Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma

Simple Summary Synovial sarcoma (SS) is associated with a high risk of recurrence and poor prognosis, and no biomarker useful in monitoring tumor burden exists. We identified monocarboxylate transporter 1 (MCT1) expressed in extracellular vesicles (EVs) derived from synovial sarcoma as a potential such marker. Circulating levels of MCT1(+)CD9(+) EVs were significantly correlated with tumor volume in a SS mouse model. Serum levels of MCT1(+)CD9(+) EVs reflected tumor burden and treatment response in SS patients. Patients with MCT1 expression on the plasma membrane have significantly worse overall survival than those with nuclear expression. Silencing of MCT1 reduced the malignant phenotype including cellular viability, migration, and invasion of SS cells. MCT1 may thus be a promising novel target for liquid biopsies and a novel therapeutic target. The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1(+)CD9(+) EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1(+)CD9(+) EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1(+)CD9(+) EVs and indicates the therapeutic potential of MCT1 in SS

Denosumab for Treatment of a Recurrent Cervical Giant-Cell Tumor

A 43-year-old male patient with C5 giant cell tumor (GCT) underwent tumor resection and anterior bone fusion of C4–C6. The tumor recurred locally 9 months after surgery with the patient complaining of neck and shoulder pain similar to his preoperative symptoms. Denosumab was administered and his pain disappeared after a two-month administration, with a sclerotic rim formation seen at the tumor site on computed tomography. He has been followed for 18 months with no evidence of tumor recurrence. Complete resection is generally recommended, but is not easy for many patients with cervical GCT because of the existence of neurovascular structures. Some patients suffer from recurrence and treatment becomes more difficult. As such, denosumab may be an efficacious option for treatment of recurrent GCT of the cervical spine, although long-term follow-up is required to monitor for presence or absence of recurrence

Effectiveness of Clavicula Pro Humero Reconstruction for Elderly Patients: Report of Two Cases

Clavicula pro humero (CPH) reconstruction is a method that is used after proximal humeral excision. During CPH reconstruction, the ipsilateral clavicle is rotated downward and connected to the preserved distal humerus by using plates and screws. This method is frequently used for reconstruction surgeries involving young patients and has positive outcomes. In this study, we describe two cases of CPH reconstruction that were performed on elderly individuals after wide resection of the proximal humerus; postoperative results from these surgeries were satisfactory. The average Musculoskeletal Tumor Society (MSTS) functional score after surgery was 68.5%, indicating that CPH reconstruction is suitable for not only younger but also elderly patients, particularly those over the age of 65 years

Efficacy of carbon-ion radiotherapy and high-dose chemotherapy for patients with unresectable Ewing\u27s sarcoma family of tumors

Background Treatment for unresectable Ewing\u27s sarcoma family of tumors (ESFT) is a formidable challenge because of its high tendency for local and distant failure. Recently, carbon-ion radiotherapy (CIRT) has been applied to unre- sectable bone and soft tissue sarcoma. Additionally, high- dose chemotherapy (HDC) with stem cell rescue has been used to improve the survival of patients with relapsed ESFT. Here we report our experience with CIRT and HDC in the treatment of unresectable ESFT.\nMethods Five unresectable ESFT patients including 4 who underwent CIRT and HDC and one who underwentCIRT from 1999-2009 were retrospectively studied. After neoadjuvant chemotherapy, CIRT was conducted at the National Institute of Radiological Sciences in Chiba as local therapy. Consecutively, we employed HDC including busulfan, melphalan, and thiotepa with stem cell rescue.\nResults Two patients showed tumor shrinkage afterCIRT, including 1 patient who achieved partial response

Giant Protruding High-Grade Undifferentiated Pleomorphic Sarcoma Arising in a Keloid Scar on the Abdominal Wall

Undifferentiated pleomorphic sarcoma (UPS) is a high-grade, aggressive, soft tissue sarcoma that is often fatal. Although there are reports describing associations of sarcoma and skin lesions such as burns, radiation, and trauma, to our knowledge, UPS development in a keloid scar has not been reported. Herein, we present the case of a 76-year-old woman who had undergone surgery for endometrial cancer, 5 years before. She presented with a protruding lesion that was continuous to a keloid scar on the abdominal wall. The tumor appeared clinically malignant as it was protruding and doubled in size within three weeks, reaching approximately 6 × 6 × 2 cm. Since the tumor was diagnosed as UPS after pathological evaluation by needle biopsy, wide resection was performed. Intraoperatively, the tumor was apparently continuous to the keloid, protruding and pedunculated outside the body, and had not invaded the abdominal cavity. Histopathological examination of the resected tumor showed evidence of UPS and no suspicion of metastasis of endometrial cancer. No recurrence, metastases, or other complications were noted 6 months after surgery. The current case study reminds us that keloids may cause high-grade sarcoma such as UPS, and careful follow-up is required

Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome with Purely Osteolytic, Not Osteosclerotic, Lesions Mimicking a Malignant Tumor

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare inflammatory disorder with multiple phenotypes. The syndrome has identifiable radiologic characteristics that are the most important when making a diagnosis. X-rays of cases diagnosed with SAPHO syndrome reveal sclerotic lesions or mixed lytic and sclerotic lesions. Pure osteolytic lesions in SAPHO syndrome are rare, and to the best of our knowledge, no study has reported the radiologic change of purely osteolytic lesions to osteosclerotic lesions over time. Herein, we report on the case of a woman experiencing severe left thigh acute pain and having a medical history of palmoplantar pustulosis. Although SAPHO syndrome was suspected because of palmoplantar pustulosis, based on radiologic findings, bone metastasis of a malignant tumor or chronic bacterial osteomyelitis owing to a purely osteolytic lesion was suspected. However, needle biopsy revealed no malignancy and bacterial culture was negative, thus suggesting SAPHO syndrome. Nonsteroidal anti-inflammatory drugs, bisphosphonates, and corticosteroids were administered, which improved the left thigh pain. Furthermore, the radiologic change of osteolytic lesions to osteosclerotic lesions over time was confirmed, leading to the diagnosis of SAPHO syndrome. Our case demonstrates that knowledge of atypical radiologic findings is necessary to diagnose initial SAPHO syndrome

Successful Treatment of a Massive Desmoplastic Fibroma of the Ilium without Surgery: A Case Report with Long-Term Follow-Up

Desmoplastic fibroma of the bone (DFB) is a notably rare, lytic, locally aggressive but nonmetastatic, primary benign bone tumor in patients less than 30 years old. As the recommended primary treatment for DFB, wide resection is preferred to curettage from the perspective of recurrence but wide resection of DFB in the pelvis such as in the acetabulum could result in greater functional loss, suggesting the need for conservative treatments. However, there is no report on long-term follow-up following conservative treatment for DFB. The present case involved a 21-year-old woman with right hip pain. Radiological evaluation revealed a massive lesion throughout the right ilium and acetabulum with partial osteolysis, cortical destruction, marginal sclerosis, slight pseudotrabeculation, and bone expansion. Open biopsy from the ilium showed the proliferation of spindle cells in an abundant collagenous matrix without atypia and mitosis, suggesting a diagnosis of DFB. Conservative treatment was selected considering the risk of greater functional loss following wide ilium resection. An evaluation 10 years after follow-up showed a partially sclerotic lesion of the ilium and the absence of pain. The current case demonstrates that conservative therapy may be effective even in some cases of aggressive DFB