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Gestational Trophoblastic Diseases Dr. Maribel Emma E. Co - Hidalgo MD, MSPH, March 29 2018
Gestational Trophoblastic Diseases
Dr. Maribel Emma E. Co - Hidalgo MD, MSPH, March 29 2018
3.05

I. Overview

II. WHO Classification

III. Hydatidiform Mole

IV. Gestational Trophoblastic Neoplasms

LEARNING OBJECTIVES

To be able to classify the gestational trophoblastic diseases

To identify the signs and symptoms of the different gestational trophoblastic disease

To be able to know the management and follow - up of patients with partial and complete molar pregnancies

To be able to know the different diseases under gestational trophoblastic neoplasia including management an appropriate follow - up

I. OVERVIEW OF GESTATIO NAL TROPHOBLASTIC DI SEASES (GTD)

Is a heterogeneous spectrum of diseases which is characterized as an abnormal trophoblastic proliferation

It can be benign, premalignant or malignant

Can follow any gestational event – abortion, ectopic, normal pregnancy

Is the most curable of all gynecologic diseases due to :

o

Early recognition

o

Responds ve ry well to chemotherapy

o

Accurate way to monitor with B – HCG

These tumors originate from cells that would have developed into the placenta during normal pregnancy

Ethnic groups like Native American Indians, Inuits, Hispanics, and American Africans have increased incidence of GTD

Actual incidence rate is unknown and one of the rea sons is because the data used are deliveries rather than pregnancies, which means a lot of cases are missed or mistaken as abortion

Now, the denominator for inc idence is pregnancies rather than del iveries

III.B RISK FACTORS

Age

o

<16 y/o a nd >45 years old

o

Note: in Comprehensive Gynecology 6 th edition , it’s <15 and >40 years old

o

Risk increases after age 35

o

5 – 10 fold increase if conceiving after age 40, rising precipitously thereafter , accounted for by abnormal gametogenesis or abnormal fertilization with advanced maternal age

o

Teenagers have a 1.5 – 2 fold increased risk

o

Paternal age factor has inconsistent results

o

Maternal age is a more consistent risk factor on complete moles compared to partial mol es

Reproductive history

o

A past history of HM increases the risk of future pregnancies by 5 – 40 fold that of the general population

o

Subsequent pregnancies have approximate 1% risk increasing to 25% when the number of previous molar pregnancies is 2 or more

o

Risk is not affected even by changing partners

o

Patients with recurrent molar pregnancies are also at increased risk f or the malignant sequelae of GTN

 

Diet

II. WHO CLASSIFICIATION OF GESTATIONAL TROPH OBLASTIC DISEASES

o

Conflicting results regarding diet as risk factor

o

Increased risk of CHM with decrease consumption of animal fat and beta – carotene (precursors of vitamin A)

Benign Trophoblastic Lesions

o

P lacental site nodule (Very rare)

o

High er incidence of G TD in countries where vitamin A deficiency is prevalent

Other studies failed to show decreased incidence with increasing consum ption of dietary protein or fat

§ L esion of the intermediate trophoblast which is thought to represent an incomplete evolution of the placental implantation site

o

§ Although rare, it is important because it shares

Genetics

 

features with a malignant lesion, the placenta l site trophoblastic tumor

o

Familiar recurrent HM, a rare autosomal recessive disorder was identified on Chromosom e 19q

o

Exaggerated placental reaction (rare)

o

Affected women have a mutation of NLRP7 gene and more rarely the KHDC3L gene – predisposed to abnormal pregnancies characterized by CHM

§

Also an infiltration of intermediate trophoblast on placental implantation site

Hy d atidiform Mole (most common)

o

These CHM cases with familial recurre nce are genetically normal with chromosome from one parent ( diploid biparent al ) , as opposed to the spot sporadic cases whom have CHM which are parent al

o

Complete hy d atidiform mole (CHM)

o

Partial hy d atidiform mole (PHM)

Ges tational Tr ophoblastic N eoplasia (GTN)

o

Invasive mole

§ C omplete moles are androgenic

o

Choriocarcinoma

§ These women with recurrent HM (the ones with diploid

o

Placental site trophoblastic tumor

biparent al variant) a re unlikely to have normal

o

Epitheloid trophoblastic tumor

pregnancy. They usuall y require techniques such as in - vitro fertilization .

