{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:11:19Z","timestamp":1792782679398,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi di Verona","id":[{"id":"https:\/\/ror.org\/039bp8j42","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metabolic renal cell carcinomas (RCC) deficient in succinate dehydrogenase (SDH) or fumarate hydratase (FH) are rare but clinically significant entities formalized in the last WHO classification. Their recognition typically starts from morphology and is corroborated by targeted immunohistochemistry (IHC) and, where appropriate, molecular and germline testing. In routine practice, however, implementation may be uneven. Hence, we conducted a nationwide, web-based survey (made by 25 items) among members of the Italian Study Group of Uropathology (GIUP) to map real-world awareness, diagnostic pathways, and test availability across Italian centers. Twenty-one pathologists responded; 18\/21 (85.7%) reported dedicated uropathology practice with heterogeneous seniority (\u2264\u20095\u00a0years, 28.6%; 5\u201310\u00a0years, 19.0%; 10\u201320\u00a0years, 14.3%;\u2009&gt;\u200920\u00a0years, 38.1%). Despite substantial renal-tumor workloads (12\/20, 57.1% handled\u2009&gt;\u2009100 cases in the previous 5 years), direct exposure to metabolic RCCs remained limited (FH-deficient\u2009\u2265\u20091 case, 11\/21, 52.4%; SDH-deficient\u2009\u2265\u20091 case, 9\/21, 42.9%). Suspicion was predominantly morphology-led: for SDH-deficient RCC, morphology ranked first in 16\/21 (76.2%) with the commonest sequence morphology\u2009&gt;\u2009age\u2009&gt;\u2009number of lesions (76.2%); for FH-deficient RCC, morphology was top-ranked in 19\/21 (90.5%). Key morphologic cues were mixed architectural patterns\/papillary elements\/macronucleoli for FH-deficient RCC, and eosinophilic cytoplasm with solid\u2013alveolar architecture for SDH-deficient RCC. IHC mirrored these priorities (FH top for FH-deficient, 85.7%; SDHB top for SDH-deficient, 76.2%), whereas 2-succinocysteine (2SC) was rarely available (1\/21, 4.8%). Critically, this FH-loss-only workflow can miss non-truncating FH variants (FH immunoreactive but enzymatically inactive) tumors, contributing to under-recognition. Molecular testing would be requested in all suspected cases by 12\/21 (57.1%); among selective users, equivocal IHC was the leading trigger (6\/8, 75%). Overall, metabolic RCC recognition in Italy is primarily morphology-driven but constrained by uneven access to confirmatory IHC, particularly 2SC, and to molecular assays. The findings argue for harmonized diagnostic algorithms, regional reference laboratory networks, and routine involvement of molecular tumor boards, supported by targeted educational initiatives (including curated digital slide repositories), to standardize practice and improve patient pathways from morphologic suspicion to genetic counselling and tailored surveillance.<\/jats:p>","DOI":"10.1007\/s00428-026-04431-3","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T03:18:08Z","timestamp":1770175088000},"page":"653-668","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diagnostic practice and awareness of SDH- and FH-deficient renal cell carcinoma: results from an Italian Study Group of uropathology (GIUP) survey"],"prefix":"10.1007","volume":"489","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-7980","authenticated-orcid":false,"given":"Giuseppe Nicol\u00f2","family":"Fanelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7352-6327","authenticated-orcid":false,"given":"Anna","family":"Cali\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7881-8767","authenticated-orcid":false,"given":"Stefano","family":"Marletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ballotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-9101","authenticated-orcid":false,"given":"Marco","family":"Barella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6337-1701","authenticated-orcid":false,"given":"Guido","family":"Bellezza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1365-6995","authenticated-orcid":false,"given":"Paola","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6050-3222","authenticated-orcid":false,"given":"Angelo