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Paget's sarcoma is a rare complication of Paget's disease and isolated Paget's disease of the patella is extremely rare. We describe a unique case of Paget's sarcoma of the patella in a 69-year-old male farmer who had a remote history of a fracture in the same patella 40 years previously. In this case, imaging and pathogenesis of Paget's disease of bone is described and factors implicated in the development of Paget's disease in this patient are evaluated.

General orthopedic surgeons frequently encounter patients with conditions affecting multiple bones. It is important to recognize common polyostotic diseases. This article describes five polyostotic conditions: Multipe Enchondromatosis (Ollier Disease and Maffucci syndrome), Multiple Hereditary Exostosis (Diaphyseal Aclasis), Fibrous Dysplasia (McCune-Albright syndrome and Mazabraud syndrome), Paget's Disease of bone (Osteitis Deformans), and Skeletal Metastases. This is a survey of the clinical, pathologic and radiographic features that assist in diagnosing these conditions. Also, an overview of the laboratory findings, treatment, follow-up, and prognosis is presented. Recognizing these diseases will aid in prompt and accurate diagnosis and appropriate referral and therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Paget's disease of bone is common in some parts of Europe and in countries inhabited by European emigrants. In Western Countries, Paget's bone disease is one of the priorities in differential diagnosis for elderly patients who present osteoblastic lesions, so it is unlikely to be overlooked, even though patients may present symptoms unrelated to bone lesions. However in Asian countries where Paget's disease is rare, metastatic prostate cancer appears to be the most common cause for osteoblastic lesions, thus, the Paget's disease is unlikely to be of much concern. This may lead to undue emphasis on investigations to support the diagnosis of prostate cancer. In this report, a 69 year-old man presented pain in the right leg and difficulty urinating. The plain film showed osteoblastic lesions of the right pelvic bone and lumbar spine. The pertinent routine laboratory findings revealed increased levels of serum alkaline phosphatase 125 U/L (normal 27-86). Metastatic prostate cancer was highly suspected and investigations focused upon this, including a serum prostate specific antigen assay, a transurethral cystoscopic examination, an intravenous pyelogram, and an ultrasonogram of the prostate gland. However all of these investigations failed to support prostate cancer. Bone biopsy was performed twice, resulting in a report supporting Paget's disease of bone. The patient was treated with alendronate for three months. Radiologic findings, six months later, showed signs of improvement. He died one year later of heart failure that could plausibly had been a cardiovascular complication of Paget's disease. Better awareness of Paget's disease in Thailand and other Asian countries should reduce the incidence of unnecessary investigations and avoid a misleading diagnosis, which could lead to inappropriate treatment for metastatic prostatic cancer and undesirable psychological impact associated with being misinformed regarding malignancy.

One of the serious complications of Paget's disease (PD) is a significant increase in the risk of developing osteosarcoma. Approximately 1% of the patients with PD develop osteosarcoma. This contributes significantly to the mortality and morbidity of the patients with PD. We present the case of an elderly person, who developed osteosarcoma 1 year after being diagnosed to have PD. The patient had been diagnosed to have lymphoma 8 years prior to the diagnosis of PD. The association between PD and follicular lymphoma is discussed.

A 32-year-old man with a painful osteoblastic osteosarcoma of the right hip was initially diagnosed as having Paget's disease of bone. He was treated with alendronate for presumptive Paget's disease. The patient's bone pain was dramatically reduced by the administration of alendronate for 7 months. Following discontinuation of alendronate, his pain promptly recurred, culminating in a more thorough evaluation that led to the correct diagnosis. Despite chemotherapy, the patient succumbed to metastatic osteosarcoma. The main purpose of this publication is to report the potential for pain relief when an osteosarcoma is treated with bisphosphonate medication. Clinicians are advised not to consider an alendronate-associated pain reduction in an osteoblastic lesion as an indicator of an underlying benign process of bone. The evaluation of painful sclerotic bone lesions is briefly reviewed.

