{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:34:46Z","timestamp":1787589286231,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273047"],"award-info":[{"award-number":["82273047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Renal cell carcinoma with hemangioblastoma\u2010like features (RCC\u2010HB) is a rare renal cell carcinoma (RCC) subtype. It consists of renal cell carcinoma with fibromyomatous stroma (RCC FMS)\u2010like and hemangioblastoma (HB)\u2010like components. However, its molecular characteristics and whether it is a subtype of clear cell renal cell carcinoma (CCRCC), a part of the morphologic spectrum of RCC FMS, or a distinct entity remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We conducted clinicopathological evaluation, immunohistochemistry testing, and next\u2010generation sequencing (NGS) on seven RCC\u2010HB cases of tumour tissue, non\u2010tumour tissue, and blood samples. The cohort included five female and two male patients, aged 33\u201368\u2009years, with no personal or family history of syndromic disease. Six cases were unifocal, and one was multifocal. Tumours measured 1.2\u20136.0\u2009cm and were well\u2010circumscribed by a thick fibrous capsule, with fibromuscular bundles extending into and dividing the lesions. RCC FMS\u2010like regions resembled CCRCC, RCC FMS, or clear cell papillary renal cell tumour (CCPRCT) and showed CK7 positivity. HB\u2010like regions featured polygonal or short spindle\u2010shaped neoplastic stromal cells interspersed with rich capillary networks and were highlighted by S100, \u03b1\u2010inhibin, and GPNMB. DNA sequencing revealed pathogenic variants in\n                      <jats:italic>MTOR<\/jats:italic>\n                      ,\n                      <jats:italic>TSC1<\/jats:italic>\n                      , and\n                      <jats:italic>TSC2<\/jats:italic>\n                      in six cases, while one case did not detect these gene mutations. All patients were alive without recurrence or metastasis after surgery, with a mean follow\u2010up of 47.7\u2009months (range: 4\u2013111\u2009months) and a median of 46\u2009months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This is the largest clinicopathological study to date on RCC\u2010HB. Our findings support that the vast majority of RCC\u2010HB harboured\n                      <jats:italic>TSC\/MTOR<\/jats:italic>\n                      mutations, different from CCRCC, expanding the morphological spectrum of\n                      <jats:italic>TSC\/MTOR<\/jats:italic>\n                      \u2010mutated renal tumours.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70003","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:46:16Z","timestamp":1758635176000},"page":"488-502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinicopathological and molecular characterization of seven rare cases of renal cell carcinoma with hemangioblastoma\u2010like features: Expanding the morphological spectrum of renal tumours with tuberous sclerosis complex\/mammalian target of rapamycin mutations"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6244-7852","authenticated-orcid":false,"given":"Xuan","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital, Fujian Medical University  Fuzhou China"},{"name":"Department of Pathology National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1991-1754","authenticated-orcid":false,"given":"Xiao\u2010tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1843-6075","authenticated-orcid":false,"given":"Peng\u2010cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital, Fujian Medical University  Fuzhou China"},{"name":"Department of Pathology National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-5778","authenticated-orcid":false,"given":"Yu\u2010peng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital, Fujian Medical University  Fuzhou China"},{"name":"Department of Pathology National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5794-4303","authenticated-orcid":false,"given":"Yi\u2010juan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0952-7437","authenticated-orcid":false,"given":"Qiu\u2010yuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Pathology Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-1937","authenticated-orcid":false,"given":"Qiu","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Pathology Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3548-0567","authenticated-orcid":false,"given":"Xiao\u2010ming","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pathology Longyan First Hospital  Longyan 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2793-6461","authenticated-orcid":false,"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital, Fujian Medical University  Fuzhou China"},{"name":"Department of Pathology National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.04.022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/0377-4929.162898"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1066896919840435"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-022-02844-3"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15098"},{"key":"e_1_2_10_7_1","first-page":"1","article-title":"Renal cell carcinoma with fibromyomatous stroma (RCC FMS) and with hemangioblastoma\u2010like areas is part of the RCC FMS spectrum in patients with tuberous sclerosis complex","author":"Baranova K","year":"2025","journal-title":"Histopathology"},{"key":"e_1_2_10_8_1","first-page":"1467","article-title":"Current knowledge and prospects for renal hemangioblastoma and renal cell carcinoma with hemangioblastoma\u2010like features","volume":"11","author":"Kojima F","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001955"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts146"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1486"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.127"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001422"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13791"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5875"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/327721a0"},{"key":"e_1_2_10_18_1","first-page":"4707","article-title":"A detailed deletion mapping of the short arm of chromosome 3 in sporadic renal cell carcinoma","volume":"51","author":"Yamakawa K","year":"1991","journal-title":"Cancer Res."},{"key":"e_1_2_10_19_1","first-page":"3","article-title":"Review: mammalian target of rapamycin (mTOR) pathway is critical in developing Most renal cell tumors","volume":"53","author":"Zhang KJ","year":"2023","journal-title":"Ann. Clin. Lab. Sci."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006242"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.13425"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-22-0171"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002211"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-03137-7"},{"key":"e_1_2_10_26_1","first-page":"698","article-title":"Human embryonic genetic mosaicism and its effects on development and disease","volume":"25","author":"Waldvogel SM","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13735"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T08:16:08Z","timestamp":1765786568000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/his.70003"],"URL":"https:\/\/doi.org\/10.1111\/his.70003","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,23]]},"assertion":[{"value":"2025-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}