Salivary Epithelial-Myoepithelial Carcinoma: Clinical, Histopathological and Molecular Study from A Latin American Case Series with a Novel MSH3 Driver.

Abstract

Purpose: Epithelial-myoepithelial carcinoma (EMC) is a rare malignant neoplasm of the salivary glands. Although most studies have reported the predominant, recurring driver mutation is in HRAS, its molecular pathogenesis is not yet fully understood. The aim of this study is to describe the clinical and histopathological characteristics of a case series of salivary EMC with non-RAS genetic variants.

Methods: Fifteen formalin-fixed paraffin-embedded (FFPE) samples of EMC were retrospectively retrieved. Clinicopathological data was recovered from medical records. Two cases with sufficient tissue were assessed through next-generation sequencing (NGS).

Results: EMC occurred more frequently in females (60%). The mean age at diagnosis was 59.5 (± 14.5) years. The parotid was the most common primary site (80%). Time from first symptoms to diagnosis was 41 months in average. Pathological staging I, II and III occurred in 21.4%, 28.6% and 50% of the cases, respectively. Only one participant had regional lymph node involvement, and none were metastatic. The margins were involved in 41.6% of cases. All the patients were surgically treated, including neck dissection in two subjects, and 33% received adjuvant radiotherapy. One patient relapsed (6.7%) after an average of 32.4 months of follow-up. NGS analysis revealed 160 germline mutations in 46 genes of interest, of which 11 were previously described as pathogenic or as variant of uncertain significance (VUS). Only one somatic frameshift deletion involving MSH3 (c.1148del p.K383Rfs*32) gene was detected.

Conclusion: This study explores EMC in a Latin American cohort. The findings align with global literature, and a novel MSH3 mutation was identified. However, further research is needed to confirm its significance and potential impact on tumor behavior.