Primary and radiation induced skull base osteosarcoma: a systematic review of clinical features and treatment outcomes.

PURPOSE: We aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced skull-base osteosarcoma (SBO). METHODS: PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including SBO cases and sufficient clinical outcome data were included. A comprehensive clinical characteristic review and survival analysis were also conducted. RESULTS: Forty-one studies describing 67 patients were included. The median age was 31 years (male = 59.7%). The middle skull-base was most commonly involved (52.7%), followed by anterior (34.5%) and posterior (12.7%) skull-base. Headache (27%), exophthalmos (18%), and diplopia (10%) were common presenting symptoms. Sixty-eight percent of patients had primary SBO, while 25% had radiation-induced SBO. Surgery was the main treatment modality in 89% of cases. Chemotherapy was administered in 65.7% and radiotherapy in 50%. Median progression-free survival (PFS) was 12 months, and the overall 5-year survival was 22%. The five-year survival rates of radiation-induced SBO and primary SBO were 39% and 16%, respectively (P < 0.05). CONCLUSION: SBO is a malignant disease with poor survival outcomes. Surgical resection is the primary management modality, in conjunction with chemotherapy and radiotherapy. Radiation-induced SBO has a superior survival outcome as compared to its primary counterpart. Complete surgical resection showed a statistically insignificant survival benefit as compared to partial resection.

Primary osteosarcoma of the parietal bone.

Osteosarcoma is the most common primary bone tumor and usually involves the long bones. Osteosarcoma of the skull, on the other hand, is relatively rare. Here, we present a 29-year-old man with a growing mass in the skull he first noticed after a fall while skateboarding. The initial clinical diagnosis was hematoma. While undergoing an evacuation surgery for a hematoma, a suspicious mass was detected which was biopsied. Histopathological evaluation showed high-grade osteosarcoma. The patient was referred to our hospital where he underwent definitive resection followed by adjuvant chemotherapy. His course was complicated by wound infection. Even though osteosarcoma of the skull is a rare finding, it should be suspected in a patient with a skull mass, and the history of prior head trauma does not exclude the diagnosis.

Primary Osteosarcoma in the Elderly Revisited: Current Concepts in Diagnosis and Treatment.

PURPOSE OF REVIEW: Osteosarcoma is mostly seen in bones of children and young adults. When it occurs in older persons, the tumor is considered secondary usually complicating Paget disease or irradiated bone. However, there is a second incidence peak of primary osteosarcoma later in life when these tumors occur de novo. This article describes the clinical, imaging, and treatment of POS in older patients, including demographic data of patients from our institution. FINDINGS: We present our experience with 920 cases of osteosarcoma that were seen between 1984 and 2003 at the University of Texas MD Anderson Cancer Center in Houston, TX, USA. Among the 868 primary osteosarcoma of bones, there were 100 (11.52%), which comprised 69% of the tumors in patients over the age of 50 years. Older patients with primary osteosarcoma tend to have relatively more common axial skeleton involvement, have more distant disease, and are difficult to treat because of concomitant comorbidities. Despite that, most adult patients treated with chemotherapy have shown good results with longer disease-free survival. A lytic bone lesion seen in radiographs of elderly patients should include primary osteosarcoma among differential diagnoses. Radical surgery and chemotherapy seem to ensure long-term disease-free survival in most cases. The elderly patients with POS in pelvis, spine, and upper extremities and those with distant disease (metastases) have worse prognosis.

Primary osteogenic sarcoma of the skull: Report of two cases with review of literature.

Primary calvarial (excluding jaw) osteosarcoma is rare. We report two cases highlighting their unusual presentation and histopathologic variability - a 30-year-old female who presented with progressively increasing headache and a rapidly growing frontal swelling and a 16-year-old girl who had a rapidly growing mass in the left frontoparietal region which had recurred thrice but was otherwise asymptomatic. The lesions were osteolytic on neuroimaging and histopathological examination confirmed osteosarcoma. These two unusual cases are discussed along with a brief review of literature.

