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

Abstract

Introduction: Chondroblastoma has a wide range of differential diagnosis encompassing various benign and malignant entities. The closest differential diagnosis is giant cell tumor of the bone due to overlapping radiological and histomorphological features. Extensive aneurysmal bone cyst like changes and lack of adequately sampled chondroid matrix often masquerades the primary bone lesion and amplifies the diagnostic difficulty in small biopsies with limited tissue. Immunohistochemistry is helpful in such instances to resolve the diagnostic dilemma. Objectives: To analyze the immunohistochemical expression of anti-histone H3F3K36M antibody inchondroblastoma and validate its utility in differentiating chondroblastomafrom its histological mimics. Material and methods: Immunohistochemistry was performed using anti-histone antibody H3.3K36M in 44 histologically diagnosed chondroblastoma and 92 other histological mimickers. All chondroblastoma and giant cell tumor of the bone included in the study were also tested for anti-histone H3.3 G34W antibody. Of the 33 giant cell tumors of bone with classic morphology and imaging findings, 24 H3.3 G34W positive and 9 negative tumors were included intentionally to rule out the possibility of chondroblastoma. The sensitivity, specificity, positive and negative predictive value of marker with regard to chondroblastoma was calculated. Results: Immunohistochemistry revealed unequivocal nuclear positivity for H3.3K36M in the mononuclear cells in all the 44 Chondroblastoma tested, denoting a sensitivity of 100% cases. Allthesetumors tested simultaneously for anti-histone H3.3G34W were negative. None of the histological mimickers were positive H3.3K36M indicating a specificity of 100%. The positive and negative predictive value was 100%. Conclusion: H3.3K36M mutant antibody is highly sensitive and specific IHC marker and can be used as a valuable adjunct to distinguish chondroblastomafrom its histological mimics especially on small biopsies.