Giovanni","family":"Bonadio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-6138","authenticated-orcid":false,"given":"Piergiuseppe","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"D\u2019Amuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0894-8544","authenticated-orcid":false,"given":"Giovanni","family":"De Chiara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Errigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Fiorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Franzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Liscia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Marcolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9590-2351","authenticated-orcid":false,"given":"Daniela","family":"Onnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pagliuca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Panicci\u00e0","family":"Bonifazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-4131","authenticated-orcid":false,"given":"Francesco","family":"Pierconti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Pozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Stefanizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9998-8762","authenticated-orcid":false,"given":"Marina","family":"Valeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-3252","authenticated-orcid":false,"given":"Mariavittoria","family":"Vescovo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-7274","authenticated-orcid":false,"given":"Guido","family":"Martignoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"4431_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.32074\/1591-951X-814","volume":"115","author":"A Calio","year":"2022","unstructured":"Calio A, Marletta S, Brunelli M, Martignoni G (2022) WHO 2022 classification of kidney tumors: what is relevant? An update and future novelties for the pathologist. Pathologica 115:23\u201331. https:\/\/doi.org\/10.32074\/1591-951X-814","journal-title":"Pathologica"},{"key":"4431_CR2","volume-title":"Urinary and male genital tumours","author":"World Health Organization","year":"2022","unstructured":"World Health Organization (2022) Urinary and male genital tumours, 5th edn. International Agency for Research on Cancer, Lyon","edition":"5"},{"key":"4431_CR3","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/path.2932","volume":"225","author":"C Bardella","year":"2011","unstructured":"Bardella C, El-Bahrawy M, Frizzell N, Adam J, Ternette N, Hatipoglu E, Howarth K, O\u2019Flaherty L, Roberts I, Turner G, Taylor J, Giaslakiotis K, Macaulay VM, Harris AL, Chandra A, Lehtonen HJ, Launonen V, Aaltonen LA, Pugh CW, Mihai R, Trudgian D, Kessler B, Baynes JW, Ratcliffe PJ, Tomlinson IP, Pollard PJ (2011) Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status. J Pathol 225:4\u201311. https:\/\/doi.org\/10.1002\/path.2932","journal-title":"J Pathol"},{"key":"4431_CR4","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/s41586-020-2363-0","volume":"582","author":"PL Sulkowski","year":"2020","unstructured":"Sulkowski PL, Oeck S, Dow J, Economos NG, Mirfakhraie L, Liu Y, Noronha K, Bao X, Li J, Shuch BM, King MC, Bindra RS, Glazer PM (2020) Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature 582:586\u2013591. https:\/\/doi.org\/10.1038\/s41586-020-2363-0","journal-title":"Nature"},{"key":"4431_CR5","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/j.euf.2021.12.002","volume":"8","author":"A Yoo","year":"2022","unstructured":"Yoo A, Tang C, Zucker M, Fitzgerald K, DiNatale RG, Rappold PM, Weiss K, Freeman B, Lee CH, Schultz