Mucoepidermoid Carcinoma of the Minor Salivary Glands Diagnosed by High-Definition Ultrasound and Fine-Needle Aspiration: A Milan System-Based Retrospective Study

<b>Background/Objectives</b>: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the minor salivary glands, often affecting the hard palate. Preoperative diagnosis and surgical planning are challenging due to anatomical complexity and limitations in sampling, generally obtained by fine-needle aspiration (FNA). This study retrospectively evaluated the diagnostic and therapeutic performance of a high-definition ultrasound (HDUS)-guided fine-needle aspiration cytology/biopsy (FNAC/FNAB) protocol in diagnosing intraoral MEC, based on the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), with the relative clinical outcomes. <b>Methods</b>: A cohort of 64 patients with histologically confirmed MEC of the minor salivary glands, treated between 2000 and 2022, was retrospectively analyzed. All patients underwent HDUS-guided FNAC/FNAB, imaging (CT, MRI, and panoramic X-ray), and subsequent surgical treatment. The cytological specimens were classified using the MSRSGC. Surgical margins, histopathological findings, lymph node status, and follow-up outcomes were recorded. <b>Results</b>: Of 64 MECs, 42 cases were finally diagnosed as low-grade (LG)/intermediate grade (IG) and 22 as high-grade (HG) carcinomas, using a two-tier histological classification system. HDUS accurately delineated the lesion size, infiltration depth, and bone proximity, with excellent correlation with surgical specimens (difference ≤ 0.6 mm). MSRSGC classification distributed the cases across all categories, with 28 classified as malignant (category VI). Repeat FNAC improved the diagnostic yield in non-diagnostic and atypical cases. FNAB confirmed the cytological findings in all cases, with immunohistochemistry investigation with Ki-67 supporting tumor grading. Surgical margins were clear in all resections. Lymph node metastases were identified in all patients who underwent neck dissection (<i>n</i> = 18), all with HG-MEC. No recurrences occurred among the LG/IG-MEC patients during a median 2-year follow-up. <b>Conclusions</b>: The combined use of HDUS and FNAC/FNAB, interpreted through the MSRSGC framework, offers a highly accurate, minimally invasive approach for preoperative diagnosis and surgical planning in intraoral MEC. HDUS-guided cytology significantly improves diagnostic reliability, particularly in LG/IG and cystic variants, facilitating tailored surgical management. Also, the clinical outcomes may support the possibility of using a simplified grading classification for two histopathological types.