Epithelial-myoepithelial carcinoma (EMC) can be a challenging diagnosis due to a lack of obvious invasion and bland cytology. We report an unusual case of a low-grade EMC with prominent fibrous stroma, an extensive solid-oncocytic differentiation and limited areas of morphological clearly identifiable characteristic biphasic (tubular) differentiation, clear cells and PAS-positive secretions/calcifications. Both areas were investigated by next generation sequencing (Oncomine comprehensive assay) and revealed a typical concordant HRAS p.Q61R mutation. An additional heterogeneous ARID1A (p.E672*) terminating mutation with loss of heterozygosity, which could be visualized predominantly in the solid-oncocytic differentiation by immunohistochemical loss of ARID1A protein expression, was found. This is the first case of an EMC of the salivary gland to be described with two separate tumor clones involving concordant HRAS and heterogeneous ARID1A mutations. The latter seem to be a "second hit" and was predominantly found in the solid-oncocytic differentiation, suggesting a potential morpho-molecular association.

Department of Otorhinolaryngology Head and Neck Surgery University Hospital Zurich Zurich Switzerland

Department of Pathology and Molecular Pathology University Hospital Zurich Schmelzbergstr 12 8091 Zurich Switzerland

Institute of Pathology Enge Zurich Switzerland

Sikl's Department of Pathology Faculty of Medicine in Plzen Charles University Pilsen Czech Republic

University of Zurich Zurich Switzerland

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

SalvGlandDx - a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets