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Background: Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB., Methods: Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6 months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups., Results: Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021 mU/dL) than the non-GCTB group (415 ± 219 mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001)., Conclusion: TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: There can be a diagnostic challenge in differentiating giant cell tumor of bone (GCTB) from its mimics. Lately, histone H 3 F 3 A (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., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Giant cell tumors of bone (GCT) are rare soft tissue tumors, that account for 3%-5% of primary bone tumors with <2% occurring in the head and neck. The nasal cavity is a highly unusual site of presentation. We reviewed 15 cases of GCT of nasal cavity and paranasal sinuses. We add 1 case to the literature. The case herein reported, appears to be the second nasal fossa GCT described in the literature and the first documented case with multifocal localization. A case of multifocal GCT of the nasal cavity is described. Although rare in the general population, GCT should be included among the possibilities in the differential diagnosis when evaluating tumors of the head and neck. Management of this particular tumor remains challenging; surgical removal is still the gold standard treatment, preferring a minimally invasive trans-nasal approach to reduce intra and post-operative morbidity. Laryngoscope, 134:2774-2778, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: Giant cell tumor of bone (GCT) is a benign tumor of bone that is known to be locally aggressive rarely metastasizing to distant sites, most commonly to the lungs. The reported pulmonary metastasis incidence is 1 - 9%. We report a case of GCT with solitary pulmonary metastasis who had significant clinical benefit and disease control with sequential application of surgical resection of pulmonary metastasis, local external beam radiation therapy (EBRT), and systemic Denosumab. We wish to highlight that even in metastatic GCT, there is significant clinical benefit in aggressive treatment., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

In the past few years, numerous new insights have been gained in the field of giant cell tumor of bone (GCTB). On the one hand, the detection of the highly characteristic histone mutation in the H3F3A gene in GCTB is becoming increasingly important in diagnostics in differentiating GCTB from other giant cell-rich lesions of bone as well as for defining rare variants of GCTB without osteoclastic giant cells. On the other hand, the effects of the H3F3A mutation were shown to have an impact on the epigenetic profile of tumor-driving stromal cells, providing new insights into tumorigenesis of GCTB., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma)., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

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 chondroblastoma from 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 chondroblastoma from its histological mimics especially on small biopsies.

Objective: This study aimed to examine the expression of Histone H3.3 glycine 34 to tryptophan (G34W) mutant protein in Giant Cell Tumor of Bone (GCTB)., Methods: This analytic observation research used a cross-sectional study design on 71 bone tumors. The cases involved 54 tissue samples diagnosed as GCBT. It was divided into GCTB primer (n=37), recurrent GCTB (n=5), GCTB with metastasis (n=9), and malignant GCTB (n=3). There were 17 samples mimics of GCTB also tested, including chondroblastoma (n=1), giant cell reparative granuloma (n=2), giant cell of tendon sheath (n=7), chondromyxoid fibroma (n=2), aneurysmal bone cyst (n=2), and giant cell-rich osteosarcoma (n=3). The Immunohistochemistry was used to evaluate the expression of G34W-mutated protein in these bone tumors., Result: The representation H3.3 (G34W) was expressed in the nuclei of mononuclear stromal cells but not stained on osteoclast-like giant cells. This study was analyzed by the Chi-square test, Fisher's test, specificity test, and sensitivity test. We obtained p = 0.001 for Histone H3.3 (G34W) mutant expression in GCTB vs Non-GCTB. Statistically, there was no significant difference in the expression level of Histone H3.3 (G34W) in the GCTB and its variants p-value = 0.183. We also obtained that the specificity of Histone H3.3 expression on GCTB was 100% and the sensitivity of Histone H3.3 on GCTB was 77.8%., Conclusion: Histon H3.3 mutant as a mutated driver gene in an Indonesian GCTB can assist to diagnose GCTB and compare it from other bone tumors.

Giant cell tumor of bone (GCTB) consists of a mixture of neoplastic mononuclear cells and non-neoplastic cells, including polynuclear giant cells. Recently, with the spread of the immunohistochemical staining marker H3.3 G34W corresponding to specific genetic abnormalities, the histological diversity of GCTB has been recognized. GCTB without giant cells is uncommon, although it has also been reported previously. Herein, we describe a 45-year-old man with GCTB without giant cells who was successfully diagnosed using H3.3 G34W immunohistochemistry. Other unusual findings in GCTB that were identified in this patient include bone and osteoid formation with a long clinical course of 13 years. We also compared the histological findings of the current patient to those who received denosumab therapy.

