Updates from the 2020 World Health Organization Classification of Soft Tissue and Bone Tumours.

The fifth edition of the World Health Organization (WHO) classification of soft tissue and bone tumours was published in May 2020. This 'Blue Book', which is also available digitally for the first time, incorporates an array of new information on these tumours, amassed in the 7 years since the previous edition. Major advances in molecular characterisation have driven further refinements in classification and the development of ancillary diagnostic tests, and have improved our understanding of disease pathogenesis. Several new entities are also included. This review summarises the main changes introduced in the 2020 WHO classification for each subcategory of soft tissue and bone tumours.

The 2020 WHO Classification of Tumors of Bone: An Updated Review.

Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other mesenchymal and nonmesenchymal bone lesions can complicate diagnosis. Accurate histologic diagnosis is crucial for appropriate management and prognostication. Since the publication of the fourth edition of the World Health Organization (WHO) classification of tumors of soft tissue and bone in 2013, significant advances have been made in our understanding of bone tumor molecular biology, classification, prognostication, and treatment. Detection of tumor-specific molecular alterations can facilitate the accurate diagnosis of histologically challenging cases. The fifth edition of the 2020 WHO classification of tumors of soft tissue and bone tumors provides an updated classification scheme and essential diagnostic criteria for bone tumors. Herein, we summarize these updates, focusing on major changes in each category of bone tumor, the newly described tumor entities and subtypes of existing tumor types, and newly described molecular and genetic data.

Advances in targeted therapy for osteosarcoma based on molecular classification.

Osteosarcoma, a highly malignant tumor, is characterized by widespread and recurrent chromosomal and genetic abnormalities. In recent years, a number of elaborated sequencing analyses have made it possible to cluster the osteosarcoma based on the identification of candidate driver genes and develop targeted therapy. Here, we reviewed recent next-generation genome sequencing studies and advances in targeted therapies for osteosarcoma based on molecular classification. First, we stratified osteosarcomas into ten molecular subtypes based on genetic changes. And we analyzed potential targeted therapies for osteosarcoma based on the identified molecular subtypes. Finally, the development of targeted therapies for osteosarcoma investigated in clinical trials were further summarized and discussed. Therefore, we indicated the importance of molecular classification on the targeted therapy for osteosarcoma. And the stratification of patients based on the genetic characteristics of osteosarcoma will help to obtain a better therapeutic response to targeted therapies, bringing us closer to the era of personalized medicine.

A comparison of depth of necrosis among adjuvant therapies used for the treatment of benign bone tumors.

BACKGROUND AND OBJECTIVES: Benign bone tumors are often treated with extended curettage utilizing an adjuvant therapy to eliminate any remaining tumor cells. The purpose of this study was to explore and compare the histologic depth of necrosis created by various adjuvant therapies used in the treatment of benign bone tumors. METHODS: A high-speed burr was utilized to create cortical defects within porcine humeri and femora. Phenol, polymethyl methacrylate (PMMA), argon beam coagulation (ABC), liquid nitrogen, and the Bipolar Hemostatic Sealer (BHS) were each applied to five defects, with an additional five defects left untreated as a control. The maximal depth of necrosis was determined under microscopic examination. RESULTS: The phenol, PMMA, ABC, liquid nitrogen, and BHS demonstrated an average histologic depth of necrosis of 0.30, 0.78, 2.54, 2.54, and 0.92 mm, respectively, each of which was significantly increased compared to the control group (p = .001, .003, .003, .01, and  <.001). Their respective variances, a measure of reproducibility, were 0.01, 0.09, 0.96, 1.93, and 0.03 mm2 . CONCLUSION: This study confirms, through histologic analysis, adjuvant therapies create a rim of cellular necrosis beyond that of burring during extended curettage, supporting their use in the treatment of benign bone tumors. Furthermore, it provides a head-to-head comparison.

Derivation and validation of risk groups in patients with osteosarcoma utilizing regression tree analysis.

