GESTATIONAL

TROPHOBLASTIC
PRESENTED BY : DR TAHMEENA
DISEASE
DR SHWETA
SR GUIDE: DR MANJEERA
MODERATOR : DR K USHA RANI
 CASE PRESENTATION
• A 20 YEAR OLD PRIMIGRAVIDA WITH H/O 3 MONTHS OF AMENORRHOEA PRESENTED WITH C/O
IRREGULAR BLEEDING PER VAGINUM FOR 5 DAYS
• NO H/O TRAUMA / FALL / SEXUAL INTERCOURSE PRECEDING BLEEDING/ FEVER/ DRUG INTAKE/
FOUL SMELLING DISCHARGE
• NO H/O HYPEREMESIS / PASSAGE OF VESICLES / PAIN ABDOMEN
• M/H : LMP : 2/11/2020 ; REGULAR CYCLES
• O/H : PRIMI, MARRIED SINCE 1 YEAR
• PAST H/O - NO H/O CHRONIC MEDICAL OR SURGICAL ILLNESS ; NO H/O ANY PREVIOUS
SURGERIES
• PERSONAL H/O : NON SMOKER , NON ALCOHOLIC , VEGETARIAN , NORMAL BLADDER BOWEL
HABITS
• FAMILY H/O : NOT SIGNIFICANT
• GENERAL EXAMINATION : PATIENT WAS CONSCIOUS AND ORIENTED.
AFEBRILE , BP :110/70 MMHG , PR 86/MIN , PALLOR + (8GM%) , NO NECK SWELLINGS ,
CVS/RS :WNL

• P/A: UTERUS WAS 18 WEEKS SIZE , NO BALLOTTEMENT, UTERUS- RELAXED.

• P/S: CERVIX/VAGINA NORMAL, BLEEDING THROUGH OS PRESENT WITH PASSAGE OF
CLOTS ,OS CLOSED
• P/V: UTERUS WAS UNIFORMLY ENLARGED SOFT, AROUND 18 WEEK SIZE , BILATERAL
FORNICEAL CYSTIC MASS OF 4CM * 4CM , SMOOTH SURFACE , WITH REGULAR
MARGINS , MOBILE , NON TENDER
 DIFFERENTIAL DIAGNOSIS

• THREATENED ABORTION
• PREGNANCY WITH WRONG DATES
• PREGNANCY WITH MYOMA/ADENOMYOSIS
• MOLAR PREGNANCY
 MANAGEMENT
• INVESTIGATIONS:

• LABORATORY
 COMPLETE BLOOD COUNT : HB :9.2 GM% , TLC 8600/MM3 ,
PLT : 1.5 LAKH/MM3
 BLOOD GROUP : O POSITIVE
 THYROID FUNCTION TESTS: TSH : 2.3
• PELVIC USG : UTERUS APPEAR BULKY WITH COMPLEX ECHOGENIC MASS SHOWING
MULTIPLE ROUNDED ANECHOIC CYSTIC AREAS WITHIN ; WITH NO FETAL POLE
• OVARIES BILATERALLY ENLARGED SHOWING MULTIPLE CYST WITHIN, LARGEST OF
SIZE 3.5*4CM LIKELY SUGGESTIVE OF THECA LUTEIN CYST
• IMP: F/S/O COMPLETE HYDATIFORM MOLE WITHIN BILATERAL THECA LUTEIN CYST
 MANAGEMENT
• INVESTIGATIONS:

• LABORATORY
 ELECTROLYTES, BUN, CREATININE : KFT : 33/0.7 , SE: 135/5.2
 LIVER FUNCTION TESTS : TOTAL BIL 0.7 , SGOT : 23, SGPT :34 ,
ALP : 112
 THYROID FUNCTION TESTS: TSH : 2.3
 BLOOD GROUP : O POSITIVE
 B-HCG : 3,09, 716
 CHEST XRAY : NORMAL
 AFTER BLOOD SOS PATIENT WAS UNDERTAKEN FOR SUCTION AND
EVACUATION
HISTOPATHOLOGICAL EXAMINATION OF CURETTAGE :
GROSS : MULTIPLE BROWNISH PIECES RECEIVED
MICROSCOPY: DIFFUSE HYDROPIC SWELLING AND
TROPHOBLASTIC PROLIFERATION ON THE SURFACE OF

CHORIONIC VILLI , WITH ABSENCE OF EMBRYONIC TISSUE .

