Role of H3F3A (H3G34W) antibody in the diagnosis of giant cell tumour of bone in the paediatric age group

Abstract

Giant cell tumour of the bone (GCTB) occurring in paediatric patients is rare and may presents with atypical histology. Given that giant cell tumour mimics, such as osteosarcoma, are more prevalent in this demographic, diagnosing GCTB can often be challenging. This study aimed to investigate the efficacy of H3F3A immunohistochemistry (IHC) in the diagnosis of GCTB in the immature skeleton. This retrospective study included paediatric patients who were diagnosed with GCTB between 2009 and 2024. Histological features were re-evaluated and IHC staining was performed. Giant cell tumour mimics were included in the control group. 72 biopsy proven GCTB were reported in the paediatric patients during the study period. The age ranged from 12 to 18 years, with a median age of 16 ( ± 1.8) years. 49 (68.1 %) were females and 23 (31.9 %) were males (female to male ratio of 2.1:1). Tibia was most common site (23) involved followed by femur (12), fibula (8) and small bones of hand and feet (8). H3G34W was positive in 61 (84.7 %) of GCTB cases (p < 0.01); and negative in all 33 GCTB mimics. H3G34V was positive in 3 of 11 H3G34W negative cases. All these 11 cases were negative for H3G34R and keratin AE1/AE3. Significant association of GCTB was found with gender (p = 0.02) and site of the tumour (p < 0.01). HG34W was not associated with tumour site (p = 0.4533) or biopsy yield (p = 0.4533). A sensitivity of 84.74 %, specificity of 100 %, positive predictive value of 75 % and negative predictive value of 100 % was established. An ROC was constructed, with area under the curve of 0.924 (95 % CI 0.88–0.97). In conclusion H3G34W antibody is a valuable diagnostic tool for accurately diagnosing GCTB and distinguishing it from other giant cell mimics. Additionally, since a minimal tissue yield is adequate for determining the diagnosis, the need for larger biopsies is reduced.