Introduction: Paget's disease of bone (osteitis deformans) is a rare metabolic disorder of bone remodeling with complex etiology. In the most cases, it is detected by coincidence, during nuclear medicine and radiological diagnostic procedures. Herein we report a case of advanced prostate cancer coexisting with asymptomatic Paget's disease., Case Report: We present a 69-year-old patient, with biochemical recurrence two years after radical prostatectomy for localized prostate cancer and period of stable remission. During the evaluation of metastatic spread of prostate cancer, the bone scintigraphy with technetium diphosphonate showed diffuse areas of increased radiotracer uptake in the left leg long bones and focal changes in the axial part of the skeleton. Scintigraphic findings led to a differential diagnostic dilemma regarding etiology of bone changes, so it was supplemented by standard radiologic methods and laboratory evaluation of bone metabolism parameters. The existence of asymptomatic polyostotic Paget's disease and metastatic bone changes was found at the same time., Conclusion: Metastatic bone lesions, in this case from prostate cancer, and asymptomatic Paget's disease may closely resemble each other. They both need careful evaluation in order to determine the proper stages of malignant disease and selection of appropriate therapies for patients.

Background: Osteosarcoma is a rare complication of Paget's disease with a very poor prognosis. Treatment is controversial: the older age of the patients affected by Paget's disease may limit the use of chemotherapy and axial involvement may limit the practicality of surgery., Questions/purposes: The purposes of this study are (1) to report the survival in patients treated for osteosarcoma in Paget's disease; (2) to identify correlations between type of treatment and survival comparing our data with those in the literature; (3) to determine if the extent of Paget's disease and risk of malignant transformation are associated; (4) to assess if prognosis is related with site; and (5) to identify the variations of histologic subtypes of these osteosarcomas., Methods: We retrospectively reviewed the medical records of 26 patients treated between 1961 and 2006 who had bone sarcoma arising from a site of Paget's disease. Twenty two of the 26 patients had surgery. In six surgery only was performed; three had surgery, adjuvant chemotherapy, and radiotherapy; one surgery and radiotherapy; 12 underwent surgery and chemotherapy, adjuvant in 10 patients and neoadjuvant in two; two had only radiotherapy and two had only chemotherapy. We performed survival analyses between various combinations of treatment., Results: At last followup four patients had no evidence of disease (NED) at a minimum followup of 42.6 months (mean, 139 months; range, 42.6-257.4 months) and 22 died with disease (DWD) at a minimum time of 1 month (mean, 20.2 months; range, 1-84 months). One of the six patients (11%) treated with surgery only had NED at 10 years; the other five died from disease at a mean of 30 months. Three of 12 patients (25%) treated with surgery and chemotherapy are NED at a mean followup of 12 years; nine died of disease at a mean of 24 months. All patients treated without surgery died at a mean of 7.5 months (range, 1-13.7 months)., Conclusions: Despite improvements in surgery and medical treatments the prognosis remains poor in patients with Paget's sarcoma.

The diagnosis of Paget's bone disease (PD) is often reached fortuitously with X-ray or scintigraphy. The peculiar distribution of the bone tracer in some skeletal locations, such as vertebra, may be highly suggestive of this disorder. Indeed, there are two distinct vertebral images on the bone scan highly specific of PD: the "clover" and the "heart" images. It has been previously reported that the specificity of these images for PD diagnosis is very high, nearly 100%, then suggesting that these findings could be patognomonic of this process. We have recently observed a 55-year-old male patient with back pain secondary to a vertebral metastasis due to a hepatocellular carcinoma. Initially, the bone scan showed the characteristic "clover" image at T-12 level and he was misdiagnosed with PD. Afterwards, the MRI suggested the diagnosis of a vertebral metastasis, and a computed tomography-guided needle biopsy further confirmed the diagnosis. In view of the present data, this image cannot be considered as patognomonic of PD.

