Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissue: a Japanese Musculoskeletal Oncology Group (JMOG) multi-institutional study.

PURPOSE: Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissues are rare mesenchymal neoplasms, some of which are malignant. However, their clinical and pathological characteristics remain unclear. This study was performed to investigate the clinical and pathological characteristics of PEComas in bone and soft tissues by leveraging information from the Japanese Musculoskeletal Oncology Group. METHODS: Nine patients, including four male and five female patients with a median age of 50 years, were retrospectively reviewed. PEComas of the visceral organs, including the uterus and retroperitoneum, were excluded. RESULTS: Eight tumors arose in the soft tissue and one in the bone, with a mean size of 8.8 cm. Four patients showed local recurrence or distant metastasis. The 1-year survival rate was 78%. Pathologically, eight tumors were classified as malignant and one as having uncertain malignancy potential. Half of the tumors showed high MIB-1 index values of > 30%. Immunohistochemically, the melanocyte marker HMB45 was expressed in 89% of the cases, and muscle-specific markers were expressed only in 30-50% of the cases. Transcription factor binding to IGHM enhancer 3 (TFE3) expression was positive in 100% of the patients. Tumors with high expression of TFE3 were classified as PEComas with malignant potential according to Folpe's classification. CONCLUSIONS: Bone and soft tissue PEComas may have a higher malignancy potential than other visceral PEComas and are more likely to develop as TFE3-rearranged PEComas.

Prevalence of Precursory Signs of Atypical Femoral Fractures in Patients Receiving Bone-Modifying Agents for Bone Metastases: A Cross-Sectional Study.

Patients on bone-modifying agents (BMAs) for bone metastases are at risk of atypical femoral fractures (AFFs), which can lead to a sudden deterioration in performance status. In this study, we sought to determine the prevalence of radiographic precursory signs of AFF in patients on oncologic BMAs. Forty-two patients (23 men, 19 women; mean age 68.8 ± 10.0 years) on oncologic BMAs (zoledronate for >3 years and/or denosumab for >1 year) and without clinical symptoms were enrolled between 2019 and 2021. All patients were receiving denosumab at enrollment and 5 had previously used zoledronate. The mean duration of BMA use was 31.2 ± 18.5 months. Radiographs of both femurs were screened for precursory signs of AFF (e.g., thickening of the lateral cortex). The patients were divided into two groups according to thickening status and compared by duration of BMA use. They were also divided into three groups by duration of BMA use (12-23 months, n = 18; 24-59 months, n = 19; ≥60 months, n = 5), and the prevalence of apparent thickenings was examined. As a result, 18 patients (42.9%) showed minute local or diffuse thickening and 10 (23.8%) showed apparent local thickening. The duration of BMA use was significantly longer in patients with apparent thickening than in those without (47.3 ± 23.6 months [n = 10] versus 26.2 ± 13.5 months [n = 32]; p < 0.05). The prevalence of apparent thickening increased with increasing duration of BMA use (12-23 months, 5.6%; 24-59 months, 31.6%; ≥60 months, 60.0%). In conclusion, radiographic precursory signs of AFF are common in patients on oncologic BMAs. Radiographic screening for AFF could be relevant in patients who have been on long-term oncologic BMAs, even if asymptomatic. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Incidence of atypical femoral fractures in the treatment of bone metastasis: An alert report.

BACKGROUND: As the life expectancy of cancer-bearing patients has increased, more patients with bone metastasis are receiving long-term treatment with bone-modifying agents (BMAs; e.g., zoledronate and denosumab), which are a risk factor for developing atypical femoral fracture (AFF). In this study, we surveyed the risk of iatrogenic AFF using a clinical database on treatment of bone metastasis in the past 10 years. METHODS: From April 2011 through October 2019, 721 patients with bone metastasis (436 men, 285 women; mean age, 65.7 ± 12.4 years) were registered under the bone metastasis consultation system, which has been run by orthopaedic surgeons since 2011, at a university hospital in Japan. We retrospectively reviewed the database to identify patients who had received BMAs for treatment of bone metastasis, and we investigated the incidence of critical skeletal-related events (including AFF) which required surgical interventions by orthopaedic surgeons. RESULTS: BMAs were administered to 529 patients (73.4%). Orthopaedic surgery for the treatment of skeletal-related events was performed in 36 patients (5.0%): femur, 13 (1.8%); others, 23 (3.2%). Eight AFFs in 5 patients (breast cancer, n = 4; prostate cancer, n = 1), who all had prior exposure to zoledronate or denosumab before onset of AFF, were treated with internal fixation using intramedullary nailing. In 192 patients with no BMA exposure, critical (surgically treated) AFF was not detected. In summary, the incidence of critical AFF was 0.9% among 529 patients who received BMAs for treatment of bone metastasis, and the incidence was 6.6% when limited to breast cancer patients (4 of 61). CONCLUSION: In treatment of bone metastasis using BMAs, especially for breast cancer patients, attention should be paid to the risk of developing AFFs. Routine radiographic screening for AFF might be necessary in patients with prolonged BMA use for bone metastasis, even if asymptomatic. This report alerts all physicians and surgeons involved in the management of cancer patients, especially those with bone metastasis, regarding the risk of AFF following BMA use.