III. HYDA TIDIFORM MOLE

III.A EPIDEMIOLOGY

2 types of hy d atidiform mole

o

Partial hy d atidiform mole

o

Complete hy d atidiform mole

Incidence varies greatly between different parts of the world

Highest in Asia than in Nor th America or Europe

Incidence of PHM in the United Kingdom is 3/1000 pregnancies

Incidence is 2.4/1000 pregnancies (2008 - 2010) in the Philippines

3.05 Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]
3.05
Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]
3.05 Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ] Figure 1.Comparison between complete and partial

Figure 1.Comparison between complete and partial hy d atidiform mole. An empty ovum results into a complete mole while an ovum with gametes will produce a partial mole. Type B is the most common mole. The mechanism for the production of empty ovum is currently unknown.

Although triploid variants are usually partial moles, not all partial moles are triploid. Some triploid moles do not exhib it the histologic appearance consistent with partial moles.

III.C PATHOLO GIC FEATURES

III.C.1 COMPLETE HY D ATIDIFORM MOLE

Gross examination reveals bulky “bunch of grapes” appearance

Has semi - transparent vesicles (1 – 30mm)

Absence of normal placental structures or fetal parts

May sometimes pass through the vaginal canal.

parts • May sometimes pass through the vaginal canal. Figure 2. Gross features of hy d

Figure 2. Gross features of hy d atidiform mole. Has “bunch of grapes” appearance ranging from 1 – 30mm in size.

Microsc opic features

ranging from 1 – 30mm in size. • Microsc opic features Figure 3. Complete hy d

Figure 3. Complete hy d atidiform mole. A. Histologic low power view showing numerous edematous villi with frequent cistern formation (arrow). B. Histological high power view showing hyperplastic trophoblast (arrow).

III.C.2 PARTIAL H Y D ATIDIFORM MOLE

Gross examination reveals smaller volume of hydrophic cells and possible presence of fetus or fetal tissues

cells and possible presence of fetus or fetal tissues Figure 4. Gross examination of PHM. •

Figure 4. Gross examination of PHM.

Microscopic features

o

Presence of fetal or embryonic tissues

o

Less diffuse, focal hydrophic swelling of villi

o

Focal trophoblastic atypia at the molar implantation site

o

Presence of trophoblastic scalloping and stromal inclusions

o

1 – 5% of partial moles develop into GTN

Table 1. Genetic and Histopathological differences between CHM and PHM

Feature

Complete

Partial

Fetal or embryonic tissue

Absent

Present

Hydatidiform swelling of chorionic villi

Diffuse

Focal

Trophoblastic Hyperplasia

Diffuse

Focal

Trophoblastic hyperplasia

Absent

Present

Genetic Parentage

Paternal

Bipaternal

Karyotype

46,XX; 46,XY

69XXY; 69XYY

Persistent hCG

20% of cases

0 .5% of cases

III.D HOW TO DI FFERENTIATE BETWEEN CHM AND PHM

Differentiation between the two in the early stages of pregnancy is difficult because of the less pronounced trophoblastic invasion , and the hyrdophic swelling is subtle

Presence of fetal tissue is automatically partial

o

Lack of fetal , placental, or e mbryonal tissues

Absence of i mmunohistochemical nuclear stain p57 suggests

o

Hydropic (edematous villi)

paternal origin - > complete hy d atidiform mole

o

Diffuse trophoblastic hyperplasia

Other tests to differentiate between CHM from PHM and

o

Marked atypia of trophoblasts at the implantation site

nonmolar hy drop ic abortions ( nice to know according to doc )

o

Absence of trophoblastic stromal inclusions

o

Flow Cytometry

o

15 – 20% of complete moles develop GTN

o

Ploidy Analysis by in situ hybridization

 

o

Molecular genotyping

3.05 Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]
3.05
Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]

III.E CLINICAL FEATURES

III.E.1 COMPLETE HY D ATIDIFORM MOLE

Table 2 . Changing Clinical Presentation of Complete Hydatidiform Mole at the New England Trophoblastic Disease Center (from the book)

the New England Trophoblastic Disease Center (from the book) From the lecture: • Delayed Menses •

From the lecture:

Delayed Menses

Vaginal Bleeding

Large for date uterus

Absent fetal movement

Anemia secondary to occult hemorrhage

Gestational hypertension before 20 w ee ks

Presence of theca lutein cysts

Hyperemesis

Hype rthyroidism

Respiratory distress from t rophoblastic emboli to the lung

Average time of diagnosis for CHM is 9.6 weeks Uterus is enlarged in about 14 – 16 weeks, 25% of cases would develop medical complications becaus e of the increase in hc G levels B - hc G i s homologous to TRH and LH , which would result to theca lutein cysts Patients are now more likely t o present with minimal symptoms, which makes diagnosis o f complete moles more difficult

