High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland
carcinomas, including
acinic cell carcinoma, secretory
carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial
carcinoma, polymorphous
adenocarcinoma, low-grade
mucoepidermoid carcinoma, and hyalinizing clear cell
carcinoma. High-grade (HG) transformed
tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated
adenocarcinoma,
carcinoma not otherwise specified, or
undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive
necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland
carcinomas are largely unknown, though p53 inactivation and
human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland
carcinomas with HGT are more aggressive than conventional
carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical
lymph node metastasis suggesting a need for a wider resection and
neck dissection. HGT of salivary gland
carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative
radiotherapy. The potential for HGT in almost any type of salivary gland
carcinoma warrants a thorough sampling of all salivary gland
malignancies to prevent oversight of a HG component.