Keratin-Positive Giant Cell Tumor of Bone and Soft Tissue With HMGA2::NCOR2 Fusion in Children Under 10 With Response to Imatinib Therapy: A Case Series.

HMGA2::NCOR2 keratin-positive giant cell tumors in children with response to imatinib in an infant.

Management of Lateral Condyle Humeral Fracture Associated With Elbow Dislocation in Children. A Retrospective International Multicenter Cohort Study.

OBJECTIVES: Lateral humeral condyle fractures account for 12% to 17% of all distal humerus fractures in children, and usually occur as an isolated injury or are associated with radial neck and/or proximal ulna fractures. The presentation with a concomitant dislocation of the elbow is rare. Therefore, literature on young patients with this uncommon combination is sparse and mostly limited to case reports and small case series. The aim of the present study is to identify the best treatment strategy for this injury, recognize potential risk factors for the development of complications, and identify predictors of outcome. METHODS: This is a multicenter retrospective review of electronic and written medical records for skeletally immature patients who were diagnosed with a lateral condyle fracture of the humerus associated with elbow dislocation (ED). Data recorded included patient demographics, fracture classification, direction of the dislocation, treatment strategy, time to union, elbow range of motion, complications, and additional procedures. The modified Flynn criteria were used to determine the outcomes. RESULTS: We identified 23 patients who presented to 3 institutions with a concomitant lateral humeral condyle fractures and an ED. The mean age at the time of injury was 8.7 years (range: 6 to 13 y). The median time from injury to surgery was 1 day (interquartile range: 0.5, minimum to maximum: 0 to 29 d). The median follow-up was 24 weeks (interquartile range: 16, minimum to maximum: 4 to 120 wk). The injury occurred more commonly in males (79%) with Weiss type 3 fractures. The direction of the dislocation was posterior or posteromedial in most cases. Open reduction through a modified Kocher lateral approach and fixation with either Kirschner wires (N = 12) or cannulated screws (N = 9) was the preferred method of treatment. Eight patients (34.8%) developed complications, including persistent elbow stiffness (N = 5), elbow instability (N = 1), and avascular necrosis (N = 2). There were no cases of delayed union, nonunion, malunion, heterotopic ossification, neurological injury, or hardware failure. Patients treated with casting or Kirschner wire fixation had a significantly increased rate of elbow stiffness compared with screw fixation (50%, 25%, and 11%, respectively, P = 0.015). According to Flynn's criteria, 65% of the patients had good or excellent outcomes, and 35% had poor. CONCLUSION: The findings of this study demonstrate a higher than previously described rate of complications in children with lateral condyle humerus fracture associated with ED, including persistent elbow stiffness, avascular necrosis, and chronic elbow instability, leading to unsatisfactory clinical outcomes in over one-third of the cases. Our findings suggest that the internal fixation with screws, combined with a shorter postoperative immobilization period (2 wk) may lead to improved clinical outcomes. LEVEL OF EVIDENCE: Level III-therapeutic, case series.

Novel method to biopsy aneurysmal bone cysts in children.

