Fibroblastic Osteosarcoma Research Articles

Survival and analysis of prognostic factors for fibroblastic osteosarcoma patients: a population-based study.

Osteosarcoma is the most common mesenchymal cell malignancy, 10% of which is fibroblastic osteosarcoma (FOS). Due to the low incidence of osteosarcoma, the impact of many pathological factors on survival is still unclear, especially FOS. The goal of this study was to assess the latest survival rates for FOS and the risk factors affecting survival using the Surveillance, Epidemiology, and End Results (SEER) database. Age, sex, race, SEER stage, surgery, radiation, chemotherapy, site of FOS, and survival time were collected from the SEER database for survival and prognostic factor analysis. The patients were randomly assigned to either the training cohort or the testing cohort. The overall survival (OS) curves were obtained by Kaplan-Meier according to different factors. A multivariate Cox regression model and a predictive nomogram have also been constructed. The study enrolled a total of 120 patients. OS at 1, 3, and 5 years for all patients was 90.83%, 79.17%, and 70.83%, respectively. In the 5-year survival analysis, in distant of SEER stage (P<0.01), radiation (P=0.03), and no surgery (P<0.01) were associated with a worse prognosis in patients with FOS. Multivariate analysis showed that age, and in distant of SEER stage were independent indicators of unfavorable prognosis. A nomogram was used to predict the prognosis of FOS and a calibration curve was used to validate the nomogram prediction against the actual observed survival outcomes. In summary, older age, and worse SEER stage were associated with poorer OS. The nomogram effectively predicted the probabilities of 1-, 3-, and 5-year OS, demonstrating strong concordance with the actual observed outcomes.

Osteogenic and fibroblastic osteosarcoma associated with the alveolar bulla and zygomatic arch in a pet rabbit

AbstractA 2.5‐year‐old, 2.9 kg, neutered, male domestic rabbit presented for sudden onset of sneezing and wheezing of 2‐day duration. Upon physical examination, there was mild dyspnoea characterised by mild to moderate increased inspiratory effort and audible wheeze, without evidence of ocular or nasal discharge. An aggressive expansile lytic mass lesion of the right caudal maxilla extending into the zygomatic arch was identified on skull radiographs. Computed tomography confirmed a large heterogeneously contrast enhancing soft tissue mass associated with the lytic lesion, likely originating from the right alveolar bulla, extending into the zygomatic arch. Histopathological diagnosis was osteosarcoma with areas of osteogenic and fibroblastic patterns. Diseases of the nasal cavity are common in rabbits; while infectious rhinitis remains the most common diagnosis, increasing number of cases of neoplasms involving the maxilla and nasal cavity should remind clinicians to include it in the differential diagnosis list.

Fibroblastic osteosarcoma in a guinea pig (Cavia porcellus)

The article describes the case of a 3 year 6 months old Guinea Pig (Cavia porcellus) that was assisted at the Wildlife and Exotic Animal Practice of the Faculty of Veterinary Sciences, National University of Asunción. The patient presented a hard mass in the right hind limb extending from the proximal portion of the femur, projecting caudally to the proximal tuberosity of the calcaneus, with an increase in temperature, and a marked increase in sensitivity. Radiographic diagnosis refers to a mass with amorphous areas of mineral density. Fine needle aspiration puncture revealed an undifferentiated malignant proliferative process, requiring histopathological analysis to characterize the process. Disarticulation was performed and subsequent histopathologic diagnosis under hematoxylin-eosin and Masson’s trichrome stain revealed fibroblastic osteosarcoma.

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series.

IntroductionStroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome.Materials and MethodsWe retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study.ResultsThe underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4–34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients.ConclusionsSLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management.

Malignant Transformation of an Aneurysmal Bone Cyst to Huge Fibroblastic Osteosarcoma without Radiation Exposure: Proper Surgical Management is More than a Challenge

In this study, we present a case of aneurysmal bone cyst presenting as pathologic fracture of the left proximal femur. The patient, who had history of multiple surgeries, was referred to us with a giant mass. The patient was found to develop osteosarcoma without radiation exposure. External hemipelvectomy was performed.Appropriate surgical management of a huge tumor that repeatedly operated is more than a challenge like this case. Aneurysmal bone cysts rarely present as pathologic fractures initially. In addition, to the best of our knowledge, the number of aneurysmal bone cysts (ABCs) exhibiting malignant transformation to osteosarcoma without radiation exposure is less than ten in the literature.Keywords: aneurysmal bone cyst, osteosarcoma, malignant transformation, hemipelvectomy