Surgical stabilization of spinal metastasis in diffuse idiopathic skeletal hyperostosis ("Mets-on-DISH"): Two case reports.

RATIONALE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification along the anterolateral aspect of at least 4 contiguous vertebral bodies. A fracture involving the fused vertebra in patients with DISH often leads to severe instability and spinal cord injury. Spinal metastasis (Mets) and DISH can coexist in elderly patients and increase their risk of pathologic vertebral fractures. However, there are few reports on concomitant spinal Mets and DISH. PATIENT CONCERNS: A 78-year-old man who complained of gradual onset of paraparesis, sensory loss below the umbilicus, and incontinence (case 1) and a 63-year-old woman who complained of severe back pain and urinary incontinence (case 2). DIAGNOSIS: Two patients were diagnosed with spinal Mets and DISH. INTERVENTIONS: Decompression surgery was performed at the metastatic sites in case 1 whereas instrumentation surgery was performed in case 2 despite the fracture having a benign appearance with no associated neurologic symptoms. OUTCOMES: A vertebral fracture developed at the metastatic vertebra after decompression surgery in case 1. Severe instability of the surgical site in this case resulted in persistent paralysis even after subsequent revision surgery with instrumentation. In contrast, the clinical course was benign without any neurologic dysfunction at the 2-year follow-up in case 2. LESSONS: Instrumentation surgery should be performed in patients with DISH who develop spinal Mets even if there is no apparent instability.

Malignant primary pulmonary meningioma with bone metastasis.

Primary pulmonary meningioma is extremely rare and only <45 cases have been reported since its first report by Kemnitz and Heinrich (Meningioma of lung: first report with light and electronmicroscopic findings. Ultrastruct. Pathol. 1982;3:359-65). Among these cases, only five cases were malignant or atypical. A 67-year-old female with primary pulmonary meningioma underwent thoracoscopic pulmonary wedge resection of the left lower lobe a year before. She had been aware of left thigh pain for 9 months, then she was referred to our division. Positron emission tomography-computed tomography suspected multiple bone metastasis including frontal bone, mandible, left scapula, rib, vertebra, pubis, left femur and sternum. We performed a needle biopsy of the sternum. Histopathological diagnosis was metastasis of primary pulmonary meningioma, World Health Organization grade III. We treated her with denosumab and radiation therapy targeting the left femur. Two months after the treatment, the pain had decreased and she could walk with no cane. No case of malignant extracranial meningioma with bone metastasis have been reported.

Risk factor for wound complications following wide resection of soft tissue sarcoma in the adductor compartment of the thigh.

BACKGROUND: The purpose of this study was to investigate deep-seated soft tissue sarcoma (STS) occurring in the adductor compartment of the thigh that underwent wide resection and to clarify the high-risk group for wound complications. PATIENTS AND METHODS: From 2000 to 2017, we reviewed 104 cases of deep-seated STS occurring in the adductor compartment of the thigh that were treated at four specialized facilities with expertise in sarcoma treatment. RESULTS: Wound complications occurred in 40 cases (38.5%), of which 23 cases (22.1%) were cases with major wound complications (MWC). In univariate analysis, BMI (P < 0.01), maximum tumor diameter (P < 0.01), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P < 0.01) were significantly associated with wound complications. In multivariate analysis, the associated parameters were BMI (P < 0.01), maximum tumor diameter (P = 0.02), and intraoperative intervention to the femoral artery and vein (P = 0.01). When limited to cases with MWC, univariate analysis showed that maximum tumor diameter (P < 0.01), diabetes mellitus (P = 0.03), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P = 0.02) were significantly associated parameters. In multivariate analysis, maximum tumor diameter (P = 0.02) and amount of intraoperative bleeding (P = 0.04) were associated parameters. CONCLUSIONS: For patients with risk factors for wound complications, control of bleeding are crucial when resecting deep-seated STS in the adductor compartment of the thigh. In cases with large tumors, surgeons should be especially cautious of cases requiring interventions that surround the femoral artery and vein in order to attain an appropriate surgical margin.

Massive bone reconstruction with heat-treated bone graft loaded autologous bone marrow-derived stromal cells and ß-tricalcium phosphate composites in canine models.

Bone marrow-derived stromal cells (BMSCs) contain mesenchymal stem cells that are capable of forming various mesenchymal tissues. We hypothesized that BMSCs and ß-tricalcium phosphate (ß-TCP) composites would promote the remodeling of large-sized autologous devitalized bone grafts; therefore, the aim of this study was to evaluate the effects of the composites on the remodeling of autologous devitalized bone grafts. Autologous BMSCs cultured in culture medium containing dexamethasone (10(-7) M) were loaded into porous ß-TCP granules under low-pressure. Theses BMSC/TCP composites were put into the bone marrow cavity of autologous heat-treated bone (femoral diaphysis, 65-mm long, 100°C, 30 min) and put back to the harvest site. In the contralateral side, ß-TCP without BMSC were used in the same manner as the opposite side as the control. Treatment with the BMSC/TCP composites resulted in a significant increase in thickness, bone mineral density, and matured bone volume of the cortical bone at the center of the graft compared to the control. Histological analysis showed matured regenerated bone in the BMSC loaded group. These results indicate that BMSC/TCP composites facilitated bone regeneration and maturation at the graft site of large-sized devitalized bone. This method could potentially be applied for clinical use in the reconstruction of large bone defects such as those associated with bone tumors.

