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.

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

FRANCHI, ALESSANDRO
2017-01-01

Abstract

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.
2017
Mancini, Irene; Righi, Alberto; Gambarotti, Marco; Picci, Piero; Dei Tos, Angelo P.; Billings, Steven D.; Simi, Lisa; Franchi, Alessandro
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/876373
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