Prognostic value of CAF marker expression in the intratumoral and marginal areas of soft tissue sarcoma.

INTRODUCTION: The tumor microenvironment of sarcomas has not been studied in detail; in particular, little is known about cancer-associated fibroblasts (CAFs). Sarcoma cells are difficult to distinguish from CAFs, either histomorphologically or immunohistochemically. METHODS: We scored expression of individual CAF markers (fibroblast activating protein (FAP), CD10, and podoplanin) in the intratumoral and marginal areas of 133 sarcomas. We also examined the association between these markers, as well as the number of CD163-positive macrophages (i.e., tumor-associated macrophages), and clinical outcome. RESULTS: In all cases, the log-rank test revealed that those with high marker scores and macrophage counts (except for marginal CD10+ CAFs) showed significantly worse disease-free survival (DFS). Grade 2/3 cases with high CAF scores (excluding the marginal FAP and CD10 scores) showed significantly worse DFS, whereas those with high intratumoral FAP/CD10 and marginal podoplanin scores showed significantly worse metastasis-free survival (MFS), and those with a high intratumoral CD10 score showed significantly worse local recurrence-free survival (LFS). Multivariate analysis identified intratumoral CD10/podoplanin scores and marginal FAP/podoplanin scores as independent prognostic factors for DFS, intratumoral FAP/CD10 and marginal FAP/podoplanin/CD163-positive macrophage scores as independent prognostic factors for MFS, and the intratumoral podoplanin score as an independent prognostic factor for LFS. There was a weak-to-moderate correlation between each score and CD163-positive macrophage counts. CONCLUSION: Patients with high CAF marker expression in the intratumoral and marginal areas have a poorer outcome.

Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST). METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS. CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.

The Prognostic Significance of Surgical Treatment for Excessive Elderly Soft Tissue Sarcoma Patients over 90 Years Old: A Clinicopathological Study of 16 Cases.

OBJECTIVES: The incidence of soft tissue sarcomas (STSs) among older patients is increasing. Although surgical treatment of elderly patients with STS has been reported to improve their prognosis, most of these studies included patients with STS aged <85 years. This study aimed to analyze the clinical features and prognostic factors of STS in elderly patients aged ≥90 years. SUBJECT AND METHODS: We retrospectively identified patients aged ≥90 years with STS who were treated at our two hospitals between 1994 and 2022. Data on clinical information and detailed assessments were collected. We evaluated the features and factors affecting the prognosis of patients with older-extremity STS. In addition, we compared the clinical courses and results of patients treated with surgery and radiotherapy for primary tumors. RESULTS: Among 454 patients with STS, 16 were aged ≥90 years. Kaplan-Meier curves for overall survival showed a significantly poorer prognosis in patients who did not receive surgical treatment (p = 0.0348) and those who received radiotherapy (p = 0.0070). Moreover, we investigated the difference in prognosis between surgical treatment and radiotherapy, excluding two cases with distant metastasis at initial diagnosis and one case with no treatment. Kaplan-Meier curves for overall survival showed a significantly better prognosis in patients who underwent surgical treatment (p = 0.0161). Univariate analysis revealed that only primary tumor size was a significant predictor of poor prognosis (p = 0.0426). CONCLUSION: In patients with STS aged ≥90 years old, aggressive surgical treatment may improve the prognosis more than radiotherapy.

Non-ossifying fibromas and fibrous cortical defects around the knee - an epidemiologic survey in a Japanese pediatric population.

