Molar PregnancyDiagnosis of the Usual and Unusual

Hydatidiform mole: Classified as gestational trophoblastic disease

An abnormal conceptus usually with a double complement of paternal DNA:

Complete Mole: An ovum with no maternal DNA is fertilized by two sperm or one sperm that duplicates to create a diploid state.

Partial Mole: An ovum with a normal complement of maternal DNA is fertilized by two sperm or one sperm that duplicates to create a diploid paternal complement.

Biparental Mole: A diploid conception from one egg (with a maternal component) and one sperm that becomes molar due to gene mutations.

Diploid - Diandric

Triploid - Diandric

Biparental diploid

Triploid Karyotype

CISH FISH Flow Cytometry Image Cytometry

PLOIDY ANALYSIS

Test for Triploidy:

• Many methods

• FISH/CISH most reliable- CEP 17 FISH available at PhenoPath

• In my experience, FISH produces cleaner results than flow cytometry.

If it histologically looks like a partial mole and is triploid – call it a partial mole.

If triploidy was discovered on karyotype and original histology was not regarded as molar, it may be a dygynic triploid. Would need STR to determine. Rarely pursued.

Non-Molar Hydropic Abortus

Round to oval – lightly basophilic stromal ground substanceNo trophoblastic hyperplasia – rarely cisterns.

Non-Molar Hydropic Abortus

p57 staining of nuclei of villous cytotrophoblasts and stromal cells.

p57

Classic Complete Mole:- Very high b-HCG (>100,000 IU/L)- Classic US with no fetus and

multicystic mass.- Diploid if karyotyped- Classic gross and microscopic

appearance.

Complete Mole

Circumferential trophoblastic hyperplasia

Complete Mole

Central Cisterns

Complete Mole

Loss of p57 nuclear staining in the villous cytotrophoblasts and stromal cells

p57

Partial Mole

Two populations of villi: 1. edematous ; 2. cellular and fibrous stoma.

• Focal trophoblastic hyperplasia

• Scalloping and trophoblastic inclusions

• Evidence of a fetus

> fetal tissue> circulating nucleated erythrocytes.

Partial Mole

Partial Mole

p57

p57 staining of nuclei of villous cytotrophoblasts and stromal cells.

Less Obvious Moles - Possibly Early First Trimester

Partial Mole:• Subtle scalloping • Circumferential trophoblastic

hyperplasia but evidence of a fetus(nrbc).

Complete mole:• Rare villi with obvious trophoblastic

hyperplasia.• Villous stromal cell apoptosis.• Twins – normal and complete mole

Diagnostic criteria

Partial mole: morphology and ploidy study (triploid).

Complete mole: morphology and p57 immunostain.loss of nuclear stain in villous cytotrophoblasts and stromal cells.intermediate trophoblasts are positive internal control.

Biparental mole: not diandric diploid, one complement each from mother and fatherlooks like typical complete molep57 loss as expectedwill only see in STRclue is repeat molar pregnancymutations in NLRP7 and KHD3CL

• Many reported disease causing mutations – often a compound heterozygote (acts like a homozygote, both alleles affected, just in different loci).

• In addition to a high rate of repeat molar pregnancy, delivering a live fetus is also markedly diminished.

Ngoc Minh Phuong Nguyen & Rima Slim, Curr Obstet Gynecol Rep (2014) 3:55–64

Diagnostic criteria

Partial mole: morphology and ploidy study (triploid).

Complete mole: · morphology and p57 immunostain.· loss of nuclear stain in villous cytotrophoblasts and stromal cells.· intermediate trophoblasts are positive internal control.

Biparental mole: · not diandric diploid, one complement each from mother and father.· looks like typical complete mole.· p57 loss as expected.· will only see in STR.· clue is repeat molar pregnancy.· mutations in NLRP7 and KHD3CL.

Mesenchymal dysplasia: · usually seen in a placenta attached to a fetus.· mesenchymal and cystic expansion of stem villi.· rarely seen without a fetus in D&C.· nuclear p57 lost in villous stromal cells but not in villous

cytotrophoblasts.· may co-exist with a complete mole.

Mesenchymal expansion of stem villus

P57: loss in villus stromaretained in cytotrophoblast

Placental Mesenchymal Dysplasia (PMD) in Placenta with Fetus

Mesenchymal expansion of stem villiMay resemble partial mole on US

Placental Mesenchymal Dysplasia in a D&C

Non-molar Hydropic Villi

Placental Mesenchymal Dysplasia in a D&C

Central Cistern

p57

Placental Mesenchymal Dysplasia in a D&C

p57 staining only cytotrophoblast, not stroma

Placental Mesenchymal Dysplasia in a D&C

Subtrophoblastic Vascular Plexus

Placental Mesenchymal Dysplasia in a D&C

Atypical Cytotrophoblast

p63

Placental Mesenchymal Dysplasia in a D&C

p63 highlights atypical cytotrophoblasts

p63p57

Placental Mesenchymal Dysplasia in a D&C

p57 lost in cytotrophoblasts and stroma (= Complete Mole component)

p63p57Sall-4

Placental Mesenchymal Dysplasia in a D&C

Sall-4 marking cytotrophoblasts, potentially ominous finding

The End

Mark Luquette, M.D. LUQUE007@UMN.EDU