S/O COMPLETE MOLAR PREGNANCY

 DIAGNOSIS

• COMPLETE HYDATIFORM MOLE

 HCG
• HUMAN CHORIONIC GONADOTROPIN (HCG) IS A HORMONE PRODUCED BY the placenta
after implantation by synctiotrophoblast , smaller amounts can also be produced by pituitary gland ,
liver and colon.
• FORMS : 1.total hCG (regular intact heterodimeric form)
• 2. C-terminal peptide total hCG,
• 3.intact hCG, 4.free β-subunit hCG,
• 5.β-core fragment hCG, 6.hyperglycosylated hCG,
• 7.nicked hCG, 8. FREE alpha SUBUNIT hCG, and
• 9. pituitary hcg
• Regular hCG is the main form of hCG associated with the majority of pregnancy and in non-invasive
molar pregnancies. This is produced in the trophoblast cells of the placental tissue. Hyperglycosylated
hCG is the main form of hCG during the implantation phase of pregnancy, with invasive molar
• STRUCTURE :It is heterodimeric , with an α (alpha) subunit identical to that
of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating
hormone(TSH), and β (beta) subunit that is unique to hCG.
• 1.The α (alpha) subunit is 92 amino acids long coded by chromosome no 6.
• 2. The β-subunit of hCG gonadotropin (beta-hCG) contains 145 amino acids,
on chromosome 19q13.3
• HCG is primarily catabolized by the liver, although about 20% is excreted in the urine.
The beta subunit is degraded in the kidney (PCT) to make a core fragment which
is measured by urine hCG tests.
 HCG TESTING
• Most tests employ a monoclonal antibody, which is specific to the β-subunit of hCG (β-
hCG) to ensure that tests do not make false positives by confusing hCG with LH and FSH.
• Based on the sandwich principle, which uses antibodies to hCG labeled with an enzyme or
a conventional or luminescent dye. Pregnancy urine dipstick tests are based on the lateral
flow technique.,
• The urine test is a a chromatographic immunoassay, thresholds range from 20 to 100
mIU/ml.
• The serum test, using 2-4 mL of venous blood, is typically a chemiluminescent or
fluorometric immunoassay that can detect βhCG levels as low as 5 mIU/ml and allows
quantification of the βhCG concentration.
• An hCG level of less than 5 mIU/mL is considered negative for pregnancy, and
anything above 25 mIU/mL is considered positive for pregnancy. Serial increase in levels
are more informative
 INTERFERING FACTORS
WHILE UNCOMMON, FALSE POSITIVE HCG TESTS CAN RESULT IN UNNECESSARY MEDICAL
CARE AND/OR IRREVERSIBLE SURGICAL INTERVENTIONS. FALSE NEGATIVES CAN LEAD TO DELAY
IN DIAGNOSIS
• SERUM FALSE POSITIVES (1/1000 TO 1/10,000)
• ECTOPIC PRODUCTION OF HCG (MULTIPLE MYELOMA, STOMACH, LIVER, LUNG, BLADDER,
PANCREATIC, BREAST, COLON, CERVICAL, AND ENDOMETRIAL CANCERS)
• HETEROPHILE ANTIBODIES (AUTOANTIBODIES AND ANTIBODIES FORMED AFTER EXPOSURE TO
ANIMAL PRODUCTS THAT INTERACT WITH THE ASSAY ANTIBODIES)
• RHEUMATOID FACTORS (CAN BIND THE ANTIBODIES IN THE ASSAY )
• IGA DEFICIENCY
• RED BLOOD CELL OR PLASMA TRANSFUSION OF BLOOD WITH HCG IN IT HAVE BEEN REPORTED
• EXOGENOUS HCG PREPARATIONS FOR WEIGHT LOSS, ASSISTED REPRODUCTION, DOPING
• PITUITARY HCG
• POSTMENOPAUSAL WOMEN
• SERUM FALSE NEGATIVES
• EARLY MEASUREMENT AFTER CONCEPTION
• "HOOK EFFECT" CAN OCCUR WHEN HCG LEVELS ARE ABOUT 500,000 MIU/ML.

• URINE FALSE POSITIVES

• BLOOD OR PROTEIN IN THE URINE
• HUMAN ERROR IN RESULT INTERPRETATION
• ECTOPIC PRODUCTION OF HCG
• EXOGENOUS HCG
• DRUGS (ASPIRIN, CARBAMAZEPINE, METHADONE, HIGH URINARY PH AND SEMINAL FLUID
• URINE FALSE NEGATIVES
• EARLY MEASUREMENT AFTER CONCEPTION
• DILUTE URINE SPECIMEN
Human Chorionic Gonadotropin (HCG)
• "HOOK EFFECT" Danielle Betz; Kathleen Fane.
 PHANTOM HCG
• PERSISTENT MILD ELEVATIONS OF BHCG ARE DETECTED THAT LEADS TO
ERRONEOUS TREATMENT OF PATIENTS WITH CYTOTOXIC CHEMOTHERAPY OR EVEN
HYSTERECTOMY OR BOTH IN ABSENCE OF BHCG MOLECULE OR TROPHOBLASTIC
DISEASE
• REASON : HETEROPHILE ANTIBODY
• RAISED LH LEVELS
• PITUITARY HCG
• PREVENTION : 1. UPT : AS HETEROPHILE ANTIBODIES ARE NOT FILTERED AND
EXCRETED IN URINE , TEST WILL BE NEGATIVE ( ENSURE SERUM BHCG LEVEL TO BE
SIGNIFICANTLY HIGHER THAN DETECTION THRESHOLD OF UPT)
2. SPECIALISED LABORATORY TESTS THAT BIND HETEROPHILE ANTIBODIES
3. SWITCHING BHCG ASSAY KITS
4.HORMONE SUPPRESSION TO SUPPRESS LH AND PITUITARY HCG
 HOOK EFFECT
• IN MOLAR PREGNANCY EXCESS BETA HCG IS SECRETED.
• EXCESS HCG SIMULTANEOUSLY SATURATE THE FIXED, SOLID-PHASE ANTIBODY AND THE
LABELLED, SOLUBLE ANTIBODY, PREVENTING SANDWICH FORMATION. THIS IS KNOWN AS
HOOK EFFECT PHENOMENON RESULTS IN ABSENCE OF A SIGNAL AND THUS FALSE NEGATIVE
RESULTS.
 INTRODUCTION
• GESTATIONAL TROPHOBLASTIC DISEASE REFERS TO A SPECTRUM OF INTER-RELATED BUT
HISTOLOGICALLY DISTINCT TUMOURS ORIGINATING FROM THE PLACENTAL TROPHOBLASTS
• PROGNOSIS : EXCELLENT , EVEN WIDESPREAD METASTASIS IS CURABLE.
• MODIFIED WHO CLASSIFICATION OF GTD (FIGO 2018)
Premalignant Gestational trophoblastic neoplasia

