Osteoid Production Research Articles

Primary extraskeletal osteosarcomas of the pleura: A clinicopathological, immunohistochemical, and molecular analysis of 4 cases

Four primary extraskeletal osteosarcomas of the pleura are presented. The patients were men between the ages of 63 and 78 years (average: 70.5 years) who presented with symptoms of chest pain, cough, and shortness of breath. Diagnostic imaging showed variably calcified, pleural-based masses and/or diffuse pleural thickening, clinically mimicking mesothelioma. Thoracoscopic surgical material was obtained for histopathological diagnosis. Histological findings showed the presence of a neoplastic spindle cell proliferation composed of fusiform cells with scant cytoplasm, elongated nuclei and inconspicuous nucleoli. Mitotic activity was easily identified. Additionally, all tumors showed extensive osseous differentiation in the form of osteoid matrix production; one tumor demonstrated additional chondrosarcomatous elements and another showed focal myxoid changes. Immunohistochemical analysis revealed that the tumor cells were uniformly negative for a wide variety of antibodies, including keratin AE1/AE3, keratin 5/6, D2-40, EMA, calretinin, WT-1, BerEP4, and HEG1; BAP1 was retained in all cases. In addition, fluorescence in situ hybridization for CDKN2A (p16) was negative for homozygous deletion in all tumors. Clinical follow-up showed that one patient had died 8 months after diagnosis and one had remained alive with short post-diagnostic follow-up. The tumors herein described highlight a challenging issue in the separation of mesothelioma with heterologous elements from true osteosarcomas of pleural origin. We propose that a diagnosis of extraskeletal osteosarcoma of the pleura is rendered for tumors with malignant osseous and/or cartilaginous differentiation in which comprehensive immunohistochemical studies and FISH analysis have failed to provide support for a diagnosis of mesothelioma with heterologous elements.

Contrast-enhanced Susceptibility Weighted Imaging (CE-SWI) for the Characterization of Musculoskeletal Oncologic Pathology: A Pictorial Essay on the Initial Five-year Experience at a Cancer Institution

Susceptibility-weighted imaging (SWI) is based on a 3D high-spatial-resolution, velocity-corrected gradient-echo MRI sequence that uses magnitude and filtered-phase information to create images. It SWI uses tissue magnetic susceptibility differences to generate signal contrast that may arise from paramagnetic (hemosiderin), diamagnetic (minerals and calcifications) and ferromagnetic (metal) molecules. Distinguishing between calcification and blood products is possible through the filtered phase images, helping to visualize osteoblastic and osteolytic bone metastases or demonstrating calcifications and osteoid production in liposarcoma and osteosarcoma. When acquired in combination with the injection of an exogenous contrast agent, contrast-enhanced SWI (CE-SWI) can simultaneously detect the T2* susceptibility effect, T2 signal difference, contrast-induced T1 shortening, and out-of-phase fat and water chemical shift effect. Bone and soft tissue lesion SWI features have been described, including giant cell tumors in bone and synovial sarcomas in soft tissues. We expand on the appearance of benign soft-tissue lesions such as hemangioma, neurofibroma, pigmented villonodular synovitis, abscess, and hematoma. Most myxoid sarcomas demonstrate absent or just low-grade intra-tumoral hemorrhage at the baseline. CE-SWI shows superior differentiation between mature fibrotic T2* dark components and active enhancing T1 shortening components in desmoid fibromatosis. SWI has gained popularity in oncologic MSK imaging because of its sensitivity for displaying hemorrhage in soft tissue lesions, thereby helping to differentiate benign versus malignant soft tissue tumors. The ability to show the viable, enhancing portions of a soft tissue sarcoma separately from hemorrhagic/necrotic components also suggests its utility as a biomarker of tumor treatment response. It is essential to understand and appreciate the differences between spontaneous hemorrhage patterns in high-grade sarcomas and those occurring in the therapy-induced necrosis process in responding tumors. Ring-like hemosiderin SWI pattern is observed in successfully treated sarcomas. CE-SWI also demonstrates early promising results in separating the T2* blooming of healthy iron-loaded bone marrow from the T1-shortened enhancement in bone marrow that is displaced by the tumor. SWI and CE-SWI in MSK oncology learning objectives: SWI and CE-SWI can be used to identify calcifications on MRI. Certain SWI and CE-SWI patterns can correlate with tumor histologic type. CE-SWI can discriminate mature from immature components of desmoid tumors. CE-SWI patterns can help to assess treatment response in soft tissue sarcomas. Understanding CE-SWI patterns in post-surgical changes can also be useful in discriminating between residual and recurrent tumors with overlapping imaging features.

