Choriocarcinoma, Gestational trophoblastic neoplasia, EMACO Regimen, Hydatidiform mole

1. CHORIOCARCINOMA
Presented by:
Bibek Bhandari
Astha Shrestha
Benju Pandit
IInd Batch

2. Gestational Trophoblastic Disease
• Gestational Trophoblastic Disease (GTD) is a
spectrum of proliferative abnormalities of
trophoblasts associated with pregnancy
• GTD includes
- complete & partial H. mole
- invasive mole
- choriocarcinoma
- placental site trophoblastic tumour

3. PATHOLOGIC
CLASSIFICATION
CLINICAL
CLASSIFICATION
Hydatidiform mole
*complete
*incomplete
Benign gestational
trophoblastic disease
Invasive mole
Malignant
trophoblastic disease
Nonmetastatic
Placental site
trophoblastic
tumor
Metastatic
Choriocarcinoma High risk Low risk
Pathologic and clinical classifications for
gestational trophoblastic disease

4. Hydatidiform mole (vesicular mole)
• Neoplasm of trophoblast involving both
cytotrophoblast and syncytotrophoblast
• Abnormal condition of placenta where there is
partly degenerative and partly proliferative
changes in young chorionic villi
• It is regarded as a benign neoplasia of chorion
with malignant potential.

5. Incidence
• Incidence varies widely
• 1 out of 1500-2000 pregnancy in US and
Europe
• Highest in asia – 1 out of 600 pregnancies in
asian countries (? Rice eating population)

6. Risk factors for molar pregnancy
• Age: extreme of reproductive age group <15
years and >40 years
• Prior H. mole and spontaneous abortion
• Faulty nutrition: inadequate intake of protein,
animal fat, vitamin A (explain its prevalence in
oriental countries). Low dietary intake of
carotene

7. Diagnosis
A. Symptoms
• Amenorrhea (8-12 weeks)
• Hyperemesis gravidarum
• Vaginal bleeding(90%) with or without
passage of vesicles. Blood mixed with
gelatinous fluid from ruptured cysts
(white currant in red currant juice)

8. • Varying degree of lower abdominal pain
• Abdominal mass
• Respiratory symptoms: dyspnoea
haemoptysis
• Features of hyperthyroidism: tremor
palpitation.
• Expulsion of grapes like
vesicles(diagnostic)
• Past history of molar pregnancy

9. B. Signs
–Patient looks ill
–Features of shock, pallor
–Features of thyrotoxicosis, enlarged thyroid
gland
–Uterine size may not correspond to period of
amenorrhea
–Uterus may feel firm elastic, doughy(absence
of amniotic fluid sac)
–Absent fetal heart sound

10. • Pelvic findings
oMetastatic lesion (purple to blue-black
papules or nodules, which are
extremely vascular and may bleed
profusely if biopsied )
oVesicles and bleeding seen
oAbsent internal ballotement
oPalpable unilateral or bilateral
enlargement of ovary (25-50%) due to
theca lutein cysts

11. C. Investigations
–Sonography: characteristic snow storm
appearance

12. –Quantitative estimation of chorionic
gonadotrophin:
–CXR to exclude metastatic lung disease
–Other supportive investigations
• Complete blood count
• Blood grouping and Rh typing
• PIH investigations
• TSH level

13. Treatment
• Suction evacuation is the gold standard
method of treatment
• Anemia and infection should be treated if
present
• Hysterectomy is not recommended

14. Follow up
• Every 2 week till serum/urine β-hCG is normal
for 3 consecutive visit
• Then once a month for 6 months and 6
monthly for 1 year
• Total is around one and half to two years after
β-hCG becomes normal

15. Complication
• Immediate
– Hemorrhage and shock
– Sepsis
– Preeclampsia
– Perforation of uterus
– Coagulation failure
– Acute pulmonary insufficiency

16. • Late
– choriocarcinoma(2-10%) (GTN)
Risk factors for malignant change
1. Patient age >40 / <20years irrespective of parity
2. Parity > 3 (age more important than parity)
3. Serum hCG >100000mlU/ml
4. Previous history of molar pregnancy
5. Theca lutein cysts: large >6cm diameter

