From: Subject: CancerLink - Gestational Trophoblastic Disease Date: Sun, 16 Sep 2007 08:03:07 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_00E3_01C7F838.03EAE050" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3138 This is a multi-part message in MIME format. ------=_NextPart_000_00E3_01C7F838.03EAE050 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.njh.u-net.com/cgest.html CancerLink - Gestational Trophoblastic = Disease

Gestational Trophoblastic Disease

By William M. Rich MD

This is a term that includes several conditions that are associated = with the=20 results of a pregnancy. The conditions are molar pregnancy, invasive = mole,=20 metastatic mole and gestational choriocarcinoma. These are cancers and = cancer=20 like conditions of placental elements. The concept is so far beyond most = people's experience, that unless they have been to medical school they = will=20 never have heard of it. It is not uncommon.=20

The easiest way to explain this disease is to start at the beginning. = In the=20 beginning, a single egg produced by the mother is fertilized by a single = sperm=20 from the father. The egg and the sperm are unique because each has only = one=20 chromosome from each of the 23 pairs of chromosomes. At fertilization = the=20 complete complement of 23 pairs is thus restored. The fertilized egg = divides and=20 forms two daughter cells. Before division occurs it must duplicate its=20 chromosomes so that each daughter cell has a complete complement of 23 = pairs.=20 This type of cell division is called mitosis. These two daughter cells = divide by=20 mitosis and so there are now four identical cells each with the normal = 23 pairs=20 of chromosomes. Further cell division results in 8, then 16, then 32, = then 64=20 identical cells. Then things start to become complicated.=20

Certain cells begin to differentiate and become different from the = other=20 cells. Some of the cells will eventually form the extra-embryonic = tissues. That=20 means the placenta, the membranes (bag of water), and the umbilical = cord. The=20 fetus is eventually formed by the remaining cells. The placenta is = composed of=20 three elements. The villi, the cytotrophoblast cells and the = synctiotrophoblast=20 cells. The villi, or villus when describing only one, is a microscopic = finger=20 like structure containing a fetal blood vessel that invades into the = lining of=20 the uterus. The synctio- and cytotrophoblast cells create the villi and = help the=20 villi to erode into the maternal blood vessels in the wall of the = uterus.=20

There are millions of villi in a placenta. Oxygen and nutrients that = are=20 supplied to the fetus from the mother's blood must traverse the villus = to be=20 picked up by the fetal blood vessel in the villus. There is one fetal = blood=20 capillary per villus. The fetal blood is separate from the maternal = blood. The=20 villi and the cyto- and synctiotrophoblasts have to invade the lining of = the=20 uterus to reach the maternal blood vessels. As the pregnancy progresses = the=20 number of villi initially increases then begin to decrease as the = placenta ages.=20 At birth the placenta separates and along with the membranes and = umbilical cord=20 are discarded. They have done their job. This is the normal way the = placenta=20 functions. The invasion into the lining of the uterus is similar to the = invasion=20 of a cancer, but in pregnancy this is normal.=20

Sometimes something goes wrong very early in pregnancy. The fetus = does not=20 develop but the placental elements continue to grow. There is swelling = of the=20 villi and overgrowth of the cyto-and synctiotrophoblast cells. The villi = can=20 become so swollen that they are visible and look like drops of water. = The=20 scientific (Latin) name for this mass of water drops is hydatidiform = mole, and=20 it is referred to as a molar pregnancy. The trophoblastic cells make the = pregnancy hormone, Human Chorionic Gonadotropin, HCG, which is the basis = for all=20 pregnancy tests. There is an overproduction of HCG as well as = exaggerated=20 symptoms of pregnancy.=20

Eventually, the patient will spontaneously miscarry and pass the = mole. If the=20 molar pregnancy is detected before that happens then an abortion has to = be done=20 to evacuate the uterus. Obstetricians are well familiar with this = condition and=20 can diagnose it by a sonogram. There is a characteristic appearance to = the=20 uterine contents, and there are no fetal structures or heart beat. Very = rarely=20 there may be a coexisting fetus. Why molar pregnancies occur is unknown, = but=20 there are some remarkable features about them:=20

They have the ability to invade into the wall of the uterus.=20
They can metastasize to other organs.=20
They can develop into choriocarcinoma which is a virulent cancer.=20
They have 23 pairs of chromosomes, all of which are paternal in = origin.=20
They are XX, and both of the X chromosomes are also of paternal = origin.=20
The incidence in Asia is about 1 in 120 pregnancies.=20
The incidence in Northern Europe is 1 in 2000 pregnancies.=20
In the USA the incidence is about 1 in 1500 pregnancies.=20
Metastatic disease sometimes undergoes spontaneous regression.=20

