Central Osteosarcoma Research Articles

Juvenile ossifying fibroma accompanied with low-grade central osteosarcoma in sinonasal: a rare case report

Sinonasal osteosarcoma is comparatively rare and accounts for 6.5% of all osteosarcomas. The five-year survival rate is less than 25% and may be improved to 60% when chemotherapy is initiated earlier. The diagnosis of low-grade central osteosarcoma requires a meticulous histopathological examination because histopathologically the tumor may mimic fibro-osseus neoplasm. We report a 12 y.o. male patient who complained of a lump on the face for 4 yr with symptoms of nasal discharge, congestion, epistaxis, and a feeling of fullness in the ears. Sinonasal biopsy was later performed and revealed an inverted papilloma. Two months after the biopsy procedure, mass extirpation and medial maxillectomy were performed. Histopathology examination confirms the diagnosis of ossifying fibroma accompanied by low-grade central osteosarcoma. Low-grade central osteosarcoma is an exceptionally rare variant, and the diagnosis is occasionally difficult. It can be misdiagnosed as a benign lesion, especially fibrous dysplasia or ossifying fibroma. Histomorphological, the discovery of atypical tumor cells producing osteoid matrix can be used to confirm that the lesion is a malignant lesion of low-grade central osteosarcoma. As demonstrated in our case, the tumor can consist of a trabecular and curvilinear arrangement of immature bone, at the edges of which there is an osteoblastic rimming appearance with a background of connective tissue stroma which is a histopathological feature of ossifying fibroma.

Oncology

The June 2024 Oncology Roundup360 looks at: Chondrosarcoma of the femur: is local recurrence influenced by the presence of an extraosseous component?; Diagnostic challenges in low-grade central osteosarcoma; Single osteotomy technique for frozen autograft (pedicled freezing) in patients with malignant bone tumours; Unplanned resection for small superficial soft-tissue sarcomas: disastrous or simply bad?; Inactivation and replantation of the knee joint: an infeasible surgical method; Active surveillance of diffuse-type tenosynovial giant cell tumours: a retrospective, multicentre cohort study.

Living with a tumor: A case of osteosarcoma involving the medullary region in Phrynops cf. P. geoffroanus (Testudines: Chelidae).

The individual Geoffroy's side-necked turtle, Phrynops cf. P. geoffroanus, was diagnosed postmortem with osteosarcoma associated with the forelimb through morphological and histological analysis. Osteosarcoma stands as the most prevalent primary malignant bone tumor in tetrapods. The tumor presents itself as a large mass in the distal epiphysis, characterized by spicular outgrowths and a rugose external texture. Histologically, the afflicted humerus displayed a high degree of vascularity and exhibited an extensive bone resorption process involving the medullary and endosteal regions. Notably, a clear transition between the bone marrow and cortical bone was absent, indicative of a remodeling process featuring Haversian bone system apposition. Additionally, the diaphyseal region displayed the progression of neoplastic bone tissue along the bone. For comparative purposes, we describe a humeral thin section from a healthy specimen revealing compact primary bone interrupted by cyclical growth marks which differs from the continuous growth observed in the neoplastic humerus. To assess the neoplastic bone growth rate at the mid-diaphysis level, phylogenetic eigenvector maps (PEM) were employed, utilizing osteocyte density and vascular density as explanatory variables. The findings indicated that the osteosarcoma exhibited a slow-growing nature, suggesting that the turtle had to live with this condition for years. As the neoplasia continued to expand, it likely led to disadvantages for the pathological Phrynops individual due to humeral deformity. Furthermore, malignancy was associated with angiogenesis and the invasion of the medullary region by neoplastic bone tissue, raising the likelihood of metastasis as an additional factor contributing to the individual's sickness. The presence of numerous vascular canals in the diaphyseal thin section suggested a low-grade central osteosarcoma. It is worth noting that osseous neoplasms are rarely documented in Testudines, making this case of osteosarcoma in a South American freshwater chelid specimen a unique and rare occurrence.