Rationale: Giant cell tumor of bone is a locally aggressive and rarely metastasizing neoplasm that typically affects the ends of long bones or the axial skeleton of young to middle-aged adults. As many as 69% to 100% of giant cell tumors harbor H3F3A gene mutations, while H3F3B gene mutations have rarely been reported., Patient Concerns: A 53-year-old male patient who underwent right distal femoral tumor resection., Diagnoses: Preoperative CT plain scan indicated giant cell tumor of bone with pathological fracture. Laboratory findings were as follows: serum calcium was 2.23 mmol/L (reference range: 2.1-2.55 mmol/L) and serum phosphorus was 1.35 mmol/L (reference range: 0.81-1.45 mmol/L)., Interventions: The histological morphology showed the typical features of a conventional GCT. The immunoprecipitation analysis results were as follows: H3.3G34W(-), H3.3G34R(-), H3.3G34V(-), and H3K36M(-). Sanger sequencing showed that the H3F3A and H3F3B gene mutations were wild type. The high-throughput gene sequencing results revealed the H3F3B gene mutations H3.3p.Gly35Trp and H3.3p.Val36Leu., Outcomes: The patient was stable with no recurrence in 12 months follow-up., Lessons: Giant cell tumor of bone with H3F3B gene mutations is extremely rare. In the pathological diagnosis of bone tumors, we need to analyze clinical presentation, imaging features, histology, immunophenotype, and cytogenetic/molecular alterations, in order to get a correct diagnosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Giant cell tumor of bone (GCTB) is an enigmatic tumor. Despite its benign histological appearance and clinical behavior in most cases, it is associated with recurrences, uncommonly metastasis, and rarely with a malignant transformation. During the last few years, there has been a significant evolution in the diagnosis and management of GCTB, including discoveries related to the underlying pathogenesis (RANK/RANK/OPG pathway), with treatment-related implications in the form of denosumab (approved inhibitor for targeting RANKL), leading to improved surgical resections, especially in cases of recurrent, large and borderline resectable tumors. Lately, a specific Histone mutation, namely H3.3G34W underlying almost all GCTBs has been discovered, further leading to the identification of a highly sensitive and specific immunohistochemical antibody marker, H3.3G34W, which is very useful for an exact diagnosis of a GCTB, including its differentiation from its various mimics, which has significant implications. This review describes clinicopathological features of a GCTB, including its variable features, recent concepts, underlying pathogenesis, post-denosumab related changes and various entities that constitute its differential diagnosis, including their molecular signatures, with treatment-related implications., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Non-ossifying fibroma (NOF) and central giant cell granuloma (CGCG) are both benign tumours of bone with overlapping morphology and similar mutations in the RAS/MAPK pathway. However, NOF is located in the long bones with regression after puberty in contrast to CGCG which is located in the jaw bones and does not regress spontaneously. We hypothesised that endocrine regulation by oestrogen plays a role in the spontaneous regression in NOF. Therefore, we examined the expression of ERα in a series of NOF and CGCG. ERα expression (EP1) was determined using immunohistochemistry on 16 NOFs (whole slides), and 47 CGCGs (tissue microarrays (TMA's n = 41 and whole slide n = 6)). As comparison, we included TMAs of other giant cell containing bone lesions: giant cell tumour of bone (n = 75), chondroblastoma (n = 12), chondromyxoid fibroma (n = 12), aneurysmal bone cyst (n = 6) and telangiectatic osteosarcoma (n = 6). All 16 NOF samples demonstrated ERα protein expression, while all 47 CGCG and all other giant cell containing bone tumours were negative. Most NOF samples had moderate staining intensity and between 24 and 49% of the spindle cells were ERα-positive. Our findings further support the role of endocrine regulation via oestrogen in the spontaneous regression in NOF. Whether oestrogen signalling at puberty is involved in the induction of senescence in the neoplastic cells of NOF harbouring RAS/MAPK pathway mutations needs further research. Since ERα expression was not observed in other giant cell containing bone lesions with overlapping morphological features, positive ERα expression may favour the diagnosis of NOF in challenging diagnostic cases., (© 2022. The Author(s).)

Aims: The present study investigated the combined clinical significance of fibrinogen and neutrophil-lymphocyte ratio (F-NLR) in predicting postoperative recurrence of giant cell tumor of bone. Methods: A total of 113 participants were included in this retrospective study to examine the effects of inflammatory factors on postoperative tumor recurrence. Results: The high-score F-NLR group was significantly associated with larger tumor size (p = 0.001), advanced tumor stage (p = 0.018), wide resection (p = 0.004) and greater local recurrence (p = 0.014). Univariate and multivariate survival analyses revealed that F-NLR (p = 0.035) remained an independent factor influencing tumor recurrence rates. Conclusions: This study reveals that the F-NLR score is a promising blood biomarker for predicting giant cell tumor recurrence.

Context: The diagnosis of giant cell tumor of bone (GCTB) is difficult in small biopsies with unusual age of presentation, location, and extensive secondary changes. Most of the GCTBs harbor H3F3A G34W mutations with a subset of cases showing alternate G34V, G34R, and G34L mutations., Objectives: To analyze the expression of anti-histone H3.3G34W antibody in different cellular components of GCTB across different locations and presentations (including the unusual ones) and validate the utility of this antibody in the diagnosis of GCTB and differentiate it from the other osteoclast-like giant-cell-rich lesions., Design: Immunohistochemistry was performed using anti-histone H3.3G34W antibody in the diagnosed cases of GCTB (136 cases of GCTB from 133 patients, including two malignant GCTBs) and other giant cell-containing lesions (62 cases). The presence of unequivocal crisp nuclear staining was considered positive., Results: Immunohistochemistry revealed unequivocal nuclear positivity in the mononuclear cells in 87.3% of the cases of GCTB. Of these, most showed diffuse expression with moderate to strong intensity staining. The positive staining was restricted to the nuclei of mononuclear cells with the nuclei of osteoclastic giant cells being distinctly negative. In addition to conventional GCTBs, two cases each of multicentric and malignant GCTB showed positive staining. The other giant-cell containing lesions were distinctly negative. The present study showed a sensitivity of 87.3% with specificity and positive predictive value of 100%., Conclusion: The anti-histone G34W antibody is a highly sensitive and specific marker for the diagnosis of GCTB and differentiating it from its mimics. The positive staining is restricted to the mononuclear cell component of GCTB with sparing the osteoclastic giant cells further reiterating the fact that the mononuclear stromal cells are the true neoplastic component of GCTB., Competing Interests: None

