Apoptosis, Mitosis, and Cell Turnover in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Narrative Review on Histochemical Assessment and Clinicopathological Relevance.

Maintenance of oral epithelial integrity depends on the equilibrium between cellular proliferation, differentiation, and programmed cell death. Disruption of this equilibrium contributes to the development and progression of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). Apoptotic index (AI), mitotic index (MI), turnover index (TI), and nuclear-cytoplasmic morphometric parameters provide measurable representations of epithelial kinetics and cytological atypia. This narrative review examines alterations in these parameters across oral leukoplakia, oral epithelial dysplasia (OED), oral submucous fibrosis (OSMF), and OSCC. It also evaluates hematoxylin and eosin (H&E), methyl green-pyronin Y, Feulgen, fluorescent Feulgen, and acridine orange staining for identifying apoptotic bodies, mitotic figures, and nuclear alterations. Available evidence indicates that apoptotic and proliferative activity generally increases with epithelial dysplasia and malignancy, although the relationship is not consistently linear. Histochemical techniques can enhance nuclear contrast and facilitate quantitative assessment, particularly in settings where immunohistochemistry or molecular testing is unavailable. Nevertheless, variation in fixation, staining, field selection, counting criteria, and observer calibration limits comparison across studies. Moreover, associations with histological grade should not be interpreted as evidence of prognostic prediction without longitudinal clinical outcomes. Standardized counting protocols, appropriate normal controls, blinded observer assessment, digital image analysis, and validation against established proliferation and apoptosis markers are required. Quantitative cell-turnover assessment should presently be regarded as an adjunct to conventional histopathological diagnosis rather than a replacement for established grading systems.