Pitfalls in Diagnosis of Myoepithelial Carcinoma of Salivary Glands: A Study of 3 Cases with Cytologic-histologic Correlation and Molecular Analysis

Myoepithelial carcinoma (MECA) represents < 1% percent of salivary gland (SG) tumors with a mean age of 55 years. These tumors can arise de novo or in association with pre-existing pleomorphic Adenoma (PA). The cytologic features of MECA overlap with other SG neoplasms including the more common benign entities like PA and myoepithelioma and can pose a diagnostic challenge.

A database search for MECA was performed spanning 10 years. 3 cases qualified with available cyto-histologic correlation. All were morphologically MECA with one case diagnosed as MECA ex-PA. The cases were subjected to a comprehensive immunohistochemical and molecular evaluation (Case#1 has been previously reported and published in head and neck pathology in 2021).

A comparative analysis of these cases is presented in Table 1. All three cases were initially diagnosed as PA on cytology. On review of cytology slides, presence of metachromatic stromal fragments and bland myoepithelial cells was found to be the most common diagnostic pitfall. S100 was positive in all cases while myosin, p63, and GFAP were variably positive. Molecular analysis revealed novel, previously undescribed mutations in the three cases. Additionally, two of three cases expressed PD-L1, suggesting a role for immunotherapy in treatment.

Cytomorphology of MECA is poorly described in literature and can pose a diagnostic challenge due to overlapping features with salivary gland benign neoplasms. A conclusive diagnosis on cytology is often not possible. However, a high cellularity, predominant oncocytoid/ myoepithelial cell population on smears and cell block, along with a strong clinical and radiologic suspicion for malignant salivary gland tumor, should alert the cytopathologist and help avoid an erroneous benign diagnosis on cytology.