Molecular and immunohistochemical testing of bone tumours: review and update

Primary bone tumours can pose diagnostic problems due to their overlapping radiologic and histologic features. Given the recent advancement in our understanding of the biology of bone tumours, multiple immunohistochemical and molecular markers have been devised to aid in their diagnosis. This review provides brief updates on select bone tumours, including chondrosarcomas, benign chondrogenic tumours, osteosarcomas, benign osteogenic tumours, fibroosseous lesions, vascular tumours, osteoclastic giant cell‐rich or cystic tumours, chordoma, adamantinoma, small round blue cell sarcomas, and others. We discuss their salient molecular features and novel immunohistochemical correlates, along with some tips to avoid common diagnostic pitfalls.

[1]  A. Flanagan,et al.  Brown Tumors Belong to the Spectrum of KRAS-driven Neoplasms , 2022, The American journal of surgical pathology.

[2]  A. Franchi,et al.  Chondroblastoma‐like osteosarcoma: a clinicopathological and molecular study of a rare osteosarcoma variant , 2022, Histopathology.

[3]  M. Larsen,et al.  Integrated proteomics, phosphoproteomics and metabolomics analyses reveal similarities amongst giant cell granulomas of the jaws with different genetic mutations. , 2022, Journal of Oral Pathology & Medicine.

[4]  Jonathan C. Baker,et al.  Xanthogranulomatous epithelial tumors and keratin-positive giant cell-rich soft tissue tumors: two aspects of a single entity with frequent HMGA2-NCOR2 fusions , 2022, Modern Pathology.

[5]  Jianyun Zhang,et al.  GNAS mutation analysis assists in differentiating chronic diffuse sclerosing osteomyelitis from fibrous dysplasia in the jaw , 2022, Modern Pathology.

[6]  C. Kunder,et al.  GRM1 Immunohistochemistry Distinguishes Chondromyxoid Fibroma From its Histologic Mimics , 2022, The American journal of surgical pathology.

[7]  T. Shibata,et al.  Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall , 2022, Modern Pathology.

[8]  D. Baumhoer,et al.  Methylation and copy number profiling: emerging tools to differentiate osteoblastoma from malignant mimics? , 2022, Modern Pathology.

[9]  Christopher Davies,et al.  A genetic model for central chondrosarcoma evolution correlates with patient outcome , 2021, Genome Medicine.

[10]  L. Gorunova,et al.  Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone , 2022, Cancer Genomics & Proteomics.

[11]  Y. Oda,et al.  Histological and immunohistochemical features and genetic alterations in the malignant progression of giant cell tumor of bone: a possible association with TP53 mutation and loss of H3K27 trimethylation , 2021, Modern Pathology.

[12]  E. Wardelmann,et al.  Recurrent CTNNB1 mutations in craniofacial osteomas , 2021, Modern Pathology.

[13]  Liang Jiang,et al.  CIC-NUTM1 Sarcomas Affecting the Spine: A Subset of CIC-Rearranged Sarcomas Commonly Present in the Axial Skeleton. , 2021, Archives of pathology & laboratory medicine.

[14]  M. Hameed,et al.  Recurrent loss of chromosome 22 and SMARCB1 deletion in extra‐axial chordoma: A clinicopathological and molecular analysis , 2021, Genes, chromosomes & cancer.

[15]  C. Antonescu,et al.  A unique epithelioid vascular neoplasm of bone characterized by EWSR1/FUS‐NFATC1/2 fusions , 2021, Genes, chromosomes & cancer.

[16]  Edward J. Fox,et al.  Novel fusion sarcomas including targetable NTRK and ALK. , 2021, Annals of diagnostic pathology.

[17]  E. Montgomery,et al.  Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens , 2021, Genes, chromosomes & cancer.

[18]  A. Cleton-Jansen,et al.  NTRK fusions are extremely rare in bone tumours , 2021, Histopathology.

[19]  M. Rivera,et al.  Clinical Utility of Anchored Multiplex Solid Fusion Assay for Diagnosis of Bone and Soft Tissue Tumors , 2021, The American journal of surgical pathology.

[20]  B. Mavčič,et al.  The role of molecular diagnostics in aneurysmal and simple bone cysts – a prospective analysis of 19 lesions , 2021, Virchows Archiv.