Synchronous Low-Grade Central Osteosarcoma and Ewing Sarcoma: A Rare Case Report.

A 23-year-old female patient presented with radicular back pain, perineal numbness, and urinary retention. The patient was diagnosed with cauda equina syndrome and magnetic resonance imaging (MRI) of the spine revealed an enhancing osseous lumbar lesion causing severe central stenosis. A core needle biopsy of the lumbar spine showed microscopic features compatible with a small round blue cell tumor. CD99 and FLI1 were positive in the tumor cells. Next-generation sequencing demonstrated a EWSR1::FLI1 fusion. Given these findings, the spine lesion was diagnosed as Ewing sarcoma. The patient underwent surgical decompression of L2. On further workup, an MRI revealed an ill-defined enhancing mass of the right distal femur. This area was biopsied, demonstrating a fibro-osseous lesion with osteoblast proliferation containing nuclear atypia, low mitotic activity, and SATB2 positivity, diagnosed as low-grade central osteosarcoma (LGCOS). The patient underwent resection, which showed a classic LGCOS by histomorphology. Although fluorescence in-situ hybridization study for MDM2 gene amplification was negative, the overall findings are most consistent with LGCOS. These neoplasms are considered to be synchronous due to the presentation of each entity within 6 months. Considering the aggregate yearly incidence of Ewing sarcoma (approximately 1 case per 750 000 per year) and LGCOS (approximately 1 case per 10 million per year), the aggregate yearly probability of developing both of these genetically unrelated tumors in a single individual is 1 per 7.5 trillion per year, and it is likely such an event has never happened in the past.

Detection of MDM2 gene amplification by fluorescence in situ hybridization and its diagnostic value in low-grade osteosarcoma

Objective: To investigate the diagnostic value of detecting MDM2 gene amplification by fluorescence in situ hybridization (FISH) in low-grade osteosarcoma (LGOS). Methods: Thirty cases of parosteal osteosarcoma (POS) and 14 cases of low-grade central osteosarcoma (LGCOS) from April 2009 to August 2022 at Beijing Jishuitan Hospital, Capital Medical University were analyzed for the presence of MDM2 gene amplification by FISH. Fifty-eight additional cases were used as negative controls (including 28 cases of fibrous dysplasia, 5 cases of giant cell tumor, 4 cases of conventional osteosarcoma, 2 cases each of periosteal osteosarcoma, reparative changes after fracture, pleomorphic undifferentiated sarcoma, low grade myofibroblastic sarcoma, fibrous dysplasia with malignant transformation, one case each of leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant peripheral nerve sheath tumor, desmoplastic fibroma of bone, solitary fibrous tumor, aneurysmal bone cyst, clear cell chondrosarcoma, osteofibrous dysplasia, and 3 cases of unclassified spindle cell tumor). Results: Among the 30 patients with POS, 15 were male and 15 were female, ranging in age from 10 to 59 years (mean 35 years, median 30.5 years). Among the 14 patients with LGCOS, four were male and 10 were female, ranging in age from 15 to 56 years (mean 37 years, median 36 years). All except one case were successfully detected by FISH. MDM2 gene amplification was detected in 27 cases of POS (27/29,91.3%) and 8 cases of LGCOS (8/14). All the negative controls were negative for MDM2 gene amplification. The positive rate of MDM2 gene amplification was significantly different between the case group and the control group (P<0.05). The sensitivity and specificity of MDM2 gene amplification in diagnosing POS and LGCOS were 91.3% and 100.0%; and 57.1% and 100.0%, respectively. The sensitivity and specificity of MDM2 gene amplification in diagnosing LGOS (including POS and LGCOS) were 81.3% and 100.0%, respectively. In cases where MDM2 gene was amplified, the MDM2 amplified signal was clustered. Nine cases showed increased CEP12 signal different from polyploidy which was displayed as small and weak signal points or cloud flocculent and cluster signals. Conclusions: Detection of MDM2 gene amplification by FISH is a highly sensitive and specific marker for LGOS. The interpretation criteria for FISH detection of MDM2 amplification are currently not unified. The signal characteristics need more attention when interpreting.

