Correlation of High-Grade Osteosarcoma Response to Chemotherapy with Enhanced Tissue Immunological Response: Analysis of CD95R, IFN-γ, Catalase, Hsp70, and VEGF.

High-grade osteosarcoma, a primary malignant bone tumour, is experiencing a global increase in reported incidence with varied prevalence. Despite advances in management, which include surgery and neoadjuvant chemotherapy often an unsatisfactory outcome is found due to poor or heterogeneous response to chemotherapy. Our study delved into chemotherapy responses in osteosarcoma patients and associated molecular expressions, focusing on CD95 receptor (CD95R), interferon (IFN)-γ, catalase, heat-shock protein (Hsp)70, and vascular endothelial growth factor (VEGF). Employing immunohistochemistry and Huvos grading of post-chemo specimens, we analysed formalin-fixed paraffin-embedded (FFPE) osteosarcoma tissue of resected post-chemotherapy specimens from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia (DSGAH), spanning from 2016 to 2020. Results revealed varied responses (poor 40.38%, moderate 48.08%, good 11.54%) and distinct patterns in CD95R, IFN-γ, catalase, Hsp70, and VEGF expression. Significant differences among response groups were observed in CD95R and IFN-γ expression in tumour-infiltrating lymphocytes. The trend of diminishing CD95R expression from poor to good responses, accompanied by an increase in IFN-γ, implied a reduction in the count of viable osteosarcoma cells with the progression of Huvos grading. Catalase expression in osteosarcoma cells was consistently elevated in the poor response group, while Hsp70 expression was highest. VEGF expression in macrophages was significantly higher in the good response group. In conclusion, this study enhances our understanding of immune-chemotherapy interactions in osteosarcoma and identifies potential biomarkers for targeted interventions.

Characteristic of Apparent Diffusion Coefficient and Time Intensity Curve Analysis of Dynamic Contrast Enhanced MRI in Osteosarcoma Histopathologic Subtypes.

Background: According to WHO criteria, osteosarcoma (OS) consists of various histopathological subtypes. Thus, contrast-enhanced MRI is a very useful modality in the diagnosis and evaluation of osteosarcoma. Magnetic resonance imaging with dynamic contrast enhancement (DCE-MRI) studies was used to determine the apparent diffusion coefficient (ADC) value and the slope of the time-intensity curve (TIC). This study aimed to determine the correlation between ADC and TIC analysis using %Slope and maximum enhancement (ME) of histopathological osteosarcoma subtypes. Methods: This was a retrospective study with observational analysis on OS patients. The obtained data were 43 samples. Moreover, the interpretation was conducted by placing three regions of interest (ROI) in determining ADC value. It was observed by two radiologist observers with more than 10 years of experience. In this case, as many as six obtained ROIs were averaged. The inter-observer agreement was evaluated by Kappa test. TIC curve was analyzed and slope value was obtained afterward. Through SPSS 21 software, the data was analyzed. Results: The mean of ADC values of OS was (1.031x10-3±0.31mm2/s), where the highest value was found in chondroblastic subtype (1.470 x10-3±0.31mm2/s). However, the mean of TIC %slope of OS was (45.3%/s), where the highest result was found in the osteoblastic subtype (70.8%/s) followed by small cell subtype (60.8%/s) and the mean of ME of OS was 100.55% with the highest values was in osteoblastic subtype 172.72% followed by chondroblastic subtype (144.92%). This study found a significant correlation between the mean of ADC value and the OS histopathologic results as well as the correlation between the mean of ADC value and ME. Conclusion: The various types of osteosarcoma have a characteristic of radiological appearances which may similar to some bone tumor entities. The analysis of ADC values and TIC curves using % slope and ME of osteosarcoma subtypes can improve the accuracy of diagnosis as well as the monitoring of the treatment response and the disease progression.

Advance MR evaluation of synchronous multifocal osteosarcoma with pathologic fracture.

OBJECTIVE: Synchronous multifocal osteosarcoma is a rare condition in which the osteosarcoma presents with multiple bone lesions at the time of diagnosis, usually without any visceral metastases. The first case was described in early 1930s by Silverman. To report a case of synchronous multifocal osteosarcoma in adolescent with pathologic fracture. METHODS: An 18-year-old girl presented with a painful mass in the right thigh of 4 months' duration and a history of thigh bone fracture a month ago. Patient's medical records and family history was unremarkable. Physical examination showed angulation and shortening at right femoral region with tenderness and swelling. Initial radiograph and magnetic resonance (MR) images showed multiple lesions in right femoral shaft and pelvic bone with primary tumor in right distal femur with pathologic fracture and multiple bone marrow lesions found in the contralateral bones. Imaging and histopathological results supported the diagnosis of synchronous multifocal osteosarcoma. After following the chemotherapy as the treatment of choice, the radiograph and MRI evaluation were done and showed reduction of the mass size with union of the destructed part with the formation of callus. The advance MRI revealed reduction of the overall mass and the composition of the viable area compared to previous study. The patient had satisfying response to chemotherapy series and a better functional outcome on subsequent visits. RESULTS: Diagnosis of synchronous multifocal osteosarcoma was based on patient and family history and finding of multiple lesions in the MR images, meanwhile the plain radiograph only revealed the primary tumor. Amstutz described multifocal osteosarcoma as presence of one primary tumor and several smaller lesions. Most recent reviews concluded that multifocal osteosarcoma is bone-to-bone metastatic process rather than multicentric origin. The limitation in this case was absence of thoracic CT which is suggested to rule out any pulmonary metastases instead of routine chest radiograph. CONCLUSION: Although satisfying improvement was clinically achieved, further advanced MRI would be indicated to evaluate the progression of tumor and its respond to therapy.

Recurrent Cervical Sarcoma Botryoides in a 3-Year-Old Female: Approach in a Limited Resource Setting.

BACKGROUND Sarcoma botryoides, known as embryonal rhabdomyosarcoma (ERMS), is a malignant tumor which arises from embryonic muscle cells. The incidence of ERMS in the uterine cervix rarely occurs at a very young age. With sufficient resources, management of this disease is not difficult. However, in limited resources settings, such as in Indonesia, the situation is more challenging. This case report aims to highlight the difficulties encountered in diagnosing and treating patients with sarcoma botryoides. CASE REPORT A 3-year-old female patient came the outpatient clinic of our hospital with a protruding mass from her vagina resembling a bunch of grapes which easily bled. She underwent surgery to remove the mass. After the procedure, she did not return to the hospital for the recommended adjuvant chemotherapy treatment due to limited funds. Three months later, she came to the outpatient clinic with the same complaint, despite smaller size. Due to limited resources, we only evaluated the metastasis using chest x-ray and did not perform intra-operative biopsy. In the second surgery, a wide excision with 1-2 cm margin was performed, followed by adjuvant chemotherapy for 6 series. We achieved a satisfactory outcome in this case, and 18 months after the surgery, the patient was still in remission. CONCLUSIONS Sarcoma botryoides is a rare malignancy. The effective treatment for sarcoma botryoides is wide excision with safe margin of 1-2 cm, followed by 6-12 cycles of vincristine, actinomycin D, and cyclophosphamide (VAC) regiment as an adjuvant chemotherapy. A family's understanding of the treatment plan is important to achieve desired outcomes. Even with limited resources, this malignancy can still be properly treated.