Gestational Trophoblastic Disease

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Gestational Trophoblastic Disease

• Current management

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Background

• Incidence U.S. and Europe 1/1500
• South East Asia 1/150 (? Carotene, animal fat
  and Vit. A)
• Can follow any gestational event abortion,
  miscarriage, ectopic, normal pregnancy
• Curable in vast majority chemotherapy 1956
• Complete partial mole
• Invasive mole
• Placental-site trophoblastic tumour
• Choriocarcinoma ( always if follows term
  pregnancy 1/50,000 )
• Latter 3 usually derive from molar pregnancy

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Complete Mole

• Pathology Generalized hydatidiform swelling and
  trophoblastic hyperplasia
• fetal/embryonic tissue absent
• Karyotype 90 46XX haploid sperm fertilizes
  ovum and duplicates
• ovum nucleus either absent or inactivated
• 10 46XY
• Clinical Vaginal bleeding 95 (prune
  juice, anaemia)
• Enlarged uterus 50
• Theca lutein cysts 50 (often gt6cm.- may
  take 3 months)
• Hyperemesis 25
• PET 25 (no reported case of eclampsia)
• Hyperthyroidism 5 (if free T4? -
  B-blockade)
• Trophoblastic emboli 2
• Diagnosis U/S usually very sensitive
  generalized swelling (snow-storm )

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Complete Mole
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Complete Mole Histology
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Partial Mole

• Triploid karyotype extra haploid set paternal
• Sometimes fetus present usually triploid
  growth restricted / multiple anomalies
• Pathology differs from complete focal
  hydatidiform swelling
• varying size of chorionic villi
• marked villous scalloping
• focal trophoblastic hyperplasia
• identifiable embryonic or fetal tissues
• Clinical Usually as a regular incomplete or
  missed abortion
• Excessive uterine enlargement / PET very rare
• No hyperemesis / hyperthyroidism / theca-lutein
  cysts
• Diagnosis U/S may detect focal cystic spaces of
  varying diameter
• Diagnosis on histology of curettings

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Partial Mole Histology
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Management

• Pre-operative assessment medical complications
  / CXR
• Evacuation - oxytocin infusion after curettage
• heavy bleeding should not deter from cervical
  dilatation
• suction curettage (fundal massage)
• uterus usually dramatically reduces in size /
  bleeding controlled
• complete with sharp curettage
• Histological evaluation of all tissue
• Natural history Complete - 15 local uterine
  invasion
• 4 metastatic disease
• High risk - hCG gt 100000
• (40) large uterus 30 local invasion
• theca lutein cysts gt 6cm. 9 metastases
• Partial mole - 4 local uterine persistence/no
  cases choriocarcinoma
• Many centres have abandoned follow-up

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Follow up

• Weekly ?-hCG (syncytiotrophoblast)
• levels until
• normal for 3 consecutive weeks
• Can take 12-14 weeks
• Then monthly until normal
• for 6 months
• Contraception Immediate
• Oral / barrier / permanent
• No IUCD until hCG normal (perforation)
• No ? persistent disease on OCP and regression
  time not influenced

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GTN Follow-up
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WHO Prognostic Scoring

• Original assessment and scoring system 1984
  changed in 2000
• Metastatic disease occurs in 4 patients with
  molar pregnancy
• Plateau 4 values over 3 weeks
• Rise ? 10 for 3 values over 2 weeks
• Clinical examination especially pelvis, vagina
  and vulva
• U/S to exclude pregnancy
• Brain MRI superior to CT scan
• Chest CXR adequate for counting metastases / CT
  scan also acceptable
• Abdomen CT scan

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WHO Prognostic Scoring

• Prognostic score
• Prognostic factor 0 1 2
  4
• Age lt39 gt39
• Antecedent pregnancy Mole Abortion Term
  pregnancy
• Interval (months) 4 4-6 7-12
• Pre-treatment ?-hCG (log) lt3 lt4 lt5
  gt5
• Largest tumour 3-4 5
• Site of metastases Spleen
  GI tract Brain
• Kidney
  Liver
• Number of metastases 1-4 5-8
  gt8
• Previous Chemo. Failed Single drug 2
  or more
• Changes ABO group deleted, Liver mets
  score upgraded, no medium risk group
• Low risk ? 6 ? single agent chemotherapy
• High risk ? 7 ? combination chemotherapy
  

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FIGO Staging

• Stage 1 Tumour confined to uterus
• Stage 2 Tumour confined to pelvis
• Stage 3 Metastases to lung ( with/without pelvic
  metastases )
• Stage 4 Distant organ metastases ( with/without
  lung metastases )

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Chemotherapy

• Low-risk If non-metastatic -
  always curable ( Hysterectomy if chemo fails)
• Methotrexate Many regimes
• I.M. Methotrexate 1mg/Kg days 1,3,5,7
• I.M./ P.O. Folinic acid 0.1mg/Kg days
  2,4,6,8
• I.M. Methotrexate 40mg/m² weekly
• Actinomycin D I.V. push 1.25mg/m² every 14 days
• Follow-up ?-hCG, FBC, LFTs and U/Es, creatinine
  prior to each cycle
• Continue treatment cycle for 1-3 weeks after
  normal ?-hCG
• Check ?-hCG monthly for 12 months, then 2
  monthly for 12 months
• Contraception for 12 months
• Complete remission in 85-90 80 require only
  one course
• Toxicity Thrombocytopenia 2, neutropenia 6 and
  hepatotoxicity 14

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High Risk GTN

• Invasive mole invades myometrium / diagnosed at
  hysterectomy / can metastasize
• mets may be choriocarcinoma
• Placental site trophoblastic tumour Locally
  invasive composed of cytotrophopblast
  small if any rise in hCG (lt3000)
• vaginal bleeding usually after
  amenorrhoea
• Large polypoid tumour /
  insensitive to chemotherapy Curettage
  sometimes successful / Hysterectomy
• Choriocarcinoma Accounts for majority of
  metastatic disease
• Early vascular invasion and widespread
  dissemination
• Fragile vessels ? haemorrhagic complications
• 80 have lung mets any respiratory symptom
• 30 have vaginal mets highly vascular
  (avoid biopsy)
• 10 have liver mets usually only with
  extensive tumour elsewhere
• 10 have brain mets never isolated ( lung /
  vagina)
• Treatment EMA-CO chemotherapy /- surgical
  resection / radiotherapy
• Prognosis 75 complete response rate Salvage
  chemo BEP varying success

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Pregnancy After GTN

• No evidence of increased congenital anomalies
  after one year contraception
• Recent Japanese data Women who concieved
  during follow-up period lt 1 year
• No adverse effect on anomalies nor preterm
  delivery
• Risk of further molar pregnancy 0.5-2.5 if one
  previous molar
• 33 if two previous molar
• 3 molar pregnancies poor live birth rate
• Risk of molar pregnancy increases with number of
  previous spontaneous abortions
• Previous term pregnancies reduce risk of GTN

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Conclusions

• GTN is rare
• Ultrasound diagnosis becoming more common
• Senior staff should perform ERPC ( suction and
  sharp curettage)
• Follow-up clinical and serum ?-hCG measurements
  in specialized clinics
• Chemotherapy curative in vast majority low risk
  patients