Beyond 5-year survival. A report from the Cooperative Osteosarcoma Study Group (COSS).

Prognostic factors have been well described for osteosarcoma, but analyses evaluating the further course of long-term survivors are lacking. We used the large database of the Cooperative Osteosarcoma Study Group (COSS) to perform such an analysis. The COSS database 1980-04/2019 was searched for 5-year survivors of primary high-grade central osteosarcoma of the extremities or trunk. Identified patients were analyzed for their further survival outcomes, assessing potentially prognostic and predictive factors already evident at initial disease presentation and treatment as well as their disease course during the first 5 years of follow-up. Two thousand and nine former eligible patients were identified (median age at initial diagnosis 15.1 (2.5-63.0) years; male vs. female 1149 (57.2%) vs. 860 (42.8%); extremities vs. trunk 1927 (95.9%) vs. 82 (4.1%); extremity primaries <1/3 vs. ≥1/3 of the involved bone 997 (67.8%) vs. 474 (32.2%) (456 unknown); localized vs. primary metastatic 1881 (93.6%) vs. 128 (6.4%); osteosarcoma as a secondary malignancy 41/2009 (2.0%)). Therapy starting by chemotherapy versus primary surgery 1860 (92.6%) versus 149 (7.4%); definitive tumor surgery by limb salvage versus ablative 1347 (67.0%) versus 659 (1 no surgery, 2 unknown); tumor response to preoperative chemotherapy documented for 1765 (94.9%) patients receiving neoadjuvant chemotherapy, good (<10% viable tumor) versus poor 1130 (64.0%) versus 635 (36.0%), local radiotherapy documented for 19 (0.9%) tumors. Recurrence during preceding 5 years no versus yes 1681 (83.7%) versus 328 (16.3%). Median follow-up starting 5 years after initial diagnosis 6.1 (0.002-32.2) years; 1815 survivors and 194 deaths. Overall survival after another 5/10/15/20 years 91.7%/88.9%/85.8%/83.4% for all patients; 97.5%/95.2%/92.4%/89.9% if in remission years 1-5 versus 62.7%/57.3%/53.0%/51.2% if recurrence year 1-5 (p < 0.001). Significant predictors of survival for all patients age at diagnosis (p = 0.038), tumor site (p = 0.030), having experienced the osteosarcoma as secondary malignancy (p < 0.001), tumor response to preoperative chemotherapy (p = 0.002). Multivariate Cox regression testing possible for 1759 (87.6%) patients with complete dataset: Having had a recurrence in years 1-5 (p < 0.001), older age at diagnosis (p = 0.009), and osteosarcoma as secondary malignancy (p = 0.013) retained significance. Highly important predictors of death such as the extent of tumor response to chemotherapy no longer remain valid after 5-year survival. The individual history of malignancies and their outcomes seems to gain pivotal importance. This benchmark analysis clearly defined risk factors for the further course of 5-year survivors from osteosarcoma. It argues for large disease-oriented databases as well as for very long follow-up periods. Novel findings will most likely require innovative statistical models to analyze such cohorts.

Diagnostic challenges in low-grade central osteosarcoma.

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder's grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome. Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002). The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins.

