Definition/General
Introduction:
Invasive mole (chorioadenoma destruens) is a form of gestational trophoblastic neoplasia (GTN)
It shows villous structures invading the myometrium and blood vessels
It represents progression from complete or partial hydatidiform mole
It carries significant risk of perforation and metastasis.
Origin:
Develops from antecedent molar pregnancy (complete or partial mole)
Results from persistence of trophoblastic tissue after molar evacuation
Shows invasive behavior into myometrium
May arise de novo without prior molar pregnancy (rare)
Represents intermediate between benign mole and choriocarcinoma.
Classification:
Classified as gestational trophoblastic neoplasia (GTN)
Part of spectrum including invasive mole
Choriocarcinoma
Placental site trophoblastic tumor
Epithelioid trophoblastic tumor
WHO classification includes in gestational trophoblastic disease.
Epidemiology:
Develops in 15-20% of complete moles
Less common after partial mole (<5%)
More common in Asian populations
Risk factors include large uterine size
Markedly elevated hCG levels
Age >40 years
Delayed or incomplete evacuation.
Clinical Features
Presentation:
Persistent vaginal bleeding after molar evacuation
Persistently elevated hCG levels
Uterine enlargement or subinvolution
Signs of perforation (abdominal pain, peritonitis)
Pulmonary symptoms (dyspnea, chest pain)
Vaginal metastases (blue-purple nodules).
Symptoms:
Irregular vaginal bleeding (persistent)
Abdominal pain and cramping
Acute abdomen (if perforation occurs)
Respiratory symptoms (pulmonary emboli)
Thyrotoxicosis symptoms (rarely)
Anemia symptoms (fatigue, weakness).
Risk Factors:
Large uterine size at initial presentation
hCG levels >100,000 mIU/ml
Age >40 years
Delayed evacuation of mole
Incomplete evacuation
Degree of trophoblastic proliferation
Previous history of GTD.
Screening:
Serial serum hCG monitoring (plateau or rising levels)
Pelvic ultrasound showing myometrial invasion
Chest imaging for pulmonary metastases
CT/MRI for staging
Complete blood count
Liver and kidney function tests.
Master Invasive Mole Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Hemorrhagic, necrotic tissue with grape-like vesicular structures
Deep invasion into myometrium visible grossly
May show perforation through uterine wall
Vesicular structures similar to original mole
Areas of hemorrhage and necrosis prominent.
Characteristics:
Vesicular tissue extending into myometrium
Variable sized vesicles with clear fluid
Hemorrhagic and necrotic areas
May show vascular invasion
Perforation sites if present
Friable tissue that bleeds easily.
Size Location:
Size depends on extent of invasion
May involve entire uterine wall thickness
Commonly in fundal or cornual regions
May extend to parametrial tissues
Vesicular structures range 0.5-3.0 cm
Depth of invasion variable.
Multifocality:
Shows deep invasive pattern into myometrium
May have multiple invasion sites
Vascular invasion commonly present
Can involve uterine vessels
May show parametrial extension
Perforation may occur at multiple sites.
Microscopic Description
Histological Features:
Chorionic villi invading myometrium and blood vessels
Trophoblastic proliferation around invading villi
Absence of decidual interface
Vascular invasion with thrombus formation
Myometrial destruction and hemorrhage
Inflammatory response around invasive tissue.
Cellular Characteristics:
Trophoblastic cells show increased atypia and mitotic activity
Both cytotrophoblast and syncytiotrophoblast present
Nuclear pleomorphism and hyperchromasia
Mitotic figures increased
Invasive trophoblast lacks basement membrane.
Architectural Patterns:
Villous structures with central vessels invading myometrium
Trophoblastic proliferation around villi
Loss of basement membrane integrity
Vascular invasion pattern
May show choriocarcinomatous areas (lacking villi).
Grading Criteria:
Assessed based on depth of myometrial invasion
Degree of trophoblastic atypia
Presence of vascular invasion
Extent of necrosis
Mitotic activity level
Risk stratified as low-risk vs high-risk GTN.
