Multifocal osteogenic sarcoma in Paget’s disease

The most serious complication of Paget’s disease is sarcomatous degeneration of pagetic bone. Multifocal sarcomatous degeneration occurs mainly in polyostotic Paget’s disease. Multifocal Paget’s sarcoma is uncommon and can arise in any site. We report two cases of synchronous multifocal sarcomatous degeneration. The two patients were elderly women (aged 77 and 86 years, respectively) who developed sarcomatous lesions concomitantly, in the first case report in left ilium, left tibia, and first lumbar vertebra and in the second case report in the skull, right ilium, and sacrum. Whether these cases are due to the simultaneous development of several primaries or to metastases from a single primary remains unclear. Received: 3 August 1998 Revision requested: 14 September 1998 Revision received: 6 March 2000 Accepted: 14 March 2000     

Giant-cell-rich pseudotumour in Paget’s disease

Paget’s disease (PD) of the bone is a disorder of bone remodelling that may be polyostotic or monostotic. Although development of a sarcoma in PD is well-recognised, it is less well recognised that pseudosarcomas in bone and soft tissue can also arise in this condition. In this report we document the case of a large giant-cell-rich pseudotumour that developed in the tibia and overlying soft tissues in a case of polyostotic PD. Bone and soft tissues were highly vascular and contained abundant haemorrhage with focal areas of new bone formation and a diffuse infiltrate of osteoclastic giant cells. The lesion has not recurred or produced metastases 3 years after removal. Clinicians should be aware that a benign giant-cell-rich pseudotumour can develop in PD and that it needs to be distinguished from other giant-cell-rich tumours.     

The spine in Paget’s disease

Paget’s disease (PD) is a chronic metabolically active bone disease, characterized by a disturbance in bone modelling and remodelling due to an increase in osteoblastic and osteoclastic activity. The vertebra is the second most commonly affected site. This article reviews the various spinal pathomechanisms and osseous dynamics involved in producing the varied imaging appearances and their clinical relevance. Advanced imaging of osseous, articular and bone marrow manifestations of PD in all the vertebral components are presented. Pagetic changes often result in clinical symptoms including back pain, spinal stenosis and neural dysfunction. Various pathological complications due to PD involvement result in these clinical symptoms. Recognition of the imaging manifestations of spinal PD and the potential complications that cause the clinical symptoms enables accurate assessment of patients prior to appropriate management.     

Atypical vertebral Paget’s disease

A 40-year-old Mauritanian man consulted for back pain. A computed tomography of the spine showed patchy sclerosis of the fifth and seventh thoracic vertebral bodies with normal neural arch of T5 and sclerosis and hypertrophy of the neural arch of T7, as well as diffuse sclerosis of the T11 vertebral body with a normal neural arch. At MRI, low signal-intensity on T1-weighted images and high signal-intensity on T2-weighted images involved the whole T5 and T7 vertebrae and the vertebral body of T11. Working diagnoses included metastatic disease and lymphoma, and a biopsy of T7 and then T11 was carried out. Both showed pathological findings very suggestive of Paget’s disease. Since CT is usually the more specific radiological examination in vertebral Paget’s disease, we thought it could be useful to report this atypical CT presentation (patchy sclerosis of the vertebral body without diffuse bone texture changes and isolated involvement of the vertebral body) of vertebral Paget’s disease.     

Radiographic features of Ewing’s sarcoma of the bones of the hands and feet

The radiographic features of Ewing's sarcoma of the bones of the hands and feet are reviewed utilizing cases obtained from the Mayo Clinic patient files and the consultation files of Drs. D.C. Dahlin and K.K. Unni. This series consists of a total of 43 cases of pathologically proven Ewing's sarcoma involving the small bones of the hands and feet. The classic radiographic features of Ewing's sarcoma in the long bones, including lytic, permeative destruction, aggressive periosteal reaction, cortical violation, and a soft tissue mass, are also seen in the bones of the hands and feet, with similar frequency. These classic features are most commonly present in lesions affecting the short tubular bones. Lesions affecting the tarsal bones more often demonstrate atypical radiographic features. These atypical radiographic appearances may play a role in the reported delay in diagnosis of Ewing's sarcoma within the tarsal bones.     