Malignant Transformation of Ossifying Fibroma to Juvenile Aggressive Ossifying Fibroma to Fibroblastic Osteosarcoma: A Case Report

AbstractThe researchers present a case of mandibular juvenile ossifying fibroma (JOF) undergoing malignant transformation to fibroblastic osteosarcoma (FOS) and propose to use this unique case report. In contrast to extragnathic OS (osteosarcoma), comprehensive genomic studies of gnathic OS are lacking and, hence, there are no validated diagnostic and therapeutic molecular targets for gnathic OS. Distinguishing fibroblastic OS of the jaws from its close mimics, such as ossifying fibroma (OF) and fibromatosis of the jaws, poses major challenge for pathologists. Identification of genomic aberrations of gnathic OS is an unmet clinical need that is critical for diagnosis and therapeutic targeting of these rare malignant tumors of the head and neck. PurposeThe purpose of this article to present a rare case of pathologic transformation from OF to JOF to a FOS. MethodsHistopathology was completed at each stage of biopsy. A thorough review of the literature was completed to identify other cases of this phenomenon, along with a search of genetic heterogeneity and clonal evolution during JOF recurrence and malignant transformation. ResultsA 62 -year-old female presented with a JOF of the right mandible and was treated with curettage. This tumor recurred in 2016, and the patient underwent surgical resection of the recurrent tumor. In 2019, this patient presented with large rapidly growing tumor at the same site with paresthesia suspicious for malignancy. The patient underwent right hemi-mandibulectomy with bilateral selective neck dissection. Evaluation of the histopathology revealed evidence of transformation from a benign fibro-osseous lesion to a fibroblastic osteosarcoma. ConclusionTo the researchers' knowledge, there have not been any previously published reports of malignant progression of JOF to FOS, and this case series offers a unique opportunity to explore the genetic heterogeneity and clonal evolution during JOF recurrence and malignant transformation.

Abstract 696: Palliative benefits of oral mifepristone treatment for metastatic fibroblastic osteosarcoma

Abstract Treatment with the progesterone receptor modulator, mifepristone, has provided patients with advanced adenocarcinomas, even those devoid of the classic nuclear progesterone (P) receptor, who had previously progressed off of standard chemotherapy, immunotherapy, or targeted therapy, significant palliative benefits and extension of life. The purpose of this research was to determine if mifepristone could similarly provide benefits for a sarcoma, namely, a metastatic fibroblastic osteosarcoma, that had progressed despite treatment with surgery, radiation, and chemotherapy. A 51 year old male was diagnosed at age 46, with an osteosarcoma of the right leg. He had neoadjuvant radiation therapy and a resection of the right proximal tibia to remove a 6cm tumor. This was followed by a chemotherapy cocktail of doxorubicin, cisplatin and high dosages of methotrexate for 9 months. Unfortunately, a tumor recurred and it was again resected. Since he was also found to have a 1.6 × 1.3cm upper lung nodule and another right lower lung nodule, he was also treated with ifosamide and etoposide for 5 months. Subsequently, these 2 drugs were continued for another 6 months alternating with high dose methotrexate. Foundation one testing revealed targeted mutations for CD104, FGRI, and KRAS, leading to treatment with a targeted therapy, regorafenib. However, 8 months later imaging studies showed progression of disease. Mifepristone, 200mg orally, was then added. CT scans had shown a steady decline in his condition until mifepristone was started. After 3 months of therapy, he showed stable disease with no increase in size of his metastatic lesions, or any new ones. He feels better on mifepristone than he has felt on any of his previous therapies, even when his disease was not as advanced. He has now completed five months of the combination therapy. He has neuropathies, manifested as pain in his hands and feet and somnolence from the regorafenib and no new side effects from mifepristone. This is the first non-gynecologic sarcoma, not known to be associated with the presence of the nuclear P receptor, reported to respond to mifepristone. There had been a previous case of widely metastatic leiomyosarcoma that showed dramatic response to mifepristone. The hypothesized mechanism of action for mifepristone in inhibiting growth and spread of metastatic cancer, is by inhibiting the production of the immunomodulatory protein the progesterone induced blocking factor (PIBF), actually secreted by the cancer cells themselves into the tumor microenvironment that results from activation of membrane P receptors. PIBF protein suppresses the cellular immune reaction to the tumor cells. Mifepristone, by blocking this membrane P receptor, inhibits PIBF production. Fibroblastic osteosarcoma can be added to the long list of advanced cancers, resistant to standard cancer therapy, yet demonstrating palliative benefits from mifepristone treatment. Citation Format: Jerome H. Check, Diane Check, Trina Poretta, James Aikins, Carrie Wilson. Palliative benefits of oral mifepristone treatment for metastatic fibroblastic osteosarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 696.