17. Choriocarcinomas are divided into
three subtypes
1. Gestational choriocarcinoma
2. Non gestational choriocarcinoma
3. Unclassified choriocarcinoma

18. 1. Gestational choriocarcinoma:
• Is related to pregnancy & divided further into
a. Uterine choriocarcinoma:
• most common
• Develops in the uterus after hydatidiform
mole or after abortion and normal delivery.
• Also choriocarcinoma with an intact
pregnancy has been reported

19. b. Extrauterine choriocarcinoma
• develops primarily at the place of ectopic
pregnancy, where there is no tumor in the
uterus
c. Intraplacental choriocarcinoma
• found in the placenta mainly after delivery.
• These cases were reported to be associated
with viable pregnancy

20. 2. Non gestational choriocarcinoma is
divided into two categories:
a. Choriocarcinoma of germ cell
• Origins from subtype of the germ cell tumor
which develops in the ovary of the woman
before marriage or the testis of an adult male.
• more resistant to chemotherapy than a
gestational tumor.

21. b. Choriocarcinoma derived from other
carcinomas
– involves choriocarcinomatous change of other
3. Unclassified choriocarcinoma

22. Gestational choriocarcinoma
• A malignant neoplasm composed of large sheets of
biphasic, markedly atypical trophoblast without
chorionic villi

23. • Gestational choriocarcinoma may occur
subsequent to:
– Molar pregnancy (50%)
– Abortion (25%)
– Normal gestation (22.5%)
– Ectopic pregnancy (2.5%)
• Rarely an intraplacental choriocarcinoma is
diagnosed immediately following pregnancy
from placental pathological examination

24. Morphology
• The choriocarcinoma is
classically a soft, fleshy,
yellow-white tumour
with a marked tendency
to form large pale areas
of ischemic necrosis, foci
of cystic softening, and
extensive haemorrhage

25. Histopathology
• The classic pattern of choriocarcinoma has
been described as bilaminar, dimorphic, or
biphasic.
• Alternating arrangement of mononucleate
trophoblastic cells and syncytiotrophoblastic
cells characterizes choriocarcinoma.
• The intermediate trophoblast in
choriocarcinoma may show marked variation
in the degree of cytologic atypia.

26. • Vascular invasion often is prominent
• Chorionic villi are not a component of
choriocarcinoma that differentiates
choriocarcinoma from invasive mole
• Choriocarcinoma lacks the intrinsic
endothelium-lined vascular channels in
the centre of a tumour, making it a
unique malignant solid tumour.

28. Tumour spread and staging
1. DIRECT SPREAD : to the parametrium, tubes
and ovaries.
2. BLOOD SPREAD : occurs early to distant
organs. The commonest sites are
–Lungs(80 %)
–Vagina(30 %)
–Brain(10 %) and
–Liver(10 %)

29. CLINICAL FEATURES
• Persistent or irregular vaginal bleeding:
–It is the commonest symptom occurring after
labour, abortion or evacuation of a vesicular
mole. Bleeding can occur within days or
months but rarely after 2 years
• Vaginal discharge:
–which is blood stained and offensive due to
ulceration and infection of the growth .

30. • Amenorrhea:
–may be present due to continuous hCG
production.
• Pelvic pain or pressure
–If an enlarged uterus or ovarian cysts are
present, the patient may report pelvic pain
or pressure

31. Clinical features due to metastasis
• Dyspnoea, cough, chest pain and haemoptysis
are noticed with lungs metastasis.
• Irregular and at times brisk hemorrhage in
vaginal metastasis
• The appearance of neurological symptoms like
hemiplegia, seizures, headache, dizziness and
visual disturbances suggest brain metastasis.
• Epigastric pain and jaundice in liver metastasis

32. • Rapid growth, widespread dissemination, and
a high propensity for hemorrhage makes this
tumor a medical emergency

33. • Vaginal metastasis

34. Signs
• The uterus may be enlarged/boggy
• Vaginal metastasis appears as a bluish red
vascular tumour which bleeds easily on touch
Theca lutein cysts are palpable in some cases.
• Metastasis to the lower genital tract present
as purple to blue-black papules or nodules.
These are extremely vascular and might bleed
profusely if biopsied.

