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Browsing by Author "Colecchia, Maurizio"
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Item Evaluation of an institutional series of low-grade oncocytic tumor (LOT) of the kidney and review of the mutational landscape of LOT(Springer, 2023) Ricci, Costantino; Ambrosi, Francesca; Franceschini, Tania; Giunchi, Francesca; Grillini, Alessia; Franchini, Eugenia; Grillini, Marco; Schiavina, Riccardo; Massari, Francesco; Mollica, Veronica; Tateo, Valentina; Bianchi, Federico Mineo; Bianchi, Lorenzo; Droghetti, Matteo; Maloberti, Thais; Tallini, Giovanni; Colecchia, Maurizio; Acosta, Andres Martin; Lobo, João; Trpkov, Kiril; Fiorentino, Michelangelo; de Biase, Dario; Pathology and Laboratory Medicine, School of MedicineThe 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43–79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9–3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without “canonical” mutations.Item 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 MedicineRenal 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.