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Gestational Trophoblastic Disease GTD

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Gestational Trophoblastic Disease GTD Powered By Docstoc
					Gestational Trophoblastic
     Disease (GTD)
    Department of Obs.& Gyn.,
  First Hospital of Xi‘an Jiaotong
            University

       Gao Shang Feng
          Introduction
   What is GTD ?
 It is a rare kind of disease in which
  abnormal trophoblastic proliferation
  occurs.
 It is too among the rare human
  malignancies that can be cured even
  in the presence of widespread
  metastases.
Which does it include?
 It includes a spectrum of interrelated
tumors, including
 hydatidiform mole (HM)
 invasive mole (IM)
 Choriocarcinoma (CH)
 Placental-site trophoblastic tumor
(PSTT, borderline, very rare)
  Relationship of HM. IM. CH
hydatidiform    therapeutic or
mole            spontaneous abortion
                 term pregnancy
                ectopic



invasion mole       choriocarcinoma.
What is GTT (Gestational trophoblastic
 tumor)?
 GTT is all GTD except hydatidiform
 mole.
They has its unique pathologic
 characteristics and biological
 behavior.
Even the most malignant case can be
 cured by chemotherapy.
Hydatidiform mole
Hydatidiform mole
            Hydatidiform mole
It is a neoplastic
 proliferation of
 the trophoblast
 in which the
 terminal villi
 are
 transformed
 into vesicles
 filled with clear
 viscid material.
 It is usually benign but has
  malignant potentiality.
 Incidence:

 south east Asia is 1/500-600
 the US and Europe:1/500-2000
 China:1/1238
           Classification
It is divided into two classification

    complete hydatidiform mole
    partial hydatidiform mole
complete hydatidiform mole(CHM):
   the entire
    uterus
    filled with
    abnormal
    vesicles,
    no signs of
    fetus.
       partial hydatidiform mole

   partial
    hydatidiform
    mole with
    evidence of
    a conceptus.
           Etiology
Though it is not known a number of
associated factors have been noted:
the absence of fetal circulation;
dietary protein deficiency
viral infection;
age:>45 years women are 10 times
more likely to develop HM than
those younger
 abnormal fertilization process:
 the fertilization of a normal ovum
with a duplicated haploid
sperm:46XX
 the fertilization of an empty egg by
two sperms(dispermy):46XY
            Chromosomes
complete hydatidiform moles
 Cytogenetic studies have demonstrated
  that complete hydatidiform moles usually
  have a 46xx karyotype, and the molar
  chromosomes are entirely of paternal
  origin.
 Complete moles appear to arise from an
  ovum that has been fertilized by a haploid
  sperm, which then duplicates its own
  chromosomes, and the ovum nucleus may
  be either absent or inactivated
Although most complete moles have
a 46xx chromosomal pattern,
approximately 10% have a 46xy
karyotype.
Chromosomes in a 46xy complete
mole also appear to be entirely of
paternal origin, but in this
circumstance, an apparently empty
egg is fertilized by two sperm.
                      .
partial hydatidiform mole
  partial moles usually have a triploid
 karyotype (69 chromosomes ), with the
 extra haploid set of chromosomes derived
 from the father.
  When a fetus is present in conjunction
 with a partial mole, it usually exhibits the
 stigmata of triploidy, including growth
 retardation and multiple congenital
 malformations.
Pathologic findings
complete hydatidiform mole

 pathology
   Complete moles lack identifiable
  embryonic or fetal tissues, and
  the chorionic villi exhibit
  generalized hydatidiform swelling
  and diffuse trophoblastic
  hyperplasia.
                 Gross
we see a mass of
vesicles, vary in
size, grape-like
with stems, blood
and clot filling the
inter-vesicle space
   partial hydatidiform mole
It are characterized by the following
  pathologic features :
   Chorionic villi if varying size with
  focal hydatidiform swelling and
  cavitation.
   It contain identifiable embryonic or
  fetal tissues.
                Gross
we see a
mass of
vesicles,
vary in size,
grape-like
and
identifiable
embryonic
or fetal
tissues.
       Microscopic
                       ‗


trophoblastic proliferation.
 hydropic degeneration of
the stroma.
 absence of blood vessels or
extreme scantiness of blood
vessels.
   trophoblastic proliferation is
    considered the most important single
    criteria.
   Ovaries respond to hCG
    stimulation ,30-50% theca-lutein
    cysts develop, bilateral
   Clinical course