N, Motzer R, Russo P, Coleman J, Reuter VE, Chen YB, Carlo MI, Gill AJ, Kotecha RR, Ari Hakimi A, Reznik E (2022) Genomic and metabolic hallmarks of SDH- and FH-deficient renal cell carcinomas. Eur Urol Focus 8:1278\u20131288. https:\/\/doi.org\/10.1016\/j.euf.2021.12.002","journal-title":"Eur Urol Focus"},{"key":"4431_CR6","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.5858\/arpa.2018-0216-RA","volume":"142","author":"SL Skala","year":"2018","unstructured":"Skala SL, Dhanasekaran SM, Mehra R (2018) Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC): a contemporary review and practical discussion of the differential diagnosis for HLRCC-associated renal cell carcinoma. Arch Pathol Lab Med 142:1202\u20131215. https:\/\/doi.org\/10.5858\/arpa.2018-0216-RA","journal-title":"Arch Pathol Lab Med"},{"key":"4431_CR7","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1097\/PAS.0000000000000163","volume":"38","author":"YB Chen","year":"2014","unstructured":"Chen YB, Brannon AR, Toubaji A, Dudas ME, Won HH, Al-Ahmadie HA, Fine SW, Gopalan A, Frizzell N, Voss MH, Russo P, Berger MF, Tickoo SK, Reuter VE (2014) Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. Am J Surg Pathol 38:627\u2013637. https:\/\/doi.org\/10.1097\/PAS.0000000000000163","journal-title":"Am J Surg Pathol"},{"key":"4431_CR8","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.ejca.2021.04.009","volume":"151","author":"L Carril-Ajuria","year":"2021","unstructured":"Carril-Ajuria L, Colomba E, Cerbone L, Romero-Ferreiro C, Crouzet L, Laguerre B, Thibault C, Vicier C, de Velasco G, Flechon A, Saldana C, Benusiglio PR, de Bressac- Paillerets B, Guillaud-Bataille M, Gaignard P, Scoazec JY, Richard S, Caron O, Escudier B, Albiges L (2021) Response to systemic therapy in fumarate hydratase-deficient renal cell carcinoma. Eur J Cancer 151:106\u2013114. https:\/\/doi.org\/10.1016\/j.ejca.2021.04.009","journal-title":"Eur J Cancer"},{"key":"4431_CR9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s10585-025-10368-9","volume":"42","author":"N Kuhrer","year":"2025","unstructured":"Kuhrer N, Huebner-Resch I, Mayr R, Agaimy A, Kronbichler A, Hartmann A, Schmidinger M, Pichler R (2025) Targeting metabolic and epigenetic reprogramming in metastatic fumarate hydratase-deficient renal cell carcinoma. Clin Exp Metastasis 42:47. https:\/\/doi.org\/10.1007\/s10585-025-10368-9","journal-title":"Clin Exp Metastasis"},{"key":"4431_CR10","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1097\/PAS.0000000000000292","volume":"38","author":"AJ Gill","year":"2014","unstructured":"Gill AJ, Hes O, Papathomas T, Sedivcova M, Tan PH, Agaimy A, Andresen PA, Kedziora A, Clarkson A, Toon CW, Sioson L, Watson N, Chou A, Paik J, Clifton-Bligh RJ, Robinson BG, Benn DE, Hills K, Maclean F, Niemeijer ND, Vlatkovic L, Hartmann A, Corssmit EP, van Leenders GJ, Przybycin C, McKenney JK, Magi-Galluzzi C, Yilmaz A, Yu D, Nicoll KD, Yong JL, Sibony M, Yakirevich E, Fleming S, Chow CW, Miettinen M, Michal M, Trpkov K (2014) Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients. Am J Surg Pathol 38:1588\u20131602. https:\/\/doi.org\/10.1097\/PAS.0000000000000292","journal-title":"Am J Surg Pathol"},{"key":"4431_CR11","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1038\/s41379-022-01108-5","volume":"35","author":"MB Amin","year":"2022","unstructured":"Amin MB, McKenney JK, Martignoni G, Campbell SC, Pal S, Tickoo SK (2022) Low grade oncocytic tumors of the kidney: a clinically relevant approach for the workup and accurate diagnosis. Mod Pathol 35:1306\u20131316. https:\/\/doi.org\/10.1038\/s41379-022-01108-5","journal-title":"Mod Pathol"},{"key":"4431_CR12","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/s41379-021-00998-1","volume":"35","author":"TL Fuchs","year":"2022","unstructured":"Fuchs TL, Maclean F, Turchini J, Vargas AC, Bhattarai S, Agaimy A, Hartmann A, Kao