Endotyping of Cholesteatoma: Which Molecular Biomarkers? A Systematic Review

Background: So far, no medical treatment is available for cholesteatoma (C) and the only effective therapy is complete surgical removal, but recurrence is common even after surgical treatment. While C is classically divided into two clinical phenotypes, congenital and acquired, only a few studies have focused on its potential biomarkers. This study aims to revise the literature to identify which biomarkers can define the endotype of C. Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process to identify published experimental articles about molecular biomarkers in C. Results: KGF and its receptor, MMP-9, KRT-1, KRT-10, and MIF might be considered biomarkers of recurrence, whereas Ki-67, TLR-4, RANKL, IL17, MMP-2, MMP-9, IL6, TNF-alpha, should be considered more specifically as biomarkers of bony erosion. Conclusions: These results are interesting especially from a prognostic point of view, nevertheless more studies are needed to search new biomarkers of C that could completely change not only the therapeutic standards of the disease, but also the clinical history of C itself in the era of precision medicine.