Indications for and surgical complications of rotationplasty.

BACKGROUND: Rotationplasty is one treatment option for femoral bone sarcomas in skeletally immature patients. This procedure can also be used to save failed limb salvage procedures such as infected prostheses and failed bone grafts in adults. Rotationplasty is only rarely indicated, and the surgical complications and risk factors for failure of the procedure that might influence the treatment or patient choices have not been well described. METHODS: We retrospectively reviewed 19 patients who underwent rotationplasty focusing on surgical indications, surgical procedures such as the type of rotationplasty, and whether vessels were sacrificed and reconstructed with vascular anastomosis or preserved. Risk factors for failure of rotationplasty were categorized into either early or late postoperative complications. RESULTS: Thirteen of 19 rotationplasties were done for patients diagnosed with primary sarcoma, 3 patients for unplanned excisions of sarcomas, and 3 patients for infection. Two of 19 patients did not have sufficient circulation resulting in amputation. Six of 19 patients underwent vascular anastomoses, and all of these anastomoses were successful. Three patients had multiple operations for infection before rotationplasty, and one patient's treatment failed so an amputation was required. As late complications, one patient had delayed bone union and one had postoperative infection that healed after removal of plate fixation. Two patients had malrotation of the tibia that resolved with revision surgery. One patient had a skin ulcer that healed with conservative treatment. One patient who had an unplanned excision had a hemipelvectomy for non-union 11 months after rotationplasty. CONCLUSIONS: Rotationplasty was successfully accomplished in 16 of the 19 patients (84 %) with sarcomas, unplanned excision of sarcomas or infection. Vascular anastomosis did not increase the risk of rotationplasty failure in our series. Patients appeared to have a higher risk of failure of rotationplasty after multiple operations, possibly because of inflammation around the vessels. The surgeon should be aware of the higher potential risk and consider vascular anastomosis for these patients.

Long-term results from use of pasteurized bone.

BACKGROUND: Pasteurized bone (PB) is recycled bone. The pasteurization has a tumor cell-killing effect wit retention of initial strength. However, few reports have been published on its long-term course; thus, in this study, we evaluated the long-term course of use of PB and examined appropriate reconstruction methods. PATIENTS AND METHODS: We reviewed 27 cases in which reconstructive surgery using PB was performed between 1990 and 2002. Of these, we excluded 12 fatal cases and 1 case in which follow-up was discontinued. Therefore, our final analysis consisted of 14 cases with an average follow-up period of 165 months. The reconstruction methods used were: osteoarticular graft in 6 cases, composite graft with prosthesis in 3 cases, intercalary graft in 1 case, and reconstruction using PB from the pelvis in 4 cases. RESULTS: The PB survived in 7 of the 14 cases. Five and 10-year survival of the PB was 78.6 and 47.6%, respectively. Three of the 6 osteoarticular cases failed because of late-onset absorption or infection of the PB. For patients with composite graft or intercalary graft, long-term survival was achieved when small amounts of PB were used. For patients with pelvic grafts, long-term survival was achieved in a case of P1 pelvis, but large PB grafts on small bone-junction surfaces were not successful in the long term. On the basis of these results, we were able to achieve successful long-term results with small PB grafts on large bone-junction surfaces. CONCLUSIONS: To prevent bone absorption and achieve long-term survival of PB, it is important to use a small PB graft and create a large surface area of contact with normal bone. These factors are advantageous to PB survival and to gaining limb function.

Surgery for dedifferentiated liposarcoma, presenting two radiologically and pathologically distinctive patterns.

In this paper, we report three cases with dedifferentiated liposarcoma in the lower extremities, presenting two patterns that are distinctively different radiologically and pathologically. The first case was a 67-year-old male who had discovered a mass in his left thigh, which was shown as a low and iso density mass between the muscles on computed tomography (CT). The second case was a 61-year-old male who had suffered from an intramuscular tumor with a non-fatty sarcomatous area within the fatty components as shown on magenetic resonance imaging (MRI). The third case was a 52-year-old female who had presented with an intramuscular tumor of the left thigh, consisting of a mass with fat and another soft tissue tumor adjacent to the lipomatous component as detected with CT and MRI. The final pathological diagnoses of the resected specimens in all three cases were concluded to be dedifferentiated liposarcoma, composed of well-differentiated liposarcomas and spindle and/or pleomorphic sarcomas, compatible with malignant fibrous histiocytoma. In all three cases, wide resection of the tumor was successfully carried out, and all patients have been continuously disease-free up to the most recent follow-up. Evaluation of the surgical margins for the resected specimens indicated that the safety margin for a dedifferentiated lesion should be accomplished as an adequate margin or more, and a marginal margin or more could be considered as safe only for the confined part of a well-differentiated liposarcoma.