CS, Ellis C, Bonert M, Leroy X, Kunju LP, Schwartz L, Matsika A, Williamson SR, Rao P, Divatia M, Guarch R, Algaba F, Balancin ML, Zhou M, Samaratunga H, da Cunha IW, Brimo F, Ryan A, Clouston D, Aron M, O\u2019Donnell M, Chan E, Hirsch MS, Moch H, Pang CY, Wah C, Yin W, Perry-Keene J, Yilmaz A, Chou A, Clarkson A, van der Westhuizen G, Morrison E, Zwi J, Hes O, Trpkov K, Gill AJ (2022) Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients. Mod Pathol 35:836\u2013849. https:\/\/doi.org\/10.1038\/s41379-021-00998-1","journal-title":"Mod Pathol"},{"key":"4431_CR13","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1007\/s00428-024-03978-3","volume":"485","author":"F Santa","year":"2024","unstructured":"Santa F, Dabaghian A, Posfai B, Vasas B, Kaizer L, Jenei A, Scheich B, Teglasi V, Sapi Z, Biro K, Maraz A, Stelios M, Butz H, Martinek P, Pivovarcikova K, Melegh Z, Akgul M, Kuthi L (2024) Morphological diversity in SDH-deficient renal carcinomas: a three-case exploration of variant features and dedifferentiation. Virchows Arch 485:1167\u20131173. https:\/\/doi.org\/10.1007\/s00428-024-03978-3","journal-title":"Virchows Arch"},{"key":"4431_CR14","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/modpathol.2014.86","volume":"28","author":"SR Williamson","year":"2015","unstructured":"Williamson SR, Eble JN, Amin MB, Gupta NS, Smith SC, Sholl LM, Montironi R, Hirsch MS, Hornick JL (2015) Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma. Mod Pathol 28:80\u201394. https:\/\/doi.org\/10.1038\/modpathol.2014.86","journal-title":"Mod Pathol"},{"key":"4431_CR15","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/PAS.0000000000001372","volume":"44","author":"HD Lau","year":"2020","unstructured":"Lau HD, Chan E, Fan AC, Kunder CA, Williamson SR, Zhou M, Idrees MT, Maclean FM, Gill AJ, Kao CS (2020) A clinicopathologic and molecular analysis of fumarate hydratase-deficient renal cell carcinoma in 32 patients. Am J Surg Pathol 44:98\u2013110. https:\/\/doi.org\/10.1097\/PAS.0000000000001372","journal-title":"Am J Surg Pathol"},{"key":"4431_CR16","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.pathol.2024.08.013","volume":"57","author":"S Lee","year":"2025","unstructured":"Lee S, Kim B, Park JH, Moon KC (2025) Fumarate hydratase-deficient renal cell carcinoma: a single institution-based study of 29 patients by clinicopathological, immunohistochemical and genetic approaches. Pathology 57:10\u201316. https:\/\/doi.org\/10.1016\/j.pathol.2024.08.013","journal-title":"Pathology"},{"key":"4431_CR17","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1097\/PAS.0000000000001476","volume":"44","author":"SR Williamson","year":"2020","unstructured":"Williamson SR, Gill AJ, Argani P, Chen YB, Egevad L, Kristiansen G, Grignon DJ, Hes O (2020) Report from the International Society of Urological Pathology (ISUP) consultation conference on molecular pathology of urogenital cancers: III: molecular pathology of kidney cancer. Am J Surg Pathol 44:e47\u2013e65. https:\/\/doi.org\/10.1097\/PAS.0000000000001476","journal-title":"Am J Surg Pathol"},{"key":"4431_CR18","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1097\/PAS.0000000000000626","volume":"40","author":"B Buelow","year":"2016","unstructured":"Buelow B, Cohen J, Nagymanyoki Z, Frizzell N, Joseph NM, McCalmont T, Garg K (2016) Immunohistochemistry for 2-succinocysteine (2SC) and fumarate hydratase (FH) in cutaneous leiomyomas may aid in identification of patients with HLRCC (hereditary leiomyomatosis and renal cell carcinoma syndrome). Am J Surg Pathol 40:982\u2013988. https:\/\/doi.org\/10.1097\/PAS.0000000000000626","journal-title":"Am J Surg Pathol"},{"key":"4431_CR19","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.humpath.2022.12.013","volume":"134","author":"R Mannan","year":"2023","unstructured":"Mannan R, Wang X, Bawa PS, Chugh S, Chinnaiyan AK, Rangaswamy