title: Symplastic/pseudoanaplastic giant cell tumor of the bone.
abstract: OBJECTIVE
  Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor. Its malignant counterpart is quite rare. Rarely, a conventional GCTB shows marked nuclear atypia, referred to as symplastic/pseudoanaplastic change, which can mimic sarcomatous transformation. Recently, somatic driver mutations of histone H3.3 exclusively in H3F3A have been described in GCTB. We report a series of 9 cases of GCTB with symplastic/pseudoanaplastic change, along with analysis of H3F3A variants.
  
  
  METHODS
  Nine cases of GCTB with symplastic change were identified. Clinico-radiological features, morphological features, and immunohistochemical stain for Ki-67 stain were reviewed. H3F3A variants were also analyzed using Sanger sequencing.
  
  
  RESULTS
  Histologically, conventional giant cell tumor areas with scattered foci of markedly atypical cells were seen in all of the cases and all showed rare if any Ki-67 labeling. One patient had received denosumab treatment and another radiation therapy. Radiological features were characteristic of conventional GCTB. Mutation in H3F3A (p.Gly34Trp [G34W]) was found in 6 of the 7 cases. Clinical follow-up ranged from 6 to 208 months. Local recurrences were seen in 4 cases (44 %).
  
  
  CONCLUSIONS
  GCTB with symplastic/pseudoanaplastic change is an uncommon variant of conventional GCTB, which can mimic primary sarcoma or sarcomatous transformation. These tumors possess the same missense mutation in histone H3.3 as conventional GCTB.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY, 10065, USA. sarungbj@mskcc.org.
authors.forename: Judy
authors.initials: J
authors.lastname: Sarungbam
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Narasimhan
authors.initials: N
authors.lastname: Agaram
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Sinchun
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: John
authors.initials: J
authors.lastname: Healey
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Hameed
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics*; D000069448:Denosumab; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000000981:diagnostic imaging* / Q000235:genetics*; D006657:Histones / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies
chemical_list: D006657:Histones; D000069448:Denosumab
keywords: Giant cell tumor of bone; Symplastic/pseudoanaplastic