title: Periosteal chondrosarcoma: a histopathological and molecular analysis of a rare chondrosarcoma subtype.
abstract: OBJECTIVE
  Periosteal chondrosarcoma is a rare, malignant cartilage-forming neoplasm originating from the periosteal surface of bone. We collected 38 cases from the archives of the Netherlands Committee on Bone Tumours, with the aim of studying histological features and evaluating the involvement of isocitrate dehydrogenase 1 (IDH1), EXT, Wnt/β-catenin, the pRB pathway (CDK4 and p16), and the TP53 pathway (p53 and MDM2).
  
  
  RESULTS
  Histology showed a moderately cellular matrix with mucoid-myxoid changes and, in 42% of cases, formation of a neocortex. Occasional intramedullary extension (26%) and subsequent host bone entrapment (40%) were seen. Histological grading revealed grade 1 (53%) and grade 2 (45%). The EXT1 protein was normally expressed, and mutations in IDH1 were observed in only 15% of cases. pRb signalling was deregulated by loss of p16 expression in 50% of cases, and Wnt signalling was lost in 89%. No alterations were found in CDK4, p53, or MDM2.
  
  
  CONCLUSIONS
  We report the first large histological and molecular study on periosteal chondrosarcoma showing that histopathological examination and molecular aberrations do not predict prognosis. Although the mutation frequency of IDH1 was low, we confirm the supposed relationship with central chondrosarcoma. Moreover, we identify loss of canonical Wnt signalling and deregulation of pRb signalling as possible events contributing to its histogenesis.
authors: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Arjen H G
authors: AH
authors: Cleven
authors: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Evita
authors: E
authors: Zwartkruis
authors: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Pancras C W
authors: PC
authors: Hogendoorn
authors: Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Herman M
authors: HM
authors: Kroon
authors: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Inge
authors: I
authors: Briaire-de Bruijn
authors: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Judith V M G
authors: JV
authors: Bovée
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010521:Periosteum / Q000473:pathology*; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: IDH1; bone tumour; chondrosarcoma; periosteal chondrosarcoma