Morphofunctional Variability of the Laryngeal Epithelium and Stromal Cells in Chronic Laryngitis: Correlation with Immune Markers CD3, CD20, and CD168

Abstract

Background: Chronic laryngitis is a heterogeneous inflammatory disorder of the larynx characterized by persistent mucosal irritation,
epithelial adaptation, stromal remodeling, and variable local immune activation. Although tissue inflammation is recognized as central to
disease persistence, the morphofunctional variability of the laryngeal epithelium and stromal compartment, particularly in relation to immune
markers CD3, CD20, and CD168, has not been systematically synthesized.
Objective: To systematically review the human literature on chronic laryngitis and related chronic inflammatory laryngeal conditions in order
to characterize epithelial and stromal morphologic variability and to assess reported correlations with CD3-positive T cells, CD20-positive B
cells, and CD168-associated matrix-signaling pathways.
Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, PsycINFO, Cochrane CENTRAL,
and selected grey-literature sources was performed from database inception to 2026-03-26. Studies were eligible if they included human
laryngeal tissue and reported histologic, morphometric, immunohistochemical, or immune-phenotypic findings in chronic laryngitis or closely
related chronic inflammatory laryngeal phenotypes. Screening, full-text review, and data extraction were conducted independently by two
reviewers, with disagreements resolved by consensus and third-reviewer adjudication. Risk of bias was assessed using design-appropriate tools.
A random-effects meta-analysis was prespecified; however, quantitative synthesis required at least two sufficiently comparable studies with
extractable marker-specific data.
Results: Eleven studies were included in qualitative synthesis. The evidence base consisted primarily of small cross-sectional or archival
histopathology investigations with heterogeneous disease definitions, tissue compartments, and outcome reporting. The available literature
demonstrated substantial region-specific variability in laryngeal epithelial phenotype, stromal organization, and mucosal immune architecture.
CD3-related findings supported a recurrent T-cell component in chronic inflammatory laryngeal tissue. CD20-positive cells were identified,
but their interpretation was complicated by the presence of organized larynx-associated lymphoid tissue, particularly in supraglottic and falsevocal-fold regions. No eligible human chronic-laryngitis study directly quantified CD168 in tissue. Because no primary outcome was reported
by at least two sufficiently comparable studies with extractable effect estimates, meta-analysis was not validly estimable.
Conclusions: Current evidence supports a qualitative model in which chronic laryngitis reflects anatomically patterned epithelial-stromal
immune disequilibrium rather than a single uniform lesion. CD3-positive inflammation appears more consistently documented than CD20-
positive involvement, while CD168 remains an important but unstudied target in human chronic-laryngitis tissue. Standardized,
compartment-specific immunohistochemical studies are needed before robust quantitative synthesis can be undertaken.