Gestational trophoblastic
disease (GTD)
introduction
Definition:gestational trophoblastic disease(GTD)is a group
of disease originated from placental villose trophoblastic
cells,including hydatidiform mole,invasive mole,choriocarci-
noma and a kind of less common trophoblastic cell tumor in
placenta
Relations among the diseases:certain relations exist
among the diseases,benign mole is considered to be abnormal
formation of placenta accompanied by the special abnormal
hereditary ; invasive mole results from benign mole; chorio-
carcinoma and the trophoblastic cell tumor in placenta may
result from benign mole,term pregnancy,abortion and ectopic
pregnancy.invasive mole,choriocarcinoma and trophoblastic cell
tumor in placenta are also called gestational trophoblastic tumor
(GTT).
Hydatidiform Mole
[Definition]:hydatidiform mole means that after pregnancy
the placental trophoblastic cells proliferate abnormally,there
is stromal edema,and forms vesicula which is like grape on
its apparence.
[Classification]:hydatidiform mole is divided into
complete and incomplete type among which the majority is
complete type,and its malignant change rate is relitively
high;less mole is incomplete type and rarely has malignant
change,the cause and the clinical course of the two types
mole are different.
[Etiology]:the etiology is not clear
I.Etiology of complete hydatidiform mole
Epidemiology,the morbidity of hydatidiform mole is different in
different area.
High risk factors:
1.nourishing status,social economy
2.age:over 35 and 40 years old;below 20 years old.
3.hydatidiform mole history:if a patient has the history of 1 or 2
times hydatidiform mole,then the morbidity of the hydatidiform
mole when pregnant again is 1% and 15~20% respectively.
Genetic factors:
1.enucleate egg fertilization:chromosome karyotype of complete
mole is diploid,90% is 46XX,10% is 46XY
II,Etiology of incomplete hydatidiform mole
the morbidity of incomplete mole is much lower than that of the
complete type,and it is not associated with age.
1.Genetic factors,chromosome karyotype of 90% incomplete mole
is triploid,which is formed by the fertilization of a monoploid egg
and two monoploid sperm,or by the fertilization of a monoploid
egg(sperm) and a meiotic deficiency sperm(egg).
The most common chromosome karyotype is 69XXY,and then is
69XXX or 69XYY.
[Pathology]
The comparison of morphology and karyotype of complete and
incomplete mole
Complete mole incomplete mole
Embryotic or fetal tissue - +
Villus stromal edema diffuseed localized
Trophoblastic hyperplasia diffuseed localized
Villus outline regular irregular
Villus stromal blood vessel - +
Karyotype diploid triploid or tetraploid
[Clinical manifestation]:
I.complete mole:usually complete mole has the following typical
symptoms
i.vaginal bleeding after amenorrhea:the most common
symptom,often occurs after 8~12 week of gestation
(i).clinical manifestation（ 8~12 week after amenorrhea）
(ii).cause of bleeding
(iii).complication
ii.uterus is abnormally enlarged and become soft
(i).cause:over 1/2 patients;1/3 patients;a few patients
iii.theca lutein ovarian cyst:large amount HCG stimulate internal
theca cells……
(i).symptom
(ii).disappearance:within 2~4 month after operation
iv.gestational vomitting and PIH
(i).gestational vomitting
(ii).PIH:when uterus is abnormally enlarged and HCG↑↑
v.hyperthyroidism:
(i)7% is complicated with slight hyperthyroidism
(ii)cause:HCG ↑↑,T3T4 ↑↑
vi.abdominal pain:generally not severe,often before bleeding.
occurrence of acute abdomen
II.partial hydatidiform mole:may have the major symptoms
of complete mole but it is slightly manifested.no luteinizing
cyst,the histologic examination of curettage sample may
confirm the diagnosis
[Prognosis],complete mole has the latent risk of local invasion or
telemetastasis,research proved that after emptying the mole,the rate
of uterine invasion or telemetastasis is 15% and 4% respectively.if the
patient has the following high-risk factors,the risk of local invasion
or telemetastasis may increase 10 times.
The high-risk factors includes:
(i).β-HCG>100000IU/L;
(ii).uterine size is obviously larger than that with the same
gestational time.
(iii).the luteinizing cyst is >6cm.
(iv),If >40 years old,the risk of invasion and metastasis may be
37%,If >50 years old,the risk of invasion and metastasis may be
56%.
(v).repeated mole:the morbidity of invasion and metastasis increase
3~4 times.