It has eight of
 symptoms and
 physical signs.
 amenorrhea
       because it is a pregnancy.
 vaginal bleeding
   after a period of amenorrhea
 (average 12 weeks) may continue
 intermittently for several weeks---
 profuse bleeding---anemia and
 infection.
 abdominal cramps
 abnormally
 enlarged and
 soft uterus
  in about half the
 cases, the
 uterus growth is
 rapid, it is larger
 than the dates
 suggest.
 ovarian cyst
 torsion
when we do pelvic
 examination
 adnexal masses
 may be found. it is
 theca lutein cyst in
 about one third of
 the cases
 severe and early –onset PIH
 (Pregnancy Induced Hypertension
 syndrome)
 hyperthyroidism
 plasma thyroxin concentration
 elevates
 exaggerated early pregnancy
 symptoms
  nausea, vomit etc
             Diagnosis
suspicion:
   abnormal bleeding after amenorrhea
   inappropriately enlarged uterus;
   absence of fetal heart sounds or
  could not feel fetal parts by palpation
  between 16-20th week
   hyperemesis gravidarum
   bilateral ovarian cysts
   serum hCG monitor
    an unusually high titer of chorionic
    gonadotropin, especially after the
    one-hundredth day of pregnancy,
    help to confirm the diagnosis of HM.
   Ultrasonography:
    It is a reliable and sensitive technique
    for the diagnosis of complete molar
    pregnancy. Because the chorionic villi
    exhibit diffuse hydatidiform swelling.
    Complete moles produce a
    characteristic vesicular sonographic
    pattern, usually referred to as a
    ―snowstorm‖ pattern.
   Ultrasonography may also
    contribute to the diagnosis of
    partial molar pregnancy by
    demonstrating focal cystic
    spaces in the placental tissues
    and an increase in the transverse
    diameter of the gestational sac.
Differential diagnosis

  abortion;
  multiple pregnancy;
  polyhydramnios
            Treatment
 the uterus should be evacuated as
 soon as possible after the diagnosis
 is made.(by suction curettage)
  suction;
  oxytocin administration:we can use
 blood transfusion or/and fluid
 infusion.it is used to decrease the
 size of the uterus;
 tissue sent for histology:
it should be routine
practice with all cases of
incomplete miscarriage;
 acute pulmonary
complications
 total abdominal
hysterectomy
in older
  multiparas
hysterectomy may
be indicated.
management of theca-
 lutein cysts
 these tumors should not be
 excised because they
 regress after the
 trophoblastic tissue has
 been removed.
chemotherapy
  HM don‘t need usually
 chemotherapy because
 HM is benign disease.
㈧Follow-up examinations

  follow up mode in the 2
   years after discharge

   on each follow-up
   check, the following
   should be addressed
 symptom
 abnormal vaginal bleeding,
 cough, hemoptysis
 signs of metastasis
 pelvic examination
 hCG evaluation
 B-ultrasound
 chest X-ray film
  contraceptive method
   required for 1-2 years
condom is recommended.
IUD (intrauterine device)and
 pills are contraindicated for their
 potentiality of causing abnormal
 vaginal bleeding.
          Ask question
1. What is the etiology of GTD?
2. What is the classification of HM?
3. What is the main pathologic
   changes of HM?
4. What is the clinical course of
   HM?
5. How Follow-up examinations is
   we?
   About 80% of the cases of HM
    have a benign course. one-half
    of patients become pregnant
    subsequently. about 16% of HM
    become invasion moles and
    some 2.5% progress into
    choriocarcinoma
Invasion Mole
           Introduction
 Invasion Mole arises from HM
 it has malignant potentialities,
 invades the myometrium and
 penetrates the uterine wall,
 extends into the broad ligament
 or peritoneal cavity.
 in half or more of all cases
 invasive mole metastasizes
 through the peripheral
 circulation to distant sites,
 mostly to the lung.
    Pathologic findings

