Preeclampsia at 17 weeks

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Preeclampsia at 17 weeks

• Diana Kaufman M.D.
• March 12, 2008

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Gestational Trophoblastic Disease

• GTD
• Pregnancy related trophoblastic proliferative
  abnormalities
• Two Types
• 1. Mole
• Complete
• Partial (Incomplete)
• 2. Gestational trophoblastic neoplasia
• Invasive Mole
• Choriocarcinoma
• Placental-site trophoblastic tumor

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Molar Pregnancy

• Characterized histologically by abnormalities of
  chorionic villi that consist of trophoblastic
  proliferation and edema of villous stroma.
• Usually found in the uterus, may be in tube or
  ovary

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Complete Mole

• Ovum typically fertilized by haploid sperm which
  duplicates its own chromosomes.
• Chromosomes of ovum absent or inactive
• Karyotype is 46 XX in 85
• Rarely 46 XY if dispermic fertilization

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Complete Mole

• Chorionic villi transform into a mass of clear
  vesicles of varying sizes
• Histological structure
• Hydropic degeneration and swelling of villous
  stroma
• Absence of blood vessels in swollen villi
• Implantation site trophoblast has diffuse marked
  atypia
• Proliferation of trophoblastic epithelium
• Absence of fetal amnion

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Partial Mole

• Ovum typically fertilized by two sperm
• Karyotype typically 69 XXX or XXY
• Fetus usually with multiple malformations and
  abnormal growth

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Partial Mole

• Some element of fetal tissue seen
• Hydatidiform changes are focal and less advanced
• Slowly progressive swelling within the stroma of
  avascular chorionic villi
• Focal mild atypia of implantation site
  trophoblast

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Molar Pregnancy

• Risk Factors
• Age
• Less than 15 or greater than 45
• Previous Mole
• Risk is higher incomplete (2.4) vs complete
  (1.4)
• New partner has no influence
• History of prior SAB or infertility

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Molar PregnancySigns and Symptoms

• Vaginal bleeding
• 89 to 97 complete moles
• Spotting to profuse hemorrhage
• Occur at any time for any length of time
• Enlarged uterus
• Secondary to retained blood and tissues
• Preeclampsia before 24wks
• Highest risk with excessive uterine size and high
  hCG levels

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Molar PregnancySigns and Symptoms

• Hyperemesis
• 20 to 26 complete moles
• Secondary to high levels estrogen and hCG
• Thyrotoxicosis
• Plasma thyroxine often elevated, but clinically
  apparent hyperthyroidism unusual
• May be due to thyrotropin-like effect of hCG
• Watch for thyroid storm at time of anesthesia
  induction

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Molar Pregnancy Signs and Symptoms

• Embolization
• Trophoblastic cells escape the uterus into the
  venous outflow at the time of evacuation
• May give signs/symptoms of PE or pulmonary edema
• Incidental finding on path
• Partial mole often presents as missed or
  incomplete SAB and diagnosis made on review of
  curettage specimen

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Molar PregnancyTheca Lutein Cysts

• Vary from microscopic to 10 cm or greater
• Generally 6 to 12cm, may enlarge to 20cm
• Usually multicystic and bilateral
• Contain serosanguineous fluid
• Smooth yellow surface, lined with lutein cells

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Molar PregnancyTheca Lutein Cysts

• Secondary to an overstimulation of the lutein
  elements by excessive amounts of hCG
• Regress after delivery generally over an interval
  of 8 weeks
• Do not remove unless infarcted ovary,
• May aspirate large cyst if symptomatic
• Other signs of ovarian hyperstimulation may
  develop
• Ascites
• Pleural effusion

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Molar PregnancyDiagnosis

• Ultrasound sensitive and reliable for detecting
  complete mole
• Characteristic vesicular pattern
• Snowstorm
• Cluster of Grapes

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Molar PregnancyPrognosis

• Mortality reduced to zero by prompt diagnosis and
  therapy
• Early evacuation has not reduced the risk for GTN

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Molar PregnancyTreatment

• Two phases
• 1. Evacuate the mole
• Dont forget Rhogam when indicated
• 2. Evaluate for persistent trophoblastic
  proliferation or malignant change
• Serial hCG

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Molar PregnancyTreatment

• Vacuum Aspiration
• Treatment of choice
• If large mole, have blood products available
• U/S helpful to document if cavity empty
• Oxytocin/Prostaglandins
• Rarely used
• Hysterectomy
• Logical choice in women gt40y/o
• 1/3 develop GTN
• Doesnt eliminate risk of recurrent disease, but
  significantly reduces
• Aspirate theca lutein cyst at time of surgery

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Molar PregnancyTreatment

• Prophylactic Chemotherapy
• Controversial
• Doesnt improve long-term prognosis
• Toxicity may be significant
• Consider with high risk moles, hCG testing
  unavailable, follow-up impossible

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Molar PregnancyFollow-Up

• 1. Prevent pregnancy for entire follow-up
  interval
• Minimum of 6 months
• Dont use IUD until hCG normal
• Risk of perforation and infection if residual
  tumor present
• 2. Monitor hCG every week until normal for 3
  weeks
• 3. If rise or plateau in hCG evaluate for GTN
• 4. Once hCG normal, monitor monthly for 6 months

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Gestational Trophoblastic Neoplasia

• AKA Malignant Gestational Trophoblatic Disease
• Includes
• Invasive Mole
• Choriocarcinoma
• Placental Site Trophoblastic Tumor