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.

PLK2 modulation of enriched TAp73 affects osteogenic differentiation and prognosis in human osteosarcoma.

There are three subtypes of undifferentiated human conventional osteosarcoma (HCOS): osteoblastic osteosarcoma (OOS), chondroblastic osteosarcoma (COS), and fibroblastic osteosarcoma (FOS). HCOS also exhibits heterogeneous pathological maldifferentiation in individual patients. Currently, the mechanism regulating HCOS differentiation remains unclear, and therapies are ineffective. Osteopontin (OPN) and osteocalcin (OCN) are markers of osteoblast maturation, and their expression is inhibited in HCOS. A previous study found that PLK2 inhibited TAp73 phosphorylation and consequent anti‐OS function of TAp73 in OS cells with enriched TAp73. TAp73 was also reported to regulate bone cell calcification. Here, OOS was found to have higher TAp73 levels and PLK2 expression than those in COS, which is correlated with HCOS maldifferentiation according to Spearman analysis and affects patient prognosis according to Kaplan‐Meier survival analysis. In the conventional OS cell‐line Saos2 and in patient‐derived xenograft OS (PDX‐OS) cells, increased PLK2 expression owing to abundant TAp73 levels affected OPN and OCN content as measured by RT‐PCR and Western blotting, and alizarin red staining showed that PLK2 affected calcium deposition in OS cells. In addition, PLK2 inhibition in PDX‐OS cells prohibited clone formation, as indicated by a clonogenic assay, and sensitized OS cells to cisplatin (CDDP) (which consequently limited proliferation), as shown by the CCK‐8 assay. In an established PDX animal model with abundant TAp73 levels, PLK2 inhibition or CDDP treatment prevented tumor growth and prolonged median survival. The combined therapeutic effect of PLK2 inhibition with CDDP treatment was better than that of either monotherapy. These results indicate that increased PLK2 levels due to enriched TAp73 affect osteogenic differentiation and maturation and OS prognosis. In conclusion, PLK2 is a potential target for differentiation therapy of OS with enriched TAp73.

Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546±105 days) in comparison with dogs having appendicular osteoblastic (257±48 days) or appendicular chondroblastic (170±28 days) OS (P=0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P=0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

The Utility of MDM2 and CDK4 Immunohistochemistry and MDM2 FISH in Craniofacial Osteosarcoma.

Craniofacial osteosarcoma is rare (2-10% of all osteosarcomas). Most low grade fibroblastic osteosarcomas of the long bones are characterized by amplification of chromosome12q including MDM2 and CDK4 genes. This study aims to investigate the utility of MDM2 and CDK4 immunostains as well as MDM2 FISH in craniofacial osteosarcomas as a means of distinguishing them from benign fibro-osseous lesions. Cases of primary osteosarcoma and benign fibro-osseous lesions of the craniofacial bones were identified in the diagnostic pathology archives. MDM2 (SMP14 and/or IF2) and CDK4 (D9G3E and/or DCS-31) immunostains were performed on a representative block from each osteosarcoma and benign case. Fluorescence in situ hybridization (FISH) for MDM2 was performed on non-decalcified osteosarcomas. In osteosarcomas, the rate of expression of either MDM2 IF2, MDM2 SMP14, CDK4 DCS-31, or CDK4 D9G3E was 72.7% (8/11 cases), usually focal and weak. Using the MDM2 IF2 clone and the CDK4 DCS-31 clone, MDM2 and CDK4 were negative in lesional cells in all 14 benign fibro-osseous lesions. Using the IF2 and SMP14 clones, MDM2 nuclear expression was present in associated osteoclast-like giant cells in both benign and malignant cases. Of 4 successful cases, 1 high grade osteosarcoma was positive for MDM2 amplification. MDM2 or CDK4 expression or MDM2 amplification may aid in a diagnosis of head and neck osteosarcoma. However, when absent, sarcoma is not excluded. Due to focal weak expression of MDM2 in tumor cells in conjunction with nuclear expression in associated giant cells, caution should be exercised when interpreting positive stains.