After the molar pregnancy is evacuated there must be rigorous = surveillance=20 for any sequelae. The consequences of a mole can be persistent mole, = invasive=20 mole, metastatic mole or choriocarcinoma. The follow up is done by a = weekly=20 blood test for HCG. Actually, it is for a specific sub-unit of the HCG = molecule=20 called B-HCG ( Beta HCG). The B-HCG may be in the millions and has to = fall to=20 less than 2. Usually the blood test is normal within 8 weeks. Then it is = repeated every month for 6 months and then every other month for 6 = months.=20 During this time the woman should not become pregnant again because that = will=20 also increase the B-HCG, and make things complicated.=20

If the B-HCG decreases but then levels off and starts to rise again, = then the=20 diagnosis is Gestational Trophoblastic Disease. This may be either = invasive mole=20 (mole growing into the wall of the uterus), metastatic mole, usually to = the=20 lungs, or choriocarcinoma. At this point the patient is reexamined, a = chest=20 x-ray obtained and perhaps a scan of the liver. But for sure the patient = needs=20 chemotherapy. This is one case where chemotherapy is given on the basis = of a=20 blood test without a tissue diagnosis. If there is B-HCG, and the = patient is not=20 pregnant, she must be treated. Sometimes molar tissue will regress=20 spontaneously. Treatment is usually easy. A single chemotherapeutic = agent is=20 given and repeated every two weeks until one course of treatment is = given after=20 the titer is normal (titer is the level of B-HCG in the blood). Then the = patient=20 is followed for a year with B-HCG titers. As long as they remain normal=20 everything is normal,. There is no source of B-HCG other than the = trophoblasic=20 cells. After the year is up the patient can become pregnant again. The = risk for=20 another molar pregnancy is about doubled. But that is still a small = number. If=20 it were 1 in 500 for the first mole it would be 1 in 250 for the next = pregnancy.=20

Molar pregnancies and their management is the easy part. The problem = is when=20 they are ignored, not followed adequately, or inadequately treated = because then=20 major problems occur. If a previous pregnancy ended in a miscarriage and = there=20 was no pathologic specimen it may have been an unknown molar pregnancy. = If the=20 last pregnancy was a normal term pregnancy and delivery, then nobody = would be=20 expecting choriocarcinoma to develop. But it can and it is usually not = diagnosed=20 promptly. It can be anywhere in the body and is a very aggressive = cancer. It=20 metastasizes widely and early. It is very invasive and destroys the = tissue. It=20 bleeds profusely. If it is in the brain then signs of a stroke or = seizure may=20 occur; if in the lung then the patient may cough up blood; if in the = uterus then=20 irregular bleeding. A simple pregnancy test that is positive will = indicate the=20 diagnosis.=20

Gestational trophoblastic disease is characterized as either = metastatic or=20 nonmetastatic. If nonmetastatic then treatment is by single agent = chemotherapy=20 or sometimes by hysterectomy. If metastatic, then it is divided into = good=20 prognosis and poor prognosis disease.=20

Parameter Good Prognosis Poor Prognosis=20
Last pregnancy event less than 4 months more than 4 months=20
B-HCG level less than 40,000 more than 40,000=20
Prior pregnancy mole term=20
Treatment no prior treatment failed prior chemo

There is also a World Health Organization Scoring System.=20

Prognostic factor 0 1 2 4=20
Age <39 >=3D39 . .=20
Prior pregnancy mole abortion term .=20
Interval <4 mo 4-6 mo 7-12 mo >12 mo=20
B-HCG <1,000 <10,000 <100,000 >100,000=20
ABO blood group . OxA or AxO B or AB .=20
Size of largest tumor . 3-5cm >5cm .=20
Site of metastases . spleen,kidney GI,liver brain=20
Number of metastases . 1-4 4-8 >8=20
Prior chemotherapy . . single agent two or more

Total score: 0-4 low risk, 5-7 intermediate risk, >8 high risk for = death.=20

The scoring systems indicate the need for multi-agent chemotherapy. = The high=20 risk groups and the poor prognosis group requires aggressive multi-drug=20 regimens. Resistant areas that can be irradiated are irradiated. = Involved organs=20 or parts of organs that can be removed are removed surgically, because = if the=20 B-HCG titer does not go down to normal and stay there, the patient is = going to=20 die.=20

These patients should be treated at a center experienced in treating = this=20 disease. They will need extensive therapy and support. The treatment is = vigorous=20 and at times ruthless. This is a cancer that can be cured, even though = widely=20 metastatic.=20

The prognosis depends on the extent of disease and the aggressiveness = of=20 treatment. If a molar pregnancy is managed properly, the cure rate is = about=20 100%. If non metastatic trophoblastic disease is vigorously treated the = cure=20 rate is also about 100%. Widely metastatic disease if recognized = promptly and=20 treated aggressively with multi-agent chemotherapy, surgery and = radiation if=20 necessary, is curable in about 80% of the cases.=20

William M. Rich,=20 MD
Clinical Professor of Obstetrics and Gynecology
University = of=20 California San Francisco
Director of Gynecologic Oncology
Valley = Medical=20 Center
Fresno, Ca.

3DBack=20CancerLink

Last updated 2 July 1996=20

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