Engineering a metastatic stroma directs the osteosarcoma tumour transcriptome in a spatially specific manner

The biological behaviour of the cancer cell is in part controlled by its microenvironment and in part by underlying genetics. The interaction of cancer cells with the surrounding stroma directs cancer progression. The most common primary malignant tumour of the bone, osteosarcoma, is a highly complex disease in terms of its progression, invasion, and metastasis. To better understand disease characteristics and develop accurate therapies for osteosarcoma, novel tissue models have been developed to systematically understand how facets of the tumour microenvironment (TME) can influence cancer cell behaviour. This study aims to understand how osteosarcoma invasion and metastasis is influenced by different types of stromal cells in the TME. The engineering of complex tumouroids, which segregate the tumour and stromal cells in specific 3D compartments, allows for the study of tumour-stroma interaction and invasion of cells between different compartments. Complex tumouroids comprised a central osteosarcoma tumour mass with different engineered stromal compartments, representative of the primary bone or metastatic lung. Spatial Transcriptomics (ST) unveiled that osteosarcoma cells upregulated metastatic genes such as IFI27 in the presence of a lung stromal compartment, whereas a bone stromal compartment resulted in the upregulated of oncogenes and drug resistance genes such as DUSP1 and HIF1A within the osteosarcoma compartment. Engineering a primary stromal cell compartment compared to a metastatic stromal cell compartment unveiled how the regulation of cell proliferation, invasion, extracellular matrix (ECM) remodelling, metastasis markers and tumour suppressor markers was altered in the osteosarcoma transcriptome.

Sarcoma care in the era of precision medicine.

Sarcoma subtype classification is currently mainly based upon histopathological morphology. Molecular analyses have emerged as an efficient addition to the diagnostic workup and sarcoma care. Knowledge about the sarcoma genome increases, and genetic events that can either support a histopathological diagnosis or suggest a differential diagnosis are identified, as well as novel therapeutic targets. In this review, we present diagnostic, therapeutic, and prognostic molecular markers that are, or might soon be, used clinically. For sarcoma diagnostics, there are specific fusions highly supportive or pathognomonic for a diagnostic entity-for instance, SYT::SSX in synovial sarcoma. Complex karyotypes also give diagnostic information-for example, supporting dedifferentiation rather than low-grade central osteosarcoma or well-differentiated liposarcoma when detected in combination with MDM2/CDK4 amplification. Molecular treatment predictive sarcoma markers are available for gastrointestinal stromal tumor (GIST) and locally aggressive benign mesenchymal tumors. The molecular prognostic markers for sarcomas in clinical practice are few. For solitary fibrous tumor, the type of NAB2::STAT6 fusion is associated with the outcome, and the KIT/PDGFRA pathogenic variant in GISTs can give prognostic information. With the exploding availability of sequencing technologies, it becomes increasingly important to understand the strengths and limitations of those methods and their context in sarcoma diagnostics. It is reasonable to believe that most sarcoma treatment centers will increase the use of massive-parallel sequencing soon. We conclude that the context in which the genetic findings are interpreted is of importance, and the interpretation of genomic findings requires considering tumor histomorphology.

Limb Salvage Surgery Using Autogenous Irradiated Bone Graft for Low-grade Central Osteosarcoma of the Distal Tibia: A Case Report

Limb Salvage Surgery Using Autogenous Irradiated Bone Graft for Low-grade Central Osteosarcoma of the Distal Tibia: A Case Report

Three-Dimensional Printed Custom-Made Prostheses after Partial Scapulectomy: A Case Report

This case study focuses on scapula reconstruction using three-dimensional printing in a patient with low-grade osteosarcoma. Malignant tumors originating from the scapula often lead to destructive surgery, with poor functional status and quality of life for the patients. Using custom prosthetic technology through three-dimensional printing could be a possible solution for reconstruction with greater long-term functional outcomes. This study aims to assess the functional outcomes of the reconstruction. A 39-year-old patient with low-grade central osteosarcoma involving the lateral two-thirds of the scapula underwent a custom prosthetic reconstruction. The patient subsequently followed a rehabilitation protocol for 12 months. The results indicate that even though there was a slight decrease in the range of movement, and an increase in the disabilities of the arm, shoulder, and hand (DASH) score, no relevant increase in activities of daily living (ADL) disability was present at follow-up. The patient returned to carry out his daily activities without pain and with a minimal functional reduction in movement. In conclusion, three-dimensional prosthetic reconstruction is a valid alternative for scapula reconstruction, allowing excellent functional and aesthetic results in oncological cases.

