Destructive Bone Lesions Research Articles

The disappearance of femoral head and neck resulting from extensive bone defect caused by secondary syphilis: a case report and literature review

BackgroundTreponema Pallidum (TP), the pathogen of syphilis, commonly infects bones in cases of congenital and tertiary syphilis, but it is rare in the primary and secondary stages. With its mild symptoms and rare clinical findings, it might be easy to dismiss the diagnosis of early syphilis. Usually, effective results can be achieved after the conventional strategy of antibiotic treatments, mainly penicillin. To our knowledge, our case is so far the most serious reported case of destructive bone lesion in secondary syphilis, and our treatment for the case is the first strategy using total hip arthroplasty in secondary syphilis.Case presentationWe present the case of a 71-year-old man with local repeated pain and dysfunction in the right hip. Radiologic examinations showed the disappearance of the ipsilateral femoral head and neck. After excluding the aetiologies of cancer metastasis and tuberculosis, we confirmed the diagnosis of syphilitic arthritis. The patient received the medical treatment of antibiotics and the surgical treatment of total hip arthroplasty. At the follow-up of 1, 3, and 5.5 years after the operation, the patient presented with a pain-free and functional hip prosthesis without local signs of infection and loosening.ConclusionsThis report highlights the difficulties of early diagnosis of secondary syphilis with bone involvement. Bone defect of the femur with secondary syphilis, especially at the proximal femur, was an extremely rare complication in the previous reports. Our case was the first case of a patient who experienced the disappearance of femoral head and neck caused by secondary syphilis. Follow-up after the operation proved the successful treatment of the extensive bone defect of femur by total hip arthroplasty.

Surgical resection of a giant spine aneurysmal bone cyst in a child

Introduction: Aneurysmal bone cyst is a benign and destructive bone lesion of unknown etiology. Current approaches to treatment include surgical en bloc excision, curettage, selective arterial embolization and radiotherapy. A giant aneurysmal bone cyst in the lumbar vertebra is reported, along with a brief review of the literature on the topic. Method: A 15- year old boy presents with lumbar pain and a 3 months history of paraparesis. Diagnostic imaging revealed an expansile lytic lesion in the spinous process and lamina of the fourth andfifth lumbar vertebra. Surgical treatment consisted of excisional biopsy and a segmental instrumented posterior fusion from L2-S1. Histopathology was consistent with an aneurysmal bone cyst. After one year, the patient improved his neurological function with only a L5 bilateral paresis. Discussion: Treatment of aneurysmal bone cysts of the spine is challenging when it occurs in close proximity to neural and vascular structures. Fusion and stabilization with instrumentation are often necessary. One vertebra is involved in most cases and extensive lesions are uncommon. Complete tumor resection and fusion of lumbar spine, using stabilization with instrumentation provide both cure and preservation of lumbar spine stability. Neurological deficits can be improved by surgical removal of the tumor

A Case of Precursor B-cell Acute Lymphoblastic Leukemia Occurre d with Rapid Hip Bone Destruction and Femoral Neck Fracture

Background: Precursor B-cell lymphoblastic lymphoma is a rare subtype of acute lymphoblastic lymphoma and sometimes presents as lytic bone lesions. Diagnosis and treatment of lytic bone lesions are always challenging. This is a rare case of delayed leukemic change of precursor B-cell acute lymphoblastic lymphoma presented with a rapid hip bone destruction.Case presentation: A 12-year-old Japanese girl presented with progressive left hip pain, and bone destruction of her left hip two months after the onset of symptoms. She had no past medical or family history of malignancy and had no genetic abnormality. Radiograph and MRI examination showed bone destruction and osteolytic lesions in her left femoral neck and pelvis. Blast cells were not found in our initial examination of the peripheral blood and aspirated bone marrow cells. The case was finally diagnosed as Precursor B-cell lymphoblastic lymphoma as the results of bone biopsy, and blast cells were then detected after preforming multiple bone marrow aspirations. She also had pathological femoral neck fracture, but after treatment regimen by chemotherapy, her osteolytic lesions cured with obtainment of femoral neck fusion. She could walk at the final period.Conclusion: This case highlights the importance of early diagnosis of this disease for greater curing rates. Diagnosis of Precursor B-cell lymphoblastic lymphoma was finally made based on the results of biopsy of tissues because of the delayed appearance of leukemic changes. Orthopaedic surgeons should be aware of Precursor B-cell lymphoblastic lymphoma, when making diagnosis of patients exhibiting a rapid hip bone destruction.

