Carla S. P. van Rijswijk

The Clinical Approach Towards Chondrosarcoma

This review provides an overview of the histopathology, classification, diagnostic procedures, and therapy of skeletal chondrosarcoma. Chondrosarcomas that arise de novo are primary chondrosarcomas, whereas chondrosarcomas developing superimposed on pre-existing benign cartilage neoplasms such as enchondromas or osteochondromas are referred to as secondary chondrosarcomas. Conventional chondrosarcomas can be categorized according to their location in bone into central, peripheral, and juxtacortical chondrosarcomas. Histological grading is related to prognosis; however, it is also subject to interobserver variability. Rare subtypes of chondrosarcoma, including dedifferentiated, mesenchymal, and clear cell chondrosarcoma, are discussed as well. Magnetic resonance imaging is necessary to delineate the extent of the intraosseous and soft tissue involvement preoperatively. Computed tomography is especially recommended in the pelvis and other flat bones where it may be difficult to discern the pattern of bone destruction and the presence of matrix mineralization. Wide, en-bloc excision is the preferred surgical treatment in intermediate- and high-grade chondrosarcoma. In low-grade chondrosarcoma confined to the bone, extensive intralesional curettage followed by local adjuvant treatment and filling the cavity with bone graft has promising long-term clinical results and satisfactory local control. Chondrosarcomas are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in attempts to achieve local control after incomplete resection. Irradiation with protons or other charged particles seems beneficial in this curative situation. Chemotherapy is only possibly effective in mesenchymal chondrosarcoma, and is of uncertain value in dedifferentiated chondrosarcoma. Potential new systemic treatment targets are being discussed.

Comparison of dixon and T1-weighted MR methods to assess the degree of fat infiltration in duchenne muscular dystrophy patients

To compare different lipid multipeak spectral models to the single‐peak model in Dixon‐based fat‐water separation and to evaluate differences between visually scored magnetic resonance (MR) images and quantitatively assessed fat fractions in muscle of Duchenne muscular dystrophy patients.

Magnetic resonance imaging of skeletal muscles in sporadic inclusion body myositis

OBJECTIVE To analyse whether MRI of upper and lower extremity muscles in a large patient group with sporadic IBM (sIBM) is of additional value in the diagnostic work-up of sIBM. METHODS Thirty-two sIBM patients were included. Magnetic resonance (MR) parameters evaluated in 68 muscles of upper and lower extremity were muscle atrophy, fatty infiltration and inflammation. These findings were correlated with disease duration, weakness and serum creatine kinase (sCK) levels. RESULTS Fatty infiltration was far more common than inflammation. Muscles most frequently infiltrated with fat were the flexor digitorum profundus (FDP), anterior muscles of the upper leg and all muscles of the lower leg, preferentially the medial part of the gastrocnemius. The rectus femoris was relatively spared compared with other quadriceps muscles as well as the adductors of the upper leg. Inflammation was common in general, but individually sparse, present in 78% of the patients with a median of two inflamed muscles per patient. A statistically significant correlation was found between the amount of fatty infiltration and disease severity, disease duration and sCK. CONCLUSION We provide a detailed description of the MRI in sIBM and show a distinct pattern of muscle involvement. Relatively severe affliction of the medial compartment of the gastrocnemius, combined with relative sparing of the rectus femoris or involvement of the FDP can be indicative of sIBM. MRI can contribute to the diagnosis in selected patients with clear clinical suspicion, but lacking the mandatory set of muscle biopsy features.

The Clinical Approach Toward Giant Cell Tumor of Bone

We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta-epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%-27%) or cryosurgery and PMMA (0%-20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra-articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB-derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate-dose radiotherapy (40-55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable.

Soft tissue tumors in adults: ESSR-approved guidelines for diagnostic imaging

Soft tissue sarcomas are rare, but early, accurate diagnosis with subsequent appropriate treatment is crucial for the clinical outcome. The ESSR guidelines are intended to help radiologists in their decision-making and support discussion among clinicians who deal with patients with suspected or proven soft tissue tumors. Potentially malignant lesions recognized by ultrasound should be referred for magnetic resonance imaging (MRI), which also serves as a preoperative local staging modality, with specific technical requirements and mandatory radiological report elements. Radiography may add information about matrix calcification and osseous involvement. Indeterminate lesions, or lesions in which therapy is dependent on histology results, should be biopsied. For biopsy, we strongly recommend referral to a specialist sarcoma center, where an interdisciplinary tumor group, with a specialized pathologist, radiologist, and the surgeon are involved. In sarcoma, a CT scan of the chest is mandatory. Additional staging modalities are entity-specific. There are no evidence-based recommendations for routine follow-up in surgically treated sarcomas. However, we would recommend regular follow-up with intervals dependent on tumor grade, for 10 years after the initial diagnosis.

