HIGH-YIELD FACTS IN - Gestational Trophoblastic Neoplasias pptx

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DEFINITION OF GTN

Gestational trophoblastic neoplasias are neoplasms arising from placental syn￾cytiotrophoblasts and cytotrophoblasts.

The four tumors are:

Hydatidiform mole (complete or partial)

Invasive mole

Choriocarcinoma

Placental site trophoblastic tumor

HYDATIDIFORM MOLE

Complete Mole

A placental (trophoblastic) tumor forms when a maternal ova devoid of DNA

is “fertilized” by the paternal sperm:

Karyotype: Most have karyotype 46XX, resulting from sperm penetration

and subsequent DNA replication. Some have 46XY, believed to be due to

two paternal sperms simultaneously penetrating the ova.

Epidemiology: Incidence is:

1 in 1,500 pregnancies in the United States

1 in 200 in Mexico

1 in 125 in Taiwan

Partial Mole

A mole with a fetus or fetal parts. Women with partial (incomplete) molar

pregnancies tend to present later than those with complete moles:

Karyotype: Usually 69XXY, and contains both maternal and paternal

DNA

Epidemiology: 1 in 50,000 pregnancies in the United States

HIGH-YIELD FACTS IN

Gestational Trophoblastic

Neoplasias (GTN)

DNA of complete mole is

always paternal.

DNA of a partial mole is

both maternal and

paternal.

Invasive Mole

A hydatidiform mole that invades the myometrium: It is by definition malig￾nant, and thus treatment involves complete metastatic workup and appropri￾ate malignant/metastatic therapy (see below).

HISTOLOGY OF HYDATIDIFORM MOLE

Trophoblastic proliferation

Hydropic degeneration (swollen villi)

Lack/scarcity of blood vessels

SIGNS AND SYMPTOMS

Passage of vesicles (look like grapes)

Preeclampsia < 20 weeks

Abnormal painless bleeding in first trimester

DIAGNOSIS

hCG > 100,000 mIU/mL

Absence of fetal heartbeat

Ultrasound- “snowstorm” pattern

Pathologic specimen—grapelike vesicles

Histologic specimen (see above)

Treatment of Complete or Partial Moles

Dilation and curettage (D&C) to evacuate and terminate pregnancy

Follow-up with the workup to rule out invasive mole (malignancy):

Chest x-ray (CXR) to look for lung mets

Liver function tests to look for liver mets

Weekly hCG level: The hCG level should decrease and return to

normal within 2 months. If the hCG level rises, does not fall, or falls

and then rises again, the molar pregnancy is considered malignant,

and metastatic workup and chemotherapy is necessary.

Contraception should be used during the 1-year follow-up.

Metastatic Workup

CXR, computed tomography (CT) of brain, lung, liver, kidneys

Treatment (For Nonmetastatic Molar Pregnancies)

Chemotherapy—methotrexate or actinomycin-d (as many cycles as

needed until hCG levels return to normal)

or

Total abdominal hysterectomy + chemotherapy (fewer cycles needed)

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HIGH-YIELD FACTS GTN

All early (< 20 weeks)

preeclampsia is molar

pregnancy until proven

otherwise.

GTN secrete human chorionic

gonadotropin (hCG),

lactogen, and thyrotropin.

Any of the following on

exam indicates molar

pregnancy:

Passage of grape-like

vesicles

Preeclampsia early in

pregnancy

Snow storm pattern on

ultrasound

Ten to 15% of complete

moles will be malignant.

Two percent of partial

moles will be malignant.

A young woman who passes

grape-like vesicles from her

vagina should be diagnosed

with hydatidiform mole.

Nonmetastatic malignancy

has almost a 100%

remission rate following

chemotherapy.

Treatment for metastatic molar pregnancy is the same as for choriocarcinoma

(see below)

CHORIOCARCINOMA

An epithelial tumor that occurs with or following a pregnancy (including ec￾topic pregnancies, molar pregnancies, or abortion):

Histopathology: Choriocarcinoma has characteristic sheets of tropho￾blasts with extensive hemorrhage and necrosis, and unlike the hydatid￾iform mole, choriocarcinoma has no villi.

Epidemiology: Incidence is about 1 in 40,000 pregnancies.

Diagnosis

Increased hCG

Absence of fetal heartbeat

Uterine size/date discrepancy

Specimen (sheets of trophoblasts, no villi)

As with invasive mole and malignant hydatidiform mole, a full metastatic

workup is required when choriocarcinoma is diagnosed.

Treatment of Nonmetastatic Choriocarcinoma and Prognosis

Chemotherapy—methotrexate or actinomycin-d (as many cycles as

needed until hCG levels return to normal)

or

Total abdominal hysterectomy + chemotherapy (fewer cycles needed)

Remission rate is near 100%.

Treatment of Metastatic Choriocarcinoma, Metastatic Invasive Mole,

or Metastatic Hydatidiform Mole

Treatment is determined by the patient’s risk (high or low) or prognostic

score.

Prognostic Group Clinical Classification

Low risk:

hCG < 100,000 IU/24-hr urine or < 40,000 mIU/mL serum

Less than 4 months from antecedent pregnancy event or onset of symp￾toms to treatment

No brain or liver metastasis

No prior chemotherapy

Pregnancy event is not a term pregnancy.

High risk: Opposite of above (i.e., hCG > 100,000 IU/24-hr urine, more than

4 months from pregnancy, brain or liver mets, etc.)

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HIGH-YIELD FACTS GTN

Sheets of trophoblasts =

choriocarcinoma.

World Health Organization (WHO) Prognostic Scoring System

SCORE

Risk Factor 0 1 2 4

Age (years) ≤ 39 > 39

Pregnancy H. mole Abortion Term

Interval from < 4 4–6 7–12 > 12

pregnancy

event to

treatment

(in months)

hCG (IU/mL) < 103 103–104 104–105 > 105

ABO blood O × A B

group A × O AB

(female ×

male)

Number of 1–4 5–8 > 8

metastases

Site of Spleen GI Brain

metastasis Kidney Liver

Size of largest 3–5 > 5

tumor (cm)

Prior Single Multiple

chemotherapy

agent

Scores are added to give the prognostic score.

Treatment According to Score/Prognostic Factors

Low risk (score Single-agent therapy Remission rate 90 to 99%

≤ 4) (methotrexate)

Intermediate Multiple-agent therapy Remission rate ≈ 50%

risk (score 5 to 7) (MAC therapy—methotrexate,

actinomycin, and

cyclophosphamide)

High risk Multiple-agent therapy

(score ≥ 8) (EMACO therapy—etoposide,

MAC, and vincristine)

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HIGH-YIELD FACTS GTN