Osteoblastic Skeletal Metastases Research Articles

Wnt1 induces osteoblastic changes in a well-established osteolytic skeletal metastatic model derived from breast cancer.

Osteoblastic skeletal metastasis is frequently observed in prostate cancer. An effective therapy has not been developed due to the unclear molecular mechanism. The Wnt family is involved in various biological phenomena including bone metabolism. There is no direct evidence that the family causes osteoblastic skeletal metastasis. The present study aims to evaluate whether overexpressed Wnt induces osteoblastic bone metastasis in a well-established osteolytic bone metastatic model. The breast cancer-derived 5a-D-Luc-ZsGreen cells were transfected with Wnt1, Wnt3A, and Wnt5A expression vectors, producing stably highly expressing cells. These cells were intracardially transplanted in nude mice. Bone metastasis development was confirmed by fluorescence imaging. Hind-limb bones including metastasis were dissected and visualized through micro-CT imaging. After imaging, sections were stained with hematoxylin and eosin (H&E), and immunohistochemically stained with an anti-SATB2 antibody. Luminescent imaging confirmed mice with bone metastases in the hind limbs. Micro-CT imaging found an osteoblastic change only in bone metastasis of mice transplanted with Wnt1-expressing cells. This was confirmed on H&E-stained sections. SATB2 immunostaining showed differentiated osteoblasts were at the site of bone metastases in the diaphysis. SATB2 in the Wnt/β-catenin pathway activated by overexpressed Wnt1 could induce osteoblastic change. Our findings provided direct evidence Wnt1 is involved in osteoblastic bone metastasis development. Our model would be a powerful tool for further elucidating molecular mechanisms underlying the disease and developing effective therapies.

Osteopoikilosis mimicking osteoblastic bone mets: A Case report

Background: Osteopoikilosis is a benign, uncommon disorder that is inherited by the autosomal dominant gene. Multiple benign enostoses are present in this specific kind of sclerosing skeletal dysplasia, which can be mistaken for osteoblastic skeletal metastases. Case Presentation: We present here a case of 50-year-old male patient with pain in lower back for 3 months. His pelvic X-ray showed few sclerotic rounded lesions in ilium, acetabulum and proximal femur. His MRI pelvis showed T1WI and T2WI hypo intense focal lesions in ilium and acetabulum. His 99mTc MDP bone scan was done showing no focal abnormal uptake in lesion reported on pelvic X-ray and MRI. These features are suggestive of Osteopoikilosis, ruling out osteoblastic skeletal metastasis. Conclusion: Osteopoikilosis is usually an incidental finding on radiograph. Both x-ray and MRI findings can mimic skeletal metastasis, but a normal bone scan can rule out metastasis and is useful if metastatic disease is thought to be a possibility.

Metastatic Ewing’s Sarcoma of the Adrenal Gland in a Young Indian Male: a Rare Fate

Ewing’s sarcoma of the adrenal gland is rare, and only a few cases have been reported in literature so far. We report a case of a young male with a large mass in the left suprarenal region with infiltration into the surrounding organs and multiple osteoblastic skeletal metastases. Biopsy and immunohistochemistry were consistent with a diagnosis of Ewing’s sarcoma. He was started on vincristine, adriamycin, and cyclophosphamide alternating with ifosfamide and etoposide (VAC/IE) chemotherapy. A post chemotherapy scan showed a progressive disease, and an alternative regimen of vincristine, irinotecan, and temozolomide was started. He could receive only one cycle before he succumbed to his illness. This case underlines the natural course of disease in patients with de novo metastatic Ewing’s sarcoma, and although the treatment of metastatic Ewing’s is not standardized, this case highlights the best treatment strategies for patients with such poor prognosis so as to preserve valuable resources and provide maximal survival benefit.