Multidisciplinary management for primary uterine osteosarcoma, including gene panel testing: case report and literature review.

Primary osteosarcoma of the uterus (uOS) is rare, and its standard treatment has not yet been established. Herein, we present the case of a 50-year-old woman with uOS who demonstrated an improved prognosis after multiple surgeries to the metastatic sites. After the initial diagnosis of uOS, the patient showed recurrence and distant metastasis and hence expected to exhibit a poor prognosis. The patient underwent multiple surgical resections of the metastatic as well as primary tumors, which enabled the patient to survive for 24 months after the initial surgery. Considering that the median survival time of patients with uOS is approximately 6 months, the survival rate of our patient is noteworthy. Based on our observations, it is suggested that the resection of the primary and metastatic tumors might contribute to the extension of the survival period of the patient with chemo-resistant uOS.

Primary chondroblastic osteosarcoma of the mitral valve without metastasis.

Primary osteosarcomas of the heart are extremely rare entities, with common subtypes including osteoblastic, chondroblastic and fibroblastic subtypes. We describe a case of a 53-year-old female with history of treated breast cancer who presented with progressive dyspnea on exertion. A pulmonary artery protocol CTA demonstrated an anterior mitral leaflet lobulated mass without an osteoid or chondroid matrix. Additional cross-sectional imaging demonstrated no evidence of distant metastasis. The mass was surgically excised with pathology demonstrating a malignant neoplasm with spindle cells, bone, cartilage and rare osteoid, most consistent with a high grade chondroblastic osteosarcoma. After the expected postsurgical recovery, the patient was initiated on adjuvant therapy consisting of ifosfamide and etoposide and is currently disease free for 9 years now. Review of literature demonstrates that cardiac primary osteosarcomas typically involve the left atrium. Imaging usually shows a lobulated or irregular mass with heterogenous attenuation/enhancement and, counterintuitively, a lack of a calcified matrix. Complete surgical excision is challenging leading to poor prognosis, even in cases undergoing post-surgical chemotherapy. Median survival has been reported as about 20 months.

Characteristics and prognosis of primary pulmonary osteosarcoma: a pooled analysis.

BACKGROUND: Primary pulmonary osteosarcoma (PPOS) is an uncommon malignancy originating from the lung with low incidence, and its clinical characteristics and prognosis have not been systematically reported. Therefore, we aimed to recognize the prognostic factors and constructed a survival prediction model for PPOS. METHODS: We collected the data from the Surveillance, Epidemiology, and End Results database and systematic review of previous studies. Demographical and clinical characteristics, radiographic manifestations, treatment modalities, and prognosis were analyzed. A prediction model via nomogram was constructed and then evaluated by the concordance index (C-index) and the receiver operating characteristic (ROC) curve. RESULTS: A total of 49 cases were included for analysis with a median age of 67 years old (range 33-94 years), of which 32 (65.3%) were male. The median size was 6 cm (range 1.8-25 cm), and the median overall survival (OS) was eight months (interquartile range 4.5-12 months) with a 1-year OS rate of 30.8%. Tumor size over 7 cm (hazard ratio [HR] = 2.98; P = 0.018) and those without microscopic findings of osteoid found in the tumors (HR = 2.11; P = 0.048) were referred to a poor OS, while surgery was associated with an improved OS (HR = 0.20; P < 0.001). The C-index of the nomogram prediction model was 0.771, and the area under curve, sensitivity and specificity of the ROC curve were 0.818, 0.848 and 0.800, respectively. CONCLUSIONS: Patients with PPOS had a poor prognosis, and tumor size was mostly prognostic. Surgery seemed to be an effective treatment, and the prediction model with a nomogram in our study could effectively predict the prognosis of patients with PPOS.

Primary renal osteosarcoma: A case report and review of literature.

