Giant Cell Tumor of Bone

These cases reinforce that preoperative CNB with a targeted immunohistochemistry panel - explicitly distinguishing GCTB from ectopic axillary breast carcinoma - should be strongly recommended for any suspicious axillary tail mass; Case 1, in which the patient declined CNB and proceeded directly to surgery, illustrates by counter-example the diagnostic uncertainty that results when this step is omitted. We present these cases in accordance with the CARE reporting guidelines.

The results suggest the potential involvement of CXCR4 in the pathogenesis of giant cell granulomas of the jaws and GCTB. This chemokine receptor may also contribute to differences in the biological behavior of these MGC-containing lesions. The relevance of CXCL12 for the development of the giant cell lesions studied appears to be variable.

P3, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Feb 2026 --> Mar 2027

This case supports the existence of a shared pathogenic mechanism linking PPGLs and GCTBs, likely mediated by postzygotic H3F3A mutations. Recognition of this association is crucial for early diagnosis, genetic counseling, and management of similar cases.

P1/2, N=120, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Trial primary completion date: Jul 2026 --> Aug 2028

P2, N=9, Completed, Daiichi Sankyo Co., Ltd. | Active, not recruiting --> Completed

CYP26A1 expression was most frequent in giant cell tumors of bone. While also detected in a subset of other bone tumors, expression was limited or absent in most benign and malignant lesions, and entirely absent in normal bone tissue. These findings provide novel descriptive insight into CYP26A1 distribution and support further investigation into its role in retinoid-related pathways in bone tumor biology.

Stromal p63 and CD10 were commonly expressed in GCTB. CD10-high expression was associated with recurrent-case status in univariate analysis, but this exploratory finding should not be interpreted as recurrence prediction.

Intraoperative frozen section examination indicated a pathological diagnosis of low-grade malignant salivary gland tumor. Thus, comprehensive histopathological and molecular analyses are essential, as the morphological features of this tumor may be deceptively bland.

HtrA1 expression patterns in GCTB may provide preliminary insight into recurrence risk. Although no statistically significant association was demonstrated, the observed trends suggest potential prognostic relevance and warrant validation in larger cohorts.

Differentiating benign intra-articular tumors from SAH remains difficult, particularly among younger and female patient populations with acute presentations of TGCT which, as observed in the present study, may be explained by histopathologic evidence of tumor pedicle torsion and resultant necrosis. MRI can be valuable in identifying intra-articular lesions given that clinical and laboratory findings are frequently equivocal. The proposed diagnostic algorithm offers a framework for identifying cases where preoperative MRI may be beneficial, though it requires validation in larger studies.

Overall, our findings indicate that PMMRDGs represent a distinct type of IDH-wildtype gliomas with potential for long-term survival likely driven by immune activation.