Faculty Bibliography

INTRODUCTION: This study evaluated the safety and efficacy of radiotherapy (RT) with concurrent novel agents (NAs), cytotoxic therapy (CTx), or both in the management of osteolytic bone lesions in multiple myeloma (MM). PATIENTS AND METHODS: A total of 39 patients with MM received RT to 64 different bone sites during the 2007-2012 period, with a dose of 8 to 37.5 Gy (mean, 26.8 Gy) delivered in 1 to 15 fractions (median, 10 fractions). Of these patients, 21 also received concurrent NAs or CTx. Pain response, M protein and kappa light chain response, and adverse events were evaluated. RESULTS: RT was completed in 35 of 39 patients (89.7%) in this study. Pain relief was observed in 30 of 31 patients (96.7%). Hematologic toxicity (grade 3 or 4 by the Radiation Therapy Oncology Group system) was seen in 43.2% of treated patients, and NA therapy was stopped in 2 patients owing to grade 4 toxicity. RT adverse effects resolved at 4 to 6 weeks posttreatment. Changes in pre- and posttreatment levels of M protein trended toward significance in patients treated with RT + systemic therapy (ST) versus. RT alone (DeltaM ProteinRT+ST = 5.6 g/L; DeltaM ProteinRT = 0 g/L; P = .089). CONCLUSION: Treating MM with RT concurrently with CTx including NAs was safe and well tolerated in the majority of patients (14 of 16 [87.5%] for those taking NAs and 19 of 21 [90.5%] for all patients). Excellent clinical pain response (> 95%) was also seen in patients regardless if they were treated with RT + ST or RT alone.

Glomus tumors are neuromyoarterial glomus body neoplasms that most commonly occur in the subungual areas of the hand. These tumors typically present as painful solitary lesions with localized tenderness. Extradigital glomus tumors are rare and difficult to diagnose because of their varying symptoms and presentation. Misdiagnosis can result in significant chronic pain, disuse syndromes, and disability over prolonged periods. Timely diagnosis and surgical resection are generally curative with complete resolution of symptoms. Surgeons should be aware of this rare condition and consider it in the differential diagnosis when treating a painful soft-tissue mass of the wrist. We report a case of a large solitary glomus tumor that occurred on the volar-radial aspect of the wrist and involved the radial artery. The patient was successfully treated with complete surgical excision of the tumor. There were no symptoms or recurrence at 3-year follow-up. In the literature, this is the first case of large atypical wrist glomus tumor involving the radial artery to be reported with corresponding magnetic resonance imaging, intraoperative, histology, and immunohistochemistry findings.

Bone and soft tissue sarcomas are rare diagnoses in the orthopedic patient population. Without rapid evaluation and proper treatment, mortality is increased in these patients. The purpose of our study is to identify factors associated with a variance of care in bone and soft tissue sarcoma patients within a large urban hospital system. Our study retrospectively reviewed the charts of 117 patients with orthopedic tumors at both private and public hospital settings, and we recorded their treatment course. Race, insurance type, and hospital type were associated with variations in sarcoma care in our large urban hospital system. Surgeons should be aware of these variances when treating these groups of patients.

Both early and late complications following open reduction and internal fixation of proximal humerus fractures have been reported extensively in the literature. Although orthopedic implants are known to cause irritation and inflammation, to our knowledge, this is the first case report to describe a patient with rice bodies secondary to an orthopedic implant. Although the etiology of rice bodies is unclear, histological studies reveal that they are composed of an inner amorphous core surrounded by collagen and fibrin. The differential diagnosis in this case included synovial chondromatosis, infection, and the formation of a malignant tumor. Additional imaging studies, such as magnetic resonance imaging, and more specific tests were necessary to differentiate the rice bodies due to bursitis versus neoplasm, prior to excision. The patient presented 5 years following open reduction and internal fixation of a displaced proximal humerus frature, with swelling in the area of the previous surgical site. Examination revealed a large, painless tumor-like mass on the anterior aspect of the shoulder. The patient's chief concern was the unpleasant aesthetic of the mass; no pain was reported. Upon excision of the mass, the patient's full, painless range of motion returned.

Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor-initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine osteosarcoma (mOS) cell lines as well as in the tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by short-hairpin RNAs in independent mOS-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted osteosarcoma cells can no longer form osteospheres and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these cells maintain a requirement for Sox2 for tumorigenicity. Our data indicate that Sox2 is required for osteosarcoma cell self renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self renewal in osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of osteosarcomas.Oncogene advance online publication, 19 September 2011; doi:10.1038/onc.2011.405

Aneurysmal bone cysts are rare skeletal tumors that most commonly occur in the first two decades of life. They primarily develop about the knee but may arise in any portion of the axial or appendicular skeleton. Pathogenesis of these tumors remains controversial and may be vascular, traumatic, or genetic. Radiographic features include a dilated, radiolucent lesion typically located within the metaphyseal portion of the bone, with fluid-fluid levels visible on MRI. Histologic features include blood-filled lakes interposed between fibrous stromata. Differential diagnosis includes conditions such as telangiectatic osteosarcoma and giant cell tumor. The mainstay of treatment is curettage and bone graft, with or without adjuvant treatment. Other management options include cryotherapy, sclerotherapy, radionuclide ablation, and en bloc resection. The recurrence rate is low after appropriate treatment; however, more than one procedure may be required to completely eradicate the lesion.

Incidental bone tumors are, by definition, asymptomatic lesions that are discovered through routine radiographs obtained for other reasons. Generally, these lesions are benign and latent, requiring no further intervention except observation. However, occasionally these radiographs will detect benign aggressive processes or even malignant lesions that do require further treatment and referral to a tumor specialist. Oftentimes, there are characteristic findings on radiographs that are pathognomonic. Knowledge of these findings can simplify the treatment algorithm for a practicing general orthopaedist. This article will describe radiographic characteristics of benign and malignant bone lesions and their typical presentations. It will then focus on the types of bone lesions that are often found incidentally by routine radiography. Specific recommendations, including recommendation for referrals to orthopaedic tumor specialists, will be noted for lesions described. Most malignant lesions will present with pain and a constellation of history and physical exam findings that will signal the patient to seek medical care; although they will be mentioned for the sake of comparison and completeness, they will not be the focus of this review.

Skeletal metastases are common in the adult population. The proximal femur is a frequently affected bone in the appendicular skeleton. The orthopaedic surgeon may be the first to find a pathologic lesion of the proximal femur and appropriate diagnosis and nonoperative management is essential prior to surgical treatment. Bisphosphonates and radiation therapy are used in conjunction with surgical management to minimize pain and prevent further destruction. Surgical management may consist of internal fixation, with or without polymethylmethacrylate, or endoprosthesic replacement. The goal of treatment is to relieve pain and allow for function while minimizing systemic complications

Musculoskeletal tumors, both primary neoplasms and metastatic lesions, present a therapeutic challenge for the physician who wishes to provide palliative pain relief using the least invasive approach. The increasing sophistication of imaging modalities such as CT in precisely localizing neoplasm, coupled with the widespread use of radiofrequency ablation (RFA) for treatment of other types of tumor, has generated interest in using RFA to treat musculoskeletal tumors. Primary bone tumors (eg, osteoid osteoma) and metastatic bone tumors have been successfully treated with RFA. Success rates with RFA are equal to those with standard surgical curettage, but RFA has the advantage of decreased surgical morbidity. The procedure is relatively safe, is well-tolerated by the patient, and typically can be performed on an outpatient basis. The most common serious complication reported is localized skin necrosis, which occurs rarely. RFA appears to be a viable minimally invasive approach for palliative treatment of selected bone tumors.