Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy

Schaefer, Inga‐Marie; Fletcher, Jonathan A.; Nielsen, G. Petur; Shih, Angela R.; Ferrone, Marco; Hornick, Jason L.; Qian, Xiaohua

doi:10.1002/cncy.22000

Cited by 52 publications

(39 citation statements)

References 24 publications

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“…Nohr et al 16 . have suggested the diagnostic value of H3K36M and Schaefer et al 12 . have attempted H3K36M IHC in biopsy and give the conclusion that H3K36M IHC is a highly specific method in limited biopsies.…”

Section: Discussionmentioning

confidence: 99%

“…Behjati et al 6 has revealed the mutations on histone H3F3A and H3F3B are the driver mutations in the generation of CB and GCTB, respectively. Previous studies have reported that the H3K36M and H3G34W mutations distinguish CB cases and GCTB cases, both in immunohistochemistry (IHC) 12 and gene mutation analysis 13 . In our studies, we collected three suspected CB cases once treated as CB on admission, not obvious on diagnosis, and compared their results of immunohistochemistry and gene mutation analysis with the confirmed CB cases (Figs 2 and 4 E1-E4 and F).…”

Section: Discussionmentioning

confidence: 99%

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

Yafei

Xue

et al. 2021

Orthopaedic Surgery

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Yafei

Xue

et al. 2021

Orthopaedic Surgery

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“…Recent studies have shown that the vast majority of CB harbour K36M substitutions resulting from H3F3B , or rarely H3F3A , mutations . Immunohistochemistry for monoclonal antibodies directed against the mutant histone H3.3 K36M proteins have been shown to be highly specific for the diagnosis of CB and are useful in challenging cases, particularly when the tumours are sampled with limited biopsy specimens …”

Section: Discussionmentioning

confidence: 99%

“…14,16,17 Immunohistochemistry for monoclonal antibodies directed against the mutant histone H3.3 K36M proteins have been shown to be highly specific for the diagnosis of CB and are useful in challenging cases, particularly when the tumours are sampled with limited biopsy specimens. 14,18 Clear cell chondrosarcoma is a rare, low-grade variant of chondrosarcoma that typically occurs in the third to fourth decades of life, and shows a predilection for the epiphyseal ends of long bones. The radiological findings overlap significantly with that of CB, as both may present as well-defined lytic lesions with a sclerotic rim often containing stippled calcific densities characteristic of cartilage matrix.…”

Section: Discussionmentioning

confidence: 99%

Chondroblastomas presenting in adulthood: a study of 39 patients with emphasis on histological features and skeletal distribution

et al. 2019

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Aims Chondroblastomas (CB) are rare bone tumours that typically arise in the epiphysis/apophysis of long bones in skeletally immature patients. We explore the clinicopathological features of CB presenting in adults. Methods and results CB in patients ≥20 years of age were retrieved from our institutional archives. Thirty‐nine CB were identified (29 male/10 female; aged 20–54 years). Twenty (51%) cases occurred in long tubular bones, 10 (26%) in small bones of the feet, five (13%) in flat bones and four (10%) in the patella. All cases showed classic cytological features of CB, and chondroid matrix was universally present. Calcification was identified in 10 cases (26%), including various combinations of serpiginous (n = 7), punctate (n = 6), classic chicken‐wire (n = 4) and psammomatous (n = 2) patterns. Haemosiderin (n = 19), woven bone (n = 13), secondary aneurysmal bone cyst formation (n = 8), foamy macrophages (n = 4), hyalinised vascular spaces (n = 2) and cholesterol clefts (n = 2) were noted. Follow‐up information (n = 32, 1–452 months) revealed local recurrence in three patients, all >40 years of age with flat bone origin, one of which developed pulmonary metastases 132 months after initial diagnosis. Conclusions CB in patients >20 years of age more frequently involves the short bones of the hands/feet and flat bones compared to those arising in their younger counterparts. A subset may harbour extensive serpiginous or psammomatous calcification rather than the classic chicken‐wire pattern. Although the overall local recurrence rate in adulthood is approximately 10%, all three patients with recurrent disease had tumours involving flat bones, suggesting that tumours arising in these sites may behave more aggressively.

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“…Similar to H3G34W, a histone H3K36M antibody has been developed; nuclear positivity is a strong predictor of underlying mutation. Both H3G34W and H3K36M have developed in parallel to become very useful diagnostic adjuncts, particularly in small biopsies and fine‐needle aspiration samples where the differential diagnosis among GCTB, CB, and aneurysmal bone cyst can be very challenging …”

Section: Single Nucleotide Variantsmentioning

confidence: 99%

Immunohistochemical correlates of recurrent genetic alterations in sarcomas

Anderson

Hornick

2018

Genes Chromosomes & Cancer

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Accurate diagnosis of sarcomas relies on the integration of clinical, histopathological and molecular features. Our understanding of the latter has increased dramatically in recent years with the application of high‐throughput sequencing. Concomitantly, the role of immunohistochemistry has expanded as genomic alterations have been exploited by the development of diagnostic markers that serve as surrogates for their detection. Herein, we review selected immunohistochemical markers that can infer the presence of diverse molecular events. These include gene fusions in vascular neoplasms (FOSB, CAMTA1 and TFE3), round cell sarcomas (BCOR, DUX4 and WT1), and fibroblastic/myofibroblastic tumors (STAT6, ALK and Pan‐TRK); amplifications in well‐differentiated and dedifferentiated liposarcomas (MDM2 and CDK4); and deletions in several aggressive neoplasms (SMARCB1 and SMARCA4). Protein correlates of single nucleotide variants (beta‐catenin in desmoid fibromatosis) and epigenetic alterations (histone H3K27me3 in malignant peripheral nerve sheath tumor) and markers discovered through gene expression profiling (NKX2.2 and MUC4) are also discussed.

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Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy

Cited by 52 publications

References 24 publications

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

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

Chondroblastomas presenting in adulthood: a study of 39 patients with emphasis on histological features and skeletal distribution

Immunohistochemical correlates of recurrent genetic alterations in sarcomas

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