{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T20:03:19Z","timestamp":1784404999182,"version":"3.55.0"},"reference-count":16,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572540"],"award-info":[{"award-number":["81572540"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572541"],"award-info":[{"award-number":["81572541"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872107"],"award-info":[{"award-number":["81872107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872108"],"award-info":[{"award-number":["81872108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2019,6,11]]},"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a newly recognised entity in the WHO 2016 classification defined as the germline mutation of\n                      <jats:italic>FH<\/jats:italic>\n                      gene. Fumaratehydratase-deficient renal cell carcinoma (FH-deficient RCC) is recommended for tumours with FH deficiency but lacking of genetic evidences of\n                      <jats:italic>FH<\/jats:italic>\n                      germline mutation. In this study, we described the clinicopathological and molecular changes of 13 FH-deficient RCCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Histology features, clinicopathological data, radiology performance and outcomes were collected for each patient. Next-generation sequencing and DNA sequencing of\n                      <jats:italic>FH<\/jats:italic>\n                      gene were performed to examine FH mutations. The patient group included five females and eight males. Different morphological patterns of papillary, nested, adenoid, foam adenoid, cribriform, tubular, tubulocystic, cystic and loose oedema stroma were observed. Except typical big nuclei with or without eosinophilic nucleoli and perinucleolar halos, raisin-like, hobnail-like and even low-grade nuclei were also observed in these tumours. Eleven cases with high-grade nuclei showed disease progression or death, but no disease progression was detected in two cases with low-grade nuclei and eosinophilic cytoplasm. FH expression was absent in tumour cells except for case 11. Next-generation sequencing and DNA sequencing verified seven FH germline mutations and four somatic mutations out of 13 cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FH-deficient RCC is a rare renal tumour and has a wide morphological spectrum. Most of the tumours had high-grade nuclei and were aggressive. However, we observed a morphological subtype of FH-deficient RCC with low-grade nuclei and eosinophilic cytoplasm, which might mainly occur in young women and show a relatively good prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2019-205924","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T17:15:41Z","timestamp":1562001341000},"page":"748-754","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Fumaratehydratase-deficient renal cell carcinoma: a clinicopathological and molecular study of 13 cases"],"prefix":"10.1136","volume":"72","author":[{"given":"Xiuyi","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengni","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Urology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-0723","authenticated-orcid":false,"given":"Ni","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2025120519323775000_72.11.748.1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2147\/IJNRD.S42097","article-title":"Hereditary leiomyomatosis and renal cell carcinoma","volume":"7","author":"Schmidt","year":"2014","journal-title":"Int J Nephrol Renovasc Dis"},{"key":"2025120519323775000_72.11.748.2","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1097\/PAS.0000000000000617","article-title":"Fumarate Hydratase-deficient renal cell carcinoma is strongly correlated with fumarate hydratase mutation and hereditary leiomyomatosis and renal cell carcinoma syndrome","volume":"40","author":"Trpkov","year":"2016","journal-title":"Am J Surg Pathol"},{"key":"2025120519323775000_72.11.748.3","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1097\/PAS.0000000000000520","article-title":"Morphology and immunohistochemistry for 2SC and FH aid in detection of fumarate hydratase gene aberrations in uterine leiomyomas from young patients","volume":"39","author":"Joseph","year":"2015","journal-title":"Am J Surg Pathol"},{"key":"2025120519323775000_72.11.748.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051633798"},{"key":"2025120519323775000_72.11.748.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng849"},{"key":"2025120519323775000_72.11.748.6","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1097\/PAS.0000000000000719","article-title":"Tubulocystic carcinoma of the kidney with poorly differentiated foci: a frequent morphologic pattern of fumarate Hydratase-deficient renal cell carcinoma","volume":"40","author":"Smith","year":"2016","journal-title":"Am J Surg Pathol"},{"key":"2025120519323775000_72.11.748.7","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jaad.2017.01.023","article-title":"Hereditary leiomyomatosis and renal cell cancer syndrome: an update and 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