Acinic Cell Carcinoma With High-grade Transformation

Abstract

High-grade transformation of acinic cell carcinoma (AciCC) (previously referred to as dedifferentiation) is a rare phenomenon characterized by histologic progression of low-grade AciCC to high-grade adenocarcinoma or undifferentiated carcinoma. We report 9 new cases with immunohistochemical analysis and examination of HER-2/neu and p53 genes to further define the profile of this tumor. Histologically, the high-grade component was composed of polymorphic cells with a high mitotic rate arranged in glandular and solid growth patterns with comedonecrosis. The MIB-1 labeling indices were elevated in the high-grade component, as compared with the low grade conventional AciCC. The high-grade component of AciCC was characterized by strong membrane staining for CK18 and beta-catenin, and nuclear staining for cyclin-D1. HER-2/neu, androgen receptor, C-kit, and epidermal growth factor receptor were absent from both low-grade and high-grade components. In contrast, S-100 protein, alpha-1-antitrypsin, and lysozyme were lost only in high-grade foci of transformed AciCC. The median age was 61 years (with range from 43 to 76 y). Lymph node (LN) metastases were found in 5 of 9 cases (56%). Distant metastases to the lungs (n=4), pleura (n=2), brain (n=3), and peritoneum (n=1), and paraaortic, paratracheal, and mediastinal LNs (n=2) were observed. Six of 9 patients (66%) died from tumor dissemination, all with a median overall survival of 4.3 years (range: 1 to 9 y). The high propensity for LN metastases indicates the need for neck dissection at the time of diagnosis.

The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis‐generating study

“…The presence of poorly differentiated tumors adjacent to ACCs is not an uncommon finding in the breast [7,23] and it has also been reported in the context of ACCs of the salivary glands [54]. The non-ACC components of the mixed cases included in this study were all high-grade, highly proliferative triple-negative breast carcinomas (Figure 2 and Table 2).…”

Distant Metastases in Patients with Carcinoma of the Major Salivary Glands

“…3 Myoepithelial carcinoma had the lowest rate of DM (6 %) of any histologic subtype in our study group. Acinic cell cancer usually is a low-grade cancer, although some forms can behave more aggressively, 12 and thus it falls into the intermediate-risk group.…”

Molecular advances in salivary gland pathology and their practical application

“…Alteration of the p53 pathway has been shown to play a critical role in progression of head and neck cancer 44 and in high grade transformation of adenoid cystic carcinomas, 45 and epithelialmyoepithelial carcinoma, 46 but it does not seem to have any role in HG transformation of acinic cell carcinomas. 12 Molecular mechanisms responsible for malignant transformation of pleomorphic adenoma and tumour progression Carcinoma ex pleomorphic adenoma (CXPA) is defined as a carcinoma developing within a pre-existing benign pleomorphic adenoma (PA). As PA is characterized by a recurrent rearrangement involving transcription factors PLAG1 on chromosome 8q12 and HMGA2 on chromosome 12q15 it is not surprising finding, that these aberrations are found in CXPA 47,48 as well.…”

“…2,8,9 This review will also discuss recent molecular evidence of clonality in the entity of sclerosing polycystic adenosis, which suggests that its nature is neoplastic rather than reactive or inflammatory. 10 Finally, new molecular developments in salivary duct carcinoma 11 and molecular mechanisms responsible for high grade transformation 12 and tumour progression will be considered. 13,14 Oncogenic translocations in salivary gland carcinomas Mucoepidermoid carcinoma Mucoepidermoid carcinoma (MEC) represents about 5% of all salivary gland tumours and 20% of salivary malignancies.…”