Osteoid Production Research Articles

Dedifferentiated soft tissue leiomyosarcoma with heterologous osteosarcoma component: case report and review of the literature

BackgroundSoft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature.Case presentationWe report the case of a 65-year-old male patient who, after initial inadequate surgery of a tumor of the left forearm, developed local recurrence that was treated with neoadjuvant chemotherapy, surgery and postoperative radiation therapy. Histologically the tumor showed an abrupt separation of two different patterns. One component consisted of interlacing fascicles of spindle cells with cigar-shaped nuclei strongly positive for smooth muscle actin, desmin and H-caldesmon. The other component consisted of a high-grade pleomorphic sarcoma with osteoid and chondroid matrix production, which positive for SATB2. Thus, a final diagnosis of dedifferentiated leiomyosarcoma was rendered. Fifteen months after treatment, the patient presented further local and distant relapse with pulmonary metastases and died 23 months after the first presentation.Discussion and conclusionsDedifferentiated leiomyosarcoma is a highly malignant neoplasm with a poor outcome. Extensive sampling of soft tissue leiomyosarcomas is recommended to detect possible dedifferentiated areas as they represent a crucial prognostic parameter.

Cystic extraskeletal osteosarcoma: Three case reports and review of the literature.

Extraskeletal osteosarcoma is a rare soft tissue sarcoma and typically appears as a solid mass with variable mineralization. A few cases of extraskeletal osteosarcoma have shown extensive hemorrhagic changes or bleeding due to its high-grade malignancy; however, to the best of our knowledge, no previous reports have described the pathological characteristics of tumors with non-hemorrhagic cystic change. The present report discusses three cases involving cystic lesions with a solid area at the periphery that arose in soft tissues. The large cystic spaces contained only yellowish-brown fluid and little or no blood, with no clear pathological necrotic tissue. The solid component comprised a focal area of osteoid production by highly anaplastic sarcomatous cells. All of the cases showed high-grade malignancy histologically, and the average maximum diameter was approximately 175 mm. The tumors were located at the adductor muscles in two cases and at the intermuscular region of the hamstring muscles in one case. All of the patients consulted a doctor after more than half a year had passed since the recognition of swelling or a mass on their affected extremities. Surgical treatment was performed for all patients. One patient had lymph node metastasis, and another had lymphoedema after surgery, but no histological invasion to the lymphatic ducts was observed in the excised specimen. Degenerative changes in the fluid content over a long time-course as a result of tumor bleeding or necrosis, rather than lymphorrhea by lymphatic channel invasion of the tumor, might have contributed to the formation of the cystic lesion. Only 1 patient who underwent chemotherapy remained clinically disease-free over 10 years after surgery. Chemotherapy regimens for osteosarcoma rather than those for soft tissue sarcoma are mostly effective for extraskeletal osteosarcoma, so the diagnosis by a biopsy is essential. It is important to consider extraskeletal osteosarcoma in the differential diagnosis of soft tissue tumor with cystic form and calcification and a long clinical course before consulting a doctor.

Corded and Hyalinized Endometrioid Adenocarcinoma (CHEC) of the Uterine Corpus are Characterized by CTNNB1 Mutations and Can Show Adverse Clinical Outcomes

Corded and hyalinized endometrioid adenocarcinoma (CHEC) is a morphologic variant of endometrioid adenocarcinoma that is typically low-grade [International Federation of Gynecology and Obstetrics (FIGO) grade 1-2]. CHEC exhibits a biphasic appearance with gland forming adenocarcinoma merging with a diffuse component with corded growth often in a hyalinized matrix; squamous differentiation is frequent and osteoid production can be seen. This morphologic appearance can invoke a large differential diagnosis including carcinosarcoma. CHEC is thought to be associated with good clinical outcome although the available data is sparse. We performed detailed clinical, morphologic, immunohistochemical, and molecular analyses on a cohort of 7 CHEC. Six cases exhibited features of classic low-grade CHEC while one case showed greater cytologic atypia (high-grade CHEC). Patient age ranged from 19 to 69 yr. Four patients presented at stage I, 2 at stage II, and 1 at stage III. All tumors demonstrated nuclear staining for beta-catenin and loss of E-cadherin in the corded and hyalinized component. There was relative loss of epithelial markers. Loss of PTEN and ARID1A was seen in 4 and 3 tumors, respectively, and 1 tumor displayed loss of MLH1 and PMS2. Next-generation sequencing revealed CTNNB1 and PI3K pathway mutations in all 7 cases with TP53 and RB1 alterations in the high-grade CHEC. Clinical follow-up was available for 6 patients; 2 died of disease (48 and 50 mo), 2 are alive with disease (both recurred at 13 mo), and 2 have no evidence of disease (13 and 77 mo). Our study shows that CHEC universally harbors CTNNB1 mutations with nuclear staining for beta-catenin, can rarely show high-grade cytology, and can be associated with adverse clinical outcomes.

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression.

Osteosarcoma is a malignant primary tumor of bone, arising from transformed progenitor cells with osteoblastic differentiation and osteoid production. While categorized as a rare tumor, most patients diagnosed with osteosarcoma are adolescents in their second decade of life and underscores the potential for life changing consequences in this vulnerable population. In the setting of localized disease, conventional treatment for osteosarcoma affords a cure rate approaching 70%; however, survival for patients suffering from metastatic disease remain disappointing with only 20% of individuals being alive past 5 years post-diagnosis. In patients with incurable disease, pulmonary metastases remain the leading cause for osteosarcoma-associated mortality; yet identifying new strategies for combating metastatic progression remains at a scientific and clinical impasse, with no significant advancements for the past four decades. While there is resonating clinical urgency for newer and more effective treatment options for managing osteosarcoma metastases, the discovery of druggable targets and development of innovative therapies for inhibiting metastatic progression will require a deeper and more detailed understanding of osteosarcoma metastasis biology. Toward the goal of illuminating the processes involved in cancer metastasis, a convergent science approach inclusive of diverse disciplines spanning the biology and physical science domains can offer novel and synergistic perspectives, inventive, and sophisticated model systems, and disruptive experimental approaches that can accelerate the discovery and characterization of key processes operative during metastatic progression. Through the lens of trans-disciplinary research, the field of comparative oncology is uniquely positioned to advance new discoveries in metastasis biology toward impactful clinical translation through the inclusion of pet dogs diagnosed with metastatic osteosarcoma. Given the spontaneous course of osteosarcoma development in the context of real-time tumor microenvironmental cues and immune mechanisms, pet dogs are distinctively valuable in translational modeling given their faithful recapitulation of metastatic disease progression as occurs in humans. Pet dogs can be leveraged for the exploration of novel therapies that exploit tumor cell vulnerabilities, perturb local microenvironmental cues, and amplify immunologic recognition. In this capacity, pet dogs can serve as valuable corroborative models for realizing the science and best clinical practices necessary for understanding and combating osteosarcoma metastases.

Chondromyxoid fibroma-like osteosarcoma: a case series and literature review

BackgroundChondromyxoid fibroma-like osteosarcoma (CMF-OS) is an exceedingly rare subtype of low-grade central osteosarcoma (LGCO), accounting for up to 10% of cases and making it difficult to diagnose. CMF-OS is frequently misdiagnosed on a radiological examination and biopsy, even after the initial operation. Its treatment is a controversial issue due to its low-grade classification and actual high-grade behavior.Case presentationWe retrospectively reviewed the medical charts of more than 2000 osteosarcoma patients between 2008 and 2019; 11 patients with CMF-OS were identified, of which six patients were treated by our institution with complete clinical characteristics, including treatment and prognosis, radiological and pathological features were reviewed. Three males and three females with a median age of 46 (range 22–56) years were pathologically proven to have CMF-OS. The radiological presentation of CMF-OS is variable, thus radiological misdiagnoses are common. However, one must not ignore a malignant radiologic appearance. The most distinctive pathological feature conferring the diagnosis of CMF-OS is the presence of osteoid production directly by the tumor cells under a chondromyxoid fibroma (CMF)-like background. Differential diagnoses based on comprehensive data from CMF, LGCO, chondrosarcoma (CHS), conventional osteosarcoma (COS), etc., are needed. All patients were treated with an operation and chemotherapy, and one patient received additional radiotherapy. Nevertheless, recurrence and metastasis are common in CMF-OS patients. Relatively invasive biological behavior of CMF-OS is against the low-grade classification of this disease.ConclusionsIt is important to recognize CMF-OS and distinguish it from CMF, CHS, COS and other LGCOs. CMF-OS has a relatively poor prognosis despite its low-grade classification.

Mammary Osteosarcoma with Neoplastic Emboli in Cerebellum

Background: The mammary neoplasms are highly frequent in female dogs. It is characterized by the proliferation of epithelial or mesenchymal cells. The mammary osteosarcoma is a example of the proliferation of the last group and its main feature is production of osteoid matrix production and areas of mature bone tissue formation. Metastases to the lungs and regional lymph nodes are frequent, however some other metastasis sites have been reported. The aim of this study is to report a mammary osteosarcoma in a mixed-breed female dog of 12 years old with multiple metastases and neoplastic emboli to the central nervous system.Case: The animal was brought to the Veterinary Hospital of the Uberlândia Federal University (HV/UFU) with the complaint of increase in the volume of the mammary glands. The cytopathological exams was performed in the mass that measured 15 cm of diameter and covering a large region of the mammary gland, from the right cranial thoracic to the right cranial abdominal mammary gland. The cytological diagnostic was inconclusive because of the lack of material for diagnosis. Therefore, total unilateral mastectomy was performed for histopathology analysis. The material was then sent to the Animal Pathology Laboratory of the HV/UFU where routine processing was performed. The microscopy showed proliferation of mesenchymal cells arranged in bundles with intense pleomorfism and producing osteoid matrix, leading to the diagnosis of mammary osteosarcoma. Around 15 days after the diagnostic the animal died and was sent the Animal Pathology Laboratory of the HV/UFU for necropsy. During the external exam there was a mass at the same site of the primary mass previously extracted. Besides it, there were masses affecting lungs, intestine and kidneys. The histopathological exam showed sites of metastasis of osteosarcoma in the organs described, as well as neoplastic emboli in the cerebellum, fortifying the metastatic potential of this neoplasm. Discussion: Mammary osteosarcomas are classified mainly based on the appearance of osteoid matrix produced by osteoblast-like cells or presence of mature bone formation. In the mammary gland it is important to highlight that the neoplasia should not show tubular epithelial cells proliferation, otherwise a better classification of the disease would be carcinosarcoma. The origin of the osteoid cells in this neoplasia is still in discussion. Some authors believe that, like in other regions as thyroid gland, the osseous metaplasia in this region can lead to malignant differentiation of the metaplastic tissue originating the osteosarcoma. The gross appearance, age and breed of the animal are frequently associated with this neoplasia, and it is in agreement of other cases reported previously by different authors. Although metastases are common in this neoplasia, the involvement of the central nervous system is rare and the reports of this condition are usually associated to osteosarcoma of the appendicular skeleton origin. Even though the dog did not show any neurological clinical sign or macroscopic lesion in the central nervous system, this report highlights the importance of complementing these exams with histopathology. In this case we show a microscopic finding made only with an accurate exam of serial transversal cuts of the brain. In conclusion, more descriptive studies of mammary osteosarcoma must be made to a better interpretation of this neoplasm behavior.

Extraskeletal osteosarcoma of the hand: a case report and literature review of the pathophysiology and treatment

Extraskeletal osteosarcoma (ESOS) is a very rare form of primary osteosarcoma that is histologically characterized by tumorous osteoid production with no association with bone. ESOS accounts for less than 5% of all osteosarcoma and 1% of all soft-tissue tumor. The prevalence of ESOS in the upper limbs is approximately 20% and only five cases of ESOS of the hand have been reported. To achieve curative surgical margin for hand sarcomas, amputation is essential for certain cases, and ESOS is not exceptional. Although adjuvant chemotherapy and radiotherapy remain controversial in the treatment of ESOS, because of the hand’s functional importance, adjuvant therapies with surgery should be considered. We report a case of ESOS of the hand treated successfully with marginal resection and subsequent adjuvant chemotherapy and radiotherapy. The function of the affected hand was satisfactorily preserved and no evidence of relapse occurred for 46 months from the initial diagnosis. In this case report, we reviewed the previous reports of ESOS, namely, five cases of ESOS of the hand, and even though the role of adjuvant chemo- and/or radio-therapy remains controversial, we propose that marginal resection with adjuvant chemo- and radio-therapy are recommended for ESOS of the hand to achieve satisfactory oncological and functional outcome.

A rare presentation of carcinosarcoma of the bone in a young female; response with gemcitabine and docetaxel

BackgroundSarcomatoid carcinoma, or carcinosarcoma, is a neoplasm that contains both sarcomatous and carcinomatous elements. It is an extremely rare cancer most often arising from visceral organs. Here we report the seventh documented de novo case of carcinosarcoma of the bone, in a young female who showed initial clinical improvement with gemcitabine and docetaxel.Case presentationA 36-year-old Caucasian female presented with diffuse musculoskeletal pain that had progressed from her shoulder to her back, arm, and knee over 6 months. Imaging revealed diffuse sclerotic lesions of bilateral humeral heads, iliac and ischial bones, and thoracic and lumbar spine. Histopathologic examination of biopsies from the T9 vertebra and left femur showed mainly sarcomatous spindle cells with focal osteoid production. Immunostaining showed the cells to be OSCAR cytokeratin, patchy positive for pankeratin, and negative for CK7, GATA3, S100, SOX10, CD99, EMA, AE1/AE3, and HMW keratin indicative of an epithelial origin. After thorough clinical correlation, sarcomatoid carcinoma of a visceral organ was excluded and the diagnosis of primary sarcomatoid carcinoma of the bone was ultimately favored. She received chemotherapy with gemcitabine and docetaxel, and showed improvement at 6 months but ultimately passed 1 year post diagnosis.ConclusionsPrimary carcinosarcoma of the bone is an extremely rare malignancy. Early diagnosis is crucial as localized disease may be curable with resection. As shown in this case, combination chemotherapy with gemcitabine and docetaxel is a potential option in patients with unresectable or metastatic disease.

Abstract 82: Transforming of human osteoblasts with the combination of hTERT (T), SV40Tag (S) and c-Myc: Changes in phenotype and tumorigenesis capability

Abstract The etiology of osteosarcoma (OS), the most common primary malignant bone cancer in pediatric patients, still remains unknown. It is not clear where tat which point he osteosarcoma is originated from the osteogenic lineagein the osteogenic osteosarcoma arises., some consider Potential candidates in the literature include the human mesenchymal cells (hMSC) as the cell of origin in OS, whereas others believe theand osteoblast (OB) to be the most likely cell of origin. To understand the origin and molecular pathogenesis of osteosarcoma, we have transformed hMSCs and OBs differentiated from the same MSC with oncogenes hTERT (T), SV40Tag (S) and H-RAS (R) in series to check evaluate for spindle cell tumor formation in mice. Transformed MSC did not form osteoid, whereas OB-TSR tumor showed only scant production of osteoid, suggesting MSC may not be the origin of OS and the hTERT, SV40Tag and h-Ras may not be sufficient for osteoblast to form OS. C-Myc is one of the genes that play a major role in oncogenic transformation of normal cells. It has been shown that c-Myc is overexpressed in OS cells and more than 10% OS patients carry c-Myc amplification mutations. We further decide to look intoThis served as the basis to examine the role of c-Myc in OS formation in the background of cells transformed by hTERT and SV40. OB transformed with hTERT and SV40Tag cells were further transfected with a retrovirus containing human c-Myc to obtain stable cell lines. Quantitative PCR and western blots assays detected both gene and protein expression patterns of c-Myc, respectively, in the transformed cell lines. Transformed cell lines were analyzed for proliferation, invasion, migration, and spheroid formation to determine the tumorigenic capacity capability. TThe tumorigenesis capability is found to be correlated with the level of c-Myc expression level based onby RT-PCR data. Furthermore, we used RNA-seq to analyze gene expression profiles of the transformed cell lines, compared with those forin comparison to primary OS cell lines and patient derived xenografts (PDXs). In -vivo tumorigenic assays, histological examination for osteoid production and chromosome analysis are still under way. Our study using an osteosarcoma model with transformed human cells may provide new insights on the cell origin of OS. Citation Format: Zhongting Zhang, Yifei Wang, Wendong Zhang, Michael Roth, Jonathan Benjamin Gill, Zhaohui Xu, Xiangjun Tian, Jing Wang, Richard Gorlick. Transforming of human osteoblasts with the combination of hTERT (T), SV40Tag (S) and c-Myc: Changes in phenotype and tumorigenesis capability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 82.

PRIMARY LEIOMYOSARCOMA OF BONE: CLINICOPATHOLOGIC AND PROGNOSTIC FACTORS ANALYSIS IN A SINGLE INSTITUTION.

ABSTRACTObjective:Primary leiomyosarcoma of bone (PLB) is a rare type of malignant bone tumor considered as a variant of the spindle cell sarcomas (SCS). The objective of this study was to analyze the clinicopathologic and the prognostic factors of patients with PLB treated at a single institution.Methods:We retrospectively reviewed the records of 22 patients with pathologically confirmed PLB. The data collected were: age, sex, tumor size and location, grade and stage of the disease and histopathologic features. Mean age was 45.5 years (range, 17 to 73 y). Location was: upper limb (27.3%), lower limb (68.2%) and pelvis (4.5%). Patients had high grade in 90.9% of the reports. Margins were negative in 77.3% of the cases. Histological reports describe spindly sarcomatous cells arranged in fascicles with increased vascular formation without osteoid or chondroid matrix production. On immunohistochemistry, smooth muscle actin and desmin where positive in all cases.Results:Mean follow-up time was 73.5 months (range, 5.3 to 331.1 m). We found 22.7% of local recurrence (LR). Distant metastasis (DM) was reported in 9 (40.9%) patients. Lung metastasis was the only DM affected site. Overall survival (OS) rate in 5 years was 59.1%. Predictors of OS were LR and DM.Conclusions:PLB is an extremely rare malignant bone tumor that has a higher rate of DM and similar OS prognosis compared with other bone sarcomas. Level of Evidence IV, Case Series.

HACE1 is a potential tumor suppressor in osteosarcoma

Osteosarcoma is a malignant bone sarcoma characterized by extensive genomic disruption and a propensity for metastatic spread. Osteoid production suggests a close relationship with normal osteoblasts, and the latter are the presumptive cell of origin of this disease. The HACE1 gene, localized to human chromosome 6q21, encodes the HACE1 HECT E3 ligase, a tumor suppressor in diverse tumors that acts in part by targeting the activated form of RAC1 GTPase for proteasomal degradation. Disruption or loss of 6q21 is relatively common in osteosarcomas, and Hace1−/−/Tp53+/− mice frequently develop osteosarcomas, in contrast to Tp53+/− mice, which do not. This suggests an unexplored link between HACE1 loss and osteosarcoma. Here we compared HACE1 expression in normal osteoblasts and osteosarcoma cell lines in vitro by western blotting and quantitative RT-PCR, and in human osteosarcoma specimens by immunohistochemistry. Both HACE1 transcript and protein levels were reduced in osteosarcoma compared to osteoblasts in vitro. Reduced HACE1 expression in osteosarcoma tumors was observed in 76% of cases and associated with high-grade lesions. Further, clonally derived pairs of high and low metastatic osteosarcoma cell lines showed significant downregulation in the high compared to corresponding low metastatic cells. Ectopic expression of HACE1 markedly inhibited anchorage-independent growth and cell motility of HACE1 osteosarcoma cell lines, and was associated with reduced RAC1 activation and decreased reactive oxygen species (ROS). Finally, HACE1 overexpression blocked osteosarcoma xenograft growth and dramatically reduced pulmonary metastases. These findings point to a potential tumor suppressor function for HACE1 in osteosarcoma.

Aggressive Chondroblastic Osteosarcoma Arising in a Mature Cystic Teratoma: A Case Report and Literature Review

Mature cystic teratoma (MCT) is the most common ovarian germ cell tumor with a typically excellent prognosis. Malignant change in a somatic component of an MCT is rare, occurring in approximately 1% of cases, and most commonly occurs in the sixth to seventh decades. Osteosarcoma arising within an MCT is exceedingly rare, with only seven previously reported cases. The median age affected is 54 years. At presentation, the tumor is often large with intra-abdominal metastases. The prognosis is dismal, with only one long-term survivor. We are reporting on the clinical, radiographic, and cytohistologic features of the eighth documented case of an osteosarcoma arising in an MCT. A 29-year-old female with a medical history of scimitar syndrome (partial anomalous pulmonary venous return) presented to the emergency room with pelvic pain concerning for ovarian torsion. Computed tomography showed a 14-cm cystic, solid, and fatty mass of the left ovary consistent with an atypical dermoid cyst. She underwent laparoscopic surgery notable for filmy adhesions and friability of the mass. Microscopically, the cyst was composed of dermal elements while the solid component demonstrated lobules of malignant cartilage in addition to osteoid production. The tumor cells stained positively for SATB2 and vimentin and were negative for EMA, cytokeratin AE1/AE3, S100, SALL4, PLAP, and OCT3/4. The abdominal fluid was positive for bizarre malignant cells that were strongly SATB2 positive. A subsequent PET scan highlighted extensive metastatic peritoneal deposits. The patient received one round of chemotherapy before dying 46 days after diagnosis. Osteosarcoma arising in an MCT is a rare and aggressive malignancy with almost all cases resulting in death within months after diagnosis. While not entirely specific, SATB2 immunohistochemistry in conjunction with cytohistomorphology can aid in making the correct diagnosis, particularly in cytologic specimens where background tumor matrix is not present.

Osteoinduction and -conduction through absorbable bone substitute materials based on calcium sulfate: in vivo biological behavior in a rabbit model.

Calcium sulfate (CS) can be used as an antibiotically impregnated bone substitute in a variety of clinical constellations. Antibiotically loaded bone substitutes find specific application in orthopedic and trauma surgery to prevent or treat bone infections especially in relation to open bone defects. However, its use as a structural bone graft reveals some concerns due to its fast biodegradation. The addition of calcium carbonate and tripalmitin makes CS formulations more resistant to resorption leaving bone time to form during a prolonged degradation process. The aim of the present study was the evaluation of biocompatibility and degradation properties of newly formulated antibiotically impregnated CS preparations. Three different types of CS bone substitute beads were implanted into the tibial metaphysis of rabbits (CS dihydrate with tripalmitin, containing gentamicin (Group A) or vancomycin (Group B); Group C: tobramycin-loaded CS hemihydrate). Examinations were performed by means of x-ray, micro-computed tomography (micro-CT) and histology after 4, 6, 8 and 12 weeks. Regarding biocompatibility of the formulations, no adverse reactions were observed. Histology showed formation of vital bone cells attached directly to the implanted materials, while no cytotoxic effect in the surrounding of the beads was detected. All CS preparations showed osteogenesis associated to implanted material. Osteoblasts attached directly to the implant surface and revealed osteoid production, osteocytes were found in newly mineralized bone. Group C implants (Osteoset®) were subject to quick degradation within 4 weeks, after 6-8 weeks there were only minor remnants with little osteogenesis demonstrated by histological investigations. Group A implants (Herafill®-G) revealed similar degradation within atleast 12 weeks. In contrast, group B implants (CaSO4-V) were still detectable after 12 weeks with the presence of implant-associated osteogenesis atlatest follow-up. In all of these preparations, giant cells were found during implant degradation on surface and inside of resorption lacunae. None of the analyzed CS preparations triggered contact activation. All implants demonstrated excellent biocompatibility, with implants of Group A and B showing excellent features as osteoconductive and -inductive scaffolds able to improve mechanical stability.

Adjuvant radiotherapy using intensity-modulated radiotherapy (IMRT) technique for localized extraskeletal osteosarcoma (ESOS): case report and literature review

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal malignancy. It is characterized by osteoid production without attachment to bone or periosteum. In contrast to conventional osteosarcoma, whose peak incidence is in the second decade, ESOS primarily affects adults in their fourth decades or older. Surgical resection is considered the mainstay treatment, but the relapse rate is high with unsatisfying prognosis. Due to its rarity, there is no universally accepted treatment algorithm for ESOS. Adjuvant radiotherapy (RT) in order to decrease local recurrence is considered. However, there is lack of studies demonstrating the dose, treatment field, technique, and adverse effects of RT in patients with ESOS. Here we report a 70-year-old man with ESOS at left thigh. The patient received tumor resection followed by adjuvant radiotherapy via modern intensity-modulated radiotherapy (IMRT) technique. The patient completed treatment course and maintained good limb function without devastating adverse effects. Current literatures regarding the clinical outcome and the debate of adjuvant treatment modalities are also reviewed.

Sarcomatoid Carcinoma of Renal Pelvis Involving Ureter and Renal Parenchyma with Heterologous Osteosarcomatous Differentiation: A Case Report and Review of Literature

Sarcomatoid carcinoma is a highgrade rare malignant tumor with both epithelial and mesenchymal components. Sarcomatoid carcinoma in the upper urinary tract is very rare. We reported here a case of sarcomatoid carcinoma of renal pelvis with osteosarcomatous differentiation, with involvement of the ureter and renal parenchyma in a 68-year-old female. Histologically, predominant pleomorphic spindle cell sarcoma component with osteoid production and urothelial carcinoma component with in situ areas were identified. Immunohistochemical analysis showed vimentin positivity in sarcomatous component and cytokeratin positivity in carcinomatous component.

A large osteosarcoma in the mandible of an ox

A three years old ox was referred to the University of Zambia Veterinary Clinic with a large protruded mass in the mouth. The slow growing oral mass was noticed three months earlier and contained displaced, loosely embedded incisor teeth. On clinical examination the mass was firm, large, round and located anterio-dorsally in the mandible. Histo-pathologically, tumor mass composed of neoplastic osteoblasts exhibiting osteoid and immature trabecular bony production. Neoplastic cells were positive for osterix marker expression. Gross pathology, radiology, cytology, immunohistochemistry and histopathology confirmed the mass as a mandibular osteosarcoma. This is a first and rare case of mandibular osteosarcoma being reported in cattle from Zambia and should be included in differential diagnosis of oral mass in cattle.

Abstract 1950: Introducing c-Myc into transformed human mesenchymal stem cells and osteoblasts to recapitulate the osteosarcoma phenotype

Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults. It remains unclear at what point in the pathway of differentiation between human mesenchymal stem cells (hMSCs) and osteoblasts (OBs), OS originates. Since high grade OS frequently demonstrates histologic variability, as well as the potential for multi-lineage differentiation, some consider the hMSC as the cell of origin in OS, whereas others believe the osteoblast to be the most likely cell of origin. Identifying the primary cell of origin is crucial in understanding the molecular pathogenesis of OS. To address the potential for hMSCs or OBs to transform into OS, we have performed insertional mutagenesis in hMSCs and OBs with defined genetic elements which have the potential to lead to tumorigenesis and whose pathways have been altered in OS patient specimens. Serial introduction of the viral constructs hTERT (T), SV40Tag (S), and H-RAS (R), led to spindle cell tumor formation in mice. However, MSC-TSR tumors did not form osteoid, whereas OB-TSR tumors showed only scant production of osteoid. Also the addition of β-catenin to MSC-TS cells failed to lead to tumor formation in mice. Based on these findings, MSC-TS and OB-TS cell lines may be ideal platforms for further analysis of the impact of the genetic transformation of hMSCs and OBs into OS. c-Myc has been shown to be overexpressed in OS cells and hence has been suggested as an oncogene. It has been also suggested as a novel target of RUNX2 through rescue from the apoptosis. MSC-TS and OB-TS cells were transformed with a retrovirus containing human c-Myc. Drug resistant colonies were picked up 21 days after selection to obtain stably transformed cell lines. Quantitative PCR and western blots were carried out to detect both gene and protein expression patterns in transformed cell lines, respectively. Furthermore, in order to determine the expression pattern of c-Myc in OS, quantitative PCR and western blots were also performed on human osteosarcoma primary samples, xenografts and cell lines. All functional assays outlined below will be performed to determine the tumorigenic properties of transformed cell lines. Six out of seven (86%) osteosarcoma primary samples showed a significantly greater c-Myc gene expression level compared to the positive control cell lines. Selection of stably transformed clones and comparison between cell lines and characterizations are underway. Further ongoing characterization includes: soft agar assays, in-vivo tumorigenic assays, histological examination for osteoid production and other OS specific immunohistochemical markers, proliferation, invasion and migration, and differentiation assays. It is our hope that this study will highlight the model that closely recapitulates the human osteosarcoma phenotype by forming a malignant spindle cell tumor that produces aberrant osteoid, and has the potential for multi-lineage differentiation. Citation Format: Sajida Piperdi (Thein), Wendong Zhang, Daria Ivenitsky, Yidan Zhang, Yunjia Zhang, David S. Geller, Bang Hoang, Rui Yang, Jonathan B. Gill, Michael Roth, Richard Gorlick. Introducing c-Myc into transformed human mesenchymal stem cells and osteoblasts to recapitulate the osteosarcoma phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1950. doi:10.1158/1538-7445.AM2017-1950

