Phenotypic and molecular differences between giant‐cell tumour of soft tissue and its bone counterpart

• Published in: Histopathology 2017-09, Vol.71 (3), p.453-460
• Main Authors: Mancini, Irene, Righi, Alberto, Gambarotti, Marco, Picci, Piero, Dei Tos, Angelo P, Billings, Steven D, Simi, Lisa, Franchi, Alessandro
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; bone; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Cbfa-1 protein; CD14 antigen; Child; Codons; Deoxyribonucleic acid; DNA; Female; Formaldehyde; Genotype; Giant Cell Tumor of Bone - genetics; Giant Cell Tumor of Bone - immunology; Giant Cell Tumor of Bone - pathology; Giant Cell Tumors - genetics; Giant Cell Tumors - immunology; Giant Cell Tumors - pathology; Giant cells; giant‐cell tumour; H3F3A gene; Humans; Immunohistochemistry; Leukocytes (mononuclear); Male; Middle Aged; Mutation; Neoplasia; Osteoblasts; Paraffin; Phenotype; Sequences; soft tissue; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - immunology; Soft Tissue Neoplasms - pathology; TRANCE protein; Tumors; Young Adult
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13249

Aims Giant‐cell tumour (GCT) of soft tissue (GCT‐ST) is a primary soft tissue neoplasm that is histologically similar to GCT of bone (GCT‐B). Recently, it has been reported that >90% of GCT‐Bs have a driver mutation in the H3F3A gene. As the relationship between GCT‐ST and GCT‐B is unclear, the aim of this study was to compare a series of GCT‐STs and GCT‐Bs with regard to the presence of H3F3A mutations and several immunophenotypic markers. Methods and results Eight GCT‐STs were retrieved from our institutional archives. Fifteen GCT‐Bs served as controls. Direct sequencing for H3F3A mutations in coding regions between codons 1 and 42, including the hotspot codons (28, 35, and 37), was performed on DNA extracted from formalin‐fixed paraffin‐embedded tissue. Tumours were studied immunohistochemically for the expression of CD14, CD33, RANKL, RANK, p63, and the osteoblastic markers SATB2 and RUNX2. None of the seven GCT‐STs that could be analysed showed H3F3A mutations, whereas 14 GCT‐Bs (93.3%) were mutated. All eight GCT‐STs were positive for RANK and RUNX2, whereas RANKL and SATB2 were detected in only two cases (25%). CD14 was detected only in mononuclear elements, whereas multinucleated giant cells and a proportion of the mononuclear population expressed CD33. Few mononuclear cells of GCT‐STs expressed p63. In comparison, GCT‐Bs showed higher expression of p63 (14 of 15 cases with >50% of positive mononuclear cells), RANKL, and SATB2, whereas CD14, CD33, RANK and RUNX2 were similarly expressed. Conclusions Although GCT‐ST and GCT‐B are similar in histological appearance, our results indicate that they are immunophenotypically and genetically distinct.