Association of EWS-FLI1 Type 1 Fusion with Lower Proliferative Rate in Ewing’s Sarcoma

The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway

Prostatic sarcoma after treatment of rectal cancer

<p>Abstract</p> <p>Background</p> <p>The relationship between radiation exposure for treatment of cancer and occurrence of a second primary cancer at the irradiated site is well known. This phenomenon is however rare in prostate.</p> <p>Case presentation</p> <p>A 75-year-old farmer was treated for rectal cancer with preoperative 45 Gy of radiotherapy and abdominoperineal resection. Four years later he developed symptoms of bladder outlet obstruction and acute urinary retention. He underwent a transurethral resection of the prostate. Histological examination of the removed prostate tissue and immunohistochemistry revealed it to be a poorly differentiated sarcoma.</p> <p>Conclusion</p> <p>We believe this to be the first reported case of radiation-induced sarcoma following radiotherapy treatment for rectal cancer. Since radiotherapy plays a pivotal role in the contemporary treatment of rectal adenocarcinoma, it is relevant to be aware of the potential long-term carcinogenic complications of radiotherapy of the pelvis.</p

Osteoid osteoma of the ethmoid bone associated with dacryocystitis

BACKGROUND: Osteoid osteomas (OO) are small, benign osteoblastic lesions. Ethmoid bone OO has been very rarely reported so far. CASE PRESENTATION: We report a case of a 16-year-old boy suffering from persistent epiphora and a mild pain in the area of median canthus, due to a bone density mass within the right ethmoid air cells extending to the ipsilateral right orbit. The mass was removed via an external ethmoidectomy approach. Histopathologic examination of the specimen set the diagnosis of OO. One year after the operation the patient is free of symptoms, while no recurrence occurred. CONCLUSION: A case of ethmoid bone OO associated with dacryocystitis is reported. Although benign and rare, OO should be considered in differential diagnosis of the ethmoid bone osteoblastic lesions

CT and MR imaging in the local staging of primary malignant musculoskeletal neoplasms: Report of the Radiology Diagnostic Oncology Group.

PurposeTo assess the relative accuracies of computed tomography (CT) and magnetic resonance (MR) imaging in the local staging of primary malignant bone and soft-tissue tumors.Materials and methodsAt four institutions, 367 eligible patients (aged 6-89 years) with malignant bone or soft-tissue neoplasms in selected anatomic sites were enrolled. Patients underwent both CT and MR imaging within 4 weeks before surgery. In each patient, CT scans were interpreted independently by two radiologists and MR images by two other radiologists at the enrolling institution. The CT and MR images were then interpreted together by two of those radiologists and subsequently reread at the other institutions. Imaging and histopathologic findings were compared and were supplemented when needed with surgical findings. Receiver operating characteristic curve analysis and descriptive statistical analysis were performed.ResultsCases were analyzable in 316 patients: 183 had primary bone tumors; 133 had primary soft-tissue tumors. There was no statistically significant difference between CT and MR imaging in determining tumor involvement of muscle, bone, joints, or neurovascular structures. The combined interpretation of CT and MR images did not statistically significantly improve accuracy. Interreader variability was similar for both modalities.ConclusionCT and MR imaging are equally accurate in the local staging of malignant bone and soft-tissue neoplasms in the specific anatomic sites studied

Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma: 63 patients with a minimum follow-up of 4 years

Background and purpose The Scandinavian Sarcoma Group (SSG) XIV protocol is based on experience from previous SSG trials and other osteosarcoma intergroup trials, and has been considered the best standard of care for patients with extremity localized, non-metastatic osteosarcoma. We analyzed the outcome in 63 consecutive patients. Patients and methods From 2001 through 2005, 63 patients recruited from centers in Sweden, Norway, and Finland were included. They received preoperative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m(2)), cisplatin (90 mg/m(2)), and doxorubicin (75 mg/m(2)). 3 cycles were administered post-operatively, and poor histological responders were given 3 additional cycles of ifosfamide (10-12 g/m(2)) as a salvage strategy. Results With a median follow-up of 77 months for survivors, the estimated metastasis-free and sarcoma-related survival at 5 years was 70% and 76%, respectively. 53 patients were treated with limb salvage surgery or rotationplasty and 2 patients experienced a local recurrence. 3 toxic deaths were recorded, all related to acute toxicity from chemotherapy. The 5-year metastasis-free survival of poor histological responders receiving add-on treatment with ifosfamide was 47%, as compared to 89% for good histological responders. Interpretation Outcome from the SSG XIV protocol compares favorably with the results of previous SSG trials and other published osteosarcoma trials. However, salvage therapy given to poor responders did not improve outcome to a similar degree as for good responders. In a multi-institutional setting, more than four-fifths of the patients were operated with limb salvage surgery or rotationplasty, with few local recurrences

Drugs in early clinical development for the treatment of osteosarcoma

Introduction: Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma

Malignant fibrous histiocytoma of the distal femur after an arthroscopic anterior cruciate ligament reconstruction: A case report and a review of the literature

<p>Abstract</p> <p>Background</p> <p>Malignant degeneration in association with orthopaedic implants is a known but rare complication. To our knowledge, no case of osseous malignant fibrous histiocytoma after anterior cruciate ligament reconstruction is reported in the literature.</p> <p>Case presentation</p> <p><b>We report a </b>29-year-old male Turkish patient who presented with severe pain in the operated knee joint 40 months after arthroscopic anterior cruciate ligament reconstruction. X-ray and MR imaging showed a large destructive tumor <b>in </b>the medial femoral condyle. Biopsy determined a malignant fibrous histiocytoma. After neoadjuvant chemotherapy, wide tumor resection and distal femur reconstruction with a silver-coated non-cemented tumor knee joint prosthesis was performed. Adjuvant chemotherapy was continued according to the EURAMOS 1 protocol.</p> <p>Conclusions</p> <p>Though secondary malignant degeneration after orthopaedic implants or prostheses is not very likely, the attending physician should take this into consideration, especially if symptoms worsen severely over a short period of time.</p

Pathological validation and significance of micrometastasis in sentinel nodes in primary breast cancer

In embracing a multidisciplinary approach to the management of patients with sentinel node biopsy in breast cancer, the pathologist task is to screen sentinel nodes for possible metastasis. The consequences of missing sentinel node micrometastasis can directly influence treatment strategies, and this screening therefore has to be performed with more attention than usual. There is presently great diversity in the histopathological work-up of sentinel nodes, with many centres employing additional techniques such as immunohistochemistry, reverse transcription polymerase chain reaction or flow cytometry in addition to routine haematoxylin and eosin staining. In this review, we address the pathological validation and significance of micrometastasis in sentinel node biopsy in primary breast cancer