III.E.2 PARTIAL HY D ATIDIFORM MOLE

Found incidentally following histo path ology of products of conception from missed abortion or therapeutic abortion - are therefore more difficult to diagnose

Medical complications are rare

III.F DIAGNOSIS

III.F.1 COMPLETE HY D ATIDIFORM MOLE

Ultrasound is the most useful and therefore the st andard in diagnosing molar pregnancies

o

Echogenic endomet rial mass in an enlarged uterus

o

“S now storm appe a rance”

§ Absence of fetal or embryonic tissue

§ Absence of amniotic fluid

§ Enlarged placenta with multiple cysts

§ Ovarian theca lutein cysts

placenta with multiple cysts § Ovarian theca lutein cysts Fi gure 5 . C omplete hyd
placenta with multiple cysts § Ovarian theca lutein cysts Fi gure 5 . C omplete hyd

Fi gure 5 . C omplete hyd atidiform mole. Note the massive theca lutein cysts visible .

III.F.2 PARTIAL HY D ATIDIFORM MOLE

Ultrasound

o

Presence of fetal or embryonic tissue

o

Presence of Amniotic fluid

o

Abnormal placenta with multiple cysts or increased echogenicity of chorio nic villi

o

Inc reased transverse diameter of gestational sac

o

Absence of theca lutein cysts

of gestational sac o Absence of theca lutein cysts Figure 6 . PHM on ultrasound. III.F.3

Figure 6 . PHM on ultrasound.

III.F.3 BETA HCG LEVELS

HCG levels is produced by syncytiotrophoblast cell of the placenta

Similar to FSH, LH, and TSH except in their beta subunits

In normal pregnancy, its max amount is produced at approximately 10 weeks with levels peaking at 100,000 IU/L and then falling thereafter

Elevated levels outside of pregnancy signify:

o

Gestational Trophoblastic Neoplasia

o

Non - gestational tumor s secreting HCG

o

False positives

o

Menopause (secondary to LH elevation and cross reactivity of assays)

III.G TREATMENT

III.G.1 PRE – EVACUATION WORKUP

Chest X – ray

Complete blood count, blood type with antibody screen

Beta – HCG levels

Liver function tests , for preparation to give chemotherapy

III.G.2 DEFINITIVE TREATMENT

Suction dilation and curettage

o

The preferred method

o

Under general anesthetic

o

For a patient who still wishes to give birth

3.05 Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]
3.05
Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]

o

The cer vix is serially dilated and then a large suction curette i s advan ced into the endometrial canal

o

After activating the suction device, a solution of crystalloid and oxyto cin (20 IU/L) is infused to increase uterine tone - this is continued post operatively to reduce bleeding

o

A gentle sharp cur ettage may be performed to complete the procedure

o

Care must be taken during D&C to avoid perforation of the enlarged soft uterus in HM

o

RH negative with RH positive or RH unknown partner should be treated with Rho(D) immune globulin post evacuation

o

Suction dilatation and curettage is different compared to simple dilatation and curettage , because the former removes all the cells from the uterus

Total Abdominal Hysterectomy with Preservation of Adnexae

o

For patients with hy d atidifor m moles who do not plan to get pregnant

o

Risk of devel oping gestational trophoblastic neoplasia

§ 53% in >40 year old with HM

§ 60% in women older than 50

o

After hysterectomy, risk of postmolar GTN is 3% - 5%, which necessitate s continuous hCG monitoring

o

After surgical evacuation, locally invasive mole occurs in 15 – 20% of CHM

o

Postmolar GTN rarely occurs with PHM (<5%)

Prophylactic Chemotherapy

o C onsidered in patients where poor follow – up is anticipated post evacuation, though routine use is not recommended

III.G.3 S URVEILLANCE FOLLOWIN G HY D ATIDIFORM MOLE EVACU ATION

Baseline serum Beta – HCG should be done within 48 hours of evac uation

Weekly evaluation until levels become normal (<5 mIU/mL)

Monthly Beta – HCG monitoring is recommended after a normal count for an additional 6 – 12 months

