Histopathological and Inflammatory Features of Chronically Discharging Open Mastoid Cavities Secondary Analysis of a Randomized Clinical Trial

IMPORTANCE: Many patients with an open radical mastoid cavity experience therapy-resistant otorrhea. Little is known about the underlying histopathological substrate of unstable cavities and the correlation with treatment failure. OBJECTIVE: To study the histopathological and inflammatory features of chronically discharging open radical mastoid cavities and the influence of different treatments. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial was a histopathology study of tissue samples of a cohort of 30 patients with a chronically discharging open mastoid cavity. Samples were taken from the cavities, which were treated with either honey gel or conventional eardrops in a tertiary center between 2012 and 2013. Tissue staining was performed in May 2014; final computer analysis/correlation studies were performed in June 2016. MAIN OUTCOMES AND MEASURES: Differences of epithelial tissue coverage, infiltration of T cells (CD3, CD4, CD8) and macrophage (CD68, isoenzyme nitric oxide synthase, arginase 1) (sub-)populations, infection status, and the correlation with clinical presentation. RESULTS: There were 30 patients (24 [80%] male; mean [SD] age, 59 [14] years). Cavities were covered with either stratified squamous (keratinized) epithelium (n=10), respiratory columnar epithelium (n=9), or granulation tissue (n=10). The presence of respiratory epithelium was associated with lower treatment success (posttreatment VAS improvement of 3.1 [95% CI, 0.5 to 5.8] for discomfort and 3.6 [95% CI, 0.2 to 6.9] for otorrhea in the group with granulation tissue coverage vs 4.9 [95% CI, 0.2 to 9.6] and 5.8 [95% CI, -0.1 to 11.6] in the group with squamous [keratinized] epithelium coverage and 1.4 [95% CI, -1.2 to 4.1] and 2.5 [95% CI, -1.3 to 6.2] in the group with respiratory columnar epithelium coverage). In all 3 tissue types of cavity-covering tissues, T-cell infiltrates consisted of helper T cells and cytotoxic T cells, together with a lower number of macrophages. The immunopositivity for isoenzyme nitric oxide synthase and arginase 1 was high and not restricted to a macrophage subpopulation, but seen in various cell types. Inflammatory infiltrations varied strongly in all 3 tissue modalities. CONCLUSIONS AND RELEVANCE: Discharging open mastoid cavities can be classified histologically into 3 different types, based on their coverage: squamous epithelium, respiratory epithelium, or granulation tissue. Treatment is less successful in cavities covered with respiratory epithelium, possibly explained by the status of bacterial infection and local immunological differences.