Histopathogenesis of Non-HPV-related Differentiated Oral Squamous Intraepithelial Neoplasia

Introduction: A study of immunohistopathologic and cytohistopathologic changes of the parabasal/basal layers in the differentiated squamous intraepithelial neoplasia (DSIN) may elucidate the histopathogenesis and reveal changes aiding early diagnosis and grading of the lesion. Materials and Methods: A total of 55 consecutive resection specimens of nonbasaloid squamous cell carcinoma of the anterior oral cavity and 8 biopsies before resections displaying DSIN in the overlying squamous epithelium were examined. Results: Squamous epithelium that is continuous/immediately adjacent to invasive squamous cell carcinoma (type 1) and the more peripheral (type 2) epithelium of resection specimens displayed consistent changes in the parabasal/basal layers: (A) cytologic atypia with proliferation of parabasal cells with downward expansion causing reactive proliferation of the basal cell layer in the early stage, invading the basal layer in the late stage; (B) disordered nuclear/cytoplasmic arrangement; (C) "Cobblestone" appearance. Immunoreactivity for TP53 and Ki67 was helpful in the diagnosis. The epithelial spectrum of changes decreased as one moved from type 1 to type 2 lesions. Five out of 8 biopsies showed type 1 lesions (followed by resection in a period of 11 +/- 6 mo) and 3 showed type 2 lesions (followed by resection in a period of 55 +/- 20 mo). In addition, resections were margin positive for type 2 lesions in 5 cases associated with recurrence at the site of resection during a period of 69 +/- 9 months. Conclusions: DSIN is characterized by a proliferation of neoplastic parabasal cells with dyskeratosis, downward expansion/ pushing of the basal layer with elongation of rete ridges. We proposed grading of DSIN based on the changes of the parabasal/basal layers.