Minimum conventional per iod for observation is 6 months

IV. GESTATIONAL TROPHOBL ASTIC NEOPLASMS

IV.A PROGNOSTIC FACTORS

Advanced maternal age

Beta – HCG level higher than 100,000 IU/L on presentation

Uterine size large for date and bilateral ovarian enlargement (>8cm theca lutei n cysts) at time of presentation

Ultrasound findings

o

Presence of hyperechoic lesions (nodules) within the myometrium

o

I ncreased signal intensity suggesting hypervascularization on Doppler ultrasound

IV.B PHANTOM BETA – HCG

False positive assay results

Rare

Secondary to heterophilic antibodies or proteolytic enzymes that mimic hCG

Diagnosis is done when serum B - HCG is positive but a corresponding urine B - HCG samples taken at the same time are negative

o

Urine is negative because these antibodies / enzymes are lipoproteins and therefore unable to pass through the glomeruli - > not excreted through the urine

o

These antibodies are mostly derived from sheep, some through vaccination

IV.C QUIESCENT GESTATIONA L TROPHOBLASTIC DISE ASE

Follows hy d atidiform mole, chorioca rcinoma , or spontaneous abortion

Persistence of low l evels ranging from 1 – 212 IU/L of B – HCG for 3 months or longer with no obvious increase or decrease in B – HCG level trend with absence of clinical or radiographic evidence of GTN

More common than com plete moles

Premalignant = 25% progress to GTN – choriocarcinoma over a time frame of 6 months to 10 years

Hyperglycosylated HCG (HCG - H)

o

A mark er of invasive cytotrophoblasts

o

W ill detect 100% of quiescent GTD case that requires no further treatment and 9 6% of self – resolving HM cases that require surveillance

o

Differentiating these from GTN choriocarcinoma cases that require treatment

o

Further evaluation with prospective studies is needed

IV.D SEQUELAE OF GESTATIONAL TROPH OBLASTIC NEOPLASIA

Invasive / Pos tmolar GTN (about 50% cases occur after molar pregnancy and 25% of cases occur after normal pregnancy, and the remaining 25% follow abortion or ectopic pregnancies)

Choriocarcinomas

Placental Site Trophoblastic Tumors (PSTT)

Epitheloid trophoblastic tumor (ETT)

IV.D.1 INVASIVE MOLE

HM characterized by syncytiotrophoblast or cytotrophoblast hyperplasia , with the presence of villi extending into the myometrium

Mostly diploid, except anaplastic tumors

Mostly associated with trophoblastic hyperplasia with atypia

Could spread extra – uterine and metastasize to distant areas like the lungs, va gina, vulva, and broad ligament

Ves icular chorionic villi are ident ifiable

IV.D.2 CHORIOCARCINOMA

Dominant histology in metaplastic GTN (most common type)

May follow an HM or a normal pregnancy

Occurs in approximately 1 out of 50,000 pregnancies

tissue containing

cytotrophoblast and syncytiotrophoblast cells without chorionic villi

Cells normally invade adjacent tissues but have a predilection for vascular tissues

Sheets of anaplastic trophoblastic

IV.D.3 PRIMARY GONADAL CHOR IOCARCINOMA (NONGESTATIONAL)

Ovarian germ cell tumor that can develop without pregnancy

Occurs in 1 out of 369,000,000

Very aggressive

S ecretes Beta – HCG

3.05 Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]
3.05
Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]

Same histologic appearance as gestational chorio carcinoma

Absence of paternal DNA with in the tumor using DNA analysis , which differentiates nongestational from gestational choriocarcinoma

IV.D.4 EXTRAGONADAL GERM CE LL TUMORS

Rare: originating from midline locations such as mediastinum and retroperitone um

No primary tumor in the ovaries but secretes B – HCG

FISH (fluor escence in situ hybridization) is used to identify single – nucleotide variants in exons and introns on individual RNA transcripts

o T his would differentiate gestational choriocarcinoma from extragonadal germ cell tumor

IV.D.5 PLACENTAL SITE TROPH OBLASTIC TUMORS (PSTT)

Rare but very malignant

Composed almost entirely of intermediate trophoblasts

No syncytiotrophoblasts and cytotrophoblasts

Infiltrative pattern, nests or sheets of cells invad ing between myometrial cells and fibers

W hen patients come in, they usually already have metastatic lesions

Less prone for vascular invasion, necrosis, and hemorrhage compared to choriocarcinoma

