Papillary-Predominant FLCN-Mutated Renal Epithelial Neoplasm in Birt-Hogg-Dubé Syndrome

Papillary architecture is rare in FLCN-mutated renal epithelial neoplasms in Birt-Hogg-Dubé syndrome. We report a papillary-predominant FLCN-mutated renal epithelial neoplasm in a 79-year-old woman with known Birt-Hogg-Dubé syndrome and a pathogenic germline FLCN frameshift mutation, who presented with bilateral renal masses and underwent right partial nephrectomy. Gross examination revealed a 2.5 cm well-circumscribed yellow mass confined to the kidney (pT1a). Histologically, the tumor demonstrated predominantly papillary architecture with focal cystic change and rare nested oncocytic cells at the periphery. Fibrovascular cores were lined by oncocytic cells admixed with clear cells, the latter more prominent along the apical surface. Tumor cells showed round to oval nuclei with prominent nucleoli, focal coarse eosinophilic cytoplasmic granules, multifocal nuclear palisading, and rare multinucleated cells. The background renal parenchyma contained cysts lined by hobnail oncocytic cells with focal clear cell change. The tumor was positive for PAX8, AMACR, GPNMB, and cathepsin K, and negative for KIT, KRT7, and CA9, with diffuse weak-to-moderate TFE3 staining. The clinical history, morphology, and immunophenotype support a diagnosis of FLCN-mutated renal epithelial neoplasm with papillary features. This report highlights potential diagnostic pitfalls and the morphological heterogeneity of FLCN-mutated tumors.