choriocarcinoma, workup and follow up

2. TYPES OF GTD
Benign
• Hydatidiform mole/molar pregnancy (complete
or incomplete)
Malignant
• Invasive mole
• Choriocarcinoma (chorioepithelioma)
• Placental site trophoblastic tumor

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. Risk factor for malignant change
1. Pre-evacuation uterine size larger than expected for
gestational duration
2. Bilateral ovarian enlargement (> 9 cm theca lutein
cysts)
3. Age greater than 40 years
4. Very high hCG levels(>100,000 m IU/ml)
5. Medical complications of molar pregnancy such as
toxemia, hyperthyroidism and trophoblastic
embolization (villi come out of placenta )
6. repeat hydatidiform mole

5. COMMON SITES FOR METASTATIC
GESTATIONAL TROPHOBLASTIC
TUMORS
Site Per cent
Lung 60-95
Vagina 40-50
Vulva/cervix 10-15
Brain 5-15
Liver 5-15
Kidney 0-5
Spleen 0-5
Gastrointestinal 0-5

6. HYDATIDIFORM MOLE
(MOLAR PREGNANCY)

7. DEFINITION AND ETIOLOGY
Molar pregnancy is characterized
histologically by abnormalities of the
chorionic villi consisting of varying degree of
trophoblastic proliferation and edema of
villous stroma.
The etiology of hydatidiform mole
remains unclear, but it appears to be due to
abnormal gametogenesis and fertilization.

8. 2 types of H-mole
Complete Mole :
 In a ‘complete mole’ the mass of tissue is completely
made up of abnormal cells
 There is no fetus and nothing can be found at the time of
the first scan.
Partial Mole :
 In a ‘partial mole’, the mass may contain both these
abnormal cells and often a fetus that has severe defects.
 In this case the fetus will be consumed ( destroyed) by
the growing abnormal mass very quickly.
Complete Mole Partial Mole

9. CYTOGENETICS
Complete molar pregnancy
Chromosomes are paternal , diploid
46,XX in 90% cases
46,XY in a small part
Partial molar pregnancy
Chromosomes are paternal and maternal, triploid.
69,XXY 80%
69,XXX or 69,XYY 10-20%

10. COMPARATIVE PATHOLOGIC FEATURES OF COMPLETE AND
PARTIAL HYDATIDIFORM MOLE
Feature Complete Mole Partial Mole
Karyotype Usually diploid 46XX Usually triploidy 69XXX most common.
Villi All villi hydropin; no normal
adjacent villi
Normal adjacent villi may be present
vessels present they contain no fetal blood
cells
blood cells
Fetal tissue None present Usually present
Trophoblast Hyperplasia usually present to
variable degrees
Hyperplasia mild and focal
Uterine size More than date Less than date
Theca Lutein cyst 30-60% common Uncommon
b HCG High more than 50 thousand Less than 50 thousand
Risk of persistent
GTN
20% <5%
Classical clinical
symptoms
Common Uncommon

11. Signs and Symptoms of complete Hydatidiform Mole
 Vaginal bleeding
 Hyperemesis ( severe vomit)
 Size inconsistent with gestational age( with no fetal heart
beating and fetal movement)
 Preeclampsia
 Theca lutein ovarian cysts
Signs and Symptoms of Partial Hydatidiform Mole
 Vaginal bleeding
 Absence of fetal heart tones
 Uterine enlargement and preeclampsia is reported in only 3% of
patients.
 Theca lutein cysts, hyperemesis is rare.

12. Complete hydatidiform mole demonstrating
enlarged villi of various size

13. Partial hydartidiform mole

14. Here is a partial mole in a case of triploidy. Note the
scattered grape-like masses with intervening normal-
appearing placental tissue.

15. INCIDENCE
 1 out of 1500-2000 pregnancies in the U.S. and Europe
 1 out of 500-600 (another report 1%) pregnancies in some
Asian countries.
 Complete > incomplete
 Repeat hydatidiform moles occure in 0.5-2.6% of patients,
and these patiens have a subsequent greater risk of
developing invasive mole or choriocarcinoma
 There is an increased risk of molar pregnancy for women
over the age 40.
 Approximately 10-17% of hydatidiform moles will result in
invasive mole
 Approximately 2-3% of hydatidiform moles progress to
choriocarcinoma ( most of them are curable)

16. CLINICAL RISK FACTORS FOR MOLAR PREGNANCY
Age (extremes of reproductive years)
<15
>40
Reproductive history
prior hydatidiform mole
prior spontaneous abortion
Diet
Vitamin A deficiency
Birthplace
Outside North America( occasionally has
this disease)

