Development of a Model System to Evaluate Local Recurrence in Osteosarcoma and Assessment of the Effects of Bone Morphogenetic Protein-2.

PURPOSE: It is increasingly relevant to better define what constitutes an adequate surgical margin in an effort to improve reconstructive longevity and functional outcomes following osteosarcoma surgery. In addition, nonunion remains a challenging problem in some patients following allograft reconstruction. Bone morphogenetic protein-2 (BMP-2) could enhance osseous union, but has been historically avoided due to concerns that it may promote tumor recurrence. EXPERIMENTAL DESIGN: An orthotopic xenograft murine model was utilized to describe the natural temporal course of osteosarcoma growth. Tumors were treated either with surgery alone, surgery and single-agent chemotherapy, or surgery and dual-agent chemotherapy to assess the relationship between surgical margin and local recurrence. The effect of BMP-2 on local recurrence was similarly assessed. RESULTS: Osteosarcoma tumor growth was categorized into reproducible phases. Margins greater than 997 µm resulted in local control following surgery alone. Margins greater than 36 µm resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 µm resulted in local control following surgery and dual-agent chemotherapy. The application of exogenous BMP-2 does not confer an increased risk of local recurrence. CONCLUSIONS: This model reliably reproduces the clinical, radiographic, and surgical conditions encountered in human osteosarcoma. It successfully incorporates relevant chemotherapy, further paralleling the human experience. Surgical margins required to achieve local control in osteosarcoma can be reduced using single-agent chemotherapy and further decreased using dual-agent chemotherapy. The application of BMP-2 does not increase local recurrence in this model.

Aspergillus osteomyelitis of the proximal humerus: a case report.

Aspergillus osteomyelitis is an extremely rare manifestation of invasive aspergillosis. Generally, patients in states of significant immune deficiency are very susceptible to invasive aspergillosis. We report a case of Aspergillus osteomyelitis of the proximal humerus in an immunocompetent patient that required aggressive oral antifungal therapy, surgical debridement, and placement of an antifungal-impregnated cement spacer. Subsequently, her shoulder was reconstructed using a reverse total shoulder prosthesis The clinical course, radiographic findings, histology, and management rationale are presented.

Mesenchymal chondrosarcoma: clinicopathologic study of 20 cases.

CONTEXT: Mesenchymal chondrosarcoma is a rare, high-grade malignancy of bone or soft tissue with a unique, biphasic histology and poor prognosis. Because of its rarity and variable length of disease-free survival, the natural history of the disease remains poorly understood. OBJECTIVE: To present clinical, radiographic, and histopathologic features of mesenchymal chondrosarcoma from one of the largest case series collected by a single, senior-level bone pathologist. DESIGN: Twenty cases were reviewed in consultations spanning 45 years. RESULTS: Eighteen tumors (90%) originated in bone, and 2 tumors (10%) were of extraskeletal origin. Of the skeletal tumors, locations included craniofacial bones (n  =  9; 50%), ribs and chest wall (n  =  4; 22%), sacrum and spinal elements (n  =  3; 17%), and lower extremities (n  =  2; 11%), whereas soft tissue tumors were located about the scapula (n  =  1; 50%) and lower extremity (n  =  1; 50%). Plain radiographs demonstrated calcified, osteolytic lesions with extraosseous extension. Typical histologic features were identified consisting of small, round or spindled cells, interspersed with hyaline cartilage islands. Seventeen patients (85%) were treated surgically, and 8 patients (40%) received adjuvant treatment. Seven patients (35%) were living at last follow-up, 1.8 to 12.5 years after diagnosis, and 8 patients (40%) died between 1.2 and 21.8 years after diagnosis. CONCLUSIONS: Mesenchymal chondrosarcoma presents multiple challenges. Diagnostic pitfalls include inadequate biopsy samples, which may result in sample error. Sox9 has been proposed as a unique marker for mesenchymal chondrosarcoma which may improve diagnostic specificity. Treatment and prognosis vary considerably. Patients who receive surgery and chemotherapy seem to fare better. Multicenter studies with higher sample numbers may improve our understanding of this malignancy.

A novel EWSR1-CREB3L1 fusion transcript in a case of small cell osteosarcoma.

Cellular morphology of small cell osteosarcoma, an aggressive variant of osteosarcoma, is similar to Ewing sarcoma, but its molecular pathogenesis is largely unknown. We report the case of a 12-year-old girl with multifocal small cell osteosarcoma positive for the Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement by interphase fluorescent in situ hybridization and negative for EWSR1-FLI1, EWSR1-ERG, and EWSR1-WT1 fusion transcripts by reverse transcriptase PCR. Rapid amplification of cDNA ends revealed exon 6 of the cAMP-responsive element binding protein 3-like 1 gene (CREB3L1, also known as "OASIS," NM_52854.2) fused in-frame to the EWSR1 exon 11, consistent with the EWSR1-CREB3L1 fusion transcript expressed in tumor tissue. The corresponding chimeric gene was confirmed by amplification and subsequent sequencing of the genomic breakpoint between introns 11 and 5 of EWSR1 and CREB3L1, respectively. An ∼70 kDa product in the tumor tissue lysate reacted with the CREB3L1 carboxyterminal antibody, consistent with a 656-amino acid predicted chimeric protein. Immunohistochemistry with the same antibody showed signal translocation from the physiologic perinuclear compartment observed in glia and unrelated osteoblasts to nuclei of tumor cells, consistent with the likely function of EWSR1-CREB3L1 as a transcriptional regulator predicted by its structure. This is the first report of a fusion transcript in osteogenic sarcoma; it demonstrates a relation between molecular mechanisms of small cell osteogenic and Ewing sarcomas. The 3'-end partner and the inferred structure of EWSR1-CREB3L1, however, are different from those of Ewing sarcoma, suggesting different targets of the new oncogene.

Aggressively recurrent infantile myofibroma of the axilla and shoulder girdle.

Infantile myofibroma is the most common fibrous tumor of infancy, typically affecting neonates and children under 2 years of age. Though the multicentric variant portends a grave prognosis, solitary lesions have an excellent prognosis and frequently undergo spontaneous regression. Surgical excision of solitary lesions is usually curative. In this report, we describe a pediatric patient with an unusually aggressive solitary myofibroma of the axilla who ultimately required a forequarter amputation as a lifesaving measure following multiple tumor recurrences and progressive tumor growth. The clinical course, radiographic findings, histology, and management rationale are presented.

Cryptococcal pyarthrosis and sarcoidosis.

Cryptococcus neoformans is an infrequent cause of septic arthritis. Cryptococcal infections have been linked to sarcoidosis because of both inherent immunologic consequences of the disease and its typical immune modulating treatments. Cryptococcal infections should be suspected in patients with underlying immune deficiencies, and a high degree of vigilance should be exercised to avoid misdiagnosis, dissemination of infection, and meningitis.

Aggressive (epithelioid) osteoblastoma arising in soft tissue.

Aggressive (epithelioid) osteoblastoma arising in soft tissue has never been described. It is important to differentiate this benign osteoblastoma, a potentially locally aggressive tumor, from extraskeletal osteosarcoma. This report describes an aggressive (epithelioid) osteoblastoma arising in a focus of heterotopic ossification in the axilla of a 21-year-old man.