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

Trpkov K, Hes O, Williamson SR, Adeniran AJ, Agaimy A, Alaghehbandan R, Amin MB, Argani P, Chen YB, Cheng L, Epstein JI, Cheville JC, Comperat E, Da Cunha IW, Gordetsky JB, Gupta S, He H, Hirsch MS, Humphrey PA, Kapur P, Kojima F, Lopez JI, Maclean F, Magi-Galluzzi C, Mckenney JK, Mehra R, Menon S, Netto GJ, Przybycin CG, Rao P, Rao Q, Reuter VE, Saleeb RM, Shah RB, Smith SC, Tickoo S, Tretiakova MS, True L, Verkarre V, Wobker SE, Zhou M, Gill AJ (2021)

Publication Type: Journal article

Publication year: 2021

Journal

DOI: 10.1038/s41379-021-00779-w

Abstract

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.

Authors with CRIS profile

Involved external institutions

University of Calgary Canada (CA) Univerzita Karlova v Praze / Charles University in Prague Czech Republic (CZ) Cleveland Clinic United States (USA) (US) Yale University United States (USA) (US) University of British Columbia Canada (CA) The University of Tennessee Health Science Center United States (USA) (US) Johns Hopkins Hospital United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Indiana University – Purdue University Indianapolis United States (USA) (US) Mayo Clinic United States (USA) (US) University of Paris 4 - Paris-Sorbonne / Université paris IV Paris-Sorbonne France (FR) Hospitais Rede D'Or São Luiz Brazil (BR) Vanderbilt University United States (USA) (US) Peking University (PKU) / 北京大学 China (CN) Harvard University United States (USA) (US) University of Texas Southwestern Medical Center (UT Southwestern) United States (USA) (US) Wakayama Medical University Japan (JP) Hospital Universitario de Cruces Spain (ES) Macquarie University Australia (AU) University of Alabama at Birmingham (UAB) United States (USA) (US) University of Michigan United States (USA) (US) Tata Memorial Hospital India (IN) University of Texas MD Anderson Cancer Center United States (USA) (US) Nanjing University China (CN) University of Toronto Canada (CA) University of Washington United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) Tufts University United States (USA) (US) University of Sydney (USYD) Australia (AU) Virginia Commonwealth University (VCU) United States (USA) (US)

How to cite

APA:

Trpkov, K., Hes, O., Williamson, S.R., Adeniran, A.J., Agaimy, A., Alaghehbandan, R.,... Gill, A.J. (2021). New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia. Modern Pathology. https://doi.org/10.1038/s41379-021-00779-w

MLA:

Trpkov, Kiril, et al. "New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia." Modern Pathology (2021).

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