Definition/General

Introduction:
-Placental villitis is the inflammatory infiltration of chorionic villi by maternal inflammatory cells
-It represents a chronic inflammatory process affecting the placental parenchyma
-The condition may be infectious or of unknown etiology (VUE)
-It occurs in 5-15% of term placentas
-Associated with adverse pregnancy outcomes.
Origin:
-Results from maternal immune response to fetal antigens
-Infectious agents may trigger inflammation
-Autoimmune mechanisms involved in some cases
-Maternal T-cell infiltration of villi
-Loss of maternal-fetal tolerance.
Classification:
-Classified by etiology: Infectious villitis (known pathogen)
-Villitis of unknown etiology (VUE)
-By pattern: Focal villitis
-Multifocal villitis
-Diffuse villitis
-By severity: Low-grade
-High-grade.
Epidemiology:
-Incidence: 5-15% of term placentas
-VUE comprises 90% of cases
-More common in late pregnancy
-Associated with IUGR (15-30%)
-Recurrence rate: 10-25%.

Clinical Features

Presentation:
-Often asymptomatic
-IUGR (intrauterine growth restriction)
-Oligohydramnios
-Abnormal fetal testing
-Preterm labor
-Stillbirth (severe cases)
-Maternal hypertension.
Symptoms:
-Decreased fetal movements
-Abnormal growth
-Maternal symptoms often absent
-Associated infections may cause fever
-Preterm contractions.
Risk Factors:
-Advanced maternal age
-Previous pregnancy complications
-Autoimmune disorders
-Chronic hypertension
-Diabetes mellitus
-Smoking
-Recurrent pregnancy loss.
Screening:
-Fetal growth monitoring
-Doppler studies
-Biophysical profile
-Maternal serology (infections)
-Amniotic fluid assessment.

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Gross Description

Appearance:
-Often grossly normal
-Pale, firm areas in severe cases
-Decreased placental weight
-Areas of infarction may be present
-Thickened membranes if associated chorioamnionitis.
Characteristics:
-Normal external appearance usually
-Cut surface may show pale areas
-Firm consistency in affected areas
-Associated findings: infarction, calcification.
Size Location:
-Focal or diffuse involvement
-Random distribution
-Central areas more commonly affected
-Peripheral sparing possible.
Multifocality:
-Multifocal pattern common
-Skip lesions
-Progressive involvement
-Associated with other placental pathology.

Microscopic Description

Histological Features:
-Chronic inflammatory cells within villous stroma
-Lymphocytes and plasma cells predominant
-Histiocytes and macrophages
-Villous fibrosis
-Stromal collapse
-Loss of capillaries.
Cellular Characteristics:
-Maternal T-lymphocytes
-Plasma cells
-Macrophages (Hofbauer cells increased)
-Few neutrophils
-Syncytiotrophoblast may show damage
-Stromal fibroblasts increased.
Architectural Patterns:
-Expansion of villous stroma
-Loss of fetal vessels
-Villous sclerosis
-Obliterative endarteritis
-Trophoblast basement membrane thickening.
Grading Criteria:
-Low-grade: <10 villi per focus
-High-grade: >10 villi per focus
-Basal villitis: maternal surface involvement
-Obliterative endarteritis: vessel involvement
-Extent assessment: focal vs diffuse.

Immunohistochemistry

Positive Markers:
-CD3 (T-lymphocytes)
-CD20 (B-lymphocytes)
-CD68 (macrophages)
-CD138 (plasma cells)
-Smooth muscle actin (vessel walls)
-Trichrome (fibrosis).
Negative Markers:
-Cytokeratin (trophoblast - may be decreased)
-CD34 (endothelium - may be lost)
-Specific infectious agents usually negative.
Diagnostic Utility:
-Characterizes inflammatory infiltrate
-Assesses severity
-Rules out infections
-Demonstrates vascular involvement
-Quantifies tissue damage.
Molecular Subtypes:
-T-cell mediated villitis
-Mixed inflammatory pattern
-Obliterative villitis
-Infectious villitis.

Molecular/Genetic

Genetic Mutations:
-HLA associations
-Complement system variants
-Cytokine gene polymorphisms
-FcγR variants
-KIR gene variations.
Molecular Markers:
-Pro-inflammatory cytokines
-Th1 response markers
-Complement activation
-Apoptosis markers
-Fibrosis mediators.
Prognostic Significance:
-High-grade villitis: worse outcomes
-Recurrence risk in subsequent pregnancies
-Associated IUGR
-Increased stillbirth risk
-Preterm delivery.
Therapeutic Targets:
-Immunosuppressive therapy (experimental)
-Antithrombotic agents
-Fetal surveillance
-Early delivery if indicated
-Treatment of underlying conditions.

Differential Diagnosis

Similar Entities:
-Acute chorioamnionitis
-Chronic intervillositis
-Massive perivillous fibrin
-Decidual vasculopathy
-Infectious placentitis.
Distinguishing Features:
-Villitis: Villous inflammation
-Lymphocytic infiltrate
-Maternal cells
-Chorioamnionitis: Membrane inflammation
-Neutrophilic infiltrate
-Intervillositis: Intervillous space inflammation
-Perivillous fibrin.
Diagnostic Challenges:
-Distinguishing infectious from non-infectious
-Grading severity
-Assessing clinical significance
-Sampling variations
-Correlation with outcomes.
Rare Variants:
-Necrotizing villitis
-Granulomatous villitis
-Eosinophilic villitis
-Giant cell 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 with chronic villous inflammation

Diagnosis

Chronic villitis [of unknown etiology/infectious]

Clinical Correlation

[IUGR/oligohydramnios/normal pregnancy]

Gross Findings

[Normal appearance/pale firm areas], weight [X] grams

Microscopic Findings

Chronic inflammatory cells within villous stroma

Villitis Grade

[Low-grade/High-grade] villitis

Distribution Pattern

[Focal/Multifocal/Diffuse] involvement

Vascular Changes

Obliterative endarteritis: [present/absent]

Associated Findings

[Infarction/fibrosis/calcification]: [present/absent]

Clinical Significance

[Mild/Moderate/Severe] based on grade and extent

Final Diagnosis

Chronic villitis of unknown etiology, [grade]