A review of the musculoskeletal manifestations of sarcoidosis.

Sarcoidosis is a systemic disease of unknown aetiology that is characterized by granulomatous inflammation that can develop in almost any organ system. Musculoskeletal manifestations are seen in up to one-third of patients, ranging from arthralgia through to widespread destructive bone lesions. Inflammatory tendon lesions and periarticular swelling are more common than true joint synovitis. Despite advances in our understanding of the pathophysiology of the disease, diagnosis remains challenging. Definitive diagnosis, irrespective of organ site involvement, hinges on histological confirmation of non-caseating granuloma combined with an appropriate clinical syndrome. Musculoskeletal involvement usually develops early in the disease course. Imaging modalities, particularly fluorodeoxyglucose PET, are helpful in delineating the extent of involvement and measuring disease activity. Bone involvement may only become apparent following isotope imaging. Corticosteroids remain the cornerstone of treatment. MTX is the steroid-sparing agent of choice unless there is renal involvement. Biologic therapies are sometimes used in severe disease, although the evidence base for efficacy is inconsistent.

METASTATIC COLORECTAL ADENOCARCINOMA MIMICKING ENDODONTIC DISEASE

Bone metastases of the jaw are rare and can mimic diseases of the teeth. The objective of this study is to report a case of metastatic colorectal adenocarcinoma (CA) of the jaw in a 64-year-old female patient complaining of intense pain for 5 months, even after endodontic and extraction of the supposed involved teeth. She was referred to the Stomatology Service and reported CA treated 3 years earlier. At clinical examination, gingival overgrowth filling the space of the extracted tooth was found. Biopsy and imaging studies were performed. The tomography showed destructive bone lesion with about 5 cm in the surrounding areas of teeth 33, 34, and 35. The pathologic study revealed metastatic colorectal adenocarcinoma. The patient was referred for cancer service and died after 6 months. Despite of the rarity of metastasis of the jaw, this condition should be considered in patients with oral symptoms and history of malignancies.

Tertiary syphilis in the lumbar spine: a case report

BackgroundThe incidence of tertiary syphilis involvement in the spinal column with destructive bone lesions is very rare. It is difficult to establish the correct diagnosis from radiographs and histological examination alone. Limited data are available on surgical treatment to tertiary syphilitic spinal lesions. In this article, we report a case of tertiary syphilis in the lumbar spine with osteolytic lesions causing cauda equina compression.Case presentationA 44-year-old man who suffered with low back pain for 6 months and progressive radiating pain at lower extremity for 1 week. Radiologic findings showed osteolytic lesion and new bone formation in the parts of the bodies of L4 and L5. Serum treponema pallidum hemagglutination (TPHA) test was positive. A surgery of posterior debridement, interbody and posterolateral allograft bone fusion with instrumentation from L3 to S1 was performed. The low back pain and numbness abated after operation. But the follow-up radiographs showed absorption of the bone grafts and failure of instrumentation. A Charcot’s arthropathy was formed between L4 and L5.ConclusionIt is challenging to diagnose the tertiary syphilis in the spine. Surgery is a reasonable auxiliary method to antibiotic therapy for patients who suffered with neuropathy. Charcot’s arthropathy should be considered as an operative complication.

An extremely rare neoplasm, histiocytic sarcoma: A report of two cases with an aggressive clinical course

Abstract Histiocytic sarcoma (HS) is an extremely rare malignant neoplasm accounting for less than 1% of all hemato-lymphoid neoplasms. Sixty percent of all cases are metastatic at presentation and the prognosis is poor. Two cases of HS with an aggressive clinical course are presented. The first case was a 58-year-old man admitted to our hospital with back pain and paresthesia of the lower extremities. Magnetic resonance imaging (MRI) of the thoracic spine revealed a mass measuring 48 × 15 mm between the T2‒T5 paravertebral area, entering the spinal channel via the neural foramen and compressing the spinal cord. The mass was completely resected and pathological and immunohistochemical staining confirmed the diagnosis of HS. After three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and two cycles of carboplatin/paclitaxel, the patient died due to disease progression after 9 months. The second case is a 48-year-old man who presented with fever and weight loss, and complained of back pain for 2 months. Thoracic vertebral MRI revealed a lesion destructing the T6, T7 and T9 vertebral corpus and a mass measuring 2.5 × 2 cm near the T6‒T7 transverse process. Total-body fluorodeoxyglucose positron emission tomography (FDG-PET) imaging revealed bilateral inguinal hypermetabolic lymph nodes measuring 10 × 14 mm and osteolytic destructive bone lesions on the vertebral colon and pelvic bones. Pathological and immunohistochemical staining of bone marrow aspirate confirmed the diagnosis of HS. After three cycles of ifosfamide, carboplatin, etoposide (ICE) chemotherapy, the patient died due to disease progression after 3 months. Conclusions HS is an extremely rare malignant neoplasm of the monocytic/macrophage lineage, with no standardized chemotherapy regimen for multisystemic disease. Metastatic patients have a more aggressive clinical course than those with unifocal disease.

