Definition/General
Introduction:
Massive perivillous fibrin deposition (MPFD) is characterized by excessive fibrin deposition around chorionic villi
It involves >20% of villous surface area
It results in impaired materno-fetal exchange
It is associated with poor pregnancy outcomes.
Origin:
Results from abnormal coagulation cascade activation in intervillous space
Maternal thrombophilia may predispose
Complement activation triggers fibrin formation
Endothelial dysfunction may initiate process
Leads to intervillous space obliteration.
Classification:
Classified by extent of involvement: Focal (<20%), Massive (≥20%)
By pattern: Perivillous vs intervillous
By associated features: With/without villous infarction
Recurrent vs sporadic forms.
Epidemiology:
Rare condition with incidence <1% of pregnancies
Associated with recurrent pregnancy loss (recurrence rate 15-30%)
More common in pregnancies with thrombophilia
Increasing recognition with improved pathological examination.
Clinical Features
Presentation:
Intrauterine growth restriction
Stillbirth
Preterm delivery
Oligohydramnios
Non-reassuring fetal heart rate patterns
Recurrent pregnancy loss
Often poor outcomes across multiple pregnancies.
Symptoms:
Decreased fetal movements
Measuring small for gestational age
Oligohydramnios on ultrasound
Abnormal fetal Doppler studies
No specific maternal symptoms
Signs of chronic fetal compromise.
Risk Factors:
Maternal thrombophilia (Factor V Leiden, Prothrombin mutation)
Antiphospholipid syndrome
Previous pregnancy with MPFD
Autoimmune disorders
Advanced maternal age
Complement system abnormalities.
Screening:
Thrombophilia workup
Antiphospholipid antibody screening
Complement studies
Fetal growth assessment
Doppler studies
Enhanced fetal surveillance
Detailed pregnancy history.
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Gross Description
Appearance:
Placenta shows firm, white-gray areas
Increased placental weight
Lobulated maternal surface
Cut surface reveals white, firm tissue
Geographic distribution of affected areas.
Characteristics:
Increased placental weight for gestational age
Firm, rubbery consistency
White-gray discoloration of affected areas
Well-demarcated lesions
May involve entire cotyledons
Maternal surface irregularities.
Size Location:
Affects ≥20% of placental volume (by definition)
May involve multiple cotyledons
Random distribution pattern
Can affect central or peripheral areas
Confluent areas common.
Multifocality:
Often shows multifocal involvement
Multiple discrete areas of fibrin deposition
Confluent pattern in severe cases
May have geographic distribution
Normal areas interspersed.
Microscopic Description
Histological Features:
Massive fibrin deposition surrounding chorionic villi
Intervillous space obliteration
Villous entrapment in fibrin matrix
Syncytiotrophoblast loss
Villous crowding and distortion
Absence of significant inflammation.
Cellular Characteristics:
Eosinophilic fibrin deposits
Entrapped villi within fibrin matrix
Loss of syncytiotrophoblast layer
Villous stromal fibrosis
Fetal capillary compression
Minimal inflammatory infiltrate.
Architectural Patterns:
Complete intervillous space obliteration
Villous architecture distortion
Fibrin lakes between villi
Loss of normal intervillous circulation
Villous crowding
Secondary villous infarction.
Grading Criteria:
Based on percentage of villous surface involved
Focal MPFD: <20% involvement
Massive MPFD: ≥20% involvement
Severity: Complete vs partial intervillous obliteration.
Immunohistochemistry
Positive Markers:
Fibrin (confirms fibrin nature of deposits)
Factor VIII (may show vascular damage)
Complement components (C3, C4, C5b-9)
Fibrinogen (precursor of fibrin)
Platelet markers (if thrombi present).
Negative Markers:
Inflammatory cell markers (CD3, CD20, CD68 minimal)
Infectious organism stains
Smooth muscle actin (vessel integrity assessment)
Cytokeratin (trophoblast viability).
Diagnostic Utility:
Fibrin stains confirm diagnosis
Quantifies extent of deposition
Rules out inflammatory conditions
Assesses complement activation
Essential for accurate diagnosis.
Molecular Subtypes:
Thrombophilia-associated MPFD
Complement-mediated MPFD
Antiphospholipid syndrome-associated
Idiopathic forms
Recurrent MPFD.
Molecular/Genetic
Genetic Mutations:
Thrombophilia mutations (Factor V Leiden, Prothrombin G20210A)
Complement system variants
MTHFR polymorphisms
Fibrinogen gene variants
Protein C, S, Antithrombin deficiencies.
Molecular Markers:
Coagulation studies
D-dimer levels (elevated)
Fibrinogen levels
Complement activation markers
Antiphospholipid antibodies
Genetic testing for thrombophilia.
Prognostic Significance:
High risk of adverse outcomes
Recurrence risk in subsequent pregnancies
Associated with stillbirth
Severe growth restriction
Poor perinatal outcomes.
Therapeutic Targets:
Anticoagulation therapy
Low-dose aspirin
Heparin therapy in high-risk cases
Complement inhibition (experimental)
Enhanced fetal surveillance
Timing of delivery optimization.
Differential Diagnosis
Similar Entities:
Maternal floor infarction (basal plate fibrin)
Chronic intervillositis (inflammatory infiltrate)
Villous infarction (tissue necrosis)
Normal perivillous fibrin (<20% involvement)
Placental abruption with fibrin.
Distinguishing Features:
MPFD: Perivillous fibrin ≥20%
MPFD: No significant inflammation
MFI: Basal plate location
Intervillositis: Inflammatory infiltrate present
Normal fibrin: <20% involvement
Infarction: Tissue necrosis present.
Diagnostic Challenges:
Quantifying extent of fibrin deposition
Distinguishing from normal fibrin
Adequate sampling for assessment
Correlation with clinical outcomes
Recognition of early changes.
Rare Variants:
MPFD with villous infarction
Combined MPFD and chronic intervillositis
Familial recurrent MPFD
MPFD with fetal thrombotic vasculopathy
Complement-mediated variants.
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
Placenta weighing [weight]g with firm white areas involving approximately [percentage]% of parenchyma
Diagnosis
Massive Perivillous Fibrin Deposition
Classification
Classification: [Focal/Massive] perivillous fibrin deposition involving [percentage]% of villous surface
Histological Features
Shows extensive fibrin deposition around chorionic villi with intervillous space obliteration
Quantitative Assessment
Fibrin deposition involves approximately [percentage]% of examined villous surface area
Special Stains
Fibrin stain: Positive, confirming extensive fibrin deposition around villi
Inflammatory Assessment
No significant inflammatory infiltrate identified. Findings consistent with coagulation disorder.
Clinical Correlation
Findings correlate with [fetal outcomes]. Associated with impaired materno-fetal exchange.
Final Diagnosis
Massive Perivillous Fibrin Deposition involving [percentage]% of villous surface with associated [clinical outcomes]