Increase in Chymase-Positive Mast Cells in Recurrent Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland

Abstract

Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFβ1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.

Recurrent pleomorphic adenoma of the parotid gland: A population‐based study with emphasis on re‐recurrence and malignant transformation

“…In addition, biological and genetic factors may also be considered as potential causes of RPA. [19][20][21] In our cohort, only recurrence times (single/multiple) is an independent prognostic factor for recurrence-free survival of the parotid RPA. It is consistent with previous research.…”

“…If the benign parotid tumor is near the facial nerve, the tumor must be resected extra‐capsular to preserve the facial nerve, which may result in PA recurrence even after proper superficial parotidectomy or total parotidectomy. In addition, biological and genetic factors may also be considered as potential causes of RPA 19–21 …”

Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights

“…The role of CAFs in CXPA seems to have been explored only recently. A single study available in the literature using immunolabeling of vimentin and α-SMA showed that CAFs are abundantly present in carcinomatous areas of CXPA ( 79 ). Several clinical trials targeting CAFs are currently active in different tumors, such as head and neck cancer, gastrointestinal carcinoma, hepatocellular carcinoma, breast carcinoma, melanoma, and other solid tumors ( 80 ).…”

Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland

“…Immunostaining with the abovementioned antibodies was performed following the protocols described elsewhere [6,42]. In brief, deparaffinized sections were incubated with the respective antibodies overnight at 4 • C, followed by a reaction with components from a labeled streptavidin-biotin peroxidase kit (Dako LSAB kit; Dako, Carpinteria, CA, USA).…”

“…Recently, research on the relationship between chymase and malignant tumor pathology has attracted a great deal of attention. For example, Kinoshita et al recently reported that the number of chymase-positive mast cells, as well as chymase gene expression, was increased markedly in carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland when compared to the benign parotid tumor, pleomorphic adenoma (PA) [6]. Chymase-positive cells were also significantly increased in human lung and gastric cancers [7,8], indicating the importance of chymase in cancer.…”