PURPOSE: The thin and friable septations composing aneurysmal bone cysts (ABC) may be challenging to target for percutaneous biopsy. The purpose of this study was to describe and evaluate a novel method of ABC biopsy using endomyocardial biopsy forceps as an attempt to capture larger fragments of tissue for diagnosis. METHODS AND MATERIALS: This was a retrospective study performed over a 17-year period. Patients <18 years old who underwent percutaneous biopsy for a presumed ABC, based on pre-procedure imaging, were included. Medical records were reviewed to identify age, sex, lesion location, biopsy procedure details, complications, and pathology results. A diagnostic biopsy was defined as conclusive histologic confirmation. Inconclusive findings or findings suggestive of but not diagnostic of an ABC were treated as non-diagnostic, even if imaging and clinical findings were characteristic. Biopsy device selection and quantity of tissue obtained was at the discretion of the pediatric interventional radiologist. Fisher's exact test was used to compare the diagnostic yield of standard biopsies to those employing biopsy forceps. RESULTS: Twenty-three biopsies were performed in 18 patients (11 female) with a median age of 14.7 years (IQR 10.6-15.6). Lesions were located in the extremities (7, 30.4%), chest (6, 26.1%), pelvis (5, 21.7%), spine (4, 17.4%), and mandible (1, 4.3%). Specimens were obtained using a 13- or 15-gauge bone coring needle (11, 47.8%); 14-, 16-, or 18-gauge soft tissue needle (6, 26.1%); or a combination of bone and soft tissue (4, 17.4%) needles. Endomyocardial biopsy forceps were utilized in 7 cases (30.4%), 2 in which it was the only device used. Overall, a conclusive pathologic diagnosis was made in 13/23 (56.5%) biopsies. Of the diagnostic biopsies, 1 was a unicameral bone cyst and all others were ABCs. No malignancy was identified. Compared to the standard approach, the use of forceps was more likely to result in a diagnostic biopsy (40.0% vs 100.0%, p = 0.008). There were no complications. CONCLUSIONS: Endomyocardial biopsy forceps offer an additional, novel technique to biopsy presumed ABCs and may improve diagnostic yield.

Outcomes following Free Fibula Physeal Transfer for Pediatric Proximal Humerus Reconstruction: An International Multi-Institutional Study.

BACKGROUND: Vascularized fibula epiphyseal flap was first described in 1998 for proximal humeral reconstruction in children/infants. The authors aim to review their international, multi-institutional, long-term outcomes. METHODS: An international, multi-institutional review (2004 to 2020) was conducted of patients younger than 18 years undergoing free vascularized fibula epiphyseal transfer for proximal humeral reconstruction. Donor- and recipient-site complications, pain, and final ambulatory status were reviewed. Growth of the transferred bone was assessed under the guidance of a pediatric musculoskeletal radiologist. RESULTS: Twenty-seven patients were included with a median age of 7 years (range, 2 to 13 years). Average follow-up was 120 ± 87.4 months. There were two flap failures (7.4%). Recipient-site complications included fracture [ n = 11 (40.7%)], avascular necrosis of the fibula head [ n = 1 (3.7%)], fibular head avulsion [ n = 1 (3.7%)], infection [ n = 1 (3.7%)], and hardware failure [ n = 1 (3.7%)]. Operative fixation was necessary in one patient with a fracture. The case of infection necessitated fibula explantation 2 years postoperatively, and ultimately, prosthetic reconstruction. Sixteen patients developed peroneal nerve palsy (59.3%): 13 of these cases resolved within 1 year (81% recovery), and three were permanent (11.1%). One patient (3.7%) complained of upper extremity pain. Longitudinal growth was confirmed in all but three cases [ n = 24 (88.9%)] at an average rate of 0.83 ± 0.25 cm/year. CONCLUSIONS: The vascularized fibula epiphysis for proximal humerus reconstruction in children preserves the potential for future growth and an articular surface for motion. Peroneal nerve palsy is common following harvest, although this is often transient. Future efforts should be geared toward reducing postoperative morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Pediatric Osteosarcoma: Correlation of Imaging Findings with Histopathologic Features, Treatment, and Outcome.

Osteosarcoma is the most common primary bone sarcoma in children. Imaging plays a pivotal role in diagnostic workup, surgical planning, and follow-up monitoring for possible disease relapse. Survival depends on multiple factors, including presence or absence of metastatic disease, chemotherapy response, and surgical margins. At diagnosis, radiography and anatomic MRI are used to characterize the primary site of disease, whereas chest CT and whole-body bone scintigraphy and/or PET are used to identify additional sites of disease. Treatment starts with neoadjuvant chemotherapy, followed by en bloc tumor resection and limb reconstruction, and finally, adjuvant chemotherapy. Preoperative planning requires precise tumor delineation, which traditionally has been based on high-spatial-resolution anatomic MRI to identify tumor margins (medullary and extraosseous), skip lesions, neurovascular involvement, and joint invasion. These findings direct the surgical approach and affect the options for reconstruction. For skeletally immature children, the risk of cumulative limb-length discrepancy and need for superior longevity of the reconstruction have led to the advent and preferential use of several pediatric-specific surgical techniques, including rotationplasty, joint preservation surgery, autograft or allograft reconstruction, and extendible endoprostheses. A better understanding of the clinically impactful imaging features can directly and positively influence patient care. Online supplemental material is available for this article. ©RSNA, 2022.

