"Dedifferentiation" and high-grade transformation in salivary gland carcinomas

Abstract

"Dedifferentiation" and/or high-grade transformation (HGT) has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, myoepithelial carcinoma, low-grade mucoepidermoid carcinoma and hyalinizing clear cell carcinoma, although the phenomenon is a rare event. Recent authors tend to preferably use the term HGT instead of "dedifferentiation" in these cases. HGT-tumors are composed of conventional carcinomas juxtaposed with areas of HG morphology, usually either poorly differentiated adenocarcinoma or "undifferentiated" carcinoma, in which the original line of differentiation is no longer evident. The HG component is generally composed of solid nests, sometimes occurring in cribriform pattern of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli and abundant cytoplasm. Frequent mitoses and extensive necrosis is evident. The Ki-67 labeling index is consistently higher in the HG component. p53 abnormalities have been demonstrated in the transformed component in a few examples, but the frequency varies by the histologic type. HER-2/neu overexpression and/or gene amplification is considerably exceptional. The molecular-genetic mechanisms responsible for the pathway of HGT in salivary gland carcinomas largely still remain to be elucidated. Salivary gland carcinomas with HGT have been shown to be more aggressive than conventional carcinomas with a poorer prognosis, accompanied by higher local recurrence rate and propensity for cervical lymph node metastasis, suggesting the need for wider resection and neck dissection.

Fig. 1

High-grade transformation of acinic cell carcinoma. a Low-power view of the biphasic histology of the tumor comprising a high-grade carcinoma with solid and cribriform patterns of growth and comedonecrosis (right portion), and a conventional acinic cell carcinoma with a lymphoid stroma (left portion). The two components are sharply separated from each other. b Conventional acinic cell carcinoma showing microcystic and focal solid growth of tumor cells of a unifying nuclear feature. Mixture of basophilic acinar-type cells is evident. c High-grade carcinoma exhibiting solid patterns of growth with extensive necrosis. Carcinoma cells contain large vesicular pleomorphic nuclei and prominent nucleoli. Several mitoses are also observed. d High-grade carcinoma displays a high Ki67 labeling index (right portion), in contrast to a low index in conventional acinic cell carcinoma (left portion)

Fig. 2

High-grade transformation of adenoid cystic carcinoma. a Low-power view showing two distinct carcinomatous components: conventional adenoid cystic carcinoma (left portion) and high-grade carcinoma with a predominantly solid growth pattern, forming irregular and confluent tumor nests (right portion). Comedo-like necrosis is evident in the high-grade component. b Conventional adenoid cystic carcinoma exhibiting cribriform pattern with excessive extracellular basal lamina material and two cell-layered tubular structures. The tumor cell nuclei have a bland, uniform appearance. c and d High-grade carcinoma component. Solid (c) and micropapillary (d) growth patterns of carcinoma cells exhibiting large pleomorphic nuclei with a moderate amount of cytoplasm. Note prominent necrosis. e Ki-67 labeling index of the high-grade carcinoma component (right portion) is much higher than that of the conventional adenoid cystic carcinoma component (left portion). f Only high-grade carcinoma on the right is strongly and diffusely positive for p53

Fig. 3

High-grade transformation of epithelial-myoepithelial carcinoma. a Two distinct carcinomatous components: epithelial-myoepithelial carcinoma (left portion) and high-grade carcinoma (right portion), are evident. b Conventional epithelial-myoepithelial carcinoma exhibits biphasic ductal structures, comprising inner eosinophilic cells and outer clear cells of minimal atypia. c High-grade carcinoma is composed of pleomorphic tumor cells with prominent nucleoli. There is focal squamous differentiation. d Higher Ki-67 labeling index is noted in the high-grade carcinoma component (right portion)

Fig. 4

High-grade transformation of low-grade mucoepidermoid carcinoma. a Low-power view showing a low-grade mucoepidermoid carcinoma component composed mainly of cystic structures (left portion) and a high-grade anaplastic carcinoma component with a solid and sheet-like growth pattern (right portion). Note that the two components are sharply separated from each other. b The low-grade mucoepidermoid carcinoma component consisting of cystic and glandular formations (left upper portion) and the solid growth of the high-grade anaplastic carcinoma component (right lower portion) are intimately connected. c Low-grade mucoepidermoid carcinoma component showing a mixture of intermediate, mucous goblet, and epidermoid cells. Note the bland appearance of the tumor cell nuclei. d High-grade carcinoma component showing solid growth of markedly pleomorphic tumor cells with prominent nucleoli