[21]  Daja Šekoranja,et al.  Fibroma of tendon sheath is defined by a USP6 gene fusion—morphologic and molecular reappraisal of the entity , 2021, Modern Pathology.

[22]  A. Cleton-Jansen,et al.  Expanding the Spectrum of EWSR1-NFATC2-rearranged Benign Tumors , 2021, The American journal of surgical pathology.

[23]  R. Seethala,et al.  Clinicopathologic and Genomic Characterization of Inflammatory Myofibroblastic Tumors of the Head and Neck , 2021, The American journal of surgical pathology.

[24]  A. Luebke,et al.  H3F3A‐mutated giant cell tumour of bone without giant cells—clinical presentation, radiology and histology of three cases , 2021, Histopathology.

[25]  A. Folpe,et al.  Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors , 2021, Modern Pathology.

[26]  Yuehua Wu,et al.  Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including FGFR2, FGFR1, MERTK, NTRK1, and TEK: a molecular and clinicopathologic analysis , 2021, Modern Pathology.

[27]  D. Baumhoer,et al.  FOS Rearrangement and Expression in Cementoblastoma , 2021, The American journal of surgical pathology.

[28]  A. Vargas,et al.  NKX3.1 immunohistochemistry is highly specific for the diagnosis of mesenchymal chondrosarcomas: experience in the Australian population. , 2021, Pathology.

[29]  Y. Yatabe,et al.  Confirmation of NKX3-1 Expression in EWSR1-NFATC2 Sarcoma and Mesenchymal Chondrosarcoma Using Monoclonal Antibody Immunohistochemistry, RT-PCR, and RNA In Situ Hybridization. , 2021, The American journal of surgical pathology.

[30]  Narasimhan P. Agaram,et al.  Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases , 2020, Histopathology.

[31]  A. Iafrate,et al.  Identification of EWSR1–NFATC2 fusion in simple bone cysts , 2020, Histopathology.

[32]  A. Horvai,et al.  Genomic Profiling of Low-grade Intramedullary Cartilage Tumors Can Distinguish Enchondroma From Chondrosarcoma. , 2020, The American journal of surgical pathology.

[33]  A. Horvai,et al.  Targeted Next-Generation Sequencing Identifies Molecular and Genetic Events in Dedifferentiated Chondrosarcoma. , 2020, Archives of pathology & laboratory medicine.

[34]  Ž. Snoj,et al.  FUS-NFATC2 or EWSR1-NFATC2 Fusions Are Present in a Large Proportion of Simple Bone Cysts , 2020, The American journal of surgical pathology.

[35]  M. Hameed,et al.  Poorly differentiated chordoma with whole‐genome doubling evolving from a SMARCB1‐deficient conventional chordoma: A case report , 2020, Genes, chromosomes & cancer.

[36]  C. Fletcher,et al.  NKX3.1 immunoreactivity is not identified in mesenchymal chondrosarcoma: a 25‐case cohort study , 2020, Histopathology.

[37]  C. Fletcher,et al.  Clinicopathologic characterization of malignant chondroblastoma: a neoplasm with locally aggressive behavior and metastatic potential that closely mimics chondroblastoma-like osteosarcoma , 2020, Modern Pathology.

[38]  D. Spierings,et al.  Loss of NF2 defines a genetic subgroup of non‐FOS‐rearranged osteoblastoma , 2020, The journal of pathology. Clinical research.

[39]  David C. Jones,et al.  Drivers underpinning the malignant transformation of giant cell tumour of bone , 2020, medRxiv.

[40]  A. Franchi,et al.  Synovial chondrosarcoma: a single‐institution experience with molecular investigations and review of the literature , 2020, Histopathology.

[41]  F. Tirode,et al.  NFATc2-rearranged sarcomas: clinicopathologic, molecular, and cytogenetic study of 7 cases with evidence of AGGRECAN as a novel diagnostic marker , 2020, Modern Pathology.

[42]  Narasimhan P. Agaram,et al.  Myositis ossificans-like soft tissue aneurysmal bone cyst: a clinical, radiological, and pathological study of seven cases with COL1A1-USP6 fusion and a novel ANGPTL2-USP6 fusion , 2020, Modern Pathology.