HCG resolution law:It is very important for predicting the
prognosis,Normally after emptying the mole,the β-HCG
regression curve is steadly decreased,and reach normal
level within 9~14 weeks
persistent mole:
if the HCG is still positive 3 months after the mole is
completely emptied,called persistent mole
[Diagnosis],
according to the irregular vaginal bleeding after amenorrhea,soft
and abnormally enlarged uterus,no fetal body can be palpated in 5
gestational month size uterus,no fetal movement and no fetal heart
beat can be heard,the hydatidiform mole should be suspected, the
hyperemesis gravidarum,preeclampsia befor 28 weeks gestation
and bilateral ovarian cyst all support the diagnosis.if the vesicular
tissue is found in the vaginal expelling blood,the diagnosis is
basically confirmed,if there is suspicion on diagnosis,the following
accessory examination should be made
i.HCG measurement:in mole the HCG is over 100kIU/L,and
often over 1000kIU/L
ii.ultrasound examination:an important accessory diagnosing
method
(i).B-ultrasound:in normal pregnancy gestational sac can be
seen between 4-5 gestational week,and the heart-tube
beat between 6-7 week;in hydatidiform mole
(ii).detecting the fetal heart beat by ultrasound Doppler:in
normal pregnancy the fetal heart beat can be heard in the
6th week of gestation and after 12 weeks the positive rate
is 100%;in hydatidiform mole
[Differential diagnosis]
(i).abortion
(ii).twin pregnancy
(iii).polyhydramnios
[Management]
i.emptying uterine cavity:once the diagnosis is confirmed
the uterine cavity should be emptied as soon as possible
i).uterine aspiration and curettage
ii).application of oxytocin during operation
iii).indication of the second curettage(>12week)
ii.hysterectomy
i).over 40 years old with high-risk factors
ii).uterine size is over 14 gestational weeks
iii.management of luteinizing cyst
iv.preventive chemotherapy:the malignant change rate is 14.5%
in our country,if the patient has the following condition,the
chemotherapy should be given
(i).over 40 years old
(ii).the β-HCG is over 100kIU/L before emptying mole
(iii).the HCG regresion curve is not progressively declined
(iv).uterus is obviously larger than the size of the amenorrhea
(v).luteinizing cyst is >6cm
(vi).there is still over hyperplasia of trophoblastic cells in the
second curettage
(vii).no follow up conditions
[follow up]:regular follow up can find persistent or metastatic
trophoblastic cells tumor
(i).HCG measurement:after emptying the mole,the HCG
should be mesured once a week until it is to the normal
level
(ii).follow up:once a week in the first 3 monthes,then once 2
weeks in the next 3 monthes and once a month for half
a year,once half a year in the second year,and totally follow
up for 2 year
(iii).contents of follow up:HCG,abnormal vaginal bleeding,
cough,hemoptysis,metastatic symptoms,gynecologic exam-
ination,pelvic ultrasound and chest x-ray,the hydatidiform mole
patients should take contraception for 2 years after
treatment,condom is the best.
Invasive mole
and
choriocarcinoma
introduction
Definition:Invasive mole means the hydatidiform mole invade
the uterine myometrium or metastasize to extrauterine tissue,
because it has the behavior of malignant tumor,so it is called
invasive mole,invasive mole originates from benign mole,mostly
occurs within 6 monthes after emptying the mole.Choriconoma is
trophoblastic tumor secondary to normal and abnormal
pregnancy,which 50%after hydatidiform,
25% after abortion,22.5%after term pregnancy,and 2.5% after
ectopic pregnancy.
Biologic behavior:invasive mole villus may invade myometrium
or blood vessels or both,at beginning it spread locally,invade
myometrium,sometimes penetrate the uterine wall and spread
to the broad ligament or abdominal cavity.half of the patients
may have telemetastasis along blood circulation and chiefly to
the lung and vagina.prognosis is better
Pathology
1.Invasive mole
Macro examination,different size of viscula in myometrium,there may
be or may not be primary focus in uterine cavity.when the invasion is
near serosal layer……
Microexamination:villose structure and trophoblastic cells proliferation
and differentiation deficiency.villose and trophoblastic cells can be
found in most patients,and cause vascular wall necrosis and bleeding.
2.Choricarcinoma
Macro examination,mostly occurs in uterus,and often located in the
myometrium,it can also protrude in uterine cavity or penetrate the
serosal layer.it border is clear and there is necrosis and bleeding.there
is no stroma and intrinsic blood vessels in tumor.
? II.Clinical manifestation:most invasive mole occurs within
? 6 month after emptying the hydatidiform mole.while choriocar-
? cinoma secondary to benign mole usually occurs over 1 year
? after emptying the hydatidiform mole,and 50% choriocarcinoma
? secondary to abortion or term delivery may occur within 1 year.
? (i),trophoblastic cells tumor with no metastasis
? i).the most common symptoms is irregular vaginal bleeding
? ii).uterine subinvolution(4-6weeks after emptying uterus)
? iii).abdominal pain:tumor uterine penetration,necrosis and
? infection,pedicletorsion of theca lutein cyst.
