Nuclear fractal dimension in oral squamous cell carcinoma: a novel method for the evaluation of grading, staging, and survival

Fractal dimension (FD) in tissue specimens from patients with oral squamous cell carcinoma (OSCC) was evaluated. FD values in different stages of OSCC, and the correlations with clinicopathological variables and patient survival were investigated. Histological sections from OSCC and control non-neoplastic mucosa specimens were stained with hematoxylin–eosin for pathological analysis and with Feulgen for nuclear evaluation. FD in OSCC groups vs. controls revealed statistically significant differences (P < 0.001). In addition, a progressive increase of FD from stage I and II lesions and stage III and IV lesions was observed, with statistically significant differences (P = 0.003). Moreover, different degrees of tumor differentiation showed a significant difference in the average nuclear FD values (P = 0.001). A relationship between FD and patients' survival was also detected with lower FD values associated to longer survival time and higher FD values with shorter survival time (P = 0.034). These data showed that FD significantly increased during OSCC progression. Thus, FD could represent a novel prognostic tool for OSCC, as FD values significantly correlated with patient survival. Fractal geometry could give insights into tumor morphology and could become an useful tool for analyzing irregular tumor growth patterns.