Primary Cerebral Plasmacytoma: A Rare Case Report with Review of Literature

AbstractSolitary craniocerebral plasmacytoma is the least common form of extramedullary solitary plasmacytoma (SP). Cerebral SP is very rare. The world literature counts only seven intracranial cases. The authors report a case of cerebral tumor of SP in a 52-year-old female who presented to a hospital with headache and difficulty in walking for 6 months. Contrast-enhanced computed tomography (CECT) brain showed left occipital intracranial space occupying lesions (ICSOL) of size 26 mm × 14 mm adjacent to superior sagittal sinus with disproportionate perilesional edema and midline shift toward the right. She underwent gross total tumor excision with left fronto-temporo-parietal decompressive craniectomy. Microscopic sections showed highly cellular tumor infiltrating white matter and gray matter. Histopathology revealed plasmacytoma. These plasma cells were seen infiltrating the adjoining brain parenchyma. Immunohistochemistry study showed the following pattern of antigens: most of the cells were negative to CD138 antibody, and majority of cells were positive (++ to +++) to CD56 antibody, more groups of cells were positive to lambda antibody than KAPPA. Bone marrow biopsy showed only 1% polyclonal plasma cells. Whole body bone scan showed no evidence of any osteoblastic skeletal metastasis. The patient recovered well, and cranioplasty was done after 6 weeks. Conclusion Cerebral SP is rarely found in clinical practice and if diagnosed properly can save patients life. This case report would definitely address many unexplored facts about cerebral SP and set milestone in the field of clinical research.

Presumptive Late-Onset Ankylosing Spondylitis Simulating Osteoblastic Skeletal Metastasis in a Patient With a History of Prostate Carcinoma: A Diagnostic Challenge

ObjectiveThe purpose of this report is to present a presumptive case of ankylosing spondylitis with late stage progression that simulated osteoblastic metastasis in a patient with a history of prostate carcinoma. Clinical FeaturesA 67-year-old white man presented to a chiropractic clinic complaining of severe and worsening acute low back pain and right foot “numbness.” Further questioning also revealed a history of prostate carcinoma. Intervention and OutcomeImaging examination revealed a sclerotic pedicle and increased uptake of radiopharmaceutical on a nuclear medicine bone scan highly suggestive of osteoblastic skeletal metastasis. Further evaluation, however, revealed that the bone sclerosis was not the result of skeletal metastasis, but more consistent with a seronegative spondyloarthritis such as ankylosing spondylitis. ConclusionThis report describes a presumptive case of ankylosing spondylitis simulating skeletal metastasis in a patient with a past medical history of prostate cancer. This atypical presentation illustrates the inherent uncertainty of diagnosis and how that uncertainty can be challenging in clinical practice. It also reinforces that it is critical for healthcare providers to consider a wide spectrum of differential diagnoses to avoid misdiagnoses and inappropriate interventions.

Dormant Metastases in Medullary Thyroid Carcinoma.

Report on a patient in whom an extensively metastasizing medullary carcinoma of the thyroid was diagnosed at the age of 32 years. Noteworthy in her case history were watery diarrheas that had persisted for two years, suggesting that the medullary thyroid carcinoma had already existed for some time. Besides locoregional lymph node metastases, small foci of diffuse pulmonary metastases with lymphangitis carcinomatosa as well as osteoblastic skeletal metastases were present and intramammary metastases were detected later. The patient died from bilateral pleuropneumonia with empyema formation at the age of 47 years after an observation period of 15 years. During that period, no major changes in the pattern of metastatic spread were observed and one may therefore speak of "dormant" metastases in this case, although some manifestations showed increases and decreases in size.

Pontine glioma with osteoblastic skeletal metastases in a child

BACKGROUND The development of systemic metastases from primary intracranial gliomasis rare. We report here a rare case of pontine glioma with osteoblastic skeletal metastases. CASE This 12-year-old boy presented with a 4-month history of hoarseness, dysphagia, and a progressively ataxic gait. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) revealed a brain stem tumor that was diagnosed as a low grade glioma by stereotactic biopsy. Twelve months later following chemotherapy and radiotherapy, neurologic examination and neuroradiologic studies disclosed a recurrence of the pontine glioma. Skeletal roentgenograms revealed widespread osteoblastic metastases in the skull, vertebral bodies, pelvis, and long bones. A specimen from the iliac bone demonstrated cells that were immunoreactive glial fibrillary acidic protein (GFAP). DISCUSSION The mechanism of how glioma cells determine their biologic behavior at bony metastatic sites is not known. Infratentorial gliomas, which occur frequently in young patients and demonstrate active bony metabolism, may stimulate osteoblastic cells, and induce osteoblastic changes.

Induction of urinary plasminogen activator by retinoic acid results in increased invasiveness of human prostate cancer cells PC-3.