? iv).theca lutein cyst does not disappear after emptying uterus
? v).false pregnant symptom
?
? (ii).metastatic focus manifestation:symptoms and body
signs depends upon the location of the metastatic focus.the
most site is lung then vagina,parauterus,there is less brain
or liver metastasis
i).pulmonary metastasis
? ii).vaginal metastasis
iii).brain metastasis:
? tumor embolus stage
? brain tumor stage
? cerebral hernia stage
iv).liver metastasis:bad prognosis index
v).metastasis to other organs
? III.Diagnosis
? i.history and clinical manifestation:the typical clinical
? manifestation or metastatic focus symptoms appear within
? 0.5 or over 1 year or between 0.5~1 year after emptying the
? mole,combined with accessory diagnosing methods,the
? diagnosis can be made
? ii.successive measurement of HCG:?-HCG is still high
? over 9 weeks after emptying uterus,or over 4weeks after
? abortion,ectopic pregnancy or term pregnancy,or HCG once
? decreased to normal level then is increased rapidly again,and
? the remained mole or pregnant again are excluded,in this
? condition the invasive mole can be diagnosed
? iii.ultrasound examination:ultrasonography can reveal the
? myometrium invasion
? iv.X-ray and CT
? v.histologic diagnosis:curettage sample can not be as the
? diagnosing evidence,but if the villose structure is found in
? the myometrial or extrauterine metastatic focus sections,the
? diagnosis of invasive mole can be made.
if there is trophoblastic cells invasion,necrosis and bleeding,
no villose structure,then the diagnosis of choriocarcinoma
can be made.
? IV.Differential diagnosis
Clinical stage
? Anatomic stage of trophoblastic cell tumor
? stageI tumor is located in uterus
stageII tumor spread to adnex,vagina,broad ligament
stageIII tumor spread to lung,there is or not tumor in
reproductive system
stageIV metastasis to other organs
Treatment
Chemotherapy is the main treating method,operation and radiotherapy
is accessory method
1.Chemotherapy:MTX,Act-D,KSM,5-Fu and so on.
2.treating effect:blood HCG should be measured once a week after every
treating course.if HCG decreases one logarithm within 18 days after
each course,means there is effect.
3.side effects:
4.indicaton of stoping drugs:after the symptoms,physical signs,primary
focus and metastatic focus are disappeared,and 3 successive blood
HCG measurement(once a week) are all normal,another 2~3 course
is needed,Follow up for 5 years and there is not recurrence means
cured.
5.operation:accessory treatment
(1).hysterectomy:
for large focus,drug-resistant focus or there is penetrating and
bleeding,hysterectomy should be performed based on chemo-
therapy.
for reproductive age women….
for young women who desire pregnancy…,
for patient who does not desire pregnancy……
(2).pneumonectomy
6.radiotherapy
7.drug-resistant and recurrent case
Follow up
Once a time every month in the first year,once every
3 month in the second and third year,then once a year
in the fouth and fifth year
Choriocarcinoma
Introduction
? Choriocarcinoma is a highly malignant tumor,it can metastasize
? to the whole body through blood circulation,damage tissues and
organs,cause bleeding and necrosis.
? The most common metastatic site is lung,then vagina,brain and
liver
? 50%gestational choriocarcinoma result from hydatidiform mole
? (generally occurs over 1 year after emptying the mole),the rate of
? occurrence after abortion or term delivery is 25% and 25% respe-
? ctively,seldom occurs after ectopic pregnancy
? I.Pathology
? i.macroexamination:most choriocarcinoma occurs in uterus,
? the tumor diameter 2-10cm,its color,section,cancer embolus
? is often found in parauterine veins,ovarian luteinizing cyst may
? be formed
? ii.histologic examination:the most obvious difference betw-
? een choriocarcinoma and common cancer is that the choriocar-
? cinoma do not have tumor intrinsic connective stromal cells
? and intrinsic blood vessels.under microscope the hyperplastic
? cytotrophoblastic cells and syntrophoblastic cells invade the
? myometrium and blood vessels accompanied by the bleeding
? and necrosis,so the cancer cells can not be found in the center
?
