Reliability and Role of Mutation-specific H3F3A (Histone 3-3) G34W Immunohistochemistry to Differentiate Giant Cell Tumor of Bone From its Clinicoradiologic and Histologic Mimics: An Institutional Study

Abstract

Giant cell tumor of bone (GCTB) is a benign neoplasm, which can sometimes be a diagnostic challenge, especially in small biopsies, due to its histologic benign and malignant mimics. We evaluated the role of H3.3 G34W immunohistochemistry (IHC) antibody in diagnosing GCTB and its role in differentiating it from its close histologic mimics. A total of 120 cases (80 cases of GCTB and 40 cases of histologic mimics) were retrieved and subjected to IHC. Of 80 cases of GCTB, 72 cases showed a positive nuclear immunoexpression, while all 40 cases of histologic mimics of GCTB showed a negative staining for H3.3 G34W IHC. Sensitivity and specificity of this mutation-specific antibody for diagnosis of GCTB was 90% and 100%, respectively, while, the positive predictive value and the negative predictive value were 100% and 83.3%, respectively. A positive expression of H3.3 G34W was seen in all 5 cases of GCTB, postdenosumab therapy, as well as, in all 3 cases of malignant giant cell tumor. The presented study showed that H3.3 G34W mutation-specific IHC is a reliable and specific marker for GCTB and can help distinguish it from the histologic mimics due to distinct therapeutic implications.

Secondary Malignancy in Giant Cell Tumor: A Single-Center Study

“…Several recent studies have demonstrated that the H3F3A mutation might contribute to distinguishing GCTB-related tumors from those that are giant-cell-rich [ 10 , 52 , 53 , 54 ]. However, there are differences in the frequency of H3F3A mutations found in previous reports; these mutations were identified in 69–100% of GCTB [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. One study [ 54 ] suggested that diagnosis of GCTB without the H3F3A alteration should be confirmed with considerable caution.…”

Progress on Denosumab Use in Giant Cell Tumor of Bone: Dose and Duration of Therapy

“…The expression of H3.3 G34W mutant protein in GCTB after denosumab therapy suggests that tumor stromal cells may play a role in the formation of a new bone. Therefore, the detection of H3F3A by IHC or sequencing is extremely helpful for the diagnosis of bone tumors lacking giant cells [ 45 , 46 , 47 ]. Some scholars have compared the sensitivity and specificity of sequencing and IHC for detecting the H3F3A gene for GCTB diagnosis.…”