Definition/General
Introduction:
Chronic villitis is characterized by persistent inflammatory infiltrate in chorionic villi
It involves lymphocytes, plasma cells, and macrophages
It may be infectious or non-infectious in etiology
It represents prolonged inflammatory response (>1 week duration).
Origin:
May result from viral infections (CMV, HSV, EBV)
Bacterial infections (Listeria, Treponema)
Parasitic infections (Toxoplasma, Malaria)
Unknown etiology (villitis of unknown etiology)
Maternal immune response to fetal antigens.
Classification:
Classified by etiology: Infectious vs non-infectious
By severity: Low-grade vs high-grade
By distribution: Focal, multifocal, or diffuse
Duration-based: Acute (<1 week) vs chronic (≥1 week).
Epidemiology:
Overall incidence 5-20% of pregnancies
Infectious villitis less common (1-5%)
VUE accounts for majority of cases
More common in third trimester
Higher incidence with maternal age >35 years.
Clinical Features
Presentation:
Fetal growth restriction
Stillbirth (severe cases)
Preterm delivery
Congenital infections (if infectious etiology)
Hydrops fetalis (severe cases)
Often asymptomatic discovery
Recurrent pregnancy loss.
Symptoms:
Maternal symptoms vary by underlying etiology
Fever and malaise (infectious causes)
Decreased fetal movements
Flu-like symptoms (viral infections)
Rash (some viral infections)
Often no specific maternal symptoms.
Risk Factors:
Immunocompromised state
Advanced maternal age
Exposure to infectious agents
Previous pregnancy with villitis
Autoimmune disorders
Poor prenatal care
Environmental exposures.
Screening:
TORCH screening (Toxoplasma, Rubella, CMV, HSV)
Maternal antibody titers
Fetal growth monitoring
Ultrasound for fetal anomalies
Amniocentesis for suspected infections
Complete blood count with differential.
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Gross Description
Appearance:
Placenta may appear grossly normal
May show pale, firm areas
Placental weight often reduced
Irregular maternal surface
Hemorrhagic areas occasionally present
Cut surface may be granular.
Characteristics:
Decreased placental weight for gestational age
Firm consistency in affected areas
Patchy discoloration
May show surface irregularities
Villous edema in some cases
Chorionic plate usually normal.
Size Location:
Distribution varies from focal to diffuse
May affect any placental region
Random distribution pattern
Can involve single or multiple cotyledons
Skip lesions commonly present.
Multifocality:
Often shows multifocal involvement
Patchy distribution throughout placenta
Geographic pattern
Normal areas interspersed
Confluent areas in severe cases.
Microscopic Description
Histological Features:
Chronic inflammatory cell infiltrate in villous stroma
Lymphocytes, plasma cells, and macrophages
Villous architecture disruption
Syncytiotrophoblast damage
Villous fibrosis and sclerosis
Inflammatory cell aggregates.
Cellular Characteristics:
Inflammatory infiltrate consists of T-lymphocytes (predominant)
B-lymphocytes and plasma cells
Macrophages with phagocytic activity
Occasional eosinophils
Giant cells in some cases
Activated endothelial cells.
Architectural Patterns:
Villous swelling and edema
Loss of normal branching pattern
Villous agglutination
Fibrin deposition
Avascular villi in severe cases
Chronic deciduitis may coexist.
Grading Criteria:
Low-grade: Minimal inflammatory infiltrate, preserved architecture
High-grade: Dense infiltrate, significant architectural disruption
Based on inflammatory cell density
Degree of villous destruction
Extent of involvement.
Immunohistochemistry
Positive Markers:
CD3 (T-lymphocytes)
CD20 (B-lymphocytes)
CD68 (macrophages)
CD138 (plasma cells)
CD8 (cytotoxic T-cells)
CD4 (helper T-cells)
Ki-67 (proliferation index).
Negative Markers:
CD15 (neutrophils typically absent in chronic cases)
Tryptase (mast cells minimal)
Infectious organism stains (negative in VUE)
CMV immunostain (negative in non-CMV cases).
Diagnostic Utility:
Helps characterize inflammatory cell populations
Distinguishes T-cell from B-cell predominance
Rules out infectious causes
Quantifies inflammatory response
Aids in etiology determination.
Molecular Subtypes:
Infectious villitis: Organism-specific patterns
VUE: CD8+ T-cell predominance
Autoimmune-associated: Mixed inflammatory pattern
Plasma cell-rich variants (chronic infections).
Molecular/Genetic
Genetic Mutations:
No specific mutations for chronic villitis
Host genetic factors influence susceptibility
HLA polymorphisms
Immune response gene variants
Cytokine gene polymorphisms.
Molecular Markers:
PCR for infectious agents (CMV, HSV, EBV, Parvovirus B19)
In situ hybridization for viral nucleic acids
Inflammatory markers (TNF-α, IL-1β, IL-6)
T-cell receptor gene rearrangement.
Prognostic Significance:
High-grade villitis associated with adverse outcomes
Infectious etiology may require specific treatment
Risk of fetal transmission
Recurrence risk varies by etiology
Long-term developmental outcomes.
Therapeutic Targets:
Antiviral therapy (if indicated)
Antibiotic treatment (bacterial infections)
Enhanced fetal surveillance
Timing of delivery optimization
Immunomodulatory therapy (experimental).
Differential Diagnosis
Similar Entities:
Acute villitis (neutrophilic infiltrate)
Villous infarction (no inflammation)
Villitis of unknown etiology (specific subtype)
Chronic intervillositis (intervillous space involvement)
Maternal floor infarction.
Distinguishing Features:
Chronic villitis: Lymphoplasmacytic infiltrate
Chronic villitis: >1 week duration
Acute villitis: Neutrophil predominance
Acute villitis: <1 week duration
Infarction: No inflammatory cells
Intervillositis: Intervillous space involvement.
Diagnostic Challenges:
Determining infectious vs non-infectious etiology
Adequate sampling for organism identification
Special stains and molecular studies
Correlation with clinical history
Severity assessment.
Rare Variants:
Granulomatous villitis
Necrotizing villitis
Eosinophilic villitis
Combined chronic villitis and chorioamnionitis
Massive chronic villitis.
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 [distribution] chronic inflammatory changes
Diagnosis
Chronic Villitis ([Infectious/Unknown Etiology/Specified cause])
Classification
Classification: [Low-grade/High-grade] chronic villitis with [focal/multifocal/diffuse] distribution
Histological Features
Shows chronic inflammatory infiltrate in villous stroma with [degree] architectural disruption
Inflammatory Pattern
Inflammatory cells: [lymphocytes/plasma cells/macrophages] with [T-cell/B-cell] predominance
Infectious Studies
Special stains: [results], PCR studies: [results], Organisms: [identified/not identified]
Severity Assessment
Severity: [Grade] based on inflammatory density and villous destruction
Clinical Correlation
Correlates with [clinical findings]. Risk assessment: [level] for adverse outcomes.
Final Diagnosis
Chronic Villitis, [Grade], [Etiology], with [clinical significance]