? of the tumor.the trophoblastic cells group,blood clot and
? the necrosis tissues can be seen at the tumor edge,but the
? villose structure can not be found
? iii.metastasis,the telemetastasis of choriocarcinoma is
? chiefly by blood circulation,the metastasis is early and
? extensive,the most common site is lung(80%),then vagina
? (30%),brain(10%) and liver(10)
? II.Clinical manifestation:the time between the pregnancy
? and the occurrence of the choriocarcinoma is within 3 monthes
? accounts for 44%,within 1 year accounts for 67.2%,1year or
? over 1 year accounts for 32.8%
? i.vaginal bleeding,the most common symptom,irregular vagi-
? nal bleeding after delivery,abortion or emptying the mole(cau-
? se).sometimes the primary focus disappear,the development of
? secondary focus will cause no vaginal bleeding
? ii.abdominal pain:myometrial invasion or uterine cavity hema-
? tocele will cause low abdominal pain;uterine penetration or
? the rupture of metastatic focus will cause acute abdominal
? pain
? iii.pelvic mass:intrauterine pathologic change,parauterine
? metastatic mass or ovarian luteinizing cyst may cause pelvic
? mass
? iv.metastatic focus manifestation:symptoms and body
? signs depends upon the metastatic sites
? (i).pulmonary metastasis:
? i).bronchus invasion
? ii).bronchus obstruction
? iii).metastatic focus near pleura
? iv).acute pulmonary embolism
? v).chest x-ray
? (ii).vaginal metastasis:caused by retrograde metastasis through
? parauterine vein.the metastatic focus is usually located on
? the anterior wall of the low part of vagina,its rupture may
? cause heavy bleeding
? (iii).brain metastasis:often secondary to the pulmonary metast-
? asis,the chiefly cause of death.its clinical course is divided
? into 3 stages
? i).tumor embolus stage
? ii).brain tumor stage
? iii).cerebral hernia stage
? (iv).liver metastasis:often coexist with pulmonary or vaginal
? metastasis,one of the bad prognosis factors
?
? III.Diagnosis
? i.clinical characters,the diagnosis of choriocarcinoma can be
? made according to the following conditions
? (i),the typical symptoms or metastatic focus appears after
? abortion,delivery or ectopic pregnancy which is accompanied
? by the increasing of HCG
? (ii).clinical manifestation appears over 1 year after abortion of
? hydatidiform mole
? (iii).if the clinical manifestation appears between half a year and
? 1 year after abortion of hydatidiform mole,there is the possi-
? bility of invasive mole and choriocarcinoma,the histologic
? examination can differentiate the diagnosis
?
? ii.HCG measurement:the most important method to diagnose
? choriocarcinoma.the time of ?-HCG decreasing to normal level
? after artificial abortion,natural abortion,term delivery,and ecto-
? pic pregnancy is 30,19,12 and 8-9 days respectively.if HCG is
? still high over above time and combined with clinical manifest-
? ation,the diagnosis of choriocarcinoma can be made
? iii.image diagnosis:B-ultrasound,chest x-ray,CT
? iv.histologic diagnosis:if the sample contains undifferentiated
? cytotrophoblastic and syntrophoblastic cells and bleeding and
? necrosis,no villose structure,the choriocarcinoma can be made
? I.Pathology
? i,Macroexamination:different size viscula and blood clot
? ii.microscopic examination:villose structure can be seen,
? different degree of over hyperplasia and atypical hyperplasia
? of trophoblastic cells which have over invasive ability
? iii.histologic types
? (i).type 1:on gross examination large amount of vesculas
? which have invaded myometrium or blood sinus can be seen
? but seldom bleeding and necrosis
? (ii).type 2:on gross examination moderate or less amount of
? vesculas can be seen,trophoblastic cells are moderately hyp-
? erplastic and a partial of cells is undifferentiated,there is
? bleeding and necrosis in tissues
? IV.Differential diagnosis
? Hydatidiform mole
? Invasive mole
? Placental site trophoblastic tumors
? Rudimental placenta
?V.Clinical stage
Stage I disease confined to uterus
Stage II disease extending outside of the terus
but limited to the genital structures(adnexa,
vagina,broad ligaments)
Stage III disease extending to the lungs,with
or without known genital tract involvement
Stage IV disease at other metastatic sites
?VI.prognosis(P 326 Tab34-4)
? VII.Treatment
? treating principle:chemotherapy is the first selection,operation as
? the accessory treatment,but operation is also important in contro-
? lling bleeding,infection,complication and in removing remained
? or drug-resistant focus
? i.chemotherapy
? (i).principle:single drug for stage I;combined chemotherapy for
? stageII-III;EMA-CO scheme is for the stage IV or drug-resis-
? tant case
? (ii).side-effects
? (iii).indications of stopping chemotherapy:symptoms and body
? signs disappeared,3 successive HCG measurement(once a
? week) are all normal,and then continues 2-3 course
? ii.operation:subradical hysterectomy should be performed on
? the patients whose pathologic change is in the uterus and the
? chemotherapy is not effective
? for young patients:
? (iii).type 3:the tumor is almost completely replaced by necrosis
? tissues and blood clots,on gross examination only a few
? vesiculas can be seen,sometimes the remained edematous
? villi can only be found under microscope.the trophoblastic
? cells are over hyperplastic and undifferentiated which is
? very like choriocarcinoma
disease (GTD)
introduction
Definition:gestational trophoblastic disease(GTD)is a group
of disease originated from placental villose trophoblastic
cells,including hydatidiform mole,invasive mole,choriocarci-
noma and a kind of less common trophoblastic cell tumor in
placenta
Relations among the diseases:certain relations exist
among the diseases,benign mole is considered to be abnormal
formation of placenta accompanied by the special abnormal
hereditary ; invasive mole results from benign mole; chorio-
carcinoma and the trophoblastic cell tumor in placenta may
result from benign mole,term pregnancy,abortion and ectopic
pregnancy.invasive mole,choriocarcinoma and trophoblastic cell
tumor in placenta are also called gestational trophoblastic tumor
(GTT).
