Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities.

• Keywords
• Emerging, Eosinophilic, Oncocytic, Renal neoplasms, Uropathologists,
• MeSH
• Carcinoma, Renal Cell * pathology   diagnosis   MeSH
• Humans MeSH
• Biomarkers, Tumor analysis   MeSH
• Kidney Neoplasms * pathology   diagnosis   MeSH
• Adenoma, Oxyphilic * pathology   diagnosis   MeSH
• Pathologists * MeSH
• Surveys and Questionnaires MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

The category of "oncocytic renal tumors'' includes well-recognized entities, such as renal oncocytoma (RO) and eosinophilic variant of chromophobe renal cell carcinoma (eo-ChRCC), as well as a group of "gray zone" oncocytic tumors, with overlapping features between RO and eo-ChRCC that create ongoing diagnostic and classification problems. These types of renal tumors were designated in the past as "hybrid oncocytoma-chromophobe tumors". In a recent update, the Genitourinary Pathology Society (GUPS) proposed the term "oncocytic renal neoplasm of low malignant potential, not further classified", for such solitary and sporadic, somewhat heterogeneous, but relatively indolent tumors, with equivocal RO/eo-ChRCC features. GUPS also proposed that the term "hybrid oncocytic tumor" be reserved for tumors found in a hereditary setting, typically arising as bilateral and multifocal ones (as in Birt-Hogg-Dubé syndrome). More recent developments in the "gray zone" of oncocytic renal tumors revealed that potentially distinct entities may have been "hidden" in this group. Recent studies distinguished two new entities: "Eosinophilic Vacuolated Tumor" (EVT) and "Low-grade Oncocytic Tumor" (LOT). The rapidly accumulated evidence on EVT and LOT has validated the initial findings and has expanded the knowledge on these entities. Both are uniformly benign and are typically found in a sporadic setting, but rarely can be found in patients with tuberous sclerosis complex. Both have readily distinguishable morphologic and immunohistochemical features that separate them from similar renal tumors, without a need for detailed molecular studies. These tumors very frequently harbor TSC/MTOR mutations that are however neither specific nor restricted to these two entities. In this review, we outline a proposal for a working framework on how to classify such low-grade oncocytic renal tumors. We believe that such framework will facilitate their handling in practice and will stimulate further discussions and studies to fully elucidate their spectrum.

• MeSH
• Carcinoma, Renal Cell * genetics   MeSH
• Kidney pathology   MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Kidney Neoplasms * genetics   MeSH
• Adenoma, Oxyphilic * pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

A number of recently described renal tumor entities share an eosinophilic/oncocytic morphology, somewhat solid architectural growth pattern, and tendency to present as low-stage tumors. The vast majority of such tumors follow a non-aggressive clinical behavior. In this review, we discuss the morphological, immunohistochemical, and molecular genetic profiles of the three most recent novel/emerging renal entities associated with TSC/mTOR pathway mutations. These are eosinophilic solid and cystic renal cell carcinoma, eosinophilic vacuolated tumors, and low-grade oncocytic tumors, which belong to a heterogeneous group of renal tumors, demonstrating mostly solid architecture, eosinophilic/oncocytic cytoplasm, and overlapping morphological and immunohistochemical features between renal oncocytoma and chromophobe renal cell carcinoma. All three tumors also share a molecular genetic background with mutations in the mTORC1 pathway (TSC1/TSC2/mTOR/RHEB). Despite the common genetic background, it appears that the tumors with TSC/mTOR mutations represent a diverse group of distinct renal neoplasms.

