The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

Ancient Schwannoma of the Thigh: Metaplastic Ossification, Cartilage Formation, and Extensive Calcification.

Benign soft tissue masses that present with atypical features on imaging may erroneously be diagnosed as malignant processes. An ancient schwannoma, a schwannoma variant with pronounced degenerative features, is one possible etiology of an incidental soft tissue tumor. This case report describes a 69-year-old male with a history of lung carcinosarcoma who presented to the orthopedic oncology office following an incidental positron emission tomography-computed tomography (PET-CT) finding of a posterior, lateral thigh mass with extensive calcifications. Subsequent excision and pathological analysis revealed an ancient schwannoma with advanced degenerative features, including metaplastic bone and cartilage formation. Various degenerative changes may typically be identified with pathological analysis. In addition to the degenerative findings on pathological analysis, our case highlights an atypical instance where extensive calcification and ossification are evident radiographically. This case emphasizes the importance of considering ancient schwannoma when a calcified soft tissue mass is encountered, in addition to the list of more common calcified soft tissue masses.

Right Biceps Pseudo-Tumor from COVID-19 Vaccination.

Delayed hypersensitivity reactions (DHRs) have been reported in association with COVID-19 vaccines, particularly those that are mRNA-based. Classic DHRs result in induration, erythema, tenderness, and urticaria. However, soft tissue mass is an uncommon complication of a COVID-19 vaccination-associated DHR and is rarely reported in the literature. We present a case of a 49-year-old male who recognized a mildly painful, firm soft tissue mass within the biceps mimicking neoplasm six months after receiving the booster dose of the Moderna vaccine. Non-operative conservative treatment modalities, including heating pads, ice packs, acetaminophen, and ibuprofen, failed to improve the patient's mass. The mass, which proved histologically to be an inflammatory pseudo-tumor, did not recur after complete excision. While there have been many reported cases of DHRs following COVID-19 vaccinations, we present this case to raise awareness of the development of pseudo-tumors as a possible, yet rare, clinical manifestation of DHRs following vaccination.

Nonossifying Fibroma Involving Epiphysis of Long Bone-Case Report and Review of the Literature.

Nonossifying fibroma (NOF) is a common benign bone neoplasm and is usually observed in the first 2 decades of life. Most NOFs occur in the metaphysis of long bones of the lower extremities and migrate toward the diaphysis during skeletal maturation. Epiphyseal involvement by NOF has been rarely reported, with only one case found in the English literature. The authors report the second case of NOF involving the epiphysis of a long bone, the proximal tibia of a 21-year-old woman. Clinicians and pathologists should be aware of the rare possibility of epiphyseal involvement of long bones by this condition. Pathologists should select appropriate immunohistochemistry markers to rule out alternative diagnoses.

A Case Report of Progressive Paget Disease Mimicking a Malignancy: A Second Episode 21 Years Later.

Paget osteosarcoma is a rare but serious complication of Paget disease requiring immediate management before further malignant transformation. This case report examines the progression of a previously reported case of Paget disease with atypical pseudotumor manifestation, mimicking osteosarcoma over a 21-year time lapse. After presenting with substantial pain and elevated alkaline phosphatase levels, imaging proved extensive bony expansion of the lesion with high-grade trabecular and cortical thickening and extraosseous soft-tissue extension, prompting the need for biopsy to rule out Paget sarcoma. The atypical features of the pseudotumor's development helps distinguish key radiographic and clinical criteria for malignant development.

Extramedullary Hematopoiesis Adjacent to Vertebral Fracture in a Patient with Pernicious Anemia: Support for a Mechanical Extrusion Mechanism.

CASE: A 68-year-old woman presented with a paraspinal mass of indeterminate imaging characteristics. Workup and computed tomography-guided Fine Needle Aspiration (FNA) aspiration revealed extramedullary hematopoiesis (EMH) adjacent to a prior compression fracture in the setting of pernicious anemia. CONCLUSION: The combination of findings suggests a possible relationship of the compression fracture and the EMH because of traumatic extravasation of marrow contents, with the patient's underlying anemia possibly providing an underlying predisposition to EMH.

Shoulder Pseudo-Tumor from COVID-19 Vaccine.

Hypersensitivity reactions to the COVID-19 mRNA vaccines were identified in the initial 2020 trials. Appearance of a soft tissue mass is a rare manifestation of this hypersensitivity reaction. In this patient, bilateral injections resulted in the appearance of shoulder masses. Magnetic resonance imaging showed localized pseudo-tumorous edema in both shoulders, one subcutaneous and the other intramuscular. This is only the second case of a mass-like reaction to the COVID-19 vaccine mimicking a possible soft tissue neoplasm. Improper vaccination administration technique may have contributed to this complication. The case is presented to increase awareness of this potential pseudotumor.

Cell cycle arrest and apoptosis are early events in radiosensitization of EWS::FLI1+ Ewing sarcoma cells by Mithramycin A.

PURPOSE: The oncogenic fusion protein EWS::FLI1 is an attractive therapeutic target in Ewing sarcoma (ES). Mithramycin A (MithA) is a potent and specific inhibitor of EWS::FLI1 that can selectively radiosensitize ES cells through transcriptional inhibition of DNA double-strand break (DSB) repair. Here, we evaluate temporal changes in cell cycle progression and apoptosis in ES cells treated with MithA and/or ionizing radiation (RTx), testing the hypothesis that combining MithA with ionizing radiation would synergistically impair cell cycle progression and enhance apoptotic elimination to a greater extent than either agent alone. MATERIALS AND METHODS: Four EWS::FLI1+ ES cell lines TC-71, RD-ES, SK-ES-1, and A673, and one EWS::ERG cell line (CHLA-25) were exposed to 10nM MithA or vehicle and followed 24 h later by exposure to 2 Gy x-radiation or sham irradiation. Reactive oxygen species (ROS) activity was evaluated by cytometric assay, and assay of antioxidant gene expression by RT-qPCR. Cell cycle changes were evaluated by flow cytometry of nuclei stained with propidium iodide. Apoptosis was assessed by cytometric assessment of Caspase-3/7 activity and by immunoblotting of PARP-1 cleavage. Radiosensitization was evaluated by clonogenic survival assay. Proliferation (EdU) and apoptosis (TUNEL) were evaluated in SK-ES-1 xenograft tumors following pretreatment with 1 mg/kg MithA, followed 24 h later by a single 4 Gy fraction of x-radiation. RESULTS: MithA-treated cells showed reduced levels of ROS, and were associated with increased expression of antioxidant genes SOD1, SOD2, and CAT. It nonetheless induced persistent G0/G1 arrest and a progressive increase of the sub-G1 fraction, suggesting apoptotic degeneration. In vitro assays of Caspase-3/7 activity and immunoblotting of Caspase-3/7 dependent cleavage of PARP-1 indicated that apoptosis began as early as 24 h after MithA exposure, reducing clonogenic survival. Tumors from xenograft mice treated with either radiation alone, or in combination with MithA showed a significant reduction of tumor cell proliferation, while apoptosis was significantly increased in the group receiving the combination of MithA and RTx. CONCLUSIONS: Taken together, our data show that the anti-proliferative and cytotoxic effects of MithA are the prominent components of radiosensitization of EWS::FLI1+ ES, rather than the result of acutely enhanced ROS levels.

Modification to Mirels scoring system location component improves fracture prediction for metastatic disease of the proximal femur.