Hydatidiform Mole
[Definition]:hydatidiform mole means that after pregnancy
the placental trophoblastic cells proliferate abnormally,there
is stromal edema,and forms vesicula which is like grape on
its apparence.
[Classification]:hydatidiform mole is divided into
complete and incomplete type among which the majority is
complete type,and its malignant change rate is relitively
high;less mole is incomplete type and rarely has malignant
change,the cause and the clinical course of the two types
mole are different.
[Etiology]:the etiology is not clear
I.Etiology of complete hydatidiform mole
Epidemiology,the morbidity of hydatidiform mole is different in
different area.
High risk factors:
1.nourishing status,social economy
2.age:over 35 and 40 years old;below 20 years old.
3.hydatidiform mole history:if a patient has the history of 1 or 2
times hydatidiform mole,then the morbidity of the hydatidiform
mole when pregnant again is 1% and 15~20% respectively.
Genetic factors:
1.enucleate egg fertilization:chromosome karyotype of complete
mole is diploid,90% is 46XX,10% is 46XY
II,Etiology of incomplete hydatidiform mole
the morbidity of incomplete mole is much lower than that of the
complete type,and it is not associated with age.
1.Genetic factors,chromosome karyotype of 90% incomplete mole
is triploid,which is formed by the fertilization of a monoploid egg
and two monoploid sperm,or by the fertilization of a monoploid
egg(sperm) and a meiotic deficiency sperm(egg).
The most common chromosome karyotype is 69XXY,and then is
69XXX or 69XYY.
[Pathology]
The comparison of morphology and karyotype of complete and
incomplete mole
Complete mole incomplete mole
Embryotic or fetal tissue - +
Villus stromal edema diffuseed localized
Trophoblastic hyperplasia diffuseed localized
Villus outline regular irregular
Villus stromal blood vessel - +
Karyotype diploid triploid or tetraploid
[Clinical manifestation]:
I.complete mole:usually complete mole has the following typical
symptoms
i.vaginal bleeding after amenorrhea:the most common
symptom,often occurs after 8~12 week of gestation
(i).clinical manifestation（ 8~12 week after amenorrhea）
(ii).cause of bleeding
(iii).complication
ii.uterus is abnormally enlarged and become soft
(i).cause:over 1/2 patients;1/3 patients;a few patients
iii.theca lutein ovarian cyst:large amount HCG stimulate internal
theca cells……
(i).symptom
(ii).disappearance:within 2~4 month after operation
iv.gestational vomitting and PIH
(i).gestational vomitting
(ii).PIH:when uterus is abnormally enlarged and HCG↑↑
v.hyperthyroidism:
(i)7% is complicated with slight hyperthyroidism
(ii)cause:HCG ↑↑,T3T4 ↑↑
vi.abdominal pain:generally not severe,often before bleeding.
occurrence of acute abdomen
II.partial hydatidiform mole:may have the major symptoms
of complete mole but it is slightly manifested.no luteinizing
cyst,the histologic examination of curettage sample may
confirm the diagnosis
[Prognosis],complete mole has the latent risk of local invasion or
telemetastasis,research proved that after emptying the mole,the rate
of uterine invasion or telemetastasis is 15% and 4% respectively.if the
patient has the following high-risk factors,the risk of local invasion
or telemetastasis may increase 10 times.
The high-risk factors includes:
(i).β-HCG>100000IU/L;
(ii).uterine size is obviously larger than that with the same
gestational time.
(iii).the luteinizing cyst is >6cm.
(iv),If >40 years old,the risk of invasion and metastasis may be
37%,If >50 years old,the risk of invasion and metastasis may be
56%.
(v).repeated mole:the morbidity of invasion and metastasis increase
3~4 times.