Subperiosteal ganglion associated with Paget’s disease of bone

Tumoral lesions related to Pagets disease may be classified as malignant, benign or pseudotumoral. While sarcomatous degeneration is the most feared complication, awareness of benign and pseudotumoral lesions is essential for assisting in accurate histological interpretation of the biopsy sample, which may avoid unnecessary repeat biopsies. We present the first case of a juxta-articular subperiosteal ganglion associated with Pagets disease, with classic imaging characteristics, especially on CT examination. The well-defined soft tissue mass at the medial aspect of the obturator rim, adjacent to a small fracture in pagetic quadrilateral plate, showed an ossified rim and internal gas lucencies, these being the hallmarks of a juxta-articular subperiosteal ganglion. On MRI, the lesion was of intermediate signal intensity on T1-weighted sequences, increased signal intensity on T2-weighted sequences, with rim enhancement after gadolinium contrast injection and preservation of fatty marrow signal of the underlying pagetic bone. Identification of the entity avoided an unnecessary biopsy or surgical intervention.     

Dynamic contrast-enhanced MRI for monitoring bisphosphonate therapy in Paget’s disease of bone

Purpose

The purpose of this study was to evaluate changes in regional bone perfusion in Paget’s disease (PD) following bisphosphonate therapy. We used dynamic contrast-enhanced MRI (DCE-MRI) for assessment of bone perfusion and compared MRI findings with alkaline phosphatase (AP) as a serum marker of bone turnover.

Materials and methods

We examined 20 patients (8 women, 12 men, 66?±?11 years) with symptomatic PD of the axial skeleton. Patients were selected for infusion therapy with the bisphosphonate pamidronate. The most affected bone of lumbar spine or pelvis was examined by DCE-MRI prior to therapy and after a 6-month follow-up. The contrast uptake was evaluated using a two-compartment model with the parameters amplitude A and exchange rate constant K_ep. Color-coded parametric images were generated to visualize bone vascularization.

Results

After a 6-month follow-up there was a significant decrease in alkaline phosphatase and in DCE-MRI parameters A and K_ep (p?<?0.0001). Patients without previous bisphosphonate treatment showed a significantly greater decrease in alkaline phosphatase and K_ep (p?<?0.001).

Conclusion

DCE-MRI shows a significant reduction in regional bone perfusion in PD following parenteral bisphosphonate treatment. Reduction in bone perfusion is greater in bisphosphonate-naïve patients than in those who had been previously treated.     

MR imaging of pseudosarcoma in Paget’s disease of bone: a report of two cases

Pseudosarcoma is a rare manifestation of Paget’s disease of bone. We report the MR imaging of two cases highlighting the difficulties in diagnosis. One of the cases is the first time this condition has been described outside the long bones of the lower limb. Received: 11 July 2000 Revision requested: 10 August 2000 Revision received: 8 November 2000 Accepted: 15 November 2000     

Ewing’s sarcoma of the patella

Ewing’s sarcoma is a relatively rare malignancy, occurring mainly between 4 and 25 years of age. It usually arises from the pelvis, followed by the femur, tibia, and remainder of both the long bones of the extremities and flat bones of the axial skeleton. To the best of our knowledge, Ewing’s sarcoma of the patella has never been reported previously. Patellar tumors occur infrequently and represent an uncommon etiology of anterior knee pain. We describe the rare case of a 41-year-old man who presented with a 3–4 month history of escalating right anterior knee pain and swelling. Imaging demonstrated an aggressive patellar tumor with an adjacent soft tissue mass. The diagnosis of Ewing’s sarcoma was confirmed by pathology. Physicians should be aware of atypical locations for Ewing’s sarcoma and, conversely, of rare tumors arising in the patella and accounting for anterior knee pain. Early recognition of such malignancies allows prompt initiation of treatment, hence improving prognosis.     

Ewing’s sarcoma of the larynx

Extraskeletal Ewing’s sarcoma arising in the head and neck region is an extremely rare malignant neoplasm. We describe the unusual case of a tumor originating in the larynx of a 68-year-old male with hoarseness and occasional aphonia. We report successful treatment with sequential chemo- and radiotherapy. Complete regression and larynx preservation with voice function recovery was achieved. To our knowledge, this is the first report of this type of tumor in the larynx with cartilage invasion that documents the effectiveness of radiotherapy as an alternative to surgical management. At present, after 30 months of follow-up, the patient is free of tumor relapse and in very good condition.     