Crystal induced arthropathies-a comparative study of 40 patients with apatite rheumatism, chondrocalcinosis and primary synovial chondromatosis.

Introduction: Apatite rheumatism (AR), chondrocalcinosis (Ch-C), and primary synovial chondromatosis (prSynCh) are regarded as distinct clinical entities. The introduction of the non-staining technique by Bély and Apáthy (2013) opened a new era in the microscopic diagnosis of crystal induced diseases, allowing the analysis of MSU (monosodium urate monohydrate) HA (calcium hydroxyapatite), CPPD (calcium pyrophosphate dihydrate) crystals, cholesterol, crystalline liquid lipid droplets, and other crystals in unstained sections of conventionally proceeded (aqueous formaldehyde fixed, paraffin-embedded) tissue samples. The aim of this study was to describe the characteristic histology of crystal deposits in AR, Ch-C, and prSynCh with traditional stains and histochemical reactions comparing with unstained tissue sections according to Bély and Apáthy (2013). Patients and methods: Tissue samples of 4 with apatite rheumatism (Milwaukee syndrome), 16 with chondrocalcinosis, and 20 with clinically diagnosed primary synovial chondromatosis were analyzed. Results and conclusion: Apatite rheumatism, chondrocalcinosis, and primary synovial chondromatosis are related metabolic disorders with HA and CPPD depositions. The authors assume that AR and Ch-C are different stages of the same metabolic disorder, which differ from prSynCh in amorphous mineral production, furthermore in the production of chondroid, osteoid and/or bone. prSynCh is a defective variant of HA and CPPD induced metabolic disorders with reduced mineralization capabilities, where the deficient mineralization is replaced by chondroid and/or bone formation. The non-staining technique of Bély and Apáthy proved to be a much more effective method for the demonstration of crystals in metabolic diseases than conventional stains and histochemical reactions.

TRANSFECTION OF HMSCS WITH CHEMICALLY MODIFIED MRNA CODING FOR BMP-7 ENHANCES OSTEOGENESIS

Bone morphogenetic proteins (BMPs) have been widely investigated for treating non-healing fractures. They participate in bone reconstruction by inducing osteoblast differentiation, and osteoid matrix production.1 The human recombinant protein of BMP-7 was among the first growth factors approved for clinical use. Despite achieving comparable results to autologous bone grafting, severe side effects have been associated with its use.2 Furthermore, BMP-7 was removed from the market.3 These complications are related to the high doses used (1.5-40 miligrams per surgery)2 compared to the physiological concentration of BMP in fracture healing (in the nanogram to picogram per milliliter range).4 In this study, we use transcript therapy to deliver chemically modified mRNA (cmRNA) encoding BMP-7. Compared to direct use of proteins, transcript therapy allows the sustained synthesis of proteins with native conformation and true post-translational modifications using doses comparable to the physiological ones.5 Moreover, cmRNA technology overcomes the safety and affordability limitations of standard gene therapy i.e. pDNA.6 BMP-7 cmRNA was delivered using Lipofectamine™ MessengerMAX™ to human mesenchymal stromal cells (hMSCs). We assessed protein expression and osteogenic capacity of hMSCs in monolayer culture and in a house-made, collagen hydroxyapatite scaffold. Using fluorescently-labelled cmRNA we observed an even distribution after loading complexes into the scaffold and a complete release after 3 days. For both monolayer and 3D culture, BMP-7 production peaked at 24 hours post-transfection, however cells transfected in scaffolds showed a sustained expression. BMP-7 transfected hMSCs yielded significantly higher ALP activity and Alizarin red staining at later timepoints compared to the untransfected group. Interestingly, BMP-7 cmRNA treatment triggered expression of osteogenic genes like OSX, RUNX-2 and OPN, which was also reflected in immunostainings. This work highlights the relevance of cmRNA technology that may overcome the shortcomings of protein delivery while circumventing issues of traditional pDNA-based gene therapy for bone regeneration.Acknowledgement: This work has been performed as part of the cmRNAbone project and has received funding from the European Union's Horizon 2020 research and innovation programme under the Grant Agreement No 874790.