Polyostotic Fibrous Dysplasia in a Six-year-Old Boy.

Fibrous dysplasia (FD) is a rare congenital benign bone disease that manifests as a defect in the bone remodeling process, affecting the function, differentiation, and maturation of osteoblasts. This process is located in the bone marrow, where the normal marrow tissue is replaced with immature bone islands and fibrous stroma. The etiology is unclear so far, but it is known to be connected with a point mutation of the gene that encodes Gs α protein at the time of embryogenesis, and because of that, all of the affected somatic cells become dysplastic. It is important to determine whether the mutation occurred earlier in the process of embryogenesis so that there will be more mutant cells and the disease will appear in a more severe form. The clinical presentation of FD is variable, so there are plenty of potential differential diagnoses. The most common include Paget disease, non-ossifying fibroma, osteofibrous dysplasia, aneurysmal bone cyst, adamantinoma, giant cell tumor, fracture callus, and low-grade central osteosarcoma.

Ultra-Late Osteosarcoma Recurrences: An Analysis of 17 Cooperative Osteosarcoma Study Group Patients with a First Recurrence Detected More Than 10 Years After Primary Tumor Diagnosis.

Purpose: Osteosarcoma is a typical malignancy of childhood and adolescence. Recurrences usually occur early, but rarely may arise after decades of remission. Little is known about these very late events and we set out to fill this knowledge gap. Methods: The database of the Cooperative Osteosarcoma Study Group (COSS) was searched for patients with a first recurrence of a high-grade central osteosarcoma occurring >10 years after diagnosis of the primary disease. Identified patients were analyzed for demographic, tumor-, and treatment-related factors as well as outcomes. Results: Among a total of 1,178 10-year relapse-free survivors, 17 affected patients were identified. Only five of these had a documented good response to initial chemotherapy. No presenting factor was identified to predict these very late events. Prognosis was generally very poor despite intensive multimodal therapy. Inoperability of the recurrences seems to have constituted a major limiting factor. Conclusion: Osteosarcoma patients should be followed for potential recurrences for well >10 years from initial diagnosis. Only through such an extended truly long-term follow-up and a structured transition of young patients can these be detected while they are still operable and, hence, potentially curable.

Lung metastases pattern in limb osteosarcoma: A population-based study from 2010 to 2018.

Osteosarcoma (OS) is one of the most prevalent malignant bone tumors. The proportion of limb OS is relatively high, and lung metastases (LM) are one of the most prevalent metastatic types. A total of 1694 new cases of limb OS were identified in the surveillance, epidemiology and end results (SEER) database from 2010 to 2018. Cox regression analyze was performed to identify prognostic factors for limb OS with LM, and univariate and multivariate logistic regression analyses were used to assess risk factors for LM. Kaplan-Meier analysis was performed to calculate overall survival for LM, and a log-rank test was used for comparison. A total of 287 patients (16.94%) were diagnosed with limb OS with LM. 25 to 59 years old (odds ratio, OR 0.68; 95% confidence interval, CI: 0.46-0.99), larger than 100 mm tumors (OR 3.65, 95% CI: 1.54-8.64), telangiectatic osteosarcoma type (OR 0.24, 95% CI: 0.07-0.81), central osteosarcoma type (OR 0.44, 95% CI: 0.19-0.99), T2 stage (OR 2.59, 95% CI: 1.18-5.69), N1 stage (OR 7.79, 95% CI: 3.90-15.56), presence of bone metastases (OR 4.58, 95% CI: 2.43-8.63) and surgical treatments of primary site (OR 0.22, 95% CI: 0.14-0.33) were significant correlations with lung metastases. Elderly age, black race and absence of surgery were harmful for survival. Age between 25 and 59 years, telangiectatic osteosarcoma and central osteosarcoma were identified as high-risk factors in limb OS patients with LM, and surgical treatment of the primary site significantly increased the survival rate of LM in these patients.