HCG resolution law:It is very important for predicting the
prognosis,Normally after emptying the mole,the β-HCG
regression curve is steadly decreased,and reach normal
level within 9~14 weeks
persistent mole:
if the HCG is still positive 3 months after the mole is
completely emptied,called persistent mole
[Diagnosis],
according to the irregular vaginal bleeding after amenorrhea,soft
and abnormally enlarged uterus,no fetal body can be palpated in 5
gestational month size uterus,no fetal movement and no fetal heart
beat can be heard,the hydatidiform mole should be suspected, the
hyperemesis gravidarum,preeclampsia befor 28 weeks gestation
and bilateral ovarian cyst all support the diagnosis.if the vesicular
tissue is found in the vaginal expelling blood,the diagnosis is
basically confirmed,if there is suspicion on diagnosis,the following
accessory examination should be made
i.HCG measurement:in mole the HCG is over 100kIU/L,and
often over 1000kIU/L
ii.ultrasound examination:an important accessory diagnosing
method
(i).B-ultrasound:in normal pregnancy gestational sac can be
seen between 4-5 gestational week,and the heart-tube
beat between 6-7 week;in hydatidiform mole
(ii).detecting the fetal heart beat by ultrasound Doppler:in
normal pregnancy the fetal heart beat can be heard in the
6th week of gestation and after 12 weeks the positive rate
is 100%;in hydatidiform mole
[Differential diagnosis]
(i).abortion
(ii).twin pregnancy
(iii).polyhydramnios
[Management]
i.emptying uterine cavity:once the diagnosis is confirmed
the uterine cavity should be emptied as soon as possible
i).uterine aspiration and curettage
ii).application of oxytocin during operation
iii).indication of the second curettage(>12week)
ii.hysterectomy
i).over 40 years old with high-risk factors
ii).uterine size is over 14 gestational weeks
iii.management of luteinizing cyst
iv.preventive chemotherapy:the malignant change rate is 14.5%
in our country,if the patient has the following condition,the
chemotherapy should be given
(i).over 40 years old
(ii).the β-HCG is over 100kIU/L before emptying mole
(iii).the HCG regresion curve is not progressively declined
(iv).uterus is obviously larger than the size of the amenorrhea
(v).luteinizing cyst is >6cm
(vi).there is still over hyperplasia of trophoblastic cells in the
second curettage
(vii).no follow up conditions
[follow up]:regular follow up can find persistent or metastatic
trophoblastic cells tumor
(i).HCG measurement:after emptying the mole,the HCG
should be mesured once a week until it is to the normal
level
(ii).follow up:once a week in the first 3 monthes,then once 2
weeks in the next 3 monthes and once a month for half
a year,once half a year in the second year,and totally follow
up for 2 year
(iii).contents of follow up:HCG,abnormal vaginal bleeding,
cough,hemoptysis,metastatic symptoms,gynecologic exam-
ination,pelvic ultrasound and chest x-ray,the hydatidiform mole
patients should take contraception for 2 years after
treatment,condom is the best.
Invasive mole
and
choriocarcinoma
introduction
Definition:Invasive mole means the hydatidiform mole invade
the uterine myometrium or metastasize to extrauterine tissue,
because it has the behavior of malignant tumor,so it is called
invasive mole,invasive mole originates from benign mole,mostly
occurs within 6 monthes after emptying the mole.Choriconoma is
trophoblastic tumor secondary to normal and abnormal
pregnancy,which 50%after hydatidiform,
25% after abortion,22.5%after term pregnancy,and 2.5% after
ectopic pregnancy.
Biologic behavior:invasive mole villus may invade myometrium
or blood vessels or both,at beginning it spread locally,invade
myometrium,sometimes penetrate the uterine wall and spread
to the broad ligament or abdominal cavity.half of the patients
may have telemetastasis along blood circulation and chiefly to
the lung and vagina.prognosis is better
Pathology
1.Invasive mole
Macro examination,different size of viscula in myometrium,there may
be or may not be primary focus in uterine cavity.when the invasion is
near serosal layer……
Microexamination:villose structure and trophoblastic cells proliferation
and differentiation deficiency.villose and trophoblastic cells can be
found in most patients,and cause vascular wall necrosis and bleeding.
2.Choricarcinoma
Macro examination,mostly occurs in uterus,and often located in the
myometrium,it can also protrude in uterine cavity or penetrate the
serosal layer.it border is clear and there is necrosis and bleeding.there
is no stroma and intrinsic blood vessels in tumor.
? II.Clinical manifestation:most invasive mole occurs within
? 6 month after emptying the hydatidiform mole.while choriocar-
? cinoma secondary to benign mole usually occurs over 1 year
? after emptying the hydatidiform mole,and 50% choriocarcinoma
? secondary to abortion or term delivery may occur within 1 year.
? (i),trophoblastic cells tumor with no metastasis
? i).the most common symptoms is irregular vaginal bleeding
? ii).uterine subinvolution(4-6weeks after emptying uterus)
? iii).abdominal pain:tumor uterine penetration,necrosis and
? infection,pedicletorsion of theca lutein cyst.