Invasive mole

Complete hydatidiform mole Choriocarcinoma

Partial hydatidiform mole Placental site trophoblastic

tumours

Atypical placental site nodule (APSN) Epitheloid trophoblastic tumours

APSN 10-15% may coexist with or develop into PSTT/ Berek and Novak ed16
ETT
 MOLAR PREGNANCIES

• EPIDIMIOLOGY AND RISK FACTORS

• INCIDENCE : 2/1000 in southeast asia, japan and china , 0.5-1 in North America and
Europe
• Ethinicity : more in Asian , Hispanics and American Indians.
• Socioeconic status : incidence decreases with improved socioeconomic conditions
• Mutations in NLRP7 and KHDC3L located on chromosome 19q13.4 have been reported
in women with recurrent molar pregnancy
•

Williams gyanec ed4 ; Berek and Novak ed16

EPIDIMIOLOGY AND RISK FACTORS (CONT..)
• AGE
• >40 years : 5 to 10 fold greater risk
• >50 years : 33% risk

• Adolescents : 7 fold increased risk

• History of previous GTD-

• Previous 1 mole- 1%

• Previous 2 mole- 16-28%

• Women with blood type A or AB are at slightly higher risk than those with type B or O.
• History of irregular menstruation and OCP usage
• Decrease in consumption of Dietary carotene and animal fat
SOPER ET AL OBSTET GYNECOL. 2006 JUL. 108(1):176-87
 KARYOTYPE
COMPLETE MOLE
Empty 23x 23x 46xx homozygous
1
ovum

endoduplication

23x
Empty
2 ovum 46xx heterozygous

23x

Berek and Novak ed16

 KARYOTYPE
COMPLETE MOLE

23x
3 Empty
ovum 46xx

23x

4
46yy Non viable gamete
 KARYOTYPE
PARTIAL MOLE

23x
23x 69XXX
1

23x

23x
2 23x
69XXY

23Y
 KARYOTYPE
PARTIAL MOLE

23Y
3 23x 69XYY

23Y

4 69YYY Non viable gamete

 CLINICAL PRESENTATION OF
HYDATIFORM MOLE
features Complete mole Partial mole
Most common presentation Irregular vaginal bleeding (46%) Sponataneous sbortion
Excessive uterine enlargement 28% 3.7%
Early onset preeclampsia 27% 2%
hyperemesis 8% rare
hyperthyroidism 7% rare
Theca lutein cyst (6cm ) 50% rare
Acute respiratory distress rare rare

Williams gyanec ed4 ; Berek and Novak ed16

 ULTRASOUND FINDINGS
Partial mole Complete mole
Presence of fetus Absence of fetus
Presence of amniotic fluid Absence of amniotic fluid
Placenta with abnormal findings , cystic spaces (swiss Central heterogenous uterine mass with discrete
cheese pattern) increased echogenicity of chorionic villi anechoic cystic spaces (snowstorm) . The small
cystic area correspond to chorionic villi

Absence of theca lutein cyst Ovarian theca lutein cyst , often bilateral

Focal cystic spaces in the placental tissue and an

increase in transverse diameter of gestational sac is
seen in partial mole (PPV of 90%) , ratio of transverse:
AP diameter >1.5

Williams gyanec ed4 ; Berek and Novak ed16

PARTIAL MOLE
COMPLETE MOLE
 HISTOPATHOLOGY
• Characterised by : 1. trophoblastic proliferation
2.hydropic villi
• Complete mole : diffuse hydropic swelling and trophoblastic proliferation on the
surface of chorionic villi , often atypical and absence of embryonic tissue .
• Partial mole : 3 of the 4 major diagnostic criteria must be present
1.two populations of villi
2.enlarged irregular, dysmorphic villi with trophoblastic inclusions
3. enlarged cavitated villi (>/= 3-4mm )
4.synctiotrophoblast hyperplasia /atypia
• P57kip2 is a nuclear protein whose gene is paternally imprinted and maternally
Williams gyanec ed4 ; Berek and Novak ed16
expressed ,thus absent in complete moles
PATHOLOGY
 FEATURES OF HYDATIDIFORM
MOLES
Features Complete mole Partial mole
Foetal embryonic tissue Absent Present
Hydatidiform swelling of Diffuse Focal
chorionic villi

Trophoblastic hyperplasia Diffuse Focal

Scalloping of villi Absent Present
Trophoblastic stromal inclusions Absent Present
Karyotype 46XX Triploid 69 XXX, 69XXY
P57KIP2 immunostaining Negative Positive
Typical diagnosis Molar gestation Missed abortion
Postmolar malignant sequelae 15% 4-6%
Baseline b-hcg very high; >1lakh mIU in 50% High; >1lakh in <10%
 TREATMENT
2018 FIGO GUIDELINES

• SUCTION EVACUATION AND CURETTAGE ideally performed under ultrasound guidance, is

method of choice of molar pregnancy
• 12-14 MM SUCTION CANNULA IS USED.
• INTRAVENOUS OXYTOCIN infusion is started at the onset of suction curettage.
• Rh immune globulin should be given to rh-negative women as rhd factor is expressed on the trophoblast.
• Prolonged cervical preparation, particularly with prostaglandins, should be avoided where possible to reduce
the risk of embolization of trophoblastic cells. (RCOG 2010)
• Product of conception to be sent for histopathological examination.
• HYSTEROTOMY and MEDICAL INDUCTION OF LABOUR are not recommended because these methods
increase maternal morbidity and the development of post molar GTN.
• HYSTERECTOMY is an alternative to suction curettage if childbearing
is completed and high risk factors are present.
• Hysterectomy is performed with the mole in situ.
• Ovaries may be preserved , even in the presence of prominent theca lutein
cyst.
• Decreases the need for subsequent chemotherapy by eliminating the risk
for local myometrial invasion.
• Beta HCG follow up is required after hysterectomy.
 PROPHYLACTIC CHEMOTHERAPY
• Single dose of methotrexate/ dactinomycin decreased the incidence of post molar
GTN to 3%-8%.
• DUE TO SIGNIFICANT TOXICITY IT IS ONLY RECOMMENDED IN VERY
LIMITED CASES:
• Risk of postmolar gtn is much greater than normal
• Adequate HCG follow up is not possible

