A Case of Products of Conception

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A Case of Products of Conception

• Nora K Frisch M.D.
• 4.19.12

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Definition

• The human fetus, placenta and other such products
  which occur with a miscarriage or abortion

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Our patient

• 38yo G4P3 woman
• Positive home pregnancy test at 6 weeks and
  office test 4 days later.
• Bleeding beginning at 8 weeks. Enlarged uterus
  with no fetus/heart tones seen on ultrasound.
• D/C performed

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Surgical Pathology Gross

• No fetal parts identified
• Edematous appearing villi/placental tissue
• Clotted blood

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Microscopic Findings

• Villi with marked edema
• Cellular, myxoid villous stroma
• Circumferential trophoblastic hyperplasia
• Irregular and scalloped borders of villi
• Occasional central cisterns

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Differential Diagnosis

• Complete mole vs partial mole vs hydropic
  degeneration of spontaneous abortion

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Quick review

• A complete mole is caused by a single (90) or
  two (10) sperm combining with an egg which has
  lost its DNA (the sperm then reduplicates forming
  a "complete" 46 chromsome set) The genotype is
  typically 46,XX (10 are 46XY)
• A partial mole occurs when an egg is fertilized
  by two sperm or by one sperm which reduplicates
  itself yielding the genotypes of 69,XXY
  (triploid) or 92,XXXY (quadraploid)

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Ancillary Test to Aid in the Diagnosis of Molar
Pregnancy

• Cytogenetics
• P57 immunoshistochemistry
• FISH analysis
• Flow cytometry

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Cytogenetics

• Not sent. hmmmmmm

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Indications for Cytogenetic Analysis on POC

• history of more than two miscarriages
• abnormalities on ultrasound prior to pregnancy
  loss
• confirmation of abnormal prenatal results
• pregnancy loss after IVF

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Use of p57 Immunohistochemistry

• p57kip2 (p57) is the protein product of the
  maternally expressed gene CDKN1C located on
  chromosome 11p15.5 --- thus is absent in complete
  molar pregnancies (paternal only contribution)
• Helpful in differentiating complete mole from
  partial or complete from hydropic degeneration.
• Cannot distinguish partial mole from hydropic
  degeneration (both will be positive)

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Photo from RMLonline.com
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Our patient

• Diagnosis confirmed with immunohistochemisty
• complete hydatidiform mole

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Cytogenetics of Complete Mole
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Cytogenetics of Partial Mole
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FISH Testing

• Why? Differentiating hydropic degeneration,
  partial and complete moles can be very difficult
  in early pregnancy loss with evacuation.
• Low clinical suspicion OFTEN leads to no fresh
  tissue being sent for cytogenetics.
• Diagnosis has important clinical considerations

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Procedure

• Test is performed on formalin fixed, paraffin
  embedded tissue
• In one study, centromeric probes for chromosomes
  9 and 18 are used. In another, Her2 probe was
  used.
• Simple anaylsis count the signals!

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Prognosis

• After D C women are followed with serial
• B-HCG measurements until they return to 0
• Persisent gestational trophoblastic disease
  occurs
• 0.5-4 incomplete mole
• 10-30 complete mole
• Progression to invasive molar disease or more
  rarely choriocarcinoma can occur

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Back to our patient

• Her B-HCG levels were followed. They dropped
  slowly to 175 mIU/ml but then plateaued and then
  rose to 320 mIU/ml
• Patient reported abdominal pain worsening since
  initial procedure
• U/S was concerning for retained products with
  possible myometrial involvement of invasive
  disease
• Patient desired hysterectomy

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PGTD

• Persistent gestational trophoblastic disease is a
  term used to describe GTD that is not cured by
  initial surgery. Persistent GTD occurs when the
  hydatiform mole has grown from the surface layer
  of the uterus into the deeper uterine tissues
• The most common type of PGTD is invasive mole
• More rarely choriocarcinoma, placental site
  trophoblastic tumor or epithelioid trophoblastic
  tumor

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Invasive Mole

• Formerly known as chorioadenoma destruens
• Molar villi grow into the myometrium or blood
  vessels of the uterus.
• May rarely spontanteously regress
• May grow through uterine wall and cause
  hemorrhage
• May metastasize to lungs, vagina, and other sites
• Primary treatment is chemotherapy and continuing
  to follow B-HCG levels
• Hysterectomy if perforation or other complications

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Invasive Mole vs. Choriocarcinoma

• Differs from choriocarcinoma by the presence of
  villi in the invasive component
• Although it can metastasize, has slightly better
  prognosis than choriocarcinoma
• Metastatic choriocarcinoma has cure rates ranging
  from 75 to near 100
• Metastatic invasive mole has cure rates near 100

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Thank you

• Dr. Richard Lieberman

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References

• -Benirschke, Kurt et al. Pathology of the Human
  Placenta. Fifth Edition. Springer (2006)
• -Catrillon, DH, et al. Discrimination of
  complete hydatidiform mole from its mimics by
  immunohistochemistry of the paternally
  imprinted gene product p57KIP2. Am J Surg
  Pathol. 2001 Oct25(10)1225-30.
• -Ronnett, Brigitte et al. Hydatiform Moles
  Ancillary Techniques to Refine Diagnosis.
  International Journal of Gynecologic Pathology.
  2011 (30) 101-116.