Osteosarcoma and causes of death: A report of 1520 deceased patients from the Cooperative Osteosarcoma Study Group (COSS)

PurposeMost aspects of osteosarcoma have been addressed in detail, but there is no comprehensive analysis of deceased patients and causes of death. MethodsThe database of the Cooperative Osteosarcoma Study Group COSS (1980-03/31/2021; 4475 registered high-grade central osteosarcoma patients) was searched deaths from any cause. Affected patients were analyzed for demographic and baseline variables and disease-status at the time of demise. Deaths from causes other than osteosarcoma were analyzed in detail. ResultsA total of 1520 deceased patients were identified (median age (range) at osteosarcoma diagnosis 16 (2–78) years; 908 (59.7%) male, 612 (40.3%) female; primary tumor: extremities 1263 (83.1%), trunk 208 (13.7%), craniofacial 47 (3.1%) (site unknown 2); metastases at registration: absent 1.051 (69.1%), present 466 (30.7%) (3 no data). The median time from diagnosis to death was 2.22 (0.08–32.02) years. 1286 (84.6%) patients succumbed to osteosarcoma (370 without achieving complete remission, 488 first, 428 more than one recurrences), 146 (9.6%) to other, 88 (5.8%) to unknown causes. Chemotherapy-related infections (40), secondary malignancies (39), and perioperative complications (19) were among the most frequent potentially treatment-related causes, and high-dose methotrexate (19), doxorubicin (17), and ifosfamide (15) were the drugs most commonly held responsible. Patients with unknown causes of death had an unusually long median follow-up. ConclusionThe major cause of death of patients after osteosarcoma is this malignancy, mostly from one of its multiple relapses. However, almost 10% of fatalities are due to other documented causes. Some of these deaths may be preventable with the knowledge gained from comprehensive analyses such as this.

