Differentiated oral intraepithelial neoplasia (doin), an underrecognized entity

Background Differentiated oral intraepithelial dysplasia (DOIN) was described by Japanese pathologists in 2007 but is not recognized by the World Health Organization. As in the vulva and penis, differentiated dysplasia in the oral cavity is a diagnostic challenge. Objective We determined reliable histologic criteria for the diagnosis of DOIN and assessed the usefulness of cytokeratins (CK) 13 and 17, combined with proliferation marker KI67. The frequency of DOIN in oral squamous cell carcinoma (OSCC) was also estimated. Methods All OSCC cases from 2014 to 2017 were reviewed for the presence of dysplasia. For differentiated dysplasia, histologic features were studied in detail and diagnostic criteria were established. Interobserver agreement was measured. Immunohistochemistry with CK13 and CK17/Ki67 was performed. Results We noted DOIN in 69% of OSCC cases (143/207). The histologic changes of DOIN were conspicuous in only 27% of cases, whereas in 73% the changes were subtle. Immunohistochemistry with CK13 and CK17 correlated with the histology: loss of CK13 and expression of CK17 in dysplasia, combined with KI67 altered expression. Conclusions DOIN is more frequently associated with oral carcinoma than usual dysplasia. In most cases the histologic changes are subtle. In this study we have attempted to define the histologic criteria. Cytokeratins 13 and 17/KI67 can be useful to support the diagnosis, especially in cases with subtle histologic changes. Recognition of subtle dysplastic changes will lead to progress in knowledge and treatment. We hope that the World Health Organization will recognize DOIN in the future.