Survival Differences of Patients with Resected Extraskeletal Osteosarcoma Receiving Two Different (Neo)Adjuvant Chemotherapy Regimens: A Systematic Review and Meta-analysis

AimsExtraskeletal osteosarcoma (ESOS) is a malignant tumour developing in soft tissues, characterised by the production of osteoid or bone matrix by tumour cells. The standard treatment for localised ESOS is wide resection. Radiotherapy and chemotherapy are usually incorporated into the management of patients. Two types of chemotherapy regimen are mostly used: an osteosarcoma-type chemotherapy, based on cisplatin, and a soft-tissue sarcoma (STS)-type chemotherapy, using the combination of doxorubicin and ifosfamide. To investigate the difference in survival between these two chemotherapy regimens, a systematic review of studies reporting the 5-year disease-free survival (DFS) rates among patients with ESOS submitted to surgery and who received (neo)adjuvant chemotherapy with osteosarcoma-type or STS-type chemotherapy was carried out. Materials and methodsOf the 401 articles identified by systematically searching the PubMed, Embase and Cochrane Central Register of Controlled Trials databases, six retrospective studies were included in the final analysis. In total, 319 patients with localised/resected ESOS were included in the study. ResultsOur meta-analysis showed a benefit in 5-year DFS favouring the use of osteosarcoma-type chemotherapy (relative risk = 1.32, 95% confidence interval 1.03–1.69; P = 0.54); I2 heterogeneity was 0%. The 5-year DFS rate was 56.3% (95% confidence interval 48.3–64.3) with osteosarcoma-type chemotherapy and 45.2% (95% confidence interval 34.5–55.9) with STS-type chemotherapy, with I2 heterogeneity of 27% and 0%, respectively. ConclusionsOur analysis suggests that there may be a difference regarding the type of (neo)adjuvant chemotherapy regimen used in the treatment of patients with resected ESOS in favour of osteosarcoma-type chemotherapy. Future studies evaluating the role of this treatment modality in this scenario need to consider the type of chemotherapy regimen when comparing with an arm of surgery with/without radiotherapy alone.

Penile osteosarcoma

IntroductionExtraskeletal osteosarcoma arising in the penis is exceedingly rare and its major differential diagnosis is sarcomatoid carcinoma.Case presentationA 19-year-old patient noticed a deep nodule in the dorsal side of the penis 2 years before this presentation. No skin lesions were noted until recent ulceration. In both biopsy and penectomy specimen, atypical mononuclear cells were diffusely positive for SATB2 (a marker of osteoblastic differentiation), CD99 and vimentin. These cells were negative for pan-keratin, SOX10, S100, EMA, GATA3 and CD68 was expressed only in multinucleated giant (osteoclast-like) cells. Few areas suggestive of osteoid production were noted.ConclusionIn high-grade sarcomas, including in the penis, SATB2 staining may be useful to identify extraskeletal osteosarcoma.

Primary cutaneous extraskeletal osteosarcoma: a series of 16 cases

Extraskeletal osteosarcoma (EOS) is a high grade soft tissue tumour characterised by the production of malignant osteoid, without attachment/involvement of underlying bone/periosteum. Rarely, EOS presents as a cutaneous tumour. The clinical behaviour of primary cutaneous EOS (PC-EOS) remains incompletely characterised. Herein we present the largest case series of PC-EOS reported to date. Sixteen PC-EOS cases from the archives/consultation files were retrieved (male:female 1:1; age 31-96 years, mean age 66 years). The tumours measured 1-10 cm (mean 3.2 cm) and were located on the lower extremity (7), head (6), upper extremity (2), and trunk (1). They consisted of pleomorphic, spindled-to-epithelioid cells, with fascicular, nodular, or sheet-like growth patterns and foci of malignant osteoid. Immunohistochemistry did not reveal specific lines of differentiation, and there was no evidence of other tumour types. A literature review was conducted to identify all well characterised cases of PC-EOS. A combined analysis of present and past cases was performed to determine overall trends in clinical characteristics and outcomes. The mean follow-up period was 23.9 months, during which 67.5% of patients experienced progression-free survival and 18% of patients died of disease. Rates of local recurrence and metastasis were 10% and 25%, respectively, approximately double past estimates. These data suggest that the prognosis of PC-EOS is less favourable than previously thought. The differential diagnosis includes benign entities (e.g., ossifying pyogenic granuloma) and malignant neoplasms with heterologous osteosarcomatous differentiation (e.g., carcinosarcoma, transdifferentiated melanoma). Wide excision remains the standard of care, and the role of chemotherapy and radiation remains inconclusive. Recognition of this rare entity can facilitate prompt diagnosis and appropriate treatment.

