Multiple Osteolytic Bone Lesions Research Articles

A Rare Case of Adult Precursor B-Cell Lymphoblastic Lymphoma/Leukemia Presenting with Multiple Osteolytic Bone Lesions as Sole Manifestation

Abstract Primary precursor B-lymphoblastic lymphoma/leukemia (B-LBLL) of bone is uncommon neoplasm that accounts for less than 1% of primary bone tumors. It has been commonly reported in pediatric population but is rare in adults. We present a case of a 20-year-old man with multiple osteolytic lesions as sole presentation of acute lymphoblastic leukemia, whose diagnosis was established by bone biopsy. A peripheral blood smear and the bone marrow aspirate showed no blast cells. The patient received treatment according to BFM 99 protocol and achieved complete response confirmed by F-FDG-PET/CT.

Successful treatment of SAPHO syndrome (chronic nonbacterial osteomyelitis and acne) with anakinra and denosumab. Case report and review of therapy.

SAPHO is an acronym derived from capital letters of Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO). SAPHO syndrome is an umbrella term covering a constellation of bone lesions and skin manifestations. A 40-year-old male complained about his jaw and back pain, swelling of multiple joints and weight loss accompanied byphysical deterioration and acne type skin lesions. Laboratory tests revealed abnormal elevation of inflammatory markers. Imaging studies illustrated multiple osteolytic bone lesions and paraosseal infiltrates. According to the set of criteria diagnosis of SAPHO syndrome was stated. The patient was treated with glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs), but only high dose dexamethasone and prednisone were effective. Daily subcutaneous administration of anakinra at the dose of 100 mg was initiated due to limited response to more classical therapies. Because of planned mandibular osteosynthesis initiation of denosumab was preferred before bisphosphonates. Therapeutic response was confirmed by FDG-PET/MR after 5 months of anakinra and denosumab therapy, showing decreased accumulation of FDG in periosteal and paraosseal infiltrates. Inflammatory markers significantly decreased, bone pain deferred but skin manifestation receded only partially. Therefore the response was evaluated as partial remission.

Role of autopsy imaging-computed tomography in the post-mortem study of farm animals.

BackgroundAutopsy imaging (Ai) is used to determine the cause of death, providing pre‐dissection information. Ai is often used in the field of human forensic medicine but has never been applied on farm animals.MethodsAi‐computed tomography (CT) was performed before necropsy for farm animals (one goat, one ox, one cow and three calves) that died or were euthanised.ResultsAi‐CT findings of rib fractures (case 1), urethral calculi (case 2), multiple osteolytic bone lesions (case 3 and 4) and hair balls (case 4) were confirmed by dissection. However, a tentative diagnosis of actinomycosis was made in an ox (case 5) using antemortem radiography and Ai‐CT, and the mass was identified as ameloblastic fibro‐odontoma on histological examination. A tentative diagnosis of maxillary abscess was made from antemortem radiography in a cow (case 6); however, the lesion was shown to be maxillary neoplasia on Ai‐CT. The mass was identified as hemangiosarcoma on histopathological examination.ConclusionAi is helpful in pathological examination because the specific findings are known before the dissection, the lesions can be pinpointed in the pathological dissection, facilitating workflow; furthermore, the oversight of lesions can be reduced. In addition, Ai‐CT images, including three‐dimensional images and a three‐dimensional printed model, allowed an easy understanding of pathology among students and farmers. Ai‐CT for farm animals represents a novel option for veterinary education.

Computed tomography characteristics of multiple myeloma and other osteolytic metastatic bone lesions.

Differentiation of multiple myeloma (MM) from osteolytic metastatic (OM) bone lesions may be critical in patients with lytic bone lesions but can be challenging for radiologists. To determine whether computed tomography (CT) can be used to distinguish between MM and other OM bone lesions. In this retrospective study, 320 lesions of 207 patients diagnosed with MM or OM, based on biopsy or clinical examination, were evaluated. Eight qualitative features were evaluated by two radiologists blinded to the diagnoses. The chi-square and Fisher exact tests, and logistic regression analysis, were used to evaluate the relationships between the CT findings and diagnoses. High-density areas were more common in OM than MM lesions (85.2% and 19%, P < 0.001), as were perilesional sclerosis (38.9% vs. 13.2%, P < 0.001), heterogeneity (on non-contrast CT images, 60% vs. 19.1%, P < 0.001; on contrast enhanced CT images, 80.6% vs. 28.2%, P < 0.001), and ill-defined margins (34.6% vs. 9.1%, P < 0.001). Similarly, OM lesions showed high-density areas more than MM in evaluation of skeletal system subgroups (vertebrae, 93.8% vs. 29.8%, P < 0.0001; thoracic cage bones, 69.6% vs. 19.2%, P < 0.001; pelvic bones and sacrum, 84.8% vs. 7.7%, P < 0.001; peripheral skeletal bones, 81.5% vs. 8.3%, P < 0.001). Logistic regression analysis revealed that the presence of a high-density area in the lesion increased the probability of a metastasis 25.88-fold (R2 = 0.516, P < 0.001). MM and OM lesions can be differentiated by CT; OM lesions exhibit high- density areas.

