Chondroblastoma (CB) is a benign bone tumor that occurs in the metaphysis to epiphysis of long bones of younger people [1]. In imaging findings, CB exists as an eccentric osteolytic lesion, accompanied by an edematous lesion around the tumor. In terms of its histological character, CB reveals a proliferation of oval to short spindle-shaped cells having grooved nuclei, osteoclast-like multinucleated giant cells, eosinophilic “chondroid” matrix, and calcification, which is called “chicken wire calcification.” Cartilaginous islands can be seen focally. Historically, CB was classified as a chondrogenic tumor; however, it has been reported that the eosinophilic matrix is similar to osteoid rather than true cartilage [2]. Genetically, CB is reported to harbor H3F3B p.K36M mutation and rarely H3F3A mutation p.K36M [3]. Immunohistochemically, the vast majority of CBs are immunoreactive for H3K36M mutant-specific antibody [4].

Giant cell tumor of bone (GCTB) is an intermediate-malignancy bone tumor located in the metaphysis to epiphysis like CB. Histologically, it shows a proliferation of mononuclear neoplastic cells with histiocytes, osteoclast-like multinucleated giant cells, and limited bone formation. The majority of GCTBs have H3F3A p.G34W mutation and are immunohistochemically positive for H3G34W mutant-specific antibody [5], [6], [7]. Interaction between receptor activator of nuclear factor kappa-B ligand (RANKL) and its receptor (RANK) is known to play an important role in GCTB [8]. Denosumab, an inhibitor of the RANK/RANKL axis, is widely used for patients with GCTB [6], [9], [10], [11], [12]. In histological specimens after denosumab treatment, remarkable bone formation is often seen [7], [8]. In such cases, the bone-forming cells are immunopositive for H3G34 mutant protein, suggesting that the neoplastic cells harboring H3F3A mutation may be responsible for new bone formation. Moreover, Kerr reported that neoplastic cells in denosumab-treated GCTB showed the immunohistochemical expression of osteoblastic markers [13]. These reports suggest that neoplastic cells of GCTB may have a feature of an osteoblastic precursor.

There are some osteogenic and chondrogenic markers applicable to histological specimens. Special AT-rich sequence-binding protein 2 (SATB2) [14], [15], [16] and runt-related transcription factor 2 (RUNX2) play essential roles in osteoblastic differentiation [17], [18] and are used as osteoblastic markers. p63 is also involved in osteoblastic differentiation and is frequently expressed in GCTB [19], [20], [21], [22]. As for chondrogenic markers, SRY-box transcription factor 9 (SOX9) is a transcription factor that is essential for chondroblastic differentiation [23]. In addition, RUNX2 also participates in chondrocyte maturation and can be expressed in chondroblastic cells [17], [18]. Although CBs can show osteoid formation and share morphological and genetic features with GCTBs, the status of their expression of osteoblastic differentiation markers has remained unclear. In this study, we aimed to clarify potential osteoblastic differentiation in CB.