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Abstract Objective To evaluate the impact of a postoperative baseline (PB) MRI on diagnostic confidence and performance in detecting local recurrence (LR) of soft-tissue sarcoma (STS) of the limb. Materials and methods A total of 72 patients (8 with LR, 64 without LR) with primary STS of the limb were included. Routine follow-up MRI (1.5 T) at 6 and approximately 36 months (meanLR: 39.7 months; meanno LR: 34.9 months) after multimodal therapy or at time of LR were assessed by three independent readers using a 5-point Likert scale. Furthermore, the following imaging parameters were evaluated: presence of a mass, signal characteristics at T2- and T1-weighted imaging, contrast enhancement (CE), and in some of the cases signal intensity on the apparent diffusion coefficient (ADC). U-test, McNemar test, and ROC-analysis were applied. Interobserver reliability was calculated using Fleiss kappa statistics. A p value of 0.05 was considered statistically significant. Results The presence of a PB MRI significantly improved diagnostic confidence in detecting LR of STS (p κ: 73.1–83.6; 0.34) followed by T2-hyperintensity (50.8–66.7; 0.08), CE (52.4–62.5; 0.13), and T1-hypointensity (54.7–77.3; 0.23). ADC showed an AUC of 65.6–96.6% and a κ of 0.55. Conclusion The presence of a PB MRI increases diagnostic confidence in detecting LR of STS of the limb.

Hydroxyapatite deposition disease (HADD) is a mostly uniarticular, self-limiting condition caused by deposition of hydroxyapatite (HA) crystals in tendons or in the peritendinous soft tissues. Commonly, the glenohumeral joint is affected. More rarely, the HA depot can be cause of a carpal tunnel syndrome due to an acute inflammatory reaction and space-occupying soft tissue oedema. We report a case of acute HA depot located at the volar site of the right wrist with affection of the deep flexor tendons and intraosseous migration into the lunate bone in a 50-year-old female. There are two main goals of this case report: First, to remind the diagnosis of HADD as a cause of wrist pain and also of carpal tunnel syndrome, as this entity being often misdiagnosed clinically, and second, to report a rare case of intraosseous migration of HA crystals into the lunate bone.

(1) Background: The expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor on T cells, has been associated with dismal outcomes and advanced tumor stages in various solid tumors. The blockade of TIM-3 is currently under examination in several clinical trials. This study examines TIM-3 expression in high-risk soft tissue sarcomas (HR-STS). (2) Methods: Tumor cell expression of TIM-3 on protein level was analyzed in pre-treatment biopsies of patients with HR-STS. TIM-3 expression was correlated with clinicopathological parameters including tumor-infiltrating lymphocyte (TIL) counts, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) expression in patients with HR-STS. Survival dependent on the expression of TIM-3 was analyzed. (3) Results: TIM-3 expression was observed in 101 (56%) out of 179 pre-treatment biopsies of patients with HR-STS. TIM-3 expression was significantly more often observed in undifferentiated pleomorphic sarcomas (UPS) compared to other histological subtypes (p < 0.001), high TIL counts (p < 0.001), and high PD-1 (p < 0.001) and PD-L1 expression (p < 0.001). TIM-3 expression did not have a prognostic impact on survival in patients with HR-STS. (4) Conclusions: This is the first study to demonstrate a significant tumor cell expression of TIM-3 in specific subsets of patients with HR-STS. TIM-3 qualifies as a potential immunotherapeutic target in HR-STS.

