New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2021 Mar 04 [Epub ahead of print]

Kiril Trpkov, Ondrej Hes, Sean R Williamson, Adebowale J Adeniran, Abbas Agaimy, Reza Alaghehbandan, Mahul B Amin, Pedram Argani, Ying-Bei Chen, Liang Cheng, Jonathan I Epstein, John C Cheville, Eva Comperat, Isabela Werneck da Cunha, Jennifer B Gordetsky, Sounak Gupta, Huiying He, Michelle S Hirsch, Peter A Humphrey, Payal Kapur, Fumiyoshi Kojima, Jose I Lopez, Fiona Maclean, Cristina Magi-Galluzzi, Jesse K McKenney, Rohit Mehra, Santosh Menon, George J Netto, Christopher G Przybycin, Priya Rao, Qiu Rao, Victor E Reuter, Rola M Saleeb, Rajal B Shah, Steven C Smith, Satish Tickoo, Maria S Tretiakova, Lawrence True, Virginie Verkarre, Sara E Wobker, Ming Zhou, Anthony J Gill

Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. ., Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Plzen, Plzen, Czech Republic., Robert J Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA., Department of Pathology, Yale School of Medicine, New Haven, CT, USA., Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany., Department of Pathology, Faculty of Medicine, University of British Columbia, Royal Columbian Hospital, Vancouver, BC, Canada., Department of Pathology and Laboratory Medicine and Urology, University of Tennessee Health Science, Memphis, TN, USA., Departments of Pathology and Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA., Departments of Pathology, Urology and Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA., Department of Pathology, Mayo Clinic, Rochester, MN, USA., Department of Pathology, Hôpital Tenon, Sorbonne University, Paris, France., Pathology Department, Rede D'OR-Sao Luiz, Sao Paulo, SP, Brazil., Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Pathology, Health Science Center, Peking University, Beijing, China., Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Departments of Pathology, Urology, Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Human Pathology, Wakayama Medical University, Wakayama, Japan., Department of Pathology, Cruces University Hospital, Biocruces-Bizkaia Institute, Bizkaia, Spain., Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia., Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA., Department of Pathology and Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA., Department of Surgical Pathology, Tata Memorial Hospital, Parel, and Homi Bhabha National Institute, Mumbai, India., Department of Pathology MD Anderson Cancer Center, Houston, TX, USA., Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China., Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Departments of Pathology and Urology, VCU School of Medicine, Richmond, VA, USA., Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA., Department of Pathology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université de Paris, PARCC, INSERM, Equipe Labellisée par la Ligue contre le Cancer, Paris, France., Departments of Pathology and Laboratory Medicine and Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Department of Pathology, Tufts Medical Center, Boston, MA, USA., Sydney Medical School, University of Sydney, Sydney, NSW, Australia.