Primary renal osteosarcoma is an exceedingly rare tumor with poor prognosis. It tends to spread to distant sites and has a low survival rate. In this report, we present a case of a 43-year-old female patient presented with flank pain, gross hematuria, weakness, and weight loss. The patient was diagnosed with primary renal osteogenic sarcoma. This case report aimed to describe the clinical and pathological features, pathogenesis, and treatment modalities of this neoplasm.

Primary Osteosarcoma of the Breast: A Rare Case Report and Literature Review.

Background: Primary osteosarcoma of the breast (POB) is an extremely aggressive and heterogeneous neoplasm that originates from nonepithelial elements of the mammary gland and accounts for fewer than 1% of breast cancers and fewer than 5% of all sarcomas. Case Presentation: An 83-year-old Chinese woman went to our hospital because of a palpable mass she had had for 8 months in the left breast accompanied by persistent dull pain for 10 days. This mass was initially misdiagnosed as a degenerating fibroadenoma and was graded as probably benign (BI-RADS category 3) by ultrasonography (US) and computed tomography (CT) plain scan and contrast enhancement of chest. Eight months later, it was presumed to be highly malignant and graded as BI-RADS category 4C because of its rapid growth and more calcifications by US and CT. 99mTc-MDP whole-body bone imaging showed that there was a mass-like abnormal radioactive concentration of Tc-99m outside the bone of the left chest. The lumpectomy of the left breast was indicated, and the pathological findings were POB. She succumbed to respiratory failure caused by multiple lung metastases 4 months after the operation. Conclusion: POB is rare, and US and CT cannot reliably distinguish the causes of calcified breast masses between benign and malignant tumors. It can be diagnosed by pathology when metaplastic carcinoma, malignant phyllodes tumor, or carcinosarcoma containing osteoid and bone is excluded. This case could help clinicians to improve the prognosis and treatment of this disease.

Primary Osteosarcoma in Patients Over 75 Years of Age: A Case Series and Literature Review.

BACKGROUND/AIM: Little is known about the clinical characteristics in older patients of ≥75 years of age with primary osteosarcoma due to its rarity. We aimed to understand the clinical characteristics in these patients in order to make an appropriate diagnosis and provide treatment. PATIENTS AND METHODS: The medical records of eight patients of ≥75 years of age with primary osteosarcoma were retrospectively reviewed. We investigated their clinical features, imaging findings, histopathological findings, treatment methods, and oncological outcomes. RESULTS: There were two male and six female patients, with a mean age of 80 years. The mean follow-up period was 44 months. The initial symptom was pain in five, swelling in two, and a mass in one. The initial diagnosis was osteoarthritis in two, lumbar canal stenosis in two, benign bone tumor in four. The mean period from the first time the patient noticed symptoms to referral was 25 months. Two patients had a history of surgical curettage at their previous hospital for bone tumor that was considered benign. Lung metastasis was observed at presentation in three patients. The mean tumor size was 129 mm in its greatest dimension. Surgical treatment was performed on six patients, including frozen autograft reconstruction in one. Carbon-ion radiotherapy was conducted in one patient due to an unresectable pelvic lesion. CONCLUSION: Diagnosis requires care because the radiological and histological findings of primary osteosarcoma in patients ≥75 years of age are often non-specific, in addition to their delayed consultation. Individualized treatment including surgical procedure and radiotherapy is essential for older patients to maintain a good quality of their lives.

The First Mouse Model of Primary Osteosarcoma of the Breast.

BACKGROUND/AIM: Sarcomas of the breast are extremely rare malignant tumors and comprise only 5% of all sarcomas and fewer than 1% of breast cancers. Primary osteosarcoma of the breast is histologically indistinguishable from osteosarcoma of the bone. Effective therapies of this recalcitrant disease have not yet been developed. MATERIALS AND METHODS: A patient-derived xenograft (PDX) mouse model of primary osteosarcoma of the breast was established by subcutaneous implantation of the surgical specimen, along with surrounding normal tissue. Hematoxylin and eosin (H&E) staining was performed on paraffin-embedded histological sections of the original tumor resected from the patient and from implanted tumors that grew in nude mice. RESULTS: Tumors grew in 46 of 51 mice implanted with the original surgical specimen. The H&E-stained slides of the mouse-grown tumor and the original patient tumor matched, both showing large areas of spindle-shaped cells, characteristic of osteosarcoma. CONCLUSION: The first PDX mouse model of primary breast osteosarcoma was established which will enable testing of novel therapeutics as well as basic research of osteosarcoma of the breast.