BACKGROUND: The aim of the present study was to evaluate the prevalence of non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) in a Japanese pediatric population and the association between the lesion size and pain. METHODS: This retrospective study, conducted across 10 Japanese institutions, included patients aged 5-15 years who had undergone standard antero-posterior and lateral view radiography of the knee. Using these radiographs, we diagnosed the lesion as a NOF or FCD. Patient demographics, including age, sex, the size and location of the NOF, and chief complaint were recorded. The lesion size was determined using radiographs. Student's t-test was used to compare the associations between the lesion size and spontaneous pain. RESULTS: A total of 6222 subjects (3567 boys and 2455 girls) were included in this study. The number of NOF and FCD cases was 143 and 437, respectively, and the prevalence of NOF and FCD was 2.3% and 7.0%, respectively. The average size of NOF and FCD was 22.1 mm (range: 4-102 mm) and 13.2 mm (range: 5-21 mm), respectively. Three patients (2.1%) had pathological fractures due to NOF. Of the 140 NOFs and 437 FCDs, we obtained complaints from the medical records of 126 and 393 patients, respectively. The number of patients with spontaneous pain or other problems with NOF was 68 (54%) and 58 (46%), respectively, that of patients with FCD was 195 (50%) and 198 (50%) patients, respectively. The lesion size was not associated with spontaneous pain in either lesion (p = 0.67 and p = 0.27, respectively). CONCLUSION: The prevalence of NOF and FCD around the knee was lower than that reported in previous studies. The prevalence of NOF increased and that of FCD decreased with advancing age. In both lesions, the lesion size may not be associated with pain.

Tumor Lysis Syndrome due to Eribulin Administration for Metastatic Undifferentiated Pleomorphic Sarcoma of the Buttock.

Tumor lysis syndrome (TLS) is a complication of cancer treatment that requires urgent intervention. It is extremely rare in the treatment of soft tissue sarcoma (STS) of the limbs or trunk, and there are currently no reports of TLS occurrence from eribulin therapy. We report the case of a 78-year-old woman with an undiffer-entiated pleomorphic sarcoma on the right buttock. We initiated chemotherapy with intravenous eribulin mesylate. Deterioration of renal function, mild hyperkalemia, hyperuricemia, hypocalcemia, and hyperphos-phatemia were confirmed on examination, suggesting the presence of TLS. We present an extremely rare case of TLS from eribulin for STS.

Deep Angiomyxoma of the Thigh That Is Difficult to Diagnose: A Case Report and Literature Review.

We present an extremely rare case of deep angiomyxoma (DAM) in the thigh that was misdiagnosed as desmoid-type fibromatosis. A 40-year-old Japanese woman presented with a mass on the left thigh. The histological diagnosis by needle biopsy was desmoid-type fibromatosis; the tumor grew slowly and was resected 4 years later. The histological diagnosis from the resected tumor was DAM. As of 16 months post-surgery, the patient has not noticed any local recurrence. Although DAM in a lower extremity is extremely rare, clinicians must be aware of its possible occurrence in areas relatively close to the pelvis.

The value of the black fiber sign on T1-weighted images for predicting stability of desmoid fibromatosis managed conservatively.

OBJECTIVES: It is challenging to know at the first which patients with desmoid fibromatosis (DF) are better suited to conservative or aggressive treatment. To investigate whether the low signal intensity bundles on T1- or T2-weighted images (WI), termed the "black fiber sign (BFS)," can predict non-progressive behavior in the conservative approach. METHODS: This retrospective study included 59 patients with primary DF managed with wait-and-see approach from 2005 to 2018 and serial MR images were analyzed. Three observers blinded to the patient information verified the presence or absence of BFS on baseline T1 or T2WI. The likelihood of progression-free survival (PFS) after ascertaining the presence or absence of the BFS was estimated using the Kaplan-Meier method and analyzed with the log-rank test. RESULTS: PFS was significantly higher in cases with BFS than without BFS on T1WI (p < 0.01), but there was no significant difference in PFS between cases with and without BFS on T2WI. Multivariable Cox proportional hazards analysis revealed that the absence of BFS on T1WI was a high-risk factor for progression (hazard ratio, 14.9; p < 0.01). Drastic tumor regression was apparent with significantly increased low-signal area in cases with BFS on T1WI. Intra- and interobserver reliabilities of BFS on T1WI were in almost-perfect agreement (κ > 0.8). CONCLUSION: Our retrospective observational data support that presence of BFS in baseline MRI may be a predictor for progression-free survival of DF. BFS on T1WI is easily identifiable and can be utilized clinically in patients with DF. KEY POINTS: • We proposed a new imaging marker for prediction of desmoid fibromatosis progression. • The absence of black fiber sign predicted a high risk of disease progression.

Effects of bazedoxifene and low-intensity aerobic exercise on bone and fat parameters in ovariectomized rats.