Immunomodulatory Drugs (IMiDs) in Multiple Myeloma

Multiple myeloma (MM) is a hematological cancer caused by a proliferation of clonal plasma cells, leading to anemia, renal failure, hypercalcemia and destructive bone lesions resulting in significant morbidity. The overall survival has significantly improved with the incorporation of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI). Here we provide a comprehensive review on IMiDs including molecular mechanisms, recent advances in therapeutic applications and management of toxicities in the treatment of MM. Relevant publications in peer reviewed journals were retrieved by a selective search of PubMed. Systemic reviews, meta-analyses, randomized controlled trials, and treatment recommendations were reviewed and are summarized here. Thalidomide, a first generation IMiD, is associated with significant toxicity in older patients. Lenalidomide, a more potent second generation IMiD with fewer side effects than thalidomide, is commonly used in newly-diagnosed multiple myeloma, relapsed refractory myeloma and as maintenance therapy after autologous stem cell transplantation (ASCT). Pomalidomide, a third generation IMiD, is 10 times more potent than lenalidomide and has shown impressive results in relapsed MM patients and in those refractory to both lenalidomide and bortezomib. The clinical use of IMiDs in MM has significantly improved long-term survival and quality of life. Future studies are looking into novel biomarkers predictive of outcome in MM and new combinations of lenalidomide and pomalidomde with PI, monoclonal antibodies, immune checkpoint blockers and several other chemotherapies.

Progress of miR-214 and miR-135b in multiple myeloma bone disease

Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80 % of MM patients. MicroRNAs have been reported to be involved in the development of bone lesions in MM. However, it is still unclear that microRNAs can be considered as diagnostic and prognostic biomarkers for bone lesions. MiR-214 and miR-135b may participate in the pathogenesis of bone marrow, which has shown a certain guiding significance in its prognosis. This paper will introduce the relationship between miR-214, miR-135b and myeloma bone disease. Key words: Multiple myeloma bone disease; MiR-214; MiR-135b

Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity.

Objectives Cholesteatoma is a nonneoplastic destructive lesion of the temporal bone with debated pathogenesis and bone resorptive mechanism. Both molecular and cellular events chiefly master its activity. Continued research is necessary to clarify factors related to its aggressiveness. We aimed to investigate the expression of Ki-67, cytokeratin 13 (CK13) and cytokeratin 17 (CK17) in acquired nonrecurrent human cholesteatoma and correlate them with its bone destructive capacity.Methods A prospective quantitative immunohistochemical study was carried out using fresh acquired cholesteatoma tissues (n=19), collected during cholesteatoma surgery. Deep meatal skin tissues from the same patients were used as control (n=8). Cholesteatoma patients were divided into 2 groups and compared (invasive and noninvasive) according to a grading score for bone resorption based upon clinical, radiologic and intraoperative findings. To our knowledge, the role of CK17 in cholesteatoma aggressiveness was first investigated in this paper.Results Both Ki-67 and CK17 were significantly overexpressed in cholesteatoma than control tissues (P<0.001 for both Ki-67 and CK17). In addition, Ki-67 and CK17 were significantly higher in the invasive group than noninvasive group of cholesteatoma (P=0.029, P=0.033, respectively). Furthermore, Ki-67 and CK17 showed a moderate positive correlation with bone erosion scores (r=0.547, P=0.015 and r=0.588, P=0.008, respectively). In terms of CK13, no significant difference was found between cholesteatoma and skin (P=0.766).Conclusion Both Ki-67 and CK17 were overexpressed in cholesteatoma tissue and positively correlated with bone resorption activity. The concept that Ki-67 can be a predictor for aggressiveness of cholesteatoma was supported. In addition, this is the first study demonstrating CK17 as a favoring marker in the aggressiveness of acquired cholesteatoma.

