Better grade of tumor differentiation of oral squamous cell carcinoma arising in background of oral submucous fibrosis.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral cavity. Most of the people affected by OSMF are betel quid chewers. It is characterized by epithelial atrophy and progressive accumulation of collagen fibers in lamina propria and submucosa of the oral mucosa. 7.6% of OSMF cases undergo oral squamous cell carcinoma (OSCC) transformation of which majority display low grade of tumor differentiation. In the present paper, a hypothesis has been proposed to correlate atrophy, turnover rate and surface keratization in OSMF with degree of tumor differentiation in OSCC. A novel hypothesis for epithelial atrophy in OSMF has also been emphasized. High proliferative activity and basal cell hyperplasia in conjunction with rapid exfoliation of superficial cells and epithelial atrophy suggest that epithelial turnover rate is very high in OSMF. Presence of surface keratinized layer in this situation suggests faster maturation or differentiation of epithelium in OSMF. Thus, the epithelial cells are genetically programmed for high turnover rate and faster differentiation or maturation to form keratin. During malignant transformation of OSMF, the transformed epithelial cells may retain the genetic memory of faster differentiation and maturation resulting in better grade of tumor differentiation. The well differentiated OSCC has good prognosis, better survival rate and less chances of recurrence of regional and distant metastasis. Studies are needed to explore the biomarkers or molecular markers associated with carcinogenesis like genetic instability, oncogenes, tumor suppressor genes and angiogenesis in OSCC associated with OSMF. If investigated in the suggested direction, it might provide some important clues about the pathogenesis of OSCC arising in background of OSMF and for the future development of treatment strategies.