Hemipelvectomia total em um gato com osteossarcoma osteoblástico

Background: Osteosarcoma (OSA) is a malignant neoplasm of mesenchymal tissue that exhibits various histological features and a differentiated biological clinical behavior. The combination of clinical, radiological, and histopathological features is important for diagnosis. Surgical treatment of neoplasms with pelvic involvement is a challenge. Primary bone tumors are rare in cats and are mostly reported in older animals. The objective of this paper was to report the case of a feline subjected to total hemipelvectomy as primary treatment of pelvic OSA; the surgical technique and histological analysis of the tumor are described. No signs of recurrence were seen during seven months of follow-up.Case: A 4-year-old female mixed breed cat weighing 3 kg was presented with a one year history of increased volume on the hip joint region. Palpation of the increased volume on the hip showed a firm, adhered, and painful mass. Radiographic examination of the pelvis in the dorso ventral projection exhibited a severe osteoblastic bone reaction on the proximal femur, as well as marked periosteal reaction of the hip joint with involvement of the acetabulum. A ventral approach total hemipelvectomy technique was adopted for excision of the tumor. The animal was placed on a lateral position and a circumferential skin incision was performed on the ipsilateral limb of the affected hemipelvis, on the medial portion of the femur, and was extended cranially up to the thoracolumbar region. The pubic symphysis was exposed with a periosteal elevator and a pubic symphysiotomy was performed on the midline using a Liston bone cutter; next, the sacroiliac junction was resected. No drain was used after surgery, only compressive bandages. The patient was hospitalized for post-operative monitoring which included opioids for pain management and a non-steroidal anti-inflammatory drug and a cephalosporin class antibiotic. The wound was cleaned with saline, rifamycin spray (Rifocina Spray®) was applied, and dressing was changed every 12 h. The excised bone was submitted for pathological analysis. Gross examination revealed a 4.2 cm hardened increase in volume on the area of the femoral head and acetabulum, with irregular surface; cut surface was hard and white with black and red spots. Histology revealed osteoblastic OSA with intense and solid fusiform and stellate cells distributed in a solid pattern with no capsular border, with marked infiltration of the bone tissue, marked osteolysis, moderate proliferation of osteoclasts, and moderate anisocytosis and anisokaryosis.Discussion: Bone tumors in cats are rare and develop spontaneously. They exhibit aggressive behavior and promote local bone destruction. Firm consistency and local swelling usually occur in more advanced cases when there is a delay between the onset of clinical signs and the veterinary consultation. Radiological findings such as bone destruction and bone formation are commonly seen in this type of tumor. Hemipelvectomy is considered an aggressive surgical technique, but necessary in many cases, especially when tumors are located in the pelvis and nearby tissues. In the case presented here, this surgery was the most viable and advised therapeutic option because of tumor location. No incidents (i.e. hemorrhage) occurred during the perioperative period. After surgery, the patient continued to perform all custom functions. The hind limb, which was affected in this case, is commonly reported to be affected in the literature; however, it is unusual to have involvement of both bones (pelvis and femur) since vascularization of these bones are independent. Diagnosis was confirmed by histopathology in which a characteristic malignant mesenchymal tumor of primitive bone cells was present, with production of osteoid of variable shapes and quantity with the presence of osteoclastic giant cells.

In vitro osteoblast gene expression and differentiation atop of titanium blocks laser coated with multilayer biphasic calcium phosphate/titanium nanocomposites

In this paper, we presented a comprehensive and complete study of the biological behavior of the bone forming cells, osteoblasts, on the graded nano-biphasic calcium-phosphate/Ti coatings of different compositions by investigating bone cell proliferation, bone cell viability, markers for bone cell differentiation and key genes that encode for known proteins which are important for de novo extracellular matrix and osteoid production. We prepared the gradient nano hydroxyapatite and titanium nanoparticles (nanoTi) composite coating on Ti-6Al-4V implants. Due to the size effects of nano-Ti, this process could be used to sinter nano HA/nanoTi composite coating at low temperature. The gradient coating with different concentration of HA could be prepared by controlling the composition of the nanoparticles, and the composition of nanoHA and beta-tricalcium phosphate in the coating could be varied by controlling the laser power. The coating was characterized with XRD and SEM, and exhibited excellent biocompatibility as well as bioactivity to UMR-106 cells.

Histologic Spectrum of Giant Cell Tumor (GCT) of Bone in Patients 18 Years of Age and Below: A Study of 63 Patients.

Although the majority of giant cell tumors (GCTs) of the bone occur in adult patients, occasionally they arise in the pediatric population. In this setting they may be mistaken for tumors more commonly seen in this age group, including osteosarcoma, aneurysmal bone cyst, and chondroblastoma. All cases of primary GCT of the bone arising in patients 18 years and below were retrieved from our institutional archives and examined with emphasis on the evaluation of various morphologic patterns. Clinical/radiologic records were reviewed when available. Analysis for H3F3A/H3F3B mutations was performed in a subset of cases. Sixty-three (of 710) patients treated at our institution for GCT were 18 years of age and below. The following morphologic patterns were identified: fibrosis (31 cases, 49%), reactive-appearing bone (26, 41%), cystic change (7, 11%), foamy histiocytes (6, 10%), secondary aneurysmal bone cyst (3, 5%), and cartilage (2, 3%). Infarct-like necrosis was present in 17 tumors (27%), and the mitotic rate ranged from 0 to 35 mitoses/10 high-power fields (median 5 mitoses/10 high-power field). Follow-up information (n=55; 6 mo to 69.6 y; median, 11.6 y) showed 21 patients with local recurrence (38%) and 2 patients with lung metastasis (4%). Polymerase chain reaction with sequencing showed that 5 of 5 tested cases harbored H3F3A mutations. In summary, GCT arising in the pediatric population is rare, representing 9% of GCTs seen at our institution. The morphologic spectrum of these tumors is broad and similar to that seen in patients above 18 years of age. It is important to recognize that matrix formation may be observed in GCT, including reactive-appearing bone and cartilage, as well as areas of fibrosis mimicking osteoid production, to avoid misclassification as osteosarcoma or other giant cell-rich lesions common in children.