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8.1 Diagnosis

Gestational trophoblastic diseases (GTD) are characterized by abnormal proliferation of trophoblasts. When they cause local invasion or metastasize, they are called gestational trophoblastic neoplasia (GTN).

Diagnostic entities

Gestational trophoblastic disease:

  • Molar pregnancy
    • Complete mole
    • Partial mole
  • Placental site nodule
  • Exaggerated placental site reaction

Gestational trophoblastic neoplasia:

  • Invasive mole
  • Choriocarcinoma
  • Placental site trophoblastic tumor (PSTT)
  • Epithelioid trophoblastic tumor (ETT)

Risk factors

Commonly cited risk factors for development of GTD/GTN include ethnicity (increased risk for patients from Japan, South East Asia and South Africa), extremes of maternal age (<18 or >40 years old) and nutritional deficiencies (low protein diets, vitamin A and carotene deficiency). Patients who had a previous molar pregnancy are at increased risk of developing again a molar pregnancy in the future: after one molar pregnancy this risk is 1-2% (10 times the risk of the general population) and up to 28% if two prior molar pregnancies.

There are also some genetic mutations associated with an increased risk of developing molar pregnancies. The two genes identified are NLRP7 (on chromosome 19) and KHDC3L (on chromosome 6) which are inherited in an autosomal recessive fashion. NLRP7 mutation is present in approximately 60% of patients with a history of two molar pregnancies and is associated with other poor obstetrical outcomes (non-molar spontaneous abortions, stillbirths and intrauterine growth restriction).

Clinical presentation

GTD:

  • Complete moles represent 70% of molar pregnancies. They have a diploid karyotype (most commonly 46,XX but also 46,XY) that contains only paternal genetic material and are p57 negative. p57 is paternally imprinted, maternally expressed gene. Complete moles do not contain any embryonal/fetal tissue. Complete moles will usually present with vaginal bleeding (95%) and uterine size larger than expected for the dates. Other presenting symptoms include preeclampsia, hyperemesis gravidarum, hyperthyroidism, theca lutein cysts and trophoblastic embolization.
  • Partial moles represent 30% of molar pregnancies. They have a triploid karyotype (more commonly 69, XXX or 69, XXY) and are p57 positive (they contain both maternal and paternal genes). They contain embryonal/fetal tissue. If a fetus develops, it will likely have triploidy. Partial moles usually present as missed abortion with abnormal vaginal bleeding. Often, the diagnosis will be made only on the pathology specimen of a D&C.

GTN:

  • The diagnosis of GTN does not require histopathology. Diagnosis is made solely with serum testing of hCG levels. If GTN is not confirmed histopathologically (e.g. the uterine dilation and curettage only identified products of conception), a pre-treatment pelvic ultrasound is required to rule out a previously undetected viable ultra-uterine pregnancy.
  • The index pregnancy (last pregnancy before development of the GTN) is most often a molar pregnancy (50%) but can also be a spontaneous abortion/ectopic pregnancy (25%) or a term/preterm pregnancy (25%).
  • The diagnostic criteria for a GTN are:
    • A plateau (+/- 10%) in hCG levels over at least 3 weeks (i.e. 4 consecutive values);
    • A rise (≥ 10%) in hCG levels over at least 2 weeks (i.e. 3 consecutive values);
    • Persistence of hCG at ≥ 6 months after molar evacuation
    • Histologic evidence of choriocarcinoma
    • Presence of metastatic disease

Staging

FIGO 2000 Anatomical staging

Stage
Description
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

  • Staging for GTN is dynamic (i.e. patients need to be staged for each recurrence)

Scoring


FIGO Scoring
0
1
2
4
Age
< 40
≥ 40
-
-
Antecedent pregnancy
Mole
Abortion
Term
-
Interval months from index pregnancy
< 4
4 - < 7
7 - < 13
≥ 13
Pre-treatment serum hCG (IU/L)
< 103
103 - < 104
104 - < 105
≥ 105
Largest tumor size in cm (including uterus)
< 3
3 - < 5
≥ 5
-
Site of metastases
Lung
Spleen, kidney
Gastro-intestinal
Liver, brain
Number of metastases
-
1-4
5-8
> 8
Previous failed chemotherapy
-
-
Single drug
2 or more drugs

  • Score ≤ 6 --> low/moderate-risk GTN
  • Score ≥ 7 --> high-risk GTN
  • Patients with stage I are generally considered low-risk
  • Patients with stage IV are generally considered high-risk

SOURCE: 8.1 Diagnosis ( )
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