Conventional Osteosarcoma Research Articles

Giant cell-rich osteosarcoma: A match pair analysis of 11 new cases and literature review of 56 patients.

Limited remains known on giant cell-rich osteosarcoma (GCRO) with current studies being case reports or smaller series. This investigation compared GCRO and conventional osteoblastic osteosarcoma (OOS) with regard to demographics and survival. An institutional tumor registry was used to identify 11 patients (six males) treated for GCRO. Mean age was 43 years. Staging showed American Joint Committee on Cancer (AJCC) stagesIIA in four and IIB in seven patients. Mean follow-up was 14 years. Study initiatives were: (1) Comparison of demographics between GCRO and 167 OOS from our institutional registry, (2) Differences in survival between GCRO and 33 OOS case controls (based on sex and AJCC stage), as well as 10 OOS using an age-based propensity match, and (3) Summary of all GCRO cases reported in the literature. (1) Sex (p = 0.53), grading (p = 0.56), AJCC stage (p = 0.42), and chemotherapeutic response rate (p = 0.67) did not differ between groups. Age was significantly increased in GCRO (p = 0.001). (2) Case-control and propensity-matched groups revealed no difference in disease-free survival, local recurrence, and distant disease-free survival at 2 years (p > 0.05). (3) Mean age of 56 patients (50% males) reported in the literature was 26 years. After merging with our 11 cases, the 2-year disease-free survival was 66%. GCRO remains a rare disease with high short-term mortality. Although affecting older patients more than conventional osteosarcoma, GCRO should not be viewed as a predictor of survival compared to OOS.

Monitoring early responses to neoadjuvant chemotherapy and the factors affecting neoadjuvant chemotherapy responses in primary osteosarcoma.

This study sought to predict the early responses to neoadjuvant chemotherapy (NACT) of patients with primary conventional osteosarcoma (COS) using the apparent diffusion coefficient (ADC) and to evaluate the factors affecting the tumor necrosis rate (TNR). The data of 41 patients who underwent magnetic resonance imaging (MRI) and diffusion-weighted imaging sequence scans before NACT, 5 days after the end of the first phase of NACT, after the end of the whole course of chemotherapy, were prospectively collected. ADC1 refers to the ADC before chemotherapy, ADC2 refers to the ADC after the first phase of chemotherapy, and ADC3 refers to the ADC before surgery. The change in values before and after the first phase of chemotherapy was calculated as follows: ADC2-1 = ADC2 - ADC1. The change in values before and after the last phase of chemotherapy was calculated as follows: ADC3-1 = ADC3 - ADC1. The change in values after the first phase and the last phase of chemotherapy was calculated as follows: ADC3-2 = ADC3 - ADC2. We recorded the patient characteristics, including age, gender, pulmonary metastasis, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). The patients were divided into the following 2 groups based on their histological TNR after postoperative: (I) the good-response group (≥90% necrosis, n=13) and (II) the poor-response group (<90% necrosis, n=28). Changes in the ADCs were compared between the good-response and poor-response groups. The different ADCs between the 2 groups were compared, and a receiver operating characteristic analysis was performed. A correlation analysis was performed to assess the correlations of the clinical features, laboratory features, and different ADCs with patients' histopathological responses to NACT. The ADC2 (P<0.001), ADC3 (P=0.004), ADC3-1 (P=0.008), ADC3-2 (P=0.047), and ALP before NACT (P=0.019) were significantly higher in the good-response group than in the poor-response group. The ADC2 [area under the curve (AUC) =0.723; P=0.023], ADC3 (AUC =0.747; P=0.012), and ADC3-1 (AUC =0.761; P=0.008) showed good diagnostic performance. Based on the univariate binary logistic regression analysis, the ADC2 (P=0.022), ADC3 (P=0.009), ADC2-1 (P=0.041), and ADC3-1 (P=0.014) were correlated with the TNR. However, based on the multivariate analysis, these parameters were not significantly correlated with the TNR. In patients with COS who are undergoing neoadjuvant chemotherapy, the ADC2 is a promisingindicator for predicting tumor response to chemotherapy in early.

Different Subtypes of Osteosarcoma: Histopathological Patterns and Clinical Behaviour

Osteosarcoma (OS) is a primary malignant bone tumour that usually occurs in children and adolescents. OS is a highly aggressive tumour type with a propensity for local invasion and systemic early metastasis to the lungs or other bones. According to the World Health Organization, there are different subtypes of OS, including conventional OS (osteoblastic, chondroblastic, fibroblastic), telangiectatic OS, low-grade OS, small-cell OS, parosteal OS, periosteal OS, and high-grade surface OS. In this mini review, we will discuss the background of OS and histopathological patterns and clinical behaviour of the disease. Understanding the subtypes of OS and their pathogenesis is crucial for developing more precise and effective therapies for OS patients.

NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well-defined disease?

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.

Malignant bone tumors part I: osteosarcoma

Osteosarcoma (OS) is the most common primary non-hematological bone cancer. OS is a malignant tumor of osteocyte origin. It has two distinct peaks of incidence: among young people (<20 years) in its primary form (predominantly conventional osteosarcoma) and among older patients (>50 years) in its secondary form to Paget’s disease or other bone lesions treated by irradiation. OS is manly located in the long bone (as femur) at the diaphysis. In this paper conventional osteosarcoma and other most common subtypes will be described.

Metastatic sarcomas to pleural effusion: a 10-year large tertiary care center experience with emphasis on clinical features and cytomorphologic characteristics.

Metastatic sarcomas to pleural effusion are extremely rare, accounting for <1% of all malignant pleural effusions. We aim to present our experience with pleural effusion specimens containing metastatic sarcomas over a 10-year period. We performed a 10-year retrospective search of cytopathology archives to identify all pleural effusions that were involved by metastatic sarcoma. All available cytopathology and surgical pathology specimens were retrieved and reviewed. Twenty-eight pleural fluids from 22 patients with metastatic sarcoma were identified in our search. The patients' ages ranged from 12 to 73 years. The pleural fluid volumes ranged from 10 to 1500 ml. Rhabdomyosarcoma was the most commonly encountered metastatic sarcoma to pleural effusion (n = 7). Other metastatic sarcomas were as follows: epithelioid angiosarcoma (n = 4), Ewing sarcoma (n = 3), clear cell sarcoma (n = 2), high grade conventional osteosarcoma (n = 2), undifferentiated pleomorphic sarcoma (n = 1), epithelioid sarcoma, proximal type (n = 1), dedifferentiated liposarcoma (n = 1), and conventional chondrosarcoma (n = 1). The time between initial diagnosis and effusion varied from 3 months to 25 years. Two patients are alive with disease at 6 and 21 months of follow-up. All other patients were dead of disease and the survival after a malignant pleural effusion ranged from <1 month to 18 months. Metastatic bone and soft tissue sarcomas to pleural effusions are rare and their cytologic features can be mistaken for carcinoma, melanoma, or mesothelioma. Careful review of the patient's medical history, comparison of the previous pathology and the use of ancillary studies are crucial for the evaluation of pleural effusions involved by metastatic sarcomas.

Osteosarcoma of orbital bone-chondroblastic morphology mimics to chondrosarcoma-A rare case report &amp; review of literature

Conventional osteosarcoma, a subgroup of intramedullary osteosarcoma(OS) ,is the most common osteosarcoma that occurs in adolescents and early adulthood. We present a case of 22‑year‑old male patient with the chief complaint of proptosis, pain and swelling in the left orbital region &amp; diagnosed as chrondoblastic osteosarcoma(COS) of left orbital bone. COS is very rare at orbital location, this report aimed to discuss clinical, radiographic, histopathologic, IHC findings and diagnostic pitfalls &amp; manangement of COS in view of the literature.

Mutation characteristics of osteosarcoma: a single center study of 64 cases using next-generation sequencing

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.

Dedifferentiated Low-Grade Osteosarcoma, Outcome with or Without Chemotherapy: A Systematic Review.

The treatment of low-grade osteosarcomas is surgical resection with wide margins. In instances of dedifferentiation, a therapeutic paradigm similar to that of conventional high-grade osteosarcoma has not been adequately evaluated in these neoplasms. The main objective of this review was to define whether the addition of chemotherapy to surgical treatment has an impact on the survival of patients with dedifferentiated low-grade osteosarcomas. Secondary objectives were to observe the degree of histological response to neoadjuvant chemotherapy and to describe the percentage of de novo dedifferentiation. A systematic search of articles including dedifferentiated low-grade osteosarcomas, published between 1980 and 2022 was carried out in the PubMed, Cochrane and Scielo databases. A qualitative synthesis of the results was performed. Twenty-three articles comprising 117 patients were included. The survival of patients treated with surgery alone and surgery with chemotherapy was not statistically significant between the two groups. A good histological response was seen in 20% of specimens treated with neoadjuvant chemotherapy. De novo dedifferentiation was seen in approximately a fifth of low-grade osteosarcomas. The evidence available suggests that the addition of chemotherapy does not have an impact on the survival of patients with low-grade dedifferentiated osteosarcomas.

Osteogenic sarcomas of the hands: A case series with emphasis in its peculiarities and literature review.

