{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:08:56Z","timestamp":1782493736464,"version":"3.54.5"},"reference-count":40,"publisher":"BMJ","issue":"5","funder":[{"name":"Beijing JST Research Funding","award":["ZR202211"],"award-info":[{"award-number":["ZR202211"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2026,2,4]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Malignant transformation of fibrous dysplasia (FD) in long bones is very rare. This study aimed to explore its clinicopathological and molecular characteristics to reveal the diagnostic features and pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a clinicopathological analysis of 19 FD-associated sarcomas. Sanger and next-generation sequencing were used to detect molecular alterations, and clinical, radiological and histopathological features were reviewed in detail.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort consisted of 10 female and nine male patients (mean age, 48.4 years). Eleven patients had a previous diagnosis of FD, and eight patients presented de novo with acute symptoms like pain, swelling or dysfunction. Radiologically, in the monostotic cases (n=13), osteolytic lesions were observed with ill-defined margins, cortical destruction and soft tissue masses. Polyostotic cases (n=6) had both malignant masses and classic FD features of other skeletal sites. Histopathologically, osteosarcoma was the most common (57.9%), followed by undifferentiated pleomorphic sarcoma (26.3%), grade 2 spindle cell sarcoma (not otherwise specified, 5.3%) and low-grade central osteosarcoma (10.5%). Molecular analysis revealed identical\n                      <jats:italic>GNAS<\/jats:italic>\n                      mutations in paired FD and malignant components. Next-generation sequencing identified universal\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      alterations (100%), along with concurrent\n                      <jats:italic>TP53<\/jats:italic>\n                      (28.6%),\n                      <jats:italic>TERT<\/jats:italic>\n                      (28.6%) and\n                      <jats:italic>KDM6A<\/jats:italic>\n                      (28.6%) mutations, indicating a potential collaborative role in the FD malignant transformation process.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our analysis revealed unique clinicopathological characteristics and genetic markers in FD-associated sarcomas, deepening our knowledge of the mechanisms behind malignant transformation in FD and offering diagnostic tools for enhanced pathological assessment.<\/jats:p>\n          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