GENE REARRANGEMENTS IN PAROTID TUMORS: ROLE OF PLAG1, HMGA2, AND MAML2 FUSIONS IN DIAGNOSTIC AND PROGNOSTIC STRATIFICATION

Parotid gland tumors exhibit marked morphological and molecular heterogeneity, requiring increasingly integrated diagnostic and prognostic approaches. This study consisted of a systematic review of the literature addressing the prognostic impact of gene rearrangements involving PLAG1, HMGA2, and MAML2 in salivary gland neoplasms. The search strategy included major international databases, prioritizing studies published between 2021 and 2025, with inclusion criteria focused on molecular investigations presenting clinicopathological correlations. The findings demonstrated that, in pleomorphic adenoma, PLAG1 and HMGA2 fusions primarily act as early tumorigenic events and are generally associated with indolent clinical behavior. However, specific fusion variants and additional genetic alterations may indicate an increased risk of progression to carcinoma ex pleomorphic adenoma. In mucoepidermoid carcinoma, MAML2 rearrangement showed a more consistent association with favorable prognosis, including lower recurrence rates and improved overall survival. The clinical relevance of these molecular markers is supported by the WHO Classification of Tumours, which incorporates molecular criteria into the classification of salivary gland tumors. In conclusion, the prognostic value of gene fusions is context-dependent and should be interpreted alongside histopathological and clinical parameters. The consolidation of precision medicine in parotid tumors requires prospective multicenter studies to validate predictive models based on integrated molecular data.