High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance

Abstract

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.

Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3‐MAML2 fusions, and clinicopathological features

“…MEC cases were classified as follows: classical, clear cell, oncocytic, Warthin-like, spindle cell, sclerosing, central and others. 1,[12][13][14][15][16][17] In addition, high-grade transformation 18 and the recently described ciliated 19 and mucoacinar 20 variants were included in the variant list. In this process, central MEC was classified according to the site (intraosseous), and the other variants were classified according to the tumour histology.…”

Expanding the clinicopathological spectrum of TGFBR3‐PLAG1 rearranged salivary gland neoplasms with myoepithelial differentiation including evidence of high‐grade transformation

“… 19 In addition, hypocellular centers are described as a typical feature, 20 which were not evident in our cases. Furthermore, Her2/neu positive salivary duct CEPA is commonly encountered, 11 whereas high‐grade transformation has been only described in one case of MECA, 21 , 22 without information about the Her2/neu status. An initial diagnosis of minimal invasive low‐grade MECA of probable origin ex cellular pleomorphic adenoma was considered.…”

Diagnostic challenges and successful organ‐preserving therapy in a case of secretory carcinoma of minor salivary glands

“… 1 , 7 The rare occurrence of high‐grade transformation in SC of major and minor salivary glands is often associated with an unfavorable prognosis. 8 …”

“…Although most SC may develop over years, cases with an aggressive disease course, including lymph node metastases along with local recurrence or even distant metastases with lethal outcomes have been reported 1,7 . The rare occurrence of high‐grade transformation in SC of major and minor salivary glands is often associated with an unfavorable prognosis 8 …”

“…1,7 The rare occurrence of high-grade transformation in SC of major and minor salivary glands is often associated with an unfavorable prognosis. 8 Curative treatment strategies for SC of the salivary glands are identical to those of other salivary gland tumors concentrating on complete surgical resection. Dependent upon tumor stage and specific pathological features such as grade, perineural-and lymphovascular invasion and margin status, additional therapeutic modalities are considered, including adjuvant radiotherapy or chemoradiation.…”