H3.3 K36M Mutation as a Clinical Diagnosis Method of Suspected Chondroblastoma Cases

Abstract

Objective Whether H3.3 K36M mutation (H3K36M) could be an approach if the diagnosis of chondroblastoma (CB) patients was indistinct and it was suspected to be unclear clinically. Methods We reviewed and compared our clinical experiences of CB cases and some suspected cases, which were not diagnosed distinctly, between 2013 to 2019. A total of 15 male and four female cases included in this study were seperated into two groups, CB group and suspected case (SC) group. The CB group included 13 men and 3 women, with an age range from 9 to 54 (mean age, 22 years old). The SC group included two men and one woman, with the age range from 13 to 25 (mean age, 19 years old). In both groups the patients had been followed‐up until December 2019 and none of the patients had prior treatment history. We evaluated the clinical complaints, radiological features, and clinical‐histological features of the cases and performed an immunohistochemical (IHC) study to detect whether the H3K36M expression of cases was different, consistent with a gene‐mutation analysis. Results In both groups, the radiologic features of both groups appeared as round low‐density shadow with a clear edge, pathologic features showed diffuse proliferation of neoplastic cells with multinuclear giant cells. The radiological tumor size of CB group and SC group showed little difference, which was about 29.0*21.6 mm. Clinical‐immunohistochemical features of both groups showed chondroid matrix inside with naïve tumor cells, multinucleated giant cells, and ground substance cells. Most of them showed chondro‐related antibody positive (12 cases) but some of them showed S‐100 negative (four cases). The clear difference of both groups was the result of H3K36M IHC study and gene analysis. In our cases, the CB group showed diffuse H3K36M positive and the SC group showed negative. The gene mutation analysis revealed that H3K36M‐positive CB patients had K36M mutation, which were not found in the SC group. Sanger sequencing showed an A > T substitution at codon 36 of histone H3F3B. No other types of histone H3 mutation was detected in the CB group. Particularly, one of the suspected cases showed a G34W mutation was confirmed to be a giant cell tumor of bone (GCTB). Conclusions Our study showed H3K36M immunohistochemistry and gene mutation analysis were specific clinical diagnostic tools to distinguish suspected CB from other giant cell‐rich or cartilage matrix‐diffuse bone tumors. The clinical‐radiological and histomorphological features of patients gave suggestions on whether the H3K36M IHC and gene analysis should be required.

Anti-histone H3.3K36M Antibody is a Highly Sensitive and Specific Immunohistochemistry Marker for the Diagnosis of Chondroblastoma. A Validation Based on Study 136 Cases Comprising Chondroblastoma and its Mimics from Single a Centre in India

“…4 The monoclonal H3.3K36M antibody directed against K36M mutation is an useful ancillary diagnostic tool for the diagnosis of chondroblastoma. 8,17 Similar to the present study Rekhamper et al also found positive nuclear staining in all the cases of chondroblastoma tested. The authors further performed DOG1 IHC and found positivity in 11 out of 14 cases.…”

Metaphyseal chondroblastoma in a pediatric patient

“…Histologically, there is an increase in chondroblasts, the immature precursors to chondrocytes, and giant cells [3] . Chondroblastomas were found to express an H3F3B K36M point mutation which can aid in the correct identification of the tumor [8] . Intralesional curettage with adjuvants, such as phenol or hydrogen peroxide, is the gold standard for treatment [1] .…”