Gestational trophoplastic disease GTD

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Gestational trophoplastic diseaseGTD

• By Prof. dr. Abdurrahman Sharef

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Gestational trophoplastic diseaseGTD

• Definition It is a clinical term used to
  indicate three closely related conditions
  characterized by active abnormal proliferation
  of trophoblastic cells
• hydatidiform mole ,
• invasive hydatidiform mole and
• Choriocarcinoma

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Gestational trophoplastic diseaseGTD

• These neoplasm's retain certain characteristic of
  the normal placenta such as invasive tendencies
  and the ability to make hCG hormone

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Gestational trophoplastic diseaseGTD

• Pathological classification
• Hydatidiform mole 80 of cases.
• Invasive mole 12-15 of cases.
• Choriocarcenoma5-8 of cases.
• Clinical classification The course, and
  prognosis of the disease accurately reflected by
  hCG hormone
• Benign 80
• Malignant20

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Hydatidiform mole

• The hydatidiform mole incidence ranges from 1 in
  522 pregnancies in Japan
• To 1 in 1500 pregnancies in USA,and Sweden, this
  variation is not understood, but ethnic factors
  have been suggested .
• The incidence is higher in the poorest
  socioeconomic classes than the semiprivate(4
  times), and (8 times) than the privet , and these
  mostly related to diet especially protein
  deficiency .

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Hydatidiform mole

• The maternal age over 40 years found to have a
  5.2-fold increased risk of trophoblastic disease
  in compression to the mothers below the age of 35
  years.

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Hydatidiform mole

• Hydatidiform mole can be subdivided into
• complete and
• partial mole

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Hydatidiform mole

• Based on
• Genetic and
• Histopathological features

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complete moles

• Genetic features One of the most remarkable
  discoveries about hydatidiform mole has been the
  demonstration that complete moles have
  chromosomes exclusively from the paternal side
  ,and the karyotype is nearly always 46,xx and
  only rarely is 46,XY observed.
• The normal mechanism is for a haploid
  sperm,23X,to fertilize an empty egg, and to
  duplicate itself to form a 46,XX complement. Much
  less commonly ,two spermatozoa, one being 23,X,
  and the other,23,Y, can fertilize an empty egg,
  to give karyotype a 46,XY.

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Partial moles

• Are triploid in origin with two sets of paternal
  haploid genes and one set of maternal haploid
  genes

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Partial moles

• They occur, in almost all cases, following
  dispermic fertilization of an ovum.
• There is usually evidence of a fetus or fetal
  red blood cells

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partial moles

• In the partial moles ,the normal finding is a
  triploid karyotype ,69 chromosomes instead of
  normal 46. The most common mechanism appears to
  be fertilization of normal egg by two sperm,
  giving a complement of 69,XXY.

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Pathological features

• Complete mole
• there are numerous edematous vesicles, which
  looks like a bunch of small clear grapes,
• usually no fetus, or membranes.,

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Pathological features

• microscopically there are
• large oedematous enlarged villi ,
• a vascular ,
• with variable degree of trophoblastic
  hyperplasia.
• carries greater risk of malignancy and requires
  longer follow up than the partial mole.

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Pathological features

• Partial mole
• Shows a less clear -cut picture ,with the
  formation of vesicles usually focal ,
• fetus and membranes may present,
• the vesicles have degree of vascularity.

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Pathological features

• In general ,the more active trophoblastic
  appearance the greater the risk of malignancy.
• So the subsequent management depends more on the
  hCG results than the histological reports.

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Clinical features

• Bleeding Bleeding in early pregnancy after
  variable period of amenorrhea is the most common
  clinical sign of the mole (occurs in 90 of
  cases), with the passage of the vesicles.

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Pathological features

• Hyperemesis gravidarum Occurs into 25 of cases
  of moles ,and appears more common when the uterus
  is much enlarged and hCG levels are very high.

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Pathological features

• Uterine enlargement The uterus is commonly
  large for datein 50 of case of moles ,
• although, in a small proportion of cases the
  uterus corresponding to the gestational age or
  smaller than date.
• The uterus having a doughy consistency.
• The fetal parts are not palpable, and fetal heart
  is absent.

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Pathological features

• Large theca lutein cysts of the ovary are present
  in 20of moles , these may be exaggerated the
  clinical picture of large for date uterus. These
  cysts are manifestation of excessive hCG.