INTRODUCTION: Postmenopausal osteoporosis and dyslipidemia are well-known skeletal and metabolic changes in middle-aged women. We investigated the effects of combined treatments with a selective estrogen receptor modulator (SERM) and exercise on bone and fat parameters in ovariectomized (OVX) rats. MATERIALS AND METHODS: Sixteen-week-old female Sprague-Dawley rats underwent bilateral ovariectomy, and rats were randomized to BZA (bazedoxifene at 0.3 mg/kg/day), Exe (treadmill exercise at 12-15 m/min, 60 min/day, 5 days/week), Comb (BZA and Exe), and Cont (control treated with vehicle and no exercise) groups 8 weeks after ovariectomy. After 4 or 8 weeks of treatment, bone mineral density (BMD) of the total femur and lumbar spine and whole-body percentage fat mass were determined by dual-energy X-ray absorptiometry, and mechanical testing of the femoral shaft, and bone and fat histomorphometric analyses of the proximal tibia were performed. RESULTS: Treadmill exercise had decreased bone marrow adipocytes from 4 weeks of treatment and whole-body percentage fat mass at 8 weeks. BZA increased BMD at the lumbar spine and decreased the whole-body percentage fat mass from 4 weeks and bone marrow adipocytes at 8 weeks. Combination therapy increased BMD for the lumbar spine and decreased bone marrow adipocytes and whole-body percentage fat mass from 4 weeks. CONCLUSION: Combination therapy with BZA and exercise appears effective to improve bone and fat parameters in OVX rats.

Prognostic Factors in Patients with Distant Soft Tissue Metastasis of Carcinoma: A Clinicopathological Study of 16 Cases.

OBJECTIVES: Soft tissue metastasis (STM) is an uncommon condition in carcinoma. Although various case series related to STM have been reported, few reports have examined prognostic factors. This study aimed to evaluate the characteristics of STM and the factors affecting its prognosis. MATERIALS AND METHODS: Patients with STM from carcinoma were retrospectively studied. The patients' information, including age, sex, primary tumor, metastasis location, size of the metastatic tumor, presence of pain, histological classification, history of primary tumor treatment, and other metastasis at diagnosis of STM were collected and associated with prognosis. RESULTS: Overall, 16 patients with a mean age of 68.7 years were evaluated. The overall survival rate was not significantly different between lung cancer and non-lung cancer patients. The overall survival rate was significantly better in patients undergoing definitive treatment for the primary tumor than in those without history of treatment (p = 0.046). The overall survival rate of STM patients with no metastasis was significantly better than those with other metastasis at the diagnosis of STM (p = 0.041). On multivariate analysis, no history of primary tumor treatment and STM without pain were risk factors for prognosis (p = 0.0340 and 0.0474, respectively). None of the patients who developed STM under the skin experienced pain, while 92.3% of the patients who developed STM in the deep layer had pain. CONCLUSION: The risk factors for poor diagnosis of STM were no past treatment of the primary tumor and absence of pain. STM in the deep layer is prone to pain.

Treatment outcome of chest wall soft tissue sarcomas: Analysis of prognostic factors.

BACKGROUND: Primary soft tissue sarcomas (STSs) involving the chest wall are uncommon. The aim of this study was to identify factors that influence the prognosis of patients with primary chest wall STS. METHODS: The records of 38 patients (23 men and 15 women) who were treated at our institutions during 2002 to 2018 were reviewed. The following variables were evaluated as potential prognostic factors: sex, tumor size, chemotherapy, and completeness of surgical margins. Multivariate analysis was conducted to identify predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 38 included patients, 5 had low-grade tumors and 33 had high-grade tumors. Five patients required chest wall reconstruction including rib resection. Thirty patients (79%) underwent R0 resection. The 5-year OS and DFS rates were 45% and 27%, respectively. Local recurrence developed in 7 patients. Multivariate analysis identified tumor size (hazard ratio [HR]: 4.13; 95% confidence interval [CI]: 1.05-16.24; P = .04) and R1/2 resection (HR: 3.92; 95% CI: 1.12-13.66; P = .03) as predictors of OS. CONCLUSIONS: Prognostic factors for survival included tumor size and completeness of surgical margins. Complete tumor excision is desirable, particularly in cases of early detection.

Prognosis of Primary Osteosarcoma in Elderly Patients: A Comparison between Young and Elderly Patients.