Characterization of five newly derived canine osteosarcoma cell lines

BackgroundCanine and human osteosarcomas (OS) are notably similar and have a high rate of metastasis. There is a poor understanding of the tumor development process, predisposing causes, and varying levels of aggression among different cell lines. By characterizing newly developed canine osteosarcoma cell lines, treatments for people and pets can be developed. Of the seven subtypes of OS, three are represented in this group: osteoblastic (the most common), fibroblastic, and giant cell variant. To our knowledge, there are no other giant cell variant canine OS cell lines in the published literature and only one canine fibroblastic osteosarcoma cell line. Understanding the differences between the histologic subtypes in dogs will help to guide comparative research.ResultsAlkaline phosphatase expression was ubiquitous in all cell lines tested and invasiveness was variable between the cell lines tested. Invasiveness and oxidative damage were not correlated with in vivo growth rates, where TOT grew the fastest and had the higher percentage of mice with metastatic lesions. TOL was determined to be the most chemo-resistant during cisplatin chemotherapy while TOM was the most chemo-sensitive.ConclusionsFurther comparisons and studies using these cell lines may identify a variety of characteristics valuable for understanding the disease process and developing treatments for osteosarcoma in both species.Some of this data was presented as a poster by KMF at the August 5th, 2017 National Veterinary Scholars Program in Bethesda, MA.Characterization of 5 newly generated canine osteosarcoma cell lines.Kelli Franks, Tasha Miller, Heather Wilson-Robles.

Extensor Mechanism Allograft in Osteosarcoma of the Patella

A 24-year-old female diagnosed with fibroblastic osteosarcoma of the patella underwent a total patellectomy and surgical reconstruction with a large bone-tendon allograft of the extensor mechanism and adjuvant chemotherapy. At 5 years' postoperative, the patient has adequate disease control and excellent joint function. Reconstruction with an extensor mechanism allograft is an appropriate alternative for patients with malignant patella tumors without tumor contamination of the joint, allowing for satisfactory knee function and disease control.

Low-Grade Central Fibroblastic Osteosarcoma in an Unusual Location: A Case Report

Low-Grade Central Fibroblastic Osteosarcoma in an Unusual Location: A Case Report

Low-grade central fibroblastic osteosarcoma may be differentiated from its mimicker desmoplastic fibroma by genetic analysis

BackgroundWe studied two cases of rare fibrous bone tumors, namely desmoplastic fibroma (DF) and low-grade central osteosarcoma (LGCOS) resembling desmoplastic fibroma (DF-like LGCOS). As the clinical presentation, imaging features and histopathology of DF and DF-like LGOS show much overlap, the objective of this study was to investigate the value of cytogenetic analysis, molecular pathology and immunohistochemistry in discrimination of these two mimickers.Case presentationA mutation in CTNNB (S45F) and nuclear beta-catenin immunostaining were observed in DF. DF-LGCOS had amplification of CDK4 and showed strong nuclear expression of CDK4 by IHC. Moreover, the karyotype of DF-LGCOS showed an interstitial heterozygous deletion of the long arm of chromosome 13 (q12q32), associated with loss of the RB1 tumor suppressor gene.ConclusionsKaryotyping and molecular genetic analysis may contribute to a conclusive diagnosis.

Primary, cardiac, fibroblastic osteosarcoma

Rationale:Primary cardiac osteosarcoma is a rare tumor. To our knowledge, only 15 cases have been reported in the literature in the past 10 years. We describe a case of primary, cardiac, fibroblastic osteosarcoma in a 42-year-old woman.Patient concerns:A 42-year-old woman with a 10-day history of chest pain. Intraoperatively, a mass was found originating from the ostium of the left inferior pulmonary vein in the left atrium, extending to the mitral orifice. Histologically, the tumor contained variable amounts of spindle cells and osseous differentiation in different areas. Primary, cardiac fibroblastic osteosarcoma had the typical appearance of interlacing hyperchromatic spindle-shaped stromal cells associated with osseous matrix.Diagnoses:According to the clinicopathological features, diagnosis of primary, cardiac fibroblastic osteosarcoma was made.Interventions:Wide surgical excision of the mass was performed.Outcomes:Three months after the operation, transthoracic echocardiography demonstrated a 3.2 cm × 2 cm recurrent mass in the wall of the left atrium (LA). She died shortly afterwards as a result of the local disease recurrence.Lessons:In this report, we describe a rare case of primary, cardiac fibroblastic osteosarcoma, and findings are helpful for the pathologists would like to further identify the clinicopathological features of this rare tumor.