To present our experience on osteosarcomas of the hands and review the existing literature pertaining osteosarcomas in this extremely rare location. and results: Seven cases of osteosarcomas of the hands were reviewed, and a literature search of all primary osteosarcomas of the hands was performed. All tumors occurred in adults (mean age, 41 years) and were located mainly around the metacarpophalangeal joints. All patients presented with localized long-lasting pain as main symptom. The mean size at diagnosis was 33mm. Three tumors were low-grade central osteosarcomas, 1 low-grade central chondroblastoma-like osteosarcoma and 3 high-grade osteosarcomas. All tumors were positive for mouse double-minute 2 homolog (MDM2) immunohistochemistry. Three cases yielded results with fluorescence in-situ amplification for MDM2 (12q15)/CEP12. At last follow-up, one patient with a high-grade osteosarcoma was dead of disease. The literature review revealed similar demographic and site distribution of osteosarcomas within the hands than our series and an unusually high proportion of low-grade central and parosteal osteosarcomas when compared to the proportion of these infrequent neoplasms in the whole skeleton. osteosarcomas of hands present in older individuals compared to the population affected by conventional osteosarcomas of all sites. Importantly from a diagnostic, therapeutic and prognostic points of view, around 40% of osteosarcomas of the hands are low-grade osteosarcomas of the central or parosteal types.

Analysis of prognostic factors and histopathological response to neoadjuvant chemotherapy in osteosarcoma.

This study aims to examine the clinical results of patients who underwent medical and surgical treatment for osteosarcoma, to determine the overall survival (OS) and disease-free survival (DFS) rates, and to examine the effects of prognostic factors on these rates. Between January 2005 and January 2020, a total of 64 patients (38 males, 26 females; mean age: 20.9±11.5 years; range, 6 to 70 years) who received medical and surgical treatment for osteosarcoma were retrospectively analyzed. Demographic characteristics, follow-up period, tumor location and size, tumor stage and necrosis rate, metastatic disease, surgical treatments, postoperative complications, local recurrence, and metastasis were recorded. The relationship of these factors with the survival was examined. The median follow-up was 51.6 (range, 3 to 156) months. The most common tumor localization was in the distal femur with 42 (65.6%) patients and the most common histopathological subtypes were conventional osteosarcoma in 50 (78.1%) patients. The OS rates were 91.6% at one year, 65.9% at five years, and 51.6% at 10 years. With the exception of two patients who died during neoadjuvant chemotherapy, all patients underwent surgical treatment. The addition of chemotherapy + radiotherapy in the treatment did not provide any benefits in terms of survival and recurrence compared to the group that was not added, and the five-year OS rate was 79.3% compared to 20.7%, respectively. The overall 10-year survival rates were 83.9% and 37.2% in the group with a good response (≥90%) and poor response (<90%) to treatment (p=0.012). The mean survival time of three patients who presented with pathological fractures was shorter than the others (p>0.05). Surgical margin was ≤2 mm in 27 (42.2%) patients, >2 mm in 30 (46.9%) patients, and surgical margin was positive in five (7.8%) patients. The mean OS in the group with a surgical margin closure of >2 mm was 10.8±1.9 years and was longer than the other groups (p=0.047). Metastasis at the time of diagnosis, <90% tumor necrosis, a tumor size of ≥10 cm, and metastasis development were significantly associated with poor survival and were found to be independent prognostic factors. The OS rate in the patient group with Stage III-IV response after neoadjuvant chemotherapy given the cisplatin + doxorubicin protocol was found to be better than those given the European and American Osteosarcoma Studies (EURAMOS) protocol. More research is needed to determine the most optimal chemotherapy protocols in this patient population. In addition, a multidisciplinary approach in treatment is of utmost importance to improve oncological outcomes.

A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients. However, the highly complex cell origin involved in osteosarcoma (OS) limits the utility of traditional bulk RNA sequencing for OS subclassification. Single-cell RNA sequencing (scRNA-seq) holds great promise for identifying cell heterogeneity. However, this technique has rarely been used in the study of tumor subclassification. By analyzing scRNA-seq data for six conventional OS and nine cancellous bone (CB) samples, we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell (CSC)-like subset, which allowed us to classify OS samples into three groups. The classification model was further examined using the TARGET dataset. Each subgroup of OS had different prognoses and possible drug sensitivities, and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment. In addition, we verified the classification model through IHC staining in 138 OS samples, revealing a worse prognosis for Group B patients. Furthermore, we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS. These findings provide a novel subclassification method based on scRNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

Can we distinguish conventional osteosarcoma subtypes (osteoblastic and chondroblastic) based on their magnetic resonance signal intensities?

