Bone Neoplasms Research Articles

8295 Development of Type 1 Diabetes and Primary Adrenal Insufficiency Secondary to Immunotherapy Treatment for Chordoma in a Patient With Hypopituitarism

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: Cranio-cervical chordomas are rare locally aggressive, invasive, and slow-growing bone neoplasms. Treatment involves a combination of excision and radiation therapy, and sometimes immunotherapy for recurrent disease. Endocrine-related toxicities from immune checkpoint inhibitors are well recognized and include autoimmune thyroid disease, hypophysitis, and less commonly, type 1 diabetes mellitus (T1DM) and primary adrenal insufficiency (PAI). We present a case of a patient with hypopituitarism secondary to a recurrent and aggressive skull base chordoma with leptomeningeal spread who developed T1DM and PAI after treatment with nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody. Diagnosis of PAI was delayed because patient was on hydrocortisone replacement for secondary adrenal insufficiency. Case Report: A 38 year old male with history of primary hypothyroidism underwent endoscopic endonasal transsphenoidal resection and adjuvant proton beam radiation therapy for a sellar chordoma after presenting with diplopia. Testing was consistent with hypopituitarism and the patient was started on hydrocortisone, levothyroxine, and testosterone replacement. Due to recurrent disease and leptomeningeal spread, he subsequently underwent three additional surgeries and two courses of gamma knife radiosurgery. Five months after starting systemic therapy with nivolumab, the patient developed insulin dependent diabetes presumed to be T1DM secondary to immunotherapy. He was continued on nivolumab, and six months into treatment developed hyperkalemia and hyponatremia requiring inpatient admission. He was treated with diuretics and fluid restriction initially without improvement in his electrolyte abnormalities although he remained relatively asymptomatic. Laboratory evaluation showed a renin activity of 66 ng/mL/H and aldosterone < 4.0 ng/dL (<= 21) with sodium of 128 mmol/L (135-145) and potassium 5.8 mml/L (3.3-4.9). Due to suspicion for PAI secondary to checkpoint-inhibitor induced adrenalitis, 21-hydroxylase antibody was checked and was positive. It was felt that the patient had not had other signs or symptoms classic for PAI such as nausea and/or vomiting because he had already been on glucocorticoid replacement for his hypopituitarism. Ultimately, the patient was started on fludrocortisone, with resolution of his hyponatremia and hyperkalemia. Conclusion: Adrenal insufficiency from immunotherapy is most commonly caused by hypophysitis. T1DM and PAI due to adrenalitis are less common. In patients on steroid replacement for hypopituitarism, the development of electrolyte abnormalities with or without symptoms in a patient on immunotherapy should raise the suspicion for rarer endocrine side effects such as primary adrenal insufficiency. Presentation: 6/3/2024

Trends in malignant neoplasm of bone and articular cartilage related mortality among older adults in United States (1999 to 2020)

Introduction: Malignant neoplasms of bone and articular cartilage, although rare, are associated with substantial morbidity and mortality, posing a serious health burden. Understanding the trends in mortality related to these cancers is crucial for developing targeted interventions and improving patient outcomes. This study aims to analyze long-term mortality trends, identify demographic and geographic disparities, and uncover potential factors driving changes in mortality rates. Methods: This retrospective study analyzed mortality rates among individuals aged 65 and older from 1999 to 2020 using CDC WONDER death certificate data, abstracting demographics, geographic factors, and urban/rural status. Results: From 1999 to 2020, 18,205 adults aged 65 and older died from malignant neoplasms of bone and cartilage. The age-adjusted mortality rate (AAMR) started at 20 per 100,000 in 1999 and steadily declined until 2012 (APC: -1.12). However, from 2012 onwards, there was a notable reversal, with the AAMR rising sharply to 23.8 by 2020 (APC: 4.73). Men had higher mortality rates than women, with NH Black individuals showing the highest rates among races. Southern states and non-metropolitan areas had elevated AAMRs, suggesting targeted interventions for better outcomes and lower death rates. Conclusion: The findings highlight significant inequities, with Southern states and non-metropolitan areas showing elevated age-adjusted mortality rates (AAMRs). These geographic disparities underscore the urgent need for targeted public health interventions in these regions to improve cancer outcomes and reduce mortality. Addressing these gaps is essential for achieving more equitable health outcomes, particularly in high-risk populations.

Xanthogranulomatous osteomyelitis of pubic bone mimicking neoplasm: a case report and literature review

BackgroundXanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported.Case presentationWe present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed.ConclusionsAlthough rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases.

Sarcopenia Is Associated with Neoplasm of Bone and Articular Cartilage: Findings from Mendelian Randomized Study.

Exploring the causal relationship between sarcopenia and neoplasm of bone and articular cartilage (NBAC) by bidirectional Mendelian randomization (MR). Genome-wide association study (GWAS) data on sarcopenia-associated traits including appendicular lean mass, low handgrip strength (including criteria from the European Working Group on Sarcopenia in Older People and the Foundation for the National Institutes of Health), and usual walking speeds were obtained from the UK Biobank. GWAS data for NBAC (benign and malignant) were provided by the Finnish Genetic Database. Three different methods of MR analysis, including inverse-variance weighted, Mendelian randomized Egger regression, and weighted median methods, were utilized. MR analysis showed that high appendicular lean mass was positively associated with the risk of developing benign NBAC (odds ratio and 95% confidence interval = 1.236 (1.026,1.489), p = 0.025). At the same time, there is no statistically significant association was found between traits related to sarcopenia and malignant neoplasm of bone and articular cartilage. There was also no reverse causal correlation between NBAC and traits related to sarcopenia. In European populations, better appendicular lean body mass is positively associated with the risk of benign neoplasm of bone and articular cartilage, representing the possibility that sarcopenia may be a protective factor against neoplasm of bone and articular cartilage.

Therapeutic and diagnostic approach to craniofacial osteoma in a dog: a case report

Osteoma is a bone neoplasm that can affect dogs of any age, often underdiagnosed due to its low incidence and slow growth. The aim of this study was to discuss a case of craniofacial osteoma in a Shih-Tzu bitch, highlighting the importance of proper diagnosis and treatment of this condition. In this case, the patient presented with a rigid mass near the left eye, which was evaluated radiographically and diagnosed histopathologically after complete excision of the tumor. No signs of recurrence were observed during follow-up, demonstrating the effectiveness of the surgical treatment. The main findings of the case include an osteoproliferative reaction observed in the radiograph and well-differentiated fibrogranulomatous and osseous proliferation observed in the histopathology. The treatment consisted of complete surgical resection, and no postoperative complications were observed. The patient showed rapid recovery and absence of postoperative pain. It is concluded that osteoma is a benign neoplasm treatable with complete surgical resection, without the need for adjuvant chemotherapy. The study emphasizes the importance of considering osteoma as a differential diagnosis among bone neoplasms in dogs.

Nuclear Imaging in Orthopaedic Practice: A Critical Analysis Review.

» Nuclear imaging techniques, including bone scintigraphy, labeled leukocyte scintigraphy, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) combined with computed tomography (CT), have wide applications in orthopaedics for evaluating trauma, painful total joint arthroplasty, musculoskeletal infection, and orthopaedic oncology.» Three-phase bone scintigraphy is a first-line, highly sensitive nuclear medicine study for evaluating orthopaedic pathology when initial studies are inconclusive. However, its specificity is limited, and findings may be falsely positive for up to 2 years after total joint arthroplasty because of physiologic bone remodeling.» Labeled leukocyte scintigraphy or gallium scintigraphy can improve diagnostic accuracy in patients with a positive bone scan and suspected musculoskeletal or periprosthetic joint infection.» 18-Fluorodeoxyglucose PET/CT demonstrates high sensitivity and specificity for diagnosing bone neoplasms, infections, and metabolic disorders. Emerging PET/magnetic resonance imaging technology offers reduced radiation exposure and greater soft-tissue detail but presents technical and cost challenges.» SPECT/CT provides valuable functional and anatomic detail for characterizing the extent and location of bone pathology, serving as an important adjunct to other imaging modalities.» Ultimately, the choice of nuclear imaging modality should consider the specific clinical context, diagnostic accuracy, impact on management, and cost-effectiveness on a case-by-case basis.

Robust IMPT and follow-up toxicity in skull base chordoma and chondrosarcoma-asingle-institution clinical experience.

Chordomas and chondrosarcomas of the skull base are rare, slowly growing malignant bone neoplasms. Despite their radioresistant properties, proton therapy has been successfully used as an adjunct to resection or as adefinitive treatment. Herewith, we present our experience with robustly optimized intensity-modulated proton therapy (IMPT) and related toxicities in skull base chordoma and chondrosarcoma patients treated at HollandPTC, Delft, the Netherlands. Clinical data, treatment plans, and acute toxicities of patients treated between July 2019 and August 2021 were reviewed. CT and 3.0T MRI scans for treatment planning were performed in supine position in athermoplastic mold. In total, 21dose optimization and 28dose evaluation scenarios were simulated. Acute toxicity was scored weekly before and during the treatment according to the CTCAE v4.0. Median follow-up was 35months (range 12-36months). Overall, 9chordoma and 3chondrosarcoma patients with 1-3 resections prior to IMPT were included; 4patients had titanium implants. Brainstem core and surface and spinal cord core and surface were used for nominal plan robust optimization in 11, 10, 8, and 7patients, respectively. Middle ear inflammation, dry mouth, radiation dermatitis, taste disorder, and/or alopecia of grades 1-3 were noted at the end of treatment among 6patients without similar complaints at inclusion; symptoms disappeared 3months following the treatment. Robustly optimized IMPT is clinically feasible as apostoperative treatment for skull base chordoma and chondrosarcoma patients. We observed acceptable early toxicities (grade1-3) that disappeared within the first 3months after irradiation.

Photothermal Catalytic Reduction and Bone Tissue Engineering Towards a Three-in-One Therapy Strategy for Osteosarcoma.

Osteosarcoma is one of the most dreadful bone neoplasms in young people, necessitating the development of innovative therapies that can effectively eliminate tumors while minimizing damage to limb function. An ideal therapeutic strategy should possess three essential capabilities: antitumor effects, tissue-protective properties, and the ability to enhance osteogenesis. In this study, self-assembled Ce-substituted molybdenum blue (CMB) nanowheel crystals are synthesized and loaded onto 3D-printed bioactive glass (CMB@BG) scaffolds to develop a unique three-in-one treatment approach for osteosarcoma. The CMB@BG scaffolds exhibit outstanding photothermally derived tumor ablation within the near-infrared-II window due to the surface plasmon resonance properties of the CMB nanowheel crystals. Furthermore, the photothermally synergistic catalytic effect of CMB promotes the rapid scavenging of reactive oxygen species caused by excessive heat, thereby suppressing inflammation and protecting surrounding tissues. The CMB@BG scaffolds possess pro-proliferation and pro-differentiation capabilities that efficiently accelerate bone regeneration within bone defects. Altogether, the CMB@BG scaffolds that combine highly efficient tumor ablation, tissue protection based on anti-inflammatory mechanisms, and enhanced osteogenic ability are likely to be a point-to-point solution for the comprehensive therapeutic needs of osteosarcoma.

Therapeutic impacts of GNE‑477‑loaded H2O2 stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma.

Osteosarcoma (OS) is a highly malignant primary bone neoplasm that is the leading cause of cancer‑associated death in young people. GNE‑477 belongs to the second generation of mTOR inhibitors and possesses promising potential in the treatment of OS but dose tolerance and drug toxicity limit its development and utilization. The present study aimed to prepare a novel H2O2 stimulus‑responsive dodecanoic acid (DA)‑phenylborate ester‑dextran (DA‑B‑DEX) polymeric micelle delivery system for GNE‑477 and evaluate its efficacy. The polymer micelles were characterized by morphology, size and critical micelle concentration. The GNE‑477 loaded DA‑B‑DEX (GNE‑477@DBD) tumor‑targeting drug delivery system was established and the release of GNE‑477 was measured. The cellular uptake of GNE‑477@DBD by three OS cell lines (MG‑63, U2OS and 143B cells) was analyzed utilizing a fluorescent tracer technique. The hydroxylated DA‑B was successfully grafted onto dextran at a grafting rate of 3%, suitable for forming amphiphilic micelles. Following exposure to H2O2, the DA‑B‑DEX micelles ruptured and released the drug rapidly, leading to increased uptake of GNE‑477@DBD by cells with sustained release of GNE‑477. The in vitro experiments, including MTT assay, flow cytometry, western blotting and RT‑qPCR, demonstrated that GNE‑477@DBD inhibited tumor cell viability, arrested cell cycle in G1 phase, induced apoptosis and blocked the PI3K/Akt/mTOR cascade response. In vivo, through the observation of mice tumor growth and the results of H&E staining, the GNE‑477@DBD group exhibited more positive therapeutic outcomes than the free drug group with almost no adverse effects on other organs. In conclusion, H2O2‑responsive DA‑B‑DEX presents a promising delivery system for hydrophobic anti‑tumor drugs for OS therapy.

Reappraisal of bone and soft tissue cytopathology classification using the modified Milan system.

A standardized reporting system for bone and soft tissue tumor cytopathology has not yet been established. The objective of this study was to explore the potential utility of a classification modified from the Milan System for Salivary Gland Cytopathology and compared it with the upcoming World Health Organization (WHO) system for fine-needle aspiration of soft tissue lesions. The authors reviewed 285 cytology cases of bone/joint (n=173) and soft tissue (n=112) lesions, scoring each within diagnostic categories. The results were compared with histologic diagnoses and the risk of malignancy (ROM) for each category, and diagnostic reliability was analyzed. All 285 cases were successfully classified into one of the following categories: nondiagnostic (6.3%), non-neoplastic (11.9%), atypia of uncertain significance (11.9%), benign neoplasm (5.6%), bone and soft tissue neoplasm of uncertain malignant potential (25.3%), suspicious for malignancy (1.4%), and malignant (37.5%). The ROM was 44.4% (eight of /18 cases) in nondiagnostic, 0% (zero of 34 cases) in non-neoplastic, 32.4% (11 of 34 cases) in atypia of uncertain significance, 0% (zero of 16 cases) in benign neoplasm, 16.7% (12 of 72 cases) in bone and soft tissue neoplasm of uncertain malignant potential, 75.0% (three of four cases) in suspicious for malignancy, and 100% (107 of 107 cases) in malignant categories. Using the WHO system, the proportion and ROM of the benign category (non-neoplastic and benign neoplasm) was 17.5% and 0%, respectively. Among benign and malignant lesions, the diagnostic accuracy, sensitivity, and specificity for detecting malignancy were 99.4%, 100%, and 98.0%, respectively. The modified Milan system as well as the WHO system may be a useful cytopathologic classification tool for both bone and soft tissue lesions.

Global, regional, and national burden and trends analysis of malignant neoplasm of bone and articular cartilage from 1990 to 2021: A systematic analysis for the Global Burden of Disease Study 2021

BackgroundMalignant neoplasm of bone and articular cartilage (MNBAC) is one of the causes of cancer-related deaths worldwide. To date, there is a lack of detailed studies on the disease burden of MNBAC. MethodsData on the incidence, mortality, and disability-adjusted life years (DALYs) of MNBAC from 1990 to 2021 were obtained from the Global Burden of Disease study. We estimated the trends in the burden of MNBAC by calculating the estimated annual percentage change (EAPC) in age-standardized rates by region, country, and social development index. ResultsGlobally, the cases of incidence and deaths of MNBAC showed a significant upward trend. In 2021, the global incidence cases of MNBAC were 91,375.1 (73,780.4–102,469.7), and the number of deaths was 66,114.3 (53,305.4–74,466.9). The age-standardized incidence, mortality, and DALYs rates were all on the rise, with EAPCs of 0.59 (0.51 to 0.68), 0.11 (0.02 to 0.21), and 0.08 (0 to 0.17), respectively. In 2021, China had the highest number of incidence cases and deaths. Two peaks in incidence cases and deaths were observed in the 15–19 and 65–69 age groups, with incidence rates and death rates generally increasing with age, and higher in males than females. The region with the highest incidence cases, deaths, and age-standardized incidence rate was East Asia, while Eastern Sub-Saharan Africa had the highest age-standardized mortality, and DALYs rates. ConclusionFrom 1990 to 2021, the global burden of MNBAC has continued to increase, particularly in East Asia, which faces the highest number of incidence cases and deaths, while Eastern Sub-Saharan Africa faces the highest ASMR and ASDR. To mitigate this burden, different regions should develop cancer control actions based on their respective epidemiological characteristics, with a focus on the elderly and adolescents, and control of risk factors.

EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms.

With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.

Combining morphological and functional imaging parameters to diagnose primary bone neoplasms in the skull base, spine and sacrum.

Morphological magnetic resonance (MR) and computed tomography (CT) features are used in combination with histology for diagnosis and treatment selection of primary bone neoplasms. Isolated functional MRI parameters have shown potential in diagnosis. Our goal is to facilitate diagnosis of primary bone neoplasms of the skull base, mobile spine and sacrum, by a comprehensive approach, combining morphological and functional imaging parameters. Pre-treatment MR of 80 patients with histologically proven diagnosis of a primary bone neoplasm of the skull base, mobile spine and sacrum were retrospectively analyzed for morphological and functional MRI parameters. Functional parameters were measured in 4 circular regions of interest per tumor placed on non-adjacent scan slices. Differences in values of functional parameters between different histologies were analyzed with Dunn's test. Chordomas were the predominant histology (60.0%). Most neoplasms (80.0%) originated in the midline and had geographical (78.2%) bone destruction. Amorphous-type calcification (pre-existing bone) was seen only in chordomas. Homogeneous contrast enhancement pattern was seen only in chondrosarcoma and plasmacytoma. Ktrans and Kep were significantly lower in both chordoma, and chondrosarcoma compared to giant cell tumor of the bone (p = 0.006 - 0.011), and plasmacytoma (p = 0.004 - 0.014). Highest diffusion-weighted MRI apparent diffusion coefficient (ADC) values corresponded to chondrosarcoma and were significantly higher to those of chordoma (p = 0.008). We identified the most discriminating morphological parameters and added functional MR parameters based on histopathological features that are useful in making a confident diagnosis of primary bone neoplasms in the skull base, mobile spine and sacrum.

Intra-articular Osteoid Osteomas: Imaging Manifestations and Mimics.

Osteoid osteoma (OO) is the third most prevalent benign bone neoplasm in children. Although it predominantly affects the diaphysis of long bones, OO can assume an intra-articular location in the epiphysis or the intracapsular portions of bones. The most common location of intra-articular OO is the hip joint. The presentation of intra-articular OOs often poses a diagnostic enigma, both from clinical and radiologic perspectives. Initial symptoms are often vague and nonspecific, characterized by joint pain, stiffness, and limited range of motion, which frequently contributes to a delayed diagnosis. Radiographic findings range from normal to a subtle sclerotic focus, which may or may not have a lucent nidus. In contrast to their extra-articular counterparts, intra-articular lesions have distinct features at MRI, including synovitis, joint effusion, and bone marrow edema-like signal intensity. While CT remains the standard for identifying the nidus, even CT may be inadequate in visualizing it in some cases, necessitating the use of bone scintigraphy or fluorine 18-labeled sodium fluoride PET/CT for definitive diagnosis. Radiologists frequently play a pivotal role in suggesting this diagnosis. However, familiarity with the unique imaging attributes of intra-articular OO is key to this endeavor. Awareness of these distinctive imaging findings of intra-articular OO is crucial for avoiding diagnostic delay, ensuring timely intervention, and preventing unnecessary procedures or surgeries resulting from a misdiagnosis. The authors highlight and illustrate the different manifestations of intra-articular OO as compared with the more common extra-articular lesions with respect to clinical presentation and imaging findings. ©RSNA, 2024 Supplemental material is available for this article.

Percutaneous radiofrequency ablation of osteoid osteoma: results from 9 years of experience in a third-level center.

Osteoid osteoma is a benign bone tumor that accounts for roughly 2-3% of primary bone tumors and up to 10-12% of benigns bone neoplasms. It is most commonly seen in young adults, and shows male predominance. Over the last years, minimally invasive thermal ablation techniques such as radiofrequency ablation have gained popularity over classical surgery. In this study we evaluate results and complications of CT guided osteoid osteoma radiofrequency ablation. In this retrospective cohort study all patients that were diagnosed with osteoid osteoma and treated using radiofrequency ablation between January 2014 and December 2022 were included. Pain was assessed using Visual Analog Scale (VAS) pre and post procedure. Technical success was established as positioning of the radiofrequency electrode in the nidus. Primary clinical success was defined as absence of pain after one radiofrequency session. All patients that required a second radiofrequency ablation were included in the overall clinical success group. During the studied period, 61 osteoid osteoma radiofrequency ablations were performed. Fiftyseven of them were included in this study, 32 were men and 25 female. Pre procedure median pain was 9 according to VAS score. Only 23 patients were treated as outpatient, the rest stayed in hospital for 24 hours. Median follow up time was 21,7 months (SD 8,3). Biopsy was performed in 52 patients. Technical success was accomplished in 57 patients (100%). Primary clinical success was 80,7% (46 patients). Those who continued with pain or had recurrence after a symptoms free period (11 patients), were treated with a second radiofrequency ablation, achieving an overall success rate of 94,7%. Only one patient suffered a minor complication (1,7%). CT guided osteoid osteoma radiofrequency ablation is a safe, effective and low complication rate procedure, that can be performed on an outpatient basis. We believe it should be considered as a first line treatment option for osteoid osteoma.

Diagnostic Efficacy of Trephine Biopsy and Core Biopsy of Bone and Soft Tissue Tumors

Verification of pathomorphological diagnosis is a key stage in selection of treatment tactics in patients with neoplasms. Understanding of the nature of pathological process is especially important in context of primary tumors of the bones, soft tissues and metastases as despite active development of diagnostic techniques, they do not allow to obtain full information on histological nature of the tissues, differentiation grade, as well as molecular and genetic characteristics of the tumor. These data are associated with selection of optimal treatment tactics at every stage and disease prognosis. The optimal approach to obtaining histological materials in tumor of the bones and soft tissues are radiologically guided (X-ray, computed tomography and magnetic resonance imaging) trephine biopsy or ultra-sound-guided core biopsy.Aim. To determine information value of trephine and core biopsies of neoplasms of the bones and soft tissues of various locations, identify mistakes during manipulation affecting results of morphological diagnosis.Materials and methods. Between 2015 and 2023 at the Russian Scientific Center of Roentgenoradiology, 788 patients aged 18–85 years (380 men, 408 women) underwent 602 trephine biopsies and 248 core biopsies (n = 850) of neo-plasms of the soft tissues and bones of various locations. Absence of informational value of morphological study required repeat trephine biopsies in 19 patients, core biopsies in 2 patients, open biopsies in 13 patients.Results. Informational value of trephine biopsy of the bones was 90.5 % (long bones – 96.8 %, flat bones – 91.6 %, spine bones – 82.1 %), core biopsy of the soft tissues 98.8 %. Sufficient amount of material for immunohistochemical testing was obtained in 89 % biopsies. Interventions in cases of bone neoplasms were performed using CT (computed tomography) navigation; for core biopsies of the soft tissues, ultrasound was used. Absence of informational value in trephine bio psies was caused by insufficient amount of material (48 (7.97 %) cases), retrieval of trephine biopsy from the area of tumor necrosis (4 (0.67 %) cases), incorrect selection of access (4 (0.67 %) cases) and needle type (1 (0.17 %) case).Conclusion. Results of analysis of trephine and core biopsy data of bone and soft tissue neoplasms showed high information value, which is supported by literature data. This allows to consider these methods of histological material retrieval the “golden standard” of bone and soft tissue tumor diagnosis.

Molecular mechanism of RBM14-mediated promotion of proliferation, migration, and invasion in osteosarcoma.

Osteosarcoma (OS) is an exceptionally aggressive bone neoplasm that predominantly impacts the paediatric and adolescent population, exhibiting unfavourable prognosis. The importance of RNA binding motif protein 14 (RBM14) in the aetiology of OS is not well understood, despite its established involvement in several other types of cancer. In this study, we conducted an analysis of the expression profiles of RBM14 in cancer tissues and cell lines. To achieve this, we will utilised data obtained from various databases including The Cancer Genome Atlas Program (TCGA) project, The Genotype-Tissue Expression (GTEx) Project, Gene Expression Omnibus (GEO) database, and cancer cell line encyclopedia (CCLE) data. Furthermore, this study also aims to examine the effects of RBM14 on the proliferation, migration, and invasive properties of OS cells using cell functional gain and loss studies. In this study, we carried out an in-depth investigation to explore possible molecular pathways that underlie the regulation of the malignant phenotype found in OS by RBM14. This investigation involved integrating data from RBM14 overexpression, RBM14 knockdown RNA-seq experiments, and an array comprising 6,096 perturbed genes obtained from the Genetic Perturbation Similarity Analysis Database (GPSAdb). This research offers an opportunity to build a robust conceptual framework for the potential advancement of novel therapeutic approaches that are especially aimed at attacking OS. RBM14 plays an active role in OS by significantly contributing to the enhancement of cellular proliferation, migration, and invasion. At the molecular level, it is probable that RBM14 exerts control over the malignant characteristics of OS through its modulation of the Hippo signalling system. The above-mentioned findings underscore the significant importance of RBM14 as an intriguing target for therapy for the mitigation and management of OS. This particular protein holds an excellent opportunity for the development of novel and efficacious therapeutic approaches that possess the potential to yield favorable results for patients affected with OS.

Myoepithelial tumors of soft tissue and bone in children and young adults: A clinicopathologic study of 40 cases occurring in patients ≤ 21 Years of age

Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely understood. We studied a well-characterized series of 40 such tumors. Cases were retrieved from our archives for the period 2009–2022 and re-reviewed. Available immunohistochemical and molecular genetic data was collected. Clinical information including available follow-up was obtained. The tumors occurred in 18 males and 22 females, ranging from 3 months to 21 years of age (median 11.5 years), and involved a wide variety of soft tissue (n = 36) and bone (n = 4) locations. Histologically benign myoepithelial tumors tended to occur in adolescents (median age 14.5 years; range 5–21 years), whereas myoepithelial carcinomas occurred in younger patients (median age 8.5 years; range 3 months–20 years). Microscopically, the tumors showed a complex admixture of epithelioid, plasmacytoid and spindled cells in a variably hyalinized, myxoid, chondroid or chondromyxoid background. Small subsets of histologically malignant tumors had rhabdoid or “round cell” features. Immunohistochemistry showed 35/40 (88%) cases to be positive with at least one keratin antibody. The 5 keratin-negative tumors were uniformly positive for S100 protein and/or SOX10 and expressed EMA (4 cases) and/or p63 (3 cases). EMA, SMA and GFAP were positive in 21/25 (84%), 13/21 (62%), and 8/21 (38%) tumors, respectively. SMARCB1 and SMARCA4 expression was retained in 29/31 (94%) and 22/22 (100%) of cases, respectively. FISH for EWSR1 gene rearrangement was positive in 6/18 (33%) tested cases. Two EWSR1-negative tumors were also FUS-negative. NGS identified EWSR1::POU5F1, FUS::KLF17, and BRD4::CITED1 gene fusions in 3 tested cases. Clinical follow-up (22 patients; median 23 months; range 1–119 months) showed 3 patients with local recurrences and 5 with distant metastases (lymph nodes, lung, and brain). Three patients died of disease, 3 were alive with recurrent or unresectable disease, and 16 were disease-free. Adverse clinical outcomes were seen only in patients with malignant tumors. We conclude that myoepithelial neoplasms of soft tissue and bone are over-repesented in patients ≤21 years of age, more often histologically malignant, and potentially lethal. Histologic evaluation appears to reliably predict the behavior of these rare tumors.

Novel CRTC1::MRTFB(MKL2) Gene Fusion Detected in Myxoid Mesenchymal Neoplasms With Myogenic Differentiation Involving Bone and Soft Tissues

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present 3 cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 1 male and 2 female patients with a median age of 72 years (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). Although 1 tumor presented as an incidental finding, the other 2 tumors were noted, given their persistent growth. At the time of the last follow-up, 1 patient was alive with unresected disease at 6 months, 1 patient was alive without evidence of disease at 12 months after surgery, and 1 patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.

Metastatic intradural primary spinal osteosarcoma: illustrative case.

Osteosarcomas are a common primary bone neoplasm among adolescents but represent 0.2% of all malignancies with an incidence of two to four cases per million persons annually worldwide. Although known to have significant metastatic potential, its rare incidence, treatment resistance, and poor prognosis have rendered it a poorly understood and infrequently documented pathology. Herein the authors present the first documented case of lumbosacral intradural metastasis of a primary osteosarcoma in a young patient, possibly via intradural dissemination following pinhole durotomy in a prior thoracic surgery. Osteosarcomas remain a difficult pathology to treat, particularly upon metastatic dissemination. The utility of adjuvant radiotherapy after resection of an osteosarcoma is increasingly evident in the reduction of local recurrence. In the context of intraoperative pinhole durotomies in resections of high-grade lesions, due consideration should be given to whole-spine radiation, although this remains an evidence-free zone.