H3-3A (H3.3 Histone A)

Collectively, a TP53 abnormality at copy number (12/26, all cnLOH), sequence (55/60) and protein expression (46/48) level was detected in all 60 cases. In conclusion, integrated high-resolution copy number and histomolecular analysis expanded the spectrum of genetic changes associated with DHG-H3 G34, including the presence of universal TP53 abnormalities with frequent cnLOH-a copy number abnormality that has been largely unrecognized-for this new 2021 World Health Organization central nervous system tumor type.

The individualized regimen comprised trametinib and everolimus for dual pathway inhibition, the tissue-agnostic agent dordaviprone (ONC201), metabolic modulation with 2-deoxy-D-glucose, and electric field-based therapy. The systematic integration of comprehensive molecular profiling with mechanistically rational treatment selection may contribute to meaningful radiological and clinical benefit in this otherwise uniformly fatal disease. These observations support further investigation of individualized, pathway-targeted approaches in prospective studies and N-of-1 trial frameworks.

Soft tissue recurrence in GCTB may occur independently or following intraosseous recurrence and is frequently observed in high-grade lesions. Although not statistically significant, the findings suggest a possible association between tumor aggressiveness and STR. Histological features remain consistent with osseous lesions, but the diagnostic value of H3F3A expression in STRs warrants fur ther investigation. Importantly, STR represents a distinct recurrence pattern and may be associated with an increased risk of pulmonary metastasis, underscoring the need for vigilant long-term follow-up and systematic surveillance.   Cite this article as: Mirioğlu A, Dalkır KA, Ölke HC, et al. Soft tissue recurrence in giant cell tumor of bone: risk factors and radiological and histopathological features. Acta Orthop Traumatol Turc.,  2025;59(6):470-476.

The H3-3A gene sequencing assay demonstrated a sensitivity of 87.16% and an absolute specificity of 100% among the cases analyzed in the study. Determination of the H3-3A gene mutation by sequencing is a highly sensitive and absolutely specific diagnostic tool for the diagnosis of GCTB and differentiation from its histologic mimics.

There is only one other case that has been documented of a β-hCG-producing GCTBoccurring in the base of the skull with secondary aneurysmal bone cyst-like changes.This appears to be the first reported instance of β-hCG-secreting GCTB in the gnathicbones. This case exemplifies the diagnostic challenges of rare presentations of GCTBand alerts clinicians to the potential misleading presentation of hormone expression.

Herein, we present two cases of DIPG in which biopsy of disseminated lesions at recurrence revealed clinically significant genetic alterations, including high tumor mutational burden or a germline TP53 mutation. These findings underscore the potential clinical value of molecular genetic analysis from biopsied tissues, which may inform treatment decisions and guide patient management.

None malignant transformations occurred following denosumab or radiotherapy...SM-GCTB and osteosarcoma arise from benign GCTB but differ in morphology and prognosis. Because malignant transformation is exceptionally rare and symptomatic, a patient-centered, symptom-driven follow-up strategy is preferred over routine lifelong radiologic surveillance.

Management included repeat resection and denosumab therapy, achieving radiographic stability with preservation of vision in the right eye, although the optic nerve of the left eye remained atrophic. Given the diagnostic overlap between GCTB and ABC, the authors emphasize the importance of genetic testing for accurate and early diagnosis to enable timely treatment and reduce the risk of recurrence.

Systemic agents such as denosumab or bisphosphonates remain investigational, and radiotherapy is generally contraindicated due to malignant transformation risk...Awareness of risk factors, early imaging-based detection, and complete surgical excision are critical for optimal outcomes. Further multicenter studies are required to define surveillance protocols, validate molecular predictors, and clarify the role of systemic therapy in this challenging condition.

Serum calcium and parathyroid hormone measurements are essential in the evaluation of bone lesions. Hypercalcemia may indicate primary hyperparathyroidism but can also occur in myeloma, metastases, or granulomatous diseases.Brown tumours (BTs) and giant cell tumours (GCTs) of bone may overlap; BTs are associated with hypercalcemia and H3F3A negativity, while GCTs are characterized by normal calcium levels and H3F3A positivity.A multidisciplinary approach combining clinical, biochemical, and pathological data improves diagnostic accuracy in bone lesions by distinguishing benign, malignant and metabolic causes, ensuring appropriate management.

Immunohistochemistry with H3.3 G34W, H3.3 G34R and G34V can be used as a surrogate for detection of corresponding H3F3A gene mutations. These antibodies should be used as first-line tests for confirming the diagnosis with sequencing being restricted only to tumors negative on immunohistochemistry.

The aim of this study is to provide an account of our experience with this tumor within the Pakistani population. Here, we provide a retrospective analysis of 13 cases diagnosed at our hospital, highlighting the extremely varied morphology we encountered, along with their complete immunohistochemical workup.