R, Zhang Y, Cao X, Smith SC, Trpkov K, Williamson SR, Sangoi AR, Mohanty S, McKenney JK, Gupta S, Magi-Galluzzi C, Argani P, Osunkoya AO, Chinnaiyan AM, Dhanasekaran SM, Mehra R (2023) Characterization of protein S-(2-succino)-cysteine (2SC) succination as a biomarker for fumarate hydratase-deficient renal cell carcinoma. Hum Pathol 134:102\u2013113. https:\/\/doi.org\/10.1016\/j.humpath.2022.12.013","journal-title":"Hum Pathol"},{"key":"4431_CR20","doi-asserted-by":"publisher","DOI":"10.32074\/1591-951X-N1518","author":"S Marletta","year":"2025","unstructured":"Marletta S, Cali\u00f2 A, Fanelli GN, Bianco P, Bonadio AG, Covelli C, Francesconi S, Ivanova M, Liscia D, Moro A, Onnis D, Raspollini MR, Ricci C, Sentinelli S, Valeri M, Martignoni G (2025) TFE3-rearranged and TFEB-altered renal cell carcinoma: from classification to real-life. Insights from a national Italian survey. Pathologica. https:\/\/doi.org\/10.32074\/1591-951X-N1518","journal-title":"Pathologica"},{"key":"4431_CR21","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1097\/PAS.0000000000000617","volume":"40","author":"K Trpkov","year":"2016","unstructured":"Trpkov K, Hes O, Agaimy A, Bonert M, Martinek P, Magi-Galluzzi C, Kristiansen G, Luders C, Nesi G, Comperat E, Sibony M, Berney DM, Mehra R, Brimo F, Hartmann A, Husain A, Frizzell N, Hills K, Maclean F, Srinivasan B, Gill AJ (2016) Fumarate hydratase-deficient renal cell carcinoma is strongly correlated with fumarate hydratase mutation and hereditary leiomyomatosis and renal cell carcinoma syndrome. Am J Surg Pathol 40:865\u2013875. https:\/\/doi.org\/10.1097\/PAS.0000000000000617","journal-title":"Am J Surg Pathol"},{"key":"4431_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100561","volume":"37","author":"A Calio","year":"2024","unstructured":"Calio A, Marletta S, Stefanizzi L, Marcolini L, Rotellini M, Serio G, Bariani E, Vicentini C, Pedron S, Martelli FM, Antonini P, Brunelli M, Martignoni G (2024) Comparison of primary and metastatic fumarate hydratase-deficient renal cell carcinomas documents morphologic divergence and potential diagnostic pitfall with peritoneal mesothelioma. Mod Pathol 37:100561. https:\/\/doi.org\/10.1016\/j.modpat.2024.100561","journal-title":"Mod Pathol"},{"key":"4431_CR23","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1038\/s41379-018-0017-7","volume":"31","author":"M Muller","year":"2018","unstructured":"Muller M, Guillaud-Bataille M, Salleron J, Genestie C, Deveaux S, Slama A, de Paillerets BB, Richard S, Benusiglio PR, Ferlicot S (2018) Pattern multiplicity and fumarate hydratase (FH)\/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration. Mod Pathol 31:974\u2013983. https:\/\/doi.org\/10.1038\/s41379-018-0017-7","journal-title":"Mod Pathol"},{"key":"4431_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100303","volume":"36","author":"L Zheng","year":"2023","unstructured":"Zheng L, Zhang X, Pan X, Huang Z, Zhang M, Xian J, Wei Y, Nie L, Zhang M, Gong J, Chen X, Zhou Q, Zeng H, Chen N (2023) AKR1B10 is a new sensitive and specific marker for fumarate hydratase-deficient renal cell carcinoma. Mod Pathol 36:100303. https:\/\/doi.org\/10.1016\/j.modpat.2023.100303","journal-title":"Mod Pathol"},{"key":"4431_CR25","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s00428-025-04041-5","volume":"487","author":"S Marletta","year":"2025","unstructured":"Marletta S, Marcolini L, Calio A, Pedron S, Antonini P, Martelli FM, Stefanizzi L, Martignoni G (2025) Stimulator of interferon genes (STING) immunohistochemical expression in fumarate hydratase-deficient renal cell carcinoma: biological and potential predictive implications. Virchows Arch 487:827\u2013838. https:\/\/doi.org\/10.1007\/s00428-025-04041-5","journal-title":"Virchows Arch"},{"key":"4431_CR26","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1056\/NEJMoa1505917","volume":"374","author":"WM