Recent retrospective studies suggested that early postoperative infections might be associated with a survival benefit for extremity osteosarcoma patients, but the reported results have been conflicting. The files of 437 patients with a newly diagnosed, high-grade osteosarcoma of the extremities treated at 5 referral centers in Germany and Austria between 1989 and 2016 were retrospectively evaluated. All patients underwent multi-agent chemotherapy and limb-sparing tumor excision, followed by endoprothetic replacement. We used the Kaplan–Meier method to calculate survival curves, which we compared with the log-rank test. With a median follow-up of 100 months (interquartile range, 49–155 months), local recurrence (LR) probability, event-free survival (EFS), and disease-specific survival (DSS) after 5 years in this selected patient cohort amounted to 5%, 67%, and 79%, respectively, and 46 patients (10.5%) developed an early postoperative infection. We found no significant differences in LR, EFS, or DSS between patients with and without early infections, and there were no differences in known prognostic factors between the two groups. However, in subgroup analyses patients with a poor response to neoadjuvant chemotherapy and an early infection had a better DSS compared to patients without early infections (93% vs. 62% after 5 years, p = 0.044). Provided that our findings can be validated in separate patient cohorts, we believe that patient outcome after adjuvant immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for good and poor responders to neoadjuvant chemotherapy in future studies.

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Benign soft tissue lesions are 300 times as common as soft tissue sarcomas; hence, the likelihood of confusion is high. Lesions that are larger than 5 cm, deep, show infiltrative growth, or recur despite benign histology are suspicious for soft tissue sarcoma. The biopsy incision must be carefully chosen; in large lipomas, atypical lipomatous tumor should be considered in the differential diagnosis. Lymphomas can be misdiagnosed and treated as undifferentiated soft tissue sarcoma. Vascular tumors and epithelioid lesions require more attention in histopathologic diagnostics and staging. Inflammatory lesions and aggressive fibromatosis (desmoid tumor) should also be borne in mind. In general, staging should be adapted to the underlying tumor biology. Neoadjuvant and adjuvant multimodal therapy must be discussed with the patient and used in a targeted manner. Superficial infiltrating sarcomas are prone to intralesional resection and may require intraoperative frozen section histology. If plastic reconstruction is necessary, a two-step procedure after proven tumor-free margins can be beneficial. Cavities and seromas, tight sutures, and closing the wound with clips are particularly critical. Wound drains at the thigh, pelvis, and groin should be left longer. Early revision in cases of hematoma or critical wound healing have proven beneficial. Adjuvant therapies are best planned before discharge from hospital. Overall, tumor-specific follow-up can significantly reduce the disadvantages of a recurrence resection.

Weitere Nicht-UDE Autoren sind nicht mit aufgeführt. enosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.

Background: Although rare, the annual incidence of intraosseus sarcomas is up to 2 per 100.000 population with a peak in the sixth decade of life. Due to their slow growth and because they are often asymptomatic for a long period of time, they can be misinterpreted as a benign bony lesion. Particularly, if the tumor shows a high myxoid signal on MRI, the lesion might be mistaken for a bone cyst. Case presentation: We present the case of a 70-year-old female complaining of pain in her left knee. Initial imaging showed a grade 3 osteoarthritis, according to the Kellgren-Lawrence classification system, and a cystic lesion of the distal femur. The patient received a total knee endoprothesis and five years after the index surgery, she presented again with pain in her left knee after a fall. Radiographs showed an expansile lesion of the distal femur. A biopsy was performed and the lesion proved to be a chondrosarcoma with myxoid pattern. After en bloc-resection, a megaendoprosthesis was implanted in a palliative approach. Four years later, the patient died without local recurrence due to metastatic disease from an adenocarcinoma of unknown origin. Conclusion: Malignant tumors should be taken into consideration whenever imaging shows an expansile lesion of the bone, even when they are painless, well delimited and slowly or not at all growing. We recommend a biopsy to be performed before performing an arthroplasty in such cases.