BACKGROUND: For patients with osteosarcoma, apart from stage and primary site, we lack reliable prognostic factors for risk stratification at diagnosis. There is a need for further defined, discrete prognostic groups using presenting clinical features. METHODS: We analyzed a cohort of 3069 patients less than 50 years of age, diagnosed with primary osteosarcoma of the bone between 1986 and 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly split into test and validation cohorts. Optimal cut points for age, tumor size, and grade were identified using classification and regression tree analysis. Manual recursive partitioning was used to identify discrete prognostic groups within the test cohort. These groups were applied to the validation cohort, and overall survival was analyzed using Cox models, Kaplan Meier methods, and log-rank tests. RESULTS: After applying recursive partitioning to the test cohort, our initial model included six groups. Application of these groups to the validation cohort resulted in four final groups. Key risk factors included presence of metastases, tumor site, tumor grade, age, and tumor size. Patients with localized axial tumors were identified as having similar outcomes to patients with metastases. Age and tumor size were only prognostically important in patients with extremity tumors when assessed in the validation cohort. CONCLUSIONS: This analysis supports prior reports that patients with axial tumors are a high-risk group, and demonstrates the importance of age and tumor size in patients with appendicular tumors. Biologic and genetic markers are needed to further define subgroups in osteosarcoma.

Staging and Classification of Primary Musculoskeletal Bone and Soft-Tissue Tumors According to the 2020 WHO Update, From the AJR Special Series on Cancer Staging.

Staging of primary musculoskeletal bone and soft-tissue tumors is most commonly performed using the AJCC and the Enneking or Musculoskeletal Tumor Society (MSTS) staging systems. Radiologic imaging is integral in achieving adequate musculoskeletal neoplastic staging by defining lesion extent and identifying regional lymph node involvement and distant metastatic disease. Additional important features in surgical planning, though not distinct components of the staging systems, include cortical involvement, joint invasion, and neurovascular encasement; these features are optimally evaluated by MRI. In 2020, the WHO updated the classification of primary musculoskeletal tumors of soft tissue and bone. The update reflects the continued explosion in identification of novel gene alterations in many bone and soft-tissue neoplasms. This growth in gene alteration identification has resulted in newly designated lesions, reclassification of lesion categories, and improved specificity of diagnosis. Although radiologists do not need to have a comprehensive knowledge of the pathologic details, a broad working understanding of the most recent update is important to aid accurate and timely diagnosis given that histologic grading is a component of all staging systems. By using a multidisciplinary approach for primary musculoskeletal neoplasms involving colleagues in pathology, orthopedic oncology, radiation oncology, and medical oncology, radiologists may promote improved diagnosis, treatment, and outcomes.

Nonossifying Fibromas: A Computed Tomography-based Criteria to Predict Fracture Risk.

BACKGROUND: Nonossifying fibroma (NOF) is the most common benign osseous lesion in children; however, our understanding of which lesions progress to a fracture remains unclear. In this study, we seek to formulate a classification system for NOFs to assess for fracture risk and determine what this classification system tells us regarding fracture risk of the distal tibia and distal femur NOFs. METHODS: Charts were retrospectively reviewed for patients with NOFs. A 4-point criteria was created and used to calculate fracture risk for distal tibia and distal femur NOFs. The analysis included incidence, specificity, and sensitivity. RESULTS: One point was given for each of the following findings on computed tomography (CT) scan: (1) >50% width on coronal view; (2) >50% width on sagittal view; (3) any cortical breach; (4) lack of a neocortex. In total, 34 patients with NOFs of the distal tibia had CT scans, of which 14 fractured. Zero with a 0- or 1-point score fractured, 2 with a 2-point score fractured (20%), 4 with a 3-point score fractured (44%), and 8 with a 4-point score fractured (100%). Sensitivities of 1-, 2-, 3-, and 4-point scores were 100%, 100%, 85.7%, and 57.1%, respectively, and specificities were 71.4%, 71.4%, 80%, and 100%, respectively. A total of 41 patients with NOFs of the distal femur had CT scans, of which 5 fractured. Zero with a 0-point score fractured, 1 with a 1-point score fractured (4%), 0 with a 2-point score fractured, 1 with a 3-point score fractured (20%), and 3 with a 4-point score fractured (100%). Sensitivities of 1-, 2-, 3-, and 4-point scores were 100%, 80%, 80%, and 60%, respectively; and specificities were 60%, 87.8%, 90%, and 100%, respectively. CONCLUSIONS: Our 4-point CT criteria is easy to apply and identifies patients at high risk of fracture, helping surgeons make decisions regarding treatment. LEVEL OF EVIDENCE: Level IV-prognostic study.

New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group.

The Cancer Staging Manual of the American Joint Committee on Cancer (AJCC) has recently been revised and updated to its eighth edition. This review focuses on the new staging system of bone and soft tissue sarcomas and outlines the revision points and caveats in the latest edition. The major changes in the eighth edition of the AJCC staging for bone and soft tissue sarcomas are the following four points. (i) Tumors are described separately according to the primary sites. For bone sarcoma, three tumor locations are described: (a) appendicular skeleton, trunk, skull and facial bones; (b) spine and (c) pelvis. Meanwhile, four tumor locations are described for soft tissue sarcoma: (1) trunk and extremity; (2) retroperitoneum; (3) head and neck and (4) visceral sites. (ii) Histologic grading system in bone sarcoma is changed to three-grade classifications. (iii) For soft tissue sarcoma, AnyTN1M0 tumor in the trunk and extremity is classified as stage IV, whereas for the retroperitoneal tumor, anyTN1M0 remains as stage IIIB. (iv) For soft tissue sarcomas in the trunk, extremity and retroperitoneum, tumor size was classified into four categories: (a) ≤5 cm; (b) >5 cm and ≤10 cm; (c) >10 cm and ≤15 cm and (d) >15 cm. In addition, the notation about the depth of the tumor (superficial or deep from the superficial fascia) has been eliminated.

Benign tumours and tumour like lesions of bone.

Over the last century, there has been a remarkable development in the study of benign bone tumours. This is primarily due to the improved knowledge of the nature of these lesions and improved imaging technology. They present as a diverse group of clinical and pathological entities, which vary in their clinical behaviour and aggressiveness and, hence, multidisciplinary approach is necessary in their management. Combined opinion from an orthopaedic surgeon, radiologist and a pathologist is therefore required. Incidence of these tumours is debatable because they are often asymptomatic. Many protocols have been reported in studies with respect to the management of these tumours based on the experience of different centres and different surgeons with no set guidelines. English-language studies, including case reports, case series and systemic reviews, from PubMed, ERIC, MEDLINE, EMBASE and Cochrane Reviews databases from 2002 to 2016 were included in the current. Articles reporting all levels of evidence - Level I to V - were included.

[Use of Solid Intercalary Allografts for Reconstruction Following the Resection of Primary Bone Tumors]. / Vyuzití solidních interkalárních allostepu k rekonstrukci po resekcích primárních kostních nádoru.

PURPOSE OF THE STUDY There are several treatment options for bone tumors at diaphyseal/metadiaphyseal sites of long bones (with joint preservation) including massive intercalary allografts, autografts (vascularized or non-vascularized fibular autograft, devitalised tumor bearing bone), endoprosthetic replacement (intercalary spacer), cementoplasty with ostheosynthesis and distraction osteogenesis. Reconstruction using massive intercalary bone allografts is for us the method of choice in case of curable primary bone tumors at the diaphyseal/metadiaphyseal region. The purpose of this study is to evaluate our results and complications. MATERIAL AND METHODS Our retrospective study reviewed 41 patients after intercalary allograft reconstruction following the resection of primary bone tumors in the years 2000 - 2014. The group consists of 27 men and 14 women with the mean age at the time of diagnosis 27 years and the mean follow-up (from primary surgery) was 7 years. The patients were diagnosed with the Ewing sarcoma (14), chondrosarcoma (9), osteosarcoma (8), adamantinoma (6), OFD-like adamantinoma (2) and aneurysmatic bone cyst (2). The site of tumor were tibia (18), femur (16), humerus (5), radius (1) and ulna (1). We retrospectively evaluated the results of this intercallary allograft reconstructions, the incidence of failures and complications as well as the role of risk factors. RESULTS 14 patients (34.1%) successfully healed without complications. In the same number of patients (14 patients, 34.1%) the allograft reconstruction failed. 7 of these patients underwent amputation (17.1%), 6 of whom for oncological complications (local recurrence) and only 1 for complications of the reconstruction (infection). Other 7 patients with an allograft-related failure were successfully treated with a limb salvage procedure and underwent a new reconstruction. The remaining 13 patients (31.7%) suffered from complications that did not result in a failure of the reconstruction. The major complications of the reconstruction were the non-union (53.7%), fractures and allograft resorption (14.6%) and infection (7.3%). By statistical evaluation of common risk factors a statistically significant relationship was found between uncomplicated healing and stable bridging osteosynthesis (p = 0.014), between allograft fractures/resorptions and non-bridging osteosynthesis (p = 0.018), and the lowest reoperation rate was connected with plate osteosynthesis (0.037). DISCUSSION AND CONCLUSIONS The intercalary allograft reconstruction is an important biological method in orthopaedic tumor surgery. Even though it is connected with a high rate of complications (non-union, fracture and resorption, infection), in the vast majority of cases they can be solved, while achieving limb-salvage and good function of extremity. The essential prerequisite for successful uncomplicated healing of reconstruction is the stable bridging osteosynthesis, preferably with a plate. In high risk patients with a combination of recognized important risk factors described in literature (adult patients, large resection (more than 15 cm), femoral location and aggressive oncological treatment) we nowadays try to reduce the complication rate with a primary combination of an allograft with vascularized fibular autograft. Key words:biological bone reconstruction, massive intercallary allograft, stable bridging osteosynthesis, primary bone tumors.

123I-mIBG scintigraphy in neuroblastoma: development of a SIOPEN semi-quantitative reporting ,method by an international panel.

PURPOSE: A robust method is required to standardise objective reporting of diagnostic 123I-mIBG images in neuroblastoma. Prerequisites for an appropriate system are low inter- and intra-observer error and reproducibility across a broad disease spectrum. We present a new reporting method, developed and tested for SIOPEN by an international expert panel. METHOD: Patterns of abnormal skeletal 123I-mIBG uptake were defined and assigned numerical scores [0-6] based on disease extent within 12 body segments. Uptake intensity was excluded from the analysis. Data sets from 82 patients were scored independently by six experienced specialists as unblinded pairs (pre- and post-induction chemotherapy) and in random order as a blinded study. Response was defined as ≥50 % reduction in post induction score compared with baseline. RESULTS: In total, 1968 image sets were reviewed individually. Response rates of 88 % and 82 % were recorded for patients with baseline skeletal scores ≤23 and 24-48 respectively, compared with 44 % response in patients with skeletal scores >48 (p = 0.02). Reducing the number of segments or extension scale had a small but statistically negative impact upon the number of responses detected. Intraclass correlation coefficients [ICCs] calculated for the unblinded and blinded study were 0.95 at diagnosis and 0.98 and 0.99 post-induction chemotherapy, respectively. CONCLUSIONS: The SIOPEN mIBG score method is reproducible across the full spectrum of disease in high risk neuroblastoma. Numerical assessment of skeletal disease extent avoids subjective evaluation of uptake intensity. This robust approach provides a reliable means with which to examine the role of 123I mIBG scintigraphy as a prognostic indicator in neuroblastoma.

A Novel System for the Surgical Staging of Primary High-grade Osteosarcoma: The Birmingham Classification.

