Giant cell tumor of soft tissue is genetically distinct from its bone counterpart

Abstract

Giant cell tumors of bone are locally aggressive bone neoplasms with a predilection for young adults. Histologically, they are composed of histiocytoid to spindled mononuclear cells, admixed with numerous large osteoclastic giant cells. Giant cell tumors of soft tissue are rare tumors that bear striking histological resemblance to giant cell tumors of bone and might be regarded as a soft tissue analog thereof. Point mutations of the H3F3A gene (coding for a histone H3.3 protein) at the Gly34 codon, mostly G34W resulting from a GGG>TGG nucleotide change, have recently been identified in a vast majority of giant cell tumors of bone. To delineate the possible pathogenic linkage between both tumor types, we analyzed the H3F3A genotypes in a series of 15 giant cell tumors of soft tissue by Sanger sequencing and found no mutation in any case. We then sequenced cognate histone H3 genes with an identical nucleotide sequence ('GGG') at the codon Gly34, including the H3F3B, H3F3C, HIST2H3A, HIST2H3C, and HIST2H3D genes, and no somatic mutation was detected. These results reveal that giant cell tumors of soft tissue are probably genetically distinct from their bone counterparts and suggest that they might be pathogenically unrelated. Given the prominence of non-neoplastic cells in these tumors and the limitations of the current study, however, analyses using more sensitive techniques might be required to solve the issue.

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

“…In the present series, although we confirm that GCT‐B predominantly has H3F3A mutations at glycine 35, with no involvement of H3F3B , we show that GCT‐ST does not have this molecular alteration. These results are in keeping with a recent analysis of 15 GCT‐STs, in which no somatic mutation was detected in H3F3A , H3F3B , H3F3C , HIST2H3A , HIST2H3C , and HIST2H3D . In addition, our results were confirmed by COLD PCR analysis.…”

“…In a recent study, no H3F3 mutations were detected in a series of 15 GCT‐STs, indicating that GCT‐ST might be genetically different from its osseous counterpart . To expand these observations, we compared a series of GCT‐STs and GCT‐Bs with regard to the presence of H3F3A and H3F3B mutations and several immunophenotypic markers.…”

Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors

“…The neoplastic mononuclear cells of GCT-ST display a similar immunophenotype as their osseous counterparts. They express monocyte-macrophageassociated antigen CD68, tartrate-resistant acid phosphatase, and smooth muscle actin, but not CD45, desmin, S100 protein, and lysozyme [16][17][18][19][20]. The osteoclastic giant cells express CD68, but not CD163 [28].…”

First Case Report of a Huge Giant Cell Tumor of Soft Tissue Originating from the Retroperitoneum

“…GCT-ST is considered a tumor of low malignant potential, but giant cell tumor of bone is a locally aggressive tumor. Lee et al suggested the genetic distinction between GCT-ST and giant cell tumor of bone [ 16 ]. They analyzed the genotype of H3F3A in 15 cases of GCT-ST.…”