The Combination of Cisplatinum and Doxorubicin Regressed Primary Osteosarcoma of the Breast in a PDOX Mouse Model.

BACKGROUND/AIM: Primary osteosarcoma of the breast is an exceedingly-rare malignant tumor that shares histological characteristics with osteosarcoma of the bone. Since effective therapies have not yet been established, standard therapy for osteosarcoma of the bone was examined in the present study for efficacy against primary osteosarcoma of the breast in a patient-derived orthotopic xenograft (PDOX) nude-mouse model. MATERIALS AND METHODS: The PDOX mouse models were established by surgical implantation of the primary osteosarcoma of the breast specimen into the mammary gland of nude mice. Mice with tumors were randomized into four groups, each n=4: control group; cisplatinum (CDDP)-treatment group; doxorubicin (DOX)-treatment group; and CDDP/DOX-combination-treatment group. Mice were treated for twenty-one days, three weeks after implantation. Tumor size and body weight were measured during three weeks of treatment. RESULTS: Significant tumor growth inhibition was observed, compared to the control, in the CDDP-treatment group, the DOX-treatment group, and the combination-treatment-group. Only the combination treatment regressed the tumor. CONCLUSION: CDDP and DOX which are standard first-line therapies for osteosarcoma, may be clinically effective against primary osteosarcoma of the breast, and in particular, their combination.

Identification of GPC3 mutation and upregulation in a multidrug resistant osteosarcoma and its spheroids as therapeutic target.

BACKGROUND: Drug resistance and the lack of molecular therapeutic target are the main challenges in the management of osteosarcomas (OSs). Identification of novel genetic alteration(s) related with OS recurrence and chemotherapeutic resistance would be of scientific and clinical significance. METHODS: To identify potential genetic alterations related with OS recurrence and chemotherapeutic resistance, the biopsies of a 20-year-old male osteosarcoma patient were collected at primary site (p-OS) and from its metastatic tumor (m-OS) formed after 5 months of adjuvant chemotherapy. Both OS specimens were subjected to cancer-targeted next generation sequencing (NGS) and their cell suspensions were cultured under three-dimensional condition to establish spheroid therapeutic model. Transcript-oriented Sanger sequencing for GPC3, the detected mutated gene, was performed on RNA samples of p-OS and m-OS tissues and spheroids. The effects of anti-GPC3 antibody and its combination with cisplatin on m-OS spheroids were elucidated. RESULTS: NGS revealed 4 mutations (GPC3, SOX10, MDM4 and MAPK8) and 6 amplifications (MDM2, CDK4, CCND3, RUNX2, GLI1 and FRS2) in p-OS, and 3 mutations (GPC3, SOX10 and EGF) and 10 amplifications (CDK4, CCND3, MDM2, RUNX2, GLI1, FRS2, CARD11, RAC1, SLC16A7 and PMS2) in m-OS. Among those alterations, the mutation abundance of GPC3 was the highest (56.49%) in p-OS and showed 1.54 times increase in m-OS. GPC3 transcript-oriented Sanger sequencing confirmed the mutation at 1046 in Exon 4, and immunohistochemical staining showed increased GPC3 production in m-OS tissues and its spheroids. EdU cell proliferation and Calcein/PI cell viability assays revealed that of the anti-OS first line drugs (doxorubicin, cisplatin, methotrexate, ifosfamide and carboplatin), 10 µM carboplatin exerted the best inhibitory effects on the p-OS but not the m-OS spheroids. 2 µg/mL anti-GPC3 antibody effectively committed m-OS spheroids to death by itself (76.43%) or in combination with cisplatin (92.93%). CONCLUSION: This study demonstrates increased abundance and up-regulated expression of mutant GPC3 in metastatic osteosarcoma and its spheroids with multidrug resistance. As GPC3-targeting therapy has been used to treat hepatocellular carcinomas and it is also effective to OS PDSs, GPC3 would be a novel prognostic parameter and therapeutic target of osteosarcomas.

