Grade as a prognostic variable in tongue cancer.

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Firstly, there is a lack of consensus about the exact definition of different grades. The majority of centers use the degree of keratinization as major or only criteria. The well-keratinized tumor is considered well-differentiated while a tumor lacking keratinization with undifferentiated cells labeled as poorly differentiated, but no consensus exists for demarcation between prominent keratinization and not so prominent keratinization, hence make pathologist’s bias as potential prognostic, rather than grade. Some pathologist uses immunohistochemistry (IHC) while being comfortable without such aid to report PDC. IHC and keratinization level, interrelation might further reduce objectivity. It is advisable to document the thresholds and confirming the reproducibility of grading becomes extremely important. The majority of series including WHO criteria lack objective definitions. Secondly, the grade of the tumor is the harbinger of the degree of differentiation in cells and their nucleus hence it is plausibly a marker of disease behavior. The notion is valid in certain diseases like sarcomas, breast, or prostate cancer to forecast disease behavior. We may also take lessons from such cancers where multiple additional factors like the degree of proliferation, tubule formation, the arrangement of cells, degree of necrosis, and pleomorphism, in addition to histological differentiation. Whether these factors can be incorporated into current grading in the presence of cellular keratinization, feasibility yet to be explored in HNC. Thirdly, squamous cells are destined for the function of protection, unlike more specialized cells, which are involved in a variety of specialized functions. Having a relatively less complex functional role, their gene expression profile may be less complex, relatively simpler, and limited useful transduction pathways & driver mutations, hence limited targets for precision medicine as of now. Across the spectrum of squamous cell carcinoma, from HNC, cervical cancer, and lung cancer, researchers consistently find it difficult to assign clinical targetable molecular alteration, probably due to this notion, limited utility of grade of the tumor, beyond the degree of keratinization is relevant.

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