[43]  O. Witt,et al.  NTRK fusions in osteosarcoma are rare and non‐functional events , 2020, The journal of pathology. Clinical research.

[44]  Ž. Snoj,et al.  Novel ASAP1‐USP6, FAT1‐USP6, SAR1A‐USP6, and TNC‐USP6 fusions in primary aneurysmal bone cyst , 2020, Genes, chromosomes & cancer.

[45]  C. Antonescu,et al.  NKX3-1 Is a Useful Immunohistochemical Marker of EWSR1-NFATC2 Sarcoma and Mesenchymal Chondrosarcoma , 2020, The American journal of surgical pathology.

[46]  Narasimhan P. Agaram,et al.  A molecular study of synovial chondromatosis , 2020, Genes, chromosomes & cancer.

[47]  P. Hoffstetter,et al.  ZFP36–FOSB fusion in a haemorrhagic epithelioid and spindle cell haemangioma of bone: is there a family of FOSB‐rearranged vascular neoplasms of the bone? , 2020, Histopathology.

[48]  M. Harris,et al.  Recurrent and novel USP6 fusions in cranial fasciitis identified by targeted RNA sequencing , 2019, Modern Pathology.

[49]  J. Bovée,et al.  Utility of FOS as diagnostic marker for osteoid osteoma and osteoblastoma , 2019, Virchows Archiv.

[50]  Narasimhan P. Agaram,et al.  Genomic Profiling Identifies Association of IDH1/IDH2 Mutation with Longer Relapse-Free and Metastasis-Free Survival in High-Grade Chondrosarcoma , 2019, Clinical Cancer Research.

[51]  Narasimhan P. Agaram,et al.  Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets , 2019, Modern Pathology.

[52]  C. Antonescu,et al.  Pericytoma With t(7;12) and ACTB-GLI1 Fusion , 2019, The American journal of surgical pathology.

[53]  J. Bovée,et al.  Conventional chondrosarcoma with focal clear cell change: a clinicopathological and molecular analysis , 2019, Histopathology.

[54]  S. Salas,et al.  A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation , 2019, Modern Pathology.

[55]  M. Ladanyi,et al.  NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls , 2019, Modern Pathology.

[56]  C. Antonescu,et al.  EWSR1/FUS - NFATc2 rearranged round cell sarcoma: Clinicopathological series of four cases and literature review. , 2019, Human pathology.

[57]  T. Shibata,et al.  Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone , 2019, Modern Pathology.

[58]  D. Huen,et al.  Comprehensive Molecular Characterization of Adamantinoma and OFD-like Adamantinoma Bone Tumors , 2019, The American journal of surgical pathology.

[59]  A. Flanagan,et al.  Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement , 2019, Modern Pathology.

[60]  A. Iafrate,et al.  Molecular characteristics of poorly differentiated chordoma , 2019, Genes, chromosomes & cancer.

[61]  P. Szépe,et al.  Fibro-osseous pseudotumor of digits and myositis ossificans show consistent COL1A1-USP6 rearrangement: a clinicopathological and genetic study of 27 cases. , 2019, Human pathology.

[62]  Narasimhan P. Agaram,et al.  Expanding the Spectrum of Intraosseous Rhabdomyosarcoma: Correlation Between 2 Distinct Gene Fusions and Phenotype , 2019, The American journal of surgical pathology.

[63]  E. Wardelmann,et al.  Activating mutations in the MAP‐kinase pathway define non‐ossifying fibroma of bone , 2019, The Journal of pathology.

[64]  H. Ichikawa,et al.  Novel NTRK3 Fusions in Fibrosarcomas of Adults , 2019, The American journal of surgical pathology.

[65]  A. Cleton-Jansen,et al.  Molecular Pathology of Bone Tumors. , 2019, The Journal of molecular diagnostics : JMD.

[66]  J. Fantasia,et al.  USP6 Gene Rearrangement by FISH Analysis in Cranial Fasciitis: A Report of Three Cases , 2019, Head and Neck Pathology.

[67]  A. Flanagan,et al.  An update of molecular pathology of bone tumors. Lessons learned from investigating samples by next generation sequencing , 2019, Genes, chromosomes & cancer.