In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

GCTB is an osteolytic, locally-aggressive, rarely-metastasizing tumour, characterized by abundance of osteoclast-like giant cells, induced by neoplastic mononuclear cells expressing high-levels of the receptor activator of nuclear factor Kappa-B ligand (RANKL), a mediator of osteoclast activation. Although the mainstay of treatment is complete tumour removal with preservation of bone, therapy with denosumab, an inhibitor of RANKL, has been introduced for selected cases., Objectives: Denosumab-treated GCTB (DT-GCTB) was reported to show a wide spectrum of histological changes such as depletion of osteoclast-like giant cells and intralesional bone deposition, which may lead to diagnostic difficulties. We investigated clinicopathologic and molecular features of DT-GCTB, matched with pre-therapy samples., Participants: 21 cases were included (13 females, 8 males), aged 15 to 64 (median, 30 years)., Results: DT-GCTB showed development of sclerotic neocortex and varying degrees of osteosclerosis radiographically. Marked depletion of giant cells, different degree of ossification, fibrosis, and proliferation of mononuclear cells was observed. Staining for H3.3G34W was positive in mononuclear cells in 19 cases (90.5%), while one negative case was positive for H3.3G34V. H3F3A G34W mutation was confirmed in 17 of 19 cases (89.5%), corresponding to nuclear staining with H3.3 G34W antibody. G34L mutation was detected in one G34W negative case, in which H3.3 G34V nuclear positive staining was observed, possibly due to cross-reaction., Conclusions: Post-therapy tumours still exhibit a similar mutation profile, while significantly differing from classic GCTB morphologically. Correlation with history of denosumab administration, awareness of features of DT-GCTB, IHC and molecular studies for histone H3 mutations are important in its assessment., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The cytopathology of a giant cell tumor of soft tissue (GCT-ST), a fibrohistiocytic neoplasm distinct from other giant cell-rich soft tissue tumors, is rarely reported. The authors report their experience with a series of 4 GCT-ST fine-needle aspiration (FNA) biopsy cases and compare them with a set from giant cell tumors of bone (GCTBs)., Methods: The authors' cytopathology files were searched for GCT-ST examples with histopathologic confirmation. FNA biopsy smears were performed and examined with standard techniques., Results: Four cases of GCT-ST presenting as a primary soft tissue mass from 4 patients (3 males and 1 female; age range, 28-75 years, mean age, 53 years) were retrieved. FNA sites included the anterior tibia, buttock, shoulder, and upper back. Three cases were interpreted as suspicious for sarcoma radiographically. The specific diagnoses were atypical giant cell tumor of tendon sheath, suspicious for GCT-ST, atypical myxoid lesion with giant cells, and benign with osteoclast-like giant cells (OLGCs). No case was interpreted as malignant. Aspirates consisted of mononuclear polygonal cells, spindled fibroblast cell clusters, and large OLGCs to the near exclusion of other cell types. OLGCs possessed 10 or more nuclei per cell. A comparison with GCTB aspirates and single case reports from the literature showed comparable cytomorphology., Conclusions: GCT-ST FNA smears mimic those of GCTBs containing a limited population of uniform spindle cell clusters, single dispersed polygonal cells, and cytologically banal OLGCs. GCT-ST should be considered in the differential diagnosis of aspirates containing numerous osteoclast-like giant cells., (© 2021 American Cancer Society.)

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97-100%) and 100% (95% CI: 96.15-100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24-98.13%) and 100% (95% CI: 93.94-100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess P63 expression in giant cell-containing lesions of the bone (GCLB) and to determine its utility in differentiating giant cell tumor of the bone (GCTB) from other GCLBs., Material and Method: Cases diagnosed as GCLB on histopathology were included in the study. P63 immunohistochemistry was performed in all the cases. The percentage of cells showing nuclear positivity was assessed in the non-giant cell component. Statistical analysis was performed using the Mann-Whitney U test., Results: Of the total 53 cases studied, the majority were GCTBs (23), followed by 12 cases of chondroblastomas (CBL) and 18 other giant cell lesions (GCLs). All giant cell-containing lesions except one case of CBL and brown tumor of hyperparathyroidism (BTH) showed P63 staining in the non-giant cell component. However, the mean P63 labeling of GCT (52.6%) was higher compared to CBL (28.3%), aneurysmal bone cyst (ABC) (15.2%), non-ossifying fibroma (NOF) (24.5%), giant cell lesion of small bones (GCLSB) (11%), BTH (6.8%) and chondromyxoid fibroma (CMF) (12.3%), with a p-value of < 0.001., Conclusion: Although p63 was present in majority of the GCLBs, its percentage positivity was significantly higher in GCTB compared to the other GCLBs. The diagnosis of GCTB is likely if cut-off value of > 50% is applied.