BACKGROUND: Chemotherapy response and surgical margins have been shown to be associated with the risk of local recurrence in patients with osteosarcoma. However, existing surgical staging systems fail to reflect the response to chemotherapy or define an appropriate safe metric distance from the tumor that will allow complete excision and closely predict the chance of disease recurrence. We therefore sought to review a group of patients with primary high-grade osteosarcoma treated with neoadjuvant chemotherapy and surgical resection and analyzed margins and chemotherapy response in terms of local recurrence. QUESTIONS/PURPOSES: (1) What predictor or combination of predictors available to the clinician can be assessed that more reliably predict the likelihood of local recurrence? (2) Can we determine a better predictor of local recurrence-free survival than the currently applied system of surgical margins? (3) Can we determine a better predictor of overall survival than the currently applied system of surgical margins? METHODS: This retrospective study included all patients with high-grade conventional osteosarcomas without metastasis at diagnosis treated at one center between 1997 and 2012 with preoperative chemotherapy followed by resection or amputation of the primary tumor who were younger than age 50 years with minimum 24-month followup for those still alive. A total of 389 participants matched the inclusion criteria. Univariate log-rank test and multivariate Cox analyses were undertaken to identify predictors of local recurrence-free survival (LRFS). The Birmingham classification was devised on the basis of two stems: the response to chemotherapy (good response = ≥ 90% necrosis; poor response = < 90% necrosis) and margins (< 2 mm or ≥ 2 mm). The 5-year overall survival rate was 67% (95% confidence interval [CI], 61%-71%) and 47 patients developed local recurrence (12%). RESULTS: Intralesional margins (hazard ratio [HR], 9.9; 95% CI, 1.2-82; p = 0.03 versus radical margin HR, 1) and a poor response to neoadjuvant chemotherapy (HR, 3.8; 95% CI, 1.7-8.4; p = 0.001 versus good response HR, 1) were independent risk factors for local recurrence (LR). The best predictor of LR, however, was a combination of margins ≤ 2 mm and a less than 90% necrosis response to chemotherapy (Birmingham 2b HR, 19.6; 95% CI, 2.6-144; p = 0.003 versus Birmingham 1a; margin >2 mm and more than 90% necrosis HR, 1). Two-stage Cox regression model and higher Harrell's C statistic demonstrate that the Birmingham classification was superior to the Musculoskeletal Tumor Society (MSTS) margin classification for predicting LR (Harrell's C statistic Birmingham classification 0.68, MSTS criteria 0.59). A difference in overall survival was seen between groups of the Birmingham classification (log-rank test p < 0.0001), whereas the MSTS margin system was not discriminatory (log-rank test p = 0.14). CONCLUSIONS: Based on these observations, we believe that a combination of the recording of surgical margins in millimeters and the response to neoadjuvant chemotherapy can more accurately predict the risk of local recurrence than the current MSTS system. A multicenter collaboration study initiated by the International Society of Limb Salvage is recommended to test the validity of the proposed classification and if these findings are confirmed, this classification system might be considered the standard practice in oncology centers treating patients with osteosarcomas and allow more effective communication of margin status for research. LEVEL OF EVIDENCE: Level IV, prognostic study.

[Conventional radiological diagnosis of benign none neoplasms]. / Konventionell-radiologische Diagnose von gutartigen Knochentumoren.

BACKGROUND: Benign bone tumors are of special clinical importance because they might be confused with malignant bone tumors. OBJECTIVES: The aim of this article it to present the characteristics of benign bone tumors. The focus is orientated towards conventional x­ray as the essential pillar for primary diagnosis. Consequently, the description of signal intensities of benign bone tumors in magnetic resonance images or less helpful clues like male-female ratios are deliberately omitted. RESULTS: The classification of bone tumors introduced by Lodwick allows the identification of benign growth patterns. Growth patterns will not help, for example, in case of dedifferentiation of benign chondroid tumors towards chondrosarcomas. Therefore, each diagnosis has to incorporate the patient's clinical scenario. Furthermore, benign bone tumors might also cause aggressive growth patterns. Tumors classified as Lodwick Ic or higher should not be automatically regarded as malignant. Naturally, further clarification is mandatory for these tumors. CONCLUSIONS: Differentiation between definitely benign bone tumors and those which need further work up is a critical diagnostic step. In the majority of cases, this is possible based on the appearance in conventional x­ray images. In case of possibly malignant lesions, both the patient's symptoms and the x­ray morphology have to be considered by orthopedic surgeons, pathologists, and radiologists to determine the optimal diagnostic strategy.

[Benign tumours and tumour-like lesions of the bone : General treatment principles]. / Benigne Tumoren und tumorähnliche Läsionen des Knochens : Allgemeine Behandlungsprinzipien.

BACKGROUND: Benign bone lesions are much more common than malignant lesions. Some benign bone tumors have a characteristic and typical radiographic appearance, while others are more challenging. Therapy of benign bone tumors differs greatly. While the majority of benign bone tumors do not require surgical therapy, other specific lesions, e. g. aneurysmal bone cysts or giant cell tumors (GCT) of the bone require surgery due to their locally aggressive behavior. DIAGNOSTICS: The major challenge for the radiologist and/or pathologist is the differentiation between a benign and low-grade malignant lesion (e. g. enchondroma versus low-grade chondrosarcoma) for which all available clinical and radiographic information is mandatory. Therefore, surgical therapy is rather more often performed than necessary due to uncertainty in many cases. THERAPY: Novel systemic therapies are available for fibrous dysplasia and GCT of the bone: Fibrous dysplasia can be treated with bisphosphonates, and GCT responds to denosumab. In fact, denosumab has been approved for the treatment of irresectable GCT. Osteoid osteoma is fairly easy to recognize and also to treat given the characteristic clinical presentation and rapid and effective response to local therapy (possible as percutaneous thermo-/laser ablation). In summary, several therapeutic options exist for benign bone tumors, and the choice depends upon the tendency/risk of local recurrence, the rate of surgical complications, options for defect reconstruction, postoperative functional deficits, and specific patient characteristics.

Explant culture of sarcoma patients' tissue.

Human sarcomas comprise a heterogeneous group of rare tumors that affect soft tissues and bone. Due to the scarcity and heterogeneity of these diseases, patient-derived cells that can be used for preclinical research are limited. In this study, we investigated whether the tissue explant technique can be used to obtain sarcoma cell lines from fresh as well as viable frozen tissue obtained from 8 out of 12 soft tissue and 9 out of 13 bone tumor entities as defined by the World Health Organization. The success rate, defined as the percent of samples that yielded sufficient numbers of outgrowing cells to be frozen, and the time to freeze were determined for a total of 734 sarcoma tissue specimens. In 552 cases (75%) enough cells were obtained to be frozen at early passage. Success rates were higher in bone tumors (82%) compared with soft tissue tumors (68%), and the mean time to freezing was lower in bone tumors (65 days) compared with soft tissue tumors (84 days). Overall, from 40% of the tissues cells could be frozen at early passage within <2 month after tissue removal. Comparable results as with fresh tissue were obtained after explant of viable frozen patient-derived material. In a selected number of bone and soft tissue sarcoma entities, conventional karyotyping and/or FISH (fluorescence in situ hybridization) analysis revealed a high amount (>60%) of abnormal cells in 41% of analyzed samples, especially in bone sarcomas (osteosarcoma and Ewing sarcoma). In conclusion, the explant technique is well suited to establish patient-derived cell lines for a large majority of bone and soft tissue sarcoma entities with adequate speed. This procedure thus opens the possibility for molecular analysis and drug testing for therapeutic decision making even during patient treatment.

Identification of Discrete Prognostic Groups in Ewing Sarcoma.

BACKGROUND: Although multiple prognostic variables have been proposed for Ewing sarcoma (EWS), little work has been done to further categorize these variables into prognostic groups for risk classification. PROCEDURE: We derived initial prognostic groups from 2,124 patients with EWS in the SEER database. We constructed a multivariable recursive partitioning model of overall survival using the following covariates: age; stage; race/ethnicity; sex; axial primary; pelvic primary; and bone or soft tissue primary. Based on this model, we identified risk groups and estimated 5-year overall survival for each group using Kaplan-Meier methods. We then applied these groups to 1,680 patients enrolled on COG clinical trials. RESULTS: A multivariable model identified five prognostic groups with significantly different overall survival: (i) localized, age <18 years, non-pelvic primary; (ii) localized, age <18, pelvic primary or localized, age ≥18, white, non-Hispanic; (iii) localized, age ≥18, all races/ethnicities other than white, non-Hispanic; (iv) metastatic, age <18; and (v) metastatic, age ≥18. These five groups were applied to the COG dataset and showed significantly different overall and event-free survival based upon this classification system (P < 0.0001). A sub-analysis of COG patients treated with ifosfamide and etoposide as a component of therapy evaluated these findings in patients receiving contemporary therapy. CONCLUSIONS: Recursive partitioning analysis yields discrete prognostic groups in EWS that provide valuable information for patients and clinicians in determining an individual patient's risk of death. These groups may enable future clinical trials to adjust EWS treatment according to individualized risk.

[Grading of soft tissue and bone sarcomas]. / Grading von Weichgewebe- und Knochensarkomen.

Malignancy grading is an essential element in the classification of sarcomas. It correlates with the prognosis of the disease and the risk of metastasis. This article presents the grading schemes for soft tissue, bone and pediatric sarcomas. It summarizes the histological criteria of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system and the Pediatric Oncology Group as well as the grading of bone tumors by the College of American Pathologists (CAP). Furthermore, the potential relevance of gene expression signatures, the complexity index in sarcoma (CINSARC) and single genetic alterations (p53, MDM2, p16, SWI/SNF, EWSR1 fusions and PAX3/PAX7-FOXO1 fusions) for the prognosis of sarcomas are discussed.

Prevalence of osteoma cutis in the maxillofacial region and classification of its radiographic pattern in cone beam CT.

BACKGROUND: Osteoma cutis is a rare soft tissue ossification of cutaneous tissue and may be primary or secondary. In the majorityof cases it is clinically asymptomatic and may detected incidentally on radiographic examination. Cone beam computed tomography (CBCT) has can be of great assistance in the detection of this asymptomatic lesion. OBJECTIVES: In this retrospective study, the prevalence and different radiographic appearance of osteoma cutis was evaluated. MATERIALS AND METHODS: A total of 6,500 CBCT images were evaluated for the presence of osteoma cutis. Ectopic existence of calcified tissue within the soft tissue of the dermis or epidermis that was incompatible with the calcification of other anatomic structures or soft tissue calcifications was considered to be osteoma cutis. Accordingly, the detected patterns were divided into four distinct groups: (1) a single nodule, (2) plate-like lesion, (3) single or multiple depth lesion(s), trans-epidermal, and (4) multiple, disseminated lesions of various sizes known as multiple miliary. The data were evaluated in terms of prevalence and variations. The frequency, total prevalence, percentage and the prevalence of different radiographic forms of this lesion were calculated. RESULTS: One hundred and forty eight (2.27%) cases of 6,500 evaluated tomograms had osteoma cutis. Of these, 5 (0.07%) were in the form of a single nodule, 4 (0.06%) were single, plate-like lesions, 7 (0.1%) were multiple plate-like lesions, 2 (0.03%) were in the form of a deep thread-like lesion, and 130 (2%) presented as multiple disseminated lesions. CONCLUSION: According to the radiographic views, osteoma cutis may be categorized into single nodular, single or multiple plate- like, deep, and multiple disseminated forms. Of the mentioned radiogarphic patterns, the multiple disseminated form (miliary) hada higher prevalence in our study. CBCT images enable accurate evaluation of the nature and frequency of osteoma cutis.

NELL-1 expression in benign and malignant bone tumors.

NELL-1 (NEL-like Protein 1) is an osteoinductive protein with increasing usage as a bone graft substitute in preclinical animal models. NELL-1 was first identified to have bone-forming properties by its overexpression in fusing cranial sutures. Since this time, addition of recombinant NELL-1 has been used to successfully induce bone formation in the calvarial, axial and appendicular skeleton. With increasing interest in the use of NELL-1 as a bone-graft substitute, we sought to examine the expression of NELL-1 in a wide spectrum of benign and malignant bone-forming skeletal tumors. Immunohistochemical expression was examined in human pathologic specimens. Quantitative RT-PCR evaluated NELL-1 expression among OS cell lines in vitro. Results showed NELL-1 expression in all bone tumors. Likewise, all OS cell lines demonstrated increased NELL-1 expression in comparison to non-lesional human bone marrow stromal cells. Among, benign bone tumors (osteoid osteoma and osteoblastoma), strong and diffuse staining was observed, which spatially correlated with markers of osteogenic differentiation. In contrast, a relative reduction in NELL-1 staining was observed in osteosarcoma, accompanied by increased variation between tumors. Among osteosarcoma specimens, NELL-1 expression did not correlate well with markers of osteogenic differentiation. Surprisingly, among osteosarcoma subtypes, fibroblastic osteosarcoma demonstrated the highest expression of NELL-1. In summary, NELL-1 demonstrates diffuse and reliable expression in benign but not malignant bone-forming skeletal tumors. Future studies will further define the basic biologic, diagnostic and prognostic importance of NELL-1 in bone neoplasms.

Surface primary bone tumors: Systematic approach and differential diagnosis.

Surface primary bone tumors may appear similar to their intramedullary counterpart, but because they are rare, they may pose diagnostic challenges when showing different characteristics compared to their intramedullary counterpart. It is important for radiologists to recognize the imaging findings for various uncommon surface primary bone tumors, which may help to reduce the differential diagnosis or to lead to a specific diagnosis. Radiography is typically used for first-line imaging. If necessary, it is followed by CT or MRI for evaluation and characterization of surface bone tumors. The aim of this article is to review the imaging findings and differential diagnosis for surface primary bone tumors.