TFEB-Amplified Renal Cell Carcinoma With Focal Rhabdoid Features, Hyaline Globules, Giant Tumor Cells, and Osseous Metaplasia.

Abstract

TFEB-amplified renal cell carcinoma (RCC) is a rare, molecularly defined RCC, characterized by amplification of the TFEB gene on chromosome 6p21.1, with fewer than 100 tumors reported to date. Herein, we report a TFEB-amplified RCC with focal rhabdoid features, hyaline globules, giant tumor cells, and osseous metaplasia. This tumor further expands the histological spectrum of TFEB-amplified RCC. A 59-year-old man underwent radical nephrectomy for a 7.6-cm left renal mass. Histologically, the tumor demonstrated predominantly papillary architecture (90%) with focal solid areas (10%). Tumor cells showed voluminous eosinophilic cytoplasm and prominent nucleoli. Additional findings included multifocal rhabdoid features (10%), intracellular hyaline globules, giant tumor cells, occasionally with multinucleation, osseous metaplasia, psammomatous calcifications, and focal tumor necrosis (5%). The tumor was classified as World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade 4 and staged as pT2aNx. Immunohistochemically, the tumor cells were positive for PAX8, AMACR, and HNF1β, with rare Melan-A expression, and negative for keratin 7, CA9, GATA3, p63, ALK, cathepsin K, HMB45, and TFE3. RCC not otherwise specified (NOS) was initially diagnosed, and molecular testing was subsequently performed to further assist in the diagnosis. Chromosomal microarray analysis demonstrated amplification of chromosome 6p21.1 involving TFEB and other genes with a reported copy number of ≥7, which was confirmed by fluorescence in situ hybridization demonstrating TFEB copy-number gain with up to 9 TFEB signals per nucleus. Based on the morphology, immunoprofile, and molecular findings, the tumor was classified as TFEB-amplified RCC. The patient subsequently developed widespread metastatic disease and received radiotherapy and systemic treatment. He remains alive with progression of disease at 45 months of follow-up.