Review ArticlesThe Histologic Diversity of Chromophobe Renal Cell Carcinoma With Emphasis on Challenges Encountered in Daily PracticeAlaghehbandan, Reza MD, MSc, FRCPC, FCAP, FACE, FIAC*; Williamson, Sean R. MD†; McKenney, Jesse K. MD†; Hes, Ondrej MD, PhD‡ Author Information *Department of Pathology, Faculty of Medicine, Royal Columbian Hospital, University of British Columbia, Vancouver, BC, Canada †Robert J. Tomsich Pathology and Laboratory Medicine Institute and Glickman Urological Institute, Cleveland Clinic, Cleveland, OH ‡Department of Pathology, Faculty of Medicine and University Hospital in Plzen, Charles University in Prague, Plzen, Czech Republic Supported in part by the Charles University Research Fund (Cooperation Program, research area SURG), the Institutional Research Fund of University Hospital Plzen (Faculty Hospital in Plzen-NPl 00669806). The authors have no conflicts of interest to disclose. Reprints: Ondrej Hes, MD, PhD, Department of Pathology, Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, Plzen 304 60, Czech Republic (e-mail: [email protected]). All figures can be viewed online in color at www.anatomicpathology.com. Advances In Anatomic Pathology 29(4):p 194-207, July 2022. | DOI: 10.1097/PAP.0000000000000349 Buy Metrics Abstract Chromophobe renal cell carcinoma (ChRCC) is the third most common renal cell carcinoma in adults. The aim of this review is to provide a comprehensive overview highlighting the broad morphologic spectrum of ChRCC, and offer a practical approach for handling cases in daily practice. For the purpose of this review, we classify ChRCC subtypes as (1) classic, (2) eosinophilic, (3) sarcomatoid, and (4) other rare patterns. The concept of eosinophilic ChRCC has significantly evolved, yet it still is one of the major diagnostic challenges pathologists face in routine practice due to its morphologic overlap with renal oncocytoma. Rare patterns of ChRCC have been described over the last few decades, showing a wide histologic spectrum including those with adenomatoid microcystic pigmented, multicystic, neuroendocrine, small cell, and papillary features. ChRCC represents a heterogenous group of neoplasms, demonstrating varied but unique morphologic and genetic profiles. Although the field of ChRCC knowledge is still evolving, rare patterns can present diagnostic challenges if they are not known to pathologists and/or clinicians. Proper and generous tumor sampling along with careful histologic examination allow for recognition of these rare morphologies. The role of routine molecular testing appears to be limited. From a clinical management standpoint, the rare patterns of ChRCC seem to have no definite clinical implications at present and likely can be managed similarly to usual ChRCC. Finally, we will discuss distinctive novel/emerging renal neoplasms previously considered under the spectrum of ChRCC, low-grade oncocytic renal tumor and eosinophilic vacuolated tumor, with regard to their current significance and implications for future classification strategies. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.