A 71-year-old man with newly diagnosed malignant mesothelioma was referred for an F-18 FDG PET/CT study to evaluate the extent of disease. PET showed mild FDG uptake in the right chest, corresponding to a lobulated, mass-like right pleural effusion versus thickening involving the entire right pleural space, and some mediastinal involvement, on the accompanying CT scan. In addition, marked FDG uptake was seen in the proximal left humerus, suspicious for an osseous metastasis. The corresponding CT scan findings of cortical thickening and a "Swiss cheese" appearance were most consistent with Paget disease. The intense FDG uptake in an osseous lesion on FDG-PET in our case reminds us of the variable nature of FDG uptake in Paget disease, the possibility of false-positive findings on FDG-PET in patients with cancer, and the usefulness of the fusion techniques in the evaluation of skeletal lesions, with the potential for discriminating between benign Paget disease and other pathologic bone findings.

Primary multifocal osseous lymphoma is a rare and poorly recognized entity. Here, we present an instructive case of a young man who, six years after a local contusion of the left ankle, developed a painful polylobulated large soft tissue mass. This mass turned out to have arisen from the transformation of a centro follicular non-Hodgkin's lymphoma into a diffuse large B-cell lymphoma involving the calcaneus, talus, cuboid and navicular bones. The diagnostic difficulties as well as the implications of this aggressive transformation are highlighted here.

History and Clinical Findings: A 74-year-old man presented with bone pain of the right hip, night sweat and weight loss for 18 months. The diagnosis of Paget's disease was confirmed four months before admission, but pain and elevated serum alkaline phosphatase levels remained despite treatment with i.v. bisphosphonates. The physical examination showed no specific abnormalities., Investigations: Laboratory findings were elevated levels of serum alkaline phosphatase (AP), CA 19-9 and CEA. Radiological and tomographic images showed an aggressive periostal reaction consistent with Paget's sarcoma. The bone biopsy revealed the presence of prostatic cancer which was confirmed in a subsequent prostate biopsy., Treatment and Course: Because of the multiple bone and lung metastases the disease proved to be incurable and the patient received palliative therapy with flutamide. He died 12 months later., Conclusion: In patients with Paget's disease lacking of response to bisphosphonate administration (permanently increased AP and sustained pain) radiological and clinical re-assessment of the diagnosis is indicated and may sometimes also include bone biopsy.

Biochemical markers of bone turnover are used increasingly during the clinical development of drugs for the treatment of metabolic bone diseases such as Paget's disease, osteoporosis and cancer that has metastasised to the bone. However, assessing the optimal value of these markers is often complicated, and such an assessment is an obvious prerequisite for rational use of the markers and, consequently, potential improvement of clinical drug development. Biochemical markers of bone turnover are substances in the blood or urine that are produced or released during bone remodelling. They provide semiquantitative information on bone remodelling, and are often the most adequate tool to describe the pharmacodynamics of the drug. Their use has increased considerably because of dose-effect relationships that have been seen with certain drugs, but also because they have proven relationships with clinical outcomes in several metabolic bone diseases. However, there is a lack of information on the kinetics of these markers, and the immunoassays that are frequently used in their monitoring often measure a mixture of fragments rather than a single molecular entity. For drug development it should also be realised that different markers, but also different assays for the same marker, may provide different results, considerably limiting the ability to compare results. In postmenopausal osteoporosis, relationships have been shown between several biochemical markers of bone turnover, and either fracture risk and/or the antifracture efficacy of drugs. Such relationships can be used for the development of drugs with similar mechanisms of action, but also for the development of these drugs for closely related indications, such as corticosteroid-induced osteoporosis. In both of these instances, data on effects on biochemical markers of bone turnover are usually employed in combination with information about effects on bone mineral density. However, the relationships of these parameters with clinical outcomes may be remarkably different for drugs with alternative mechanisms of action, challenging the use of the markers for the development of new drugs for the treatment of patients with osteoporosis. At present, the pharmacological treatment of cancer that has metastasised to the bone is limited to several bisphosphonates. Recent studies have shown relationships between the normalisation of levels of biochemical markers of bone turnover and clinical outcomes, and prospective studies investigating the application of such relationships are ongoing. The markers may play an important role in the optimisation of registered bisphosphonate treatments. However, their role in the development of new drugs is still limited to dose selection, and potential relationships with clinical outcomes remain to be investigated in instances of new mechanisms of action. Biochemical markers of bone turnover are a valuable asset for drug development, but their rational use is determined by a number of variables. Correctly manipulating these may improve clinical development of drugs for the treatment of patients with metabolic bone diseases such as osteoporosis and cancer metastatic to the bone.