Are Junior Residents Competent at Closed Reduction and Casting of Distal Radius Fractures in Children?

BACKGROUND: At many institutions, junior orthopaedic surgery residents perform the closed reduction and casting of pediatric distal radius fractures (DRFs). The purpose of this study was to evaluate the competency of junior residents compared to senior residents in the initial management of pediatric DRFs. METHODS: This investigation was a case-control study analyzing the outcomes of children with displaced DRFs treated by junior versus senior residents. The cohorts were matched with respect to fracture type. Radiographs were measured to assess fracture angulation, displacement, and cast index. Comparisons of patient characteristics, fracture characteristics, and outcome variables were made between the cohorts. RESULTS: A total of 132 patients (99 males; mean age 10.7±2.6 years) were included. Junior residents achieved a similar rate of acceptable initial reduction compared to senior residents (82% versus 79%; p=0.66). Twenty-four (23%) patients were found to have loss of reduction (LOR), though the rate of LOR was similar in the junior (16.7%) and senior resident (28.9%) cohorts (p=0.13). Overall, only 6 patients (3.7%) required surgery (1.5% in junior versus 7.6% in senior; p=0.09). The odds of LOR were 2.7 times higher in the first three reductions of the rotation for all residents (p=0.049). CONCLUSION: Junior residents perform similarly to senior residents in the closed reduction and casting of pediatric DRFs. However, residents performing one of their first three closed reductions during a rotation-regardless of seniority-were more likely to experience subsequent loss of reduction, suggesting the need for close supervision during the beginning of each rotation.Level of Evidence: III.

Magnetic resonance imaging findings of synovial sarcoma in children: location-dependent differences.

BACKGROUND: While overall survival for children is greater than that for adults, synovial sarcoma remains an aggressive neoplasm with a potentially poor prognosis, and its magnetic resonance imaging (MRI) findings in children are not well described. OBJECTIVE: We aimed to characterize the spectrum of MRI findings of synovial sarcoma in children with respect to anatomical location and outcome. MATERIALS AND METHODS: Children with histologically confirmed synovial sarcoma and preoperative MRI performed within the past 11 years (2009-2020) were included. Two radiologists retrospectively reviewed each MRI to categorize location, signal characteristics and associated findings. Chi-square and Fisher exact tests were used to assess associations with locations and outcomes. RESULTS: This study included 23 children (13 girls, 10 boys; mean age: 12.7±4.2 years) with 7 axial, 8 proximal and 8 distal appendicular lesions. Kappa ranged from 0.53 to 1. MRI findings differed significantly between locations with axial lesions measuring larger (P=0.01) and more likely to contain fluid levels (P=0.02), triple sign (P=0.02), inhomogeneous signal (T1-weighted images, P=0.003; T2-weighted images, P=0.02, contrast-enhanced images, P=0.03) with all lesions containing partially solid composition (P=0.03). At a median follow-up of 14 months (interquartile range: 7-33 months), 39% relapsed. Predictors of relapse (P<0.05) included metastasis at presentation, larger lesions, axial lesions and MRI findings of fluid level, T1-weighted hyperintensity, inhomogeneous signal (T1- and T2-weighted images) and poorly circumscribed margins. CONCLUSION: A significant association was found between location and MRI findings in our cohort of children with synovial sarcoma. Axial lesions were more likely to be larger, appear heterogeneous and be associated with a worse outcome.

Nonossifying Fibroma of the Distal Tibia: Predictors of Fracture and Management Algorithm.