Immunohistochemistry
Positive Markers:
Beta-hCG (strongly positive in syncytiotrophoblast)
hPL (human placental lactogen)
Inhibin-alpha (positive in cytotrophoblast)
PLAP (placental alkaline phosphatase)
Cytokeratin (broad spectrum)
p63 (positive in cytotrophoblast).
Negative Markers:
CD68 (negative in trophoblast)
Smooth muscle actin (negative in trophoblast)
S-100 (negative)
Melanoma markers (negative)
Lymphoid markers (negative).
Diagnostic Utility:
Confirms trophoblastic origin of invasive tissue
Beta-hCG correlates with tumor burden
Distinguishes from other uterine tumors
p63 helps identify cytotrophoblast population
Essential for diagnosis confirmation.
Molecular Subtypes:
Usually shows same genetic pattern as original mole
Complete mole origin: diploid androgenetic
Partial mole origin: triploid
Genetic heterogeneity may develop
Clonal evolution possible.
Molecular/Genetic
Genetic Mutations:
Inherits genetic pattern from original molar pregnancy
Complete mole: diploid androgenetic
Partial mole: triploid diandric
May acquire additional mutations during progression
p53 mutations in some cases.
Molecular Markers:
Microsatellite analysis shows original molar pattern
Flow cytometry shows ploidy status
p57 expression depends on original mole type
CGH analysis may show additional aberrations
DNA fingerprinting confirms molar origin.
Prognostic Significance:
FIGO risk scoring determines prognosis
Age
Antecedent pregnancy type
Interval from pregnancy
hCG level
Number of metastases
Size of largest metastasis
Previous chemotherapy failure
Low-risk vs high-risk stratification.
Therapeutic Targets:
Chemotherapy is primary treatment
Low-risk disease: single-agent methotrexate or actinomycin D
High-risk disease: multi-agent chemotherapy (EMA-CO protocol)
Hysterectomy in selected cases
Fertility preservation possible with chemotherapy.
Differential Diagnosis
Similar Entities:
Choriocarcinoma (no villous structures, more aggressive)
Placental site trophoblastic tumor (intermediate trophoblast, less hCG)
Epithelioid trophoblastic tumor (epithelioid morphology)
Atypical placental site nodule
Uterine sarcoma.
Distinguishing Features:
Invasive mole: Villous structures present
Invasive mole: Moderate hCG elevation
Choriocarcinoma: No villous structures
Choriocarcinoma: Higher hCG levels
PSTT: Intermediate trophoblast
PSTT: Lower hCG levels
ETT: Epithelioid morphology.
Diagnostic Challenges:
Distinguishing from choriocarcinoma (presence of villi crucial)
Identification of villous structures in necrotic tissue
Sampling adequacy important
Correlation with hCG levels
Clinical presentation aids diagnosis.
Rare Variants:
Metastatic invasive mole (lung, vagina, brain)
Invasive mole with choriocarcinomatous areas
Coexistent choriocarcinoma
Invasive mole in extrauterine sites
Persistent low-level disease.
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
[specimen type], showing invasive vesicular tissue extending into myometrium
Diagnosis
Invasive Mole (Gestational Trophoblastic Neoplasia)
Classification
Classification: Invasive mole with [degree] myometrial invasion
Histological Features
Shows chorionic villi invading myometrium with trophoblastic proliferation and vascular invasion
Invasion Assessment
Myometrial invasion: [depth/extent], Vascular invasion: [present/absent]
Immunohistochemistry
hCG: Strongly positive, hPL: Positive, p63: Positive in cytotrophoblast
Risk Stratification
FIGO risk score: [score], Risk category: [low/high risk] GTN
Recommendations
Immediate chemotherapy recommended. hCG monitoring essential. Multidisciplinary team management advised.
Final Diagnosis
Invasive Mole (GTN) with [risk level] requiring immediate treatment