OBJECTIVES: Osteosarcoma is the most common malignant bone tumor in childhood. Although a poorer prognosis has been described in older patients, few reports have focused solely on primary osteosarcoma. We evaluated the clinical features of elderly patients with primary osteosarcoma. MATERIALS AND METHODS: Ninety-four patients were included in this retrospective study, and we divided them into 2 groups (older patients and younger patients) based on a cut-off age of 40 years. The patients' information, including age, tumor type, location, presence of metastasis, American Joint Committee on Cancer (AJCC) stage, treatment-related factors, local and distant relapse, and outcome, was collected. We compared the clinical courses between the 2 groups in all and only deceased patients. RESULTS: In all patients, the frequency of chemotherapy in the older group was significantly lower than in the younger group (p < 0.001), and tumors were more frequent in axial bone in the older patients (p = 0.041). Only in patients with surgical treatment, histological effectiveness after chemotherapy in the older group was lower than in the younger group (p = 0.041). The older patients showed a poorer prognosis (p = 0.031). However, the 5-year overall survival rate in the older patients was more favorable than that in the younger patients only among deceased patients (p =0.032). Only the existence of metastasis affected the prognosis in older patients (p = 0.012). CONCLUSION: Primary osteosarcoma in elderly patients showed a high incidence of axial bone involvement, a low rate of chemotherapy, and resistance to chemotherapy. Although the final life prognosis is poor, survival may be relatively prolonged.

The prognostic significance of surgical treatment for excessive elderly patients with soft tissue sarcoma.

BACKGROUND: Soft tissue sarcoma (STS) mainly occurs in middle-aged and senior citizens. Although a poorer prognosis has been reported for older patients, few studies have examined advanced elderly excessive older patients. We evaluated the clinical features of advanced elderly patients with STS. METHODS: One hundred and forty-four patients were included in this retrospective study, and we divided them into two groups based on a cut-off age of 85 (older and younger groups). The patients' information, including age, tumor type, location, size, presence of metastasis, AJCC stage, FNCLCC classification, treatment-related factors, local and distant relapse, and outcome, was collected. We compared the clinical courses between the 2 groups. RESULTS: In all patients, the frequency of chemotherapy in the older group was significantly lower than in the younger group (P < 0.01), and the follow-up period in the older group was significantly shorter than in the younger group (P < 0.01). Surgical treatment was refused more frequently in the older group (P = 0.01). The older group showed a significantly poorer prognosis (P < 0.05). However, in patients with localized disease at presentation treated with surgery, there was no significant difference in prognosis between the 2 groups. Only surgical treatment affected the prognosis in older patients (P < 0.01). CONCLUSION: Although the prognosis of advanced elderly STS patients is generally poor, that of STS patients with surgical treatment is not poor. Only surgical treatment intervention strongly influences the prognosis, and so the prognosis may be improved with aggressive surgical treatment.

Incidence of Persistent Left Superior Vena Cava in the Normal Population and in Patients with Congenital Heart Diseases Detected Using Echocardiography.

Reports on the incidence of persistent left superior vena cava (PLSVC) in the normal population are limited to studies involving pacemaker implantation candidates and cadavers. The incidence in patients with congenital heart diseases (CHDs) is estimated to be higher than that in the normal population; however, the details are unclear. To investigate the incidence of PLSVC in the normal population and in patients with CHDs, subjects were examined prospectively using echocardiography. Normal subjects consisted of 2841 successive neonates without intra-cardiac or congenital anomalies born in Gifu Prefectural General Medical Center. Additionally, 1920 patients with CHDs were evaluated. The incidence of PLSVC in normal neonates was 0.21% (95% confidence interval 0.042-0.38%). A high incidence (more than 7.0 times the incidence in normal subjects) was observed in all CHD patients. The high incidence group included coarctation of the aorta (CoA) (23.7%) and double outlet right ventricle (DORV) patients (24.6%). The second group consisted of CHD patients with ventricular septal defect (VSD), with an incidence ranging from 5.1 to 6.1%. The low incidence group comprised patients with other CHDs, with an incidence between 1.5 and 3.1%. The incidence of PLSVC in trisomy 21 and atrial septal defect patients was significantly higher than that in normal neonates. The incidence of PLSVC in the normal population and in patients with CHDs was systematically evaluated for the first time. The incidence in CHD patients appeared to be positively influenced by the type of CHD, particularly by DORV, CoA, and VSD.

