Immunohistochemical expression of H3.3 G34W in 100 giant cell tumors of bone and its diagnostic mimics, including its value in resolving uncommon diagnostic scenarios: A single institutional study at a tertiary cancer referral center, India

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dc.contributor.authorRekhi, Bharaten_US
dc.contributor.authorDave, Vinayaken_US
dc.contributor.authorButle, Ashwinen_US
dc.contributor.authorDharavath, Bhaskeren_US
dc.contributor.authorKhetale, Sonalien_US
dc.contributor.authorRedhu, Archana K.en_US
dc.contributor.authorSingh, Rudranshen_US
dc.contributor.authorDutt, Amiten_US
dc.date.accessioned2025-05-09T09:57:06Z
dc.date.available2025-05-09T09:57:06Z
dc.date.issued2024-09
dc.description.abstractBackground: There can be a diagnostic challenge in differentiating giant cell tumor of bone (GCTB) from its mimics. Lately, histone H 3F3A (Histone 3.3) G34W has been identified as a promising immunohistochemical marker. Aims: This study was aimed at evaluating H3.3 G34W immunostaining in 100 GCTBs, including its value in resolving diagnostic dilemmas. Materials and Methods: Immunohistochemical staining for H3.3 G34W was graded in terms of staining intensity (1+ to 3+) and the percentage of tumor cells showing crisp nuclear staining. Results: One hundred GCTBs occurred in 58 males and 42 females (M: F ratio = 1.3), of 7?66 years age (average = 31.3, median = 28), commonly in distal femur (26), followed by proximal tibia (17), distal radius (12), proximal humerus (7), metacarpals (7), sacrum (6), proximal fibula (6), and relatively unusual sites (19), including a single multicentric case. Out of 92 GCTBs, wherein H3.3 G34W immunostaining worked, 81 (88.1%) showed positive staining in the mononuclear cells, including tumors with fibrous histiocytoma?like areas, sparing osteoclast?like giant cells, with 3+ staining intensity in 65/81 (80%) tumors. All 7/7 (100%) malignant GCTBs showed positive staining, including the pleomorphic/sarcomatous cells. All 7/7 (100%) metastatic GCTBs showed positive immunostaining. Seven out of 10 post?denosumab treated GCTBs showed positive H3.3 G34W immunostaining in the residual mononuclear cells. None of the other 37 “giant cell?rich” lesions displayed H3.3 G34W immunostaining. Four of 9 GCTBs tested for H3.3 G34W mutation showed positive results. Conclusions: The diagnostic sensitivity and specificity of H3.3 G34W for GCTB were 88.1% and 100%, respectively. This constitutes one of the first reports from our country, further validating the diagnostic value of H3.3 G34W in differentiating GCTB, including metastatic and malignant forms from its mimics, including small biopsy samples. Its value in various diagnostic dilemmas is presented and utility in identifying residual tumor cells in post?denosumab treated GCTBs is worth exploring.en_US
dc.identifier.affiliationsDepartment of Pathology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI) University, Mumbai, Maharashtra, India; Department of Molecular Pathology and Translational Medicine, Tata Memorial Centre, Homi Bhabha National Institute (HBNI) University, Mumbai, Maharashtra, Indiaen_US
dc.identifier.affiliationsDepartment of Pathology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI) University, Mumbai, Maharashtra, Indiaen_US
dc.identifier.affiliationsIntegrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, Indiaen_US
dc.identifier.affiliationsIntegrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, India; HBNI Training School Complex, Maharashtra, Indiaen_US
dc.identifier.affiliationsDepartment of Molecular Pathology and Translational Medicine, Tata Memorial Centre, Homi Bhabha National Institute (HBNI) University, Mumbai, Maharashtra, Indiaen_US
dc.identifier.affiliationsIntegrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, Indiaen_US
dc.identifier.affiliationsIntegrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, Indiaen_US
dc.identifier.affiliationsIntegrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, India; HBNI Training School Complex, Maharashtra, Indiaen_US
dc.identifier.citationRekhi Bharat, Dave Vinayak, Butle Ashwin, Dharavath Bhasker, Khetale Sonali, Redhu Archana K., Singh Rudransh, Dutt Amit. Immunohistochemical expression of H3.3 G34W in 100 giant cell tumors of bone and its diagnostic mimics, including its value in resolving uncommon diagnostic scenarios: A single institutional study at a tertiary cancer referral center, India. Indian Journal of Pathology & Microbiology. 2024 Sep; 67(3): 542-552en_US
dc.identifier.issn0377-4929
dc.identifier.issn0974-5130
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/245479
dc.languageenen_US
dc.publisherWolters Kluwer – Medknowen_US
dc.relation.issuenumber3en_US
dc.relation.volume67en_US
dc.source.urihttps://doi.org/10.4103/ijpm.ijpm_886_23en_US
dc.subjectBone tumoren_US
dc.subjectdenosumaben_US
dc.subjectgiant cell tumor of boneen_US
dc.subjectH3.3 G34Wen_US
dc.titleImmunohistochemical expression of H3.3 G34W in 100 giant cell tumors of bone and its diagnostic mimics, including its value in resolving uncommon diagnostic scenarios: A single institutional study at a tertiary cancer referral center, Indiaen_US
dc.typeJournal Articleen_US
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