 excessive trophoblastic
 proliferation and
 invasiveness
 the degree of anaplasia is
 variable: completely benign-
 --highly malignant
differentiation between invasive
 mole and choriocarcinoma lies in
 whether the villous pattern is
 preserved:
if we see villi, it must be
 invasion mole;
if we can‘t see villi, it is
 choriocarcinoma.
        Clinical course
Symptoms caused by primary lesions
vaginal bleeding
 pelvic examination reveals delayed
 involution of the uterus, persisting
 cyst .
abdominal pain
 intra-abdominal hemorrhage,
 penetration of the uterus .
   Metastatic symptoms
    • cough, hemoptysis---positive X-ray
      signs
    • profuse vaginal bleeding---vaginal
      or cervical metastasis, we can see
      bluish nodule in vaginal
    • headache, nausea, vomit, paralysis
      or coma—it is caused by cerebral
      lesion.
           Diagnosis
 history and clinical manifestation
  hCG assay:
 diagnosis suspected if hCG titers
persist to be high 12 weeks after
evacuation of a HM, or once
regress to normal range but rise
rapidly.
possible reasons : retained HM
pregnancy
huge theca-lutein cyst persist
when we remove these reasons
we can diagnosis invasive mole
other measurement
B-ultrasound
X-ray
             Prophylaxis
   respond well to chemotherapeutic
    agents
    main causes of death:
    hemorrhage, metastasis and
    infection
     Treatment:


Identical to that for
 choriocarcinoma
     Choriocarcinoma

 It is highly malignant GTT
 It may follow HM,
invasion mole, abortion,
normal pregnancy, ectopic
pregnancy.
      Pathologic findings
 Gross inspection
 irregular or circumscribed
 hemorrhagic growth in the uterine
 wall
ulcerating surface opens into the
 endometrial cavity (rarely
 embedded in myometrium)
penetration into broad ligament or
 the peritoneal cavity
dark red blood:.it is filled
 metastatic nodules
ulcerating
surface opens
into the
endometrial
cavity (rarely
embedded in
myometrium)
 Histologic findings
 we see masses of anaplastic
 trophblastic cells in microscopy;
 invasion into the uterine wall,
 destroying vessels, muscle tissue
 prominent necrosis and
 hemorrhage
 villi can not be recognized
 spread through circulation
       Clinical Manifestations
    irregular bleeding after
    preceding gestation;
   malignant tumor cells enter the
    circulation through the open
    blood vessels and are
    transported to lungs, brain or to
    other distant sites.
 metastatic symptoms
 pulmonary lesions
 cerebral lesions
 metastatic nodule in the vagina,
 vulva or cervix ,it is bluish
 nodule filled dark red blood.
              Diagnosis
   Diagnosis must be suspected as
    a possible reason for continued
    (irregular) bleeding after any
    form of pregnancy.
   we assay hCG , the time of hCG
    change into normal is different in
    various diseases.
       hCG change
HM:84-100 days
Artificial abortion:30 days
Spontaneous abortion:19
days
Normal delivery:12 days
Ectopic pregnancy:8-9 days
               Staging
International staging of WHO may be
  summarized as follows:
Ⅰ: lesion localized in uterus, no
  metastasis;
Ⅱ: lesion extends beyond uterus, but
  still confined to internal genitalias;
Ⅲ: pulmonary lesion
Ⅳ: metastasis to other distant sites.
           Treatment
 highly sensitive to chemotherapy,
which is invariably the treatment
choice.
surgery has little place (because of
the high vascularity and the
effectiveness of chemotherapy). it is
indicated for tumor resistant to
chemotherapy and single metastases
persisting despite chemotherapy.
        Chemotherapy
most often used drugs
 methotrexate (MTX)
 actinomycin D (Act-D)
 5-fluorouracil (5-Fu)
 vincristine (VCR)
 cyclophosphamide (CTX)
 chlo-ranbucil, etc
   principles
   low-risk patients are usually treated with a
    single agent
   medium-risk patients are usually treated
    with EMA-CO regimen with 80-90%
    survival rate. (Etoposide,
    Methotrexate,Actinomycin,Cyclophospham
    ide,Vincristin)
   toxic reaction: marrow depression ;
   gastrointestinal ulceration;
   change in liver and renal function
       Standard for discharge
   three consecutive weekly assays
    for hCG are negative
   two more courses for
    consolidation
   all symptoms and signs
    disappear
          Operation
 unresponsive or drug fails to
reach the tumor;
 if the tumor can be eradicated
by drug therapy, esp.in young
women, there is no reason to
remove the uterus;
 the ovaries need not be
removed.
    Follow-up examinations
 at 1-month interval for 1 year:
 at 3-month interval for 2 years
 at 1-year interval for 3 years
 at 2-year interval afterwards.
 pelvic examination
 chest X-ray film
 hCG
         Ask question :

   What are the basic
    histologic and pathologic
    differences between
    invasive mole and
    choriocarcinoma?