Atypical and worrisome histological features in pleomorphic adenoma: challenging and potentially significant diagnostic pitfall.

Pleomorphic adenoma (PA), the most prevalent salivary gland tumor, exhibits a diverse histological spectrum characterized by epithelial, myoepithelial, and mesenchymal patterns, and secretory products. However, a subset of PAs presents microscopic features suggestive of malignancy, leading to challenging and potentially significant diagnostic pitfalls. A comprehensive retrospective analysis was conducted on the Salivary Gland Tumor Registry, compiled by the authors. A total of 104 cases diagnosed between 1960 and 2023 were retrieved. Clinical findings, pathological features, and molecular genetic results were analyzed. In the study of 104 PA cases, 23 (22.1%) presented features suggestive of pseudoinvasion, with satellite nodules being the most common (43.5%) along with capsular penetration, irregular growth, pseudopodia, lipomatous changes, and vascular permeation. Features of pseudomalignant cytomorphology were found in 97 cases (93.3%), characterized by increased cellularity, cellular atypia, heightened proliferative activity, oncocytic metaplasia, and necrosis. Additionally, 30 cases (28.8%) displayed features resembling other defined malignant salivary gland tumors, particularly myoepithelial carcinoma, adenoid cystic carcinoma, and polymorphous adenocarcinoma. Despite PA's generally straightforward diagnosis, cases with these features may be mistakenly interpreted as malignant tumors. The shared morphocytological features underscore the complexity of an accurate diagnosis, emphasizing the need for meticulous examination and a comprehensive assessment, incorporating morphological, molecular, and immunohistochemical analyses to differentiate between benign and malignant salivary gland tumors, in selected cases.