35. • Abdominal tenderness may be present if liver
or gastrointestinal metastases have occurred.
• Abdominal guarding and rebound tenderness
may be present if a hemoperitoneum has
occurred due to bleeding from an abdominal
metastasis.
• Bleeding from a metastasis could also result in
signs and symptoms of hemorrhagic shock.
.

36. Serum β-hCG:
• Persistent or rising titres in absence of
pregnancy are indicative of trophoblastic
neoplasia.
• Choriocarcinoma produce abundant amounts
of hCG, which can typically range from 100 to
over 100,000 mIU/mL depending on the
extent of disease
• Metastatic brain lesion is suspected when the
ratio of β-hCG in spinal fluid:serum is more
than 1:60
Management

37. Laboratory Studies
• A CBC may help detect anemia secondary to
bleeding.
• Liver enzymes levels may become elevated in
the presence of metastasis to the liver
• Thyroid function tests — Thyroid function
tests should be ordered if the hCG level is
>100,000 mIU/mL to determine if the patient
may be hyperthyroid.

38. Imaging studies
• Regardless of the imaging modality used,
choriocarcinoma often appears as a mass
enlarging the uterus. Sometimes it manifests as a
discrete, central, infiltrative mass.
• Its heterogeneous appearance correlates with
necrosis and haemorrhage
• Plain X-ray chest: may show secondaries in the
form of " cannon balls" or "snowstorm"
appearance

40. • Ultrasonography: to detect tumour,
cystic ovaries and exclude remnants
of conception
Choriocarcinoma: Patient with stage 3 choriocarcinoma, The endometrial
cavity is filled with a hyperechoic mass

41. CT scan: for lungs, liver, brain and
bone.
• Micrometastases are present in approximately
40-45% of women with nonmetastatic
gestational trophoblastic neoplasia (GTN) who
have normal chest radiograph findings.

42. • Brain metastasis

43. Diagnostic Uterine curettage
• Uterine curettage has a limited role in the
evaluation
• Pretherapy D&C reduces the intrauterine
tumor bulk
• However not used for routine histological
diagnosis
• Brisk hemorrhage may occur for which live-
saving hysterectomy may have to be done

44. FIGO classification
• Stage I Disease confined to uterus.
• Stage II Extends outside of the uterus but is
limited to the genital structures (adnexa,
vagina , broad ligament).
• Stage III Extends to the lungs, with or without
known genital tract involvement.
• Stage IV metastases to other organs ( brain,
liver , kidneys, ovaries, bowel)

45. Treatment
• Non metastatic Disease
• Low-Risk Metastatic Disease
• High-Risk Metastatic Disease

46. Treatment of Nonmetastatic GTD
• Single-agent chemotherapy is the treatment
of choice for patients wishing to preserve their
fertility.
• Methotrexate(MTX) and Actinomycin-D are
generally chemotherapeutic agents
• Treatment is continued until three consecutive
normal hCG levels have been obtained and
two courses have been given after the first
normal hCG level

47. Treatment of Nonmetastatic GTD
• Hysterectomy is advisable as initial treatment
in patients with nonmetastatic GTD who no
longer wish to preserve fertility
• This choice can reduce the number of course
and shorter duration of chemotherapy.
• Adjusted single-agent chemotherapy at the
time of operation is indicated to eradicate any
occult metastases and reduce tumor
dissemination.

48. • The use of the WHO Prognostic Scoring
System is more predictive of clinical outcome
than the use of individual risk factors
• A score of 0 to 6 suggests low risk of
resistance to single-agent chemotherapy
• A score of ≥7 predicts a high risk of resistance
to monotherapy and requires combination
chemotherapy

50. Treatment of Low-Risk Metastatic GTD
• Single-agent chemotherapy with MTX or
actinomycin-D is the treatment for patients in
this category
• If resistance to sequential single-agent
chemotherapy develops  combination
chemotherapy would be taken

51. • Approximately 10-15% of patients treated
with single-agent chemotherapy will require
combination chemotherapy with or without
surgery to achieve remission
• Single agent chemotherapy with either
actinomycin or methotrexate has achieved
comparable and excellent remission rates in
both non metastatic and low risk metastatic
GTN.

