Dirk Uyttendaele

Static, Dynamic and First-Pass MR Imaging of Musculoskeletal Lesions Using Gadodiamide Injection

Forty-five patients with known or suspected musculoskeletal tumors were examined with static and dynamic MR imaging to evaluate the safety, tolerability and diagnostic utility of gadodiamide injection and to assess the diagnostic value of dynamic MR imaging and parametric “first-pass” (FP) images. The proportion of patients presenting more diagnostic information on the contrast-enhanced compared to the precontrast spin-echo examinations was determined. The dynamic enhancement characteristics were evaluated with time-intensity curves and parametric images of the FP enhancement rate. The tolerance of gadodiamide injection was good. Contrast enhancement was useful for delineating tumor from muscle, and differentiating viable from necrotic tissue and cystic from solid lesions. Malignant tumors showed a significantly higher slope value, earlier onset of enhancement, and higher maximum enhancement than benign lesions. However, slope values could not be used to predict the malignant potential of a lesion, due to overlap between highly vascular benign and low vascular malignant lesions. By displaying highly vascular areas, parametric FP images provided useful information on the most active part in a tumor before biopsy and for assessing the incorporation of bone-chip allografts. Static, dynamic and FP MR imaging using gadodiamide injection appears safe and provides useful information for diagnosis, biopsy and follow-up of musculoskeletal lesions.

Telomere biology in giant cell tumour of bone.

Giant cell tumour of bone (GCTB) is a benign bone tumour known for the unpredictable clinical behaviour of recurrences and, in rare instances, distant metastases. It consists of uniformly distributed osteoclastic giant cells in a background of mononuclear rounded and spindle‐shaped cells. Cytogenetically, telomeric associations are the most common chromosomal aberrations, which, however, are normally almost exclusively found in high‐grade malignancies. GCTB has often been regarded as a polyclonal tumour, but more recently a recurrent specific aberration was reported, which suggests a possible role for disturbed telomere maintenance. Here we further investigate telomere maintenance in GCTB using 19 samples from 19 patients. A combination of immunofluorescence and FISH was performed, applying antibodies directed against promyelocytic leukaemia body‐related antigen and hTERT and using telomere peptide nucleic acid probes. The TRAP assay and telomere restriction fragment length analysis were performed for functional detection of telomerase activity and alternative telomere lengthening. Both osteoclastic giant cells and mononuclear cells showed positivity for hTERT and promyelocytic leukaemia body‐related antigen. In most mononuclear cells, co‐expression was present. The TRAP assay demonstrated heterogeneous telomerase activity, while telomere restriction fragment length analysis showed non‐heterogeneous telomere lengths, indicating the absence of alternative telomere lengthening. Confocal microscopy showed stereometric co‐localization of nucleolin with promyelocytic leukaemia body‐related antigen in association with telomeres in the spindle‐shaped cells. hTERT was more diffusely distributed throughout the nucleus. Our results show that GCTB demonstrates remarkable telomere maintenance of activated telomerase and inactivated alternative telomere lengthening in the presence of normal mean telomere restriction fragment lengths. These findings strongly suggest that these aggregates, while activating telomerase, are part of a structural telomere protective‐capping mechanism rather than of a telomere‐lengthening mechanism. Telomere maintenance could be considered an important key factor in the pathogenesis of GCTB. Copyright

Post-treatment complications of soft tissue tumours.

PURPOSE To identify local and distant complications of patients with soft tissue tumours and evaluate their relationships to types of therapy. METHODS AND MATERIALS Fifty-one patients (29 males and 22 females, ages 14-80 years) with 34 malignant and 17 benign soft tissue tumours were evaluated for local and distant complications after resection or amputation only (26 patients) or after the addition of radiotherapy (25 patients: 17 patients had external beam therapy, 7 patients had external beam therapy and brachytherapy, and one patient had extracorporeal irradiation and reimplantation). Duration of follow-up averaged 3.75 years for malignant tumours and 2.79 years for benign tumours. Follow-up studies included radiography, T1- and T2-weighted magnetic resonance (MR) imaging, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography for thoracic and abdominal metastases, and 3-phase technetium-99m-labeled-methylene-diphosphonate scintigraphy for bone metastases. RESULTS Recurrent tumours were 2.2 times more frequent in patients who had undergone their initial resection at an outside hospital as compared with those first treated at the university hospital. Nine of 11 recurrences occurred after marginal surgery. Metastases from soft tissue sarcomas, most commonly to lung (nine patients) and to bone and muscle (five patients), showed no specific relationship to type of therapy. DCE-MRI differentiated rapidly enhancing soft tissue recurrences (11 patients) and residual tumours (6 patients) from slowly enhancing muscle inflammation, and non-enhancing fibrosis and seromas that usually did not enhance. Seromas developed in 76% of patients who had postoperative radiation therapy and in 7.7% of patients who had only surgery. Subcutaneous and cutaneous oedema and muscle inflammation was at least four times more frequent after adjunct radiotherapy than after resection alone. Irrespective of the type of treatment, inflammatory changes in muscle and subcutaneous and cutaneous tissue and the majority of seromas were evident at the first follow-up study. Although seromas after resection and external beam therapy resolved with time, seromas after additional brachytherapy persisted. Inflammatory changes in muscle and cutaneous and subcutaneous tissue after resection alone disappeared by the second follow-up study, whereas these changes after radiotherapy resolved months to years after treatment. Fourteen of 51 patients showed MR findings of chronic muscular atrophy, predominantly located in the lower extremity. Heterotopic ossification was seen in three patients after resection and amputation without radiotherapy. Except for one patient with aggressive fibromatosis, bone and nerve complications occurred in patients with soft tissue malignancy. Twelve patients had osteoporosis. Six patients sustained fractures in irradiated osteoporotic bone of the lower extremity, and one patient had a vertebral fracture in radiographically normal but irradiated bone. In addition, one patient was found to have a medullary infarct in an irradiated femur. In nerve entrapment, DCE-MRI demonstrated the rapidly enhancing recurrent tumour or non-enhancing fibrosis surrounding the slowly enhancing nerve. T1- and T2-weighted MR images displayed the acute and chronic sequelae of nerve entrapment and nerve transection with denervation as T2-hyperintense acute muscle atrophy or T1-hypertense chronic fatty muscular atrophy with decrease in muscle volume. CONCLUSION This study suggests a possible relationship between types of treatment of soft tissue tumours and subsequent complications. Postoperative radiotherapy was associated with a significant number of patients with seromas, muscle, cutaneous and subcutaneous inflammation, and fractures. Incomplete or difficult surgery resulted in residual or recurrent tumours and heterotopic ossification. Muscle atrophy and nerve entrapment were related to both treatments (resection alone or radiotherapy after resection). Diligent follow-up of patients with soft tissue tumours with recognition of these complications and their differentiation from recurrent or residual tumour can help guide clinical care and may negate the need for surgery when benign disease is defined.

CD33+ CD14− Phenotype Is Characteristic of Multinuclear Osteoclast-Like Cells in Giant Cell Tumor of Bone†

Giant cell tumor of bone (GCTB) is a benign bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. GCTB is composed of uniformly distributed osteoclastic giant cells, thought to originate from the fusion of monocyte–macrophage lineage cells, in a background consisting of mononuclear rounded cells and spindle‐shaped cells. Several reports showed the specific expression of markers, such as CD14 on the mononuclear rounded cell population, however, lacking osteoclastic giant cells. Blood monocytes that were CD14+, CD33+, or CD14+/CD33+ have also been shown to be programmed as pre‐osteoclasts. The macrophage marker CD33 is expressed earlier than CD14 in macrophage maturation, whereas CD14 is expressed longer than CD33. The aim of this study was to investigate CD14/CD33 expression profiles in GCTB. Nineteen GCTB tumor samples of 19 patients were studied. Immunofluorescent analyses were performed with monoclonal antibodies against CD14, CD33, RANK, and CD51. To unambiguously further prove the expression of these molecules, quantitative RT‐PCR was used with subsequent sequencing of its products. All samples showed similar immunoreactivity profiles. The mononuclear rounded cell population was positive for RANK, CD51, CD14, and CD33. The osteoclastic giant cell population expressed RANK and CD51, as well as CD33, but was consistently negative for CD14 expression. The CD14 and CD33 profiles were confirmed by quantitative RT‐PCR. These RT‐PCR products were sequence verified. Osteoclasts in GCTB are the result of fusion of CD33‐expressing pre‐osteoclasts that further fuse with CD14+ mononuclear cells. Although these results reflect a static rather than a dynamic spectrum, we strongly believe that osteoclastogenesis seems not to be the exclusive result of fusion of intratumoral CD14+ mononuclear cells. Moreover, CD33‐modulated osteoclastogenesis opens up the possibility for novel therapeutic directions.

Are stand-alone cages sufficient for anterior lumbar interbody fusion?

Anterior lumbar interbody fusion (ALIF) has increased in popularity because it has advantages over posterior fusion. Because there is disagreement about the stability of stand‐alone cage ALIF, some surgeons use various types of supplementary fixation, including anterior plates, pedicle screw systems and translaminar screws, to increase segmental stability. Many factors associated with both the cages and endplates influence the time of onset and extent of subsidence after use of stand‐alone cage ALIF. A large round cage with an adequate central opening is recommended to facilitate maximum contact with the periphery of the endplate. With regard to the relationship between radiographic fusion and recurrence of symptoms with the development of subsidence, most researchers have reported finding no correlation. Subsidence may be due to a process of bone incorporation between cages and endplates. Does subsidence or nonfusion really matter clinically? Further prospective, randomized controlled trials are very much needed to answer these questions.

Comparison of vertebroplasty and kyphoplasty for complications

Vertebroplasty (VP) and kyphoplasty (KP) have been proven equally effective in providing pain relief in patients with vertebral compression fractures (VCF). Both have been reported to have multiple complications which, though rare, are potentially devastating. This literature review focuses on comparing the incidence of various types of complication of VP and KP. Local cement leakage and pulmonary cement embolism have been reported more commonly after VP than KP. It is questionable whether the relative risk of developing an adjacent level new fracture after VP is greater than after KP The relationship between a new VCF and each of these procedures has also not been clearly established. Although the majority of complications are clinically silent, their potential risks, which include a fatal outcome, should always be kept in mind by the practitioner.

Tumor grafts derived from sarcoma patients retain tumor morphology, viability, and invasion potential and indicate disease outcomes in the chick chorioallantoic membrane model

The chick chorioallantoic membrane (CAM) assay was used to evaluate whether xenotransplanted sarcomas retain the histological characteristics and functional behavior of the original tumors. Metabolically active tumor tissue, identified by dynamic-contrast MRI, from 28 patients with a bone or soft-tissue tumors was applied to the CAM. Angiogenesis and graft and host behaviors were evaluated. The essential features and immunohistochemical characteristics of the original tumors were maintained, illustrating the diversity of sarcomas. Graft viability was inversely related to patient survival, but longer follow-up and more patients are needed to relate tumor graft behavior to natural history. We conclude that the CAM assay is a potential prognostic and predictive preclinical xenograft model for tumors that are difficult to culture in vitro, such as sarcomas; therefore, the use of the CAM assay may facilitate personalized medicine.

Recurrent massive subperiosteal hematoma in a patient with neurofibromatosis

Abstract The authors report the case of a 13-year-old neurofibromatosis (NF-I) patient who suffered a blunt trauma in 1993. The diagnosis of subperiosteal hematoma was made. The pathogenesis of subperiosteal hematoma is discussed.

Complications of bone tumors after multimodal therapy

PURPOSE To define and compare the complications of bone tumors after resection, extracorporeal irradiation and re-implantation, with or without radiotherapy. MATERIALS AND METHODS Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign bone tumors were evaluated for local and distant complications after treatment. Two groups of patients were studied: (1) 53 patients had resection without (43 patients) or with external beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR) magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for bone metastases. RESULTS DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis. Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as frequent in patients after resection than after ECCRI. Although 11.3% of post-resection patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation was more common in the externally irradiated patient as compared with the patient who did not receive this therapy. However, another soft tissue complication, heterotopic ossification, was rare in the patient after RadRx, but 25.6% of patients after resection and 40.9% after ECRRI showed heterotopic ossification. Unusual complications after resection or ECRRI involved adjacent nerves with partial denervation, amputation neuroma, or entrapment (secondary to recurrence or fibrosis) after resection or ECRRI with or without RadRx. One patient developed a posterior tibial artery pseudoaneurysm after ECRRI. CONCLUSIONS Follow-up of patients with benign and malignant bone tumors demonstrated the efficacy of DCE-MRI for distinguishing rapidly enhancing viable tumor from the slowly enhancing or non-enhancing benign processes after different therapies. Although recurrences, residual tumors, metastases and seromas were more common after resection, fractures, osteoporosis, infection, and muscular atrophy predominated in the ECRRI-treated patient. RadRx further predisposed post-resection and post-ECRRI patients to develop fractures, osteoporosis and infection and was the major cause of persistent muscle inflammation at MRI. Because complications can evolve and resolve years after treatment, the patients with bone tumors, particularly sarcomas, must receive life-time multimodal imaging for maximal diagnosis and treatment.

OSTEOSARCOMA WITH EXTENSIVE CALCIFIED PLEURAL METASTASES AT DIAGNOSIS

Abstract We report the case of an 18 year old woman presenting with shortness of breath and pain in the left shoulder. Imaging of the lungs revealed pleural effusion and calcification of the left pleura. An osteosarcoma of the left humerus was the final diagnosis. A review of the literature reveals that calcified pleural metastatic disease in cases of osteosarcoma has been infrequently reported. Other causes of pleural calcification are briefl y discussed.