Linehan","year":"2016","unstructured":"Linehan WM, Spellman PT, Ricketts CJ, Creighton CJ, Fei SS, Davis C, Wheeler DA, Murray BA, Schmidt L, Vocke CD, Peto M, Al Mamun AA, Shinbrot E, Sethi A, Brooks S, Rathmell WK, Brooks AN, Hoadley KA, Robertson AG, Brooks D, Bowlby R, Sadeghi S, Shen H, Weisenberger DJ, Bootwalla M, Baylin SB, Laird PW, Cherniack AD, Saksena G, Haake S, Li J, Liang H, Lu Y, Mills GB, Akbani R, Leiserson MD, Raphael BJ, Anur P, Bottaro D, Albiges L, Barnabas N, Choueiri TK, Czerniak B, Godwin AK, Hakimi AA, Ho TH, Hsieh J, Ittmann M, Kim WY, Krishnan B, Merino MJ, Mills Shaw KR, Reuter VE, Reznik E, Shelley CS, Shuch B, Signoretti S, Srinivasan R, Tamboli P, Thomas G, Tickoo S, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis JD, Penny RJ, Shelton C, Shelton WT, Sherman M, Thompson E, Yena P, Avedon MT, Bowen J, Gastier-Foster JM, Gerken M, Leraas KM, Lichtenberg TM, Ramirez NC, Santos T, Wise L, Zmuda E, Demchok JA, Felau I, Hutter CM, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Zhang J, Ayala B, Baboud J, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Ally A, Balasundaram M, Balu S, Beroukhim R, Bodenheimer T, Buhay C, Butterfield YS, Carlsen R, Carter SL, Chao H, Chuah E, Clarke A, Covington KR, Dahdouli M, Dewal N, Dhalla N, Doddapaneni HV, Drummond JA, Gabriel SB, Gibbs RA, Guin R, Hale W, Hawes A, Hayes DN, Holt RA, Hoyle AP, Jefferys SR, Jones SJ, Jones CD, Kalra D, Kovar C, Lewis L, Li J, Ma Y, Marra MA, Mayo M, Meng S, Meyerson M, Mieczkowski PA, Moore RA, Morton D, Mose LE, Mungall AJ, Muzny D, Parker JS, Perou CM, Roach J, Schein JE, Schumacher SE, Shi Y, Simons JV, Sipahimalani P, Skelly T, Soloway MG, Sougnez C, Tam A, Tan D, Thiessen N, Veluvolu U, Wang M, Wilkerson MD, Wong T, Wu J, Xi L, Zhou J, Bedford J, Chen F, Fu Y, Gerstein M, Haussler D, Kasaian K, Lai P, Ling S, Radenbaugh A, Van Den Berg D, Weinstein JN, Zhu J, Albert M, Alexopoulou I, Andersen JJ, Auman JT, Bartlett J, Bastacky S, Bergsten J, Blute ML, Boice L, Bollag RJ, Boyd J, Castle E, Chen YB, Cheville JC, Curley E, Davies B, DeVolk A, Dhir R, Dike L, Eckman J, Engel J, Harr J, Hrebinko R, Huang M, Huelsenbeck-Dill L, Iacocca M, Jacobs B, Lobis M, Maranchie JK, McMeekin S, Myers J, Nelson J, Parfitt J, Parwani A, Petrelli N, Rabeno B, Roy S, Salner AL, Slaton J, Stanton M, Thompson RH, Thorne L, Tucker K, Weinberger PM, Winemiller C, Zach LA, Zuna R (2016) Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med 374:135\u2013145. https:\/\/doi.org\/10.1056\/NEJMoa1505917","journal-title":"N Engl J Med"},{"key":"4431_CR27","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1007\/s00428-022-03380-x","volume":"481","author":"A Calio","year":"2022","unstructured":"Calio A, Marletta S, Brunelli M, Pedron S, Portillo SC, Segala D, Bariani E, Gobbo S, Netto G, Martignoni G (2022) TFE3 and TFEB-rearranged renal cell carcinomas: an immunohistochemical panel to differentiate from common renal cell neoplasms. Virchows Arch 481:877\u2013891. https:\/\/doi.org\/10.1007\/s00428-022-03380-x","journal-title":"Virchows Arch"},{"key":"4431_CR28","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1097\/PAS.0000000000000719","volume":"40","author":"SC Smith","year":"2016","unstructured":"Smith SC, Trpkov K, Chen YB, Mehra R, Sirohi D, Ohe C, Cani AK, Hovelson DH, Omata K, McHugh JB, Jochum W, Colecchia M, Amin M, Divatia MK, Hes O, Menon S (2016) Tubulocystic carcinoma of the kidney with poorly differentiated foci: a frequent morphologic pattern of fumarate hydratase-deficient renal cell carcinoma. Am J Surg Pathol 40:1457\u20131472. https:\/\/doi.org\/10.1097\/PAS.0000000000000719","journal-title":"Am J Surg Pathol"},{"key":"4431_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2019.152532","volume":"215","author":"GN Fanelli","year":"2019","unstructured":"Fanelli GN, Fassan M, Dal Moro F, Soligo M, Munari G, Zattoni