Osteolytic lesions seen on plain radiographs can be caused by various disorders of the bones such as simple bone cyst, aneurysmal bone cyst, plasmacytoma, giant cell tumor, eosinophilic granuloma and tuberculosis. We studied prospectively Tc-99m-methylene diphosphonate bone scan findings in osteolytic lesions seen radiologically and followed them to histopathology. Interestingly, the scans in these patients helped to show if the lesions were monoostotic or polyostotic and, in some cases, ruled out malignant or infective etiology.

Pagetoid osteosarcoma is a complication of Paget's disease of bone. Sarcomatous transformation is most often seen in severe, long-standing Paget's disease. Familial clustering of Paget's disease has been described with apparent autosomal dominant inheritance with high penetrance by the sixth decade. Although definitive proof of the specific gene involved remains elusive, some researchers have shown loss of heterozygosity in a region of chromosome 18q in a relatively high percentage of studied patients affected with either Paget's disease alone, in Pagetoid osteosarcoma, and in uncomplicated osteosarcoma. Our patient was diagnosed with Pagetoid osteosarcoma and had a first-degree relative with history of the same. We hypothesized that our patient's tumor samples might contain a similar genetic abnormality. Our analysis of several polymorphic markers from the chromosome 18q21-22 region showed loss of maternally inherited alleles throughout the region. This finding is similar to those described previously and provides further evidence of a susceptibility region relating to this disease. This report describes a father and son, their young ages at diagnosis of Pagetoid sarcoma, the identical sites of disease involvement, and a loss of heterozygosity study illustrating the inheritance of the presumed defective gene.

Objective: To report five symptomatic patients, four with unequivocal Paget's disease and large areas of osteolysis and one patient with presumed osteolytic Paget's disease, evaluated by MR imaging to confirm or exclude a sarcoma., Design and Patients: Four men and one woman (median age 74 years) presented with new symptoms of pain. Four of these patients had unequivocal Paget's disease with large areas of osteolysis; one patient presented with large focal osteolysis and no other finding. MR imaging was performed in each case to exclude malignancy in the area of osteolysis., Results: Two patients whose MR images showed a low signal abnormality on the T1-weighted sequence corresponding to osteolysis on the radiograph were found to have malignant degeneration. Three patients with osteolytic lesions on T1-weighted MR imaging showed preservation of fat signal in the areas of osteolysis, were not biopsied and have been free of malignant disease for from 12 months to 2 1/2 years. One patient had one area of osteolysis in the iliac bone which showed malignancy and another area of osteolysis which showed preservation of fat signal on the T1-weighted sequence., Conclusions: The information obtained from T1-weighted MR imaging sequences performed on patients with Paget's disease who have new symptoms and large areas of osteolysis could reliably be used in the clinical decision-making process between conservative follow-up and biopsy.

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.

Bone lesions, present in two women with primary breast cancer treated more than 5 years ago, were investigated thoroughly by biochemical markers and imaging techniques. The definite diagnosis was established by bone biopsy, which revealed two totally unrelated disorders that altered the management and prognosis for these two patients. One patient had Paget's disease, and the other had metastatic hepatocellular carcinoma.

