Local inflammatory reaction to benign, pre-malignant and malignant glottic lesions: A matched case-control study

Abstract

Objectives: To study the inflammatory infiltrates associated with the different stages of laryngeal carcinogenesis.

Design: Observational, matched case-control study of histopathologic specimens.

Setting: An academic referral centre.

Participants: A total of 45 patients who underwent removal of glottic lesions between 2008 and 2015. Patients were enrolled and categorised into three matched groups according to lesions' histopathologic diagnoses, 15 patients in each group: benign, pre-malignant and squamous cell carcinoma (SCC). Matching was based on age, gender and pack-years.

Main outcome measures: Immunohistochemistry staining using monoclonal antibodies against CD4, CD8, CD68, CD20 and S100 representing T-helper cells, cytotoxic T cells, macrophages, B cells and dendritic cells, respectively. Cell counts and distributions were measured and compared between groups. Correlations between the different cells were examined.

Results: The predominant cell type was CD8+, followed by CD68+ and CD4+. All inflammatory cells increased significantly in number in SCC (P-value < 0.001), with no significant difference between benign and pre-malignant groups. Strong correlations between the different cells were demonstrated only in the malignant group. S100+ cells correlated with both T-cell subsets, CD4+ (rho = 0.769, P-value = 0.001) and CD8+ (rho = 0.697, P-value = 0.0004). Infiltrates exhibited more extensive distribution in SCC compared to pre-malignant and benign; CD8+ and CD68+ cells were demonstrated in both intraepithelial and stromal regions in 93% of SCC lesions (P-value = 0.0001).

Conclusions: Laryngeal carcinoma demonstrates a unique pattern of inflammatory infiltrates, with significant changes in cell counts and distribution. Leucocyte infiltrates increased significantly in the transition from laryngeal pre-malignant lesion to malignancy while no significant differences were seen between benign and pre-malignant lesions.

Keywords: early glottic cancer; immunology; immunotherapy; inflammatory reaction; pre-malignant lesions.