GESTATIONAL

TROPHOBLASTIC NEOPLASMS
 DEFINITION

►Gestational trophoblastic disease (GTD): form a group of

disorders spanning the conditions of complete and partial molar
pregnancies to malignant condition of :
►Invasive mole
►Choriocarcinoma
►Placental site trophoblastic tumor (PSTT)
►Epitheloid trophoblastic tumor (ETT)

Williams Gynecology
CLASSIFICATION

Stevens FT et al. Gestational Trophoblastic Disorders: ...

Geburtsh Frauenheilk 2015; 75: 1043–1050
Horii M, Kindelberger DW, Quade BJ, et al. Trophoblast Neoplasia. Diagnostic
Gynecologic and Obstetric Pathology.
Hydatidiform moles, gestational choriocarcioma and placental
site trophoblastic tumor  HISTOLOGIC DIAGNOSIS

Post-molar GTN  CLINICAL and LABORATORY criteria

CLASSIFICATION
► Complete Mole  Totally paternally
derived diploid genotype (diandric
diploidy)

► Partial Mole  Associated with

complete triploidy that incorporates an
extra haploid paternal chromosomal
complement (diandric triploidy)
SIGN & SYMPTOMS
 HISTOPATHOLOGY RESULT OF
HYDATIDIFORM MOLE

►An abnormal pregnancy characterized by varying degrees of

trophoblastic proliferation : (TRIAS of Mole)
►Trophoblast proliferation
►Avascular of villi 🡪 CLINICAL
PATHOLOGY
►Hydrophic degeneration of villi
 CLASSIFICATION
Complete Mole Partial Mole

• The chorionic villi exhibit • chorionic villi of varying size and

generalized hydatidiform swelling shape with focal edema and
• Difuse trophoblastic hyperplasia scalloping
• stromal trophoblastic inclusions
• focal trophoblastic hyperplasia
 NATURAL HISTORY

►Complete Mole  evacuation  local uterine invasion 15% and

metastasis 4%
►Signs of high risk patient with complete mole:
►hCG level >100,000 milli-IU/mL
►Excessive uterine enlargement
►Theca lutein cysts larger than 6 cm in diameter
►Patient > 40 years old  risk of GTN post-mola  53%
►Partial Mole  2–4% develop persistent postmolar tumor
 NATURAL HISTORY

► Trophoblast : derived from outer cell mass of the preimplantation embryo and has several unique
properties
► Affect the physical implantation of the embryo into endometrium and produces sufficient amount of
human chorionic gonadotropin (hcg)  to maintain pregnancy
► Normal trophoblast : lacks expression of transplantation antigens such HLA and ABO system 
allows escape from maternal immunologic rejection
► Invade into maternal decidua, vessels, and myometrium  furthermore continuously embolizes
from endometrial sinuses into maternal venous system where the trophoblast cell are filtered by
the pulmonary circulation and rarely gain access to the remainder of the systemic circulation
► GTN  normal trophoblast function are exaggerated
► Complete and partial mole, invasive mole, and choriocarcinoma; exhibit proliferation of both
cytotrophoblast and syncytiotrophoblast cell  maintain the secretion of HCG
► In contrast : The placental site tumor derived from the intermediate cytotrophoblast  produced low
level of hCG
 DIAGNOSIS

USG
► Complete mole 🡪 “swiss cheese” ► Partial Mole
pattern
DIAGNOSIS : MOLAR PREGNANCY IS USUALLY
DIAGNOSED DURING THE FIRST TRIMESTER

Diffuse mixed echogenic and vesicular pattern

replacing the placenta 🡪 “snowstorm”
appearance
 TREATMENT

► Evacuation:
► Suction Curretage  Reproductive Function (+)
► Hysterectomy  Reproductive Function (-)
FOLLOW-UP CARE – MOLAR PREGNANCY

► Avoid pregnancy for at least 6 months after the first normal B-

hCG (oral contraceptive pills is preferable)
Normal value hCG levels :
< 5mIU/ mL
POSTMOLAR SURVEILLANCE

► GTN after hydatidiform moles occur approx within 6 mo after evacuation

► 15-20% after CM , 1-5% after PM develop into GTN
► After evacuation, oral contraceptive is preferred due to suppressing LH, which can
be mistaken as false-positive hCG value (LH shares alpha- subunit with hCG)
► After remission for 6 months, pregnancy can be encouraged and hCG monitoring
can be discontinued
► Prophylactic Chemotheraphy (Single course of Methotrexate-folinic acid) 
reduce the incidence of postmolar GTN from 47.4% to 14.3%
HIGH RISK FOR GTN AFTER MOLE