Background: Giant cell tumour (GCT) is a primary benign, locally aggressive bone tumour. Treatment is surgical however, denosumab has been increasingly used as a treatment in recurrent or unresectable locally advanced GCT because of its effect in reducing tumour size. Denosumab treated GCT can exhibit a wide array of histopathological features resulting in diagnostic problems for pathologists. Our study aimed at identifying these histopathological features to aid pathologists in reaching a correct diagnosis., Methods: Our study included 20 patients of biopsy-proven GCT cases treated with denosumab. We received specimens for histopathological examination in our institution from January 2018 to March 2020. The demographic and clinical data of these patients were retrieved from the Health Management Information System (HMIS). The slides were retrieved and studied for histopathological changes., Results: The mean age of patients in our study was 29.5 years. There were 11 males and 9 females. Distal radius was most commonly involved bone. On histopathological examination, ovoid to spindle mononuclear stromal cells were seen. Total absence of osteoclast like giant cells was seen in 10 (50%) cases, whereas 3 (15%) cases showed a marked reduction in osteoclast like giant cells., Conclusions: Denosumab treated GCT of bone can exhibit a wide spectrum of histopathological features. Pathologists need to be mindful of these features. Correlation of histopathological findings with clinical history and radiological features is important to prevent erroneous diagnosis. Treatment history of patients with denosumab is essential as incorrect diagnosis can be made if the history of denosumab treatment is not provided.

Aims: Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy., Methods and Results: Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed., Conclusions: We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone., (© 2021 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Introduction: Chondromyxoid fibroma is a rare bone tumor characterized by immature myxoid mesenchymal tissue showing early primitive cartilaginous differentiation. There have been limited case reports describing the cytologic features of chondromyxoid fibroma. Herein, we reported cytologic features of chondromyxoid fibroma on fine-needle aspiration (FNA)., Materials and Methods: We performed a retrospective search in our cytopathology and surgical pathology database for cases diagnosed as chondromyxoid fibroma that had corresponding cytology specimens from three medical institutions. All available cytopathology specimens were reviewed., Results: Eight cases were retrieved from patients aged 16-77 years (mean, 51 years), and M:F ratio of 1.7:1. Seven tumors (88%) were primary, and most (62%) occurred in flat bones. Cytologic diagnoses were made in 6 cases with cytologic slides not available to review in 1 case. All cases showed metachromatic matrix in the background, while hyaline cartilage fragments were absent. All cases had two cell populations comprising oval to round cells and stellate to spindle cells. The spindle to stellate cells were more commonly embedded in matrix material. Moderate atypia (hyperchromasia and moderate anisonucleosis) was present in 4 cases (80%), while no mitotic figure was present in all cases., Conclusions: Our study highlights common cytologic features of chondromyxoid fibroma, including the presence of the spindle or stellate cells embedded in matrix material. Hyaline cartilage is uncommon and, if present, diagnostic considerations should include enchondroma or low-grade chondrosarcoma. A specific cytologic diagnosis primarily using FNA samples can be challenging but possible when evaluated in conjunction with clinical and radiologic data., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma (PMHE) is a distinct vascular neoplasm mostly observed in the lower extremities of young adults with characteristic histopathological features. In this article, we present 2 unusual cases of PMHE. Case 1: A 28-year-old male presented with pain and stiffness in his left shoulder. Radiologic examination revealed an expansile, lytic, heterogeneously enhancing, destructive lesion in his left scapula, along with multiple avid marrow lesions in his other bones. Biopsy revealed a cellular tumor composed of plump spindly and epithelioid cells arranged in fascicles and focally, in clusters, admixed with neutrophils and histiocytes, with interspersed many osteoclast-like giant cells and reactive bone. Case 2: A 63-year-old male presented pain and swelling in his right middle finger, with no other lesion elsewhere in his body. Radiologic imaging disclosed a 1.5-cm-sized lobulated, expansile, lytic, destructive lesion in the distal end of the third metacarpal bone of his right hand. Biopsy examination revealed a cellular spindle cell tumor, composed of plump spindly cells, arranged in fascicles, including "tadpole-like" or "strap-like" cells and interspersed inflammatory cells. Immunohistochemically, tumor cells in both cases were positive for AE1/AE3, CD31, and Fli1, while negative for desmin and CD34. INI11 was retained. The presented cases of PMHE, occurring at unusual locations, in an older individual in the second case, along with variable histopathological features, noted in the first case, seem to expand the clinicopathological spectrum of these uncommon neoplasms. Differential diagnoses and review of similar cases are presented.

Bone tumors of the foot are an uncommon finding. Most tumors are found incidentally on imaging and are benign. Care must be taken although due to the aggressive nature of malignant bone tumors that can occur in the calcaneus. Malignant lesions will more commonly present with symptoms of pain and swelling. Often misdiagnosed as soft tissue injuries, it is critical to be able to diagnose and treat these lesions early. Imaging plays an important role with plain films and advanced imaging. Surgical treatments can range from curettage with grafting to amputation for more aggressive lesions., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To investigate the subtypes of H3F3A DNA mutation in H3.3 immunohistochemistry (IHC) negative giant cell tumors of bone (GCTB). Methods: IHC expression of G34W mutated protein was evaluated in 181 cases GCTB. In H3.3 IHC negative cases, Sanger DNA sequencing analysis was used to detect the subtypes H3F3A mutations. Results: Overall, 164 (90.61%) cases of GCTB showed nuclear expression of H3.3, and 17 cases were negative. These 17 H3.3 negative cases were subjected to Sanger DNA sequencing analysis; results showed that eight presented rare mutation subtypes occurring at glycine 34 to leucine (G34L, 3/181, 1.66%), glycine 34 to valine (G34V, 3/181, 1.66%) and glycine 34 to arginine (G34R, 2/181, 1.10%), and the other nine cases were wild type (glycine 34, 9/181, 4.97%). Sanger DNA sequencing analysis confirmed the absence of G34W mutation in the H3.3 negative cases. Combining IHC and DNA sequencing analysis increased the detection rate of H3F3A mutation in the GCTB to 95.03%. Conclusions: H3.3 IHC could detect H3F3A G34W mutation in GCTB, but not for other rare mutation and wild types loci.

