{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:45:51Z","timestamp":1792439151402,"version":"4.5.0"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"43","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA229529"],"award-info":[{"award-number":["R01CA229529"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,27]]},"abstract":"<jats:p>\n                    Keratin-positive giant cell\u2013rich tumor (KPGCT) is a newly described bone and soft tissue tumor. The tumor is characterized by scattered keratin-positive cells and the presence of\n                    <jats:italic toggle=\"yes\">HMGA2::NCOR2<\/jats:italic>\n                    fusions. It is not known if the\n                    <jats:italic toggle=\"yes\">HMGA2::NCOR2<\/jats:italic>\n                    fusion is located in the keratin-positive cells, and little is known about how KPGCT develops. KPGCT shares some histologic features with tenosynovial giant cell tumor (TGCT), a soft tissue tumor with\n                    <jats:italic toggle=\"yes\">CSF1<\/jats:italic>\n                    rearrangements. Single-nuclei RNA sequencing and Xenium spatial transcriptomics were used to elucidate the most likely mechanisms driving KPGCT and compare KPGCT to TGCT. We identified a population of cells coexpressing keratin,\n                    <jats:italic toggle=\"yes\">HMGA2<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">CSF1<\/jats:italic>\n                    as the likely neoplastic cells; these cells constitute the minority of the cells in the tumor. These cells express no synovial markers, confirming KPGCT as a distinct entity, separate from TGCT. The bulk of the tumor consists of\n                    <jats:italic toggle=\"yes\">CSF1R<\/jats:italic>\n                    -expressing macrophages and multinucleated giant cells (MNGCs), suggesting an important role for CSF1\u2013CSF1R signaling. In addition, we find that the likely neoplastic cell population shows activation of the hippo signaling pathway, a possible central pathway in KPGCT tumorigenesis. The CSF1\u2013CSF1R axis likely stimulates the migration and proliferation of macrophages, which form the majority of cells in the tumor, as well as their differentiation into MNGCs. These results provide a rationale for the use of CSF1R inhibitors, which have already shown efficacy in TGCT, as a therapy for KPGCT.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2611959123","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:01:49Z","timestamp":1792436509000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Identification and characterization of neoplastic cells in keratin-positive giant cell\u2013rich tumors"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6580-5137","authenticated-orcid":false,"given":"Maarten","family":"van der Linde","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Stanford University","place":["Stanford"]},{"id":[{"id":"https:\/\/ror.org\/05xvt9f17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Leiden University Medical Center","place":["Leiden, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-0923","authenticated-orcid":false,"given":"John S. 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