Discussion
EMC has many histologic variations, thereby rendering an accurate diagnosis difficult.2 Immunohistochemical staining is of limited value in differentiating EMC from other salivary gland tumors with biphasic differentiation; however, HRAS  mutation testing may increase the rate of accurate diagnosis.
HRAS mutations are present in 81.7% of EMCs; however, noHRAS mutations have been identified in EMC-like salivary gland tumors, such as ACC, pleomorphic adenoma, BCA/BCAC, and myoepithelial carcinoma.2 Herein, both cases lacked characteristic features of EMC, but the presence of HRAS mutations led to a diagnosis. Additionally, we could distinguish EMC from its histologic mimic more accurately by confirming the absence of β-catenin nuclear reactivity observed in BCA/BCAC and the lack of MYB mutations, which indicate ACC. Notably, there is no significant correlation between the HRAS  mutation status and histologic indicators of tumor aggressiveness.2
EMC is generally low-grade; however, ‘high-grade transformations (HGTs)’ have been reported.1, 3 Dedifferentiation of salivary gland tumors has been described as HGTs, where a low-grade carcinoma results in a secondary high-grade carcinoma, which is associated with a worse prognosis. In case 2, a high degree of necrosis, numerous mitoses, and a high Ki-67 LI were seen, indicating that it was a high-grade tumor. It was difficult to conclude that it was an HGT of EMC based on the histopathological features; however, the HRAS mutation led to the diagnosis of EMC.
The standard treatment for EMC is complete surgical resection. The prognosis is relatively good in patients who have undergone wide surgical resection with clear margins.4
Conclusion
Genetic analysis for HRAS mutations is a crucial adjunct to pathological diagnosis of EMC and may play a decisive role, especially in difficult-to-diagnose cases.
Authors’ Contributions
Taisei Yasuda : concept/design, analysis of patient data, drafting and revision of the manuscript, final approval of the manuscript
Masami Osaki : analysis of patient data, drafting and revision of the manuscript, final approval of the manuscript
Masahiko Sugitani : analysis of patient data, drafting and revision of the manuscript, final approval of the manuscript