[68]  C. Antonescu,et al.  Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone , 2018, The Journal of pathology.

[69]  A. Flanagan,et al.  FOS Expression in Osteoid Osteoma and Osteoblastoma A Valuable Ancillary Diagnostic Tool , 2019 .

[70]  D. Sinnett,et al.  TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw , 2018, Nature Communications.

[71]  N. Hiraoka,et al.  H3K27me3 deficiency defines a subset of dedifferentiated chondrosarcomas with characteristic clinicopathological features , 2018, Modern Pathology.

[72]  Jessica L. Davis,et al.  Genetic and molecular reappraisal of spindle cell adamantinoma of bone reveals a small subset of misclassified intraosseous synovial sarcoma , 2018, Modern Pathology.

[73]  Hong Yang,et al.  Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A Genetic Study of 22 Cases With Clinicopathologic Analysis , 2018, The American journal of surgical pathology.

[74]  H. Ichikawa,et al.  PAX7 immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours , 2018, Histopathology.

[75]  J. Fletcher,et al.  Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy , 2018, Cancer cytopathology.

[76]  C. Fletcher,et al.  Evaluation of pan‐TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis‐like neural tumour and histological mimics , 2018, Histopathology.

[77]  A. Folpe,et al.  Mesenchymal chondrosarcomas showing immunohistochemical evidence of rhabdomyoblastic differentiation: a potential diagnostic pitfall. , 2018, Human pathology.

[78]  Asha A. Nair,et al.  Spindle cell rhabdomyosarcoma of bone with FUS–TFCP2 fusion: confirmation of a very recently described rhabdomyosarcoma subtype , 2018, Histopathology.

[79]  Matthew D. Young,et al.  Recurrent rearrangements of FOS and FOSB define osteoblastoma , 2018, Nature Communications.

[80]  Peter J. Park,et al.  Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing , 2018, bioRxiv.

[81]  O. Delattre,et al.  Transcriptomic definition of molecular subgroups of small round cell sarcomas , 2018, The Journal of pathology.

[82]  David T. W. Jones,et al.  Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information , 2018, Modern Pathology.

[83]  G. Nielsen,et al.  Clinicopathologic characteristics of poorly differentiated chordoma , 2018, Modern Pathology.

[84]  Y. Oda,et al.  Diagnostic utility of histone H3.3 G34W, G34R, and G34V mutant-specific antibodies for giant cell tumors of bone. , 2017, Human pathology.

[85]  Y. Ishikawa,et al.  Osteosarcoma arising in fibrous dysplasia, confirmed by mutational analysis of GNAS gene. , 2017, Pathology, research and practice.

[86]  C. Antonescu,et al.  BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas , 2017, The American journal of surgical pathology.

[87]  A. Iafrate,et al.  Clinicopathologic Features of Non-Small-Cell Lung Cancer Harboring an NTRK Gene Fusion. , 2017, JCO precision oncology.

[88]  Matthew D. Young,et al.  The driver landscape of sporadic chordoma , 2017, Nature Communications.

[89]  M. Rijn,et al.  EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma , 2017, Modern Pathology.

[90]  Wei-Lien Wang,et al.  USP6 activation in nodular fasciitis by promoter-swapping gene fusions , 2017, Modern Pathology.

[91]  T. Barth,et al.  H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant , 2017, Histopathology.

[92]  C. Antonescu,et al.  Sarcomas With CIC-rearrangements Are a Distinct Pathologic Entity With Aggressive Outcome: A Clinicopathologic and Molecular Study of 115 Cases , 2017, The American journal of surgical pathology.

[93]  Daniel Baumhoer,et al.  Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma , 2017, Nature Communications.

[94]  C. Antonescu,et al.  ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements , 2017, Genes, chromosomes & cancer.

[95]  A. Flanagan,et al.  H3F3A (Histone 3.3) G34W Immunohistochemistry , 2017, The American journal of surgical pathology.

[96]  David T. W. Jones,et al.  Histone 3.3 hotspot mutations in conventional osteosarcomas: a comprehensive clinical and molecular characterization of six H3F3A mutated cases , 2017, Clinical Sarcoma Research.