H3F3A mutations and the expression of glycine 34 to tryptophan (G34W) mutants in giant cell tumors of bone (GCTBs) and other bone tumors were detected to compare H3F3A mutation types and the expression of G34W-mutant protein in order to provide a theoretical basis for using H3F3A mutations as a diagnostic and differential-diagnostic tool for GCTBs. A total of 366 bone tumor cases were investigated. The cases involved 215 men and 151 women, whose median age was 29 years (3-84). The cases included GCTB (n=180), recurrent GCTB (n=19), GCTB with lung metastasis (n=5), pediatric GCTB (n=15), primary malignant GCTB (n=5), chondroblastoma (CB, n=61), chondrosarcoma grade II (n=15), dedifferentiated chondrosarcoma (n=17), chondromyxoid fibroma (n=9), aneurysmal bone cyst (n=9), nonossifying fibroma (n=9), osteosarcoma (n=16), and undifferentiated sarcoma (n=6). Sanger DNA sequencing analysis was used to detect H3F3A mutations. Immunohistochemistry was used to assess the expression of the G34W-mutated protein in these bone tumors. DNA sequencing results revealed H3F3A mutations in 95.00% of GCTBs (171/180), including glycine 34 to tryptophan (G34W, 163/180, 90.56%), glycine 34 to leucine (G34L, 3/180, 1.67%), glycine 34 to valine (G34V, 3/180, 1.67%), and glycine 34 to arginine (G34R, 2/180, 1.11%). Recurrent GCTBs mostly had the H3F3A G34W mutation (18/19, 94.74%), and GCTBs with lung metastasis all had the H3F3A G34W mutation (5/5, 100%). Pediatric GCTBs had a mutation rate of 93.33% (14/15), including one case with G34L. Four cases of primary malignant GCTB showed the H3F3A G34W mutation (4/5, 80.00%), and the classical GCTB component and malignant component showed consistent mutation types. Immunohistochemistry showed that GCTBs harboring G34W also expressed the mutant protein in tumor cell nuclei. Furthermore, one case of GCTB and one case of recurrent GCTB showed positive G34W immunostaining results despite being negative for the genetic mutation. Other bone tumors all showed wild-type expression in both DNA sequencing and immunohistochemistry. Our large-sample DNA sequencing analysis detected four different forms of mutations in GCTBs, including three rare mutation forms. The most common mutation of H3F3A was G34W, which was in accordance with the expression of G34W in GCTBs detected by immunohistochemistry. Although DNA sequencing analysis detected rare mutation types of H3F3A, false-negative results were also present due to the small number of cells in the samples. Detection of the most common (G34W) mutant protein by immunohistochemistry was more convenient. Given the high prevalence of these driver mutations, the detection of H3F3A mutant proteins can assist in the diagnosis of GCTB and its differential diagnosis from other bone tumors.

Giant cell tumor of bone is extremely rare in the talus and is usually observed in the third decade of life. Herein, we report a case of a 19-year-old male with a giant cell tumor of bone in the talus mimicking a simple bone cyst that was treated by intralesional curettage and, for the first time, bone grafting with a synthetic bone substitute. The patient had no evidence of recurrence at 7-year follow-up but did have non-progressing mild degenerative joint disease and slightly limited range of movement at the ankle joint.

A 30-year-old woman presented with swelling in her right thumb of 3-month duration which was slow-growing in nature without a history of trauma. On examination, firm non-tender swelling with ill-defined border over the dorsomedial aspect of the first metacarpal was noted. The swelling was mobile only in the vertical plane with restricted adduction and abduction. Plain X-ray revealed mild erosion of the first metacarpal head. Diagnostic ultrasound confirmed the lesion to arise from the extensor tendon sheath of diffuse type without any bony involvement. A wide local excision biopsy of the swelling was planned. Intraoperatively, a 3×2 cm greyish-white mass, bony hard in consistency with lobulated surface was found arising from the tendon sheath of the extensor tendon of the thumb; it was completely excised with a wide margin. Histopathological examination revealed polyhedral cells admixed with osteoclastic type giant cells. Biopsy from the first metatarsal was normal. The patient is on follow-up for the last 5 years with no evidence of recurrence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tumor protein p63 (p63) has been reported to be highly expressed in giant cell tumor of bone (GCTB). Whether p63 can be treated as a diagnostic marker for GCTB remains unclear., Objective: We conducted a meta-analysis to evaluate the applicability of p63 in diagnosing GCTB., Design and Setting: Systematic review and meta-analysis carried out in a public hospital, Hong Kong, China., Methods: We searched PubMed, EMBASE and the Cochrane Library from inception to April 30, 2019. Literature in English or Chinese about the differential diagnosis of GCTB using p63 were included. -Animal experiments, reviews, correspondence, case reports, expert opinions and editorials were excluded. Studies were also excluded if they did not provide sufficient information to construct a 2 × 2 contingency table. We calculated individual and pooled sensitivities and specificities. We used I² as an indicator of heterogeneity., Results: Out of 88 records identified, 8 articles on 788 GCTB patients fulfilled the inclusion criteria and were included in the present analysis. Bivariate analyses yielded a pooled mean sensitivity of 0.87 (95% confidence interval, CI, 0.72-0.95) and specificity of 0.71 (95% CI, 0.56-0.82) for using p63 as a biomarker in diagnosing GCTB. The area under the receiver operating characteristic curve was 0.86 (95% CI, 0.82-0.88)., Conclusion: p63 is a helpful indicator in diagnosing GCTB due to its high sensitivity and specificity. -Nonetheless, the results need to be carefully interpreted based on other diagnostic methods such as imaging., Systematic Review Registration: 164115 (PROSPERO registration number).