Abstract B027: The development of a multiscale transcriptional atlas of sarcoma

Abstract Objectives: Sarcomas are mesodermal cancers of bone and soft tissue of which there are &amp;gt;60 malignant varieties, many of which can be difficult to diagnose or subtype using traditional histopathology. A universal molecular definition of sarcoma types would therefore be an invaluable tool to the diagnostic pathologist. RNA has the potential to offer a complimentary perspective to cytogenetic- and methylation-based diagnostics, as it represents the active state of the disease at sampling and better reveals its phenotype. Recognizing the potential for RNA-based classification, we set out to create a first-generation transcriptional atlas of sarcoma. Methods: To develop transcriptional definitions of cancers with the potential to further subclassify tumor types, we designed a self-optimizing and scale-adaptive unsupervised method (RACCOON), which groups samples into hierarchically organized clusters. We used this approach on the UCSC Treehouse Childhood Cancer Compendium, a set of 2,178 pediatric and 9,400 adult tumors, 1,130 of which are sarcomas, as well as 1,735 non-neoplastic samples. We then trained an ensemble of convolutional neural networks to classify tumors to these transcriptional clusters. We have now added 624 more sarcoma samples from Toronto centers and international collaborators to better represent the breadth of sarcoma. We are actively sequencing 500 additional samples in partnership with the Gabriella Miller Kids First Research Program to yield an expanded cohort of &amp;gt;2,200 uniformly processed and analyzed sarcomas. Results: Sarcomas organize into two clusters at the highest hierarchical level: one characterized by entities which occur primarily in adults and resemble mature tissue, the other by primarily pediatric entities which exhibit high stemness and resemble embryonic tissue. Several included entities are not bona fide sarcomas but originate from the mesoderm (e.g., Wilms Tumor) signifying a common transcriptional identity for mesodermal neoplasms. Additionally, we demonstrate the first transcriptional subtypes of central osteosarcoma reflecting its major histotypes and representing divergent clinical courses. We also determine Ewing Sarcoma (ES) to be a distinct entity which clusters separately from all other cancers, raising questions of its origin and affinity to sarcoma. When classifying ongoing patients to the atlas, we correctly classified &amp;gt;85% of tumors and corrected the diagnosis of 7%. We find 14% of ES in our dataset were likely misdiagnosed CIC- or BCOR-driven sarcomas. Critically, assigned subtypes are consistent between primary and relapse pairs. Conclusion: RNA-seq is a promising tool for both subtype discovery and classifying sarcoma in ongoing patients. We have already included this tool in tumor boards to help inform patient care. Our method reveals the overarching organization of sarcoma for the first time and specifies its underlying biology. This atlas is ever-growing and is open to the community to contribute. Citation Format: Joshua O. Nash, Federico Comitani, Rose Chami, Sarah Cohen-Gogo, Astra Chang-Schwertschkow, Yael Babichev, Jodi Lees, Noa Alon, Nalan Gokgoz, Stephen Man Yu, Kyoko Yuki, Miranda Lorenti, Zhanqin Liu, Alaina McGoey, Famida Spatare, Bernarld Castro, Kim Tsoi, Hagit Peretz Soroka, Jack Brzezinski, Anita Villani, Albiruni Razak, Abha Gupta, Elizabeth Demicco, Gino Somers, Brendan C. Dickson, Jay S. Wunder, Irene L. Andrulis, David Malkin, Rebecca A. Gladdy, Adam Shlien. The development of a multiscale transcriptional atlas of sarcoma [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B027.

Low-grade central osteosarcoma of the hallux with a 7-year undiagnosed course: Case report

Low-grade central osteosarcoma usually exhibits a long course with nonspecific symptoms, while the imaging and histological findings may be easily confused with a variety of benign fibroosseous lesions. A 15-year-old boy was referred for a painless swelling of the proximal phalanx associated with shortening of the right hallux. A benign cystic bone lesion complicated by a pathological fracture had been diagnosed on the radiographs at 8 and 10 years of age after sport injuries. He was referred for evaluation and treatment of the bone lesion. Magnetic resonance imaging and computed tomography were performed. A referral centre was contacted, since there was a strong evidence of malignancy. An open biopsy was suggested, which indicated bone malignancy. The patient was then referred to the specialized tumor centre. A new biopsy was performed there, since the previous sampling was considered insufficient or inadequate to secure a differentiation from fibrous dysplasia. It ensured the diagnosis of low-grade central osteosarcoma. Radical excision of the proximal phalanx and reconstruction of the defect with an iliac graft associated with arthrodesis of both the hallux metatarsophalangeal and interphalangeal joints was the treatment of choice. Disturbed wound healing necessitated hardware removal 4 months postoperatively. No further interventions were required in the follow-up. Clinical and radiographic evaluation at 12 years confirmed no evidence of local recurrence or distant metastasis. The patient was satisfied with the final outcome and reported unrestricted participation to physical activities and sports. • The rarity and the highly variable presentation of the foot and ankle malignancies may explain why they are often not considered in the differential diagnosis and the increased likelihood of delayed or incorrect diagnosis. • A low-grade central osteosarcoma localized in the proximal phalanx of the great toe of a 15-year-old boy is presented. The imaging appearance of the lesion was not correctly assessed to suggest a potentially malignant pathology and to require an early bone biopsy leading to a 7-year delayed diagnosis. • All available clinical and imaging features should be carefully considered in decision making, during the diagnostic steps in a patient with a potentially malignant bone tumor of the foot or ankle, to ensure that the diagnosis will not be delayed or missed and that proper treatment by a specialized tumor surgeon in a designated tumor centre will be offered.