In Vivo Murine Model of Leukemia Cell-Induced Spinal Bone Destruction.

Osteolytic bone lesions can be a consequence of leukemic bone infiltration or focal bone destruction by inflammatory factors released from leukemic cells. Destructive bone lesions have a negative impact on the quality of life of leukemia patients, causing unbearable pain and, in some cases, limb paralysis. However, the mechanism, by which leukemic cells produce destructive bone lesions, and the effect of therapeutics on osteolytic lesions have not been fully elucidated yet and, thus, stand to benefit from an in vivo model. To that end, HL-60 cells were transformed by retrovirus-mediated constitutively active (CA) STAT5 expression and injected into nonobese diabetic (NOD)/SCID mice via the tail vein. After three weeks, lumbar spines were subjected to histocytometric analysis. Xenograft mice developed hind limb paralysis in 2-3 weeks, which was consistent with the consequences of spinal bone destruction by extramedullary invasion of leukemia cells. The in vivo model will improve the understanding and treatment of osteolytic bone lesions caused by myeloid leukemic cells.

Primary Occipital Ewing’s Sarcoma with Subsequent Spinal Seeding

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing's sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

The role of bone resorption in the etiopathogenesis of acquired middle ear cholesteatoma.

Cholesteatoma is a destructive squamous epithelial lesion of the temporal bone which gradually expands and leads to serious complications by destruction of nearby bony structures. Erosion caused by bone resorption of the ossicular chain and bony labyrinth may result in hearing loss, vestibular dysfunction, facial paralysis, labyrinthine fistulae and intracranial complications. The exact underlying cellular and molecular mechanism of bone resorption in acquired cholesteatoma still remains unexplained. Pubmed database and China National Knowledge Infrastructure were screened for articles focusing on bone resorption in acquired cholesteatoma. Osteoclast activation, pressure necrosis, acid lysis, enzyme mediation, inflammatory mediators and several newly discovered biomolecules are outlined as main theories behind bone resorption in acquired cholesteatoma, aiming to facilitate the development of potential therapeutic targets for preventing intracranial and extracranial complications caused by bone resorption in acquired middle ear cholesteatoma.

Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis.

Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs have been reported to be involved in development of bone lesions in MM. However, the circulating microRNA as diagnostic and prognostic biomarkers for bone lesions has not been elucidated yet. In this study, we identified differentially expressed miRNAs that are potentially involved in myeloma-related bone disease in serum of MM patients. MiR-214 and miR-135b was shown to be increased in serum of MM patients with bone lesions. Serum level of miR-214 and miR-135b was highly correlated with the severity of lytic bone lesions and demonstrated as a diagnostic tool for identifying bone diseases based on results of a receiver operating characteristic analysis (ROC). In addition, patients with high levels of serum miR-214 had a dismal survival with significantly shortened progression free survival (PFS) and overall survival (OS). Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Taken together, our findings revealed the significance of circulating miR-214 and miR-135b levels in detection of bone disease and in prediction of prognosis of patients with multiple myeloma, suggesting its potential clinical applications. The result of this study also set the foundation for searching more circulating miRNA as biomarker for tumor bone lesions.

Clinical characteristics of pain syndrome in patients with multiple myeloma

To study pain syndrome characteristics in the trunk and extremities of patients with multiple myeloma (MM). The study involved 120 patients with MM, aged from 34 to 83 years. The duration of disease was 2-37 months. The pain syndrome of trunk and extremity localization was revealed in 94% patients, its intensity according to the VAS was 65.5±25.4 mm. At all stages of disease, moderate to severe pain, predominantly related to polyneuropathy (PNP), radiculopathy and osteodestruction, was more frequent. Radicular pain syndrome was revealed in 46% of all MM patients, and in the majority of cases (92%), there were bone destruction lesions. The character of pain in MM should be specified to optimize further management of the patient.

