Hematoxylin and eosin staining of tongue (a and b) and esophagus (c and d). (a and c) Wild-type mouse at 12 months of age. (b and d) L2D1⁺/p53^+/– mouse at 12 months of age. b and d show evidence of nuclear atypia, enlargement, and hyperchromasia of cells as well as loss of polarity with migration of atypical cells into intermediate and superficial layers as cellular and histologic features of dysplasia. In particular, there is invasion of malignant cells into the submucosa and muscle of the tongue and into the submucosa of the esophagus. Cancer lesions are marked by arrows. (e) Hematoxylin and eosin staining and (f) pancytokeratin immunohistochemistry from one representative paraesophageal lymph node metastasis. There are keratin-positive epithelial cells within the lymphatic tissue. Magnification, ×400.