Systemic therapy in metastatic salivary gland carcinomas : a pathology-driven paradigm?

Salivary gland carcinomas (SGCs) represent one of the most complex tumors from a pathological point of view. According to the World Health Organization (WHO) classification (2005), twenty-four malignant histotypes are recognized, almost all characterized by specific morphological and genetic features as well as by particular clinical behavior. Loco-regional relapse and distant metastases are quite common. Distant metastases are diagnosed in 25\u201355% of the patients and only 20% of them are alive after 5\ua0years. Adenoid cystic carcinoma (ACC) is the most common (60%) malignant histotype observed in patients with metastatic disease, whilst the other histotypes such as mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified (NOS), and myoepithelial carcinoma are rarer. The most common therapeutic approach in cases of metastatic disease is systemic chemotherapy, although the results with this type of approach are poor both in terms of response rate and overall outcome. No consensus has yet been reached on what the standard regimen of chemotherapy should be in this setting. New therapies are under investigation e.g. antiangiogenic agents, histone deacetylase inhibitors, and hormonal deprivation treatment. We have focused our review on systemic treatments in ACC and in non-ACC tumors, including in this latter group all SGC histotypes other than ACC