[97]  C. Fletcher,et al.  FOSB is a Useful Diagnostic Marker for Pseudomyogenic Hemangioendothelioma , 2017, The American journal of surgical pathology.

[98]  R. Sompallae,et al.  Anchored multiplex PCR for targeted next‐generation sequencing reveals recurrent and novel USP6 fusions and upregulation of USP6 expression in aneurysmal bone cyst , 2017, Genes, chromosomes & cancer.

[99]  A. Folpe,et al.  Characterization of FN1–FGFR1 and novel FN1–FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors , 2016, Modern Pathology.

[100]  Narasimhan P. Agaram,et al.  Secondary EWSR1 gene abnormalities in SMARCB1‐deficient tumors with 22q11‐12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results , 2016, Genes, chromosomes & cancer.

[101]  Gaëlle Pérot,et al.  ETV4 is a useful marker for the diagnosis of CIC-rearranged undifferentiated round-cell sarcomas: a study of 127 cases including mimicking lesions , 2016, Modern Pathology.

[102]  C. Fletcher,et al.  Evaluation of ETV4 and WT1 expression in CIC-rearranged sarcomas and histologic mimics , 2016, Modern Pathology.

[103]  Narasimhan P. Agaram,et al.  BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities , 2016, The American journal of surgical pathology.

[104]  M. Ladanyi,et al.  Genomic aberrations frequently alter chromatin regulatory genes in chordoma , 2016, Genes, chromosomes & cancer.

[105]  A. Flanagan,et al.  The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma , 2016, Histopathology.

[106]  Narasimhan P. Agaram,et al.  Recurrent CIC Gene Abnormalities in Angiosarcomas: A Molecular Study of 120 Cases With Concurrent Investigation of PLCG1, KDR, MYC, and FLT4 Gene Alterations , 2016, The American journal of surgical pathology.

[107]  P. Brousset,et al.  Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[108]  A. Folpe,et al.  Primary Pseudomyogenic Hemangioendothelioma of Bone , 2016, The American journal of surgical pathology.

[109]  C. Fletcher,et al.  Evaluation of NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma , 2016, Modern Pathology.

[110]  Jacques P. Brown,et al.  ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor , 2016, American journal of human genetics.

[111]  C. Fletcher,et al.  Nuclear Expression of CAMTA1 Distinguishes Epithelioid Hemangioendothelioma From Histologic Mimics , 2016, The American journal of surgical pathology.

[112]  Florian Engert,et al.  Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency , 2015, Nature Communications.

[113]  M. Hisaoka,et al.  CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma , 2015, Histopathology.

[114]  A. Cleton-Jansen,et al.  Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma , 2015, The American journal of surgical pathology.

[115]  Narasimhan P. Agaram,et al.  Frequent FOS Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases With Morphologic Reappraisal , 2015, The American journal of surgical pathology.

[116]  P. Hogendoorn,et al.  Periosteal chondrosarcoma: a histopathological and molecular analysis of a rare chondrosarcoma subtype , 2015, Histopathology.

[117]  T. Forshew,et al.  GNAS mutations are not detected in parosteal and low-grade central osteosarcomas , 2015, Modern Pathology.

[118]  A. Folpe,et al.  Identification of a novel FN1–FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour , 2015, The Journal of pathology.

[119]  C. Antonescu,et al.  Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone , 2015, Genes, chromosomes & cancer.

[120]  Donna M. Muzny,et al.  BCOR-CCNB3 Fusions Are Frequent in Undifferentiated Sarcomas of Male Children , 2014, Modern Pathology.

[121]  Narasimhan P. Agaram,et al.  ZFP36‐FOSB fusion defines a subset of epithelioid hemangioma with atypical features , 2014, Genes, chromosomes & cancer.

[122]  H. Douis,et al.  BCOR-CCNB3 (Ewing-like) Sarcoma: A Clinicopathologic Analysis of 10 Cases, In Comparison With Conventional Ewing Sarcoma , 2014, The American journal of surgical pathology.

[123]  S. Miyano,et al.  Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma , 2014, Genome research.

[124]  Jianxin Shi,et al.  Characterization of T gene sequence variants and germline duplications in familial and sporadic chordoma , 2014, Human Genetics.

