{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:55:37Z","timestamp":1760316937272,"version":"build-2065373602"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fumarate hydratase\u2010deficient renal cell carcinoma (FHRCC) is an aggressive carcinoma that typically presents as advanced\u2010stage disease. Prompt recognition of FHRCC is critical for appropriate clinical care and genetic counseling for patients and family members. However, diagnosing FHRCC from cytology specimens is challenging, with limited characterization and no reports describing prospectively identified cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cytology fine\u2010needle aspiration (FNA) cases diagnosed as FHRCC were reviewed, including two prospectively identified cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five cases of FHRCC diagnosed by FNA cytology were identified in five unique patients. The cytologic samples included four FNAs with core biopsy and one FNA with cell block. Biopsy sites included kidney (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), chest wall (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), omentum (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), lung (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), and cervical lymph node (<jats:italic>n<\/jats:italic>\u00a0=\u00a01). All cases demonstrated cytologically malignant epithelial cells characterized by enlarged, round nuclei with variable pleomorphism, irregular nuclear membranes, prominent nucleoli, and moderate\u2010to\u2010abundant amounts of cytoplasm. Perinucleolar halos characterized by chromatin margination and pallor around macronucleoli were seen in all cases. Cytologic features not previously described included cytoplasmic macrovacuoles and eosinophilic globules, cytophagocytosis, and <jats:italic>floral groups<\/jats:italic>. Papillary architecture was rarely present on aspirate smears. Cell block sections showed variable architectural patterns. By immunohistochemistry, FH was definitively lost in three of five cases (60%), and 2\u2010succinocysteine was positive in all 5 cases (100%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cytologic specimens of FHRCC demonstrate salient cytomorphologic features that can support their initial diagnosis. Confirmatory immunohistochemical testing using a dual panel of fumarate hydratase and 2\u2010succinocysteine is recommended for the diagnosis in limited biopsy samples.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22931","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T10:38:48Z","timestamp":1736764728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytologic diagnosis of fumarate hydratase\u2010deficient renal cell carcinoma: A single\u2010institutional experience"],"prefix":"10.1002","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-4512","authenticated-orcid":false,"given":"Patrick C.","family":"Mullane","sequence":"first","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"},{"name":"Department of Pathology and Laboratory Medicine Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-5976","authenticated-orcid":false,"given":"Xiaohua","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2715-2779","authenticated-orcid":false,"given":"Hubert D.","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-9013","authenticated-orcid":false,"given":"Alarice Cheng\u2010Yi","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"78","volume-title":"WHO Classification of Tumours","author":"Hes O","year":"2022"},{"doi-asserted-by":"publisher","key":"e_1_2_8_3_1","DOI":"10.1097\/pas.0000000000001372"},{"doi-asserted-by":"publisher","key":"e_1_2_8_4_1","DOI":"10.1016\/j.juro.2007.01.155"},{"doi-asserted-by":"publisher","key":"e_1_2_8_5_1","DOI":"10.1097\/pas.0000000000001000"},{"doi-asserted-by":"publisher","key":"e_1_2_8_6_1","DOI":"10.1007\/s10689\u2010014\u20109735\u20102"},{"doi-asserted-by":"publisher","key":"e_1_2_8_7_1","DOI":"10.1073\/pnas.051633798"},{"doi-asserted-by":"publisher","key":"e_1_2_8_8_1","DOI":"10.1016\/s0002\u20109440(10)61757\u20109"},{"doi-asserted-by":"publisher","key":"e_1_2_8_9_1","DOI":"10.1097\/pas.0b013e31804375b8"},{"doi-asserted-by":"publisher","key":"e_1_2_8_10_1","DOI":"10.1097\/pas.0000000000000163"},{"doi-asserted-by":"publisher","key":"e_1_2_8_11_1","DOI":"10.1097\/pas.0000000000000617"},{"doi-asserted-by":"publisher","key":"e_1_2_8_12_1","DOI":"10.1111\/his.13183"},{"doi-asserted-by":"publisher","key":"e_1_2_8_13_1","DOI":"10.1002\/cncy.22071"},{"doi-asserted-by":"publisher","key":"e_1_2_8_14_1","DOI":"10.1158\/1078\u20100432.ccr\u201013\u20102993"},{"doi-asserted-by":"publisher","key":"e_1_2_8_15_1","DOI":"10.4143\/crt.2019.086"},{"volume-title":"The Art and Science of Cytopathology","year":"2012","author":"DeMay RM","key":"e_1_2_8_16_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_17_1","DOI":"10.1053\/hupa.2000.20376"},{"doi-asserted-by":"publisher","key":"e_1_2_8_18_1","DOI":"10.1038\/s41598\u2010018\u201028369\u2010y"},{"doi-asserted-by":"publisher","key":"e_1_2_8_19_1","DOI":"10.1016\/s1092\u20109134(98)80030\u20100"},{"doi-asserted-by":"publisher","key":"e_1_2_8_20_1","DOI":"10.1111\/j.1440\u20101827.2005.01805.x"},{"doi-asserted-by":"publisher","key":"e_1_2_8_21_1","DOI":"10.1007\/s00795\u2010005\u20100286\u20103"},{"doi-asserted-by":"publisher","key":"e_1_2_8_22_1","DOI":"10.1177\/106689690401200215"},{"doi-asserted-by":"publisher","key":"e_1_2_8_23_1","DOI":"10.1016\/s0046\u20108177(85)80135\u20100"},{"doi-asserted-by":"publisher","key":"e_1_2_8_24_1","DOI":"10.1016\/s0046\u20108177(97)90026\u20105"},{"doi-asserted-by":"publisher","key":"e_1_2_8_25_1","DOI":"10.1093\/ajcp\/aqaa176"},{"doi-asserted-by":"publisher","key":"e_1_2_8_26_1","DOI":"10.1309\/f4tu\u20106afe\u2010r7nu\u201039y3"},{"issue":"2","key":"e_1_2_8_27_1","first-page":"201","article-title":"Fine needle aspiration of a renal cell carcinoma with eosinophilic globules. A case report","volume":"37","author":"Unger P","year":"1993","journal-title":"Acta Cytol"},{"doi-asserted-by":"publisher","key":"e_1_2_8_28_1","DOI":"10.1016\/j.anndiagpath.2021.151844"},{"doi-asserted-by":"publisher","key":"e_1_2_8_29_1","DOI":"10.1097\/01.pas.0000163362.78475.63"},{"doi-asserted-by":"publisher","key":"e_1_2_8_30_1","DOI":"10.1016\/j.jasc.2019.10.005"},{"doi-asserted-by":"publisher","key":"e_1_2_8_31_1","DOI":"10.1038\/modpathol.2009.58"},{"doi-asserted-by":"publisher","key":"e_1_2_8_32_1","DOI":"10.1097\/pas.0000000000000203"},{"doi-asserted-by":"publisher","key":"e_1_2_8_33_1","DOI":"10.1097\/pas.0b013e318216c112"},{"doi-asserted-by":"publisher","key":"e_1_2_8_34_1","DOI":"10.1038\/s41379\u2010018\u20100017\u20107"},{"doi-asserted-by":"publisher","key":"e_1_2_8_35_1","DOI":"10.1177\/10668969221074600"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.22931","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:57:04Z","timestamp":1760299024000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.22931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,13]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/cncy.22931"],"URL":"https:\/\/doi.org\/10.1002\/cncy.22931","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"type":"print","value":"1934-662X"},{"type":"electronic","value":"1934-6638"}],"subject":[],"published":{"date-parts":[[2025,1,13]]},"assertion":[{"value":"2024-10-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22931"}}