Hemorrhagic areas as a histological prognosticator in oral cancer: A novel proposition

Determination of prognosis in oncology practice is a major challenge and many histological prognosticators have been applied because of the ease and simplicity of using them in day-to-day practice. Our histopathologic observation on 96 oral squamous cell carcinoma (OSCC) specimens revealed 34 cases associated with frank hemorrhagic areas, which were close to tumor cells. Hence, we propose that there could be a cross-talk between tumor cells and RBCs which can modulate the biological behavior of the tumor and prognosis of the patient. In the present paper, a scientific foundation is provided for this proposition. Furthermore, an experimental approach is recommended which will facilitate the identification of extracellular metabolites within the tumor microenvironment near RBCs. Such studies may pave the way for a better understanding of the clinical heterogeneity of oral cancer due to differential heme content of red blood cells (RBCs) in the tumor microenvironment (TME).