Definition/General
Introduction:
Complete hydatidiform mole (CHM) is a gestational trophoblastic disease characterized by complete absence of fetal tissue
It shows diffuse villous enlargement and trophoblastic proliferation
It represents a diploid androgenetic conception with exclusively paternal genetic material
It carries significant risk of progression to gestational trophoblastic neoplasia.
Origin:
Arises from fertilization abnormalities resulting in diploid androgenetic conceptus
Most commonly from dispermic fertilization of empty ovum
Less commonly from fertilization by diploid sperm
Results in complete absence of maternal genetic contribution
Leads to abnormal trophoblastic proliferation.
Classification:
Classified as gestational trophoblastic disease (GTD)
Part of spectrum including partial mole
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumor
Epithelioid trophoblastic tumor
Complete mole has highest malignant potential among moles.
Epidemiology:
Incidence varies geographically
Higher in Asian populations (1:500-1:1000 pregnancies)
Lower in Western countries (1:1500-2000)
Peak incidence in maternal age <20 years and >40 years
Risk factors include previous molar pregnancy
Dietary factors (low carotene).
Clinical Features
Presentation:
Vaginal bleeding (most common, 90% cases)
Uterine size-date discrepancy (70% cases, usually larger)
Absence of fetal heart sounds
Hyperemesis gravidarum (severe nausea, vomiting)
Passage of grape-like vesicles
Early onset preeclampsia (<20 weeks)
Hyperthyroidism (rare).
Symptoms:
Severe nausea and vomiting (hyperemesis)
Abdominal pain and cramping
Respiratory symptoms (trophoblastic embolization)
Thyrotoxicosis symptoms (palpitations, sweating)
Passage of vesicular tissue
Absence of fetal movement.
Risk Factors:
Maternal age <20 years or >40 years
Previous molar pregnancy (10-fold increased risk)
Asian ethnicity
Low dietary carotene
History of miscarriage
Consanguineous marriage
ABO blood group A.
Screening:
Serum beta-hCG levels (markedly elevated)
Pelvic ultrasound showing snowstorm appearance
Complete blood count (anemia)
Thyroid function tests
Chest X-ray (pulmonary metastases)
Pre-evacuation assessment.
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Gross Description
Appearance:
Grape-like vesicular tissue with abundant clear fluid-filled vesicles
Vesicles range from few millimeters to 2-3 cm
No identifiable fetal parts or membranes
Hemorrhagic and necrotic areas may be present
Total specimen weight typically increased.
Characteristics:
Multiple translucent vesicles filled with clear fluid
Vesicles have thin walls
No fetal tissue or umbilical cord identified
No amniotic membrane present
Specimen may be fragmented
Total volume typically >500 ml.
Size Location:
Involves entire placental mass
Vesicle size ranges 0.5-3.0 cm diameter
Uniform vesicular enlargement throughout
No normal placental tissue identified
May have areas of hemorrhage and necrosis.
Multifocality:
Involves entire placental tissue uniformly
No focal involvement pattern
All villi affected by vesicular change
Trophoblastic proliferation throughout
No skip lesions present.
Microscopic Description
Histological Features:
Diffuse villous enlargement with central cistern formation
Circumferential trophoblastic proliferation around villi
Absence of fetal blood vessels in villi
Marked cytotrophoblast and syncytiotrophoblast proliferation
Nuclear atypia and pleomorphism in trophoblasts.
Cellular Characteristics:
Trophoblastic cells show nuclear enlargement and hyperchromasia
Mitotic activity variably increased
Cytotrophoblasts with clear cytoplasm
Syncytiotrophoblast with multiple nuclei
Absence of fetal erythrocytes in villous vessels.
Architectural Patterns:
Avascular villi with central cavitation
Villous stroma shows myxoid degeneration
Trophoblastic proliferation may be mild to marked
Circumferential distribution around villi
May show invasive trophoblast in decidua.
Grading Criteria:
Graded based on degree of trophoblastic proliferation
Mild: Minimal trophoblastic proliferation
Moderate: Moderate proliferation with some atypia
Marked: Extensive proliferation with significant atypia
Correlates with malignant potential.