BACKGROUND: Correctly identifying patients at risk of femoral fracture due to metastatic bone disease remains a clinical challenge. Mirels criteria remains the most widely referenced method with the advantage of being easily calculated but it suffers from poor specificity. The purpose of this study was to develop and evaluate a modified Mirels scoring system through scoring modification of the original Mirels location component within the proximal femur. METHODS: Computational (finite element) experiments were performed to quantify strength reduction in the proximal femur caused by simulated lytic lesions at defined locations. Virtual spherical defects representing lytic lesions were placed at 32 defined locations based on axial (4 axial positions: neck, intertrochanteric, subtrochanteric or diaphyseal) and circumferential (8 circumferential: 45-degree intervals) positions. Finite element meshes were created, material property assignment was based on CT mineral density, and femoral head/greater trochanter loading consistent with stair ascent was applied. The strength of each femur with a simulated lesion divided by the strength of the intact femur was used to calculate the Location-Based Strength Fraction (LBSF). A modified Mirels location score was next defined for each of the 32 lesion locations with an assignment of 1 (LBSF > 75%), 2 (LBSF: 51-75%), and 3 (LBSF: 0-50%). To test the new scoring system, data from 48 patients with metastatic disease to the femur, previously enrolled in a Musculoskeletal Tumor Society (MSTS) cross-sectional study was used. The lesion location was identified for each case based on axial and circumferential location from the CT images and assigned an original (2 or 3) and modified (1,2, or 3) Mirels location score. The total score for each was then calculated. Eight patients had a fracture of the femur and 40 did not over a 4-month follow-up period. Logistic regression and decision curve analysis were used to explore relationships between clinical outcome (Fracture/No Fracture) and the two Mirels scoring methods. RESULTS: The location-based strength fraction (LBSF) was lowest for lesions in the subtrochanteric and diaphyseal regions on the lateral side of the femur; lesions in these regions would be at greatest risk of fracture. Neck lesions located at the anterior and antero-medial positions were at the lowest risk of fracture. When grouped, neck lesions had the highest LBSF (83%), followed by intertrochanteric (72%), with subtrochanteric (50%) and diaphyseal lesions (49%) having the lowest LBSF. There was a significant difference (p < 0.0001) in LBSF between each axial location, except subtrochanteric and diaphyseal which were not different from each other (p = 0.96). The area under the receiver operator characteristic (ROC) curve using logistic regression was greatest for modified Mirels Score using site specific location of the lesion (Modified Mirels-ss, AUC = 0.950), followed by a modified Mirels Score using axial location of lesion (Modified Mirels-ax, AUC = 0.941). Both were an improvement over the original Mirels score (AUC = 0.853). Decision curve analysis was used to quantify the relative risks of identifying patients that would fracture (TP, true positives) and those erroneously predicted to fracture (FP, false positives) for the original and modified Mirels scoring systems. The net benefit of the scoring system weighed the benefits (TP) and harms (FP) on the same scale. At a threshold probability of fracture of 10%, use of the modified Mirels scoring reduced the number of false positives by 17-20% compared to Mirels scoring. CONCLUSIONS: A modified Mirels scoring system, informed by detailed analysis of the influence of lesion location, improved the ability to predict impending pathological fractures of the proximal femur for patients with metastatic bone disease. Decision curve analysis is a useful tool to weigh costs and benefits concerning fracture risk and could be combined with other patient/clinical factors that contribute to clinical decision making.

Orchestrated delivery of PTH [1-34] followed by zoledronic acid prevents radiotherapy-induced bone loss but does not abrogate marrow damage.

Postradiotherapy bone fragility fractures are a frequent late-onset complication in cancer survivors. There is a critical need to develop preventative interventions, and the use of Food and Drug Administration-approved drugs remains an attractive option. Prior data from our lab and others have shown that parathyroid hormone [1-34] mitigates radiotherapy-induced bone loss, but only for the duration of drug delivery. Utilizing a murine hindlimb radiotherapy model, we investigated whether orchestrated delivery of single-dose zoledronic acid could extend these anabolic benefits after cessation of parathyroid hormone delivery. We then explored the potential use of parathyroid hormone as a bone marrow radioprotectant. While the addition of zoledronic acid to parathyroid hormone increased irradiated bone mass, there was no increase in femur bending strength. In this model, the parathyroid hormone was not effective as a marrow radioprotectant, although this could be due to the short course of parathyroid hormone treatment. Marrow repopulation kinetics differed from those in total body irradiation, with hematopoietic stem cell repopulation occurring relatively early at four weeks postirradiation. Furthermore, we found radiation induced a loss of marrow stromal cells and an increase in inflammatory monocytes. Statement of Clinical Significance: Staged delivery of parathyroid hormone and zoledronic acid shows promise as an off-the-shelf intervention to mitigate post-radiotherapy bone damage in cancer patients, but parathyroid hormone is unlikely to function as a broad-spectrum marrow radioprotectant.

Evaluation of triage tool for low-grade cartilage tumors: Four-quadrant approach.

BACKGROUND AND OBJECTIVES: The "four-quadrant approach" (FQA) for triage of benign enchondromas (E) and low-grade malignant chondrosarcomas (LGC) divides patients into treatment categories based on the presence or absence of pain and observation of aggressive or benign radiographic features. This article evaluates the usefulness of the FQA in predicting E versus LGC and operative versus nonoperative outcome. METHODS: Patients had working diagnosis of E or LGC, 1-year minimum follow-up, imaging, clinical data, outcomes, and no radiographic evidence of high-grade chondrosarcoma. Statistical analysis determined whether quadrant distribution correlated to E versus LGC and operative versus nonoperative intervention. RESULTS: Of 56 lesions (49 patients), 9 were LGC and 47 E. Twenty-five lesions (all 9 LGC, 16 E) were treated operatively and 31 (all E) nonoperatively. There were statistically significant correlations between quadrant distribution and both tumor type (p = 1.9 × 10-6 ) and operative intervention (p = 6.28 × 10-6 ). CONCLUSIONS: The FQA is a promising diagnostic tool to distinguish between E and LGC hyaline cartilage tumors, along with determining operative versus nonoperative intervention. Prospective evaluation is warranted.

Prophylactic surgical treatment using CT-based rigidity analysis vs. after the fact fracture treatment of pathologic femoral lesions.

Background: Accurate comparison of prophylactic surgical treatment (PST) to after fracture treatment (AF) of patients with femoral metastatic disease requires more accurately identifying patients for impending fracture, such as with CT-based structural rigidity analysis (CTRA). This study compares a more accurately defined PST group (of impending fractures defined by CTRA) to AF for metastatic femoral disease. Methods: PST patients were enrolled and treated by the PI in a longitudinal multicenter study of impending pathologic fractures evaluated for accuracy by CTRA. The AF patients were also treated by the senior author and were identified by retrospective chart review. Fifty-five patients were treated surgically for metastatic femoral lesions and were divided into three groups for the purpose of this study: Group I (AF), Group II (PST-high), and Group III (PST-low). Demographic information, comorbidities, and clinical variables of interest were collected by retrospective chart review; cost data was collected by collaboration with our hospital financial personnel (office of the Chief Financial Officer). Results: Survival showed statistically significant differences favoring Group II. Transfusions in Group I were nearly twice those of Groups II and III, but there was no statistically significant (NS) difference between groups. Estimated blood loss (EBL) was generally with NS difference. Similarly, there were NS differences in LOS between groups. Discharge disposition showed statistically significant differences between groups (P=0.012, global). Discharge to home was highest in Group II (76%) and lowest in Group I (27%). Discharge to rehab was lowest in Group II (24%) and highest in Group I (47%). There were no discharges to hospice or morgue in Group II, while both occurred in Group I. Mean direct and total costs were highest in Group I ($18,837 and $31,997, respectively) and lowest in Group II ($16,094 and $27,357) but the differences were NS. Conclusions: This study shows benefits of PST over AF in a group of PST patients more accurately defined to have impending pathologic fractures by CTRA definition.

Total Femoral Replacement for Complicated Echinococcus Infection: Sixteen-Year Follow-up.

CASE: Osseous hydatidosis caused by Echinococcus is rare, especially in long bones. To the best of our knowledge, this is the third femoral hydatidosis case with successful osseous eradication through total femoral resection and total femoral megaprosthesis. Unlike the previous 2 cases, we uniquely illustrate recurrent soft-tissue hydatidosis episodes requiring additional hydatid resections for local control with no evidence of disease at final 16-year follow-up, the longest follow-up period of the 3 reported cases. CONCLUSION: Despite radical bone resection for osseous hydatidosis eradication, additional complex surgical interventions may be needed to locally control soft-tissue disease.

Predicting Fracture Risk in Patients with Metastatic Bone Disease of the Femur: A Pictorial Review Using Three Different Techniques.

One of the key roles of an orthopedic surgeon treating metastatic bone disease (MBD) is fracture risk prediction. Current widely used impending fracture risk tools such as Mirels scoring lack specificity. Two newer methods of fracture risk prediction, CT-based structural rigidity analysis (CTRA) and finite element analysis (FEA), have each been shown to be more accurate than Mirels. This case series illustrates comparative Mirels, CTRA, and FEA for 8 femurs in 7 subjects. These cases were selected from a much larger data set to portray examples of true positives, true negatives, false positives, and false negatives as defined by CTRA relative to the fracture outcome. Case illustrations demonstrate comparative Mirels and FEA. This series illustrates the use, efficacy, and limitations of these tools. As all current tools have limitations, further work is needed in refining and developing fracture risk prediction.

Proximal humerus reconstruction in orthopedic oncology.

Proximal humeral reconstructive options following radical resection of proximal humeral primary and metastatic bone malignancies have evolved over time. With the relatively recent advent of the reverse total shoulder (RTSA), this technique has been increasingly employed in this setting over hemiarthroplasty techniques. An array of options, including proximal humeral allograft-prosthetic composites (including both RTSA and hemiarthroplasty), megaprostheses, and osteoarticular allografts, is reviewed from the perspective of their indications, techniques, complications, and published results. An extensive case-based pictorial presentation illustrates these options.