BACKGROUND: Nonossifying fibroma (NOF) is a common benign lesion in children and adolescents. This study investigated the risk of pathologic fracture in NOF lesions of the distal tibial based on anatomic location, clinical symptomatology, and imaging features, in order to propose an algorithm for the management of such lesions. METHODS: In an IRB-approved retrospective case-control study, all patients diagnosed with NOF between 2010 and 2017 were extracted from our database. Patients below 18 years of age at the time of diagnosis and with lesions involving the distal tibia were included. Demographic data, the reason for visit, and the mechanism of injury were recorded. Radiographs were reviewed to record the size (absolute and relative to bone width) and location of each lesion. Computed tomography and magnetic resonance imaging examinations were also reviewed when available. Two authors graded all lesions using the Ritschl classification and determined the presence of 2 novel signs: the syndesmosis sign and the Pac-Man sign. RESULTS: A total of 84 patients were included in the final analysis, of which 25 were in the fracture group and 59 in the nonfracture group. None of the patients in the fracture group was previously diagnosed with NOF, but nine (36%) patients had symptoms for >6 months preceding the fracture. Ankle sprain was the most common reason for visit in the nonfracture group. The lateral location of the lesion in the distal tibia (P=0.001), size (P<0.001 for both absolute and relative values), Ritschl stage (P=0.003), syndesmosis sign (P=0.005), and the Pac-Man sign (P=0.002) were significant predictors of fracture. All measurements had almost-perfect to perfect inter-rater agreements. CONCLUSIONS: The most significant imaging risk factors for fracture are a larger size, Ritschl stage B, and the presence of cortical thinning on anteroposterior or lateral radiographs. We introduced 2 signs for these distal tibial NOFs, a scoring system, and a management algorithm that is based on radiographs alone but incorporates advanced imaging findings in equivocal cases. LEVEL OF EVIDENCE: Therapeutic Level III-case-control study.

Do Not Miss the Tumor: A Novel Presentation of Osteosarcoma.

Antalgic gait is a common clinical presentation among pediatric patients and can have many different etiologies, with rare life-threatening etiologies including primary bone malignancies. Osteosarcoma is the most common primary malignancy of bone in pediatric and adolescent patients. The incidence rate of osteosarcoma has been reported as high as 5 to 7 per million among patients 19 years old or younger with males slightly more affected than females and African-Americans more than other racial groups. This report describes the case of a five-year-old African-American female who presented with an antalgic gait secondary to osteosarcoma in the left distal femur and follows her through treatment. In this case, the age is atypical as the peak incidence for osteosarcoma is around 16 years of age and is postulated to coincide with growth spurts. Osteosarcoma can have a range of presentations making it difficult to diagnose, which can cause delays in treatment and potential poor patient outcomes. Due to this, such a diagnosis must be included in the differential for patients presenting with antalgic gait. Because primary-care physicians and pediatricians may be the first medical providers to encounter patients with osteosarcoma, it is imperative that such clinicians are familiar with the signs and symptoms associated with osteosarcomas in order to reduce the risk of metastasis and disease progression and prevent treatment delays. Additionally, we believe these clinicians should have a low threshold to refer patients to orthopedists or oncologic specialists in the cases of persistent pain or inconsistencies with history, physical exam, and diagnostic studies. Finally, direct communication and discussion between radiologists and referring clinicians helps decrease delays in diagnosing of osteosarcoma and other life-threatening conditions.

Excision and Reconstruction of Alveolar Rhabdomyosarcoma Involving the Achilles Tendon in a Pediatric Patient: A Case Report.

CASE: We describe a case of a 9-year-old boy who presented with a left calf mass consistent with alveolar rhabdomyosarcoma involving the Achilles tendon. The patient underwent radical resection of the Achilles tendon and Achilles tendon allograft reconstruction. At 2.5-year follow-up, the child had full ankle range of motion and strength and no signs of disease. CONCLUSIONS: Radical resection of Achilles tendon in the setting of malignancy and reconstruction with allograft is a rare procedure that has not been previously described in the pediatric population. Orthopaedic oncologists can consider this option for the rare malignancies involving the Achilles tendon.

Pre-treatment MRI of leukaemia and lymphoma in children: are there differences in marrow replacement patterns on T1-weighted images?

OBJECTIVES: To investigate the prevalence and distribution of specific marrow patterns on pre-treatment magnetic resonance imaging (MRI) examinations in children with leukaemia and lymphoma and with respect to the anatomic location. MATERIALS AND METHODS: This retrospective IRB-approved and HIPAA-compliant study included children with leukaemia or lymphoma who underwent pre-treatment MRI examinations over 18 years (between 1 January 1995 and 31 August 2013). Two radiologists blinded to the clinical diagnosis reviewed each study to determine the presence or absence of abnormal marrow signal and, when present, sub-categorised the pattern into diffuse, patchy, or focal abnormal marrow. Chi-square and Fisher's exact tests were used to compare marrow patterns between leukaemia and lymphoma. RESULTS: The study included 50 children (32 males and 18 females; mean age 9.5 ± 5.3 years) with 54 MRI examinations (27 leukaemia and 27 lymphoma) that included 26 spine and 28 non-spine studies. Marrow replacement was present on 43 (80%) studies, significantly more common with leukaemia than with lymphoma (p = 0.039). The diffuse replacement pattern was significantly more common with leukaemia when compared to lymphoma (p < 0.001) and the focal pattern was only observed with lymphoma. In the spine, the diffuse pattern was observed with lymphoma (3/14, 21%). All patients with leukaemia and MRI outside of the spine showed marrow involvement. CONCLUSION: Marrow replacement is common on MRI from children with leukaemia and lymphoma. A diffuse pattern was significantly associated with leukaemia on studies outside of the spine and a focal pattern was only observed with lymphoma, independently of the anatomic location. KEY POINTS: • Bone marrow replacement on pre-treatment MRI examinations in children with leukaemia and lymphoma was observed in 93% (25/27) and 67% (18/27), respectively. • Diffuse pattern of marrow replacement was significantly more common in leukaemia even though this pattern was also observed with lymphoma on the spine MRI studies. • Focal pattern of marrow replacement was present only with lymphoma and not with leukaemia regardless of the anatomic location.

Open Reduction of Medial Epicondyle Fractures in the Pediatric Population: Supine Versus Prone Position.

BACKGROUND: Operative treatment of medial epicondyle fractures can be performed in either a supine or prone position. In the supine position, fracture visualization is sometimes difficult due to the posterior position of the medial epicondyle. However, the prone position requires extensive patient repositioning but may improve visualization. The purpose of this study was to compare the results and complications between the supine and prone position when treating medial epicondyle fractures. METHODS: In a retrospective chart review, patients below 18 who underwent open reduction and internal fixation of an acute medial epicondyle fracture from January 2011 to August 2019 were identified. Patients with <2 months follow-up and concomitant fractures were excluded. Surgical variables, outcomes, and complications were recorded and compared between the supine and prone positions. RESULTS: Sixteen surgeons treated the 204 patients evaluated in this study. The mean age was 11.7 years. In all, 122 (60%) patients were treated in the supine position, and 82 (40%) in the prone position. The mean time in the room was 113 minutes in the supine group, and 141 minutes in the prone group (P<0.001). Tourniquet time was similar between groups (P=0.4). Displacement of the fracture on the first postoperative x-rays was 2.06 mm for the supine position and 1.1 mm for the prone position (P<0.001). We also found good interobserver and intraobserver reliability for the measurements. Five patients (2.5%) required reoperation due to stiffness, 2 patients due to nonunion, 1 patient due to tardy ulnar nerve palsy, and 53 (26%) had surgical hardware removal. The surgical position was not associated with complications or reoperation. CONCLUSIONS: While the prone position requires additional time in the operating room, presumably for positioning, the length of the surgical procedure itself does not differ between the 2 positions. Although the trend of the surgeons at our center is towards the prone position, with surgeons that try it usually doing all their subsequent cases that way, both positions provide excellent clinical outcomes with minimal complications. LEVEL OF EVIDENCE: Therapeutic level III-retrospective cohort study.

Pediatric Tumor Management: Current and Controversial.

Bone and soft-tissue tumors are common in the pediatric population. It is important to be familiar with the appropriate workup, principles of biopsy, differences between unicameral and aneurysmal bone cysts, and principles of managing pathologic fractures in children. The management approach to pediatric soft-tissue masses and some of the recent advances in the field warrant discussion.

What's New in Pediatric Orthopaedic Tumor Surgery.

BACKGROUND: Pediatric Orthopaedic Oncology is a developing subspecialty within the field of Pediatric Orthopaedics. Traditionally, the field of Orthopaedic Oncology has been focused on the skeletally mature individual, and the research tends to be all encompassing rather than truly evaluating isolated populations. The purpose of this review is to summarize the most clinically relevant literature in the field of Pediatric Orthopaedic Oncology over the last 6 years. METHODS: We evaluated the PubMed database utilizing keywords for pediatric orthopaedic oncology: sarcoma, osteosarcoma, Ewing sarcoma, bone cyst. In additionally, we further broadened our search by searching for relevant articles in the contents sections of major orthopaedic surgery journals that routinely publish both pediatric and orthopaedic oncology literature. In keeping with "What's New," we selected the most clinically relevant articles published in the last 6 years from January 1, 2014 through February 2020. Basic science and systemic therapies literature was widely reviewed and the research and clinical trials most relevant to pediatric sarcoma and neoplastic processes found in the pediatric population were included. RESULTS: Our search yielded 60 articles that met general criteria, from which 14 were determined to be most relevant to the goals of this paper. Of the papers presented in this review, there were papers related to management of benign tumors/tumor-like conditions, bone cysts, limb salvage procedures, and amputation procedures. Ultimately included in the review were 5 studies related to limb salvage, 4 related to bone cysts, 1 related to multiple hereditary exostoses, 2 related to osteofibrous dysplasia, 1 related to chondroblastoma, and 1 discussing cementation in skeletally immature patients. They were level III, IV, and V studies. Basic science and systemic therapies literature was widely reviewed and the research and clinical trials most relevant to pediatric sarcoma and neoplastic processes found in the pediatric population were included. Our search of the basic science and systemic therapies literature yielded 19 sources were found to be pertinent to our aims and 18 of those sources were published between 2015 and 2020. CONCLUSIONS: There are many, varied, and creative procedures in the realm of limb salvage, though there remains a lack of high-level evidence to support some of the more novel procedures. In regards to benign bone tumors, despite a more solid base of literature, there still does not seem to be consensus as to the best treatment. In particular, there continue to be many schools of thought on the treatment of benign bone cysts. Research in the basic science arena and systemic therapies are advancing in exciting ways in regards to pediatric sarcoma. Orthopaedic oncologic research specific to the pediatric population overall continues to be impeded by low sample sizes and inadequate levels of evidence, which limits the ability of surgeons to draw definitive conclusions from the literature.

Magnetic resonance imaging features of intra-articular tenosynovial giant cell tumor in children.

BACKGROUND: Magnetic resonance imaging (MRI) plays a critical role in disease characterization of intra-articular tenosynovial giant cell tumor. OBJECTIVE: To characterize the MRI features of intra-articular tenosynovial giant cell tumor in children with respect to disease subtype and anatomical location. MATERIALS AND METHODS: This retrospective study included children with tenosynovial giant cell tumor who underwent preoperative MRI between January 2006 and May 2020. Two radiologists reviewed each examination to determine disease subtype, signal intensities and the presence of an effusion, osseous changes, chondromalacia, juxtacapsular disease and concomitant joint involvement. Fisher exact, Mann-Whitney U, and Kruskal-Wallis H tests were used to compare findings between subtypes and locations. RESULTS: Twenty-four children (16 girls, 8 boys; mean age: 13.1±3.8 years) with 19 knee and 5 ankle-hindfoot tenosynovial giant cell tumor had either diffuse (n=15) or localized (n=9) disease. An effusion (P=0.004) was significantly more common with diffuse than localized disease. There was no significant difference in MRI signal (P-range: 0.09-1) or other imaging findings (P-range: 0.12-0.67) between subtypes. Children with knee involvement were significantly more likely to present with diffuse disease while those with ankle-hindfoot involvement all presented with focal disease (P=0.004). Juxtacapsular (n=4) and concomitant proximal tibiofibular joint involvement (n=5) were observed with diffuse disease in the knee. Erosions (P=0.01) were significantly more common in the ankle than in the knee. CONCLUSION: In our study, diffuse tenosynovial giant cell tumor was more common than localized disease, particularly in the knee where juxtacapsular and concomitant proximal tibiofibular joint disease can occur.

Primary Aneurysmal Bone Cyst of the Spine in Children: Updated Outcomes of a Modern Surgical Technique.

OBJECTIVE: Aneurysmal bone cysts (ABC) are benign but locally aggressive lesions. Treating children with spinal ABC poses risks due to the proximity of the lesion to the spinal cord and the need to preserve spinal stability after surgery. This study reports the updated outcomes of a uniform aggressive initial surgical technique for the treatment of spinal ABC in children. METHODS: Twenty-nine cases of spinal ABC were collected from a tertiary pediatric tumor center over a 24-year period (January 1990-September 2014). The study patients were divided into 2 groups based on the performed procedure: a traditional approach consisting of curettage and bone grafting (group 1) and a 4-step approach consisting of intralesional curettage, high-speed bur, electrocautery, and bone grafting (group 2). RESULTS: The study population was composed of 12 males and 17 females with a mean age of 12.2 years at the time of diagnosis and a mean postoperative follow-up of 4.03 years. Twenty-one patients underwent the 4-step approach, while 8 patients were treated with the traditional technique. The recurrence rate was 50% (4/8 patients) with the traditional technique (group 1) and 19% (4/21) in the 4-step technique (group 2) (P = .164). Regardless of the technique used, the presence of sensory symptoms at the time of presentation was a statistically significant factor for recurrence (P = .016). CONCLUSIONS: We suggest that addressing spinal ABC in pediatric patients with a 4-step approach is a safe technique that may decrease long-term recurrence and reoperation rates compared to the traditional technique of intralesional curettage and bone grafting. LEVEL OF EVIDENCE: 4.

Chondroblastoma of the Navicular Bone: A Report of 2 Pediatric Cases.

CASE: Two patients presenting to the clinic with midfoot pain were found to have pathologic fractures through chondroblastomas of the navicular bone. Patient 1 was a 15-year-old boy who experienced multiple recurrences despite more aggressive interventions. Patient 2 was a 13-year-old boy who experienced full recovery after lesion resection. CONCLUSION: Navicular chondroblastoma is a rare site of presentation, with only 3 documented cases. Given the potential aggressive nature of these lesions with significant cortical destruction and soft-tissue extension, the navicular represents a difficult anatomic location to manage.

Pediatric Chondroblastoma and the Need for Lung Staging at Presentation.

PURPOSE: Chondroblastoma is a benign, but potentially locally aggressive, bone tumor with predilection for the epiphysis of long bones in growing children. Historically, there is a reported 2% risk of lung metastasis, however these cases are mostly in the form of isolated single reports and the vast majority in adults. The purpose of this study was to identify the "true" risk of lung metastases at presentation in skeletally immature patients with a benign chondroblastoma, and therefore revisit the need for routine chest staging. METHODS: This was a multi-institution, international retrospective study of children and adolescents diagnosed and treated for a benign chondroblastoma. We focused on the screening and diagnosis of lung metastasis, type of staging utilized and the incidence of local recurrence. Detailed review of the available literature was also performed for comparison. RESULTS: The final studied cohort included 130 children with an average age of 14.5 years (range: 6 to 18 y). There were 94 boys and 36 girls. Lesions more often involved the proximal humerus (32/130), proximal tibia (30/130), and proximal femur (28/130). At an average follow-up of 50 months, there were 15 local recurrences (11% rate) and no cases of lung metastasis. All patients underwent chest imaging at presentation. The overall reported lung metastases rate in the pulled literature review (larger series only) was 0.4% (7/1625), all patients were skeletally mature. CONCLUSIONS: This is the largest cohort of pediatric-exclusive chondroblastoma in the literature. Despite minor differences in management between the centers included, the recurrence rate was similar and there was no evidence of lung metastasis (0 in 130). The incidence of distant involvement in a true benign chondroblastoma in children is much lower than the 2% previously reported in the literature, and the need for routine chest staging should be revisited. LEVEL OF EVIDENCE: Level III.

De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas.

SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes have been shown to cause severe developmental and adult syndromes, referred to as SOXopathies. We here provide evidence that SOX6 variants also cause a SOXopathy. Using clinical and genetic data, we identify 19 individuals harboring various types of SOX6 alterations and exhibiting developmental delay and/or intellectual disability; the individuals are from 17 unrelated families. Additional, inconstant features include attention-deficit/hyperactivity disorder (ADHD), autism, mild facial dysmorphism, craniosynostosis, and multiple osteochondromas. All variants are heterozygous. Fourteen are de novo, one is inherited from a mosaic father, and four offspring from two families have a paternally inherited variant. Intragenic microdeletions, balanced structural rearrangements, frameshifts, and nonsense variants are predicted to inactivate the SOX6 variant allele. Four missense variants occur in residues and protein regions highly conserved evolutionarily. These variants are not detected in the gnomAD control cohort, and the amino acid substitutions are predicted to be damaging. Two of these variants are located in the HMG domain and abolish SOX6 transcriptional activity in vitro. No clear genotype-phenotype correlations are found. Taken together, these findings concur that SOX6 haploinsufficiency leads to a neurodevelopmental SOXopathy that often includes ADHD and abnormal skeletal and other features.

Premature epiphyseal growth plate arrest after isotretinoin therapy for high-risk neuroblastoma: A case series and review of the literature.

BACKGROUND: Vitamin A-derived retinoids have been reported to cause skeletal abnormalities ranging from hypercalcemia to premature epiphyseal closure. Isotretinoin is a retinoid used as standard therapy for high-risk neuroblastoma and has been reported to cause premature epiphyseal growth plate arrest. PROCEDURE: We identified patients from the Children's Hospital Los Angeles (CHLA) database with high-risk neuroblastoma diagnosed from 1991 to 2018 who experienced premature epiphyseal growth plate arrest and compared their characteristics to other patients with high-risk neuroblastoma. We then performed a literature review of this complication. Data collection included diagnosis age of neuroblastoma, presentation age, agent of exposure, dose, exposure range, and skeletal deformity. RESULTS: Among 216 patients, high-risk neuroblastoma was diagnosed before age of five years (n = 165), between ages of 5 and 10 years (n = 41), and after 10 years of age (n = 13). Three out of 216 patients developed premature epiphyseal growth arrest after isotretinoin exposure (overall incidence = 1.38%). The incidence of bony abnormalities was significantly higher in patients diagnosed in 5- to 10-year age group than in other two groups (P = 0.014). Literature review identified eight additional patients with neuroblastoma who presented with retinoid associated skeletal abnormalities. The median range of isotretinoin exposure for these 11 patients was between 6.5 and 7.625 years (range, 2-14) with no cases of isotretinoin therapy completion before age 5 years. CONCLUSION: Bone toxicity associated with isotretinoin exposure is a concern. Growth plate arrest is a serious adverse effect that is attributable to isotretinoin therapy. Our findings suggest the prepubescent growth plate may be most at risk, and we recommend special attention to this population.