The authors describe the case of a male patient who had had Paget's disease since 1973 which led to the diffuse swelling of the proximal femur in 1993. The elevated alkaline phosphatase level and the destructive lytic lesions on the X-ray of the femur raised the possibility of malignancy. The bone scan showed increased accumulation in the proximal part of the left femur. On the MR the low T1 and the elevated T2 signal intensity suggested malignity despite that in some regions signals typical of adipose tissue could also be seen, which is usually interpreted as a sign of benignity. In the histological specimens no signs of malignant tumour cells were identified. The patient received bisphosphonate treatment which decreased his pain and swelling and also the alkaline phosphatase level. The patient died because of a rapidly progressing retroperitoneal fibrosarcoma and lung metastasis in 1996. The autopsy did not prove any malignant transformation of Paget's disease of bone in the proximal femur.

A 51-year-old native of Rio de Janeiro presented with bilateral synchronous Paget's sarcomas in the tibiae, which developed in the upper right tibia and in the distal third of the left tibia. There were no other areas of Paget's disease. The largest tumor spread to the right inguinal nodes and also soft tissue. The tumor in the left tibia spread dramatically in the soft tissues up the leg and only involved the medullary cavity in its inferior portion. The patient died, but there was no autopsy. Comments are made about the prevalence of Paget's disease in Rio de Janeiro.

The development of bone sarcoma in a patient with Paget disease is a classic but rare event. The authors describe the XR, CT and MR features of an undifferentiated Paget sarcoma arising in the proximal ulna, a very rare location of this tumoral complication. Clinical symptoms, radiological pattern and epidemiology are discussed. In every Paget patient presenting with a new or different pain, with or without mass effect, the radiologist has to search for signs of sarcomatous transformation, i.e. cortical osteolysis, soft tissue mass and sometimes an associated fracture.

A rare case of mucinous adenocarcinoma presented as a solitary, metastatic deposit to a region of Paget's disease within the peripheral skeleton. Historical, physical, radiographic, and scintigraphic findings were indistinguishable from those of sarcomatous degeneration arising from pagetoid bone. This case supports the idea that when a painful, osteolytic lesion is discovered within a region of Paget's disease, bone scintigraphy has greater value of disclosing potential multifocal or multicentric disease than for providing etiologic specificity for the principal lesion.

Skeletal metastases from prostate cancer is common and usually do not pose a diagnostic dilemma. This study reviews radiographic appearances of prostatic metastases to the appendicular skeleton in four patients where the appearances simulated osteosarcoma, Paget's disease and Paget's sarcoma. Prostatic metastases to long bones can produce appearances considered characteristic of other lesions and suggest misleading alternative diagnoses.

The clinical and radiographic findings of four patients with multicentric giant cell tumor (GCT) of bone and Paget disease were retrospectively reviewed. Three patients underwent magnetic resonance (MR) imaging evaluation; all patients underwent computed tomography (CT). The MR characteristics of the bone component in pagetic GCT appeared to reflect the pagetic phase; a sclerotic pattern was largely represented by hypointense marrow signal intensity on images obtained with both long and short repetition times (TRs) and echo times (TEs). Conversely, a tumor appearing in a mixed pagetic phase demonstrated more heterogeneous signal intensity with all pulse sequences. Extensive soft-tissue components, noted in all cases, showed largely intermediate signal intensity on short TR/TE images and foci of increased signal intensity on longer TR/TE images. In most cases, dramatic reduction in tumor bulk was noted with the use of steroids alone. An awareness of this entity is important because the appearance of lytic lesions with soft-tissue extension in patients with Paget disease does not necessarily imply a grave prognosis. Serial CT or MR imaging is helpful in monitoring the remissions and exacerbations that reflect response to therapy in Paget disease and GCT.

Serum osteocalcin did not show any response to the onset of osteosarcoma in Paget's disease of bone whereas serum alkaline phosphatase increased rapidly. This suggests that osteocalcin is not useful in the diagnosis and management of Paget's osteosarcoma and does not reflect the same osteoblastic processes in bone as serum alkaline phosphatase.