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Pathological features

• Pre-eclampsia Occur in association with the
  moles with range widely from 12-54,these due to
  differing times of diagnosis, the longer
  pregnancy progresses ,the greater chance to
  developing pre-eclampsia. If the signs of
  pre-eclampsia appears early in pregnancy , the
  possibility of hydatidiform mole should be looked
  for with out delay.

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Pathological features

• Hyperthyrodism Develop in small proportion of
  women ,and this may be due to thyrotrophic
  effects of the human chorionic thyrotrophin ,
  which may lead to goitre,fine tremor
  ,supra-ventricular tachycardia, and weight loss.
• DIC can develop in long-standing hydatidiform
  moles , when there is embolization of
  trophoblastic tissue to the lung, leads to
  thromboplastic substances which stimulate
  fibrin,and platelet deposition.

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Diagnosis of hydatidiform moles

• History and examination From the history of
  amenorrhea ,passage of vesicles vaginally with
  bleeding the size and consistency of the uterus.

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Pathological features

• The increasing use of ultrasound in early
  pregnancy has probably led to the earlier
  diagnosis of molar pregnancy

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Pathological features

• By the U/S examination can be diagnosed from very
  early pregnancy ,characterized by Snow-storm"
  appearance.

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Pathological features

• By very high levels of serum hCG than the normal
  singleton pregnancy ,which is diagnostic and
  prognostic to the course of the disease ,with
  very short dappling time.

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Prognosis

• The risks of hydatidiform mole are
• Immediate hemorrhage ,sepsis, or pre-eclampsia
  the treatment of these conditions has vastly
  improved recently.
• Molar metastases
• Of a non proliferative benign type can
  occur.

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Prognosis

• Choriocarcinoma The most important danger
  association with the hydatidiform mole is the
  development of malignant GTD(Invasive mole or
  choriocarcinoma) in about 10 of cases,

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Management

• The aim of treatment is to eliminate all
  trophoblastic tissue from the maternal systems
• If the hydatidiform mole diagnosed ,steps
  should be taken to evacuate the uterus, and this
  achieved by

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Mangement

• Suction curettage (SC) The method of choice
  even when evacuation large mole

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Mangement

• Under GA.
• Cervix dilation till 12mm.and SC induced to the
  uterine cavity.
• I.V oxytocin infusion is started .
• SC started by negative pressure of about 60 to
  70cmHg.
• The curette is genteelly rotated to ovoid
  perforation of the soft uterus, and the majority
  of the molar tissue is evacuated rapidly ,and the
  uterine size decreases

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Mangement

• Uterine stimulation.

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Mangement

• Medical termination of complete molar pregnancies
  including cervical preparation prior to suction
  evacuation, should be avoided where possible.

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Mangement

• The contraction of the myometrium may force
  tissue into the venous spaces at the site of the
  placental bed.
• The dissemination of this tissue may lead to the
  profound deterioration in the woman, with embolic
  and metastases disease occurring in the lung

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Mangement

• Surgical evacuation

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Mangement

• Surgical evacuation Hysterectomy has been
  recommended as a suitable method of treating
  hydatidiform mole in older women who completed
  their family ,to reduce the risk of post-molar
  trophoblastic disease . .The hysterectomy should
  be carried out with little monopolization to
  ovoid precipitating mobilization of trophoblastic
  tissue.

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Evacuation of partial mole

• In partial molar pregnancies where the size of
  the fetal parts deters the use of suction
  curettage, medical termination can be used.

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F0llow-up

• After the uterus has been evacuated
• About 90 of cases ,the trophoblastic tissue die
  out completely.
• About 10 of cases the trophoblastic tissue does
  not die out completely and may persist or recur
  as invasive mole or choriocarcinoma.

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Follow-up

• So it is important that women who have had a
  hydatidiform mole
• should have close follow-up by serum hCG levels
  after the evacuation of the uterus,
• To ensure early recognition of persistent
  trophoblastic tissue .

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F0llow-up

• After a molar pregnancy ,the hCG levels will
  usually have returned to non pregnant levels by 4
  to 6 weeks after evacuation.
• The follow-up is recommended for 2 years in
  cases of complete moles, and 6 months of cases of
  partial moles after the evacuation of uterus.