52. MAC protocol
• If single agent fails then MAC protocol is used
Drug Dosage Routes Days
Methotrexate 1-15 mg/kg IM or IV 1,3,5,7
Folinic Acid 1-15 mg/kg IM 2, 4, 6, 8
Actinomycin D 12 μg/kg IV 1-5
Cyclophosphamide 3mg/kg IV 1-5

53. Treatment of High-Risk Metastatic
GTD
• Multiagent chemotherapy with or without
adjuvant radiotherapy or surgery should be
the initial treatment for patients with high-risk
metastatic GTD
• EMA-CO regimen formula is good choice for
high-risk metastatic GTD
• Adjusted surgeries such as removing foci of
chemotherapy-resistant disease, controlling
hemorrhage may be the one of treatment
regimen

56. Monitoring
• Serum hCG value monitoring weekly once
negative  every 2 weeks for 3 months 
every month for 1 year  every 6-12 months
for life or at least 3-5 years

57. Assessment of response to
chemotherapy
• All women with GTT should be monitored weekly
serial measurement of serum β-hcg during
therapy
• When weekly or bi-weekly single agent
chemotherapy is used the regimen is continued
till 3rd normal β-hcg level is obtained
• When infusion methotrexate is given as one time
dose β-hcg are followed weekly with additional
therapy given only if an inadequate response is
observed

58. • When combination chemotherapy with
EMACO is used the regimen is repeated every
2 weeks until β-hcg is normal and then
generally continued for an additional 3 cycles

59. ROLE OF SURGERY
• TOTAL HYSTERECTOMY is done if
required in choriocarcinoma. The ovaries
are not usually involved and if involved,
can be effectively cured with
postoperative chemotherapy, hence
bilateral salpingoopherectomy is not
done.

60. INDICATIONS OF HYSTERECTOMY
• Lesions confined to the uterus in women aged
›35 years, not desirous of fertility.
• Intractable vaginal bleeding.
• Localized uterine lesion resistant to
chemotherapy.
• Accidental uterine perforation during uterine
curettage.

61. 2. LUNG RESECTION:
• Most frequently used surgical procedure for
extirpation of extrauterine metastases of GTN
is thoracotomy with pulmonary wedge
resection.
• However, it is not always necessary to resect
lung metastases in the majority of patients
• Resection of pulmonary nodules in highly
selected patients with drug-resistant disease
may successfully induce remission after
excluding active disease elsewhere.

62. 3. CRANIOTOMY
• Brain metastases occur in 9.3%–21.4% of patients
with metastatic GTN and are associated with a
worse prognosis
• These lesions tend to be highly vascular and have
a tendency for central necrosis and hemorrhage.
• Brain irradiation has usually been integrated into
the treatment of brain metastasis in an attempt to
prevent hemorrhage and neurological
deterioration
• Craniotomy has usually been used only to prevent
acute deterioration

63. RADIATION
• Patients with brain metastasis require whole brain
radiation therapy(3000 cGy over 10 days).
• Intrathecal high dose methotrexate may be
administered to prevent haemorrhage and for
tumour shrinkage.
• Liver metastasis: Interventional radiology(hepatic
artery ligation or embolization) or whole liver
radiation(2000 cGy over 10 days) along with
chemotherapy may be effective.Hepatic metastasis
has a poor prognosis.

64. Follow up-
All patients with stage I through stage III disease
should receive follow up with-
1. Weekly measurement of HCG level until they
are normal for 3 consecutive weeks.
2. Monthly measurement of HCG value until level
are normal for 12 consecutive months.
3. Effective contraception during the entire
interval of hormonal follow up.

65. PROGNOSIS
• The cure rate is almost up to 100 percent in low
risk and about 70 percent in high risk metastatic
groups.
• Recurrence in previous one molar pregnancy is 1-
2% and if two or more than two 15-20%

66. References
• DC Dutta’s Textbook of Gynaecology
• William’s Gynaecology
• Nepal society of obstetricians and gynecologists guidelines on
management of GTD
• http://www.uptodate.com/contents/gestational-
trophoblastic-neoplasia-epidemiology-clinical-features-
diagnosis-staging-and-risk-stratification