Overproduction of uPA by prostate cancer cells in vivo results in tumor invasiveness and osteoblastic skeletal metastasis due to its mitogenic actions in osteoblasts. In the present study we have examined the effect of several growth factors and steroid hormones on regulating uPA gene expression in the human prostate cancer cell line (PC-3). Treatment of these cells with dexamethasone (Dex) caused a decrease, whereas epidermal growth factor (EGF) and fetal bovine serum (FBS) increased uPA expression in a dose-dependent manner. Trans retinoic acid (RA) also induced uPA mRNA and protein production in a dose-dependent manner (10(-6) to 10(-9) M). This increase was seen as early as 2 hr of treatment until 48 hr. Dex treatment resulted in decreased tumor cells invasiveness, whereas exposure to EGF and RA caused an increase in the invasive capacity of PC-3 cells. These studies should help to better understand the control mechanism of uPA expression in prostate cancer, where uPA has been implicated as a major pathogenetic factor.

Strontium 89 Therapy for the Palliation of Pain Due to Osseous Metastases

To present the current state of systemic radiopharmaceutical therapy for the palliation of pain in individuals with metastatic cancer and to evaluate the palliative effect and degree of hemotoxicity of strontium chloride 89 (89Sr) in patients with painful osteoblastic metastases primarily from prostate and breast cancer. A MEDLINE search through December 1994 was performed to identify English-language studies that met the following criteria. All eligible studies reported treatment of patients with painful osteoblastic bony metastases primarily from prostate or breast cancer treated with intravenous 89Sr. For study eligibility, evaluation of clinical response as assessed by the Karnofsky index, need for pain medication, or changes in mobility or sleep patterns was required. Hemotoxicity data were a requirement. A minimum of 10 prostate cancer cases was necessary for study inclusion. Only those studies assessing clinical response following one injection of 89Sr were included. Preliminary reports of cooperative studies were not included. Doses of 89Sr ranged from 0.6 MBq/kg (16 microCi/kg) to 400 MBq (10.8 mCi) per patient. Evaluation of patients for at least 3 months following 89Sr treatment was required. In addition, two studies examining issues of cost with regard to 89Sr treatment were identified. Baseline pain assessment and periodic pain estimates as measured by the Karnofsky index, medication diaries, changes in mobility, sleep patterns, and/or ability to work were the basis for assessment of response. Baseline and periodic complete blood cell counts were the basis for hemotoxicity evaluation. Palliation and hemotoxicity data were analyzed separately for each study. Some improvement occurred in as many as approximately 80% of patients. Several studies demonstrated complete relief of pain in at least 10% of patients The nadir of platelet and white blood cell counts appears at approximately 4 to 8 weeks following injection, with a partial return to baseline by 12 weeks. As many as 10 injections spaced 3 months apart have been given to some patients with repeated palliative effect and without serious hemotoxicity. Reinjection may be limited by a platelet count below 60 x 10(9)/L, a white blood cell count below 2.4 x 10(9)/L, or the absence of osteoblastic skeletal metastasis as seen on bone scan. Studies examining treatment costs suggest that 89Sr may decrease costs associated with palliation of pain due to metastatic disease. As many as 80% of selected patients with painful osteoblastic bony metastases from prostate or breast cancer may experience some pain relief following 89Sr administration. In addition, as many as 10% or more may become pain free. Duration of clinical response may average 3 to 6 months in some cases. Hemotoxicity is mild. A decrease in treatment costs with administration of 89Sr to patients with painful osteoblastic bony metastases from prostate cancer may occur. These observations reflect the preliminary nature of knowledge in this field and point to the need for larger clinical trials of the use of 89Sr palliation.

Differentiated astrocytoma with osteoblastic skeletal metastases in a child

A 13-year-old boy developed widespread osteoblastic bone metastases, with dissemination throughout the neuraxis, 1 year following treatment of a differentiated (Kernohan and Sayre grade II) astrocytoma of the left parietal cortex. This unusual clinical picture and the possible route of tumour dissemination are discussed.

Undifferential parotid carcinoma with osteoblastic metastases

Distant metastases from pamotid neoplasms are rarely detected early in the course of the disease. The highest incidence of hematogenous dissemination occurs in undifferentiated carcinoma. The skeleton is slightly less often involved than the lungs, and only destructive bony metastases have previously been reported. This report describes a young female with undifferentiated pamotid carcinoma which provoked osteoblastic reaction at the site of invasion of the skull base and rapidly gave rise to widespread osteoblastic skeletal metastases, without evidence of pulmonary metastases.