Lymphoepithelial Sialadenitis Pattern
Lymphoepithelial sialadenitis (LESA) is a histopathological pattern characterized by lymphocytic infiltration of salivary gland ducts with basal cell hyperplasia resulting in a multilayered epithelium, most commonly seen in Sjögren's syndrome and representing a key diagnostic feature with potential prognostic significance for lymphoma development. 1
Histopathological Definition
LESA is defined by two critical microscopic features:
- Lymphocytic infiltration of ductal epithelium - lymphocytes directly invade and surround the epithelial cells of salivary gland ducts 1
- Basal cell hyperplasia - the duct epithelium responds by developing multiple layers (multilayered epithelium) rather than the normal single or double layer 1
The term "lymphoepithelial lesion" is used interchangeably with LESA in the literature 1
Clinical Context and Significance
Primary Association with Sjögren's Syndrome:
- LESA occurs predominantly in the setting of autoimmune sialadenitis, particularly primary Sjögren's syndrome 1, 2
- It represents a more advanced stage of glandular involvement beyond simple focal lymphocytic sialadenitis 1
- The presence of LESA may have prognostic significance for disease progression 1
Lymphoma Risk Implications:
- LESA is associated with increased risk of lymphoma development, particularly extranodal marginal zone B-cell lymphoma of MALT type 1, 3
- The presence of LESA is more commonly observed in parotid tissue than labial salivary glands, and lymphoma development occurs more frequently in parotid glands 1
- Patients with decreased C4 complement levels at diagnosis have higher risk of developing lymphoma 1
Anatomic Distribution Patterns
Site-Specific Considerations:
- Parotid glands show LESA more frequently than minor salivary glands 1
- Labial salivary gland biopsies (the most commonly used diagnostic tissue) show LESA less commonly than parotid biopsies 1
- When present in labial biopsies, LESA still carries diagnostic and prognostic significance 1
Distinction from Other Salivary Gland Pathology
LESA differs from other inflammatory patterns:
- Focal lymphocytic sialadenitis (FLS) - shows periductal/perivascular lymphocytic aggregates (≥50 cells) but WITHOUT direct ductal invasion or epithelial hyperplasia 1
- Chronic sclerosing sialadenitis (Küttner tumor) - shows fibrosis and inflammation but is IgG4-related disease, not typically associated with LESA 4
- Lymphoepithelial sialadenitis specifically indicates ductal invasion with epithelial changes, distinguishing it from simple chronic inflammation 3
Diagnostic Evaluation
Histological Assessment:
- Standard H&E staining can identify LESA, but detection can be challenging in labial salivary gland tissue 1
- Immunohistochemistry is recommended to better characterize the lymphoid infiltrate and assess for monoclonality 1
- CD20 staining highlights B-cell infiltrates within and around ducts 1
- CD21 staining can identify follicular dendritic cell networks suggesting germinal center formation 1
Important Caveats:
- The threshold for identifying LESA varies among pathologists, contributing to diagnostic variability 1
- LESA should be distinguished from frank lymphoma, which shows dense infiltrates obliterating acini, broad halos of centrocyte-like cells around epithelial nests, and monoclonal immunoglobulin expression 3
- Molecular genetic analysis showing B-cell clones does NOT automatically indicate lymphoma in the setting of LESA, as clonality can be detected in over 50% of benign LESA cases 3
Clinical Management Implications
When LESA is identified:
- Co-management with rheumatology is essential given the systemic autoimmune nature of Sjögren's syndrome 1
- Increased surveillance for lymphoproliferative disorders is warranted, particularly in patients with additional risk factors like low C4 complement 1
- Regular monitoring for development of persistent salivary gland enlargement, which may indicate lymphoma transformation 2
- Assessment for other systemic manifestations including vasculitis, which can be life-threatening 1