Carcinoma ex benign pleomorphic adenoma of the parotid gland.

BACKGROUND: Carcinoma in pleomorphic salivary adenoma is a common histologic subtype of primary parotid malignancy. METHODS: In this study, 28 patients (predominantly male) with histologically diagnosed carcinoma in pleomorphic salivary adenoma presenting over 10 years were retrospectively reviewed. RESULTS: Only 25 percent of patients had a previously treated pleomorphic salivary adenoma. Although the presenting features suggested malignancy in some cases, overall they were nonspecific, overlapping with the presentation of benign disease. Preoperative investigations included fine needle aspiration cytology, which was only 29-percent sensitive, and computed tomography and/or magnetic resonance imaging. There were 14 superficial and 12 total or radical parotidectomies. The facial nerve was resected en bloc with the tumor in nine cases and immediately reconstructed with good reanimation results in patients with recent-onset facial paresis. Only 44 percent of patients had a complete histologic tumor clearance, and this was the most significant determinant of survival (p < 0.01, log-rank analysis). The locoregional control rate was 66 percent at 5 years, but recurrent disease proved invariably fatal. Five-year disease-specific survival was 44 percent with a high rate of disease-specific mortality (87 percent). CONCLUSIONS: Carcinoma in pleomorphic salivary adenoma is very difficult to diagnose preoperatively. Fine needle aspiration cytology had a disappointingly low sensitivity for this tumor, potentially misdirecting surgical management. While good locoregional disease control could be achieved with surgery and radiotherapy, carcinoma in pleomorphic salivary adenoma was shown to be aggressive with a high disease-specific rate of mortality. Given that incomplete tumor resection was the most important prognostic factor, a high index of clinical suspicion, radical ablative surgery, and immediate soft-tissue and nerve reconstruction for proven cases are advocated.

Mouse model for hereditary hemorrhagic telangiectasia has a generalized vascular abnormality.

BACKGROUND: Mutations in endoglin or activin like kinase-1, both involved in the endothelial transforming growth factor-beta signaling pathway, cause the autosomal dominant bleeding disorder hereditary hemorrhagic telangiectasia. We and others have reported mouse models for this disease that share the characteristic phenotype of dilated vessels and sporadic hemorrhage. The reasons for the variable phenotype in hereditary hemorrhagic telangiectasia are not understood. METHODS AND RESULTS: After a detailed immunohistochemical analysis of 129/Ola mice, which are heterozygous for a targeted deletion in the endoglin gene, we observed intrinsic abnormalities in the vascular walls throughout the cutaneous vasculature. Postcapillary venules were dilated, and up to 70% of the vascular wall had no smooth muscle cells. The supporting layers of collagens and elastin were irregular, with thin areas, adding to the fragility of these vessels. A variable hemorrhagic phenotype was observed in which local bleeding is associated not only with fragile vessels but also with regions of inflammation. CONCLUSIONS: These findings have relevance to our understanding of the molecular basis of vascular integrity in a wide range of diseases.