Importance of High Grade Transformation and Translocations in Salivary Gland Neoplasms

Abstract

CommentaryThe concept of high grade transformation in human neoplasms was introduced in 1971 by the report demonstrating that 33 of 370 cases of well differentiated (low-grade) chondrosarcomas contained areas of a high-grade sarcoma [1]. Currently at least 23 different types of primary salivary carcinomas are recognized, some of low and others of high grade malignancy. During the last decade, it has become apparent that a fair number of conventionally low grade salivary tumours do switch to tumours with much more aggressive biological behaviour. This behaviour is for example reflected by a more anaplastic, high grade histologic appearance of the tumour. The "anaplastic" focus, or foci, may be small but nevertheless command the biological behaviour of the entire neoplasm. We recently reported a review of all published salivary so-called salivary hybrid tumours, i.e. tumours with two histologically distinct components (histologically described and defined in 1996). We found 38 cases in 22 publications, and after thorough studies we concluded that most, if not all, of these hybrid tumours probably were examples of high-grade transformation (HGT) in another (pre)existing neoplasm. These are tumours where one component is of low grade malignancy and the other of high grade, proportion of which may vary, and so may the histology. Sufficient data was not available to draw a conclusion whether these two tumour components had a common molecular pathway or not. Several findings indicated that very likely the mechanism had been a highgrade transformation rather than two different tumours occurring at the same place (still to be separated from so-called collision tumours). During the same period of time more than a hundred cases of HGT in salivary gland neoplasms had been reported [2]. In another study, we investigated the clinical consequences of HGT in salivary adenoid cystic carcinoma. Conventional adenoid cystic carcinoma is already a tumour of high grade malignancy in the long term (10-20 years) but in cases with HGT their biological behaviour change drastically with early spread to lymph nodes and distant metastasis, and a more dismal short-term prognosis, prompting a more aggressive initial treatment [3]. Similar observations of HGT have been made in acinic cell carcinoma, and in also in salivary polymorphous low-grade adenocarcinoma, epithelial-myoepithelial carcinoma, lowgrade mucoepidermoid carcinoma, myoepithelial carcinoma, hyalinizing clear cell carcinoma and, mammary analogue secretory carcinoma [4].The molecular genetic mechanisms responsible for HGT in salivary neoplasms remain largely unknown. Abnormalities of a few genes, such as p53 (loss of heterozygosity at p53 microsatellite loci and p53 gene point mutation), C-MYC (amplification), cyclin D1, HER-2/neu (overexpression), and loss of pRb expression, have been documented. Chromosomal gains confined to areas of HGT of adenoid cystic carcinoma, and losses in conventional areas, have been reported.Oncogenes on chromosome 17q23 appear to be of interest. It h...

Cervical Lymph Node Metastasis in High-Grade Transformation of Head and Neck Adenoid Cystic Carcinoma: A Collective International Review

“…HGT in salivary tumors of low-grade malignancy, such as AcCC, is associated with a higher local recurrence rate, a higher propensity for local lymph node metastasis and, a dramatic worsening of prognosis. For example, AcCC has the best prognosis of all salivary malignancies (10-year survival ~90%), but HGT in AcCC significantly reduces the mean survival of patients to 4.3 years [ 5 , 25 ].…”