A Case of Products of Conception

Nora K Frisch M.D.4.19.12

Definition

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

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

Surgical Pathology Gross

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

Microscopic Findings

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

Differential Diagnosis

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

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)

Ancillary Test to Aid in the Diagnosis of Molar Pregnancy

CytogeneticsP57 immunoshistochemistryFISH analysisFlow cytometry

Cytogenetics

• Not sent…. hmmmmmm

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

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)

Photo from RMLonline.com

Our patient

• Diagnosis confirmed with immunohistochemisty

• – complete hydatidiform mole

Cytogenetics of Complete Mole

Cytogenetics of Partial Mole

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

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!

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

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

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

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

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%

Thank you

• Dr. Richard Lieberman

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 Oct;25(10):1225-30.-Ronnett, Brigitte et al. “Hydatiform Moles: Ancillary Techniques to Refine Diagnosis.” International Journal of Gynecologic Pathology. 2011; (30): 101-116.