Comparative Findings Between 68Ga-PSMA and 18F-FDG PET/CT for Hepatocellular Carcinoma

We have reported here the case of a 69-year-old man who presented with spinal cord compression due to bone metastases as the first manifestation of hepatocellular carcinoma (HCC). For the initial staging, the patient underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) imaging, which demonstrated mild 18F-FDG uptake in the multiple expansile osteolytic bone lesions, but no remarkable atypical 18F-FDG uptake in the liver lesion on low-doses CT. An additional PET/CT scan was performed to evaluate the prostate-specific membrane antigen (PSMA) expression, which has recently been reported to be a potential biological marker in a variety of tumors including HCC. High PSMA uptake was recorded in both the metastatic bone lesions and the primary liver lesion/tumor by the 68Ga-PSMA PET/CT.

Multifocal tuberculosis simulating a cancer-a case report

BackgroundTuberculosis is a disease that may affect any organ of the body. Multifocal tuberculosis involving multiple systems with associated symptoms are rare, which makes the diagnosis challenging. Distinguishing multifocal tuberculosis from lesions metastatic from system malignancy is difficult. Single detection method is difficult to make a diagnosis. A combination of multiple methods is essential.Case presentationA 17-year-old male presented with a 20 days weakness of lower limbs, which aggravated for 6 days. The PET/CT showed increased metabolism of ileocecal intestinal and terminal ileum wall, multiple enlarged lymph node (LNs), multiple osteolytic bone lesions, and soft tissue intensity belong T7 and T8 vertebrae. To confirm the diagnosis of the disease, a biopsy of the mediastinum lymph nodes was carried out. Polymerase chain reaction (PCR) test of the specimen was positive for the Mycobacterium tuberculosis, the T-SPOT and Xpert MTB/RIF test were also positive, which suggested the presence of Mycobacterium tuberculosis. The final diagnosis was multifocal tuberculosis, the patients received the resection of the mass in the spine. Anti-tuberculosis drugs were given. The myodynamia and muscle tension of the patients recovered following the therapy.ConclusionsOur results indicated that Multifocal tuberculosis should also be taken into consideration when lesions metastatic from system malignancy were suspected from images results even without the clinical symptoms of tuberculosis, and combination of multiple diagnosis methods were essential for the diagnosis of multifocal disease.

Cystic angiomatosis, pleural effusion and multiple bone lesions mimicking a metastatic malignant neoplasia: a case report

BackgroundWe report a case of a patient with a rare clinical condition: cystic angiomatosis presenting as pleural effusion and multiple bone lesions mimicking a metastatic malignant neoplasia. With only about 50 such cases published in the literature, it is important to report the clinical presentation and proposed treatment and to share information about the clinical evolution in these patients.Case presentationWe report a case of a 45-year-old white man who presented to our hospital with ventilator-dependent pain. Chest tomography detected pleural effusion and multiple osteolytic bone lesions. Oncologic investigation for metastatic malignant neoplasia was started after exclusion of an infectious process. Imaging examinations revealed diffuse osteolytic lesions as well as cystic lesions of the spleen, with discrete glycolytic hypermetabolism visualized by positron emission tomography. After negative results were obtained by investigation of the primary tumor site and a bone biopsy, a final diagnosis of cystic angiomatosis was made.ConclusionsIn view of the fact that cystic angiomatosis is a heterogeneous disorder of unpredictable prognosis and uncertain treatment, it is necessary to disseminate new cases so that further studies may be undertaken to obtain further physiopathological findings and an effective treatment.