Lymphocytic spread

Immunochemical stain is positive in 50 – 1 00% for human placental lactogen in less than 10% for B – HCG

IV.D.6 EPITHELOID TROPHOBLA STIC TUMO R (ETT)

Considered rare variant PSTT

Derived from intermediate trophoblasts

Arranged in nests or sheets and form nodules in the myometrium

Immunohistochemica l staining is positive for multiple markers like cytokeratin and inhibin A

IV.E CLINICAL FEATURES OF GTN

Irregular vaginal b leeding

Uterine sub involution: the uterus has not returned to pre – pregnancy state

Presence of t heca lutein c ysts

Most GTN is ide ntified during surveillance following evacuation on the basis of B – HCG criteria

IV.E.1 LOCALLY INVASIVE GTN

Myometrial invasion involving local capillaries and veins in invasive mole

Persistent vaginal hemorrhage is the most common symptom

Uterine perfo ration with intraperitoneal hemorrhage in f ection secondary to tumor necrosis may also occur

Most would regress spontaneously following an evacuation

Chemotherapy may be initiated

IV.E.2 MALIGNANT GTN

Most result from choriocarcinoma

PSTTs associated with metastasis at the time of initial diagnosis in 40% of cases

o Lung metastasis is the most common site

ETT is associated with metastasis in 50% of cases at the time of diagnosis

IV.F FIGO CRITERIA FOR DI AGNOSIS OF GTN

Standardized criteria for diagnosing GTN following a HM:

o

Four B – HCG values plateauing (+ or - 10%) over a 3 week period (days 1, 7, 14, 21)

o

A rising B – HCG value of 10% or greater seen on 3 values measured over a 2 – week period (days 1, 7, 14)

o

Persistence of detectable B – HCG for more than 6 months following evacuation of HM

o

Histologic diagnosis of choriocarcinoma

o

Evidence of metastasis (clinically or radio log ically)

IV.G CLASSIFICATION AND S TAGING

In 2000, a revised FIGO – WHO prognostic scoring system was adopted

o

A score of 6 or lower was associated with low risk

o

A score of 7 or greater was associated with high risk

o

Staging of the disease relates to tumor spread

Table 2. WHO Prognostic Scoring System for GTD. To utilize, the sum of the WHO prognostic scoring system is incorporated into t he FIGO stage, separated by a colon. A score of 4 on the above table coupled with a FIGO stage of II would be written as stage II:4. A score of 0 – 6 is considered low risk while 7 or higher is considered high risk. Note that the WHO prognostic scoring sys tem is not applicable to patients with placental – site trophoblastic disease (PSTT) or epitheloid trophoblastic tumor (ETT).

Prognostic Factor

0

1

2

3

Maternal Age

<40

>/=40

   

A ntecedent P regnancy

Mole

Abortion

Term

 

Interval (end of AP to chemotherapy in months)

<4

4

- <7

7

- <13

>13

Pretreatment serum

<10 3

10

3 - 10 4

10

4 - 10 5

>10 5

HCG

Number of Metastasis

0

1

- 4

5

- 8

>8

Site of Metastasis

Lung

Kidney /

GI

Brain /

Spleen

tract

liver

Largest tumor mass

<3cm

3

- <5cm

>/=

 
 

5cm

Previous failed

   

Single

2

chemotherapy

drug

drugs

Table 4 .FIGO 2000 Classification of GTN. Figo is used more commonly than the TNM staging because lymph nodes are rarely evaluated in the staging of GTN.

Staging

Features

Stage I

Disease confined to the uterus

Stage II

GTN extends o utside the uterus, but limited to the genital structures (adnexa, vagina, broad ligament)

Stage III

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

Stage IV

All other metastatic sites

3.05 Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]
3.05
Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]

IV.H DIAGNOSIS OF GTN

Invasive mole and cho riocarcinoma

o Have high B – HCG level ranging f rom 100 to 100,000 mIU/ mL

PSTT and ETT

o Produce low levels of B – HCG usually <1000 mIU/mL

Ultrasound will rule out concurrent pregnancy

Doppler ultrasound may show hypervascularity

Chest x – ray, to rule in / o ut lung metastasis

IV.J MANAGEMENT

IV.J.1 LOW RISK (WHO SCORE OF 6 OR LOWER)

Following metastatic evaluation and determine of low – risk disease

1. Initiate single – agent methotrexate or acinomycin D; consider hysterectomy if fertility is not desired . If fe rtility is still desired, we can do suction dilatation and curettage followed by a single dose prophylactic chemotherapy.