F, Gardiman MP, Prayer-Galetti T (2019) Thyroid-like follicular carcinoma of the kidney: the mutational profiling reveals a BRAF wild type status. Pathol Res Pract 215:152532. https:\/\/doi.org\/10.1016\/j.prp.2019.152532","journal-title":"Pathol Res Pract"},{"key":"4431_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14184359","author":"E Francini","year":"2022","unstructured":"Francini E, Fanelli GN, Pederzoli F, Spisak S, Minonne E, Raffo M, Pakula H, Tisza V, Scatena C, Naccarato AG, Loda M, Nuzzo PV (2022) Circulating cell-free DNA in renal cell carcinoma: the new era of precision medicine. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers14184359","journal-title":"Cancers (Basel)"},{"key":"4431_CR31","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16030662","author":"E Francini","year":"2024","unstructured":"Francini E, Nuzzo PV, Fanelli GN (2024) Cell-free DNA: unveiling the future of cancer diagnostics and monitoring. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers16030662","journal-title":"Cancers (Basel)"},{"key":"4431_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.labinv.2025.104220","volume":"105","author":"M Omar","year":"2025","unstructured":"Omar M, Fanelli GN, Socciarelli F, Ullanat V, Puchala SR, Wen J, Chowdhury A, Valencia I, Scatena C, Marchionni L, Umeton R, Loda M (2025) Antibody-based multiplex image analysis: standard analytical workflows and artificial intelligence tools for pathologists. Lab Invest 105:104220. https:\/\/doi.org\/10.1016\/j.labinv.2025.104220","journal-title":"Lab Invest"},{"key":"4431_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2023.103963","volume":"185","author":"M Dameri","year":"2023","unstructured":"Dameri M, Cirmena G, Ravera F, Ferrando L, Cuccarolo P, Stabile M, Fanelli GN, Nuzzo PV, Calabrese M, Tagliafico A, Ballestrero A, Zoppoli G (2023) Standard operating procedures (SOPs) for non-invasive multiple biomarkers detection in an academic setting: a critical review of the literature for the RENOVATE study protocol. Crit Rev Oncol Hematol 185:103963. https:\/\/doi.org\/10.1016\/j.critrevonc.2023.103963","journal-title":"Crit Rev Oncol Hematol"},{"key":"4431_CR34","unstructured":"National Comprehensive Cancer Network (2025) NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer. Version 1.2026. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/kidney.pdf. Accessed 30\/09\/2025"},{"key":"4431_CR35","unstructured":"European Association of U (2025) EAU Guidelines on Renal Cell Carcinoma 2025. https:\/\/uroweb.org\/guidelines\/renal-cell-carcinoma. Accessed 30\/09\/2025"},{"key":"4431_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2023.102558","volume":"116","author":"M Rizzo","year":"2023","unstructured":"Rizzo M, Calio A, Brunelli M, Pezzicoli G, Ganini C, Martignoni G, Camillo P (2023) Clinico-pathological implications of the 2022 WHO renal cell carcinoma classification. Cancer Treat Rev 116:102558. https:\/\/doi.org\/10.1016\/j.ctrv.2023.102558","journal-title":"Cancer Treat Rev"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04431-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-026-04431-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04431-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:23:34Z","timestamp":1789550614000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-026-04431-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["4431"],"URL":"https:\/\/doi.org\/10.1007\/s00428-026-04431-3","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"assertion":[{"value":"1 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethical approval was not required for this anonymized national survey. The research was conducted ethically and in accordance with the principles of the Declaration of Helsinki.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest.","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}