Non-secretory multiple myeloma with extramedulary plasmocytoma

Non-secretory multiple myeloma (NSMM) is an uncommon variation of the classic form of multiple myeloma (MM) that has au analogous clinical and radiologic presentation except for the absence of the M-protein in sernm and/or urine. NSMM may have or not detectable monoclonal free light chain in urine/serum. We describe here a case of a 46-year-old woman who presented with back pain and lower limb weakness. A tumour lesion at DI level and multiple osteolytic bone lesions were found. This woman had no other symptoms and her basic blood biochemistry were nonnal. She had normal serum and urine protein electrophoresis. Biopsy from the D1 vertebra showed plasmocytoma. In the bone marrow, 20% atypical plasma cell fow1d, all were being CD38+ and CD 138+ in flowcytometry, confirming the diagnosis of myeloma presenting as NSMM. A high index of suspicion is needed to diagnose cases like this, as the biology ofNSMM is not completely understood.

Atypical noncontiguous multiple spinal tuberculosis: a case report.

ObjectiveSpinal tuberculosis-associated symptoms are not so unique as to immediately indicate the proper diagnosis in most cases. Distinguishing spinal tuberculosis (Pott's disease) from pyogenic spondylitis is often difficult, and lesions metastatic from systemic malignancy are the other major entity from which spinal tuberculosis must be distinguished.Clinical PresentationA 27-year-old male patient presented with a history of back pain after a minor trauma 1 month ago. Computed tomography and magnetic resonance imaging of the thoracic spine showed multiple osteolytic bone lesions at the bodies of T9, T10 and T11 vertebrae and the spinous processes of T12 and L1. Other noncontiguous osteolytic lesions were noted at S2 body and right sacro-iliac joint.InterventionTo confirm the pathologic diagnosis, the patient underwent an open biopsy for the T12 and L1 spinous process lesions and a percutaneous transpedicular biopsy on T9, T10, T11 lesions. Frozen biopsy was reported as compatible with chronic granulomatous caseating necrosis without malignant cells. The final diagnosis was an atypical presentation of multiple spinal tuberculosis. The patient received an appropriate enteral anti-tuberculosis therapy and recovered without any complications. Follow-up MRI taken after a year of medical treatment revealed marked resolution of the lesions.ConclusionCurrent research indicates the incidence of multi-level noncontiguous, remote vertebral tuberculosis is 1.1% to 16%. Because tuberculous spondylitis could represent variant and atypical pattern, the disease should be considered in differential diagnosis along with other diseases such as metastatic neoplasm, pyogenic spondylitis, especially when the radiologic studies are revealing multiple spinal lesions.

401 - Pattern of Bone Metastasis and Treatment Outcomes of Chinese Triple Negative Breast Cancers

ABSTRACT Objective To investigate the characteristics of bone metastasis, prognosis and treatment strategies of triple negative breast cancer (TNBC) patients in China. Methods 269 metastatic TNBC between Jan 1, 2005 and Dec 31, 2011 were retrospectively reviewed. Bone metastases were identified as primary metastatic site in 83 patients (30.8%). Among them, 25 patients (30.1%) had bone metastasis as the only relapse and the remaining were accompanied by involvement of other locations. Clinical pathologic characteristics and treatment outcomes were evaluated in these 83 cases. Results Median age was 48.2 (22-84) years. Median disease-free survival was 30.3 month (95% CI: 8.9-58.9 months). In these patients with bone metastasis as the primary distant site, most of them had multiple osteolytic bone lesions (78.3%). The incidence of skeletal related events was 24.1%. Chemotherapy was administered as the first choice in majority of patients (75 out of 83, 90.4%). Overall response rate was 44.0%, including 1 CR (1.3%) and 32 PR (42.7%). Median time to progression (TTP) of first-line chemotherapy was 8.0 (95%CI 8.7-16.0) months and median overall survival (OS) was 30.0 (95%CI 30.8-47.4) months. No differences were seen when comparing taxanes-based with non-taxanes regimen, platinum-based with non-platinum regimen and capecitabine-contained with non-capecitabine regimen in terms of response rate, TTP and OS. Conclusions Although the incidence of bone metastasis in mTNBC were not as high as in Luminal type, it was also common in Chinese patients, different from previous literatures reported in western countries. The survival of metastatic TNBC with bone metastases is poor. Chemotherapy was without doubt the primary treatment options, however, no the superiority of any chemo-agent have been proved now. Disclosure All authors have declared no conflicts of interest.