[125]  Narasimhan P. Agaram,et al.  USP6 gene rearrangements occur preferentially in giant cell reparative granulomas of the hands and feet but not in gnathic location. , 2014, Human pathology.

[126]  P. D. Dal Cin,et al.  Nuclear protein in testis midline carcinoma misdiagnosed as adamantinoma. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[127]  Li Ding,et al.  Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. , 2014, Cell reports.

[128]  D. Jong,et al.  GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma , 2014, Nature Genetics.

[129]  M. Stratton,et al.  Recurrent PTPRB and PLCG1 mutations in angiosarcoma , 2014, Nature Genetics.

[130]  A. Cleton-Jansen,et al.  Recurrent Chromosome 22 Deletions in Osteoblastoma Affect Inhibitors of the Wnt/Beta-Catenin Signaling Pathway , 2013, PloS one.

[131]  M. Stratton,et al.  Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone , 2013, Nature Genetics.

[132]  J. Hornick,et al.  SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumours , 2013, Histopathology.

[133]  S. Aubert,et al.  Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions , 2013, Modern Pathology.

[134]  G. Nielsen,et al.  Molecular Distinction of Chondrosarcoma From Chondroblastic Osteosarcoma Through IDH1/2 Mutations , 2013, The American journal of surgical pathology.

[135]  A. B. Hassan,et al.  Functional Profiling of Receptor Tyrosine Kinases and Downstream Signaling in Human Chondrosarcomas Identifies Pathways for Rational Targeted Therapy , 2013, Clinical Cancer Research.

[136]  A. Folpe,et al.  A Benign Vascular Tumor With a New Fusion Gene: EWSR1-NFATC1 in Hemangioma of the Bone , 2013, The American journal of surgical pathology.

[137]  Yan Chen,et al.  GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw , 2013, Modern Pathology.

[138]  R. Lothe,et al.  Whole-Transcriptome Sequencing Identifies Novel IRF2BP2-CDX1 Fusion Gene Brought about by Translocation t(1;5)(q42;q32) in Mesenchymal Chondrosarcoma , 2012, PloS one.

[139]  P. Talmud,et al.  A common single-nucleotide variant in T is strongly associated with chordoma , 2012, Nature Genetics.

[140]  T. Seemayer,et al.  Pericytoma with t(7;12) and ACTB-GLI1 fusion arising in bone. , 2012, Human pathology.

[141]  H. Tsuda,et al.  NKX2.2 is a Useful Immunohistochemical Marker for Ewing Sarcoma , 2012, The American journal of surgical pathology.

[142]  O. Delattre,et al.  A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion , 2012, Nature Genetics.

[143]  T. Shibata,et al.  MDM2 and CDK4 Immunohistochemical Coexpression in High-grade Osteosarcoma: Correlation With a Dedifferentiated Subtype , 2012, The American journal of surgical pathology.

[144]  N. Socci,et al.  Identification of a novel, recurrent HEY1‐NCOA2 fusion in mesenchymal chondrosarcoma based on a genome‐wide screen of exon‐level expression data , 2012, Genes, chromosomes & cancer.

[145]  A. Flanagan,et al.  Frequency of Mouse Double Minute 2 (MDM2) and Mouse Double Minute 4 (MDM4) amplification in parosteal and conventional osteosarcoma subtypes , 2012, Histopathology.

[146]  A. Futreal,et al.  Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2 , 2011, Nature Genetics.

[147]  R. Sciot,et al.  Somatic mosaic IDH1 or IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome , 2011, Nature Genetics.

[148]  M. Chou,et al.  Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion , 2011, Laboratory Investigation.

[149]  A. Grigoriadis,et al.  IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours , 2011, The Journal of pathology.

[150]  Julie M. Batten,et al.  Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas , 2011, PloS one.

[151]  L. Guillou,et al.  MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone , 2011, Modern Pathology.

[152]  J. Seidman,et al.  Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome , 2011, PLoS genetics.

[153]  P. Casali,et al.  Analysis of receptor tyrosine kinases (RTKs) and downstream pathways in chordomas. , 2010, Neuro-oncology.

