Gestational Trophoblastic Disease

Gestational Trophoblastic Disease

Define: Abnormal pregnancy in which the developing fetus and placenta are replaced by proliferation of throphoblastic tissue.

¬  Spectrum of disease

a)      Benign  - Complete hydatidiform moles, partial mole

b)      Malignant – Invasive mole, Choriocarcinoma, placenta site trophoblastic tumor

Gestational trophoblastic Neoplasia

Define: any evidence of persistence of GTD with persistent elevation of beta human chorionic gonadotrophin

Differentiate

Complete Hydatidiform mole	Partial mole
46XX Homozygous (75-80%) -duplication of a single sperm following fertilisation of an ‘empty’ ovum 46XY Heterozygous (20-25%) -dispermic fertilisation of an ‘empty’ ovum	69XXY triploid (from maternal & paternal) - two sets of paternal haploid genes and one set of maternal haploid genes -following dispermic fertilisation of an ovum (10% are tetraploid or mosaic conception)
No embryonic or fetal tissue	embryonic or fetal tissue
Diffuse trophoblastic hyperplasia	Focal trophoblastic – variable changes
Generalized swelling of villous tissue -all hydrophic	Focal swelling of villous tissue -some hydrophic
May develop malingnant changes	Less likely to develop malignant changes

Symptoms and signs of molar pregnancy:

¬  classic features 

a)      irregular vaginal bleeding (Passing out “grape-like structure” )

b)      hyperemesis

c)      excessive uterine enlargement

d)      early failed pregnancy.

¬  Rarer presentations : hyperthyroidism, early onset pre-eclampsia or abdominal distension due to theca lutein cysts

¬  Very rarely: acute respiratory failure or neurological symptoms such as seizures (metastatic)

Diagnosis

¬  Ultrasound examination is helpful in making a pre-evacuation diagnosis.

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

Investigation

¬  FBC, Coagulation profile

¬  Blood group cross match

¬   BhCG

In women with a complete mole, the quantitative serum beta-hCG level is higher than expected, often exceeding 100,000 IU/L. In case of a partial mole, the level of beta-hCG is often within the wide range associated with normal pregnancy and the symptoms are usually less pronounced. For these reasons the diagnosis of a partial mole is often missed clinically and made from subsequent histologic assessment of the abortive materia

¬  Ultrasound : ‘snow’storm’ appearance, no fetal parts seen, bilateral theca lutein cysts in POD

¬  Chest X-ray - exclude invasive mole in lung

Treatment

1.      Evacuation of molar pregnancy

a)      Complete molar pregnancies : Suction curettage.

b)      Partial molar pregnancies : Suction curettage  except when the size of the fetal parts deters the use of suction curettage, then medical evacuation can be used.

¬  Medical evacuation of complete molar pregnancies should be avoided because

-           the routine use of potent oxytocic agents lead to contraction of myometrium and potential to embolise and disseminate trophoblastic tissue through the venous system

-          Use of mifepristone and misoprostol increases the sensitivity of the uterus to prostaglandins

¬  Preparation of the cervix (to ripen it) immediately prior to evacuation is safe

-          Prolonged cervical preparation, particularly with prostaglandins, should be avoided  to reduce the risk of embolisation of trophoblastic cells.

2.      The use of oxytocic infusion prior to completion of the evacuation is not recommended.

¬  Excessive vaginal bleeding can be associated with molar pregnancy and a senior surgeon directly

supervising surgical evacuation is advised.

¬  If the woman had significant haemorrhage prior to evacuation, surgical evacuation should be expedited and the need for oxytocin infusion weighed up against the risk of tumour embolisation.

3.      Histologic assessment

¬  If obtained from the medical or surgical management of all failed pregnancies is recommended to exclude trophoblastic neoplasia.

¬  No need to routinely send products of conception for HPE after surgical termination of pregnancy, provided that fetal parts have been identified on prior ultrasound examination.

4.      A urinary pregnancy test should be performed 3 weeks after medical management of failed pregnancy if products of conception are not sent for histological examination.

5.      Anti-D prophylaxis is required following evacuation of a molar pregnancy (may delayed)

-          Required in partial mole

-          Not required in complete mole because of poor vascularisation of the chorionic villi and absence of the anti-D antigen

                                                                  

Women need investigated for GTN after non-molar pregnancy

¬  Any woman who develops persistent vaginal bleeding after a pregnancy event is at risk

¬  A urine pregnancy test should be performed in all cases of persistent or irregular vaginal bleeding after a pregnancy event.