• Keywords
• ESC, EVT, LOT, chromophobe, eosinophilic, kidney, mTOR, oncocytic, renal, tumor,
• Publication type
• Journal Article MeSH
• Review MeSH

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in renal neoplasia, particularly focusing on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. In the era of evolving histo-molecular classification of renal neoplasia, morphology is still key. However, entities (or groups of entities) are increasingly characterized by specific molecular features, often associated either with recognizable, specific morphologies or constellations of morphologies and corresponding immunohistochemical profiles. The correct diagnosis has clinical implications leading to better prognosis, potential clinical management with targeted therapies, may identify hereditary or syndromic associations, which may necessitate appropriate genetic testing. We hope that this undertaking will further facilitate the identification of these entities in practice. We also hope that this update will bring more clarity regarding the evolving classification of renal neoplasia and will further reduce the category of "unclassifiable renal carcinomas/tumors". We propose three categories of novel entities: (1) "Novel entity", validated by multiple independent studies; (2) "Emerging entity", good compelling data available from at least two or more independent studies, but additional validation is needed; and (3) "Provisional entity", limited data available from one or two studies, with more work required to validate them. For some entities initially described using different names, we propose new terminologies, to facilitate their recognition and to avoid further diagnostic dilemmas. Following these criteria, we propose as novel entities: eosinophilic solid and cystic renal cell carcinoma (ESC RCC), renal cell carcinoma with fibromyomatous stroma (RCC FMS) (formerly RCC with leiomyomatous or smooth muscle stroma), and anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC). Emerging entities include: eosinophilic vacuolated tumor (EVT) and thyroid-like follicular renal cell carcinoma (TLFRCC). Finally, as provisional entities, we propose low-grade oncocytic tumor (LOT), atrophic kidney-like lesion (AKLL), and biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC).

• MeSH
• Humans MeSH
• Kidney Neoplasms classification   diagnosis   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH

Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others. Papillary RCC type 2 is now known to include likely several different molecular entities, such as fumarate hydratase (FH) deficient RCC. In MIT family translocation RCC, an increasing number of gene fusions are now described. Some TFE3 fusion partners, such as NONO, GRIPAP1, RBMX, and RBM10 may show a deceptive fluorescence in situ hybridization result due to the proximity of the genes on the same chromosome. FH and succinate dehydrogenase deficient RCC have implications for patient counseling due to heritable syndromes and the aggressiveness of FH-deficient RCC. Immunohistochemistry is increasingly available and helpful for recognizing both. Emerging tumor types with strong evidence for distinct diagnostic entities include eosinophilic solid and cystic RCC and TFEB/VEGFA/6p21 amplified RCC. Other emerging entities that are less clearly understood include TCEB1 mutated RCC, RCC with ALK rearrangement, renal neoplasms with mutations of TSC2 or MTOR, and RCC with fibromuscular stroma. In metastatic RCC, the role of molecular studies is not entirely defined at present, although there may be an increasing role for genomic analysis related to specific therapy pathways, such as for tyrosine kinase or MTOR inhibitors.

• MeSH
• Neoplastic Syndromes, Hereditary diagnosis   genetics   metabolism   pathology   MeSH
• In Situ Hybridization, Fluorescence MeSH
• Immunohistochemistry MeSH
• Carcinoma, Renal Cell diagnosis   genetics   metabolism   pathology   MeSH
• Pathology, Clinical MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Pathology, Molecular MeSH
• Mutation MeSH
• Biomarkers, Tumor * genetics   metabolism   MeSH
• Kidney Neoplasms diagnosis   genetics   metabolism   pathology   MeSH
• Prognosis MeSH
• Societies, Medical MeSH
• Urology MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Consensus Development Conference MeSH
• Practice Guideline MeSH
• Names of Substances
• Biomarkers, Tumor * MeSH

Renal epithelial cell tumors are composed of a heterogeneous group of tumors with variable morphologic, immunohistochemical, and molecular features. A "histo-molecular" approach is now an integral part of defining renal tumors, aiming to be clinically and therapeutically pertinent. Most renal epithelial tumors including the new and emerging entities have distinct molecular and genetic features which can be detected using various methods. Most renal epithelial tumors can be diagnosed easily based on pure histologic findings with or without immunohistochemical examination. Furthermore, molecular-genetic testing can be utilized to assist in arriving at an accurate diagnosis. In this review, we presented the most current knowledge concerning molecular-genetic aspects of renal epithelial neoplasms, which potentially can be used in daily diagnostic practice.

• Keywords
• kidney, molecular genetic features, practical approach, renal cell carcinoma, review,
• Publication type
• Journal Article MeSH
• Review MeSH