Opinion Statement: Denosumab is a RANK ligand inhibitor approved for the treatment of giant cell tumor of bone. While the role of denosumab in the setting of advanced and unresectable disease is well established, its role in surgically resectable disease is currently under discussion. Several prospective and retrospective series on neoadjuvant therapy in potentially resectable tumor with high morbidity surgery reported a relapse rate of 10-20% after resection and 30-40% after curettage. At the same time, less morbid surgery has obvious clinical advantages for the patient, and several studies have shown the efficacy of denosumab in downgrading of the surgical procedure. Currently, the role of neoadjuvant denosumab in operable GCTB is limited to selected cases in which a diffuse reactive bone formation and peripheral ossification can make an easier surgical procedure, for example, in tumors with a large soft tissue component. A planned resection may become less morbid when preoperative denosumab is administered. Whenever a segmental resection is thought to be indicated at diagnosis, denosumab may be considered in the neoadjuvant setting. A preoperative course of 6 months is considered safe and effective. Two case scenarios are presented and critically discussed. Because of the high recurrence rates after denosumab treatment followed by curettage, we discourage the use of denosumab when curettage is considered feasible. In this setting, a short course of preoperative denosumab (2-6 months) may be considered for highly selected cases, for example in pathological fractures. The role of adjuvant denosumab needs further investigation. Long-term disease control has been reported in case of non-surgical lesions, even after treatment interruption, but there is no consensus on ideal treatment duration and dosage for these scenarios. In all cases, multidisciplinary discussion with oncology, pathologist, radiologist, and surgeons is mandatory. Patient's comorbidities, dental conditions, and preferences, including family planning, should always be taken into account.

Background: There is currently no clinical biomarker for the early diagnosis of giant cell tumor of bone. Long-chain non-coding RNAs (lncRNAs) have a wide range of important gene regulatory functions and play an important role in the occurrence and development of various malignant tumors. This study mainly screened the differential expression of lncRNAs in patients with giant cell tumor of bone by gene chip technology, verified the biological function. We tried to establish a reference basis for early diagnosis of tumor and prediction of tumor recurrence., Methods: From September 2018 to September 2019, we randomly selected 20 cases of primary giant cell tumor of bone and 20 cases of recurrent giant cell tumor of bone, and 20 cases of bone trauma tissue. First, the differential expression of incRNAs in the bone tissue of the patients was evaluated via utilizing gene chip technology. The gene chip was Human LncRNA Array v 3.0 (8 x 60 K) was completed by Shanghai Kangcheng Biotechnology Co., Ltd. The DAVID online analysis platform was used to analyze the differentially expressed genes by GO and KEGG pathways. The target lncRNAs were screened; real-time quantitative PCR (qRT-PCR) was used to verify the relative expression levels of target lncRNAs in bone tissue and serum of three groups of patients., Results: Using gene chip technology screening, fold-change (FC) value > 2.0 was used as standard. A total of 1,254 differentially expressed lncRNAs were detected of which 896 were up-regulated and 358 were down-regulated. Additionally, a total of 106 differentially expressed lncRNAs were detected with FC values > 10.0. Among these, 72 lncRNAs were upregulated and 34 lncRNAs were downregulated. We then selected two lncRNAs with up-regulation and down-regulation with the largest fold difference. qRT-PCR analytical results showcased that the expression of AK124776 in bone tissue and serum of patients in the recurrent group was significantly higher than that of the initial group and the normal group. Conversely, for RP11-160A10.2, the expression level in the recurrent group was significantly lower than that in the initial group, and the normal group was the highest; the difference was statistically significant (p < 0.05). Finally, we used the expression levels of AK124776 and RP11-160A10.2 in each group as the diagnostic indicators. According to the receiver operating curve (ROC), the accuracy of AK¬124776 and RP11-160A10.2 in the diagnosis of giant cell tumor of bone (area under the curve), the AUC was 0.865 and 0.877, respectively; the accuracy of predicting recurrence of giant cell tumor of bone was 0.832 and 0.841, respectively., Conclusions: The early detection of differential expression of lncRNAs in the serum of patients with giant cell tumor of bone is important for the diagnosis of disease and prediction of recurrence. The establishment of stable expression of lncRNAs and simple and easy detection methods are of great value for guiding clinical application.