Methodologic comparison of left ventricular stroke volumes in the early neonatal period by echocardiography.

Several methods for evaluating left ventricular stroke volume (SV) in neonates using echocardiography have been reported. However, no studies on methodologic comparison of SV with three-dimensional (3D) echocardiography are available. This is the first detailed report on a methodologic comparison of SV in the early neonatal period. The study group included 70 normal neonates (35 boys and 35 girls). An iE33 echocardiograph and Q-LAB supplied by Philips Electronics were used to examine and calculate volumes. Comparisons of SV were performed using Teichholz (T), the velocity time integral (VTI), Pombo (P), modified Simpson (MS), and 3D methods with normal neonates who had no persistent ductus arteriosus less than 7 days after birth. The mean SVs were 33.7 mL/m(2) (T), 30.6 mL/m(2) (VTI), 22.0 mL/m(2) (P), 17.5 mL/m(2) (3D), and 14.9 mL/m(2) (MS) using Haycock's formula of body surface area. The stroke volumes differed significantly depending on the different methods. The correlation coefficient was highest between the MS and 3D methods. The SVs of the T and VTI methods were significantly greater than those previously reported, and it seemed inappropriate to evaluate volumes in neonates. The 3D and MS methods were appropriate for measuring SV in neonates during the early neonatal period.

Evaluation of left ventricular volumes in the early neonatal period using three-dimensional echocardiography.

BACKGROUND: Awareness about normal cardiac volumes in the neonatal period is very important for understanding the cardiac function; however, the small cardiac size of neonates makes it difficult to perform invasive examinations. Three-dimensional echocardiography is used to evaluate cardiac volumes in children. However, no studies using this method have examined left ventricular volumes in neonates during the early neonatal period. METHODS: The study group consisted of 255 normal neonates. Comparisons of the stroke volume calculated according to the velocity-time integral and Pombo method were made. RESULTS: The volumes in both end-diastole and end-systole and the stroke volume gradually decreased over time after birth. Participants with continuous a persistent ductus arteriosus flow had higher stroke volumes than those without persistent ductus arteriosus. The average end-diastolic volume per body surface area (m2) was 30.61 ml/m2 in boys and 29.80 ml/m2 in girls, whereas the ventricular end-systolic volume was 12.89 ml/m2 in boys and 12.80 ml/m2 in girls among the participants without persistent ductus arteriosus. The average stroke volume was 17.70 ml/m2 in boys and 17.00 ml/m2 in girls. Statistically significant gender differences were observed in the end-diastolic volume (p = 0.0053), stroke volume (p < 0.0001), and ejection fraction (p = 0.039). The cardiac index was calculated to be 2.04 L/minute/m2 in boys and 1.95 L/minute/m2 in girls, which was significantly lower than that calculated using the velocity-time integral and Pombo method (p < 0.0001). CONCLUSIONS: Significant gender differences in the end-diastolic volume, stroke volume, and ejection fraction at birth were revealed. The cardiac index in the early neonatal period was found to be relatively smaller than what had previously been recognised.

Development of a New Focal Mouse Model of Bone Metastasis in Renal Cell Carcinoma.

BACKGROUND/AIM: Developing animal models of bone metastasis in renal cell carcinoma (RCC) is challenging as immunodeficient mice are required. The aim of this study was to develop a simple immune model of RCC bone metastasis. MATERIALS AND METHODS: RENCA tumor cells were injected into the right femurs of BALB/c mice. Sixty mice were grouped into each twenty-mouse group according to the tumor cell concentration, and the presence or absence and extent of bone metastasis in the total length of the femur were compared using hematoxylin and eosin staining of the excised tissues. RESULTS: Bone metastasis was significantly higher in the high concentration group than in the other groups (p<0.05), with 10 mice developing bone metastasis at two weeks and nine mice developing bone metastasis at three weeks. The extent of bone metastasis was significantly greater in the high concentration group than in the other groups (p<0.05). Multiple logistic regression analysis was performed to examine the factors influencing bone metastasis, and only the high concentration was a significant factor (p<0.05). CONCLUSION: We developed a normal immunity mouse model of local bone metastasis from RCC. This model could prove valuable for research into the treatment of bone metastases in RCC.

