Definition/General
Introduction:
Molar pregnancy (hydatidiform mole) is an abnormal fertilization resulting in placental tissue with hydropic villous swelling and trophoblastic hyperplasia
It represents a form of gestational trophoblastic disease
The condition involves abnormal genomic imprinting
It occurs in 1-2 per 1000 pregnancies globally
Higher incidence in Asian populations.
Origin:
Results from abnormal fertilization events
Complete moles: diploid androgenetic (all paternal DNA)
Partial moles: triploid (two paternal, one maternal set)
Genomic imprinting abnormalities
Loss of maternal chromosome contribution
Paternal genome excess drives trophoblastic proliferation.
Classification:
Two main types: Complete hydatidiform mole (CHM)
Partial hydatidiform mole (PHM)
By risk: Low-risk GTD
High-risk GTD
By genetics: Diploid complete
Triploid partial
Rare: Invasive mole.
Epidemiology:
Incidence: 1-2:1000 pregnancies
Higher in Asia (2-10:1000)
Bimodal age distribution
Risk <20 years: 1.5x
Risk >40 years: 5-10x
Recurrence risk: 1-2%.
Clinical Features
Presentation:
Irregular vaginal bleeding
Uterine size-date discrepancy
Absence of fetal parts
Hyperemesis gravidarum
Early preeclampsia
Hyperthyroidism
Theca lutein cysts.
Symptoms:
Vaginal bleeding (95% cases)
Passage of vesicles
Excessive nausea and vomiting
Abdominal pain
Rapid uterine enlargement
Respiratory symptoms (trophoblastic embolism).
Risk Factors:
Extremes of age (<20, >40 years)
Previous molar pregnancy
Asian ethnicity
Dietary factors (low vitamin A)
ABO incompatibility
Consanguinity
Oral contraceptive use.
Screening:
β-hCG levels (markedly elevated)
Pelvic ultrasound ("snowstorm" pattern)
Complete blood count
Thyroid function tests
Liver function tests
Chest X-ray.
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Gross Description
Appearance:
Grape-like vesicles (complete mole)
Mixed fetal parts and vesicles (partial mole)
Hydropic villi
Absence of fetus (complete)
Abnormal fetus (partial)
Clear fluid-filled vesicles.
Characteristics:
Translucent, cystic structures
Variable size vesicles
Soft, friable tissue
Abundant clear fluid content
No normal placental architecture.
Size Location:
Complete mole: entire conceptus abnormal
Partial mole: mixed normal and abnormal areas
Vesicle size: few mm to several cm
Total volume often increased.
Multifocality:
Diffuse involvement in complete moles
Focal involvement in partial moles
Skip areas possible
Associated with lutein cysts.
Microscopic Description
Histological Features:
Hydropic villous swelling
Trophoblastic hyperplasia
Absence of fetal vessels (complete)
Central cisterns in villi
Scalloped villous outlines
Stromal edema.
Cellular Characteristics:
Syncytiotrophoblast hyperplasia
Cytotrophoblast proliferation
Loss of polar arrangement
Nuclear atypia
Increased mitotic activity
Absence of stromal vessels.
Architectural Patterns:
Enlarged, rounded villi
Central cavitation
Trophoblastic proliferation
Loss of normal branching pattern
Circumferential hyperplasia.
Grading Criteria:
Complete mole: all villi abnormal
Partial mole: mixed population
Degree of hyperplasia
Atypia assessment
Mitotic index.
Immunohistochemistry
Positive Markers:
β-hCG (syncytiotrophoblast)
hPL (human placental lactogen)
Cytokeratin (trophoblast)
Inhibin-α
p57 (maternal genome - absent in complete mole)
Ki-67 (increased proliferation).
Negative Markers:
p57 (absent in complete mole)
CD68 (Hofbauer cells decreased)
Factor VIII (fetal vessels absent)
Smooth muscle actin (vessel walls).
Diagnostic Utility:
p57 staining distinguishes complete from partial mole
β-hCG confirms trophoblastic origin
Proliferation markers assess activity
Genetic studies may be needed.
Molecular Subtypes:
Complete mole (diploid androgenetic)
Partial mole (triploid)
Invasive mole
Rare genetic variants.
Molecular/Genetic
Genetic Mutations:
Complete mole: 46,XX or 46,XY (all paternal)
Partial mole: 69,XXY or 69,XXX (triploid)
NLRP7 mutations (recurrent moles)
KHDC3L mutations
Imprinting defects.
Molecular Markers:
Loss of maternal alleles (complete)
Extra paternal genome (partial)
Microsatellite analysis
Flow cytometry
Imprinting gene expression.
Prognostic Significance:
Complete moles: higher malignant potential (15-20%)
Partial moles: lower risk (<5%)
β-hCG levels predict outcome
Uterine size correlates with risk.
Therapeutic Targets:
Suction curettage (primary treatment)
β-hCG monitoring
Chemotherapy (persistent GTD)
Hysterectomy (selected cases)
Contraception during follow-up.
Differential Diagnosis
Similar Entities:
Hydropic abortion
Partial mole vs complete mole
Twin pregnancy with mole
Placental mesenchymal dysplasia
Early choriocarcinoma.
Distinguishing Features:
Complete mole: All villi abnormal
No fetal parts
p57 negative
Partial mole: Mixed villi
Fetal parts present
p57 positive
Hydropic abortion: Focal changes
Normal genetics.
Diagnostic Challenges:
Early gestational age
Small tissue samples
Distinguishing partial from complete
Hydropic changes in normal pregnancy
Genetic studies may be needed.
Rare Variants:
Invasive mole
Twin pregnancy with mole
Recurrent molar pregnancy
Familial molar pregnancy syndrome.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Products of conception with molar features
Diagnosis
[Complete/Partial] hydatidiform mole
Clinical Correlation
β-hCG: [X] mIU/mL, uterine size [X] weeks
Gross Findings
[Grape-like vesicles/Mixed vesicles and fetal parts]
Microscopic Findings
Hydropic villi with trophoblastic hyperplasia
Immunohistochemistry
p57: [positive/negative], β-hCG: positive
Mole Classification
[Complete/Partial] mole based on morphology and p57 staining
Risk Assessment
[Low/Intermediate/High] risk for persistent GTD
Follow-up Recommendations
Serial β-hCG monitoring, contraception, surveillance
Final Diagnosis
[Complete/Partial] hydatidiform mole