[154]  T. Shibata,et al.  Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics , 2010, Modern Pathology.

[155]  J. Wunder,et al.  Characterization of the 12q15 MDM2 and 12q13‐14 CDK4 amplicons and clinical correlations in osteosarcoma , 2010, Genes, chromosomes & cancer.

[156]  S. Mukherji,et al.  Sino-orbital osteoma: a clinicopathologic study of 45 surgically treated cases with emphasis on tumors with osteoblastoma-like features. , 2009, Archives of pathology & laboratory medicine.

[157]  A. Goldstein,et al.  T (brachyury) gene duplication confers major susceptibility to familial chordoma , 2009, Nature Genetics.

[158]  S. Knuutila,et al.  Genomic Profiling of Chondrosarcoma: Chromosomal Patterns in Central and Peripheral Tumors , 2009, Clinical Cancer Research.

[159]  H. Tanke,et al.  The NFATc2 Gene Is Involved in a Novel Cloned Translocation in a Ewing Sarcoma Variant That Couples Its Function in Immunology to Oncology , 2009, Clinical Cancer Research.

[160]  J. O'Connell,et al.  Epithelioid Hemangioma of Bone Revisited: A Study of 50 Cases , 2009, The American journal of surgical pathology.

[161]  A. Flanagan,et al.  A sensitive mutation‐specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone , 2007, Histopathology.

[162]  S. Henderson,et al.  Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas , 2006, The Journal of pathology.

[163]  G. Siegal,et al.  Osteosarcoma: anatomic and histologic variants. , 2006, American journal of clinical pathology.

[164]  J. Fletcher,et al.  USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. , 2004, The American journal of pathology.

[165]  A. Stemmer-Rachamimov,et al.  Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2 , 2004, Genes, chromosomes & cancer.

[166]  J. Fletcher,et al.  USP6 (Tre2) Fusion Oncogenes in Aneurysmal Bone Cyst , 2004, Cancer Research.

[167]  J. O'Connell,et al.  Chondroblastoma-Like Chondroma of Soft Tissue: An Underrecognized Variant and Its Differential Diagnosis , 2001, The American journal of surgical pathology.

[168]  Dale E. Jarka,et al.  Osteochondromyxoma of Bone: A Congenital Tumor Associated With Lentigines and Other Unusual Disorders , 2001, The American journal of surgical pathology.

[169]  C. Stratakis,et al.  Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex , 2000, Nature Genetics.

[170]  M. Ushijima,et al.  Activating Gs(alpha) mutation in intramuscular myxomas with and without fibrous dysplasia of bone. , 2000, Virchows Archiv : an international journal of pathology.

[171]  A. Cleton-Jansen,et al.  Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis , 1999, The Journal of pathology.

[172]  G. Nielsen,et al.  Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma. , 1999, The American journal of surgical pathology.

[173]  A. Cleton-Jansen,et al.  EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas. , 1999, American journal of human genetics.

[174]  A. Rosenberg,et al.  Hemorrhagic epithelioid and spindle cell hemangioma , 1999, Cancer.

[175]  K. Eppert,et al.  Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas , 1999, Oncogene.

[176]  C. Inwards,et al.  Chondromyxoid fibroma of bone: a clinicopathologic review of 278 cases. , 1998, Human pathology.

[177]  S. Knuutila,et al.  Comparative genomic hybridization of low-grade central osteosarcoma. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[178]  M. Lovett,et al.  The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes , 1996, Nature Genetics.

[179]  M. Wagner,et al.  Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1) , 1995, Nature Genetics.

[180]  T. Ishida,et al.  Massive chondroid differentiation in fibrous dysplasia of bone (fibrocartilaginous dysplasia) , 1993, The American journal of surgical pathology.

[181]  J. O'Connell,et al.  Epithelioid Hemangioma of Bone: A Tumor Often Mistaken for Low-Grade Angiosarcoma or Malignant Hemangioendothelioma , 1993, The American journal of surgical pathology.

[182]  G. Thomas,et al.  Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours , 1992, Nature.

[183]  M. Merino,et al.  Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. , 1991, The New England journal of medicine.

[184]  A. Cabrera,et al.  EWING'S SARCOMA. , 1964, Surgery, gynecology & obstetrics.