Effect of Acridine Orange and Zoledronic Acid on Bone Metastasis in Renal Cell Carcinoma.

BACKGROUND/AIM: The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel therapeutic approaches. Therefore, this study aimed to assess the impact of hematogenously administering acridine orange (AO) alone and in combination with zoledronic acid (ZA) on bone metastasis in RCC. MATERIALS AND METHODS: RENCA cells (1.0×106 cells/10 µl) were directly injected into the right femur of male BALB/c mice. The mice were categorized into four groups based on the applied therapeutic intervention and were euthanized after five weeks. Micro-computed tomography was performed to quantify the extent of periosteal reaction, indicative of bone metastasis, along the entire length of the femur. Tumor weight and volume were measured at euthanization. Hematoxylin and eosin staining was used to examine the extent of tumor development in the bone. Apoptotic cell, osteoclast, and vascular endothelial growth factor (VEGF)-positive cell counts were assessed using TdT-mediated dUTP-biotin nick end labeling, tartrate-resistant acid phosphatase staining, and VEGF staining, respectively. RESULTS: The periosteal reaction was significantly reduced in the intervention groups compared to the control group (p<0.05). The apoptotic cell numbers in the intervention groups surpassed that in the control group (p<0.05), whereas those of osteoclasts and VEGF-positive cells in the intervention groups were lower than those in the control group (p<0.05). CONCLUSION: AO hinders bone metastasis progression in RCC, and combination therapy with ZA may be more effective than AO administration alone.

Soft Tissue Tumor Without Neurofibromatosis Type 1 With Histopathological Suspicion of Atypical Neurofibromatous Neoplasm of Uncertain Biological Potential (ANNUBP).

Atypical neurofibromatous neoplasm of uncertain biological potential (ANNUBP), defined as a borderline lesion that is difficult to distinguish whether benign or malignant, is one of the intermediate stages to malignant peripheral nerve sheath tumor, a peripheral nerve-derived malignant tumor that develops from nerve sheath cells. Because ANNUBP is a new concept, only a few cases have been reported, all in patients with neurofibromatosis type 1 (NF-1).An 88-year-old woman presented with a mass on the left upper arm persisting for one year. Magnetic resonance imaging showed a large tumor spreading between the humerus and biceps muscle, which was diagnosed as undifferentiated pleomorphic sarcoma by needle biopsy. Extensive tumor resection was performed, including partial cortical bone resection of the humerus. Based on the histological features, although the patient did not have NF-1, the tumor was strongly suspected to be ANNUBP. As malignant peripheral nerve sheath tumors have been sporadically reported in patients without NF-1, it is feasible that ANNUBP could also occur in patients without NF-1.

Macrophage numbers in the marginal area of sarcomas predict clinical prognosis.

Even when treated comprehensively by surgery, chemotherapy, and radiotherapy, soft-tissue sarcoma has an unfavorable outcome. Because soft-tissue sarcoma is rare, it is the subject of fewer clinicopathological studies, which are important for clarifying pathophysiology. Here, we examined tumor-associated macrophages in the intratumoral and marginal areas of sarcomas to increase our knowledge about the pathophysiology. Seventy-five sarcoma specimens (not limited to a single histological type), resected at our institution, were collected, and the number of CD68-, CD163-, and CD204-positive macrophages in the intratumoral and marginal areas was counted. We then performed statistical analysis to examine links between macrophage numbers, clinical factors, and outcomes. A high number of macrophages positive for all markers in both areas was associated with worse disease-free survival (DFS). Next, we divided cases according to the FNCLCC classification (Grade 1 and Grades 2/3). In the Grade 1 group, there was no significant association between macrophage number and DFS. However, in the Grade 2/3 group, high numbers of CD163- and CD204-positive macrophages in the marginal area were associated with poor DFS. By contrast, there was no significant difference between the groups with respect to high or low numbers of CD68-, CD163-, or CD204-positive macrophages in the intratumoral area. Multivariate analysis identified the number of CD163- and CD204-positive macrophages in the marginal area as an independent prognostic factor. Macrophage numbers in the marginal area of soft-tissue sarcoma may better reflect clinical behavior.