Low-grade oncocytic tumor of kidney harboring TSC/MTOR mutation: clinicopathologic, immunohistochemical and molecular characteristics support a distinct entity.

Abstract

Low-grade oncocytic tumor (LOT) has recently been described as a distinct renal tumor. LOT shows consistent morphologic features and a CK7-positive/CD117-negative immunophenotype. To examine the clinicopathological, immunohistochemical, and molecular features of LOT, we searched our institutional archives and identified seven cases of LOT. All patients were female, with a mean age of 66years (range 44-79years). The average tumor size was 3.2cm (range 1.6-5.5cm). Macroscopically, the tumors showed tan-brown and solid cut surfaces. Microscopically, the tumors showed compact nested to solid growth pattern, three cases with areas of edematous stroma containing loosely connected small clusters, cords or dispersed single tumor cells. The tumor cells had uniformly round to oval nuclei with eosinophilic cytoplasm, and showed perinuclear halos. Two cases focally had nuclear irregularities and binucleated cells were occasionally seen in three cases. Immunohistochemically, diffuse positivity for CK7 and lack of CD117 expression were present in all cases. All of the tumors were negative for CD10, CK20, vimentin, CA9, TFE3, TFEB, HMB45, and Melan-A. All tumors were positive for MTOR and negative for Cathepsin-K. FH and SDHB were retained. Next generation sequencing identified genetic variations in the MTOR pathway related genes: TSC1 (4/7), TSC2 (5/7), and MTOR (1/7). All patients were alive and without disease progression, after a mean follow-up of 43months (range 6-89months). LOT is an uncommon eosinophilic renal neoplasm with unique morphological and characteristic immunophenotypic features, and may represent an emerging separate renal entity characterized by mutations in the TSC/MTOR pathway.