{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:27:52Z","timestamp":1785374872949,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T00:00:00Z","timestamp":1539907200000},"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":[[2018,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fumarate hydratase (FH)\u2010deficient renal cell carcinoma (RCC) is rare and highly aggressive and is believed to arise mostly in the setting of hereditary leiomyomatosis\u2010RCC syndrome with a germline mutation of <jats:italic>FH<\/jats:italic>. Because of the aggressiveness of these tumors and a frequent lack of ascertainable family history, these tumors may first present as metastases and be sampled by cytology. The cytologic findings of FH\u2010deficient RCC have not previously been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cytologic and limited biopsy samples from patients with FH\u2010deficient RCC were reviewed retrospectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 24 cytologic and limited biopsy samples from 19 patients (6 women and 13 men; age range, 22\u201069 years) who had FH\u2010deficient RCC and metastasis at presentation were evaluated. These included 21 cytology samples ranging from malignant effusions (n = 7) to metastases (n = 11), to samples of primary kidney tumors (n = 3). The samples exhibited cells, often in clusters and abortive papillae, with voluminous, finely vacuolated cytoplasm and large, pleomorphic nuclei with prominent, viral inclusion\u2010like nucleoli. A distinctive finding of peripheral cytoplasmic clearing frequently was apparent, and intranuclear cytoplasmic pseudoinclusions were less frequent. Of 7 cell block and biopsy samples, several of which represented sampling from the same patient, all demonstrated tissue fragments that had discernable morphologic patterns associated with FH\u2010deficient RCC, including tubulocystic and intracystic papillary growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Features characteristic and suggestive of FH\u2010deficient RCC may be identified in cytologic and small biopsy samples. Although the current samples were identified retrospectively in well characterized cases of FH\u2010deficient RCC, the authors argue that, with appropriate clinical correlation, these features are sufficiently distinctive to trigger recognition and confirmatory workup.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22071","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T09:35:34Z","timestamp":1539941734000},"page":"992-1002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clues to recognition of fumarate hydratase\u2010deficient renal cell carcinoma: Findings from cytologic and limited biopsy samples"],"prefix":"10.1002","volume":"126","author":[{"given":"Irene","family":"Shyu","sequence":"first","affiliation":[{"name":"Department of Pathology Virginia Commonwealth University (VCU) School of Medicine  Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leili","family":"Mirsadraei","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Robila","sequence":"additional","affiliation":[{"name":"Department of Pathology Virginia Commonwealth University (VCU) School of Medicine  Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Mehra","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Bei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Udager","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Gill","sequence":"additional","affiliation":[{"name":"Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research Royal North Shore Hospital and University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahul B.","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Tennessee Health Sciences  Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2089-6118","authenticated-orcid":false,"given":"Oscar","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-4607","authenticated-orcid":false,"given":"Steven Christopher","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology Virginia Commonwealth University (VCU) School of Medicine  Richmond Virginia"},{"name":"Department of Surgery VCU School of Medicine  Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,19]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"313","article-title":"Kidney tumors associated with hereditary cancer syndromes: an emerging opportunity and responsibility in surgical pathology","volume":"22","author":"Mochel MC","year":"2017","journal-title":"AJSP Rev Rep"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng849"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0017-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13183"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13395"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31804375b8"},{"key":"e_1_2_8_8_1","unstructured":"2016 IARC Press Lyon France H Moch PA Humphrey TM Ulbright VE Reuter WHO Classification of Tumors of the Urinary System and Male Genital Organs. 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