A 40-year-old woman presented with vaginal bleeding for 1 month. On examination, her uterus was enlarged to 16 weeks size with a doughy feel and grape-like structures were seen in the cervical os. Gestational trophoblastic disease was suspected. GTD includes complete and partial hydatidiform moles, invasive moles, choriocarcinoma, and placental site trophoblastic tumors. Diagnosis involves high hCG levels and ultrasound showing a "snowstorm" pattern. Treatment is surgical evacuation followed by hCG monitoring to detect persistent disease requiring chemotherapy.

1. Gestational Trophoblastic
Diseases (GTD)
By: Gautam Hariish

2. Case Scenario
• 40 year old female, G9P8 at 4 months of
amenorrhea presented with chief complaint of
bleeding per vagina for last 1 month.
• The bleeding was moderate in amount and
associated with clots.
• No other positive history.

3. Case Scenario
• Vital signs were stable.
• Uterus was about 16 weeks gestation size, relaxed
and had a doughy feel.
• No fetal parts felt and fetal heart sound was not
found.
• Speculum examination revealed cervical os was
open, presence of bleeding and grape-like structure
was coming out of the os.

4. Provisional Diagnosis

5. Discussion
Classification of GTD
1. Benign
• Hydatidiform mole
 Complete mole
 Partial mole
2. Malignant
• Invasive mole
• Choriocarcinoma
• Placental site trophoblastic tumour

6. Risk factors
• Age:
▫ <20 years
▫ >40 years
• Previous history of molar pregnancy

8. Cytogenetics
1) Complete mole
• Majority have a 46,XX karyotype.
• Only a small percentage are 46,XY.
• Both chromosomes are paternally derived.
2) Partial mole
• Karyotype usually a triploid, often 69,XXY.
• Majority of remaining lesions are 69,XXX or
69,XYY.
• Chromosomes are of paternal and maternal origin.

9. Symptoms
• Irregular or heavy vaginal bleeding during 1st or
early 2nd trimester.
• Passage of grape like vesicles from the vagina.
• Excessive nausea and vomiting.
• Irritability, dizziness and photophobia.
• Nervousness, anorexia and tremors.

10. Signs
• Vital signs: tachycardia, tachypnea and
hypertension.
• About half of patients present with uterus size
larger for dates, whereas about one-fourth have
a uterine size compatible with or smaller than
gestational age.
• No fetal parts and fetal heart sound not found.
• Doughy consistency of uterus.
• Grapelike vesicles may be detected in vagina.
• Blood clots may be present.
• Theca lutein cysts occur in about one-third of
women.

11. Diagnosis
• Beta-hCG levels are high for early pregnancy
(>100000 mIU/mL)
• Ultrasound reveals a “snowstorm” pattern.

12. Snowstorm apearance

13. Clinical Investigations
• Full blood count
• Coagulation profile
• Liver function test
• Renal function test
• Blood grouping, typing and cross matching
• Chest X-ray
• ECG

14. Management
• Suction evacuation is preferred method of choice.
• It is best to avoid prior cervical preparation, oxytocic
agents and sharp curettage.
• Anti-D prophylaxis required for partial moles.
• Pelvic ultrasound to confirm the evacuation.
• Evacuated molar tissue sent for histopathology.

15. Pathology
• Characteristic histopathologic findings of
complete mole are:
▫ Hydropic villi
▫ Absence of fetal blood vessels
▫ Hyperplasia of trophoblastic tissue.
• A partial mole has some hydropic villi, whereas
other villi are essentially normal.
• Fetal vessels are seen in a partial mole and the
trophoblastic tissue exhibits less striking
hyperplasia.

16. Complete mole

17. Partial mole

18. Follow up
• To confirm successful treatment and identify women
with persistent GTD or GTN who may require
adjuvant chemotherapy or surgery at an early stage.
• If beta-hCG has reverted to normal within 56 days of
the pregnancy event then follow up will be for 6
months from the date of uterine evacuation.
• If beta-hCG has not reverted to normal within 56
days of pregnancy then follow up will be for 6
months from normalisation of the hCG level.

19. Follow up
• Serial beta-hCG:
▫ Weekly until 3 consecutive levels have been normal.
▫ Then, monthly levels until 3 consecutive levels have
been normal.
▫ Following the evacuation, the beta-hCG levels should
steadily decline to undetectable levels, usually within
12 to 16 weeks.
• Women should be advised not to conceive until their
follow-up is complete.
• Beta-hCG levels also measured 6-8 weeks after end
of any future pregnancies to exclude disease
recurrence.