Osteitis Fibrosa Cystica Mistaken for Malignant Disease

A 65-year-old man with back pain had plain radiographs that showed multiple osteolytic bone lesions of the pelvis, femur and L-spine; an magnetic resonance imaging scan of the L-spine showed extensive bony resorption with a posterior epidural mass involving the L1 spinous process; these findings suggested multiple myeloma or bony metastasis. However, all serology testing was negative. The parathyroid hormone and serum calcium levels were found to be abnormally elevated. A fine needle aspiration biopsy suggested that the L-spine lesion was consistent with the diagnosis of osteitis fibrosa cystica. A pathological fracture of the spine compressed the spinal cord, and surgical intervention was required. The neck computed tomography and Tc-99m sestamibi scan showed a solitary parathyroid mass. A minimally invasive parathyroidectomy using intraoperative parathyroid hormone monitoring was performed and two enlarged parathyroid glands identified. This case illustrates the importance of the consideration of a rare brown tumor associated with primary hyperparathyroidism in patients with the bone lesions suggestive of a malignancy.

Non-Secretory Myeloma or Light Chain-Producing Multiple Myeloma: A Case Report

Nonsecretory multiple myeloma (NSMM) is a rare variant of the classic form of MM that has a similar clinical and radiologic presentation except for the absence of the M-protein in serum and/or urine. Depending on the author, NSMM may have or not detectable monoclonal free light chain in urine/serum. We describe here a case of a 51-year-old woman who presented with back pain and multiple osteolytic bone lesions. This woman had no other symptoms and her serum basic analyses were normal. She had normal serum and urine protein electrophoresis, but a monoclonal kappa light chain band in plasmatic and urinary immunofixation was found. A CT guide biopsy from the D4 vertebra showed 9% plasmocytes in the bone marrow, 100% of them with an abnormal phenotype, all being CD38+ and CD138+, confirming the diagnosis of light chain myeloma, initially presenting as NSMM. A high index of suspicion is needed to diagnose cases like this, as the biology of NSMM is not completely understood. The potential value of more sensitive quantitative diagnostic techniques for this disease is being studied. doi:10.4021/jmc156w

Kaposiform (Spindle Cell) Hemangioendotelioma in a Child With an Unusual Presentation

We describe a male child with multifocal kaposiform hemangioendothelioma in the right and left cervical region with development of Kasabach-Merritt syndrome. Treatment with interferon-alpha resulted in a good but only temporary clinical response.He relapsed 3 times with regrowth of the right cervical tumor. Involvement of the liver is suspected, because normalization of the liver size followed after the treatment with interferon-alpha. The question remains whether the multiple osteolytic bone lesions also reflect kaposiform hemangioendothelioma localization.

Multiple osteolytic bone lesions with high serum levels of interleukin‐6 and CCL chemokines in a patient with adult T cell leukemia

A 37-year-old woman was diagnosed as having chronic adult T-cell leukemia (ATL) of the skin by a skin biopsy and human T-cell leukemia virus type-1 serology at our hospital in August 1992. The skin lesions of ATL were improved by treatment with psoralen ultraviolet ray A. She complained of severe pain in her bilateral forearms, hands and ankles, and X-ray examination in July 1999 revealed multiple punched-out lesions of the extremities. Serum levels of parathyroid hormone-related peptide, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha and total serum receptor activator of nuclear factor kappaB ligand were not elevated. However, serum levels of IL-6, CCL2 monocyte chemoattractant protein-1 (MCP-1), CCL3 [macrophage inflammatory protein-1alpha (MIP-1alpha)] and CCL4 (MIP-1beta) were markedly elevated. Here, we have discussed the possible mechanism underlying the onset of the osteolytic lesions.

Recommendations for Zoledronic Acid Treatment of Patients with Bone Metastases

The introduction of zoledronic acid, a new-generation bisphosphonate, has greatly extended the use of bisphosphonates in the treatment of patients with bone metastases. On the basis of results from three large, randomized, phase III clinical trials enrolling more than 3,000 patients, zoledronic acid (4 mg via 15-minute infusion) was approved in the United States for the treatment of patients with documented bone metastases from solid tumors in conjunction with standard antineoplastic therapy and patients with multiple myeloma. Zoledronic acid is also approved in Europe for the prevention of skeletal-related events in patients with advanced malignancies involving bone. Current treatment guidelines published by the American Society of Clinical Oncology recommend the use of intravenous bisphosphonates at first radiographic evidence of osteopenia in patients with multiple myeloma or osteolytic bone lesions in patients with breast cancer to significantly reduce the occurrence and delay the onset of skeletal complications. Zoledronic acid has also demonstrated efficacy in the treatment of bone metastases in patients with prostate cancer, lung cancer, and other solid tumors. Bisphosphonate therapy is generally well tolerated but can be associated with increases in serum creatinine. Therefore, monitoring renal function is required for all patients receiving bisphosphonate therapy. Serum creatinine should be monitored before each dose and treatment withheld until any serum creatinine elevations have resolved to baseline levels. Caution should be exercised when treating patients who are receiving other potentially nephrotoxic therapies. With these simple precautions, intravenous bisphosphonate therapy is safe for long-term use and provides durable treatment benefits.