Williams gyanec ed4 ; Berek and Novak ed16

 FOLLOW UP (FIGO)

• b-hCG monitoring every 1–2 weeks till levels normalise

• Single additional confirmatory normal b-hCG measurement 1 month after first b-

hCG normalization is recommended for a PHM
• Monthly b-hCG measurements should be obtained for only 6 months after b-
hCG normalization for a CHM
 FOLLOW UP

• After molar evacuation bhcg is monitored weekly until levels are normal for 3
consecutive weeks

• Followed by monthly till 6 months

• Average time taken for normalisation of bhcg level after molar evacuation is 9
weeks
 FOLLOW UP
(RCOG)

• If 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 hCG has not reverted to normal within 56 days of the pregnancy event then
follow-up will be for 6 months from normalisation of the hCG level.
• All women should notify the screening centre at the end of any future pregnancy,
whatever the outcome of the pregnancy. hCG levels are measured 6-8 weeks
after the end of the pregnancy to exclude disease recurrence .
 CONTRACEPTION

Effective contraception necessary till β-hCG levels normalize to avoid

confusion with pregnancy

• OCPs are preferred post evacuation

• IUCDs –(MEC4) not used till β-hCG levels normal – risk of perforation
• Barrier methods – not recommended – high failure rate
• Avoid pregnancy minimum of 6 months to 1 year after the last normal
hCG.

Williams gyanec ed4 ; Berek and Novak ed16

 CASE

A 29 year old primigravida @14 weeks 5 days with

Amenorrhoea for 3 months
came to opd with chief complain of pain in lower abdomen since 2 month which was dull aching in nature on and off and
relieved on taking medication.
Patient was doing routine antenatal visit at dispensary when a dating ultrasound along with other routine investigations were
advised. It was informed to her that usg shows a molar pregnancy and after which beta HCG, pelvic MRI, CECT chest and
abdomen were advised and she was referred to SJH.
Menstrual history –
Menarche achieved at 13 years of age, LMP 3months back
previous cycles have been regular at 28-30 days, lasting for 4-5 days, average flow , no dysmenorrhoea
Got married 9 months back
Obstetric history-
Spontaneous conception
• PAST H/O - NO H/O CHRONIC MEDICAL OR SURGICAL ILLNESS ; NO H/O ANY PREVIOUS
SURGERIES
• PERSONAL H/O : NON SMOKER , NON ALCOHOLIC , VEGETARIAN , NORMAL BLADDER BOWEL
HABITS
• FAMILY H/O : NOT SIGNIFICANT
• GENERAL EXAMINATION : PATIENT WAS CONSCIOUS AND ORIENTED.

AFEBRILE , BP :110/70 MMHG , PR 86/MIN , PALLOR + (8GM%) , NO NECK SWELLINGS , CVS/RS :WNL

• P/A: UTERUS WAS 14 WEEKS SIZE .

• P/S: CERVIX/VAGINA NORMAL, NO BLEEDING
• P/V: UTERUS WAS UNIFORMLY ENLARGED SOFT, AROUND 14WEEK SIZE , MOBILE , NON
TENDER
BILATERAL FORNICES FREE
INVESTIGATIONS
• MBG – B+
• CBC- 11.7/8,400/3.52 LACS
• COAG-12.3/24.6/1.05
• LFT-0.2/101/91/53
• KFT- 13/0.4
• SE-133/4.1
 TVS (OUTSIDE)
24/12/20
• HETEROGENOUSLY PREDOMINANT ECHOGENIC LESION WITH MULTIPLE SMALL
CYSTIC AREAS SEEN FILLING THE G-SAC. ANTERIOR MYOMETRIUM
APPEARSTHINNED WITH IRREGULAR ECHOGENIC AREAS NOTED WITH IN IT.
• F/S/O ?GTD
?INVASIVE MOLE
 THYROID PROFILE
2/1/21 13/1/21

T3-0.8 T3- 121

T4-11.3 T4- 9.50

TSH-0.1 TSH -0.4

 ΒhCG
24//12/20 13/01/21

2.25 lacs IU/ml 3.53 lacs IU/ml

 MRI PELVIS
25/12/20
• UTERUS BULKY, AV , 10.1× 9.4 × 5.3 CM, SHOWS LARGE WELL DEFINED ,ROUNDED
SHARPLY MARGINATED MILDLY HETEROGENOUS EXPANSILE LESION OF SIZE ~5.7 × 7 × 5
CM IN THE ENDOMETRIAL CAVITY.
• MULTIPLE TINY ROUNDED CYSTIC AREAS SEEN.
• E/O PARTIAL DISRUPTION WITH SUBTLE THICKENING OF JUNCTIONAL ZONE WITH
CONTOUR IRREGULARITY SEEN IN REGION OF ANTERIOR MYOMETRIUM SUGGESTING
POSSIBILITY OF EARLY/SUPERFICIAL INVASION.
F/S/O GESTATIONAL TROPHOBLASTIC DISEASE LIKELY INVASIVE MOLE WITH
EARLY/SUPERFICIAL INVASION OF ANTERIOR MYOMETRIUM.
 IMAGING