Osteosarcoma/Ewing Sarcoma

Osteosarcoma/Ewing Sarcoma

Osteosarcoma: A case report

Osteosarcoma (OS) is a primary malignant bone tumor with a worldwide incidence. OS is a rare sarcoma that has the histological findings of osteoid production in association with malignant mesenchymal cells. Osteosarcoma is the eighth-most common form of childhood cancer. The most common site of origin is the metaphyseal region of tubular long bones, with 42% occurring in the femur, followed by the tibia, and the humerus. We reported a case of osteosarcoma of the right tibia in a 12-year-old patient.

Effect of Dietary Amino Acids L-Arginine and Lysine on Implant Osseointegration.

Background:Low protein diets have been linked to decreased bone strength in humans. Arginine and lysine can help improve the healing process and stimulate growth factors.Aim:To evaluate if dietary arginine and lysine combination aids in reducing the time frame for osseo-integration process and bone formation in animal models.Materials and Methods:Controls (Group I) and Experimental (Group II) consisted of twelve New Zealand rabbits. Animals in the experimental group were fed a conventional pellet food, water, and the amino acids L-Lysine and L-Arginine (Biovea, USA), whereas those in the control group were offered a standard diet. In both groups of animals, titanium implants measuring 2.5mm* 6mm were implanted in each tibial osteotomy. At the end of two weeks, four weeks, and eight weeks, the animals were euthanized. The tibial bone was removed and preserved in 1% formalin. The samples were analysed histologically for presence or absence of Necrosis, presence or absence of clot formation, Vascularization, Fibroblast, Osteoblasts and Osteoid Bone growth.Results:Histological outcomes on vascularization, fibroblasts, osteoblasts, osteoid bone growth inferred no significant variation between the control and experimental groups after 8 weeks (P>.05).Conclusion:Vascularity, clot organisation, osteoblasts, fibroblasts, and osteoid bone production in the protein fed experimental group animals were better in initial stages of healing when compared to control groups.

Osseous Heart- A Rare Case of Metastatic Osteosarcoma to the Heart

Osteosarcomas are uncommon malignant tumors of the bone that arise from the production of osteoid or immature bone by the malignant cells. In rare occasions this tumor metastasizes to other organs including the brain and lungs. Although hematogenous spread of osteosarcoma is well known, cardiovascular metastasis is seldomly reported. Most cases of metastatic osteosarcoma to the heart involve the myocardium rather than the pericardium. The right side of the heart is affected in 20–30% of cases and the left side in 10–33% of reported cases. Only 5% of cases affect the endocardium or chamber cavities. Clinical signs and symptoms of metastatic cardiac neoplasms include dyspnea, cough, chest pain, palpitations, superior vena cava syndrome, right ventricular outflow tract obstruction and pericardial effusion [1].

VITAMIN C DEFICIENCY-ASSOCIATED LESIONS IN A COLONY OF COMMON VAMPIRE BATS (DESMODUS ROTUNDUS) IN A ZOO FACILITY.