20. Beta-hCG regression curve

21. Invasive mole
• Usually a locally invasive tumour.
• Constitutes about 5-10% of all molar pregnancies,
representing the majority of those with persistent
beta-hCG levels after molar evacuation.
• May penetrate the entire myometrium, rupture
through the uterus and result in hemorrhage into
the broad ligament or peritoneal cavity.
• Hysterectomy usually done in patients with
persistent beta-hCG levels after molar evacuation or
in patients with persistent titers despite
chemotherapy who have no evidence of metastatic
disease.

22. Invasive mole

23. Placental Site Trophoblastic Tumour
• Extremely rare tumour that arise from placental
implantation site.
• Produce small amounts of beta-hCG and human
placental lactogen relative to their mass.
• Tend to remain confined to the uterus and
metastasize late in their course.
• Relatively insensitive to chemotherapy, so
surgical resection is important.

24. Placental Site Trophoblastic Tumour

25. Choriocarcinoma
• A malignant form of GTD.
• About half of patients with gestational
choriocarcinoma have had a preceding molar
pregnancy.
• In the rest, the disease is preceded by a
spontaneous or induced abortion, ectopic
pregnancy or normal pregnancy.
• Trophoblastic disease following a normal
pregnancy is always choriocarcinoma.
• Has a tendency to disseminate hematogenously.

26. Symptoms
• Most present with symptoms of metastatic
disease.
• Vaginal bleeding is a common presentation.
• Amenorrhea may develop, simulating early
pregnancy.
• Hemoptysis, cough or dyspnea (lung metastases)
• Headache, dizziness, “blacking out”, or other
symptoms referable to space-occupying lesion
(CNS metastases)
• Rectal bleeding, malena (GIT metastases)

27. Signs
• Uterine enlargement
• Bleeding per vagina
• Vaginal mass
• Neurologic deficits
• Abdominal tenderness
• Jaundice
• Signs of lung metastases

28. Diagnosis
• Diagnosed by rising beta-hCG following
evacuation of a molar pregnancy or any
pregnancy event.
• Once diagnosis is established, further
examinations done to determine the extent of
disease:
▫ Chest X-ray
▫ CT abdomen, pelvis and brain
▫ MRI

29. Gross pathology

30. Staging
• Stage I: Confined to uterus
• Stage II: Limited to genital structures
• Stage III: Lung metastases
• Stage IV: Other metastatic sites

31. Staging
• Substages assigned for each stage as follows:
▫ A: No risk factors present
▫ B: One risk factor
▫ C: Two risk factors
• Risk factors are:
▫ Beta-hCG greater than 100,000 mIU/mL
▫ Duration of disease longer than 6 months

32. Treatment
• Treatment either with single-agent or multi-
agent chemotherapy.
• Treatment is based on the FIGO 2000 scoring
system.
• Women with scores ≤ 6 are at low risk and
treated with single-agent IM methotrexate
alternating daily with folinic acid for 1 week
followed by 6 rest days.
• Women with scores ≥ 7 are at high risk and
treated with IV multi-agent chemotherapy which
includes combinations of methotrexate,
dactinomycin, etoposide, cyclophosphamide and
vincristine.

34. Treatment
• Treatment is continued in all cases until the hCG
level has returned to normal and then for a
further 6 consecutive weeks.
• In appropriately selected patients, hysterectomy
may be the primary therapy.
• In patients with metastatic disease, radiation is
often employed to these areas in conjunction
with chemotherapy.

35. Follow up
• All patients should have weekly beta-hCG level
measurement until 3 normal levels have been
measured.
• For GTN with good prognosis, monthly
measurements should be done until 12 normal levels
have been recorded.
• For GTN with poor prognosis, monthly levels done
until 24 normal measurements have been recorded.
• Women who undergo chemotherapy are advised not
to conceive for 1 year after completion of treatment.
• If a patient’s beta hCG levels become normal and
later is found to be rising, a second metastatic
workup must be undertaken before initiation of
secondary therapy.

36. References
• Hacker, Gambone and Hobel (2016) Essentials of
Obstetrics & Gynaecology 6th Edition. Elsevier. pp 465-
472
• Polychronis O, Basileios P, Elina P et al. Repetitive
Complete Molar Pregnancy in a 54 year old patient in
a time distance of eighteen years from first incident:
Case report and mini review. Case reports in medicine,
Hindawi Publishing Corporation, 2011.
• C.S. Vyas et al. A case series of gestational trophoblastic
tumor- benign mole to life threating perforating mole.
Gujarat Medical Journal 68, 121-123, 2013.
• N K S Tharmaseelan. Gestational Trophoblastic Disease
in a 54 year old woman: a case report. Singapore
Medical Journal 31, 627-628, 1990.
• Royal College of Obstetricians & Gynaecologists (2010)
The Management of Gestational Trophoblastic Disease.
Green-top Guideline No.38.
• https://emedicine.medscape.com/article/279116-
overview