Dedifferentiation in low-grade osteosarcoma: a Japanese Musculoskeletal Oncology Group (JMOG) study.

Low-grade osteosarcomas, namely parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LGCOS), occasionally dedifferentiate into high-grade malignancy, referred to as dedifferentiation in low-grade osteosarcoma (DLOS). This study aimed to elucidate the clinicopathologic features of DLOS, which are poorly described to date due to the extreme rarity of the disease. A total of 33 patients with DLOS were included. Clinical characteristics, including the diagnostic accuracy of tumor biopsy, multimodal treatments, and clinical course, were retrospectively reviewed. Univariate analysis was performed to identify prognostic factors associated with overall survival (OS) and metastasis-free survival (MFS). The tumor subtypes comprised 10 cases (30.3%) of LGCOS and 23 cases (69.7%) of POS. The timing of dedifferentiation was synchronous in 25 (75.8%) and metachronous in 8 (24.2%) patients. The rates of preoperative diagnosis of DLOS were 40.0% and 65.4% for core needle biopsy and incisional biopsy, respectively. All patients underwent surgery and 25 patients received perioperative chemotherapy. Of the 13 patients who received neoadjuvant chemotherapy, 11 exhibited a poor histological response. The 5-year OS and MFS rates were 88.1% and 77.7%, respectively. Univariate analysis revealed that local recurrence was associated with poor OS (P < 0.01) and MFS (P < 0.01). Perioperative chemotherapy did not affect OS or MFS. The diagnostic accuracy of tumor biopsy for DLOS was lower than that for bone sarcomas, as reported previously. In contrast to conventional osteosarcomas with high chemosensitivity, both histological responses and survival analysis revealed low efficacy of chemotherapy for DLOS.

Bone and soft tissue tumors at the borderlands of malignancy.

This review examines findings of musculoskeletal neoplasms whose equivocal imaging and/or histopathologic features make it difficult to determine if they will show aggressive behavior. We include both intermediate tumors as defined by the World Health Organization (WHO), and a single low-grade malignancy, low-grade central osteosarcoma, which mimics a benign lesion on imaging and histology. Intermediate tumors are a broad category and are subdivided into tumors that have risk of local recurrence only, and ones that have a risk of distant limb and pulmonary metastases. Difficult intermediate musculoskeletal lesions include atypical cartilaginous tumor/grade 1 chondrosarcoma, atypical lipomatous tumor/grade 1 liposarcoma, and solitary fibrous tumor. We review diagnostic criteria, differential diagnosis, and recommendations for surveillance.

Osteosarcoma of Jaw Masquerading as Calcifying Epithelial Odontogenic Tumour- A Diagnostic Dilemma

Osteogenic osteosarcoma is the most widely recognised primary malignant bone tumour involving particularly the appendicular skeleton. Osteosarcoma of jaw including maxillary and mandibular osteosarcoma accounts for about 7% of cases. The variants of osteosarcoma involving jaw include- osteosarcoma, Not Otherwise Specified (NOS) Low grade central osteosarcoma; chondroblastic osteosarcoma; parosteal osteosarcoma; periosteal Osteosarcoma. The present case was a 27-year-old male who came to the dental Outpatient Department (OPD) with the complaints of swelling in the upper vestibule and loosening of upper alveolar teeth and was reported as Calcifying Epithelial Odontogenic Tumour (CEOT) on histopathological examination and excision of the lesion was done. After two months the patient again presented with a recurrent lytic and sclerotic lesion involving the left maxillary bone with soft tissue extension in the maxillary sinus. Provisional diagnosis was made as malignant transformation of CEOT and immunohistochemistry was performed for the confirmation of the diagnosis. This case represented the challenges in the diagnosis of osteosarcoma of jaw which can be due to difficult biopsy procedure; limited imaging and challenges in legitimate resection because of the proximity to essential structures and the challenges are being faced to get the optimal treatment of jaw osteosarcoma.