§ Monitor hematologic, renal, and hepatic indices before each cycle chemotherapy

§ Monitor B – HCG levels while on treatment

§ If severe tox icity or resistance develops, consider switching to the alternative single agent

If resistance to alternative agent develops…

2. Repeat metastatic evaluation

3. Consider hysterectomy if disease is confined to uterus

4. Multi - agent therapy with EMA/CO - preferred reg imen

IV.J.2 HIGH RISK

WHO score of 7 or greater

Increased risk of treatment failure with single agent therapy

Table 4. Chemotherapy Regimen for intermediate and High – Risk Gestational Trophoblastic Disease

Drug Regimen

Dosage

Course I (EMA)

 

Day 1

Etop oside

100mg/m 2 IV over 30 min

Methotrexate

100mg/m 2 IV bolus

Methotrexate

100mg/m 2 IV as 12 – hour continuous infusion

Actinomycin D

0.5mg IV bolus

Day 2

Etoposide

100mg/m 2 IV over 320 min

Folinic Acid

15mg IV/IM/PO every 6 hours for 4 doses

Cours e II (CO)

Day 8

Cyclophosphamide

600mg/m 2 IV over 30 minutes

Vincristine

1mg/mg 2 IV bolus (up to 2mg)

IV.K HIGH – RISK SITES OF METAST ASIS

Central nervous system metastasis

o

Brain metastasis has poor prognosis

o

Favorable outcomes with combination chemo therapy

o

Select craniotomy if lesions are very focal

o

Whole brain radiotherap y

o

Chemotherapy is the preferred option

Pulmonary Metastasis

o Manifests as chest pain, cyanosis, anemia, and > 50% lung field opacification

o Operative treatment of pulmonary metastasis for recurrent drug resistant cases is recommended

Liver Metastasis

o

Increased risk of he morrhage with chemotherapy initiation

o

Management:

§ Chemotherapy

§ Radiation T herapy

§ Embolization

§ Surgical Resection

Vaginal Metastasis

o

High risk for hemorrhage

o

Management : Embolization or surgery

IV.L TREATMENT OF PLACENT AL SITE TROPHOBLASTI C TUMOR AND EPITHELOID TROPHOBLASTIC TUMOR

Rare, less than 1%

Ranging from benign to highly malignant

Surgery is the cornerstone for the treatment of non - metastatic PSTT and ETT because they are less responsive to chemotherapy alone.

Patients with metastasic ETT and PSTT have poor prognosis

Metastatic PSTT and ETT are relatively chemoresistant compared to invasive mole and choriocarcinoma

T reatment is surgery followed by radiation and ch emotherapy

IV.M S U R VEILLANCE FOLLOWING GTN

After B – HCG remission is achieved for 3 weekly cycles, repeat testing every 2 weeks for 3 weeks, monthly for 1 year

Stage IV patients need monthly testing for 24 months

Risk of relapse beyon d the first year is <1%

In p atients with relapse, sustained remissions are achieved in more than 50%

o The higher rate prolongs B – HCG monitoring to every 6 months for 5 years

Contraception is important during the post – GTN period with OCP being method of choice

o Avoid getting pregnant for 1 year

Recurrence rate:

o

Stage I: 3%

o

Stage II: 8%

o

Stage III: 4%

o

Stage IV: 9%

Recurrences

o

M ean time from last detectable B – HCG to recurrence was 6 months

o

Stages 1 – 3, remissions were achieved with additional chemotherapy

o

Stage IV patients wit h recurrences died of their disease

o

There is no relationship between time to relapse and mortality

o

Overall survival rate of patients with relapse is 78%

o

Recurrence rate for PSTT and ETT ranges from 20 to 30%

o

Only 30% will achieve long – term remission desp ite salvage treatment (chemo or surgery)

IV.N PREGNANCY AFTER GTN

Normal reproductive outcome is expected after molar pregnancy or GTN

Pregnancy outcome is similar to the general population

3.05 Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]
3.05
Gestational Trophoblastic Diseases [ Dr. Co - Hidalgo ]

There is an increased risk of subsequent molar pregnancy about 1 to 3/1000 to 1 – 2 /100 pregnancies following a molar pregnancy.