Introduction/Objectives. Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults, with a tendency to produce variable amounts of osteoid, cartilage, and fibrous matrices. The objective of this study is to differentiate between osteosarcoma subtypes: osteoblastic and chondroblastic according to their magnetic resonance imaging (MRI) signal intensities and X-ray findings. Methods. We performed a retrospective analysis for 21 pathologically proven osteosarcoma subtypes: osteoblastic (n = 14) and chondroblastic (n = 7). Conventional images of the bone of origin, periosteal reactions, lytic and sclerotic features, the presence of calcification, and pathological fractures were investigated with X-rays. We measured the mean region of interest values for each lesion with MRI sequences. Results. Among the osteosarcoma lesions, 57% were localized at the knee. X-ray evaluations of the osteoblastic osteosarcomas revealed pure lytic lesions in 35.7%, and pure sclerotic lesions in 42.9% cases. Chondroblastic osteosarcomas revealed pure lytic lesions in 14.3% and pure sclerotic lesions in 42.9% cases. Due to variable osteoblastic, chondroblastic, and fibroblastic areas and proportions of the ossified matrix, osteosarcoma lesions have a heterogeneous MRI signal. However, no statistically significant value was detected. Conclusion. According to our results, MRI signal characteristics and X-ray findings may not be able to distinguish osteosarcoma subtypes, so prospective studies with larger patient cohorts are needed.

A case of combination treatment of femoral osteosarcoma

Osteosarcomas are rare tumors with aggressive biology. It is important to refer such patients to a high-volume center, where an accurate diagnosis and optimal treatment are more likely to be performed. In contrast to Ewing's sarcoma, conventional osteosarcomas are believed to be generally resistant to radiation therapy, and the main treatment modalities are surgery and chemotherapy. In this clinical case, we demonstrate the efficacy of combined treatment of osteosarcoma of the femur.Preoperative chemotherapy allowed to evaluate tumor sensitivity to systemic treatment in vivo and optimize adjuvant treatment after R0 resection which allowed to achieve complete clinical response to treatment.

Differences in p53 Expression in High-Grade Conventional Osteosarcoma and Giant Cell Tumor of Bone

Background: Osteosarcoma is the most common primary tumor of bone. Generally, patients with osteosarcoma have a poor prognosis. So it is very important to be able to diagnose as early as possible. Histopathologically, osteosarcoma has a variety of types similar to non-malignant lesions, such as giant cell tumor of bone. Therefore, caution is needed in diagnosing because if it is misdiagnosed, it will result in different management. This study aims to look at differences in p53 protein expression in high-grade conventional osteosarcoma and giant cell tumor of bone.&#x0D; Methods: This observational analytic study used 30 samples from tissue biopsies/surgeries diagnosed with conventional high-grade osteosarcoma and 30 samples of giant cell tumor of bone at the Anatomical Pathology Installation of Dr. Saiful Anwar General Hospital Malang, Indonesia, between 2018-2022. p53 expression was examined using the immunohistochemical staining method. Positive if stained with brown on the nucleus of the cell, the percentage of 500 malignant cells was calculated in the large field of view of the objective lens (x40) randomly. Univariate and bivariate data analysis was performed using SPSS.&#x0D; Results: The average p53 protein expression in conventional high-grade osteosarcoma was 80.0% ± 26.2, with the lowest value being 19% and the highest value being 100%. Whereas in giant cell tumor of bone, the average p53 expression was 1.7% ± 4.3, with the lowest value being 0% and the highest value being 17.6%. Statistical analysis using the Mann-Whitney test showed that p53 expression in conventional high-grade osteosarcoma and giant cell tumor of bone showed a significant difference (p=0.000). &#x0D; Conclusion: There is a significant difference between p53 expression in high-grade conventional osteosarcoma and giant cell tumor of bone.

Aberrant expression of SPAG6 and NM23 predicts poor prognosis of human osteosarcoma.

