An orthotopic murine model of sinonasal malignancy.

Abstract

Malignant sinonasal tumors are clinically challenging due to their proximity to vital structures and their diverse histogenesis and biological behavior. To date, no animal models accurately reflect the clinical behavior of these malignancies. We developed an orthotopic murine model of sinonasal malignancy that reproduces the intracranial extension, bony destruction, and spread along neural fascial planes seen in patients with aggressive sinonasal malignancies of various histologies. Human squamous cell carcinoma line (DM14) and adenoid cystic carcinoma line (ACC-3) were implanted in the right maxillary sinus or soft palate in male nude mice. Animals were monitored for tumor growth and survival. Tumor specimens were removed for histopathologic evaluation to assess for intracranial extension, orbital invasion, bony invasion, perineural invasion, and distant metastasis. Statistical analysis was done to calculate P values with the Student's t test for individual tumor volumes. Differences in survival times were assessed using the log-rank test. Mice with DM14 or ACC-3 implanted in either the maxillary sinus or the soft palate developed large primary tumors. A statistically significant inverse correlation between survival and the number of tumor cells implanted was found. Histopathologic evaluation revealed orbital invasion, intracranial extension, pulmonary metastasis, lymph node metastasis, and perineural invasion. We describe the first orthotopic model for sinonasal malignancy. Our model faithfully recapitulates the phenotype and malignant behavior of the aggressive tumor types seen in patients. This model offers an opportunity to identify and specifically target the aberrant molecular mechanisms underlying this heterogeneous group of malignancies.