17. Hydatidiform mole: specimen from suction
curettage

18. A large amount of villi in the uterus.

19. The microscopic appearance of hydatidiform mole:
•Hyperplasia of trophobasitc cells
•Hydropic swelling of all villi
•Vessles are usually absent

20. Transvaginal sonogram demonstrating the “ snow storm” appearance.

21. Color Dopplor facilitates visualization of the enlarged spiral
arteriesclose proximity to the “ snow storm” appearance

22. Sign and symptoms of H. Mole
Symptoms
 Vaginal bleeding -most presenting symptom
 Lower abdominal pain
 Constitutional symptoms – hyperemisis gravidarum
 Trophoblastic embolization – respiratory distress.
 2% of patient with complete mole diagnosed in patient with excessive
uterine size and markedly elevated HCG level. This patient may
develop chest pain, dysnea, tachypnea, tachycardia, severe
respiratory distress during and after molar evacuation.
 Expulsion of grape like vesicles per vaginum is diagnostic of
vesicular mole.
Signs
 Pre-eclampsia 27% of patient with complete mole associated with
hypertension, proteinuria, hyperreflexia, (eclamptic convulsion rarely
occur).
 Hyperthyroidism – 7% of patient with complete molar gestation-
patient develop tachycardia, tremor, worm skin diagnosis confirmed
by increase level of T3 and T4.
 Theca lutein ovarian cyst

23. Large bilateral theca lutein cysts resembling ovarian germ cell
tumors. With resolution of the human chorionic gonadotropin(HCG)
stimulation, they return to normal-appearing ovaries.

24. Per abdomen findings
 Size of uterus more than that expected for period of
amenorrhoea 50% of cases.
 Feel of uterus is firm and elastic
 Fetal parts not felt nor any fetal movements, absence
of fetal heart sound.
Vaginal Examination :
 Internal ballottement can be elicited.
 Unilateral/ bilateral enlargement (theca lutein cyst) of
ovary may be palpable in 25-50% of cases.
 Presence of vesicles in vaginal discharge is
pathognomic of H mole.
 If the cervical os is open instead of membranes,
blood clot or vesicles may be felt.

25. Investigations
 ABO/RH, CBC
 Hepatic, renal thyroid function test.
 Ultrasound – is the criterion standard for identifying
both complete and partial molar pregnancies. The
classic image is of a “Snowstorm” pattern.
 Quantitative estimation of HCG – rapidly increase
value of serum HCG (HCG more than 1 l00,000
m/IU/ml) are usual with molar pregnancies. Normal
pregnancy value below 60,000m/IU/ml.

26. A sonographic findings of a molar pregnancy. The
characteristic “snowstorm” pattern is evident.

27. Transvaginal sonogram demonstrating the “ snow storm” appearance.

28. DIAGNOSIS
The most common symptom of a mole is
vaginal bleeding during the first trimester
however very often no signs of a problem
appear and the mole can only be diagnosed by
use of ultrasound scanning. (rutting check)
Occasionally, a uterus that is too large for the
stage of the pregnancy can be an indication.

29. DIFFERENTIAL DIAGNOSIS
• Abortion
• Multiple pregnancy
• Polyhydroamnios
• Fibroid or ovarian tumour with pregnancy.
COMPLICATIONS
Immediate
• Haemorrhage and shock
• Sepsis
• Perforation of uterus
• Pre-eclampsia
• Acute pulmonary insufficiency
• Co-agulation failure
Late
• Choriocarcinoma – following H mole ranges between 2-10%.

30. TREATMENT
 Suction dilation and curettage :to remove benign hydatidiform moles
When the diagnosis of hydatidiform mole is established, the molar
pregnancy should be evacuated.
An oxytocic agent should be infused intravenously after the start of
evacuation & continued for several hours to enhance uterine
contractility
Hysterectomy (Removal of the uterus) : used rarely to treat hydatidiform
moles if future pregnancy is no longer desired.
 Chemotherapy with a single-agent drug
Prophylactic (for prevention) chemotherapy at the time of or immediately
following molar evacuation may be considered for the high-risk patients( to
prevent spread of disease )

31. Follow-up Protocols
 History and clinical examination
 Patients with hydatidiform mole are curative over 80% by
treatment of evacuation.
 The follow-up after evacuation is key necessary
Enquire about
 uterine involution, ovarian cyst regression malignant deposit
in ant vaginal wall, cessation of bleeding, persistent cough,
breathlessness or haemoptysis
Investigation : Detection of HCG in urine or serum, chest X-ray
before t/t and after evacuation to exclude metastases, there
after it should be done at 3rd, 6th & 12th month.
Contraception should be practiced during this follow up period
combined oral pills and barrier method of contraception used,
IUCD is contraindication b/c of its frequent association of
irregular bleeding surgical sterlization is another alternative
when she has completed her family.