This paper deals with the paramyxovirus-like intranuclear inclusions observed in giant cells tumours of bone (GCTB). Twenty-one (49%) of 43 cases of GCTB (1977-1985), either fresh and/or cultured, show these ultrastructural inclusions. Fifty samples of various bone lesions in which giant cell lesions occurred, including aneurysmal cysts, hyperparathyroidism, osteoblastoma, human and rat osteopetrosis, GCT of tendon sheaths, and non skeletal granuloma were used as controls. These, together with 20 samples of normal bone (osteoclasts) did not contain intranuclear or intracytoplasmic viral inclusions.

99Tcm-phosphate bone scans are being increasingly used in the detection of bony metatases. The sensitivity of the bone scan and the non-specific nature of the isotope image, when compared with radiographs, make it important to be aware of the problems and limitations of the technique. This paper describes and illustrates some of the diagnostic problems encountered by the author over the past 3 years.

We have compared the value of MRI with conventional radiography and CT in 40 predominantly sclerotic skeletal lesions. We have found that sclerosis and other changes in the bone structure can be demonstrated by MRI in much the same way as with conventional radiography and CT. Using high resolution surface coils, it is possible to demonstrate small areas of new bone formation such as periosteal new bone or the calcification within the nidus of an osteoid osteoma. MRI is particularly appropriate if it is necessary to show soft tissue changes within an area of sclerosis, which may be responsible for the new bone formation and which may be masked on radiographs and CT by the surrounding sclerosis.

We have presented three patients who had bony expansion due to metastatic carcinoma of the prostate demonstrated by roentgenography and bone scintigraphy. Bony expansion must be differentiated from the blooming phenomenon which may occur in areas of high radioactivity. Bony expansion is not specific for Paget's disease, but also occurs in many other benign and malignant conditions.

It is reported on the 4-year course of a disease in a patient with chronic myeloic leukemia in whom after three years an unusual affection of the bones in the distal thigh developed. Apart from this the differential-diagnostic difficulties are discussed: fibrosis of the bone marrow--chronic myeloic leukaemia--Paget's disease metastasis of a squamous cell carcinoma.

The authors report the results they obtained by bone scintigraphy using technetium pyrophosphate. In a study of 142 patients with cancer, the authors show, as others have done, that bone scintigraphy makes it possible to find bone metastases that are radiologically undetectable and they emphasize the importance of this discovery. In 7 patients with spondylodiscitis, of whom 1 was without radiological signs at the time the scintigraphy was carried out, the authors always observed localized vertebral hyperfixation and they noted that this examination can be valuable for distinguishing spondylodiscitis from pseudo-Pott's discarthroses and from the lesions of vertebral epiphysitis, which in their experience do not result in isotopic hyperfixation. In 7 patients with epiphyseal osteonecrosis, the authors observed isotopic hyperfixation before the appearance of radiological signs. In 12 patients with osteoporosis, the authors observed hyperfixation in bone in certain compressed vertebrae, whereas other vertebrae that had probably been compressed some considerable time earlier did not fix the isotope excessively. They never observed hyperfixation in vertebrae that were not compressed. Among 5 patients with ankylosing spondylitis with radiological signs of sacro-iliac arthritis, the authors observed sacro-iliac hyperfixation in only 3 cases. Two other patients who had signs indicating ankylosing spondylarthritis, but were without radiological signs of sacro-iliac arthritis did not show sacro-iliac hyperfixation of the isotope. Among 7 patients with Paget's disease, the authors observed hyperfixation in all the bones with radiological signs of disease; in addition, in 3 patients, there was also hyperfixation in certain bones that were radiologically clear.

In primary bone tumors the possibilities of bone scans are discussed. Exact differentiation between malignant and benign disease by this method is impossible. However, scanning provides important information about extent of the disease, metastases, multiplicity of benign lesions and influence of adjoining diseases to the bone. A special indication exists in cases of cerebral meningiomas and an absolute indication for searching osteoplastic metastases, e.g. in carcinomas of the breast and the prostate gland.