The Milwaukee County Zoo has housed common vampire bats (Desmodus rotundus) since 1973. The bats are fed defibrinated cow's blood supplemented with a liquid pediatric multivitamin. From July 2013 to May 2014, multiple deaths occurred in colony bats, including five juveniles with multiple bone fractures and failure of endochondral ossification, three adults with cerebellar necrosis, and one adult with subcutaneous hemorrhage. In November 2013, an adult bat developed a nonhealing left wing hematoma and eventually succumbed 9 mo later. A postmortem examination revealed multifocal extensive necrohemorrhagic and suppurative ulcerative dermatitis with no underlying cause determined. From July to December 2014, five of nine adult bats in the colony developed similar hematomas along with gingival bleeding. One euthanized bat had a serum ascorbic acid level of 0.08 mg/dl and marked generalized subcutaneous hemorrhage. A therapeutic trial was initiated in which two bats received defibrinated cow's blood supplemented only with oral vitamin C, 100 mg/kg PO q24h for 3 d, and then 50 mg/kg PO q24h. Two other bats received nonsupplemented defibrinated cow's blood and were given vitamin K 3.3 mg/kg SC q12h for 3 d, and then 3.3 mg/kg SC q24h for 7 d. The bats supplemented with vitamin C improved, supporting a diagnosis of vitamin C deficiency. All bats were subsequently supplemented with vitamin C leading to resolution of all lesions within 10 d to 2 mo. Vitamin C is necessary for collagen synthesis, which is required for proper wound healing, capillary and cartilage strength, osteoid production, and pial membrane formation of the cerebellum. Several bat species cannot synthesize vitamin C and require a dietary source. This is the first report of vitamin C deficiency in a colony of vampire bats leading to severe chronic subcutaneous hemorrhage, bone fragility, microfractures, cerebellar necrosis, and death.

Translational cell biology of highly malignant osteosarcoma.

Highly malignant osteosarcoma (HMO) is the most frequent malignant bone tumor preferentially occurring in adolescents and children with a second more flat peak in patients over the age of 60. The younger patients benefit from combined neoadjuvant chemotherapy with 65-70% 5-year survival rate. In patients with metastatic HMO the 5-year survival rate is consistently poor with approximately 30%. In the last several years strategies for target therapies have been developed by using next generation sequencing (NGS) for defining targetable molecular factors. However, it has so far been challenging to establish an effective target therapy for so-called 'orphan tumors' without recognizable driver mutations, including HMO. The molecular genetic studies using NGS have shown that HMOs are genomically unstable tumors with highly complex chaotic karyotypes. Before the background of this genetic complexity more investigations should be performed in the future for defining targetable biological factors. As the prognosis could not be improved for 40 years one may expect improvements for patients only by gaining a deeper understanding of the cell and molecular biology of HMO. The cell of origin of HMO is being clarified now. The majority of studies indicate that an osteoblastic progenitor cell is probably the cell of origin of HMO and not an undifferentiated mesenchymal stem cell. This means that the established histopathological definition of HMO through verification of osteoid production by the osteoblastic cells is well justified and will probably be the cornerstone for a precise differential diagnosis of HMO also in the years to come.

Maxillofacial Osteosarcoma in a Five Year Old Rottweiler Dog: A Case Report

A five year old male Rottweiler presented with persistent nasal discharge and intermittent epistaxis of duration of over one year, was diagnosed with maxillofacial osteosarcoma based on radiographic findings of the skull and histological findings of the mass. Physical examination revealed severe facial swelling and distortion. Radiographs showed severe lysis of the incisive and maxillary bones, with a typical moth-eaten appearance. In addition, there was distortion of the outline of the nasal turbinate and severe soft tissue swelling. There was no evidence of metastasis both on thoracic radiograph and abdominal ultrasound. Haemato-biochemical parameters revealed moderate anaemia with neutrophilic leukocytosis, elevated serum alkaline phosphatase, hypernatremia, hyperkalemia, hypochloremia and metabolic alkalosis. Cytological evaluation of the neoplastic mass revealed numerous moderately pleomorphic round, oval, polygonal, spindle-shaped or elongated irregular cells with abundant osteoid at their background. Histologically, the neoplastic mass has different appearance with production of osteoid and invasion of the surrounding tissues. The tumor matrix contained variable quantities of osteoid, cartilage and collagen. The dog was euthanized due to poor prognosis of obtaining tumor free margin after surgical excision. It was recommended that radiographic examination of the skull should be part of the routine assessment of dogs presented with epistaxis.