¬  Symptoms from metastatic disease can occur very rarely.

Follow-up

The aims of follow-up are to confirm successful treatment and to identify women with persistent or malignant GTD who may require adjuvant chemotherapy or surgery at an early stage. Persistent vaginal bleeding and above all elevation of serum beta-hCG levels are the main indicators of residual disease.

The outcome of a partial hydatidiform mole after uterine evacuation is almost always benign. Persistent disease occurs in 1.2% to 4% of cases; metastasis occurs only in 0.1% of cases 

 In complete moles, these risks are approximately 5 times greater after treatment with uterine evacuation and 2-3 times greater after hysterectomy 

The risk of persistent or recurrent GTD is greatest in the first 12 months after evacuation, with most cases presenting within 6 months.

A variety of hCG criteria have been used to diagnose postmolar gestational trophoblastic disease. Recently, the International Federation of Gynecologists and Obstetricians (FIGO) standardized the following hCG criteria for the diagnosis of postmolar gestational trophoblastic disease

• An hCG level plateau of four values ±10% recorded over a 3-week duration (days 1, 7, 14, and 21).
• An hCG level increase of more than 10% of three values recorded over a 2-week duration (days 1, 7, and 14).
• Persistence of detectable hCG for more than 6 months after molar evacuation.

Use of reliable hormonal contraception is recommended while hCG values are being monitored. Oral contraceptives do not increase the incidence of postmolar gestational trophoblastic disease or alter the pattern of regression of hCG values 

Frequent pelvic examinations are performed while hCG values are elevated to monitor the involution of pelvic structures and to aid in the early identification of vaginal metastases. Although pregnancies after molar evacuation usually are normal gestations, pregnancy obscures the value of monitoring hCG levels during this interval and may result in a delayed diagnosis of postmolar malignant gestational trophoblastic disease. A new intrauterine pregnancy should be ruled out on the basis of hCG levels and ultrasonography, especially when there has been a long delay in follow-up of serial hCG levels and noncompliance with contraception. After completion of documented remission for 6-12 months, women who desire pregnancy may discontinue contraception, and hCG monitoring may be discontinued. 

Patients with prior partial or complete moles have a 10-fold increased risk (1-2% incidence) of a second hydatidiform mole in a subsequent pregnancy. 

Therefore, all future pregnancies should be evaluated by early obstetric ultrasonography.

Chemotherapy

Complete molar pregnancy is well recognized to have the potential for local invasion and distant spread. After evacuation, local uterine invasion occurs in about 15% and metastases in 4%. Complete molar pregnancy is usually divided into low and high risk for persistence based on signs and symptoms of marked trophoblastic proliferation at the time of evacuation, i.e.: hCG >100,000 mIU/Ml; excessive uterine enlargement; theca-lutein ovarian cyst >6 cm in diameter; older maternal age; a previous molar pregnancy. The risk of postmolar GTD is significant less with partial molar pregnancy and is seen in approximately 1-6%

Prognosis

Table 1. Gestational Trophoblastic Neoplasia (GTN)^a,b

FIGO Anatomical Staging
Stage
I	Disease confined to the uterus.
II	GTN extends outside of the uterus, but is limited to the genital structures (adnexa, vagina, broad ligament).
III	GTN extends to the lungs, with or without known genital tract involvement.
IV	All other metastatic sites.
Modified WHO Prognostic Scoring System as Adapted by FIGOb
Scores	0	1	2	4
Age	<40	≥40	–	–
Antecedent pregnancy	mole	abortion	term	–
Interval months from index pregnancy	<4	4–6	7–12	>12
Pretreatment serum hCG (iu/1)	<103	103–104	104–105	>105
Largest tumor size (including uterus)	<3	3–4 cm	≥5 cm	–
Site of metastases	lung	spleen, kidney	gastrointestinal	liver, brain
Number of metastases	–	1–4	5–8	>8
Previous failed chemotherapy	–	–	single drug	≥2 drugs

  In this scoring system, women with a score of 7 or greater are considered at high risk.

Ref:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279094/ 

http://www.cancer.gov/cancertopics/pdq/treatment/gestationaltrophoblastic/HealthProfessional/page3

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