Adult Mixed Epithelial and Stromal Tumor of the Kidney Harbors Recurrent Whole Chromosome 12 Gain

Mixed epithelial and stromal tumor (MEST), including adult cystic nephroma (CN), is an uncommon benign renal neoplasm that mostly occurs in middle-aged women. To date, a comprehensive molecular genetic investigation of MEST and/or adult CN has not been performed. Fourteen archival cases of MEST were identified, and comprehensive clinicopathologic and molecular characterization was performed. Tumors arose only in female patients (median: 49 y, range: 35 to 82 y) and showed variable admixtures of bland epithelial glands, tubules, and cysts within an ovarian-type spindle cell stroma. In total, copy number alterations (CNAs) were detected in 6/14 (42.9%) MEST by next-generation sequencing (N=5) and karyotype (N=1). Relative whole-chromosome gains of chromosome 12 were identified in 5/14 (35.7%) MESTs. Two cases showed gains on chromosome 12 alone. Three cases with chromosome 12 gains harbored additional nonrecurrent CNAs. A single case without chromosome 12 gain harbored a relative whole-chromosome gain of chromosome 8 and loss of chromosome 21. No clinically actionable alterations were identified, and there were no alterations in renal neoplasia-related genes (eg, VHL, FH, SDHA/B/D, ELOC, TFEB, TFE3, DICER1, MET, MTOR, and TSC1/2). Of 13 cases with follow-up (median: 81.2 mo), no recurrences were identified after surgery. Although not entirely sensitive nor specific, chromosome 12 gain is the first evidence of recurrent alterations in MEST, supporting its classification as a neoplasm.