Focal Bone Research Articles

Unspecific 18F-PSMA-1007 Bone Uptake Evaluated Through PSMA-11 PET, Bone Scanning, and MRI Triple Validation in Patients with Biochemical Recurrence of Prostate Cancer.

18F-PSMA-1007 PET is used in the management of patients with prostate cancer. However, recent reports indicate a high rate of unspecific bone uptake (UBU) with 18F-PSMA-1007, which may lead to a false-positive diagnosis. UBU has not been evaluated thoroughly. Here, we evaluate the frequency of UBU and bone metastases separately for 18F-PSMA-1007 and 68Ga-PSMA-11 in biochemical recurrence (interindividual comparison). Additionally, we investigate UBU seen in 18F-PSMA-1007 through follow-up examinations (intraindividual comparison) using 68Ga-PSMA-11 PET, bone scintigraphy, and MRI. Methods: First, all patients (n = 383) who underwent 68Ga-PSMA-11 PET between January 2020 and December 2020 and all patients (n = 409) who underwent 18F-PSMA-1007 PET between January 2020 and November 2021 due to biochemical recurrence were included for an interindividual comparison of bone metastases and UBU rate. In a second approach, we regarded all patients with UBU in 18F-PSMA-1007, characterized by focal bone uptake with an SUVmax > 4 and prostate-specific antigen (PSA) ≤ 5 ng/mL, who underwent additional 68Ga-PSMA-11 PET (n = 17) (interindividual comparison). Of these, 12 patients also had bone scintigraphy and whole-body MRI within a 1- to 5-wk interval. Bone uptake seen on 18F-PSMA-1007 but not on any of the other 4 modalities (CT, MRI [n = 1], bone scanning, and 68Ga-PSMA-11 PET) was recorded as false-positive. Results: Patients scanned with 18F-PSMA-1007 PET had a significantly higher rate of UBU than those scanned with 68Ga-PSMA-11 (140 vs. 64; P < 0.001); however, the rate of bone metastases was not significantly different (72 vs. 64; P = 0.7). In the intraindividual comparison group, workup by CT, MRI, bone scanning, and 68Ga-PSMA-11 PET resulted in a positive predictive value for 18F-PSMA-1007 focal bone uptake (mean SUVmax, 6.1 ± 2.9) per patient and per lesion of 8.3% and 3.6%, respectively. Conclusion: In patients with PSA ≤ 5 ng/mL and SUV > 4 at biochemical recurrence, most 18F-PSMA-1007 focal bone uptake is likely to be false-positive and therefore due to UBU. In the case of low clinical likelihood of metastatic disease, 18F-PSMA-1007 bone uptake without morphologic surrogate should be assessed carefully with regard to localization and clinical context. However, the rate of bone metastases was not higher with 18F-PSMA-1007 in the clinical routine, indicating that experienced reporting physicians adjust for UBU findings.

Detection of bone marrow metastases in children and young adults with solid cancers with diffusion-weighted MRI.

To compare the diagnostic accuracy of diffusion-weighted (DW)-MRI with b-values of 50s/mm2 and 800s/mm2 for the detection of bone marrow metastases in children and young adults with solid malignancies. In an institutional review board-approved prospective study, we performed 51 whole-body DW-MRI scans in 19 children and young adults (14 males, 5 females; age range: 1-25years) with metastasized cancers before (n = 19 scans) and after (n = 32 scans) chemotherapy. Two readers determined the presence of focal bone marrow lesions in 10 anatomical areas. A third reader measured ADC and SNR of focal lesions and normal marrow. Simultaneously acquired 18F-FDG-PET scans served as the standard of reference. Data of b = 50s/mm2 and 800s/mm2 images were compared with the Wilcoxon signed-rank test. Inter-reader agreement was evaluated with weighted kappa statistics. The SNR of bone marrow metastases was significantly higher compared to normal bone marrow on b = 50s/mm2 (mean ± SD: 978.436 ± 1239.436 vs. 108.881 ± 109.813, p < 0.001) and b = 800s/mm2 DW-MRI (499.638 ± 612.721 vs. 86.280 ± 89.120; p < 0.001). On 30 out of 32 post-treatment DW-MRI scans, reconverted marrow demonstrated low signal with low ADC values (0.385 × 10-3 ± 0.168 × 10-3mm2/s). The same number of metastases (556/588; 94.6%; p > 0.99) was detected on b = 50s/mm2 and 800s/mm2 images. However, both normal marrow and metastases exhibited low signals on ADC maps, limiting the ability to delineate metastases. The inter-reader agreement was substantial, with a weighted kappa of 0.783 and 0.778, respectively. Bone marrow metastases in children and young adults can be equally well detected on b = 50s/mm2 and 800s/mm2 images, but ADC values can be misleading.

Pseudoprogression and Sarcoidosis-like Phenomena after CART-Cells and Bispecific Antibodies in Multiple Myeloma

Introduction: CAR T-cell therapy is establishing itself as a new standard of care in relapsed and refractory multiple myeloma (RRMM). Yet, there are a number of open issues including the lack of data on optimal follow-up assessments post CAR T therapy. Appreciating the high incidence of extramedullary lesions and patchy disease patterns seen in the RRMM setting, whole body 18F-Fluorodeoxyglucose (FDG) PET/CT imaging is increasingly used. Whether FDG is the best tracer in this setting has yet to be determined, as the technique is being based not only on the quantification of increased glucose uptake by tumor cells but also by others such as inflammatory cells. A phenomenon linked to this issue is pseudoprogression, which refers to an increase in the target lesion size due to influx of immune cells that may be misinterpreted as disease relapse. Pseudoprogression is a well-known event after checkpoint blockade therapy, seen in up to 10% of patients with solid cancers. Whether myeloma patients treated with CAR T or bispecific antibodies are at risk for pseudoprogression is, to the best of our knowledge, unknown. Methods: We present a case study of a RRMM patient who experienced pseudoprogression twice during his course of disease treatment that included BCMA CAR T cells Idecabtagene vicleucel and GPRC5DxCD3 bispecific antibody talquetamab. We performed a comprehensive molecular analysis including single cell RNAseq from bronchoalveolar lavage as well as PET imaging using the three PET tracers 18F-FDG, 68Ga-DOTATOC, and 68Ga-Pentixafor (binds to CXCR4) to unravel the biology underlying pseudoprogression in this case. Results: A 61-year-old Caucasian male was diagnosed with biopsy-proven pulmonary MM and treated with BCMA targeting CAR T cells in his 4th line of therapy. Ten days after CAR T infusion, the patient started violent coughing and a FDG-PET revealed full resolution of focal bone lesions but disseminated FDG uptake at the lung and mediastinal lymph nodes reminiscent to sarcoidosis. We performed a PET using 68Ga-DOTATOC that usually detects sarcoidosis with high sensitivity and specificity, which was negative. Negative results were also seen for 68Ga-Pentixafor, which is an alternative tracer to FDG in the detection of MM. Bronchoalveolar lavage (BAL) along with endobronchial ultrasound guided biopsy was done, showing noncaseating granuloma formation in the biopsy without evidence of residual MM cells. Single cell RNA-seq on the BAL sample revealed CD4-positive T cells exhibiting simultaneous expression of genes associated with Th1 T-cells (TBX21, CXCR3, IFNG, TNF) and genes associated with Th17 T-cells (RORC, IL23R, CCR6, CCL20, KLRB1), indicative for a Th1-polarized Th17 phenotype. Furthermore, these cells expressed IL4I1, ABCB1, and CSF210-12 , while IL17A, IL17B, IL17E (IL25), and or IL17F was not expressed, highlighting presence of Th17.1 cells. This cell type has been described to be pro-inflammatory and pathogenic and implicated in several auto-immune diseases, including sarcoidosis. Together, our data suggest a non-infectious, Th17.1 T-cell driven sarcoidosis-like auto-immune phenomenon located in the lungs following anti-BCMA CAR T-cell therapy. Respiratory symptoms completely resolved following high-dose inhalative steroids. The patient relapsed from complete remission (CR), and FDG PET showed the known sarcoidosis-like pulmonary changes, but also revealed a number of new soft-tissue lesions, suspicious for extramedullary relapse. In contrast to the previous scans, these lesions were CXCR4 positive, suggesting a role of using multiple PET tracers in this setting. Later, the patient was enrolled on a trial investigating talquetamab. One week after dosing, the patient experienced severe pain crisis and a diffusion-weighted MRI revealed increase in size of multiple extramedullary lesions, but no new lesions. M- protein levels were decreasing at that time suggesting either mixed response or pseudoprogression. The patient was treated with painkillers and all lesions disappeared on a follow-up scan 6 weeks later, confirming pseudoprogression, and he is in an ongoing CR for 6 months at the time of writing. Conclusion: We present two educating episodes of pseudoprogression in one patient following immune oncology drugs in MM. While one event was transient and self-limiting, the pulmonary manifestations were similar to sarcoidosis and required treatment with steroids.

Growth differentiation factor-15 as a modulator of bone and muscle metabolism.

This study aims to clarify the potential role of growth differentiation factor-15 (GDF-15) as a myokine in bone metabolism and muscle function in females with osteoporosis. In total, 45 female participants (71.0 ± 8.5 years) with distal radius fractures were recruited. Participants were classified as healthy/osteopenic (n=28) (CON) or osteoporotic (n=17) (OP) according to their T-score from the areal bone mineral density (aBMD) of the femoral neck. Body mass index, upper arm and calf circumferences, and handgrip strength were assessed. Total hip, femoral neck, and lumbar spine aBMD was measured via dual-energy x-ray absorptiometry. The focal bone quality of the distal radius was evaluated via 3D reconstructed computed tomographic images. Serum levels of GDF-15, insulin-like growth factor-1, and inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β (IL-1β), as well as the corresponding mRNA levels in the pronator quadratus muscle were determined. Participants in the OP group had higher serum GDF-15 levels than those in the CON group. The mRNA levels of GDF-15, IL-1β, and TNF-α in the pronator quadratus muscle were significantly higher in the OP group than in the CON one. Levels of both serum GDF-15 and GDF-15 mRNA in muscle were positively correlated with age and negatively associated with the aBMD of the total hip and focal bone quality of the distal radius. Handgrip power was not correlated with circulating GDF-15 levels but was correlated with circumferences of the upper arm and calf, and levels of GDF-15 mRNA in muscle specimens. The mRNA levels of GDF-15 were correlated with those of inflammatory cytokines such as TNF-α and IL-1β. The mRNA levels of TNF-α were associated with circumferences of the upper arm and calf and with the aBMD of the total hip. The mRNA levels of GDF-15 in muscle were correlated with serum levels of GDF-15 and TNF-α. GDF-15 may have associations with bone metabolism in humans via paracrinological and endocrinological mechanisms. Maintenance of muscle mass and function would be influenced more by GDF-15 in muscle than by circulating GDF-15. The role of GDF-15 in bone metabolism and muscle homeostasis could be related to inflammatory responses.

Initial Characterization of Focal Bone Lesions with Conventional Radiographs or Computed Tomography: Diagnostic Performance and Interobserver Agreement Assessment.

Objectives: To ascertain the role of CT and conventional radiographs for the initial characterization of focal bone lesions.Methods: Images from 184 patients with confirmed bone tumors included in an ethics committee-approved study were retrospectively evaluated. The reference for benign-malignant distribution was based on histological analysis and long-term follow-up. Radiographs and CT features were analyzed by 2 independent musculoskeletal radiologists blinded to the final diagnosis. Lesion margins, periosteal reaction, cortical lysis, endosteal scalloping, presence of pathologic fracture, and lesion mineralization were evaluated. Results: The benign-malignant distribution in the study population was 68.5-31.5% (126 benign and 58 malignant). In the lesions that could be seen in both radiographs and CT, the performance of these methods for the benign-malignant differentiation was similar (accuracy varying from 72.8% to 76.5%). The interobserver agreement for the overall evaluation of lesion aggressiveness was considerably increased on CT compared to radiographs (Kappa of .63 vs .22). With conventional radiographs, 18 (9.7%) and 20 (10.8%) of the lesions evaluated were not seen respectively by readers 1 and 2. Among these unseen lesions, 50%-61.1% were located in the axial skeleton. Compared to radiographs, the number of lesions with cortical lysis and endosteal scalloping was 26-34% higher with CT. Conclusion: Although radiographs remain the primary imaging tool for lesions in the peripheral skeleton, CT should be performed for axial lesions. CT imaging can assess the extent of perilesional bone lysis more precisely than radiographs with a better evaluation of lesion fracture risk.

P178 An unusual recurrent case of Cryptococcal sacroilitis in an immunocompetent elderly female in Rajasthan, India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackground Cryptococcus lives in the environment all over the globe. Although it spreads via inhalation route still most of the exposed individuals never get sick as the majority of cases are seen in immunocompromised. Objective of this clinical case report is to highlight the rare fungal etiology associated with iliac bone abscess to avoid incorrect diagnosis and prompt management of case.Case PresentationA 70-year-old elderly female presented with hip pain for a month duration, not relieved with analgesics in September, 2021. In MRI a well-defined irregularly marginated hyperintense focal lesion was found in left iliac bone with joint effusion suggestive of infective etiology, tubercular, or less likely metastasis.CT-guided biopsy reported occasional hyphae-like fragments giving an impression of acute on chronic osteomyelitis with suspicion of fungal infection. Culture reported Cryptococcus neoformans. Fungal markers and Beta-d glucan were indeterminate and Galactomannan was found negative for the sample. Extrapulmonary TB was ruled out by AFB staining, MGIT Culture, and GeneXpert MTB. Bone scan, tumor markers, and PET scan ruled out osteolytic lesion secondary to metastasis. Though PET Scan and HRCT thorax confirm pulmonary involvement giving a picture of bilateral interstitial lung disease along with multiple enlarged lymph nodes.Patient serum was found negative for HIV, HBV, and HCV. Liver and renal function tests were within normal range and in hematology, ESR was raised (50; normal range:0-20). Patient is hypertensive with HbA1c of 5.3. There was no history of travel, avian exposure, weight loss, and COVID-19 infection. Patient was started on voriconazole and considering generalized lymphadenopathy, a therapeutic trial of anti-tubercular therapy was started which was stopped within a week on patient non-compliance. Abscess resolved with voriconazole and patient was discharged.In February 2022, Patient presented with similar complaints. CT scan of this fluctuant nodule depicted hypoechoic lesion which was ultrasound-guided drained. Sections show many rounds of oval fungal organism which were found PAS positive with mucicarmine and alcian blue positive capsule. Budding yeast cells were seen on KOH mount and India ink preparation demonstrated capsule which was confirmed by Cryptococcal Antigen test giving an overall impression in favor of Cryptococcosis. Patient was started on oral fluconazole and Injection liposomal amphotericin B 250 mg for 14 days.Discussion and ConclusionThis is the first case of skeletal Cryptococcosis at our institution which was managed by antifungals without surgical debridement resulting in resolution of abscess. Isolated focal iliac bone cryptococcosis is unusual but may occur in immunocompetent with everyday exposure to the organism. Herein, Patient had bilateral lung involvement along with multiple lymphadenopathies with no evidence of TB bacilli which inferences that the isolate most likely originated from environmental bird droppings and has disseminated from pulmonary lesion to the iliac bone. The radiological findings of iliac cryptococcosis abscess were nonspecific. A definitive diagnosis was made on histopathological and fungal examinations of ultrasound-guided drained abscess. Patient will be followed in the near future for relapse or any other medical issues related to the case.

Deep learning-based virtual noncalcium imaging in multiple myeloma using dual-energy CT.

Dual-energy CT with virtual noncalcium (VNCa) images allows the evaluation of focal intramedullary bone marrow involvement in patients with multiple myeloma. However, current commercial VNCa techniques suffer from excessive image noise and artifacts due to material decomposition used in synthesizing VNCa images. In this work, we aim to improve VNCa image quality for the assessment of focal multiple myeloma, using an Artificial intelligence based Generalizable Algorithm for mulTi-Energy CT (AGATE) method. AGATE method used a custom dual-task convolutional neural network (CNN) that concurrently carries out material classification and quantification. The material classification task provided an auxiliary regularization to the material quantification task. CNN parameters were optimized using custom loss functions that involved cross-entropy, physics-informed constraints, structural redundancy in spectral and material images, and texture information in spectral images. For training data, CT phantoms (diameters 30 to 45cm)withtissue-mimicking inserts were scanned on a third generation dual-source CT system. Scans were performed at routine dose and half of the routine dose. Small image patches (i.e., 40 × 40 pixels) of tissue-mimicking inserts with known basis material densities were extracted for training samples. Numerically simulated insert materials with various shapes increased diversity of training samples. Generalizability of AGATE was evaluated using CT images from phantoms and patients. In phantoms, material decomposition accuracy was estimated using mean-absolute-percent-error (MAPE), using physical inserts that were not used during the training. Noise power spectrum (NPS) and modulation transfer function (MTF) were compared across phantom sizes and radiation dose levels. Five patients with multiple myeloma underwent dual-energy CT, with VNCa images generated using a commercial method and AGATE. Two fellowship-trained musculoskeletal radiologists reviewed the VNCa images (commercial and AGATE) side-by-side using a dual-monitor display, blinded to VNCa type, rating the image quality for focal multiple myeloma lesion visualization using a 5-level Likert comparison scale (-2=worse visualization and diagnostic confidence, -1=worse visualization but equivalent diagnostic confidence, 0=equivalent visualization and diagnostic confidence, 1=improved visualization but equivalent diagnostic confidence, 2=improved visualization and diagnostic confidence). A post hoc assignment of comparison ratings was performed to rank AGATE images in comparison to commercial ones. AGATE demonstrated consistent material quantification accuracy across phantom sizes and radiation dose levels, with MAPE ranging from 0.7% to 4.4% across all testing materials. Compared to commercial VNCa images, the AGATE-synthesized VNCa images yielded considerably lower image noise (50-77% noise reduction) without compromising noise texture or spatial resolution across different phantom sizes and two radiation doses. AGATE VNCa images had markedly reduced area under NPS curves and maintained NPS peak frequency (0.7 lp/cm to 1.0 lp/cm), with similar MTF curves (50% MTF at 3.0 lp/cm). In patients, AGATE demonstrated reduced image noise and artifacts with improved delineation of focal multiple myeloma lesions (all readers comparison scores indicating improved overall diagnostic image quality [scores 1 or 2]). AGATE demonstrated reduced noise and artifacts in VNCa images and ability to improve visualization of bone marrow lesions for assessing multiple myeloma.

Assessment of performances of a deep learning algorithm for the detection of limbs and pelvic fractures, dislocations, focal bone lesions, and elbow effusions on trauma X-rays

PurposeTo appraise the performances of an AI trained to detect and localize skeletal lesions and compare them to the routine radiological interpretation. MethodsWe retrospectively collected all radiographic examinations with the associated radiologists’ reports performed after a traumatic injury of the limbs and pelvis during 3 consecutive months (January to March 2017) in a private imaging group of 14 centers. Each examination was analyzed by an AI (BoneView, Gleamer) and its results were compared to those of the radiologists’ reports. In case of discrepancy, the examination was reviewed by a senior skeletal radiologist to settle on the presence of fractures, dislocations, elbow effusions, and focal bone lesions (FBL).The lesion-wise sensitivity of the AI and the radiologists’ reports was compared for each lesion type.This study received IRB approval (CRM-2106-177). ResultsA total of 4774 exams were included in the study. Lesion-wise sensitivity was 73.7% for the radiologists’ reports vs. 98.1% for the AI (+24.4 points) for fracture detection, 63.3% vs. 89.9% (+26.6 points) for dislocation detection, 84.7% vs. 91.5% (+6.8 points) for elbow effusion detection, and 16.1% vs. 98.1% (+82 points) for FBL detection. The specificity of the radiologists’ reports was always 100% whereas AI specificity was 88%, 99.1%, 99.8%, 95.6% for fractures, dislocations, elbow effusions, and FBL respectively. The NPV was measured at 99.5% for fractures, 99.8% for dislocations, and 99.9% for elbow effusions and FBL. ConclusionAI has the potential to prevent diagnosis errors by detecting lesions that were initially missed in the radiologists’ reports.

Acute Leukaemia of Ambiguous Lineage Presenting as a Focal Bone Lesion: a Case Report

Acute Leukaemia of Ambiguous Lineage Presenting as a Focal Bone Lesion: a Case Report

Sowerby’s Beaked Whales (Mesoplodon bidens) in the Skagerrak and Adjacent Waters: Historical Records and Recent Post-Mortem Findings

In contrast to sparse historical observational records, five Sowerby’s beaked whales (SBW) stranded and died in Swedish waters between 2015 and 2020. Here we summarize historical records of SBWs in the Skagerrak basin and adjacent waters. The three recent stranding events from Sweden are described, and the post-mortem findings, including diet analysis, from the five SBWs are presented. Of 30 historical records of SBWs observations since 1869, 13 (43%) were documented between 2010 and 2021, and records between July and November were the most frequent. The recent stranding events occurred in October 2015 (n = 1), August 2019 (n = 3) and July 2020 (n = 1). Four of the SBWs were examined through necropsy, and one was sampled in the field. They were all sub-adults and included a single female and four males. The causes of death were emaciation, euthanasia due to traumatic injury, and live stranding of undetermined cause. Two SBWs each had a focal bone lesion consistent with osteomyelitis. Other findings included pox-like dermatitis, trauma, focal granulomas in a lymph node and intestine, and ulceration of the stomach. CT scans were performed on the heads of two animals, with inconclusive results. Three SBWs had hard parts in the gastrointestinal tract that mainly consisted of otoliths from several fish species. An eDNA-analysis confirmed and supplemented the diet analysis, revealing 17 fish species in total, including species not previously described as prey for SBW, such as Pleuronectidae spp. The apparent increase in observational records since 2010 may indicate a shift in SBW distribution or changing threats to these animals. Our results support and expand theories on SBW movements and provide data on the biology and health of this poorly known species, which are valuable for conservation and legislation efforts.

An in vitro model for discovery of osteoclast specific biomarkers towards identification of racehorses at risk for catastrophic fractures.

Focal bone microcracks with osteoclast recruitment and bone lysis, may reduce fracture resistance in racehorses. As current imaging does not detect all horses at risk for fracture, the discovery of novel serum biomarkers of bone resorption or osteoclast activity could potentially address this unmet clinical need. The biology of equine osteoclasts on their natural substrate, equine bone, has never been studied in vitro and may permit identification of specific biomarkers of their activity. (1) Establish osteoclast cultures on equine bone, (2) Measure biomarkers (tartrate resistant acid phosphatase isoform 5b [TRACP-5b] and C-terminal telopeptide of type I collagen [CTX-I]) in vitro and (3) Study the effects of inflammation. In vitro experiments. Haematopoietic stem cells, from five equine sternal bone marrow aspirates, were differentiated into osteoclasts and cultured either alone or on equine bone slices, with or without a pro-inflammatory stimulus (IL-1β or LPS). CTX-I and TRACP-5b were immunoassayed in the media. Osteoclast numbers and bone resorption area were assessed. TRACP-5b increased over time in osteoclast cultures without bone (p < 0.0001) and correlated with osteoclast number (r=0.63, p < 0.001). CTX-I and TRACP-5b increased with time for cultures with bone (p=0.002; p=0.02 respectively), correlated with each other (r=0.64, p < 0.002) and correlated with bone resorption (r=0.85, p < 0.001; r=0.82, p < 0.001 respectively). Inflammation had no measurable effects. Specimen numbers limited. Equine osteoclasts were successfully cultured on equine bone slices and their bone resorption quantified. TRACP-5b was shown to be a biomarker of equine osteoclast number and bone resorption for the first time; CTX-I was also confirmed to be a biomarker of equine bone resorption in vitro. This robust equine specific in vitro assay will help the study of osteoclast biology.

Whole body magnetic resonance imaging in healthy children and adolescents: Bone marrow appearances of the appendicular skeleton

ObjectiveTo describe the appearances of bone marrow in the appendicular skeleton on fat-suppressed T2-weighted sequences as assessed by whole-body MRI in healthy and asymptomatic children and adolescents. Material and methodsFollowing ethical approval, we assessed the bone marrow of the extremities on water-only Dixon T2-weighted images as part of a whole-body MRI in 196 healthy and asymptomatic children aged 5–19 years. Based on a newly devised and validated scoring system, we graded intensity (0–2 scale) and extension (1–4 scale) of focal high signal bone marrow areas, and divided them into minor or major findings, based on intensity and extension, reflecting their potential conspicuousness in a clinical setting. ResultsIn the upper extremity, we registered 366 areas with increased signal whereof 79 were major findings. In the lower extremities there were 675 areas of increased signal of which 340 were major findings. Hundred-and-fifteen (58.79%) individuals had at least one major finding, mainly located in the hand and proximal humerus, and the feet and knees. We found no differences according to gender, reported hours of sports activity, handedness, or age group, except for more minor findings in the upper extremities amongst 15–18-year-olds as compared to those aged 5–8 years. ConclusionFocal areas of high signal intensity on whole-body MRI, T2-weighted fat suppressed images that, in a clinical setting could cause concern, were seen in more than half of healthy, asymptomatic children and adolescents. Awareness of this is important when interpreting whole-body MRI in this age group, particularly in the assessment of clinically silent lesions.

Sciatic and median nerve neurolymphomatosis as initial presentation of B-cell lymphoma

Neurolymphomatosis (NL) is the infiltration of cranial nerves or nerves and roots from the peripheral nervous system by lymphoma, usually by B-cell non-Hodgkin’s lymphoma. It is uncommon as initial presentation of the disease and can lead to extremely heterogeneous clinical manifestations. We report the case of a 72-year old male who presented with numbness of the right hand, progressive weakness in both lower limbs and weight loss. 18F-FDG PET/CT showed bilateral hypermetabolic adrenal masses, gastric ulcer, small hypermetabolic adenopathies, multiple focal bone marrow uptake and intense uptake in both sciatic nerves and right median nerve. A node and gastric biopsy confirmed diffuse large-B-cell lymphoma, activated B cell type, with posterior resolution of peripheral nerves uptake after beginning chemotherapy.

Comminuted navicular fracture treated with an internal fixation plate – Technical Tip

Fractures of the navicular are relatively uncommon lesions. Comminuted fractures of the navicular body may be associated with focal bone collapse and loss of integrity of the medial column of the midfoot with gross instability, leading to deformities and potential early osteoarthritis. The treatment is challenging due to the difficulties to maintain the length and stability of the midfoot medial column and restoring the anatomy without damaging the vascular supply. Here we present an option for the surgical treatment of comminuted fractures of the navicular using a low-profile locking plate with the “bridge” principle as a temporary internal fixator. The technique consists of restoring the navicular anatomy by fixing the larger fragments with screws and applying indirect reduction of minor fragments. The bone length is maintained by a bridge-plating system with screws inserted into the talus and the medial cuneiform, crossing the talonavicular and naviculocuneiform joints. Implants are removed after fracture healing. Level of Evidence: V; Therapeutic Study; Expert Opinion.

18F-FDG-PET/CT in relapsed multiple myeloma: Are prognostic thresholds different from first-line therapy?

PurposeWhile 18F-FDG PET/CT yields valuable prognostic information for patients in first-line therapy of multiple myeloma (MM), its prognostic relevance in relapse is not established. Available studies of relapsed MM describe prognostic thresholds for frequently used PET/CT parameters that are significantly higher than those identified in the first-line setting. The purpose of this study was to evaluate the prognostic role of PET/CT in relapsed MM, based on parameters used in the first-line setting.MethodsOur retrospective study included 36 patients with MM who had received autologous or allogeneic stem cell transplantation, suffered at least one relapse, and underwent FDG-PET/CT at relapse. Number of focal bone lesions (FL), maximal standardised uptake value (SUVmax), and presence of PET-positive extramedullary lesions (EMD) were analysed.ResultsFor the number of FLs, the prognostic value was demonstrated with a cut-off of > 3 (median OS 3.8 months vs. not reached, p = 0.003). Median OS of patients with SUVmax ≤ 4 was not reached, while it was 3.9 months in patients with SUVmax > 4 (p = 0.014). Presence of EMD was a significant prognostic parameter too, with median OS of 3.6 months versus not reached (p = 0.004). The above-mentioned parameters showed prognostic significance for PFS as well. Combination of higher ISS stage and PET/CT parameters identified patients with particularly short OS (3.7 months vs. not reached, p < 0.001) and PFS (3.6 vs. 11.7 months p < 0.001).ConclusionThe PET/CT parameters SUVmax > 4, nFL > 3, and presence of EMD identify patients with poor prognosis not only in the first-line setting but also in relapsed MM.

Uncommon presentation of brown tumours revealing hyperparathyroidism: Three case reports.

Brown tumours (BTs) are focal bone lesions encountered in patients with uncontrolled hyperparathyroidism (HPT). They are due to a proliferation of multinucleated giant cells in osteolytic lesions. Because of early screening of bone metabolism disorders, BTs are rare bone manifestations. More importantly, they scarcely reveal the disease. We demonstrate through these two cases reports unusual locations of BT complicating the course of HPT due to parathyroid hyperplasia.

Focal osteoporosis defect is associated with vertebral compression fracture prevalence in a bone mineral density-independent manner.

IntroductionFocal osteoporosis defect has shown a high association with the bone fragility and osteoporotic fracture prevalence. However, no routine computed tomography (CT)‐based vertebral focal osteoporosis defect measurement and its association with vertebral compression fracture (VCF) were discussed yet. This study aimed to develop a routine CT‐based measurement method for focal osteoporosis defect quantification, and to assess its association with the VCF prevalence.Materials and MethodsA total of 205 cases who underwent routine CT scanning, were retrospectively reviewed and enrolled into either the VCF or the control group. The focal bone mineral content loss (focal BMC loss), measured as the cumulated demineralization within bone void space, was proposed for focal osteoporosis defect quantification. Its scan‐rescan reproducibility and its correlation with trabecular bone mineral density (BMD) and apparent microarchitecture parameters were evaluated. The association between focal BMC loss and the prevalence of VCF was studied by logistic regression.ResultsThe measurement of focal BMC loss showed high reproducibility (RMSSD = 0.011 mm, LSC = 0.030 mm, ICC = 0.97), and good correlation with focal bone volume fraction (r = 0.79, P < 0.001), trabecular bone separation (r = 0.76, P < 0.001), but poor correlation with trabecular BMD (r = 0.37, P < 0.001). The focal BMC loss was significantly higher in the fracture group than the control (1.03 ± 0.13 vs. 0.93 ± 0.11 mm; P < 0.001), and was associated with prevalent VCF (1.87, 95% CI = 1.31–2.65, P < 0.001) independent of trabecular BMD level.DiscussionAs a surrogate measure of focal osteoporosis defect, focal BMC Loss independently associated with the VCF prevalence. It suggests that focal osteoporosis defect is a common manifestation that positively contributed to compression fracture risk and can be quantified with routine CT using focal BMC Loss.

An unusual case report: normocalcemic markers and their relationship with multiple sclerosis in primary hyperparathyroidism disease revealed by radiological markers with the diagnosis of brown tumor

BackgroundBrown tumor is a giant cell focal bone lesion associated with hyperparathyroidism and is more common in long bones such as the femur, ribs, pelvis, and clavicle, rather than in the head and neck region. Brown tumors occur less frequently in patients with primary hyperparathyroidism and are not usually a diagnostic marker of the disease. In addition, when primary hyperparathyroidism shows normocalcemic values and this disease is accompanied by multiple sclerosis, diagnosis becomes difficult.Case presentationA 57-year-old female patient presented with a painless, firm, irregularly circumscribed lesion extending from the upper palate to the nasal cavity. The lesion was first noticed by the patient about 2 months ago because it started to form asymmetry. The patient, whose anamnesis was learned to have Multiple Sclerosis (MS) and Chronic Obstructive Pulmonary Disease (COPD), was immobile. The patient was using medication only for COPD. After radiological and clinical examinations, the image in the maxilla was thought to be Brown Tumor and blood values were examined. After the incisional biopsy was also performed, it was evaluated together with the blood results and the diagnosis of brown tumor due to normocalcemic primary hyperparathyroidism was made. As in this case, brown tumor cases in which the calcium level remains within normal ranges, that is, due to Normocalcemic Hyperparathyroidism, are extremely rare, and 7 cases have been reported in the literature.ConclusionsIn the presented case, the importance of the radiological and clinical markers of the brown tumor developing due to normocalcemic hyperparathyroidism in the diagnosis is stated, the relationship of MS and the effects of the drugs used for MS at brown tumor formation is examined, and the importance of the treatment follow-up with radiological findings is stated. The features of the much rarer subgroups of relatively common diseases should be well known, and it should not be forgotten that the less frequently observed features can sometimes be the first indicator. And when large-limited lesions are identified, additional systemic features should be sought instead of direct surgical intervention.

Joint Damage and Neuropathic Pain in Rats Treated With Lysophosphatidic Acid.

Joint pain is a complex phenomenon that involves multiple endogenous mediators and pathophysiological events. In addition to nociceptive and inflammatory pain, some patients report neuropathic-like pain symptoms. Examination of arthritic joints from humans and preclinical animal models have revealed axonal damage which is likely the source of the neuropathic pain. The mediators responsible for joint peripheral neuropathy are obscure, but lysophosphatidic acid (LPA) has emerged as a leading candidate target. In the present study, male and female Wistar rats received an intra-articular injection of LPA into the right knee and allowed to recover for 28 days. Joint pain was measured by von Frey hair algesiometry, while joint pathology was determined by scoring of histological sections. Both male and female rats showed comparable degenerative changes to the LPA-treated knee including chondrocyte death, focal bone erosion, and synovitis. Mechanical withdrawal thresholds decreased by 20-30% indicative of secondary allodynia in the affected limb; however, there was no significant difference in pain sensitivity between the sexes. Treatment of LPA animals with the neuropathic pain drug amitriptyline reduced joint pain for over 2 hours with no sex differences being observed. In summary, intra-articular injection of LPA causes joint degeneration and neuropathic pain thereby mimicking some of the characteristics of neuropathic osteoarthritis.

POS-239 Removal of brown tumor associated with normalization of serum parathyroid levels in a 19 year old Indian female on maintenance hemodialysis– A serendipitous discovery

Brown tumors are focal bone lesions caused by increased osteoclastic activity and fibroblastic proliferation in patients with uncontrolled hyperparathyroidism. It is usually an uncommon lesion occurring with the frequency of 4.5% in primary hyperparathyroidism and 1.5-1.7% in cases of secondary hyperparathyroidism with an overall incidence of 0.1%.