? iv).theca lutein cyst does not disappear after emptying uterus
? v).false pregnant symptom
?
? (ii).metastatic focus manifestation:symptoms and body
signs depends upon the location of the metastatic focus.the
most site is lung then vagina,parauterus,there is less brain
or liver metastasis
i).pulmonary metastasis
? ii).vaginal metastasis
iii).brain metastasis:
? tumor embolus stage
? brain tumor stage
? cerebral hernia stage
iv).liver metastasis:bad prognosis index
v).metastasis to other organs
? III.Diagnosis
? i.history and clinical manifestation:the typical clinical
? manifestation or metastatic focus symptoms appear within
? 0.5 or over 1 year or between 0.5~1 year after emptying the
? mole,combined with accessory diagnosing methods,the
? diagnosis can be made
? ii.successive measurement of HCG:?-HCG is still high
? over 9 weeks after emptying uterus,or over 4weeks after
? abortion,ectopic pregnancy or term pregnancy,or HCG once
? decreased to normal level then is increased rapidly again,and
? the remained mole or pregnant again are excluded,in this
? condition the invasive mole can be diagnosed
? iii.ultrasound examination:ultrasonography can reveal the
? myometrium invasion
? iv.X-ray and CT
? v.histologic diagnosis:curettage sample can not be as the
? diagnosing evidence,but if the villose structure is found in
? the myometrial or extrauterine metastatic focus sections,the
? diagnosis of invasive mole can be made.
if there is trophoblastic cells invasion,necrosis and bleeding,
no villose structure,then the diagnosis of choriocarcinoma
can be made.
? IV.Differential diagnosis
Clinical stage
? Anatomic stage of trophoblastic cell tumor
? stageI tumor is located in uterus
stageII tumor spread to adnex,vagina,broad ligament
stageIII tumor spread to lung,there is or not tumor in
reproductive system
stageIV metastasis to other organs
Treatment
Chemotherapy is the main treating method,operation and radiotherapy
is accessory method
1.Chemotherapy:MTX,Act-D,KSM,5-Fu and so on.
2.treating effect:blood HCG should be measured once a week after every
treating course.if HCG decreases one logarithm within 18 days after
each course,means there is effect.
3.side effects:
4.indicaton of stoping drugs:after the symptoms,physical signs,primary
focus and metastatic focus are disappeared,and 3 successive blood
HCG measurement(once a week) are all normal,another 2~3 course
is needed,Follow up for 5 years and there is not recurrence means
cured.
5.operation:accessory treatment
(1).hysterectomy:
for large focus,drug-resistant focus or there is penetrating and
bleeding,hysterectomy should be performed based on chemo-
therapy.
for reproductive age women….
for young women who desire pregnancy…,
for patient who does not desire pregnancy……
(2).pneumonectomy
6.radiotherapy
7.drug-resistant and recurrent case
Follow up
Once a time every month in the first year,once every
3 month in the second and third year,then once a year
in the fouth and fifth year
Choriocarcinoma
Introduction
? Choriocarcinoma is a highly malignant tumor,it can metastasize
? to the whole body through blood circulation,damage tissues and
organs,cause bleeding and necrosis.
? The most common metastatic site is lung,then vagina,brain and
liver
? 50%gestational choriocarcinoma result from hydatidiform mole
? (generally occurs over 1 year after emptying the mole),the rate of
? occurrence after abortion or term delivery is 25% and 25% respe-
? ctively,seldom occurs after ectopic pregnancy
? I.Pathology
? i.macroexamination:most choriocarcinoma occurs in uterus,
? the tumor diameter 2-10cm,its color,section,cancer embolus
? is often found in parauterine veins,ovarian luteinizing cyst may
? be formed
? ii.histologic examination:the most obvious difference betw-
? een choriocarcinoma and common cancer is that the choriocar-
? cinoma do not have tumor intrinsic connective stromal cells
? and intrinsic blood vessels.under microscope the hyperplastic
? cytotrophoblastic cells and syntrophoblastic cells invade the
? myometrium and blood vessels accompanied by the bleeding
? and necrosis,so the cancer cells can not be found in the center
?
