{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:33:57Z","timestamp":1793918037804,"version":"4.8.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Due to its heterogeneous morphology and its rarity, anaplastic lymphoma kinase gene-rearranged renal cell carcinoma (\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    RCC) is a diagnostically challenging entity, often leading to labelling these tumors as RCC, not otherwise classified. This may have clinical and managerial implications, given that patients with\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    oncogene rearrangement may benefit from\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    -inhibitors. Therefore, we attempted to elucidate the clinicopathologic and immunophenotypical characteristics of\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    RCC in a large international cohort. Sixteen multi-institutional tumors were included in the study. Clinical, macroscopic, microscopic, immunohistochemical (IHC), molecular (DNA and RNA sequencing, FISH) and follow-up data were evaluated. There were 9 male and 7 female patients with tumor size ranging from 2 to 12.2\u00a0cm (mean=7.1\u00a0cm). All tumors had solid, tan-white with focal cystic changes and gelatinous appearance. Cystic changes and necrosis were seen in 7 and 6 tumors, respectively. Microscopically, a heterogeneous growth pattern was observed including solid (12), tubular (7), papillary (5), tubulocystic (2), pleomorphic epithelioid cells (6), sarcomatoid (2), rhabdoid (4), and intranuclear pseudoinclusions. All tumors were ALK-positive, coexpressing PAX8, KRT7, SDH, FH, and variably CD10, Vimentin, and AMACR. Molecular analysis through next-generation sequencing (NGS) was performed on 14\/16 tumors.\n                    <jats:italic toggle=\"yes\">EML4::ALK<\/jats:italic>\n                    (n=5) was the most common gene fusion observed; others included\n                    <jats:italic toggle=\"yes\">TPM1::ALK<\/jats:italic>\n                    (n=4)\n                    <jats:italic toggle=\"yes\">, TPM3::ALK<\/jats:italic>\n                    (n=2),\n                    <jats:italic toggle=\"yes\">SLIT1::ALK<\/jats:italic>\n                    (n=2)and\n                    <jats:italic toggle=\"yes\">VCL::ALK<\/jats:italic>\n                    (n=1). Despite focal TFE3 immunoreactivity in 4\/13 cases, the absence of\n                    <jats:italic toggle=\"yes\">TFE3<\/jats:italic>\n                    gene rearrangement by molecular analysis excludes\n                    <jats:italic toggle=\"yes\">TFE3<\/jats:italic>\n                    - rearranged RCC as a differential diagnosis. Our study further expands the clinicopathologic, morphologic, and molecular genetic spectrum of\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    -RCC.\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    -RCC can be morphologically heterogeneous and mimic other well-established entities posing a misdiagnosis if appropriate IHC and\/or molecular studies are not performed. Accurate diagnosis is of clinical significance as patients with this neoplasm may potentially benefit from\n                    <jats:italic toggle=\"yes\">ALK-<\/jats:italic>\n                    inhibitors, particularly in a metastatic setting. As TFE3 immunoreactivity is not uncommon in\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    -RCC, documentation of\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    gene rearrangement is critical, either by surrogate IHC staining or cytogenetic\/molecular analysis is essential.\n                  <\/jats:p>","DOI":"10.1097\/pas.0000000000002525","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:00:09Z","timestamp":1772812809000},"page":"513-523","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["ALK-Rearranged Renal Cell Carcinoma"],"prefix":"10.1097","volume":"50","author":[{"given":"Anandi","family":"Lobo","sequence":"first","affiliation":[{"name":"Department of Pathology, Kapoor Centre of Urology and Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Akgul","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankur R.","family":"Sangoi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford Medical Center, Stanford"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaleel I.","family":"Al-Obaidy","sequence":"additional","affiliation":[{"name":"McLaren Pathology Group, McLaren Health Care, Flint, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Pathology, Indiana University Medical Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani R.","family":"Kandukuri","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Department of Urology, ILS Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav K.","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Oncology, All India Institute of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpy","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Pathology, Manipal Hospitals, Bhubaneswar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Kaushal","sequence":"additional","affiliation":[{"name":"Department of Pathology All India Institute of Medical Sciences, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Satturwar","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Wexner Medical Center\/James Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeboye O.","family":"Osunkoya","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Urology, Emory University School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil V.","family":"Parwani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasreman","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekta","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajal B.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambit K.","family":"Mohanty","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, CORE Diagnostics and CORE Group of Reference Laboratories"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-5293","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University Warren Alpert Medical 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