32. Invasive mole

33. DEFINITION
This term is applied to a molar
pregnancy in which molar villi grow
into the myometrium or its blood
vessels, and may extend into the
broad ligament and metastasize to the
lungs, the vagina or the vulva.

34. Invasive mole: the tissue invades into the myometrial layer. No
obvious borderline, with obvious bleeding.

35. A case of invasive mole: inside the uterine cavity the typical
“snow storm” appearance can be detected, The location of
blood flow suggest an invasive mole.

36. Doppler image of invasive mole

37. CHORIOCARCINOMA

38. DEFINITION
This is extremely malignant form of
trophoblastic tumour may be considered a
carcinoma of chorionic epithelium, although an its
growth and metastasis behave like sarcoma
 Characterized by abnormal trophoblastic
hyperplasia and anaplasia , absence of chorionic
villi

39. Gross specimen of choriocarcinoma

40. Microscopic image of choriocarcinoma
absence of chorionic villi

41. Incidence :
Occur in about 4% of patient after
evacuation of complete mole, but seems more
after when GTT develop after non molar
pregnancy.
Patient develops choriocarcinoma – 50%
after H. mole 15% after term pregnancy 25%
after abortion or ectopic pregnancy.

42. SYMPTOMS AND SIGNS
• Bleeding
• Infection
• Abdominal swelling
• Vaginal mass
• Lung symptoms
• Symptoms from other metastasis

43. PATIENT MAY COMMONLY PRESENT WITH SIGN OF METASTASIS
Pulmonary metastasis
• 80% of patient with metastatic GTT lung involvement
patient present with chest pain, cough, hemoptysis,
dyspnea.
Four principle pulmonary pattern
• Alveolar or snow strom pattern.
• Discrete rounded densities- cannon ball appearance
• Embolic pattern caused by pulmonary arterial occlusion
Vaginal metastasis
• occur in about 30%
Liver metastasis
• Occur in about 10%
Central Nervous System
• Involve brain in 10% cases

44. WHO Prognostic Scoring System
Score
Prognostic factor 0 1 2 4
Age(years) ≤39 >39 — —
Pregnancy history
Hydatidiform
mole
Abortion,
ectopic
Term
pregnancy
—
Interval (months) of
treatment
<4 4-6 7-12 >12
Initial hCG(mIU/ml) <103 103-104 104-105 >105
Largest tumor(cm) <3 3-5 >5 —
Sites of metastasis Lung
Spleen,
kidney
GI tract, liver Brain
No. of metastasis — 1-4 4-8 8
Previous (treatment) — — Single drug 2 or more
0-4 low risk, 5-7 intermediate risk, >8 high risk for death

45. FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR
Stage I : Disease confined to uterus
Ia : Confined to uterus with no risk factor
Ib : Confined to uterus with 1 risk factor
Ic : confined to uterus with 2 risk factor
Stage II : GTT extending outside uterus but
limited to genital str. (adenexa vagina broad
ligaments)
IIa : GTT involving genital tract with out risk
factor
Iib : GTT involving genital tract with 1 risk factor
IIC : GTT involving genital tract with 2 risk factor

46. FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR
Stage III : GTT extending of lung with or without
Known genital tract involvement
IIIa : GTT extending to lung with no risk factor
IIIb : GTT extending to lung with 1 risk factor
IIIc : GTT extending to lung with 2 risk factor
Stage IV: All other metastatic sites
IVa : All metastatic sites other site with out risk
factor
IVb : All metastatic sites other site with out 1 risk
factor
IVc: All other metastatic sites site with out 2 risk
factor
Risk Factor ; HCG > 100;000mIU/ml
Duration of ds longer then 6 months from
formenation of antedent pregnancy.

47. Diagnostic Evaluation
All Patients with persistent GTT should undergo
careful pretreatment evaluation including the
following –
Complete history and physical examination .
Measurement of serum HCG value.
. Hepatic, thyroid and renal function test.
Determination of baseline peripheral WBC and
platelet count.
Once the diagnosis established the further
examination should be done to determine the extent
of disease (Chest X- ray, CT scan of abdomen, pelvis
and Head, MRI, USG)

48. Management
1. Preventive and Curative
a. Preventive – Prophylactic CT in at risk women
following evacuation of molar pregnancy.
Risk Women –
 Age of patient >35 years.
 Level of HCG > 100,000 IU/ 24 Hours.
 Histological diagnosed infiltrative mole.
 Previous history of motor pregnancy.
- Meticulous follow up following evacuation of H. mole of
at least one years to detect early evidence of
trophoblastic reactivation.
Single agent chemotherapy is highly effective in case of
persistent trophoblastic disease.
- Selective hysterectomy in H. mole in patients of
age>35years.