Dynamic contrast-enhanced MRI in Paget’s disease of bone–correlation of regional microcirculation and bone turnover

The purpose of this study was to evaluate regional microcirculation in Paget’s disease of bone (PD) with dynamic contrast-enhanced MR imaging (DCE-MRI). Additionally, we correlated regional bone perfusion with alkaline phosphatase as serum marker of bone turnover. We examined 71 patients with PD (27 men, 44 women, 67±10 years) localized at the axial and appendicular skeleton. Contrast uptake was analyzed using a two-compartment model with the output variables amplitude A and exchange rate constant k_ep. Color-coded parametric images were generated to visualize microcirculation. Serum levels of alkaline phosphatase (AP) were compared with DCE-MRI parameters. Amplitude A and exchange rate constant k_ep were significantly increased in PD compared to unaffected bone (A_PD 0.81±0.24 vs. A_control 0.34±0.1 and k_{ep PD} 4.0±2.86 vs. k_{ep control} 1.73±0.88, p<0.001). There was a significant correlation (r_s=0.5–0.7) of DCE-MRI parameters and AP at the axial (pelvis, spine) and appendicular skeleton (femur, tibia). The long bones showed increased circulation of the advancing peripheral zones and no vascularization of the central part, which had been replaced by fatty tissue. Regional microcirculation in PD is inhomogeneous with focal areas of excessive hypervascularity, especially in the advancing peripheral zone. There is a significant correlation of bone circulation and bone turnover in PD. DCE-MRI might therefore be a diagnostic tool for monitoring therapeutic effects of bisphoshonates in Paget’s disease of bone.     

Survivin, a target to modulate the radiosensitivity of Ewing’s sarcoma

Background and purpose

Radiotherapy constitutes an essential element in the multimodal therapy of Ewing’s sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing’s sarcoma in vitro.

Material and methods

An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing’s sarcoma cell lines with and without irradiation.

Results

Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation.

Conclusion

Survivin is a radiation-inducible protein in Ewing’s sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing’s sarcoma.     

Benign tumefactive soft tissue extension from Paget’s disease of bone simulating malignancy

Osteosarcoma is a frequently fatal complication of Paget’s disease of bone typically manifesting radiographically as a lytic lesion with soft tissue extension. A clinically worrisome, but benign manifestation of Paget’s disease simulating malignancy because of an extraosseous mass is reported. Received: 19 January 2000 Revision requested: 18 August 2000 Revision received: 31 October 2000 Accepted: 3 November 2000     

Neuroimaging in Huntington’s disease

Huntington’s disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded trinucleotide CAG sequence in huntingtin gene (HTT) on chromosome 4. HD manifests with chorea, cognitive and psychiatric symptoms. Although advances in genetics allow identification of individuals carrying the HD gene, much is still unknown about the mechanisms underlying the development of overt clinical symptoms and the transitional period between premanifestation and manifestation of the disease. HD has no cure and patients rely only in symptomatic treatment. There is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease modifying drugs. Over the past years, neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have provided important advances in our understanding of HD. MRI provides information about structural and functional organization of the brain, while PET can detect molecular changes in the brain. MRI and PET are able to detect changes in the brains of HD gene carriers years ahead of the manifestation of the disease and have also proved to be powerful in assessing disease progression. However, no single technique has been validated as an optimal biomarker. An integrative multimodal imaging approach, which combines different MRI and PET techniques, could be recommended for monitoring potential neuroprotective and preventive therapies in HD. In this article we review the current neuroimaging literature in HD.     

Non-motor predictors of freezing of gait in Parkinson’s disease

BackgroundThe etiology of freezing of gait in Parkinson’s disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait.Research questionWe aimed to determine the predictive value of non-motor features in freezing of gait development.MethodsData were obtained from the Parkinson’s Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales.ResultsPatients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time.SignificanceOur findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.     

Role of DWI and MRS in diagnosis of Alzheimer’s and pre-Alzheimer’s disease

Background and purpose

Alzheimer’s disease (AD) is a major cause of dementia in elderly affecting about 30% above the age of 85 years, while mild cognitive impairment (MCI) is the impairment in cognitive functions with intact daily life activities which is described as the preclinical phase of AD.