Serum High Expression of Micorna-214 Is a Novel Predictor for Myeloma Bone Disease and Poor Prognosis

Abstract Background: Multiple myeloma (MM) originates from clonal expansion of malignant plasma cells in bone marrow, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs (miRNAs), such as miR-214, miR-34a and Mir-135 are reported to be involved in maintaining normal bone formation and development of metastatic bone lesions in cancers. Recent studies have demonstrated that miRNAs are stably expressed in human plasma and serum samples. And serum miRNAs have been used as biomarkers in diagnosis and prognosis of multiple cancers, including MM. However, the functional roles of miRNA in myeloma bone disease have not been elucidated yet. Materials and methods: In the present study, the serum miRNA expression was assessed from 152 samples including 108 MM samples and 44 healthy donors (HD) of serum. Microarray-based assay and real-time PCR was used to determine differentially expressed miRNAs. The correlation of miRNA expression and bone disease detected by whole body X-ray scanning was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Survival analysis was performed using the Kaplan-Meier method with a log-rank test and the generalized Wilcoxon procedure. Results: We performed serum miRNA profiles from 7 newly diagnosed MMs and 5 normal donors using a microarray-based assay. Our results identified that twenty-seven miRNAs which were reported to be involved in maintaining normal bone formation and development of bone lesions were significantly dysregulated, 4 miRNAs were significantly up-regulated and 23 miRNAs were significantly down-regulated in patient serum. We further performed real-time PCR to verify the expression of miR-214, miR-135, miR-132 and miR-92a in a large cohort of 108 MM patients and 44 healthy donors. We found that miR-214 (0.43±0.17 vs. 2.3±0.14, p&lt;0.0001) and miR-135 (-0.13±0.08 vs. 1.84±0.13, p=0.0022) levels were significantly increased, while serum levels of miR-92a (-0.19±0.20 vs. -1.03±0.11, p=0.0023) were significantly decreased in MM patients. However, we did not found that miR-132 was obviously altered between normal and patient serum. Furthermore, serum levels of miR-214 and miR-135 were notably increased in the patients with lytic bone lesions compared to those without bone disease (both p&lt;0.0001), and a positive correlation was observed between the expression levels of miR-214 (r=0.455, p&lt;0.0001) and miR-135 (r=0.404, p&lt;0.001) with grades of lytic bone lesions. Receiver operating characteristic (ROC) analysis revealed that serum levels of miR-214 and miR-135 can be used to distinguish bone disease in myeloma patients with area under the curve (AUC) &gt; 0.7. Moreover, patients had a significantly shortened OS with high levels of circulating miR-214 (50.0 months vs. NR (not reached); p=0.039) or miR-135 (34.0 months vs.NR; p=0.041) versus those patients with down-regulated levels of miR-214 and miR-135. Patients with higher serum levels of miR-214 were responsible to bisphosphonates with extended OS (NR comparing to 26.0 months, p=0.029), suggesting that bisphosphonates is suitable to treat patients with high expression of circulating miR-214. Conclusion: Our findings reveal that the circulating miR-214 level is a biomarker for prediction of bone disease and prognosis in multiple myeloma. The detail mechanism how miR-214 involves in disease progression will be further explored. The result of this study also set the foundation for searching more circulating miRNA as biomarkers for metastatic bone lesions. Disclosures No relevant conflicts of interest to declare.

The Src Inhibitor AZD0530 Prevents the Development of Osteolytic Bone Disease in Multiple Myeloma