The intravertebral cleft in painful long-standing osteoporotic vertebral compression fractures treated with percutaneous vertebroplasty: diagnostic assessment and clinical significance.

Study Design. Prospective follow-up study. Objective. Evaluation of the diagnostic assessment and clinical significance of the intravertebral cleft in painful, long-standing osteoporotic vertebral compression fractures (OVCFs) treated with percutaneous vertebroplasty (PVP). Summary of Background Data. Patients with painful OVCFs with intravertebral clefts provide a unique and possibly superior indication for PVP. However, comparative studies are scarce, and the results are conflicting. The extent of the difference attributable to interobserver variation in the identification of an intravertebral cleft is currently unknown. Methods. A total of 102 patients received PVP for 197 painful long-standing OVCFs and were prospectively observed, using a pain-intensity numerical-rating scale for back pain, the 36-Item Short Form Health Survey quality-of-life questionnaire, and routine spinal radiographs. Three experienced examiners retrospectively examined all preoperative radiographs and magnetic resonance imaging (MRI) T1-weighted and short-tau-inversion-recovery (STIR) sequences and the direct postoperative computed tomographic scans for the presence of an intravertebral cleft. Disagreements were re-examined and discussed for consensus. Results. Interobserver agreement for the detection of an intravertebral cleft was moderate on preoperative radiography (&kgr;, 0.55−0.59) and substantial on preoperative MRI (&kgr;, 0.71–0.79) and postoperative computed tomography (&kgr;, 0.67–0.85). On the basis of consensus, 42 (21.3%) clefts were detected. The associated sensitivity of preoperative radiography was low (31.7%–48.8%), but the specificity was high (94.7%–99.3%). The diagnostic performance of preoperative MRI T1-weighted and STIR sequences was excellent, with both high sensitivity (85.7%–88.1%) and high specificity (89.7%–98.1%). Pain decrease and increase in quality of life obtained from PVP were ultimately comparable with patients without intravertebral clefts but was obtained more gradually during the first postoperative year. An intravertebral cleft was a strong risk factor for the occurrence of cortical cement leakage (odds ratio, 4.29; 95% confidence interval, 1.51–12.2; P = 0.006). Conclusion. There is variation between observers in the identification of an intravertebral cleft, and the identification of an intravertebral cleft is not always straightforward. For preoperative assessment, we recommend MRI with T1-weighted and STIR sequences. Regarding patient-reported outcome, patients with long-standing OVCFs with intravertebral clefts benefit from PVP, but, compared with patients with OVCFs without intravertebral clefts, the benefit obtained was not superior and may be delayed.

Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

BackgroundChondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce.MethodsWe developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential.ResultsWe show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type.ConclusionsBased on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies.

Gastric Variceal Hemorrhage in a Noncirrhotic Patient Treated with Balloon-Occluded Retrograde Transvenous Obliteration

We read with great interest the recent article by Saad et al. [1]. We fully agree with the authors that balloon-occluded retrograde transvenous obliteration (BRTO) is a valuable treatment that can be used as an alternative to transjugular intrahepatic portosystemic shunt (TIPS). BRTO is also an excellent treatment option in patients for whom TIPS would not be beneficial. Gastric varices most commonly occur in patients with portal hypertension due to cirrhosis. Yet gastric varices may also develop in patients without underlying liver cirrhosis, and TIPS may not be beneficial or possible in these patients. BRTO is preferred over TIPS in such cases. We present a case of BRTO in a patient with active hemorrhage from gastric varices that were due to post pancreatitis splenic vein occlusion.

Cartilage – Forming Bone Tumours

Cartilaginous tumours form the second largest group of primary bone tumours. They all share the characteristic production of chondroid matrix by tumour cells. Cartilage tumours range from completely benign lesions to highly malignant and are sub-divided by location in intramedullary, central and surface or peripheral sites. Most cartilage lesions can be diagnosed using plain radiographs or MRI. Differentiation between benign and malignant can be very difficult, for example enchondroma versus low-grade chondrosarcoma, osteochondroma versus peripheral chondrosarcoma and chondroblastoma versus clear-cell chondrosarcoma. Biopsy of malignant lesions can be false negative due to sample error as most cartilage lesions have grades of malignancy and can even present benign sections. Benign lesions are best left be untouched if free of symptoms and radiologically inactive such as enchondroma of the phalanges. En bloc resection of osteochondroma including the pseudocapsule is curative and results in a very low recurrence rate. Malignant cartilage tumors, if low-grade central chondrosarcoma of the long bones, can be treated with intralesional surgery in combination with some adjuvant (phenol, cryosurgery). High grade chondrosarcoma (including clear-cell chondrosarcoma) and all chondrosarcoma of the axial skeleton should be surgically resected with wide margins with an intermediate risk of local recurrence.