The specialty of bone cancer has developed rapidly in China in recent years, but because of the low incidence of these diseases and the unbalanced development of different regions, the malpractice problem of diagnosis and treatment is still outstanding.The NCCN clinical practice guide for bone cancer in the United States has been updated for several years and is now more mature and has been recognized worldwide.It can provide reference for medical professionals in related fields in China, it covers the most common bone tumors such as osteosarcoma, Ewing's sarcoma, chondrosarcoma, giant cell tumor of bone and chordoma.This article describes and interprets the core diagnostic and therapeutic contents of NCCN clinical practice guide for bone cancers.

Objectives: Denosumab is Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) inhibitor which is being used in the treatment of locally advanced, recurrent and metastatic Giant Cell Tumor of Bone (GCTB). It causes reduction in monocyte recruitment and Osteoclast-Like Giant Cell (OLGC) formation which limits bone destruction. After Denosumab treatment, GCTB exhibit diverse morphological features which can pose diagnostic challenge. Our aim was to study the spectrum of histologic features seen in Denosumab treated GCTB which could be helpful in establishing correct diagnosis., Methods: We retrieved and reviewed H&E stained microscopic glass slides of 38 GCTB cases who received Denosumab as neoadjuvant treatment. These cases were treated at different institutes and diagnosed at our institute between January 2017 and October 2019. Morphologic features such as presence of residual OLGC, appearances of mononuclear stromal and bony components were assessed along with other non-specific features., Results: Patients' median age was 29 years. Male to female ratio was 1.53:1. Femur was the most commonly involved bone. Microscopically, peripheral shell of reactive bone was observed in all cases. In 20 (52.6%) cases, there was complete elimination of OLGC. Mononuclear stromal cells were predominantly bland spindle shaped and arranged in fascicular and storiform patterns. Focal atypia was noted in 3 cases. Bony component manifested as trabeculae of woven bone with osteoblastic rimming and immature trabeculae of unmineralized osteoid with haphazardly present osteoblasts. Spectrum of stromal changes included cystic spaces, foamy macrophages, inflammatory infiltrate, hemangiopericytoma-like (HPC-like) vessels, hyalinization, edematous areas and hemosiderin pigment. The tumors showed areas which resembled other bony and soft tissue lesions such non-ossifying fibroma, fibrous dysplasia, osteoblastoma, sclerosing epithelioid fibrosarcoma and osteosarcoma., Conclusion: Denosumab treatment induces a variety of changes in GCTB. Clinical history and knowledge of these features are necessary for excluding differential diagnoses and avoiding misdiagnosis., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Aneurysmal bone cyst (ABC) secondary to Giant Cell Tumor of bone (GCT) is a rare lesion, of which the incidence is about 0.011 to 0.053 per 100,000 every year. There are only a few previous case reports, and most of them occur in the spine, long bones or flat bones., Case Presentation: We report one case of a patient who complained of "progressive enlargement of the mass on right-hand fifth finger for 5 years with ulceration for 6 months". After the imaging examination in our hospital, it was diagnosed as a "huge bone tumor on the proximal phalanx of the right-hand fifth finger", then wide excision and amputation of the fifth finger were made. The pathological examination diagnosed the mass as aneurysmal bone cyst secondary to giant cell tumor, 13 × 8 × 6 cm 3 , with no local infiltration observed. No recurrence and metastasis occurred 18 months after the operation, and the patient recovered well., Conclusion: In this report, we discuss the etiology, diagnosis, differentiation, and management of Aneurysmal bone Cyst secondary to Giant Cell Tumor of bone, and review previous case studies.

Giant cell tumor of bone (GCTB) is a locally aggressive bone tumor that frequently shows local recurrence and occasionally shows malignant transformation to high-grade sarcoma. Histologically, conventional GCTB is composed mainly of three types of cells: mononuclear neoplastic cells with an osteoblastic precursor phenotype, mononuclear histiocytic cells, and osteoclast-like multinucleated giant cells. These cells interact with each other via the RANKL-RANK axis and other mechanisms for tumor formation. The vast majority of GCTBs were recently revealed to harbor H3F3A p.G34W mutation, and a minor subset have H3F3A p.G34L, p.G34M, p.G34R, or p.G34V mutation. H3.3 G34W mutant-specific immunohistochemistry is a highly sensitive and specific surrogate marker for H3F3A p.G34W mutation in GCTB and thus useful for differential diagnoses of histological mimics. H3.3 mutant-specific immunohistochemistry has also contributed to the understanding of the bone-forming ability of neoplastic cells of GCTB and the remarkable new bone formation after treatment with denosumab, an inhibitor of RANKL. In primary and secondary malignant GCTBs, the H3F3A gene allele can be preserved or lost with malignant transformation.