• CXR (2/1/20)- NAD

• CECT CHEST (9/1/21)- NAD
• CECT ABDOMEN (9/1/21)-BULKY UTERUS WITH HETEROGENOUSLY ENHANCING
LESION WITH NECROTIC AREAS IN ENDOMETRIAL CAVITY OVERLYING
MYOMETRIAL THINNING AND ADJOINING FLUID COLLECTION- LIKELY INVASIVE
MOLE.
RISK SCORING
 PROVISIONAL DIAGNOSIS
29 YEARS OLD PRIMIGRAVIDA AT 14 WEEKS 5 DAYS WITH STAGE 1 GTN WITH WHO SCORING 6
(LOW RISK GTN)
 GESTATIONAL TROPHOBLASTIC
NEOPLASIA (GTN)
THIS TERM PRIMARILY ENCOMPASSES PATHOLOGIC ENTITIES THAT ARE CHARACTERIZED BY
AGGRESSIVE INVASION OF THE ENDOMETRIUM AND MYOMETRIUM BY THE TROPHOBLAST CELLS.
HISTOLOGICAL CLASSIFICATION :
• INVASIVE MOLE
• PLACENTAL SITE TROPHOBLASTIC TUMOR (PSTT)
• EPITHELIOD TROPHOBLASTIC TUMOR
• GESTATIONAL CHORIOCARCINOMA

GTN DEVELOPS AFTER EVACUATION IN 15% OF PTS WITH COMPLETE MOLE (ONLY ¼ DEVELOP
METASTASES-3-4%)
IN 4-6% OF PTS WITH PARTIAL MOLE (METASTASES RARE- 0.1%)
MOST CASES FOLLOW H MOLE. RARELY, GTN DEVELOPS AFTER A LIVE BIRTH, MISCARRIAGE, OR
TERMINATION ( 1 IN 30,000 NON MOLAR PREGNANCIES)
 INVASIVE MOLE
• THIS COMMON MANIFESTATION OF GTN IS CHARACTERISED BY WHOLE
CHORIONIC VILLI THAT ACCOMPANY EXCESSIVE TROPHOBLASTIC
OVERGROWTH AND INVASION.
• THESE TISSUES PENETRATE DEEP INTO THE MYOMETRIUM, SOMETIMES TO
INVOLVE PARAMETRIUM, PERITONEUM, VAGINAL VAULT (LOCALLY
INVASIVE) BUT GENERALLY LACK CAPACITY OF WIDESPREAD
METASTASES.
• ORIGINATE ALMOST EXCLUSIVELY FROM A COMPLETE OR A PARTIAL H.
MOLE.
 CHORIOCARCINOMA

• EXTREMELY MALIGNANT
• SHEETS OF ANAPLASTIC TROPHOBLASTS, AND PROMINENT HAEMORRHAGE,
NECROSIS AND VASCULAR INVASION.
• FORMED VILLOUS STRUCTURE ABSENT
• DEVELOPS EARLY BLOOD BORNE METASTASIS
PLACENTAL SITE TROPHOBLASTIC TUMOR
(PSTT)
• RARE GTN VARIANT (1% OF GTN)
• CAN FOLLOW ANY TYPE OF PREGNANCY, BUT MOST COMMONLY FOLLOWS A TERM
GESTATION
• CONSISTS PREDOMINANTLY OF INTERMEDIATE TROPHOBLASTS
• TENDS TO INFILTERATE ONLY WITHIN THE UTERUS, DISSEMINATE LATER IN THE
COURSE
• PRODUCES LOW ẞ HCG LEVELS
• HYSTERECTOMY IS PRIMARY TREATMENT, ALONG WITH PELVIC
LYMPHADENECTOMY.
• IF FERTILITY IS DESIRED- EMA/EP IS CONSIDERED MOST EFFECTIVE
• OVERALL 10 YEAR SURVIVAL- 70%; STAGE IV- POORER PROGNOSIS
 EPITHELOID TROPHOBLASTIC TUMOR
• DEVELOPS FROM NEOPLASTIC TRANSFORMATION OF CHORIONIC-TYPE INTERMEDIATE
TROPHOBLASTS
• PRECEDING PREGNANCY EVENT MAY BE REMOTE
• GROSSLY , ETT GROWS IN A NODULAR FASHION THAN THE INFILTERATIVE PATTERN OF
PSTT
• MICROSCOPICALLY RESEMBLES PSTT, BUT THE CELLS ARE SMALLER AND DISPLAY LESS
NUCLEAR PLEOMORPHISM
• HYSTERECTOMY IS PRIMARY TREATMENT, ALONG WITH PELVIC LYMPHADENECTOMY.
• POOR PROGNOSIS
FIGO (2018) CRITERIA FOR POSTMOLAR
GTN DIAGNOSIS
ß-HCG level plateau persists in 4 measurements during a period of 3 weeks or longer ( days 1,7,
14 & 21)

ß-HCG level rise (more than or equal to 10%) in 3 weekly consecutive measurements or longer,
over a period of 2 weeks or more (days 1, 7 & 14)

If there is a histologic diagnosis of choriocarcinoma

Identification of clinical or radiological evidence of metastases (ESMO 2013)

exclude new pregnancy

Most GTN cases are clinically diagnosed, as tissue is infrequently available for pathologic diagnosis.
 QUIESCENT GTD

• GTD THAT IS COMPLETELY INACTIVE, BENIGN OR QUIESCENT.