Primary Fibroblastic Osteosarcoma of the Lumbar Vertebra on Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

A 37-year-old man who presented with one year history of lower back and right buttock pain was investigated with contrast enhanced computed tomography (CT), magnetic resonance imaging (MRI), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography which revealed a diagnosis of primary fibroblastic osteosarcoma of the lumbar vertebra. This case highlights the importance of PET/CT imaging.

Simultaneous occurrence of fibroblastic osteosarcoma and hypertrophic osteopathy (Marie’s disease) in a German shepherd dog

Osteosarcoma, as a progressive tumor, accounts for approximately 80% of malignant bone tumors in dogs. Since it is a highly metastatic tumor, it develops pulmonary metastasis in the majority of cases. The considerable site preference of the tumor in dogs and the possibility of hypertrophic osteopathy in a number of cases must be considered. Clinical examination of a 12-year female German shepherd dog with lameness, weakness, and cachexia revealed an abnormal thickening in the left forelimb and a severe swelling in the left proximal humerus. Radiographic examinations showed severe swelling in the arm’s soft tissue, proximal humerus osteolysis, and irregular and palisade periosteal reaction in most bones of thoracic and pelvic limbs as well as soft-tissue masses in the thoracic cavity. In postmortem examination, a semi-hard destructive mass extended from the central cavity of humerus to the surrounding soft tissue, pulmonary and splenic metastases were observed. According to microscopic features, the tumoric bone lesion was diagnosed as fibroblastic osteosarcoma. Hypertrophic osteopathy (Marie’s disease) was also diagnosed due to gross characteristics of the forearm and palm along with radiographic findings of the forearm and tibia. This is the first report of simultaneous occurrence of fibroblastic osteosarcoma and Marie’s disease in Iranian dogs.

Analysis of osteosarcoma subtypes by clinical genomic testing to identify clinically actionable alterations.

11019 Background: Genomic testing is being utilized with increasing frequency to identify matched therapies for patients (pts) with advanced disease; however, the utility of such testing has not been defined in osteosarcoma (OS). We report our experience with 36 pts with recurrent/metastatic OS who underwent testing on a genomic testing protocol, including actionable alterations across multiple histologic subtypes of OS. Methods: Standardized hotspot mutation analysis was performed in 36 pts with recurrent/metastatic OS, using either a 46-, 50-gene, or 128-gene CLIA certified multiplex platform. 12 pts had a 200-gene analysis on a companion research protocol. We used the Catalogue Of Somatic Mutations In Cancer (COSMIC) database to identify alterations that are in mutation hotspots in OS or in other cancers. Clinical outcomes were retrospectively collected. Histologic subtype classifications were made by an experienced sarcoma pathologist based upon the pre-treatment and resection specimens. Cases with only metastatic samples available were classified as “other high-grade osteosarcoma.” Additional clinical correlations are ongoing. Results: A total of 36 pediatric and adult pts were analyzed. All osteosarcomas were high grade; the most common osteosarcoma histologic subtypes were chondroblastic, osteoblastic, and other. Samples analyzed were from primary tumor in 15/36 (42%), with the remaining from metastatic specimens (58%). Mutations were identified in 26 pts (72%). The most common mutations were in TP53. An activating PIK3CA E545K mutation was found in chondroblastic OS. Other notable hotspot mutations include a GNAS R201 mutation in osteoblastic osteosarcoma and a KRASG12V mutation in a fibroblastic osteosarcoma. Conclusions: Clinical gene panel sequencing can identify a limited number of potentially actionable mutations in patients with osteosarcoma. Given the heterogeneity of osteosarcoma at the molecular level, clinical genomic testing may be warranted to identify patients for participation on matched clinical trials.

Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10-3 mm2/s) was significantly ( P < 0.001) lower than that of non-cartilaginous tumor cell necrosis without stroma disintegration (25/91, ADC =1.77 ± 0.03 × 10-3 mm2/s), cartilaginous viable tumor (14/91, ADC = 2.19 ± 0.04 × 10-3 mm2/s), and cystic areas including liquefied necrosis, blood space, and secondary aneurysmal bone cyst (14/91, ADC = 2.29 ± 0.05 × 10-3 mm2/s). The mean ADC value of non-cartilaginous tumor cell necrosis was also significantly ( P < 0.001) smaller than those of viable cartilaginous tumor and cystic/hemorrhagic necrosis whereas the mean ADC values were not significantly ( P > 0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.