Objective: To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB. Methods: Immunohistochemical (IHC) EnVision method was used to detect the expression of H3.3 G34W mutant-specific antibody and p63 in 83 GCTBs, 18 aneurysmal bone cysts, 23 chondroblastomas and 28 osteosarcomas diagnosed at Nanjing Jinling Hospital from June 2001 to April 2019. Results: Among the 83 cases of GCTB, 69 cases (69/83, 83.1%) expressed H3.3 G34W. H3.3 G34W expression was found exclusively in the mononuclear cell population with strong and diffuse nuclear staining. H3.3 G34W was expressed in 55 of 57 (96.5%) cases of GCTB in long bones, but only 14 of 26 (53.8%) cases of non-long bone GCTB. All recurrent (9/9)/metastatic GCTB (2/2), post-denosumab GCTB (3/3), primary malignant GCTB (3/3) and secondary malignant GCTB (5/5) also expressed H3.3 G34W. H3.3 G34W was negative in all aneurysmal bone cysts and chondroblastomas. H3.3 G34W was positive in 3 of 28(10.7%) cases of osteosarcomas, and giant cell-rich osteosarcoma(GCRO) was the only histological subtype of osteosarcoma that expressed H3.3 G34W. p63 was expressed in 71.1%(59/83) of GCTB, while the positive rates of p63 in aneurysmal bone cysts,chondroblastomas and osteosarcomas were 3/18, 43.5% (10/23) and 21.4% (6/28) respectively. The sensitivity and specificity of H3.3 G34W mutant-specific antibody in the diagnosis of GCTB were 83.1% and 95.7%. Conclusions: H3.3 G34W mutant-specific antibody is a highly sensitive and specific marker for GCTB and helpful for the diagnosis of GCTB and its variants. The limitation of this antibody is that as a mall number of GCTB harbor G34 mutation other than G34W, and thus that cannot be detected. The incidental expression of H3.3 G34W mutant protein in osteosarcoma could be a potential diagnostic dilemma, and the results of H3.3 G34W IHC staining needs careful interpretation.

Objectives: This study aims to investigate the choice of graft or cement, the relationship between the graft types and union rates, functional results, and complications in hand and wrist benign bone lesions while also evaluating the diagnosis and treatment modalities of lesions with high recurrence potential like giant cell- containing lesions., Patients and Methods: Between September 2005 and May 2016, 48 benign osseous hand and wrist tumors of 48 patients (22 males, 26 females; mean age 33±13.1 years; range, 11 to 70 years) were reviewed retrospectively. Patients were evaluated according to demographic data, complaints at admission, radiological findings, surgical methods, graft type, pathological diagnosis, and complications., Results: Although not statistically significant, there were differences between cement, allograft, and autograft according to union time and loss of range of motion. There was no statistical difference between cement, allograft, and autograft according to complications., Conclusion: Autograft obtained percutaneously with a trephine needle may provide earlier union with minimal donor site morbidity. Wide resection and reconstruction options should be kept in mind in giant cell-containing tumors. Further investigations are needed about the relationship between soft tissue edema in magnetic resonance imaging and the recurrence risk in hand and wrist benign bone tumors.

Giant cell tumor (GCT) of bone is a locally aggressive bone tumor, which accounts for 4% to 5% of all primary bone tumors. At present, the early diagnosis and postoperative recurrence monitoring are still more difficult due to the lack of effective biomarkers in GCT. As an effective tool, metabolomics has played an essential role in the biomarkers research of many tumors. However, there has been no related study of the metabolomics of GCT up to now. The purpose of this study was to identify several key metabolites as potential biomarkers for GCT by using nuclear magnetic resonance (NMR)-based metabolic profiles.Patients with GCT in our hospital were recruited in this study and their plasma was collected as the research sample, and plasma collected from healthy subjects was considered as the control. NMR was then utilized to detect all samples. Furthermore, based on correlation coefficients, variable importance for the projection values and P values of metabolites obtained from multidimensional statistical analysis, the most critical metabolites were selected as potential biomarkers of GCT. Finally, relevant metabolic pathways involved in these potential biomarkers were determined by database retrieval, based on which the metabolic pathways were plotted.Finally, 28 GCT patients and 26 healthy volunteers agreed to participate in the study. In the multidimensional statistical analysis, all results showed that there was obvious difference between the GCT group and the control group. Ultimately, 18 metabolites with significant differences met the selection condition, which were identified as potential biomarkers. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Human Metabolome Database (HMD) database searching and literature review, these metabolites were found to be mainly correlated with glucose metabolism, fat metabolism, amino acid metabolism, and intestinal microbial metabolism. These metabolic disorders might, in turn, reflect important pathological processes such as proliferation and migration of tumor cells and immune escape in GCT.Our work showed that these potential biomarkers identified appeared to have early diagnostic and relapse monitoring values for GCT, which deserve to be further investigated. In addition, it also suggested that metabolomics profiling approach is a promising screening tool for the diagnosis and relapse monitoring of GCT patients.

Background: Pseudomyogenic hemangioendothelioma (PMHE) is a rare endothelial neoplasm that involves the bones in only 14% of all cases. The optimal treatment strategy has not been established. We herein report a case of primary PMHE in which denosumab treatment showed activity in both imaging studies and the clinical outcome., Case Presentation: A 20-year-old woman presented with worsening pain in her left ankle. Imaging studies showed multifocal fluorodeoxyglucose (FDG)-avid [maximum standardized uptake value (SUVmax), 15.95] osteolytic lesions in the bones of her left lower extremity. While waiting for the definitive pathologic diagnosis of PMHE, denosumab, a human immunoglobulin G2 monoclonal antibody against RANKL, was initiated to treat progressive bone absorption after curettage of one of the lesions. Denosumab induced osteosclerosis around the lesions and pain relief and was discontinued 4 years after its initiation. Although all of the multifocal lesions remained, they all became less FDG-avid (SUVmax, 2.6), and the patient developed no signs of new lesions or distant metastasis., Conclusion: Denosumab plays a certain role in prevention of bone destruction by PMHE through suppression of osteoclast-like giant cells and would be an excellent treatment for bone absorption by PMHE of bone.