• PERSISTENT OR MILD ELEVATIONS OF TRUE Β-HCG (USUALLY ≤ 50 MIU/ML) & REMAIN
STATIC FOR ATLEAST 3 MONTHS
• WHEN A PINHEAD MASS REMAINS AFTER REMOVAL OF HM, SPONTANEOUS ABORTION
DUE TO HM, OR AFTER CC OR GTN CHEMOTHERAPY, IT MAY LACK CYTOTROPHOBLAST
CELLS, & HENCE H-HCG GROWTH AND INVASION SIGNAL, SO IT IS INACTIVE, BENIGN
OR QUIESCENT

WILLIAM’S Gynecology 3rd Edition

Ngu et al Curr Obstet Gynecol Rep (2014) 3:84–90
 FIGO ANATOMIC STAGING OF GTN
Stage Characteristics

1 Disease confined to the uterus

2 GTN extends outside the uterus, but is limited to the genital structures (adnexa,
vagina, broad ligament)

3 GTN extends to the lungs, with or without known genital tract involvement

4 All other metastatic sites

 MODIFIED WHO PROGNOSTIC SCORING
SYSTEM AS ADAPTED BY FIGO

Low‐risk GTN (FIGO Stages I–III: score <7)

High‐risk GTN (FIGO Stages II–III: score >7 and Stage IV)
 CLINICAL FEATURES
• Vaginal bleeding is the most common symptom in all groups.
• Abdominal distention, tenderness ,uterine sub involution or asymmetric
enlargement(24%)
• Most common site of spread- lungs (80%)- asymptomatic > cough, dyspnoea,
hemoptysis, pleuritic chest pain, signs of pulmonary hypertension.
• Other sites - vagina (30%), pelvis (20%), liver (10%), brain (10%)
• Symptoms related to site of metastasis-
• vagina- irregular bleeding or purulent discharge
• liver- epigastric or right upper quadrant pain, deranged LFT
• cns- acute focal neurologic deficit due to intracranial hemorrhage.
 DIAGNOSTIC WORK-UP
• Complete history & examination
• Blood group & rh typing
CBC , LFT, KFT and TFT
• β-hcg
• Chest x-ray
• Usg & CECT abdomen & pelvis
• CT chest- detects pulmonary micrometastases in 40-45% patients with negative cxr
• CECT/ MRI brain- in patients with vaginal/lung metastasis, choriocarcinoma or persistent
hydatidiform mole.
• Lumbar punctar to detect occult CNS mets if high suspicion , CSF HCG to serum HCG>1/60
• HPE – d&c may be part of the evaluation of a patient with elevated serum hcg levels of unknown
origin
ESMO Clinical Guidelines 2013
 IMAGING
Imaging Study
Chest radiography or CT
Pelvic USG with Doppler imaging
Pelvic MR imaging
Abdominal CT
Brain CT or MR imaging
Indications Characteristic Findings Important Findings to Report
Both post-molar and non-molar Multiple pulmonary nodules with or
Number of lesions and size in cm
GTN without halo of ground glass
attenuation
Location of mass (myometrial or
Both post-molar and non- molar Non-specific focal mass centered in endometrial)
GTN myometrium with variable Size of lesion in cm
endometrial component Resistive index
Uterine artery pulsatility index
Location of mass (myometrial or
Nonspecific focal mass centered in endometrial)
Both post-molar and non- molar
myometrium with variable Size of lesion in cm
GTN
endometrial component Extra-uterine extension
Pelvic lymphadenopathy
Post-molar GTN with confirmed
Arterially enhancing focal masses Organs involved
lung metastases
in solid abdominal organs Number of lesions and size in cm
Non-molar GTN
Post-molar GTN with confirmed
Hemorrhagic and enhancing brain
lung metastases Number of lesions and size in cm
masses
Neurologic manifestations
Non-molar GTN
Shaaban et al Radiographics. 2017 Mar-Apr;37(2):681-700
 IMAGING
Chest X-Ray features
• Alveolar or snow storm pattern
• Discrete rounded densities- cannon ball appearance
• Pleural effusion
• Embolic pattern caused by pulmonary arterial occlusion
Pelvic Ultrasound with Doppler
• Molar tissue- low resistance circulation (AV Shunting)
• Low pulsatile index of uterine artery (poor predictor of
chemotherapy response)
Chest CT
• CT ordered if the chest X-ray suggests lung metastasis, but
only lesions visible on chest X-ray should be scored.
• Lesion posterior to the heart measuring 1 cm or greater
would be scored even if only visualized on chest CT
Shaaban et al Radiographics. 2017 Mar-Apr;37(2):681-700
 MANAGEMENT-
• LOW-RISK GTN- (FIGO STAGES I–III: SCORE <7 ) SINGLE AGENT CHEMOTHERAPY
• ABOUT 95% OF PATIENTS WHO DEVELOP GTN ARE LOW RISK
• MTX-
• MTX-FA 8-DAY REGIMEN- 50 MG MTX (1-1.5 MG/KG) IM ON DAYS 1,3,5,7 WITH FOLINIC ACID 15 MG
ORALLY 24 HOURS AFTER MTX ON DAYS 2,4,6,8 ; REPEAT EVERY 2 WEEKS.
• 5 DAY REGIMEN- 0.4 MG/KG IM/IV * 5 DAYS; REPEATED EVERY 2 WEEKS
• MTX 50 MG/M2, IM, WEEKLY.
• CONTINUED TILL ẞ-HCG LEVELS ARE UNDETECTABLE, AND THEN 3 ADDITIONAL COURSES ARE GIVEN.
• MTX- MILD STOMATITIS IS THE MOST COMMON SIDE EFFECT, OTHER- SEROSAL SYMPTOMS ESP
PLEURISY
• ACTINOMYCIN D- (IN CASES OF MTX RESISTANCE OR CONTRAINDICATED)
• PULSE 1.25 MG/M2 INTRAVENOUSLY EVERY 2 WEEKS
• 5 DAY REGIMEN 10-12MCG/KG OR 0.5 MG EVERY 2 WEEKS
• ACTINOMYCIN D MORE EFFICACY, MORE SIDE EFFECTS. ( ALOPECIA- MC, MYELOSUPPRESSION,
MUCOSITIS, HEPATOTOXICITY, SECONDARY MALIGNANCY, LEUKEMIA)
 CHEMOTHERAPY REGIMENS
S.No. Chemotherapy Regimen Primary Remission Rate %

