Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis.

Among salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize; they have been called metastasizing mixed tumor (MZMT) of salivary glands. We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT. At the time of discovery of metastatic disease, the patients, six women and five men, ranged in age from 20 to 83 years. Primary sites of involvement included the parotid gland (eight cases), submandibular gland (two cases), and the nasal septum (one case). With one exception, all the patients had at least a single recurrences of their primary mixed tumor, but two or more recurrences were the norm before development of metastatic foci. The metastases were discovered from six to 52 years following the occurrence of the primary tumor. Metastatic deposits were identified in bone, lung, regional lymph nodes, skin, kidney, retroperitoneum, oral cavity, pharynx, calvarium, and central nervous system. The metastases either occurred simultaneously with an episode of recurrent mixed tumor (n = 5) or from 5 to 29 years after a recurrence (n = 6). The treatment of the primary, recurrent, and metastatic neoplasms was surgical excision. Follow-up, ranging from 8 months to 16 years following the diagnosis of MZMT, revealed seven patients to be alive without disease (64%) and two dead of causes unrelated to metastatic disease (18%). Two patients (18%) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors. Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases. Aneuploid DNA cell content was identified in two of the cases. DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors. Retrospective analysis of histologic parameters (mitotic rate, cellular pleomorphism, infiltrative growth, vascular or lymphatic invasion) and flow cytometric analysis failed to identify criteria to predict the development of metastasis in these neoplasms.