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Browsing by Author "McKenney, Jesse K."

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    Diagnostic Criteria for Oncocytic Renal Neoplasms: A Survey of Urologic Pathologists
    (Elsevier, 2017-05) Williamson, Sean R.; Gadde, Ramya; Trpkov, Kiril; Hirsch, Michelle S.; Srigley, John R.; Reuter, Victor E.; Cheng, Liang; Kunju, L. Priya; Barod, Ravi; Rogers, Craig G.; Delahunt, Brett; Hes, Ondrej; Eble, John N.; Zhou, Ming; McKenney, Jesse K.; Martignoni, Guido; Fleming, Stewart; Grignon, David J.; Moch, Holger; Gupta, Nilesh S.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Renal oncocytoma and chromophobe renal cell carcinoma have been long recognized as distinct tumors; however, it remains unknown if uniform diagnostic criteria are used to distinguish these tumor types in practice. A survey was distributed to urologic pathologists regarding oncocytic tumors. Responses were received from 17 of 26 invitees. Histologically, more than 1 mitotic figure was regarded as most worrisome (n = 10) or incompatible (n = 6) with oncocytoma diagnosis. Interpretation of focal nuclear wrinkling, focal perinuclear clearing, and multinucleation depended on extent and did not necessarily exclude oncocytoma if minor. Staining techniques most commonly used included the following: cytokeratin 7 (94%), KIT (71%), vimentin (65%), colloidal iron (59%), CD10 (53%), and AMACR (41%). Rare cytokeratin 7–positive cells (≤5%) were regarded as most supportive of oncocytoma, although an extent excluding oncocytoma was not universal. Multiple chromosomal losses were most strongly supportive for chromophobe renal cell carcinoma diagnosis (65%). Less certainty was reported for chromosomal gain or a single loss. For tumors with mixed or inconclusive features, many participants use an intermediate diagnostic category (82%) that does not label the tumor as unequivocally benign or malignant, typically “oncocytic neoplasm” or “tumor” with comment. The term “hybrid tumor” was used variably in several scenarios. A slight majority (65%) report outright diagnosis of oncocytoma in needle biopsies. The morphologic, immunohistochemical, and genetic characteristics that define oncocytic renal tumors remain incompletely understood. Further studies correlating genetics, behavior, and histology are needed to define which tumors truly warrant classification as carcinomas for patient counseling and follow-up strategies.
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    New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia
    (Elsevier, 2021) Trpkov, Kiril; Hes, Ondrej; Williamson, Sean R.; Adeniran, Adebowale J.; Agaimy, Abbas; Alaghehbandan, Reza; Amin, Mahul B.; Argani, Pedram; Chen, Ying-Bei; Cheng, Liang; Epstein, Jonathan I.; Cheville, John C.; Comperat, Eva; Werneck da Cunha, Isabela; Gordetsky, Jennifer B.; Gupta, Sounak; He, Huiying; Hirsch, Michelle S.; Humphrey, Peter A.; Kapur, Payal; Kojima, Fumiyoshi; Lopez, Jose I.; Maclean, Fiona; Magi-Galluzzi, Cristina; McKenney, Jesse K.; Mehra, Rohit; Menon, Santosh; Netto, George J.; Przybycin, Christopher G.; Rao, Priya; Rao, Qiu; Reuter, Victor E.; Saleeb, Rola M.; Shah, Rajal B.; Smith, Steven C.; Tickoo, Satish; Tretiakova, Maria S.; True, Lawrence; Verkarre, Virginie; Wobker, Sara E.; Zhou, Ming; Gill, Anthony J.; Pathology and Laboratory Medicine, School of Medicine
    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.