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GTN Risk Factors

• Complete mole
• Markedly elevated hCG
• Excessive uterine size
• Older than 40
• Repetitive molar pregnancy

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GTNEtiology

• Almost always develops with or follows some form
  of pregnancy
• 50 after mole
• 25 normal pregnancy
• 25 SAB, EAB, ectopic

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Choriocarcinoma

• Carcinoma of chorionic epithelium
• Characteristically rapidly growing mass invading
  myometrium and blood vessels leading to
  hemorrhage and necrosis

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Choriocarcinoma

• Cytotrophoblastic and syncytial elements are
  involved, but one or the other may predominate.
• Microscopically sheets of these cells penetrate
  the muscle and blood vessels
• There is an absence of a villous pattern seen in
  hydatidiform or invasive moles.
• Develop in 4 patients following complete mole

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Choriocarcinoma

• Extremely malignant
• Metastasis develop early and are blood bourne.
• Lung (75 to 80)
• Vagina (30 to 50)
• Liver (10)
• Brain (10)
• Vulva
• Kidneys
• Ovaries
• Bowel

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Choriocarcinoma

• Lung Mets
• Asymptomatic lesion on CXR
• SOB
• CP
• Cough
• Hemoptysis
• If extensive mets respiratory failure
• Vaginal Mets
• Irregular bleeding
• Purulent discharge
• DONT BIOPSY

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Choriocarcinoma

• Cerebral Mets
• Vomiting
• Seizure
• HA
• Hemiparesis
• Slurred speech
• Vision changes
• Liver Mets
• Usually asymptomatic
• Jaundice
• Intra-abdominal bleeding
• Epigastric bleeding

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Invasive Mole

• Excessive trophoblastic overgrowth and extensive
  penetration by the trophoblastic cells
• Penetrate into the myometrium, peritoneum,
  adjacent parametrium, vaginal vault
• Lack tendency for widespread mets
• Develop in 15 patients following complete mole

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Placental Site Trophoblastic Tumor

• Trophoblastic neoplasia arising from the
  placental implantation site following a normal
  pregnancy, SAB, EAB, ectopic, or mole.
• Characterized by predominantly cytotrophoblastic
  cells, many prolactin producing cells, few
  gonadotropin producing cells
• hCG may be normal to elevated
• Main symptom is bleeding

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GTN

• Most common findings
• Uterine sub-involution
• Irregular bleeding
• Any case of unusual bleeding after any type of
  pregnancy should be investigated by curettage and
  measurement of hCG

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GTNDiagnosis

• Complete HP
• Labs
• hCG
• hepatic, thyroid, renal function tests
• CXR
• CT or MRI of head and abdomen
• Only if vaginal or lung mets

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GTNStaging

• Stage 1
• Disease confined to the uterus
• Stage 2
• GTN extends outside the uterus, but is limited to
  the genital structures
• Stage 3
• GTN extends to lungs with or without known
  genital tract involvement
• Stage 4
• Mets to all other sites
• Generally seen with choriocarcinoma
• Commonly follow nonmolar pregnancy

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GTNPrognostic Scoring System

• Scoring system developed by FIGO
• Most useful for stages 2 and 3
• Variables considered
• Age
• Type of antecedent pregnancy
• Interval from pregnancy
• hCG level
• Size of tumor
• Site of tumor
• Number of mets
• Previous chemo given
• Low risk 0 6
• High risk 7 or greater

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GTNTreatment

• Stage 1
• No desire for future fertility
• TAH and single agent chemo
• Methotrexate with folinic acid
• Actinomycin D
• Desire future fertility
• Single agent chemo
• Local uterine resection
• Only if resistant to chemo

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GTNTreatment

• Stage 2 and 3
• Low risk single agent chemo
• High risk combo chemo
• EMACO
• Etoposide, MTX, Act-D, cyclophosphamide, Oncovin
  (vincristine)
• May require hysterectomy to control hemorrhage or
  sepsis
• Vaginal mets
• WLE if bleeding
• Lung mets
• Dont do thoracotomy unless diagnosis seriously
  in doubt

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GTN

• Stage 4
• Intensive combo chemo
• Selective radiation treatment
• Hepatic mets
• Excise if bleeding or resistant tumor
• Brain mets
• Whole brain irradiation

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GTNFollow-Up

• Stage 1, 2, and 3
• Weekly hCG until normal for 3 weeks, then monthly
  until normal for 12 months
• Stage 4
• Weekly hCG until normal for 3 weeks, then monthly
  until normal for 24 months

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GTNPrognosis

• Overall cure rate 90
• Nonmetastatic and low risk metastatic
• Nearly 100 if chemo started early
• High risk metastatic
• Depends on factor indicating high risk

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Pregnancy after GTN

• No difficulty with fertility or outcomes in
  complete moles
• Limited information regarding subsequent
  pregnancy experience with incomplete moles
• After GTN, can also expect normal reproduction
• Due to recurrence risk, get U/S early in
  pregnancy and check hCG 6 weeks after completion
  of any pregnancy.

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Questions?
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References

• Hoskins, William J, et. al. Principles and
  Practice of Gynecologic Oncology. Fourth
  edition. Philadelphia Lippincott Williams
  Wilkins, 2005.
• Cunningham, F. Gary, et. al. Williams Obstetrics.
  Twenty-second edition. McGraw Hill, 2005.