UNASSIGNED: @entity2967 ( @entity2967 ) of bone is a @entity146 characterized by an abundance of @entity2527 cells that are induced by the neoplastic mononuclear cells; the latter express high levels of @entity5298 ( @entity5298 ). Denosumab, a @entity5298 inhibitor, which is clinically used to treat @entity2967 , leads to a marked alteration in the histologic appearance of the @entity5 with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other @entity5 of bone. Most significantly, denosumab-treated @entity2967 (tGCT) with abundant bone deposition may @entity421 , or @entity2967 that has undergone malignant transformation. To histologically characterize tGCT, we identified 9 cases of @entity2967 biopsied or resected after denosumab treatment. tGCT cases included 16 specimens from 9 @entity1 including 6 female and 3 male individuals aged 16 to 47 (median 32) years. Duration of treatment varied from 2 to 55 months. We compared these @entity5 with @entity5 arising in GCTs (n=9). The histology of tGCT was variable but appeared to relate to the length of therapy. All tGCTs showed marked giant cell depletion. Early lesions were highly cellular, and the combination of cellularity, atypia, and haphazard bone deposition caused the lesion to resemble high-grade @entity421 . Unlike de novo high-grade @entity421 or @entity5 arising in @entity2967 , however, tGCT showed less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. @entity5 in @entity1 on prolonged therapy showed decreased cellularity and abundant new bone, deposited as broad, rounded cords or long, curvilinear arrays. The latter morphology was reminiscent of low-grade @entity421 , but, unlike low-grade @entity421 , tGCT was negative for @entity7465 and again lacked an infiltrative growth pattern. Overall, tGCT may have a wide range of morphologic appearances. Because the @entity5 bear little resemblance to their pretreatment counterparts, careful attention to the history of denosumab administration is crucial to avoid a misdiagnosis with an important impact on therapy. Unlike malignant GCTs, tGCTs lack significant nuclear atypia, mitotic activity, and infiltration of preexisting bone, but instead show a unique pattern of intralesional bone deposition.

Denosumab-treated Giant Cell XXXX of Bone Exhibits Morphologic Overlap With Malignant Giant Cell Tumor of Bone.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity146 :: ('MESH:D001523', 'Disease') :: ['locally aggressive benign neoplasm'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'primary tumors', 'treated tumors', 'Tumor', 'malignant neoplasms', 'malignancies', 'tumors'] @entity7465 :: ('4193', 'Gene') :: ['MDM2'] @entity5298 :: ('8600', 'Gene') :: ['receptor activator of nuclear factor k-B ligand', 'RANKL'] @entity2967 :: ('MESH:D005870', 'Disease') :: ['GCT', 'Giant cell tumor'] @entity421 :: ('MESH:D012516', 'Disease') :: ['central osteosarcoma', 'osteosarcoma', 'mimic de novo osteosarcoma'] @entity2527 :: ('MESH:D001862', 'Disease') :: ['osteoclastic giant']
@entity5 :: (MESH:D009369,Disease) :: ['Tumor']
