title: Histopathogenesis of non-HPV-related differentiated oral squamous intraepithelial neoplasia.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: *Department of Pathology and Laboratory Medicine †Department of Anatomical Pathology, The Ottawa Hospital and Ottawa University, Ottawa, ON, Canada.
authors.forename: Bibianna
authors.initials: B
authors.lastname: Purgina
authors.forename: Muhannad
authors.initials: M
authors.lastname: Hassan
authors.forename: Bernhard
authors.initials: B
authors.lastname: Olberg
authors.forename: Chi K
authors.initials: CK
authors.lastname: Lai
authors.forename: Kien T
authors.initials: KT
authors.lastname: Mai
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53