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F0llow-up

• Serial quantitative measurement of serum hCG
  level at weekly intervals, after evacuation of
  moles till 4 to 5 weeks when the hCG become
  normal. Then every other week .When the titer
  gets negative the measurements are done every
  month fore 1 year.

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F0llow-up

• Indication of chemotherapy after the evacuation
  of the hydatidiform mole in
• Serum hCG gt20000 i.u/L , at any time after
  evacuation of mole.
• Raised hCG at 4 to 6 weeks after evacuation of
  mole.

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F0llow-up

• Evidence of metastases ,hepatic,brain,and
  pulmonary.
• Persistent uterine hemorrhage after evacuation of
  mole with raised hCG levels.

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F0llow-up

• To achieve effective follow-up ,the pregnancy is
  better to be avoided ,and also the use of oral
  contraceptive pills until the hCG levels returns
  to normal after the evacuation of the mole.
• Early diagnosis of persistent trophoblastic
  disease ensures a good prognosis and an effective
  system of follow-up.

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Malignant trophoblastic disease

• Malignant trophoblastic disease can exist in two
  forms
• Invasive mole non-metastatic form.
• Choriocarcinoma metastatic form .

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Malignant trophoblastic disease

• Both treated with the chemotherapy and monitored
  by hCG tumor marker.
• Choriocarcinoma subdivide into
• good-prognosis (Low-risk) ,and
• poor- prognosis (High-risk).

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Invasive mole

• The diagnosis of invasive moles or chorioadenoma
  destruens is applied to the moles characterized
  by
• Abnormal peneterativeness and,
• Extensive local invasion, along with
• Excessive trophoblastic proliferation ,
• With preserved villous pattern.

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Invasive mole

• The proliferative villi may invade the myomatrum
  ,paramatrum or the vaginal wall, although there
  is rarely evidence of metastasis.
• The morbidity and mortality of this disease
  results from the penetration of the tumar through
  the myomatrum and to the pelvic vessels with the
  resultant hemorrhage the morbidity and mortality
  rate 10 .

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Choriocarcinoma

• Choriocarcinoma subdivide into
• good-prognosis (low risk).
• Poor- Prognosis (High risk).

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Epidemiology

• The incidence of choriocarcinoma in the West 1
  10000 and 170000 pregnancies and
• In Asia between 1250 and 16000 pregnancies..

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Epidemiology

• The antecedent pregnancy is
• Hydatidiform mole in about 57 of cases.
• Normal pregnancy in about 26 of cases.
• Abortion and ectopic pregnancy in about 17 of
  cases.

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Epidemiology

• The risk of Choriocarcinoma after a hydatidiform
  mole is about 2-4 which is 1000 times greater
  than after a normal pregnancy.

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Epidemiology

• Choriocarcinoma is more likely to occur after
  complete mole .
• The incidence is in excess in maternal blood
  group A, and deficit in group O.

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Pathological features

• Site In the uterus 90 of cases 10 of cases
  in the ovaries ,vagina, vulva, lung, liver, and
  brain.

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Pathological features

• Macroscopically
• Uterus It may be localized in the form of
  hemorrhagic polyp or multiple hemorrhagic
  ,necrotic masses in the cavity.
• Some times it is present in the uterine wall
  (intramural) and the cavity is empty.

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Pathological features

• Ovaries May show stormal lutein hyperplasia,
  and theca-lutein cysts. And may be site of
  secondaries.

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Pathological features

• Microscopically
• Malignant hyperplasia of both cytotrophoblasts,and
  syncytiotrophoblasts.
• Extensive hemorrhage.
• Absence of villi.
• Destruction of the surrounding myomatrum.

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Spread

• Direct Through the myomatrum and may end in
  uterine perforation ,internal hemorrhage, and
  peritonitis .Through the fallopian tubes to the
  ovaries.

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Spread

• Blood The main method of spread ,and occurs to
• Genital Vagina, vulva, and ovary.
• Extra genital Lung, liver, brain, and bones
  especially skull and spine.
• The lung is the commonest site for secondaries
  and haemoptysis may be the presenting symptom.

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Causes of death

• Vaginal bleeding.
• Haemoptysis.
• Intraperitoneal hemorrhage.
• Peritonitis.
• Metastasis to the vaital organs e.g,brain.
• Pulmonary complications.