Clinical, radiological, and pathological findings of primary nasal osteosarcoma in a Libyan cat.

Background: Although bone tumors are common pathologies in companion animals, limited reports describe nasal osteosarcoma (OSA) in cats. Case description: A case of nasal OSA in a local Libyan cat was admitted to the Veterinary Teaching Hospital at the Faculty of Veterinary Medicine, University of Tripoli-Libya, with nasal swelling and discharges and facial deformity. The radiological findings revealed nasal osteolysis with the absence of evidence of lung metastasis. In addition, fungal growth was not identified in microbiological culture. Furthermore, the pathological examination has grossly revealed a destructed nasal bone due to the presence of a tumor mass, with a mucohemorrhagic nasal discharge and absence of metastasis. OSA was confirmed histopathologically. Conclusion: This report presents the clinical, radiological, and pathological findings of a primary nasal OSA in a Libyan cat with no tumor metastasis to other body organs.

Predictors of the Survival of Primary and Secondary Older Osteosarcoma Patients.

Purpose: Older osteosarcoma patients have a very poor prognosis and treatment for them remains a challenge. The outcomes and potential prognostic factors of primary or secondary older osteosarcoma patients are rarely documented. Therefore, we examined the prognosis of the two special cohorts to identify possible prognostic factors, and provide optimal treatment strategy for them. Methods: The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify osteosarcoma patients aged over 40 years from 1973 to 2015. The prognostic analysis was performed using the Kaplan-Meier method and a Cox proportional hazards regression model. Results: In total, 1162 primary older osteosarcoma patients and 444 secondary older osteosarcoma patients were eligible for this study. The OS and CSS rates of the primary older osteosarcoma patients at 5-year were 38.5% and 37.1%, respectively. The 3- and 5-year OS rates of the secondary older osteosarcoma patients were 22.8% and 14.6%, respectively. On multivariate analysis of the primary older osteosarcoma patients, age > 60, male, axial site, high grade, metastasis, tumor size>10 cm, no surgery, and radiation treatment were negatively associated with OS. In terms of CSS, age, gender, decade of diagnosis, tumor site, tumor grade, tumor stage, tumor size, and surgery were independent prognostic factors. A multivariate Cox regression model showed that secondary older osteosarcoma patients of high grade, metastasis, tumor size > 10 cm, no surgery, and no chemotherapy were independent predictors of decreased OS. Conclusions: Surgery in combination with chemotherapy should be recommended for the treatment of the secondary older osteosarcoma patients, while for the primary older osteosarcoma patients, only surgery should be recommended.

Primary breast osteosarcoma mimicking calcified fibroadenoma on screening digital breast tomosynthesis mammogram.

Primary breast osteosarcoma is a rare malignancy, with mostly case reports in the literature. The appearance of breast osteosarcoma on digital breast tomosynthesis imaging has not yet been described. A 69-year-old woman presents for routine screening mammography and is found to have a calcified mass in her right breast. Pattern of calcification appeared "sunburst" on digital breast tomosynthesis images. This mass was larger than on the previous year's mammogram, at which time it had been interpreted as a benign calcified fibroadenoma. The subsequent workup demonstrated the mass to reflect primary breast osteosarcoma. The patient's workup and treatment are detailed in this case. Primary breast osteosarcoma, although rare, should be included as a diagnostic consideration for breast masses with a sunburst pattern of calcifications, particularly when the mammographic appearance has changed.

The Management Challenges in an Unusual Case of Primary Osteosarcoma of the Rib in an Adult Patient.

