BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16INK4 and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein. Forty-one of 48 cases (85%) showed BRAF V600E mutation; none of the other BRAF variants was detected. Of 41 BRAF-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80%, specificity 100%); in all cases we detected p16INK4 expression regardless of BRAF mutation status. All epithelial-predominant nephroblastomas were BRAF-wild-type and none expressed VE1. The following features were associated with BRAF V600E mutation: older patients (p=0.01), female predominance (p=0.005) and the presence of a predominantly acinar architecture (p=0.003). In summary, BRAF-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20%) of BRAF-mutated metanephric adenomas was not detected by VE1 immunostaining.

Department of Pathological Anatomy and Histopathology School of Medicine Polytechnic University of The Marche Region Ancona Italy

Department of Pathology and Laboratory Medicine Henry Ford Health System Detroit Michigan USA

Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis Indiana USA

Department of Pathology Charles University Hospital Plzeň Pilsen Czech Republic

Department of Pathology Emory University School of Medicine Atlanta Georgia USA

Department of Pathology Groupe Hospitalier Pitié Salpêtrière Paris France

Department of Pathology Pederzoli Hospital Peschiera Italy

Department of Pathology University of Verona Verona Italy

Departments of Pathology and Laboratory Medicine Case Western Reserve University Cleveland Ohio USA

Michigan Center for Translational Pathology University of Michigan Ann Arbor Michigan USA

Unit of Anatomical Pathology Department of Surgery Faculty of Medicine Cordoba Spain and Champalimaud Clinical Center Lisbon Portugal

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New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia

KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas