Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab.

BACKGROUND: Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who received denosumab. METHODS: This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated with denosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. RESULTS: Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. CONCLUSIONS: Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. TRIAL REGISTRATION: clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.

Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study.

BACKGROUND: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB. METHODS: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment. Patients had surgically unsalvageable GCTB (cohort 1), had surgically salvageable GCTB with planned surgery expected to result in severe morbidity (cohort 2), or were enrolled from a previous study of denosumab for GCTB (cohort 3). Patients received 120 mg subcutaneous denosumab once every 4 weeks during the treatment phase, with loading doses (120 mg subcutaneously) administered on study days 8 and 15 to patients in cohorts 1 and 2 (patients in cohort 3 did not receive loading doses). The primary endpoint was safety in terms of the type, frequency, and severity of adverse events; secondary endpoints included time to disease progression from cohort 1 and the proportion of patients without surgery at month 6 for cohort 2. The safety analysis set included all enrolled patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, number NCT00680992, and has been completed. FINDINGS: Between Sept 9, 2008, and Feb 25, 2016, 532 patients were enrolled: 267 in cohort 1, 253 in cohort 2, and 12 in cohort 3. At data cutoff on Feb 24, 2017, median follow-up was 58·1 months (IQR 34·0-74·4) in the overall patient population, and 65·8 months (40·9-82·4) in cohort 1, 53·4 months (28·2-64·1) in cohort 2, and 76·4 months (61·2-76·5) in cohort 3. During the treatment phase, the most common grade 3 or worse adverse events were hypophosphataemia (24 [5%] of 526 patients), osteonecrosis of the jaw (17 [3%], pain in extremity (12 [2%]), and anaemia (11 [2%]). Serious adverse events were reported in 138 (26%) of 526 patients; the most common were osteonecrosis of the jaw (17 [3%]), anaemia (6 [1%]), bone giant cell tumour (6 [1%]), and back pain (5 [1%]). 28 (5%) patients had positively adjudicated osteonecrosis of the jaw, four (1%) had atypical femur fracture, and four (1%) had hypercalcaemia occurring 30 days after denosumab discontinuation. There were four cases (1%) of sarcomatous transformation, consistent with historical data. Ten (2%) treatment-emergent deaths occurred (two of which were considered treatment-related; bone sarcoma in cohort 2 and sarcoma in cohort 1). Median time to progression or recurrence for patients in cohort 1 during the first treatment phase was not reached (28 [11%] of 262 patients had progression or recurrence). 227 (92%; 95% CI 87-95) of 248 patients who received at least one dose of denosumab in cohort 2 had no surgery in the first 6 months of the study. INTERPRETATION: The types and frequencies of adverse events were consistent with the known safety profile of denosumab, which showed long-term disease control for patients with GCTB with unresectable and resectable tumours. Our results suggest that the overall risk to benefit ratio for denosumab treatment in patients with GCTB remains favourable. FUNDING: Amgen.

Increased signal in the proximal patellar tendon: normal or pathologic?

OBJECTIVE: To determine the clinical significance of T2 signal hyperintensity in the proximal patellar tendon seen on MRI of the knee. MATERIALS AND METHODS: MRIs of 100 patients who underwent MRI of the knee between 1 May 2018 and 15 July 2018 were retrospectively evaluated. All examinations were performed on 3-Tesla MRI scanners with a dedicated knee coil and in accordance with our institution's standard knee MRI protocol. The presence of increased T2 signal was assessed on both sagittal and axial T2-weighted fat-saturated images. The amount of increased signal in the proximal patellar tendon on T2-weighted images was characterized as: none, mild, moderate, or severe. A corresponding chart review of the referring physicians' notes was performed to determine the presence of clinical symptoms of patellar tendinopathy. Patellar tendinopathy was considered present if the clinical notes described tenderness on palpation of the inferior patellar pole, infrapatellar tenderness, or patellar tendinosis/tendinitis. RESULTS: The majority (66%) of knee MRIs demonstrated the presence of increased T2 signal in the proximal patellar tendon. Only 4.5% of these patients had associated clinical findings of patellar tendinopathy. CONCLUSION: Although increased T2 signal in the proximal patellar tendon is a common finding, only in rare cases are there associated clinical symptoms. Thus, increased T2 signal in the proximal patellar tendon may not be a pathological finding in the absence of clinical findings of patellar tendinopathy.

Is Core Needle Biopsy Reliable in Differentiating Between Aggressive Benign and Malignant Radiolucent Bone Tumors?

BACKGROUND: Although there is widespread acceptance of core needle biopsy (CNB) for diagnosing solid tumors, there is reluctance by some clinicians to use CNB for aneurysmal bone cysts (ABCs) as a result of concerns of safety (bleeding, nerve injury, fracture, readmission, or infection) and reliability, particularly to rule out malignant diagnoses like telangiectatic osteosarcoma. This is especially true when CNB tissue is sent from an outside hospital, where the technique used to obtain the tissue may be spurious. QUESTIONS/PURPOSES: (1) Is CNB effective (provided adequate information to indicate appropriate surgical treatment without further open biopsy) as an initial diagnostic test for ABC? (2) Is CNB accurate (pathology consistent with the subsequent definitive surgical pathologic diagnosis) in differentiating between benign lesions such as primary or secondary ABCs and malignant radiolucent lesions such as telangiectatic osteosarcoma? (3) What are the complications of CNB? (4) Is there any difference in the effectiveness or accuracy of CNB performed at outside institutions when compared with a referral center? METHODS: A retrospective study of our musculoskeletal tumor board pathology database (1990-2016) was performed using search criteria "aneurysmal bone cyst" or "telangiectatic osteosarcoma." Only patients undergoing a CNB who proceeded to definitive surgical resection with final pathology were included. Excluding outside CNBs, CNB was performed after presentation at a musculoskeletal tumor board as a result of atypical features on imaging or history concerning for malignancy. Outside CNB tissue was reviewed by our pathologists. If there was sufficient tissue for diagnosis, the patient proceeded to definitive surgery. If not, the patient underwent open biopsy. CNB diagnosis, open biopsy results, and open surgical resection pathology were reviewed. Complications, including bleeding, infection, nerve injury, readmission, or fracture, between the CNB and definitive open surgical procedure (mean 1.6 months) were documented. CNBs were considered "effective" if they yielded pathology considered sufficient to proceed with appropriate definitive surgery without additional open biopsy. CNBs were considered "accurate" if they were effective and yielded a pathologic diagnosis that matched the subsequent definitive surgical pathology. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of obtaining a malignant diagnosis using CNB were also calculated. RESULTS: A total of 81% (59 of 73) of CNBs were effective. Ninety-three percent (55 of 59) of CNBs were classified as accurate. Diagnostic CNBs had a sensitivity and specificity of 89% (eight of nine) and 100% (51 of 51), respectively. The PPV was 1.00 and the NPV was 0.82. There were no complications. With the numbers available, there was no difference in efficacy (90% [37 of 41 versus 14 of 15]; odds ratio, 0.97 [95% confidence interval {CI}, 0.41-2.27], p = 0.94) or accuracy (92% [34 of 37 versus 13 of 14]; odds ratio, 0.87 [95% CI, 0.08-9.16], p = 0.91) between CNBs performed in house and those referred from outside. CONCLUSIONS: These data suggest that CNBs are useful as an initial diagnostic test for ABC and telangiectatic osteosarcoma. Tissue from outside CNBs can be read reliably without repeat biopsy. If confirmed by other institutions, CNB may be considered a reasonable approach to the diagnosis of aggressive, radiolucent lesions of bone. LEVEL OF EVIDENCE: Level III, diagnostic study.

Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone.

BACKGROUND: Denosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); however, radiologic assessment of tumors in bone is challenging. The study objective was to assess tumor response to denosumab using three different imaging parameters in a prespecified analysis in patients with GCTB from two phase 2 studies. METHODS: The studies enrolled adults and adolescents (skeletally mature and at least 12 years of age) with radiographically measurable GCTB that were given denosumab 120 mg every 4 weeks, with additional doses on days 8 and 15 of cycle 1. The proportion of patients with an objective tumor response was assessed using either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST), European Organisation for Research and Treatment of Cancer response criteria (positron emission tomography [PET] scan criteria), or inverse Choi density/size (ICDS) criteria. Target lesions were measured by computed tomography or magnetic resonance imaging (both studies), PET (study 2 only), or plain film radiograph (study 2 only). RESULTS: Most patients (71.6%) had an objective tumor response by at least one response criteria. Per RECIST, 25.1% of patients had a response; per PET scan criteria, 96.2% had a response; per ICDS, 76.1% had a response. 68.5% had an objective tumor response ≥ 24 weeks. Using any criteria, crude incidence of response ranged from 56% (vertebrae/skull) to 91% (lung/soft tissue), and 98.2% had tumor control ≥ 24 weeks. Reduced PET avidity appeared to be an early sign of response to denosumab treatment. CONCLUSION: Modified PET scan criteria and ICDS criteria indicate that most patients show responses and higher benefit rates than modified RECIST, and therefore may be useful for early assessment of response to denosumab. TRIAL REGISTRATION: ClinicalTrials.gov Clinical Trials Registry NCT00396279 (retrospectively registered November 6, 2006) and NCT00680992 (retrospectively registered May 20, 2008).

Efficacy of intraarticular corticosteroid hip injections for osteoarthritis and subsequent surgery.

OBJECTIVE: Our study aimed to determine the duration of pain relief from intraarticular hip corticosteroid injections and identify patient predictive factors on injection response. We also sought to determine the subsequent rate of hip surgery and whether severity of hip osteoarthritis or injection response correlated with the decision to undergo surgery. MATERIALS AND METHODS: All intraarticular hip steroid injections performed for osteoarthritis under fluoroscopic guidance at a single institution between January 2010 to December 2012 were retrospectively reviewed. Response was divided into three groups: no relief, immediate (≤ 2 weeks of pain relief), and continued (> 2 weeks of pain relief). Presence of hip surgery for osteoarthritis performed within 2 years following injection was obtained. Correlation between patient characteristics with injection outcome and hip surgery was analyzed. RESULTS: Of 78 patients, a total of 82 injections were analyzed. For injections, 19.5% (16/82) showed no response, 47.6% (39/82) showed immediate response, and 32.9% (27/82) showed continued response. There was no significant correlation between injection outcome with age, Tönnis grade, BMI, or duration of symptoms. In total, 48.7% had hip surgery within 2 years after initial injection. There was a significant association between Tönnis grade and surgery, with higher Tönnis grades correlating with decision to undergo surgery (p = 0.002). CONCLUSIONS: Gender, age, BMI, duration of symptoms, and radiographic severity of disease do not predict injection response. Due to high surgical rates and poor response, intraarticular hip steroid injections may be less effective in the long term, and surgical management may be considered earlier.

Magnetic resonance arthrography and the prevalence of acetabular labral tears in patients 50 years of age and older.

OBJECTIVE: Arthroscopy for acetabular labral tears has minimal impact on pain and function in older patients, especially in the setting of concomitant osteoarthritis. Still, many physicians seek this diagnosis with MR arthrography. Our purpose is to assess the frequency of acetabular labral tears in older patients with hip pain and correlate likelihood of labral pathology with severity of osteoarthritis as visualized on conventional radiograph. MATERIALS AND METHODS: From 2004 to 2013, 208 hip MRI arthrograms and corresponding radiographs on patients aged 50 years and older were identified. Age, gender, grade and location of labral tear, alpha angle, Tönnis grade, and joint space width were documented. Labral tears and alpha angle were identified and measured on MR arthrogram. Tönnis grade and joint space width were measured on radiographs. RESULTS AND CONCLUSIONS: On MR arthrography, true labral tearing was identified in 73 % of patients. There was some degree of labral pathology in 93.3 % of patients, and this increased to 100 % in patients with moderate to severe osteoarthritis, as defined by Tönnis grade 2-3 or joint space width ≤ 2 mm. There were no statistically significant correlations between labral tear grade and Tönnis grade or joint space width. Given the high frequency of labral pathology and the questionable efficacy of arthroscopic surgical intervention in older patients, MR arthrography should be primarily for those with minimal arthritis on radiograph and potential to benefit from surgery. If further imaging beyond radiographs is necessary in these patients, standard MRI may be a more appropriate imaging tool.

Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone.

BACKGROUND: Surgical resection with curative intent for giant cell tumor of bone (GCTB) may be associated with severe morbidity. This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB. METHODS: Patients with primary or recurrent GCTB, for whom the initially planned surgery was associated with functional compromise or morbidity, received denosumab 120 mg subcutaneously every 4 weeks (additional doses on days 8 and 15 of the first cycle). Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported. Patients were followed for surgical outcome, adverse events, and recurrence following resection. RESULTS: Overall, 222 patients were evaluable for surgical downstaging (54 % were women; median age 34 years). Lesions (67 % primary and 33 % recurrent) were located in the axial (15 %) and appendicular skeleton (85 %). At the data cutoff date, most patients had not yet undergone surgery (n = 106; 48 %) or had a less morbid procedure (n = 84; 38 %) than originally planned. Median (interquartile range) time on denosumab was 19.5 (12.4-28.6) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab. Native joint preservation was 96 % (n = 24/25) for patients with planned joint/prosthesis replacement and 86 % (n = 30/35) for patients with planned joint resection/fusion. Of the 116 patients who had surgery (median postsurgical follow-up 13.0 [8.5-17.9] months), local recurrence occurred in 17 (15 %) patients. CONCLUSION: For patients with resectable GCTB, neoadjuvant denosumab therapy resulted in beneficial surgical downstaging, including either no surgery or a less morbid surgical procedure.

Image-guided percutaneous core needle biopsy of musculoskeletal tumors in children.

The use of image-guided percutaneous core needle biopsy (PCNB) to obtain tissue diagnosis of musculoskeletal lesions has become the standard of care in adult patients with a success rate of over 80%. Previous reports indicate a similar success rate in diagnosing pediatric solid tumors. In this large study, we analyzed >10 years of data in which PCNB was used for tissue diagnosis of musculoskeletal lesions in children; we evaluated the histopathologic accuracy, anesthetic requirements, and complications of these procedures. In 122 children, tissue diagnosis was successfully obtained in 82% of cases, and there were 0 complications associated with the procedure. There was a significantly higher PCNB diagnostic success rate in malignant lesions (93%). These data suggest that the use of PCNB is a safe and effective means of diagnosing musculoskeletal lesions in children.

Subcutaneous panniculitis-like T-cell lymphoma: MRI features and literature review.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) represents a rare subclassification of peripheral T-cell lymphoma (PTCL). We present a case of a 21-year-old female who presented with a 1-month history of pain in the left buttock and hip, tender left inguinal lymph nodes, fevers, and night sweats. Percutaneous core needle biopsy was diagnostic for SPTCL with CD8+ cells positive for cytotoxic granules. Magnetic resonance imaging (MRI) features of SPTCL with a review of the literature are discussed.

Success rates for computed tomography-guided musculoskeletal biopsies performed using a low-dose technique.

OBJECTIVE: To evaluate the success rate of a low-dose (50% mAs reduction) computed tomography (CT) biopsy technique. This protocol was adopted based on other successful reduced-CT radiation dose protocols in our department, which were implemented in conjunction with quality improvement projects. MATERIALS AND METHODS: The technique included a scout view and initial localizing scan with standard dose. Additional scans obtained for further guidance or needle adjustment were acquired by reducing the tube current-time product (mAs) by 50%. The radiology billing data were searched for CT-guided musculoskeletal procedures performed over a period of 8 months following the initial implementation of the protocol. These were reviewed for the type of procedure and compliance with the implemented protocol. The compliant CT-guided biopsy cases were then retrospectively reviewed for patient demographics, tumor pathology, and lesion size. Pathology results were compared to the ultimate diagnoses and were categorized as diagnostic, accurate, or successful. RESULTS: Of 92 CT-guided procedures performed during this period, two were excluded as they were not biopsies (one joint injection and one drainage), 19 were excluded due to non-compliance (operators neglected to follow the protocol), and four were excluded due to lack of available follow-up in our electronic medical records. A total of 67 compliant biopsies were performed in 63 patients (two had two biopsies, and one had three biopsies). There were 32 males and 31 females with an average age of 50 (range, 15-84 years). Of the 67 biopsies, five were non-diagnostic and inaccurate and thus unsuccessful (7%); five were diagnostic but inaccurate and thus unsuccessful (7%); 57 were diagnostic and accurate thus successful (85%). These results were comparable with results published in the radiology literature. CONCLUSIONS: The success rate of CT-guided biopsies using a low-dose protocol is comparable to published rates for conventional dose biopsies. The implemented low-dose protocol did not change the success rate of CT-guided musculoskeletal biopsies.

Intra-articular calcifications following arthroscopic ACL reconstruction: prevalence and possible significance.

PURPOSE: The goal of our study was to determine the frequency of intra-articular calcifications on initial postoperative radiographs following arthroscopic ACL reconstruction, describe their appearance, hypothesize their etiology, and determine their significance. MATERIALS AND METHODS: Review of records and post-operative radiographs for individuals undergoing arthroscopic ACL reconstruction at our institution identified 758 knees between November 2002 and April 2010. All patients underwent femoral and tibial tunnel drilling regardless of graft source. All but 23 underwent notchplasty. RESULTS: Intra-articular calcifications on initial postoperative radiographs were observed in 252 knees. The majority of calcifications were curvilinear, paralleling the posterior femoral condyles. Nineteen of the patients with calcifications on initial studies had repeat radiographs within 6 years. The calcifications resolved in every case. CONCLUSIONS: This study shows that intra-articular calcifications are a common finding on initial post-operative radiographs following ACL reconstruction. We feel they are of doubtful clinical significance, and in our limited experience, they eventually resolve. They should not be confused with chondrocalcinosis or vascular calcification.

Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study.

BACKGROUND: Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB. METHODS: We did an international, open-label, parallel-group, phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease. Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg. We divided patients into three cohorts--those with surgically unsalvageable GCTB (cohort 1), those with salvageable GCTB whose surgery was associated with severe morbidity (cohort 2), and those who transferred from a previous study of denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. Investigator-determined disease status and clinical benefit were assessed every 4 weeks. Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities. Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2. Safety analyses included all patients who received at least one dose of denosumab. Efficacy analyses included all eligible patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, identifier NCT00680992. FINDINGS: 282 patients, including ten adolescents, were included between Sept 9, 2008, and March 25, 2011. Of the 281 patients analysable for safety, three (1%) had osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3-4 adverse events were hypophosphataemia, which occurred in nine (3%) patients, and anaemia, back pain, and pain in extremities, each of which occurred in three patients (1%). Serious adverse events were reported in 25 (9%) patients. No treatment-related deaths were reported. On the basis of investigators' assessment of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months (IQR 5·8-21·0). In cohort 2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients who had surgery underwent a less morbid procedure than planned. Median follow-up in cohort 2 was 9·2 months (IQR 4·2-12·9). INTERPRETATION: Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB. FUNDING: Amgen.

Increased signal of the fibular collateral ligament of the knee on MRI, clinically significant?

INTRODUCTION: The purpose of this study was to determine the clinical significance of signal hyperintensity in the proximal fibular collateral ligament (FCL) on coronal proton density (PD) fat-saturated (FS) MRI of the knee, a common finding. This study is unique in that it characterizes the FCL of a comprehensive, large cohort of both symptomatic and asymptomatic patients, which to our knowledge represents the first study with such broad inclusion criteria. METHODS: A large case series was performed analyzing MRI of the knee of 250 patients from July 2021 through September 2021 and retrospectively reviewed. All studies were performed on 3-Tesla MRI scanners with a dedicated knee coil and in accordance with standard institutional knee MRI protocol. Signal in the proximal fibular collateral ligament was assessed on coronal PDFS and axial T2-weighted FS images. Increased signal was classified as none, mild, moderate, or severe. A corresponding chart review of clinic notes was performed to determine the presence or absence of lateral knee pain. An FCL sprain or injury was considered present if the medical record described tenderness on palpation of the lateral knee, positive finding against resistance to the leg (varus stress test) or reverse pivot shift, or any clinical suspicion for lateral complex sprain or posterolateral corner injury. RESULTS: The majority (74%) of knee MRIs demonstrated the presence of increased signal in the proximal fibular collateral ligament on coronal PD FS images. <5% of these patients had associated clinical findings of fibular collateral ligament and/or lateral supporting structure injury. DISCUSSION: Although increased signal in the proximal FCL of the knee is a common finding on coronal PDFS images, the majority are not associated with clinical symptoms. Thus, this increased signal is likely not a pathological finding in the absence of clinical findings of fibular collateral ligament sprain/injury. Our study emphasizes the importance of clinical correlation in identifying increased signal in the proximal FCL as pathologic.

Relevance of compartmental anatomic guidelines for biopsy of musculoskeletal tumors: retrospective review of 363 biopsies over a 6-year period.

PURPOSE: To retrospectively assess percutaneous core needle biopsies performed by radiologists and the association with tumor seeding along the biopsy tract when anatomic compartment guidelines are not consistently observed. MATERIALS AND METHODS: Retrospective data from computerized patient records and digital images from 363 consecutive computed tomography-guided biopsies of the lower extremity (thigh and leg) performed by radiologists at a single institution from August 2002 to August 2008 were analyzed for breaches of biopsy guidelines. RESULTS: Of the 363 biopsies, 243 (67%) were of soft tissue lesions and 120 (33%) were of bony lesions. There were 188 (52%) malignant and 175 (48%) benign lesions. The following biopsy breaches were observed: 13 (3.6%) of anatomic compartment, 42 (11.6%) of "vital structures," and 82 (68.3%) of needle path for bony tumors. Vital structures as defined by the literature included, but were not limited to, the following: knee joint capsule, greater trochanteric bursa, rectus femoris and vastus intermedius muscles, tibial tubercle, peroneus brevis and peroneus longus distal tendons, and neurovascular bundles. No cases of tumor recurrences could be attributed to needle seeding along a biopsy tract for any of these biopsy guideline breaches. CONCLUSIONS: The concern for needle tract seeding with musculoskeletal tumors is more widespread than the evidence supporting it as a significant or frequent complication. In this study, breaching anatomic compartment, vital structures (other than neurovascular structures), and suggested exact needle path guidelines were not associated with needle tract seeding in the lower extremity.

Imaging of the shoulder: a comparison of MRI and ultrasound.

Magnetic resonance imaging (MRI) is well established as a powerful imaging modality for the shoulder. In the last decade, ultrasound has emerged as an effective imaging option, alongside MRI, for evaluation of the shoulder. With MRI and ultrasound, clinicians now have two viable advanced imaging options for the diagnostic evaluation of shoulder pain. This article discusses the advantages and disadvantages of ultrasound and MRI for the shoulder. Applications where ultrasound is considered the imaging test of choice, those where MRI is more advantageous, and those where both ultrasound and MRI are viable alternatives for shoulder imaging are discussed.

Initial results on development and application of statistical atlas of femoral cartilage in osteoarthritis to determine sex differences in structure: data from the Osteoarthritis Initiative.

PURPOSE: To create an average atlas of knee femoral cartilage morphology, to apply the atlas for quantitative assessment of osteoarthritis (OA), and to study localized sex differences. MATERIALS AND METHODS: High-resolution 3D magnetic resonance imaging (MRI) data of the knee cartilage collected at 3 T as part of the Osteoarthritis Initiative (OAI) were used. An atlas was created based on images from 30 male Caucasian high-risk subjects with no symptomatic OA at baseline. A female cohort of age- and disease-matched Caucasian subjects was also selected from the OAI database. The Jacobian determinant was calculated from the deformation vector fields that nonlinearly registered each subject to the atlas. Statistical analysis based on the general linear model was used to test for regions of significant differences in the Jacobian values between the two cohorts. RESULTS: The average Jacobian was larger in women (1.2 ± 0.078) than in men (1.08 ± 0.097), showing that after global scaling to the male template, the female cartilage was thicker in most regions. Regions showing significant structural differences include the medial weight bearing region, the trochlear (femoral) side of the patellofemoral compartment, and the lateral posterior condyle. CONCLUSION: Sex-based differences in cartilage structure were localized using tensor based morphometry in a cohort of high-risk subjects.

Revisiting CT-guided percutaneous core needle biopsy of musculoskeletal lesions: contributors to biopsy success.

OBJECTIVE: The purpose of this article is to investigate potential technical, imaging, and histopathologic contributors to the success of CT biopsy. MATERIALS AND METHODS: Four hundred forty-four consecutive CT biopsies of musculoskeletal lesions performed from 2005 to 2008 were retrospectively classified as diagnostic or nondiagnostic and as accurate or inaccurate. A biopsy was considered as diagnostic if it provided a definitive pathologic diagnosis or was clinically useful; as accurate if it was concordant with the ultimate diagnosis with respect to identification of malignancy, grade, and histopathologic features; and as successful if it was both diagnostic and accurate. Biopsy success rate, diagnostic yield, and accuracy were assessed according to lesion location, use of sedation, biopsy equipment type, bone lesion matrix type, and lesion histologic type (i.e., bone or soft-tissue origin, malignant or benign neoplasm, and low-or intermediate-to-high-grade neoplasm). RESULTS: Of 444 biopsies, 71% were diagnostic, 86% were accurate, and 70% were successful. Biopsy success and diagnostic yield were greater in bone lesions, malignant neoplasms, and intermediate-to-high-grade neoplasms compared with soft-tissue lesions (p < 0.01), benign neoplasms (p < 0.0001), and low-grade neoplasms (p < 0.0001). Success and diagnostic yield were not significantly associated with technical or imaging factors. Biopsy accuracy was not associated with any of the tested variables. Of the 128 nondiagnostic biopsy results, 53% were accurate with respect to subsequent surgical pathologic findings. Most of these biopsy results were of benign soft-tissue lesions. CONCLUSION: CT biopsy of musculoskeletal lesions is accurate and effective. It may be limited in the evaluation of benign and low-grade soft-tissue neoplasms.

Denosumab Treatment for Giant Cell Tumor of the Spine Including the Sacrum.

STUDY DESIGN: This was a subanalysis of an international, multicenter, open-label study. OBJECTIVE: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992). SUMMARY OF BACKGROUND DATA: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine). METHODS: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3). RESULTS: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts). CONCLUSION: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2.