Expression of receptor activator of NF-kappaB ligand (RANKL) mRNA in human multiple myeloma cells.

Increased bone resorption is a hallmark of multiple myeloma and a result of excessive osteoclast activation. Recently, the receptor activator of NF-kappaB ligand (RANKL) was found to be the critical factor for osteoclastogenesis. Studies showed that myeloma cells induce RANKL expression in bone marrow stromal cells, but it remained a controversy whether myeloma cells directly express RANKL. Therefore, we analyzed the expression of RANKL mRNA in freshly isolated CD138 positive plasma cells from patients with multiple myeloma and osteolytic bone lesions, using three different primer pairs against human RANKL. RANKL mRNA could be detected in bone marrow plasma cells from myeloma patients with osteolytic myeloma bone disease. These findings show that myeloma cells directly express RANKL and indicate that specific blockade of RANKL may be an effective treatment for myeloma bone disease.

Gingival mass as the primary manifestation of multiple myeloma: Report of two cases

Two cases of multiple myeloma with primary manifestations in the oral cavity are reported, both presenting as a mandibular gingival/alveolar mass with hypermobility of the adjacent teeth. Roentgenographic examination demonstrated concomitant "punched-out" osteolytic jawbone lesions. After biopsy of the gingival mass was performed, multiple myeloma was subsequently diagnosed in both cases. Systemic bone scanning revealed multiple osteolytic bone lesions involving the skull and various skeletal bones. Hematologic screening showed a monoclonal gammopathy in both cases. A bone marrow biopsy confirmed the diagnosis of multiple myeloma. Awareness of the maxillofacial manifestations of multiple myeloma is important for early detection of the disease, especially in patients with initial oral involvement.

393 JUVENILE HYALINE FIBROMATOSIS – CAUSED BY DISTURBED METABOLISM OF TYPE DT COLLAGEN?

A defective metabolism of collagen fibrils is the suspected cause of juvenile hyaline fibromatosis (JHF), a rare autosomal recessive disorder characterized by multiple skin tumors, hypertrophic gingivae, flexion contractures and osteolytic bone lesions. All these sites predominantly harbor type-I (TIC) and type-III (TIIIC) collagens. Therefore we analyzed fibroblasts from macroscopically normal, biopsied skin of a JHF patient and a normal individual for markers of TIC and TIIIC metabolism, i.e. propeptides PICP (TIC synthesis), ICTP (TIC degradation) and PIIINP (TIIIC metabolism). All experiments were done in triplicates using cell number-matched supernatants. Data are given as mean μg/flask. Both PICP and ICTP were significantly higher in JHF (24,I and 0,516) than in the controls (12,6 and 0,324), but their ratio remained unchanged, indicating an accelerated yet balanced TIC metabolism. PIIINP was markedly decreased in JHF (1,05 vs. 1,65), being reduced by 50% relative to TIC. The diminished stability of collagen molecules in JHF might be explained by reduced enzymatic removal of these TIIIC-terminal propeptides, which is necessary for regular crosslinking of collagen fibrils. We suggest that the increased TIC turnover, as well as the exessive production of extracellular matrix as observed previously in histological investigations of JHF tissues, are secondary effects of an upset TIIIC metabolism instrumentally involved in the pathogenesis of this disease.

Philadelphia chromosome-negative acute hematopoietic malignancy: Ultrastructural, cytochemical and immunocytochemical evidence of mast cell and basophil differentiation

We describe a patient with fever and multiple osteolytic bone lesions accompanied by hypercalcemia, a duodenal ulcer, anemia, and thrombocytopenia. Bone marrow showed a dense infiltration by abnormal cells characterized by small basophil granula, erythrophagocytosis and nuclear atypia. These cells were positive for toluidine blue and partly for myeloperoxidase and chloroacetate esterase, expressed myeloid differentiation markers, and exhibited multiple numerical and structural chromosome aberrations. Molecular genetic analysis showed no breakpoint cluster region rearrangement. Electron microscopy demonstrated granula both of basophil and mast cell type. Concluding, in this patient an acute hematopoietic malignancy with many features of malignant mastocytosis but also with signs of a basophil differentiation. This is further support for a hematopoietic stem cell origin of human mast cells.