Squamous Cell Carcinomas of the Anterior Oral Cavity Are Commonly Associated With Simplex (or Differentiated) Oral Intraepithelial Neoplasia

Introduction: We investigated the occurrence of differentiated oral intraepithelial neoplasia (DOIN) that met the criteria for differentiated intravulvar neoplasia, associated with invasive squamous cell carcinoma (SCC) of the anterior oral cavity, and its clinicopathologic significance. Materials and Methods: Sixty-nine consecutive cases of SCC of the anterior oral cavity were categorized into 2 groups: group A comprised SCC associated with DOIN; Group B consisted of cases associated with classical SCC in situ. Results: Fifty-five cases (80%) were classified as group A, or DOIN lesions, with only 14 (20%) as group B. All cases were associated with invasive SCC, except 2 cases in group B. Squamous epithelium continuous or adjacent to invasive SCC displayed consistent changes in the parabasal and basal layers with (1) cytologic atypia with proliferation of parabasal cells in downward expansion causing reactive proliferation of the basal cell layer in early stage and invading the basal layer in late stage, (2) disordered nuclear/cytoplasmic arrangement, and (3) a “cobblestone” appearance characterized by prominent intercellular spaces and cytoplasmic density involving the entire cell (dyskeratosis) of the parabasal layer. p53 and Ki67 immunostaining revealed linear reactivity mainly in the parabasal layer. Conclusions: DOIN lesions are frequently associated with invasive SCC of anterior oral cavity. Due to the subtle histopathologic changes, DOIN lesions pose potential diagnostic difficulty with differentiation from mild dysplasia or reactive atypia.