1 MTX 0.4 mg/kg (maximum 25 mg)/d IV or IM for 5 d; repeat 87–93

every 14 d
2 MTX 30-50 mg/m2 IM weekly 49–74
3 MTX 1 mg/kg IM or IV d 1, 3, 5, 7; folinic acid 0.1 mg/kg 74–90
IM or PO d 2, 4, 6, 8; repeat every 15-18 d, or as needed

4 MTX 100 mg/m2 IVP, then 200 mg/m2 in 500 mL D5W over 69–90
12 h; folinic acid 15 mg IM or PO q 12 h for 4 doses beginning
24 h after start of MTX; repeat every 18 d, or as needed
5 Act-D 10-13 μg/kg IV qd for 5 d; repeat every 14 d 77–94

6 Act-D 1.25 mg/m2 IV every 2 wk 69–90

7 Alternating MTX/Act-D regimens 1 and 5 100

ESMO Clinical Guidelines 2013

RESISTANCE TO CHEMOTHERAPY-

• HCG LEVEL PLATEAUS( +/- 10% ) OVER 2 TREATMENT CYCLES

OR
• HCG LEVEL RISES >10% FOR 1 TREATMENT CYCLES (NCCN 2021)

TREATMENT IS CHANGED TO ALTERNATIVE REGIMEN.

<300IU- ACTINOMYCIN D
>300 MIU- EMA-CO
(CHARRING CROSS HOSPITAL GUIDELINES) (ESMO 2013)
 MANAGEMENT CONTD…
• HIGH RISK GTN- (HIGH‐RISK GTN (FIGO STAGES II–III: SCORE >7 AND STAGE
IV) ARE TREATED WITH COMBINATION CHEMOTHERAPY
 MULTI AGENT CHEMOTHERAPY
• SIDE EFFECTS OF DRUGS:
o ETOPOSIDE- NAUSEA/VOMITING, LEUCOPENIA, DISTAL NEUROPATHY
o CYCLOPHOSPHAMIDE- NAUSEA/VOMITING, MYELOSUPRESSION, HEMORRHAGIC
CYSTITIS
o VINCRISTINE- PERIPHERAL NEUROPATHY

• EMA-CO REGIMEN-COMPLETE RESPONSE RATES OF 71-78% AND LONG-TERM

SURVIVAL RATES OF 85-94%
• ONCE Β-HCG NORMALISES, 4 ADDITIONAL CONSOLIDATION CYCLES OF EMA-CO
ARE ADMINISTERED

Lurain et al. Am J Obstet Gynecol 2011

Brown et al Gynecol Oncol. 2017 Jan;144(1):200-207
 MANAGEMENT CONTD…
ULTRA HIGH RISK GTN-
• For those with massive disease (liver, brain or extensive mets) WHO score >13, starting
with standard chemotherapy may cause sudden tumor collapse with severe bleeding,
metabolic acidosis, myelosuppression, septicemia, and multiple organ failure, any or all
of which can result in early death.
• To avoid this, the use of initial gentle rather than full-dose chemotherapy seems logical.
• Induction etoposide 100 mg/m2 and cisplatin 20 mg/ m2 on days 1 and 2, repeated
weekly for 1–3 weeks, before starting standard chemotherapy appears to have eliminated
early deaths.
• For patients with liver mets with or without brain mets or a very high risk score ,
EP/EMA or othe rmore intensive chemotherapy regimen rather than EMACO preferred.

FIGO 2018
 MANAGEMENT OF PSTT AND ETT
• CHEMOTHERAPY SHOULD BE USED IN
 PATIENTS WITH METASTATIC DISEASE
 PATIENTS WITH NON-METASTATIC DISEASE WITH ADVERSE PROGNOSTIC FACTORS
 INTERVAL FROM LAST KNOWN PREGNANCY TO DIAGNOSIS >2 YEARS
 DEEP MYOMETRIAL INVASION
 TUMOR NECROSIS
 MITOTIC COUNT >6/10 HIGH POWER FIELDS.

• EMA-EP OR TP/TE REGIMEN IS USED

• SAFEST OPTION - HYSTERECTOMY WITH PELVIC LYMPH NODE SAMPLING &
OVARIAN CONSERVATION UNLESS THERE IS FAMILY HISTORY OF OVARIAN
CANCER OR PATIENT IS POST-MENOPAUSAL
• OVERALL MORTALITY FROM PSTT - 16–21%

Lurain et al. Am J Obstet Gynecol 2011

METASTASIS OF GTN

SITE INCIDENCE

Lung 80%

Vagina 30%

Pelvis 20%

Liver 10%

Brain 10%

Berek and Novaks 16th Edition

 MANAGEMENT OF METASTASES
1) CNS METASTASES (9-11% OF PATIENTS WITH
METASTATIC GTN)
• WHOLE BRAIN IRRADIATION (3000 CGY IN 200-CGY
FRACTIONS), OR
• SURGICAL EXCISION WITH STEREOTACTIC
IRRADIATION OR GAMMA-KNIFE TREATMENT-GIVEN
SIMULTANEOUSLY WITH THE INITIATION OF SYSTEMIC
CHEMOTHERAPY
• INTRATHECAL METHOTREXATE- 12.5MG TOTAL
DOSE WITH EMACO REGIMEN
• CRANIOTOMY MAY BE NEEDED TO CONTROL
BLEEDING AND PROVIDE ACUTE DECOMPRESSION
• OVERALL SURVIVAL IN PATIENTS WITH CNS
METASTASES IS AS LOW AS 67%
 MANAGEMENT OF METASTASES