? of the tumor.the trophoblastic cells group,blood clot and
? the necrosis tissues can be seen at the tumor edge,but the
? villose structure can not be found
? iii.metastasis,the telemetastasis of choriocarcinoma is
? chiefly by blood circulation,the metastasis is early and
? extensive,the most common site is lung(80%),then vagina
? (30%),brain(10%) and liver(10)
? II.Clinical manifestation:the time between the pregnancy
? and the occurrence of the choriocarcinoma is within 3 monthes
? accounts for 44%,within 1 year accounts for 67.2%,1year or
? over 1 year accounts for 32.8%
? i.vaginal bleeding,the most common symptom,irregular vagi-
? nal bleeding after delivery,abortion or emptying the mole(cau-
? se).sometimes the primary focus disappear,the development of
? secondary focus will cause no vaginal bleeding
? ii.abdominal pain:myometrial invasion or uterine cavity hema-
? tocele will cause low abdominal pain;uterine penetration or
? the rupture of metastatic focus will cause acute abdominal
? pain
? iii.pelvic mass:intrauterine pathologic change,parauterine
? metastatic mass or ovarian luteinizing cyst may cause pelvic
? mass
? iv.metastatic focus manifestation:symptoms and body
? signs depends upon the metastatic sites
? (i).pulmonary metastasis:
? i).bronchus invasion
? ii).bronchus obstruction
? iii).metastatic focus near pleura
? iv).acute pulmonary embolism
? v).chest x-ray
? (ii).vaginal metastasis:caused by retrograde metastasis through
? parauterine vein.the metastatic focus is usually located on
? the anterior wall of the low part of vagina,its rupture may
? cause heavy bleeding
? (iii).brain metastasis:often secondary to the pulmonary metast-
? asis,the chiefly cause of death.its clinical course is divided
? into 3 stages
? i).tumor embolus stage
? ii).brain tumor stage
? iii).cerebral hernia stage
? (iv).liver metastasis:often coexist with pulmonary or vaginal
? metastasis,one of the bad prognosis factors
?
? III.Diagnosis
? i.clinical characters,the diagnosis of choriocarcinoma can be
? made according to the following conditions
? (i),the typical symptoms or metastatic focus appears after
? abortion,delivery or ectopic pregnancy which is accompanied
? by the increasing of HCG
? (ii).clinical manifestation appears over 1 year after abortion of
? hydatidiform mole
? (iii).if the clinical manifestation appears between half a year and
? 1 year after abortion of hydatidiform mole,there is the possi-
? bility of invasive mole and choriocarcinoma,the histologic
? examination can differentiate the diagnosis
?
? ii.HCG measurement:the most important method to diagnose
? choriocarcinoma.the time of ?-HCG decreasing to normal level
? after artificial abortion,natural abortion,term delivery,and ecto-
? pic pregnancy is 30,19,12 and 8-9 days respectively.if HCG is
? still high over above time and combined with clinical manifest-
? ation,the diagnosis of choriocarcinoma can be made
? iii.image diagnosis:B-ultrasound,chest x-ray,CT
? iv.histologic diagnosis:if the sample contains undifferentiated
? cytotrophoblastic and syntrophoblastic cells and bleeding and
? necrosis,no villose structure,the choriocarcinoma can be made
? I.Pathology
? i,Macroexamination:different size viscula and blood clot
? ii.microscopic examination:villose structure can be seen,
? different degree of over hyperplasia and atypical hyperplasia
? of trophoblastic cells which have over invasive ability
? iii.histologic types
? (i).type 1:on gross examination large amount of vesculas
? which have invaded myometrium or blood sinus can be seen
? but seldom bleeding and necrosis
? (ii).type 2:on gross examination moderate or less amount of
? vesculas can be seen,trophoblastic cells are moderately hyp-
? erplastic and a partial of cells is undifferentiated,there is
? bleeding and necrosis in tissues
? IV.Differential diagnosis
? Hydatidiform mole
? Invasive mole
? Placental site trophoblastic tumors
? Rudimental placenta
?V.Clinical stage
Stage I disease confined to uterus
Stage II disease extending outside of the terus
but limited to the genital structures(adnexa,
vagina,broad ligaments)
Stage III disease extending to the lungs,with
or without known genital tract involvement
Stage IV disease at other metastatic sites
?VI.prognosis(P 326 Tab34-4)
? VII.Treatment
? treating principle:chemotherapy is the first selection,operation as
? the accessory treatment,but operation is also important in contro-
? lling bleeding,infection,complication and in removing remained
? or drug-resistant focus
? i.chemotherapy
? (i).principle:single drug for stage I;combined chemotherapy for
? stageII-III;EMA-CO scheme is for the stage IV or drug-resis-
? tant case
? (ii).side-effects
? (iii).indications of stopping chemotherapy:symptoms and body
? signs disappeared,3 successive HCG measurement(once a
? week) are all normal,and then continues 2-3 course
? ii.operation:subradical hysterectomy should be performed on
? the patients whose pathologic change is in the uterus and the
? chemotherapy is not effective
? for young patients:
? (iii).type 3:the tumor is almost completely replaced by necrosis
? tissues and blood clots,on gross examination only a few
? vesiculas can be seen,sometimes the remained edematous
? villi can only be found under microscope.the trophoblastic
? cells are over hyperplastic and undifferentiated which is
? very like choriocarcinoma
