Middle ear cholesteatoma: biological basis, invasiveness heterogeneity, and challenges in severity assessment

Middle ear cholesteatoma (MEC) is a benign but biologically aggressive middle ear lesion characterized by progressive and destructive bone erosion. However, current evaluation systems remain heterogeneous and focus on limited anatomical structures, leading to insufficient clinical predictive value. This review aims to integrate current evidence on the biological mechanisms of MEC-associated bone erosion and assessment systems, with the goal of informing the development of more standardized and clinically meaningful severity evaluation models.

A narrative review was performed in PubMed, Web of Science, and Embase databases to summarize current knowledge on the mechanisms driving bone erosion in MEC and to evaluate the existing staging systems for assessing erosion severity. Keywords included "cholesteatoma", "bone erosion", "bone resorption", "molecular mechanisms", "staging systems" and related terms.

Available evidence indicates that bone erosion in MEC arises from the interaction between hyperproliferative epithelium, chronic inflammation, and osteoclast activation mediated by cytokines and signaling pathways, particularly RANKL-related mechanisms. Existing staging systems are largely descriptive and exhibit significant heterogeneity, which collectively undermines their clinical utility in guiding surgical management or predicting patient outcomes.

Current staging systems, valuable for describing anatomical extension, fail to capture cholesteatoma's biological heterogeneity and invasive potential, thus incompletely depicting the disease. Future evaluation strategies should integrate molecular mechanisms, comprehensive anatomical involvement, and imaging findings to develop more standardized and clinically meaningful severity assessment systems.