Immunohistochemistry
Positive Markers:
Beta-hCG (strongly positive in syncytiotrophoblast)
hPL (human placental lactogen, positive)
Inhibin-alpha (positive in cytotrophoblast)
PLAP (placental alkaline phosphatase)
Cytokeratin (broad spectrum)
p57 (negative in complete mole, diagnostic).
Negative Markers:
p57 (negative in villous cytotrophoblast and stromal cells, diagnostic feature)
CD68 (negative, helps exclude inflammatory cells)
Smooth muscle actin (negative in trophoblast)
S-100 (negative)
Melanoma markers (negative).
Diagnostic Utility:
p57 immunostaining is diagnostic (negative in complete mole, positive in partial mole)
Helps distinguish from partial mole
Confirms trophoblastic origin
Beta-hCG levels correlate with trophoblastic mass
Essential for accurate classification.
Molecular Subtypes:
Complete mole shows diploid androgenetic pattern
Most cases (90%) are 46,XX androgenetic (dispermic)
Some cases (10%) are 46,XY androgenetic
All genetic material is paternal origin
No maternal genetic contribution.
Molecular/Genetic
Genetic Mutations:
Diploid androgenetic genome (exclusively paternal)
Most common: 46,XX from dispermic fertilization
Less common: 46,XY from diploid sperm
Complete absence of maternal genetic material
Results in abnormal genomic imprinting.
Molecular Markers:
Microsatellite analysis shows androgenetic pattern
Flow cytometry shows diploid DNA content
p57 protein expression absent (maternal gene)
Genomic imprinting defects
Abnormal methylation patterns.
Prognostic Significance:
Risk of GTN (gestational trophoblastic neoplasia) is 15-20%
Higher malignant potential than partial mole
Risk factors for GTN include: large uterine size
Markedly elevated hCG (>100,000 mIU/ml)
Trophoblastic proliferation degree
Patient age >40 years.
Therapeutic Targets:
Serial hCG monitoring essential for surveillance
Chemotherapy for persistent GTD
Methotrexate for low-risk disease
Multi-agent chemotherapy for high-risk disease
Contraception during surveillance period.
Differential Diagnosis
Similar Entities:
Partial hydatidiform mole (p57 positive, triploid, fetal parts present)
Hydropic abortion (p57 positive, normal trophoblast)
Invasive mole (villous structures in myometrium)
Choriocarcinoma (no villous structures)
Twin pregnancy with mole.
Distinguishing Features:
Complete mole: p57 negative
Complete mole: No fetal parts
Complete mole: Diploid androgenetic
Partial mole: p57 positive
Partial mole: Fetal parts present
Partial mole: Triploid
Hydropic abortion: p57 positive
Hydropic abortion: Normal trophoblast
Choriocarcinoma: No villi.
Diagnostic Challenges:
Distinguishing from partial mole (p57 immunostaining crucial)
Early complete mole vs hydropic abortion
Degree of trophoblastic proliferation assessment
Recognition of invasive features
Molecular studies may be required for definitive diagnosis.
Rare Variants:
Invasive complete mole (villous structures invading myometrium)
Choriocarcinoma arising in complete mole
Complete mole with coexistent fetus (twin pregnancy)
Metastatic complete mole
Persistent GTD following evacuation.
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, measuring [volume] ml, consisting of grape-like vesicular tissue
Diagnosis
Complete Hydatidiform Mole (Gestational Trophoblastic Disease)
Classification
Classification: Complete mole with [degree] trophoblastic proliferation
Histological Features
Shows diffuse villous enlargement with circumferential trophoblastic proliferation and absent fetal vessels
Immunohistochemistry
p57: Negative (diagnostic of complete mole), hCG: Positive in syncytiotrophoblast
Genetic Analysis
Molecular analysis: [diploid androgenetic pattern/pending]
Risk Assessment
Risk of GTN: [risk level] based on clinical and pathological features
Recommendations
Serial serum hCG monitoring recommended. Contraception during surveillance period. Clinical correlation advised.
Final Diagnosis
Complete Hydatidiform Mole (Gestational Trophoblastic Disease) with [risk level] for progression to GTN