2) HEPATIC METASTASES(UNCOMMON, 2.7%)

• HEPATIC RESECTION OR SELECTIVE HEPATIC ARTERY
EMBOLIZATION TO CONTROL HEMORRHAGE FROM
HEPATIC METASTASES
• REGIONAL CHEMOTHERAPY OF LIVER

3) PULMONARY METASTASES
• RESECTION OF PERSISTENT LUNG NODULES WHEN THE
METASTASIS IS SOLITARY, LIMITED TO ONE LUNG, & Β-
HCG <1000
• GENERALLY REMISSION OCCURS WITH SINGLE
AGENT/COMBINATION CHEMOTHERAPY
• THORACOTOMY TO EXCISE THE RESISTANT FOCUS
BEREK AND NOVAKS 16 TH EDITION
 MANAGEMENT OF METASTASES

4) VAGINAL METASTASES (30%)

• LOCATED ON ANTERIOR WALL, FORNICES OR SUBURETHRALLY
• FRIABLE, HIGHLY VASCULAR - PRONE TO HAEMORRHAGE
• BLEEDING CONTROLLED BY PACKING, FOLLOWED BY A WIDE LOCAL EXCISION
• ALTERNATIVE APPROACH - ARTERIOGRAPHIC EMBOLIZATION OF THE VAGINAL
BRANCH OF THE HYPOGASTRIC ARTERY
 REFRACTORY GTN-
Resistant to all standard chemotherapy regimens
High-dose chemotherapy with autologous bone marrow or stem cell transplant
Immunotherapy with pembrolizumab

SALVAGE THERAPY-

• EMA-EP (ETOPOSIDE, METHOTREXATE AND ACTINOMYCIN-D, ETOPOSIDE,

CISPLATIN)
• TP/TE (PACLITAXEL, CISPLATIN/PACLITAXEL, ETOPOSIDE)
• BEP (BLEOMYCIN, ETOPOSIDE, CISPLATIN)
• MBE (METHOTREXATE, BLEOMYCIN, ETOPOSIDE)
• VIP OR ICE (ETOPOSIDE, IFOSFAMIDE, AND CISPLATIN OR CARBOPLATIN)
• FA (5-FLUOROURACIL, ACTINOMYCIN-D)
• FAEV (FLOXURIDINE, ACTINOMYCIN-D, ETOPOSIDE, VINCRISTINE)
ROLE OF SURGERY-
Hysterectomy prevents persistence of drug-resistant local disease,
shortens duration and amount of chemotherapy
Indications of hysterectomy:
1) Uncontrolled vaginal bleeding
2) Women with CC who do not desire future fertility,
3) Women with chemotherapy resistant disease, particularly in PSTT
4) Presence of significant pelvic sepsis

ROLE OF RADIOTHERAPY-
• Radiotherapy has a limited role in GTN, except in treatment of brain metastasis,
although its efficacy compared with intrathecal methotrexate is controversial.
 POST CHEMOTHERAPY MONITORING
• RISK OF RELAPSE AFTER CHEMOTHERAPY ∼3% (MOST OCCUR IN 1ST FOLLOW-UP YEAR)
• SERIAL MEASUREMENTS OF SERUM Β-HCG, BEGINNING AT WEEKLY INTERVALS DURING
THERAPY
• REMISSION IS DEFINED AS AN UNDETECTABLE HCG LEVEL FOR 3 CONSECUTIVE WEEKS
• AFTER REMISSION, SERUM Β-HCG SHOULD BE MEASURED MONTHLY UNTIL 1 YEAR OF
NORMAL Β-HCG LEVELS
• PATIENTS WITH HIGH RISK DISEASE ARE FOLLOWED FOR 24 MONTHS
• AVOID CONCEPTION FOR 1 YEAR AFTER COMPLETION OF TREATMENT
• CONTRACEPTION- OCPS ARE PREFERRED, IUCD CONTRAINDICATED (WHO MEC 4)

ACOG PractiDeVita’s Oncology 10th Edition

 FUTURE PREGNANCIES-

AFTER UNCOMPLICATED HYDATIFORM MOLE-

• PATIENTS CAN ANTICIPATE NORMAL REPRODUCTION IN THE FUTURE
• NO INCREASED RISK OF COMPLICATIONS IN LATER GESTATIONS
• INCREASED RISK OF HAVING A MOLAR GESTATION IN SUBSEQUENT CONCEPTIONS
• FOR ANY SUBSEQUENT PREGNANCY:
i. USG IN FIRST TRIMESTER
ii. HCG MEASUREMENT 6 WEEKS AFTER COMPLETION OF PREGNANCY TO RULE OUT
OCCULT TROPHOBLASTIC NEOPLASIA
 TAKE HOME MESSAGE
• No need for histopathological diagnosis before treatment
• Chemotherapy has markedly improved prognosis
• Essential to rule out phantom hcg, quiescent gtd
• Prophylactic chemotherapy-limited role
• Low risk gtn – single agent chemotherapy (mtx+ fa, act-d) f/b 3 courses of
consolidation chemo
• High risk gtn –EMACO regimen every 2 weekly till beta HCG normalizes f/b 4
courses of consolidation chemo if high risk factors like brain and liver mets.
• Ultra high risk GTN – Induction chemotherapy EP on d1,2 for 1-3 cycles f/b
standard doses EMA/EP
• β hcg follow up
• Role of surgery – PSTT
• Contraception - ocp
• Subsequent pregnancy outcome good
THANK YOU