Evaluation of osteonectin as a diagnostic marker of osteogenic bone tumors

Introduction: Immunohistochemistry plays an important but limited role in the diagnosis of primary bone tumors. Sometimes it is very difficult to differentiate osteosarcomas histologically from other tumors with similar morphology but with different malignant potential and treatment protocol. The correct diagnosis of OSA relies on identification of osteoid production by malignant cells which can be detected by the use of osteonectin. Materials and Methods: The present study was carried out on 200 patients of benign and malignant lesions of bone. After a detailed clinical history and local examination, paraffin section of resected specimens were studied by hematoxylin and eosin and immunohistochemical stain, osteonectin and matrix was graded on a four-tiered grading system with statistical analysis of osteonectin positivity in osteogenic bone tumours and tumour-like lesions. Results: Benign and malignant tumours accounted for 74.6% and 25.0% of the total cases. Osteoid production were seen in 36 cases (100.0%) of osteosarcomas, followed by fibrous dysplasia in 18 cases (100.0%) and osteoid osteoma in 10 cases (100.0%). Both polygonal and spindle shaped tumour cells in osteosarcoma showed Grade 4 positivity with osteonectin. Fibroblastic variant of osteosarcoma showed diffuse (Grade 4) and focal strong staining (Grade 2) alternating with negative areas. Chondroblastic variant of osteosarcoma showed Grade 4+ immunoreactivity in conventional osteosarcoma like areas, whereas chondrocyte- like tumour cells surrounded by chondro-osteoid –like matrix showed well- defined osteonectin staining. Conclusions: Osteonectin is a helpful osteogenic marker for establishing the diagnosis of osteoblastic origin of a tumour that produce no or scarcely any matrix. Keywords: Bone Tumors, Immunohistochemistry, Osteonectin.

Osteosarcoma of the jaws: An overview of the pathophysiological mechanisms.

Osteosarcoma (OS) is the most common cancer of bone. Jaw osteosarcoma (JOS) is rare and it differs from long-bone OS (LBOS) in terms of the time of onset (two decades later), lower metastatic spread, and better survival. OS is characterized by the proliferation of osteoblastic precursor cells and the production of osteoid or immature bone. OS arises from a combination of genetic aberrations and a favourable microenvironment. This local microenvironment includes bone cells, blood vessels, stromal cells, and immune infiltrates, all of which may constitute potential targets for anti-cancer drugs. Differences in the clinical and biological behaviour of JOS versus LBOS are likely to at least in part be due to differences in the microenvironment between the two sites. The present review provides a brief overview of the known pathophysiological parameters involved in JOS.

Knee osteoarthritis in young growing rats is associated with widespread osteopenia and impaired bone mineralization

Osteoarthritis (OA) leads to joint pain from intraarticular inflammation with articular cartilage erosion, deterioration of joint function and abnormal subchondral bone structure. Besides aging, chronic repetitive joint injury is a common risk factor in young individuals. Nevertheless, whether OA is associated with bone loss at other skeletal sites is unclear. Since OA-associated proinflammatory cytokines—some of which are osteoclastogenic factors—are often detected in the circulation, we hypothesized that the injury-induced knee OA could result in widespread osteopenia at bone sites distant to the injured knee. Here we performed anterior cruciate ligament transection (ACLT) to induce knee OA in one limb of female Sprague–Dawley rats and determined bone changes post-OA induction by micro-computed tomography and computer-assisted bone histomorphometry. We found that although OA modestly altered bone density, histomorphometric analyses revealed increases in bone resorption and osteoid production with impaired mineralization. The bone formation rate was also reduced in OA rats. In conclusions, ACLT in young growing rats induced microstructural defects in the trabecular portion of weight-bearing (tibia) and non-weight-bearing bones (L5 vertebra), in part by enhancing bone resorption and suppressing bone formation. This finding supports the increasing concern regarding the repetitive sport-related ACL injuries and the consequent bone loss.

