remains high.  The hCG levels rises after gets negative.  Uterine sub involution.  Persistence of theca lutein cysts in the ovaries.  Every case of secondary postpartum haemorrhage.  Every case of post abortive bleeding.
  • 29. Active treatment I. Non metastatic GTD: o Methotrexate (antimetabolite) +folinic acid. o The cytotoxic therapy is controlled by doing CBC,platelet count and LFT. o After the the hCG level gets normal ;stop the therapy and follow-up by weekly estimation of hCG levels.
  • 30. Active treatment • Women scoring: Non metastatic GTD,and(low risk) GTD receive intramuscular methotrexate on alternate days, followed by six rest days, with each course consisting of four injections
  • 31. Activetreatment o Physical examination, chest x-ray, and LFT. o Total abdominal hysterectomy ,if the patient does not desire to maintain child-bearing, in the middle of the first treatment course .
  • 32. II.Low metastatic GTD: o Methotraxate , or Actinomycin D ,if there is resistance ,change to triple chemotherapy.
  • 33. III.High risk metastatic GTD : o Triple chemotherapy : Methotraxate, Actinomycin D, and Cytoxan.
  • 34. Follow-up • After successful therapy ,the hCG levels are obtained : every 2weeks for 3 months,  every month for 3months, every 2months for 6 months then every sixes months indefinitely.
  • 35. Follow-up • If at any time hCG levels rises, repeat the evaluation , staging ,and chemotherapy. • Physical examination, and chest x-ray follow-up at 6 weeks, then every 3months for one year, then every 6 months for one year.
  • 36. Future pregnancy • If a further molar pregnancy does occur, in 68–80% of cases it will be of the same histological type
  • 37. • Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment
  • 38. INVASIVE MOLE • Hydatidiform mole : grown into →muscular layer of uterus . • Develop from both complete (common)& partialmoles. • Develop in a little less than 1 out of 5 women who had a complete mole removed. • Risk:Women> 40 years ,has had GTD in the past. • Sometimes go away on their own,bt most often more treatment is needed. • A tumor/mole that grows completely through the wall of uterus may result in bleeding into abdominal/pelvic cavity;this can be life threatening.
  • 39. CHORIOCARCINOMA • Malignant form of GTD. • Develops from: complete(common)&partial moles, normal pregnancy, miscarriage. • Rarely can develop that are not related to pregnancy(areas other than uterus) • Develop in ovaries ,testicles, chest or abdomen. • These cases :it is mixed with other types of cancer →mixed germ cell tumor.
  • 40. PLACENTAL SITE TROPHOBLASTIC TUMOR • Very rare form of GTD • Develops: placenta attaches the lining of uterus. • Develops after:normal pregnancy/abortion but may develop after a complete/partial mole. • Most of them don’t spread to other parts of body. • Tendency to grow(invade) the muscular layer of uterus. • Insensitive to chemo drugs,surgery is aimed at completely removing the disease.
  • 41. TREATMENT i)Evacuation of pregnancy : relief of symptoms prevent complication Suction curettage is prefered method of evacuation. ii) Hysterectomy : if no other pregnancy is wished by the patient. iii)Chemotherapy drugs : methotrexate (IV) systemic. iv) Advised not to get pregnant for 1 year after completion of treatment.
  • 42. MOLAR PREGNANCY QUESTIONS • History • Exam • Sonography • Pre-operative working • Histology benign • Histology malignancy DIAGNOSIS,MAGNT: • Bleeding ,nausea& vomiting →vesicles • Fundus> before date →no Fetal heart tone • Snowstorm fetus absent →honey coomb,fetus present • hCG tilter serum,chest x ray →suction empty the uterus • Complete &incomplete H.moles →hCG tilter • Good&poor prognosis →single& multiplechemotherapy
  • 43. PROGNOSIS & STAGING • Women with a hydatidiform mole have an excellent prognosis. • Choriocarcinoma →→ highly malignant tumor life threatening.
  • 44. Patient compliants ???? Vaginal bleeding…passage of grapes(villi ie vesicles) • Hyperemesis • No fetal sounds(tone) • Uterus extends to her umbilicus before dates(20wks) • proteinuria,(2+) • Hypertension(140/90)