49. Those who want to retain fertility
1. Single agent CT is preferred treatment in patients
with stage I disease who want to retain fertility.
 When patients are resistant to single agent
chemotherapy and desire to retain fertility
combination chemotherapy should be
administered.
 Stage II & III – Vaginal and pelvic metastatics.
Vaginal – In low risk cases.
Single agent chemotherapy have 80% rate of
remission.
High risk patients managed with primary intensive
combination chemotherapy.

50. Curative Management -
 Chemotherapy.
 Surgery.
 Radiation.
Management of various stages-
Stage I:
Initial – single agent chemotherapy or hysterectomy
with adjunctive chemotherapy .
Resistant – Combination chemotherapy
Hysterectomy with adjunctive chemotherapy.
Local resection, pelvic infusion.

51. Stage II & III-
Low risk –
Initial - Single agent chemotherapy.
Resistant – Combination chemotherapy.
High Risk –
Initial – Combination chemotherapy.
Resistant – second line combination chemotherapy
Stage IV-
Initial - Combination Chemotherapy.
Brain – Whole heat irradiation (3000 CGY)
craniotomy to manage complications.
Liver – Resection to manage complications.
Resistant – second line combination chemotherapy
hepatic arterial infusion.

52. Adjuvant chemotherapy is adminstered
for three resons
1. To reduce the likelihood of disseminating
viable tumour cell at surgery.
2. To maintain cytotoxic level of chemotherapy
in the blood stream and tissue in case viable
tumour cells are disseminated at surgery .
3. To treat any occult metastasis that may
already present at the time of surgery.

53. 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.

54. Chemotherapy
Single agent chemotherapy with either actinomycin D
or methotrexate has achieved comparable and excellent
remission rates in both non metastatic and low risk
metastatic GTN.
single drug regimen in low rate case –
Drug Dosage Route Days
Methotrexate 1-15 mg/kg IM/IV 1,3,5,7.
Folonic acid 1-015 mg/kg IM 2,4,6,8.
Actinomycin D 12 mg/kg IV 1-5
Cyclophosphamide 3mg/kg IV 1-5

55. EMA- CO protocol in poor prognosis
metastatic disease
The course will restart after 7-14 days. If possible, Generally 2
additional courses are given after the hCG levels become normal.
Days Drug Dose
Day-1 Etoposide 100mg /m2in 200 ml saline infused over 30
minutes.
Actinomycin D 0.5 mg IV bolus
Methotrexate 100mg /m2 bolus folllowed by 200mg /m2 IV
infusion over 12 hours.
Day -2 Etoposide 100mg /m2in 200 ml saline infused over 30
minutes.
Actinomycin D 0.5 mg IV bolus
Folinic acid 15mg IM every 12 hrs for 4 doses begnning 24
hours after starting methotrexate.
Day-8 Cycolphosphamide 600mg/m2 IV in saline over 30 min.
Vincristine
(oncovin)
1mg/m2 bolus

56. PROGNOSIS
 Cure rates should approach 100% in nonmetastatic
and low-risk metastatic GTD
 Intensive multimodality therapy has resulted in cure
rates of 80-90% in patients with high-risk metastatic
GTD

57. FOLLOW-UP AFTER SUCCESSFUL
TREATMENT
 Quantitative serum hCG levels should be obtained
monthly for 6 months, every two months for
remainder of the first year, every 3 months during
the second year
 Contraception should be maintained for at least 1
year after the completion of chemotherapy.
Condom is the choice.

58. Placenta Site Trophoblastic
Tumor (PSTT)

59. DEFINITION
 Placenta Site Trophoblastic Tumor is an
extremely rare tumor that arised from the
placental implantation site
 Tumor cells infiltrate the myometrium and
grow between smooth-muscle cells

61. DIAGNOSIS AND TREATMENT
 Serum hCG levels are relatively low compared
to those seen with choriocarcinoma.
 Several reports have noted a benign behavior of
this disease. They are relatively chemotherapy-
resistant, and deaths from metastasis have
occurred.
 Surgery has been the mainstay of treatment