Development and characterization of the novel human osteosarcoma cell line COS-33 with sustained activation of the mTOR pathway

Outcomes have not improved for metastatic osteosarcoma for several decades. In part, this failure to develop better therapies stems from a lack of understanding of osteosarcoma biology, given the rarity of the disease and the high genetic heterogeneity at the time of diagnosis. We report here the successful establishment of a new human osteosarcoma cell line, COS-33, from a patient-derived xenograft and demonstrate retention of the biological features of the original tumor. We found high mTOR signaling activity in the cultured cells, which were sensitive to a small molecule inhibitor, rapamycin, a suppressor of the mTOR pathway. Suppressed mTOR signaling after treatment with rapamycin was confirmed by decreased phosphorylation of the S6 ribosomal protein. Increasing concentrations of rapamycin progressively inhibited cell proliferation in vitro. We observed significant inhibitory effects of the drug on cell migration, invasion, and colony formation in the cultured cells. Furthermore, we found that only a strong osteogenic inducer, bone morphogenetic protein-2, promoted the cells to differentiate into mature mineralizing osteoblasts, indicating that the COS-33 cell line may have impaired osteoblast differentiation. Grafted COS-33 cells exhibited features typical of osteosarcoma, such as production of osteoid and tumorigenicity in vivo. In addition, we revealed that the COS-33 cell line retained a complex karyotype, a homozygous deletion of the TP53 gene, and typical histological features from its original tumor. Our novel cellular model may provide a valuable platform for studying the etiology and molecular pathogenesis of osteosarcoma as well as for testing novel drugs for future genome-informed targeted therapy.

Fibroblastic osteosarcoma in a white-eared opossum (Didelphis albiventris)

ABSTRACT: Osteosarcoma is characterized by the production of osteoid or woven bone, using neoplastic osteoblasts. It is the most common primary bone neoplasm in canines and humans. This neoplasm was previously reported in all vertebrate classes, including a wide variety of mammals. However, there is no case report describing this neoplasm in Didelphis albiventris. Therefore, the objective of this manuscript is to describe the clinical-pathological aspects of fibroblastic osteosarcoma in D. albiventris. A wild adult male white-eared opossum (D. albiventris) arrived at the zoological park of the “Universidade de Caxias do Sul” with a swollen left thoracic limb. After a general clinical examination, the animal was transferred to the Veterinary Clinic of “Universidade de Caxias do Sul” for radiographic examination of the left thoracic limb and thorax. Additionally, some material was collected through fine needle aspiration (FNA) for cytologic evaluation. The radiographic findings and cytologic evaluation indicated osteosarcoma. The animal was euthanized due to severe clinical conditions and guarded prognosis. During necropsy, macroscopic analysis of the viscera was performed, fragments of various organs were collected and fixed in 10% neutral buffered formalin. All fragments were processed following routine histological techniques. The histopathological evaluation confirmed osteosarcoma, which was classified as a fibroblastic subtype. Case reports are crucial for the knowledge of incidence, prevalence, and behavior of the current mentioned disease, as well as other diseases, in species with such limited information. In order to obtain a decisive diagnosis, a few different examination methods were associated. Although the observations presented are based on a single case, this neoplasm had a similar clinical presentation to that described in other species.

The correlation of prognostic factors and clinical outcomes in patients with osteosarcoma – An observational study

Context: Osteosarcoma is characterized by the production of malignant osteoid. It arises typically in the adolescent age group. Aims: The purpose of this study is to analyze the impact of various prognostic factors on survival in osteosarcoma patient admitted in our institution. Settings and Design: Retrospective observational study of 10 years duration from 2007 to 2017 Methods and Materials: There were 66 patients in the records. As a part of the staging work up, CT and MRI of the local part and CECT CHEST were performed . All patients received adriamycin and cisplatin with or without Ifosfamide, and PCVE regimen. Statistical analysis used: IBM SPSS Statistics version 20. Survival and percentage of necrosis was correlated by Spearman Rank correlation. Results: Sixty six patients were included in this study. The median survival of patient who underwent limb salvage surgery (LSS) was 28 months and that of patient underwent amputation was 17 months. No statistically significant survival advantage present between the two group (p=0.68). There is a statistically significant difference in percentage of necrosis in patient who receive neoadjuvant chemotherapy if ifosfamide is added to the regime (p=0.006). Spearman Rank correlation revealed that there was a strong positive Correlation (0.418) between the percentage of necrosis and survival. The correlation was statistically significant (p = 0.02). Conclusions: LSS in osteosarcoma is a safe alternative to amputation. Response to chemotherapy, with regards to necrosis correlates well with survival, thus clearly emphasizing the role of chemotherapy in the management of these tumors. Keywords: OSTEOSARCOMA, Limb salvage surgery, Amputation.