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Clinical feathers

• Symptoms
• Recent history of expulsion of vesicular mole
  ,or abortion, or full term pregnancy.
• Persistent vaginal bleeding is the commonest
  presentation.
• Haemoptysis.
• Abdominal swelling (uterus or ovaries).

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Clinical feathers

• Persistent GTD should be considered in any woman
  developing acute
  respiratory or neurological symptoms
  after any pregnancy.

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Clinical feathers

• Signs
• Marked deterioration of the general condition.
• An abdominal swelling may be felt.

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Clinical feathers

• Vaginally
• The uterus symmetrically enlarged (less than 12
  weeks).
• The ovaries may be enlarged.
• Hemorrhagic secondaries may be seen in the vagina
  or vulva

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Clinical feathers

• Investigation
• Serum hCG.
• Chest X-ray for pulmonary metastasis.
• L.F.T .
• Liver scan.
• CAT scan for the secondaries.
• EEG .
• U/S for abdomen and pelvis.
• Diagnostic DC.

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Clinical feathers

• The clinical classification of gestational
  trophoblastic disease
• Non-metastatic.
• Metastatic
• Low risk All patient of documented metastatic
  disease who do not have high-risk factors.

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Clinical feathers

• High risk
• B-hCG level higher than 100.000miu/ml.
• Associated pregnancy episode more than 4 months
  before the diagnosis.

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Clinical feathers

1. Following full-term pregnancy.
2. Liver or brain metastasis.
3. Failure of previous chemotherapy.
4. Symptoms of malignancy more than 4 months

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Treatment

• Prophylaxis After care of vesicular mole
• DC after one week of the evacuation.
• Monitored for the signs and symptoms of
  trophoblastic neoplassmic by.
• serial hCG.

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Treatment

• Diagnostic DC is done if
• The hCG levels remains high.
• The hCG levels rises after gets negative.
• Uterine sub involution.
• Persistence of theca lutein cysts in the ovaries.
• Every case of secondary postpartum haemorrhage.
• Every case of post abortive bleeding.

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Active treatment

• Non metastatic GTD
• Methotrexate (antimetabolite) folinic acid.
• The cytotoxic therapy is controlled by doing
  CBC,platelet count and LFT.
• After the the hCG level gets normal stop the
  therapy and follow-up by weekly estimation of hCG
  levels.

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Active treatment

• Women scoring Non metastatic GTD,and(low risk)
  GTD receive intramuscular methotrexate on
  alternate days, followed by six rest days, with
  each course consisting of four injections

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Active treatment

• Physical examination, chest x-ray, and LFT.
• Total abdominal hysterectomy ,if the patient does
  not desire to maintain child-bearing, in the
  middle of the first treatment course .

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Active treatment

• Low metastatic GTD
• Methotraxate , or Actinomycin D ,if there is
  resistance ,change to triple chemotherapy.

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Active treatment

• The criteria for initiation, and continuation of
  each methotraxate treatment
• Platelet count more than 100.000.
• WBC more than 3000.
• Absolute neutrophil count between 1000-1500.
• Normal LFT, renal function.

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Active treatment

• High risk metastatic GTD
• Triple chemotherapy Methotraxate, Actinomycin
  D, and Cytoxan.

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Active treatment

• Surgery
• TAH may be done in patients not desirous of
  further reproduction.
• Surgical extirpation of isolated metastases e.g.
  pulmonary if resistant to chemotherapy.

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Active treatment

• Irradiation Whole brain irradiation for
  cerebral metastases , The whole organ irradiation
  for hepatic metastases

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Follow-up

• After successful therapy ,the hCG levels are
  obtained
• every 2weeks for 3 months,
• every month for 3months,
• every 2months for 6 months then every sixes
  months indefinitely.

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Follow-up

• If at any time hCG levels rises, repeat the
  evaluation , staging ,and chemotherapy.
• Physical examination, and chest x-ray follow-up
  at 6 weeks, then every 3months for one year, then
  every 6 months for one year.

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Follow-up

• Pregnancy is not allowed except after one year of
  negative follow up but with danger of
• Molar pregnancy (4-5 times greater risk).
• Spontaneous abortion.
• Premature delivery.

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Future pregnancy

• If a further molar pregnancy does occur,
  in 6880 of cases
  it will be of the same
  histological type

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Future pregnancy

• Women who undergo chemotherapy are advised not to
  conceive for one year after completion of
  treatment

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