► Preevacuation uterine size greater than gestational age

or larger than 20 weeks gestation
► Theca-lutein cysts larger than 6 cm
► Age > 40 years
► Serum hCG levels > 100,000 mIU/mL
► Previous hydatidiform mole
 SIGNS & SYMPTOMS GTN

► Continued uterine bleeding, uterine perforation, enlarged irregular uterus,

persistent bilateral ovarian enlargement
► From metastatic lesions: abdominal pain, hemoptysis, melena, increased
intracranial pressure (headaches, seizures, hemiplegia), dyspnea, cough,
chest pain
 PSTT
GTN (DIAGNOSIS) • Very rare
CHORIOCARCINOMA
ETT • Pathology:
• Abnormal •
trophoblastic hyperplasia
Tumor cells infiltrate the
► GTD • and
INVASIVE MOLE
Variations
anaplasia of PSTT 🡪 rare
myometrium with vascular/
• Contain
• •Invasion neoplastic chorionic-type
No villiof the
lymphatic myometrium
invasion
► Hydatidiform mole HYDATIDIFORM intermediate
• •HydropicMOLE villi, (extravilli) trophoblast
• No
Hemorrhage villitrophoblast
and necrosis
► Invasive mole • βhCG plateu incell
•hyperplasia
Distant
surrounds
4• times
Tumor cellthe
examination
metastases
artery
staining
🡪 for 3 hPL
(+) for
weeks • 15 • • Mostly appear after aterm pregnancy
Clinical:
% metastasis
lung/brain/liver to vagina/lung
• Relative resistant to chemotherapy
• βhCG increased by ≥ 10% in 3 times
► TRUE NEOPLASIA examination for •2 weeks
hCG levels are not an indicator
• main treatment 🡪 operation
• Persistent βhCG forThe
6 months after
► Choriocarcinoma evacuation of the mole
► Placental site trophoblastic tumor (PSTT)
► Epithelioid trophoblastic tumor (ETT)
 FIGO CRITERIA FOR DIAGNOSIS OF GTNS

Update on the diagnosis and management of gestational trophoblastic disease

Article in International Journal of Gynecology & Obstetrics · October 2015 DOI: 10.1016/j.ijgo.2015.06.008
CLASSIFICATIONS
Clinical Classification of Gestational Trophoblastic Tumors
I. Nonmetastatic : No evidence of disease outside uterus
II. Metastatic
A. Good Prognostic
1. Short duration of symptoms (≤4 months)
► Hammond2. Low hCG level (≤40.000 mIU/ml serum β-hCG)
3. No metastases to brain or liver
► FIGO 4. No antecedent term pregnancy
► FIGO-WHO 5. No prior chemotherapy
B. Poor Prognostic (any high-risk factor)
1. Long duration of symptoms (> 4months)
2. High pretreatment hCG level (>40.000 mIU/ml serum β-hCG)
3. Brain or liver metastases
4. Antecedent term pregnancy
5. Prior chemotherapy (unsuccessful)
2. TREATMENT:

► Based on Stage:
►Non-metastasis (Stage I)
►Low-risk metastasis (Stage
II dan III, FIGO/WHO Survival
Single-agent
Score ≤ 6) Chemotherapy
Rate: 100%

►High-risk metastasis
(Stage II-IV, FIGO/WHO Multiagent Chemotherapy Survival
Score > 6) with/without adjuvant Rate: 80-90%
radiation and operation
TREATMENT: NON METASTATIC AND LOW-RISK
GTNS

Beware of liver function!

S.E: hematologic
suppresion, cutaneous Essentially can be cured 🡪 ~
toxicity, mucositis, 100%
alopecia,GI toxicity,
serositis

In most European centres, methotrexate with folinic

acid is preferred because it is less toxic than
methotrexate alone or single-agent actinomycin D.

Diagnosis, staging and treatment of patients with gestational

trophoblastic disease
National Clinical Guideline No. 13 (November, 2015)
CHEMOTHERAPY FOR HIGH-RISK GTN  EMACO

RESISTANT

EP-EMA

Seckl MJ, Gestational trophoblast disease: clinical

Survival rate: 65 - 94%
presentation and treatment, Diagnostic
Histopathology, https:// Most widely used regimen
doi.org/10.1016/j.mpdhp.2018.12.002
 BETA HCG OBSERVATION

• Every 2 weeks during chemotherapy

• After normalization: every week for 3
consecutive weeks
• Every month for 12 months
 CONSOLIDATION DOSE

• Consolidation Dose
 After complete remission  to prevent relapse
METASTASIS

► Brain  Radiotheraphy + chemotherapies (cure rate 75%)

►Consideration: using whole brain radiotheraphy could imply on
cognitive complications
►Rustin et al: early craniotomy with excision of isolated lesions
combined with high dose sytemic and intrathecal
chemotheraphy
► Liver and other sites of metastases: surgeries
THANK YOU.