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    Reappraisal of Morphological Differences between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-Deficient Renal Cell Carcinoma
    (Wolters Kluwer, 2018-03) Ohe, Chisato; Smith, Steven C.; Sirohi, Deepika; Divatia, Mukul; de Peralta-Venturina, Mariza; Paner, Gladell P.; Agaimy, Abbas; Amin, Mitual B.; Argani, Pedram; Chen, Ying-Bei; Cheng, Liang; Colecchia, Maurizio; Compérat, Eva; Werneck da Cunha, Isabela; Epstein, Jonathan I.; Gill, Anthony J.; Hes, Ondřej; Hirsch, Michelle; Jochum, Wolfram; Kunju, Lakshmi P.; Maclean, Fiona; Magi-Galluzzi, Cristina; McKenney, Jesse K.; Mehra, Rohit; Nesi, Gabriella; Osunkoya, Adeboye O.; Picken, Maria M.; Rao, Priya; Reuter, Victor E.; Guilherme de Oliveira Salles, Paulo; Schultz, Luciana; Tickoo, Satish K.; Tomlins, Scott A.; Trpkov, Kiril; Amin, Mahul B.; Medicine, School of Medicine
    Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.
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    Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms
    (Elsevier, 2016-11) Bonsib, Stephen M.; Boils, Christie; Gokden, Neriman; Grignon, David; Gu, Xin; Higgins, John P. T.; Leroy, Xavier; McKenney, Jesse K.; Nasr, Samih H.; Phillips, Carrie; Sangoi, Ankur R.; Wilson, Jon; Zhang, Ping L.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Tuberous sclerosis complex (TSC) results from mutation of TSC1 or TSC2 that encode for hamartin and tuberin. It affects the kidneys often in advance of extra-renal stigmata. We studied 14 TSC cases, and 4 possible TSC cases with multiple angiomyolipomas (AMLs) for hamartin and tuberin protein expression to determine if the staining profile could predict mutation status or likelihood of TSC with renal-limited disease. The 18 cases included 15 nephrectomies and 1 section of 6 TSC-associated renal cell carcinomas (RCC). Controls included the non-neoplastic kidney in 5 tumor nephrectomies, 4 sporadic cases of AML and 6 clear cell RCCs. In the 14 TSC cases, 9 had AMLs, 9 had RCCs, 5 had polycystic kidney disease and 8 had eosinophilic cysts (EC) lined by large eosinophilic cells. The controls and study cases showed luminal staining of proximal tubules (PT) and peripheral membrane staining in distal tubules/collecting ducts for hamartin and cytoplasmic staining for tuberin. Eosinophilic cysts had a luminal PT-like stain with hamartin and a cytoplasmic reaction for tuberin. Hamartin stained myoid cells in all AMLs. Tuberin was negative in all but 1AML, an epithelioid AML. All but 1 RCC were positive for tuberin; 13 RCCs (7 TSC/6 non-TSC) were negative for hamartin and 4 showed a weak reaction. We conclude that the ECs of TSC are proximal tubule-derived. The hamartin and tuberin staining profiles of AMLs and most RCCs are reciprocal precluding prediction of the mutation in TSC, and fail to predict if a patient with multifocal AML has TSC.
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    Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer
    (SpringerNature, 2015-05) Amin, Mahul B.; Smith, Steven C.; Reuter, Victor E.; Epstein, Jonathan I.; Grignon, David J.; Hansel, Donna E.; Lin, Oscar; McKenney, Jesse K.; Montironi, Rodolfo; Paner, Gladell P.; Al-Ahmadie, Hikmat A.; Algaba, Ferran; Ali, Syed; Alvarado-Cabrero, Isabel; Bubendorf, Lukas; Cheng, Liang; Cheville, John C.; Kristiansen, Glen; Cote, Richard J.; Delahunt, Brett; Eble, John N.; Genega, Elizabeth M.; Gulmann, Christian; Hartmann, Arndt; Langner, Cord; Lopez-Beltran, Antonio; Magi-Galluzzi, Cristina; Merce, Jorda; Netto, George J.; Oliva, Esther; Rao, Priya; Ro, Jae Y.; Srigley, John R.; Tickoo, Satish K.; Tsuzuki, Toyonori; Umar, Saleem A.; Van der Kwast, Theo; Young, Robert H.; Soloway, Mark S.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.
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