Low-grade oncocytic tumor (LOT) of the kidney has recently emerged as a potential novel tumor type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumors. Seventeen tumors (1 man, 16 women, 9 previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumor cells loosely stretched in edematous stroma, and the above IHC features), were analyzed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumors harbored at least one alteration in either TSC1 (n= 7, 41%), TSC2 (n=2, 12%), MTOR (n=5, 29%), or PIK3CA (n=4, 24%). Four tumors harbored a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration, and one tumor with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16/16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumors. Recurrent tuberous sclerosis / MTOR pathway gene alterations in LOT supports its consideration as a distinct morphologic, immunohistochemical, and genetic entity. PIK3CA is another pathway member that may be altered in these tumors. Further study will be necessary to determine whether tumor behavior or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.
Histopathology. 2022 Oct 08 [Epub ahead of print]
Sean R Williamson, Ondrej Hes, Kiril Trpkov, Aditi Aggarwal, Abhishek Satapathy, Sourav Mishra, Shivani Sharma, Ankur Sangoi, Liang Cheng, Mahmut Akgul, Muhammad Idrees, Albert Levin, Sudha Sadasivan, Pilar San Miguel Fraile, Joanna Rogala, Eva Comperat, Daniel M Berney, Stela Bulimbasic, Jesse K McKenney, Shilpy Jha, Nakul Y Sampat, Sambit K Mohanty
Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA., Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic., Department of Pathology and Laboratory Medicine, Alberta Precision Labs and University of Calgary, Calgary, Alberta, Canada., CORE Diagnostics, Gurgaon, Haryana, India., Advanced Medical Research Institute, Bhubaneswar, Odisha, India., Department of Pathology, El Camino Hospital, Mountain View, California, USA., Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA., Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA., Hospital Álvaro Cunqueiro, Vigo, Pontevedra, Spain., Regional Specialist Hospital, Wroclaw, Poland., Department of Pathology, Hôpital Tenon, Sorbonne University, Paris VI, Paris, France., Department of Cellular Pathology, Bartshealth NHS Trust and Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Department of Pathology, School of Medicine, Zagreb, Croatia.