Primary osteosarcomas are derived from primitive bone-forming mesenchymal stem cells and most often originate in the metaphysis of the long bones of children and adolescents, but it occurs very rare in adults. Approximately 10% of osteosarcomas are located in the flat bones, pelvis being the main site. Involvement of flat bones like rib may be seen as a metastatic process or secondary to chemotherapy, but a primary osteosarcoma rib is extremely rare. Osteosarcoma originating from such rare sites poses numerous diagnostic and therapeutic challenges, and we report one such case in a 24-year-old male patient. Our case highlights the fact that osteosarcoma of the rib, although rare, should be considered in the differential diagnosis of primary malignant neoplasms of the rib even in the adult population. Further, early prompt diagnosis and aggressive multimodality management are cornerstones of management and will help improve the survival outcomes.

Primary osteosarcoma of the breast after complete resection of a metaplastic ossification: a case report.

BACKGROUND: Primary osteosarcoma of the breast is an extremely rare lesion. The pathogenesis of primary osteosarcomas is controversial. CASE PRESENTATION: We present the case of a 63-year-old white German woman who presented with a mass in her right breast after routine screening. The core needle biopsy showed ductal hyperplasia with metaplastic ossification of the breast tissue. Complete excision of the lesion with standard safety margins was performed. The final diagnosis was metaplastic ossification. Three years later, our patient presented again with a painless lump in her right breast about 15 × 8 × 7 cm, extending to the lower part of axilla with skin ulceration. Pathologic diagnosis was osteosarcoma. Positron emission tomography and computed tomography and staging showed no other lesions. Modified radical mastectomy and axillary lymph node dissection was performed, no lymph node metastases were found. CONCLUSIONS: Our case highlights the possibility that primary osteosarcoma of the breast may develop after complete resection with the classical safety margin for metaplastic ossification. Long-term follow-up after resection of this benign breast lesion is required.

Identification of differentially expressed genes in the development of osteosarcoma using RNA-seq.

OBJECTIVE: Osteosarcoma (OS) is a malignant bone tumor with high morbidity in young adults and adolescents. This study aimed to discover potential early diagnosis biomarkers in OS. RESULTS: In total, 111 differentially expressed genes (DEGs) were identified in primary OS compared with normal controls and 235 DEGs were identified in metastatic OS compared with primary OS. AURKB and PPP2R2B were the significantly up-regulated and down-regulated hub proteins, respectively, in the PPI protein-protein network (PPI) network of primary OS. ISG15 and BTRC were the significantly up-regulated and down-regulated hub proteins, respectively, in the network of metastatic OS. The DEGs in metastatic OS compared with primary OS were significantly enriched in the arachidonic acid metabolism, malaria, and chemokine signaling pathways. Finally, we employed quantitative real-time polymerase chain reaction (qRT-PCR) to validate the expression levels of candidate DEGs and the results indicated that our bioinformatics approach was acceptable. MATERIALS AND METHODS: The mRNA expression profiling of 20 subjects was obtained through high-throughput RNA-sequencing. DEGs were identified between primary OS and normal Control, and between primary OS and metastatic OS, respectively. Functional annotation and PPI networks were used to obtain insights into the functions of DEGs. qRT-PCR was performed to detect the expression levels of dysregulated genes in OS. CONCLUSIONS: Our work might provide groundwork for the further exploration of tumorigenesis and metastasis mechanisms of OS.

A Rare Case of Primary osteosarcoma of urinary bladder.

Extraskeletal osteosarcoma is a malignant mesenchymal soft tissue tumor without attachment to the bone, and is able to produce osteoid or cartilaginous matrix. This entity accounts for 1% of all soft tissue sarcomas. Thus far, less than 35 cases of bladder osteosarcomas have been reported in the literature. These tumors are associated with very poor prognosis. We report a case of primary osteosarcoma of the urinary bladder presenting with intermittent hematuria, dysuria, and right flank pain. Contrast-enhanced computed tomography scan of the abdomen, pelvis, and chest revealed a bladder mass and pulmonary metastases with specks of calcification.