Destructive bone lesions due to osteolytic bone disease are a major cause of morbidity and mortality in multiple myeloma patients, occurring in more than 80% of cases. Underlying osteolytic bone disease is an uncoupling of the bone remodeling process, with an increased activity of osteoclasts and a decreased activity of osteoblasts. Current strategies to treat osteolytic bone disease focus on anti-resorptive agents, which do not rebuild bone loss. Src kinase has been implicated in both osteoclast and osteoblast function. In this study, we assessed the effect of Src inhibition with AZD0530 (saracatinib, Astra Zeneca) on the development of multiple myeloma and its associated osteolytic bone disease. We first determined Src family kinase expression in the multiple myeloma microenvironment and found that patient-derived myeloma cells express Src at low levels but disease stage does not correlate with Src expression levels. In accordance with the literature, Src mRNA expression was found to increase during osteoclast differentiation and decrease during osteoblast differentiation in publicly available microarray datasets. Next, we validated an inhibitory role of AZD0530 on osteoclast differentiation and function. At a pharmacological relevant concentration of 1 micromolar, AZD0530 inhibited the differentiation of RAW264.7 osteoclasts (Oc.N/FOV: 15.5+-1.6 treated vs. 53+-1.5 non-treated). AZD0530 treatment appeared to hamper efficient progenitor cell fusion and osteoclast polarization, reflected by a decrease of CTSK and DC-STAMP mRNA levels and a defective actin ring formation in treated cultures, which culminated in a complete inhibition of bone resorption. When assessing the effect of AZD0530 on osteoblast function we found that AZD0530 inhibits osteoblast differentiation, with a decreased expression of OSX and OCN, and alters osteoblast morphology. In vivo, AZD0530 did not alter myeloma cell bone marrow infiltration in both the 5TGM.1 (37+-6.3% AZD0530 treated vs. 25.2+-6.7% non-treated) and 5T2MM (26.1+-7.7% vs. 29.1+-6.4%) murine multiple myeloma models. However, bone health was significantly improved in both models following treatment with AZD0530. In the 5TGM.1 model multiple trabecular bone parameters were restored to levels observed in healthy control mice following AZD0530 treatment, including BV/TV (11.7+-0.3% treated vs. 6.4+-0.3% non-treated), Tb.N. (2.5+-6x10^-2/mm vs. 1.7+-9x10^-2/mm) and Tb.Th (46.2+-1micron vs. 37+-0.8micron). These results were confirmed in the 5T2MM model, which displays a more severe osteolytic bone disease. In addition, AZD0530 treatment resulted in an increase in cortical thickness (157.8+-0.8micron treated vs. 151.4+-0.7micron non-treated) and a decrease in the number and size of cortical lesions in 5TGM.1 mice. Finally, our findings were corroborated by histomorphometric analyses. In conclusion, we report a potent inhibitory effect of the Src inhibitor AZD0530 on the development of osteolytic bone disease in multiple myeloma. Our results indicate that AZD0530 exerts this effect via the modulation of both osteoclast and osteoblast function. These findings warrant further study of the feasibility and efficacy of AZD0530 to treat osteolytic bone disease in multiple myeloma patients. DisclosuresNo relevant conflicts of interest to declare.

New Approaches to Molecular Imaging of Multiple Myeloma.

Molecular imaging plays an important role in detection and staging of hematologic malignancies. Multiple myeloma (MM) is an age-related hematologic malignancy of clonal bone marrow plasma cells characterized by destructive bone lesions and is fatal in most patients. Traditional skeletal survey and bone scans have sensitivity limitations for osteolytic lesions manifested in MM. Progressive biomedical imaging technologies such as low-dose CT, molecularly targeted PET, MRI, and the functional-anatomic hybrid versions (PET/CT and PET/MRI) provide incremental advancements in imaging MM. Imaging with PET and MRI using molecularly targeted probes is a promising precision medicine platform that might successfully address the clinical ambiguities of myeloma spectrum diseases. The intent of this focus article is to provide a concise review of the present status and promising developments on the horizon, such as the new molecular imaging biomarkers under investigation that can either complement or potentially supersede existing standards.

Bone antiresorptive agents in the treatment of bone metastases associated with solid tumours or multiple myeloma.

Skeletal lesions contribute substantially to morbidity and mortality in patients with cancer. The disease manifestation course during metastatic bone disease is driven by tumour cells in the bone marrow, which alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. Successful therapeutic strategies for the treatment of metastatic bone disease include bisphosphonates and denosumab that inhibit osteoclast-mediated bone resorption. Inhibitors of cathepsin K, Src and activin A are under clinical investigation as potential anti-osteolytics. In this review, we describe current knowledge and future directions of antiresorptive therapies that may reduce or prevent destructive bone lesions from solid tumours and multiple myeloma.

Spindle Cell Carcinoma in a Young Man: A Case Report of a Rare Entity

Spindle cell carcinoma (SpCC), also known as sarcomatoid carcinoma, is a rare biphasic malignant neoplasm that occurs mainly in the upper aerodigestive tract. An aggressive variant of squamous cell carcinoma, SpCC has spindled or pleomorphic tumor cells, which simulate a sarcoma but are of epithelial origin. It often recurs and metastasizes, underscoring the importance of diagnosing it correctly. A 21-year-old male presented with an irregular painless mass in the anterior mandible. Panoramic radiography and computed tomography showed destructive osteolytic lesion of the mandibular bone. Histopathological analysis revealed pleomorphic spindle cells, with atypical mitoses, arranged in an irregular fascicular pattern, together with small areas of squamous cell carcinoma. The immunohistochemical analysis showed positivity for 34βE12, AE1/AE3, vimentin, and Ki-67. The patient underwent chemotherapy and radiotherapy, which, however, were ineffective. The lesion was deemed inoperable. Currently, the patient has been followed-up via palliative treatment.