Objective: To investigate the expression and clinical significance of sperm-associated antigen 6 and NM23 proteins in human osteosarcoma. Methods: The specimens of conventional osteosarcoma with follow-up from 42 Chinese patients were analyzed in this study, and 12 cases of osteochondroma were considered controls. The expression of SPAG6 and NM23 was inspected using immunohistochemical staining, qRT-PCR, and Western blotting methods. Results: The positive expression rate of SPAG6 protein (71.43%) in 42 cases of osteosarcoma tissue was significantly higher than that (33.33%) in 12 cases of osteochondroma tissues (p < 0.05), while the positive rate of NM23 protein (35.71%) in osteosarcoma tissue was lower than that (58.33%) in osteochondroma tissue (p < 0.05). The mRNA and protein levels of SPAG6 were significantly higher than those of the adjacent normal tissues, while the expression of NM23 was lower in osteosarcoma tissues than that in the controls (p < 0.05 for all). There was a positive relationship between the expression of SPAG6 and pathological grade, metastasis, and Enneking stage (p < 0.05 for all). The overall survival rate of osteosarcoma patients with SPAG6 positive expression was significantly lower than that with SPAG6 negative expression. The relationship between the expression of NM23 and pathological grade, metastasis, and Enneking stage was negative (p < 0.05 for all). The overall survival rate of the osteosarcoma patients with NM23 positive expression was higher than that of the patients with NM23 negative expression (p < 0.05). Conclusion: Overexpression of SPAG6 and low expression of NM23 are negatively related to pathological grade, metastasis, and Enneking stage and prognosis of osteosarcoma patients. This suggested that SPAG6 and NM23 should be considered candidate prognostic biomarkers for patients with osteosarcoma.

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.

T2-weighted MRI radiomics in high-grade intramedullary osteosarcoma: predictive accuracy in assessing histologic response to chemotherapy, overall survival, and disease-free survival.

To analyze radiomic features obtained from pre-treatment T2-weighted MRI acquisitions in patients with histologically proven intramedullary high-grade osteosarcomas and assess the accuracy of radiomic modelling as predictive biomarker of tumor necrosis following neoadjuvant chemotherapy (NAC), overall survival (OS), and disease-free survival (DFS). Pre-treatment MRI exams in 105 consecutive patients who underwent NAC and resection of high-grade intramedullary osteosarcoma were evaluated. Histologic necrosis following NAC, and clinical outcome-survival data was collected for each case. Radiomic features were extracted from segmentations performed by two readers, with poorly reproducible features excluded from further analysis. Cox proportional hazard model and Spearman correlation with multivariable modelling were used for assessing relationships of radiomics features with OS, DFS, and histologic tumor necrosis. Study included 74 males, 31 females (mean 32.5yrs, range 15-77years). Histologic assessment of tumor necrosis following NAC was available in 104 cases, with good response (≥ 90% necrosis) in 41, and poor response in 63. Fifty-three of 105 patients were alive at follow-up (median 40months, range: 2-213months). Median OS was 89months. Excluding 14 patients with metastases at presentation, median DFS was 19months. Eleven radiomics features were employed in final radiomics model predicting histologic tumor necrosis (mean AUC 0.708 ± 0.046). Thirteen radiomic features were used in model predicting OS (mean concordance index 0.741 ± 0.011), and 12 features retained in predicting DFS (mean concordance index 0.745 ± 0.010). T2-weighted MRI radiomic models demonstrate promising results as potential prognostic biomarkers of prospective tumor response to neoadjuvant chemotherapy and prediction of clinical outcomes in conventional osteosarcoma.

Osteosarcoma/Ewing Sarcoma

Osteosarcoma/Ewing Sarcoma

Role of MDM2, CDK4, BCL2, Parafibromin and Galectin 1 in Differentiating Osteosarcoma from its Benign Fibro-osseous Lesions.

Benign fibro-osseous lesions (BFOLs) are a diverse group of lesions showing considerable degree of overlap with low grade osteosarcoma (LGOS). Further, de-differentiated osteosarcoma (DOS) is usually indistinguishable from conventional high-grade OS (COS) if LGOS foci are not identified. Thus, there is a need for adjunctive immunohistochemical markers to differentiate OS from benign FOLs as well as DOS from COS. This study evaluated the role of immunohistochemical expression of MDM2, CDK4, parafibromin, BCL-2 and Galectin-1 (Gal-1) in accurate characterization of benign FOLs and in differentiating them from OS. From our archives, we retrieved 101 tissue samples which were diagnosed as osteosarcoma (OS) /ossifying fibroma (OF) / fibrous dysplasia (FD) or fibrous hyperplasia (FH) and examined their immunohistochemical staining pattern with the aforementioned antibodies. MDM2 showed 100% specificity for diagnosing OS. CDK4 and Gal-1 showed linear increase in immunoexpression from benign BFOLs to OS. BCL-2 showed equivocal immunopositivity in OF and OS, but the positivity was higher than that observed in FD. The highest immunoexpression for parafibromin was seen in FD followed by OF and OS cases. Thus, MDM2 is most specific, and Gal-1 is most sensitive of all the markers studied in differentiating OS from benign mimics. Combination of these two markers can be used as an adjunct to conventional imaging and microscopy in accurate characterization of these lesions. Further MDM2 overexpression can differentiate DOS and COS.