Following 2 molar pregnancies, the risk in a subsequent pregnancy may be as high as 20%

Changing partners has not been proven to change the risk

IV.O EFFECTS OF GTN ON PA TIENTS

Psychosocial sequelae for patients

o

Sadness with sense of loss

o

Low self – esteem

o

Sexual dysfunction

o

Anxiety about future pregnancies

o

50% showed psychological symptomatology suggestive of psychiatric disorder

SUMMARY

HM can be categorized as complete mole or partial mol e. Complete moles are diploid and partial moles are triploid. Complete moles typically produce higher levels of HCG.

The risk of GTN is higher for complete mole (15 - 29%) than partial mole (1 – 5 %)

The two main risk factors for GTD are extremes of maternal age (over 45 y/o or under 16 y/o) and previous GTD

Ultrasound is the standard imaging modality for the diagnosis of molar pregnancy

The classic ultrasound appearance of a complete mole is a central heterogenous mass with numerous discrete anechoic spaces (referred to as “snowstorm or swiss cheese pattern”)

The ultrasound is more likely to be indeterminate in a partial mole, but abnormalities of the gestational sac or a placenta with cystic spaces may be seen. In partial mole, a fetus is present.

Definitive diagnosis is made by histological examination of the products of conception

Suction curettage is the method of choice of evacuation for molar pregnancies

Gestational choriocarcinoma is the dominant histology in metastatic GTN

WHO score of 7 or greater con fers high risk

GTN is very sensitive to chemotherapy

REFERENCES

Dra. Co - Hidalgo’s lecture, March 29 2018 Comprehensive Gynecology 6 th edition, Chapter 35

GUIDE QUESTIONS

1)

Which of the following is TRUE of partial hydatidiform mole?

a. About 20% will have p ersistent hCG

b. Absence of fetal parts

c. All triploid pregnancies will show histologic changes

d. Trophoblastic scalloping and stromal inclusions are present

2)

Which of the following features is a suggestive of complete hydatidiform mole?

a. Absence of amnio tic fluid

b. Absences of theca lutein cells

c. Presence of embryonic tissue

d. Presence of fetus

3)

Which of the following is an important part of pre evacuation work- up in patients diagnosed to have a hydatiform mole?

a. ECG

b. CXR

c. CT Scan

d. Kidney function Test

4) Which is n ot a recognized complication of molar pregnancy?

a. DM

b. Hyperthyroidism

c. Presence of embryonic tissue

d. Respiratory distress

5) A 38 - year old G4P3(3013) post - evacuation of complete molar pregnancy has been following up and was noted to have persistent B - hCG ran ging from 150 - 190 IU/L for 4 months. Patient is asymptomatic with no other findings. What is the primary consideration?

a. Invasive mole

b. Persistent GTD

c. Phantom B - hCG

d. Quiescent GTD

6) Which of the following is TRUE of human chorionic gonadotropin?

a. hCG is prod uced by cytotrophoblast cell of the placenta

b. b. In normal pregnancy, its max amount is produced at approximately 10 weeks with levels peaking at 100,000 IU/L

c. Levels are higher in normal pregnancy than in molar pregnancy

d. Similar alpha sub unit to FSH, LH, a nd TSH

7) A 18 - year old G1P0, 3 months amenorrheic, presented with complaints of vaginal bleeding and hypogastric pain. Ultrasound result revealed a hydatidiform mole. Patient suddenly had difficulty of breathing. What is your primary consideration?

a. Asthm a in exacerbation

b. Pneumonia

c. Preeclampsia

d. Pulmonary embolism

8) A 32 - year old G1P0(0010) is undergoing follow up for a complete

hydatidiform mole. She is aware that she should not get pregnant for one year. What is the recommended contraception?

a. Barrier me thod

b. IUD for non compliant patients

c. Oral contraceptive pills

d. Any of the above

9) In which of the following is hysterectomy considered as primary management?

a. Choriocarcinoma

b. Invasive mole

c. PSTT

d. Quiescent GTD

10) Which of the following is a risk factor for gestational trophoblastic disease?

a. Age

b. Blood type

c. BMI

d. Gravidity

11) A 45 - year old G4P3(3003) consulted because of an ultrasound findings of molar pregnancy. What is the definitive management for this patient?

a. Suction curettage

b. Chemotherapy

c. Hysterectomy

d. Hy sterectomy with bilateral salpingo - oophorectomy

D ABA D D D CC A C

MOTIVATION

A million dreams for the world we’re GYNE make.