Simple Summary Sarcomas are malignant tumors of soft tissues or bone. While limb salvage surgery (LSS) is the standard treatment, amputation is an option especially in local recurrence (LR) or complications after LSS. Two groups with primary amputations (n = 120) or secondary amputations after failed LSS due to LR or complications (n = 29) were compared. Five-year LR-free survival was 84% and 17 (16%) patients developed LR, of which 16 were in group I and only one in group II. Overall survival (OS) at five years was 44%, and the rate was identical in both groups. In those group II patients who had a secondary amputation after LSS due to contaminated margins or LR (n = 12) five-year OS was 33% compared to 48% in patients with complications (n = 17). This study indicates the worse oncological outcomes with respect to OS of sarcoma patients needing an amputation as compared to LSS. Patients with primary amputation or those who had a secondary amputation after failed LSS for whatever reason showed the same results. Abstract Background: Sarcomas are rare, malignant tumors of soft tissues or bone. Limb salvage surgery (LSS) is the standard treatment, but amputation is still an option, especially in local recurrence or complications after LSS. Methods: We retrospectively reviewed indications and oncological outcomes in patients who underwent an amputation. Two groups with either primary amputations (n = 120) or with secondary amputations after failed LSS with local recurrence or complications (n = 29) were compared with the main end points of LRFS and OS. Results: Five-year LRFS was 84% with 17 (16%) patients developing local recurrence, of which 16 (13%) occurred in group I. Forty-two (28%) patients developed metastatic disease and overall survival at five years was 44%. Overall survival (OS) was the same in both groups. In those group II patients who had a secondary amputation due to LR or insufficient margins after LSS (n = 12) the five-year OS was 33% compared to 48% in patients with amputation due to complications (n = 17) (n.s.). Conclusions: This study indicates the worse oncological outcomes with respect to OS of sarcoma patients requiring an amputation as compared to LSS. Patients with primary amputation or those who had a secondary amputation after failed LSS for whatever reason showed the same oncological results.

Background. Hyperplasia of the hematopoietic bone marrow in the appendicular skeleton is common. Focal hematopoietic islands within the axial skeleton is a rare entity and can cause confusion with osteoblastic metastases. The purpose of this study was to describe the characteristic imaging findings in MRI and CT.Methods. We retrospectively analyzed the imaging findings of 14 hematopoietic islands of the axial skeleton in ten patients (nine females, median age= 65.5 years [range, 49-74]), who received both CT and MRI at the time of initial diagnosis between 2006 and 2020. In five cases CT-guided biopsy was performed to confirm the diagnosis, while the other five patients received long term MRI follow-up (median follow-up= 28 months [range, 6-96 months]). Diffusion-weighted imaging was available in three, chemical shift imaging in two, 18F fluorodeoxyglucose PET/CT in two and Technetium 99m skeletal scintigraphy in one of the patients.Results. All lesions were small (mean size=1.72 cm2) and showed moderate hypointense signals on T1- and T2-weighted MRI sequences. They appeared iso- to slightly hyperintense on STIR images and showed slight enhancement after gadolinium administration. To differentiate this entity from osteoblastic metastases, CT provides important additional information, as hematopoietic islands do not show sclerosis. Conclusions. Hematopoietic islands within the axial skeleton can occur and mimic osteoblastic metastases. However, the combination of MRI and CT allows for making the correct diagnosis.

Background Reconstruction of the skeletal defects resulting from the resection of bone tumors remains a considerable challenge and one of the possibilities is the orthotopic replantation of the irradiated bone autograft. One technical option with this technique is the addition of a vital autologous fibular graft, with or without microvascular anastomosis. The aim of our study was to evaluate the clinical results of the treatment of our patient cohort with a specific view to the role of fibular augmentation. Methods Twenty-one patients with 22 reconstructions were included. In all cases, the bone tumor was resected with wide margins and in 21 of them irradiated with 300 Gy. In the first case, thermal sterilization in an autoclave was used. The autograft was orthotopically replanted and stabilized with plates and screws. Fifteen patients underwent an additional fibular augmentation, 8 of which received microvascular anastomoses or, alternatively, a locally pedicled fibular interposition. Results the most common diagnosis was a Ewing sarcoma (8 cases) and the most common location was the femur (12 cases). The mean follow-up time was 70 months (16–154 months). For our statistical analysis, the one case with autoclave sterilization and 3 patients with tumors in small bones were excluded. During follow-up of 18 cases, 55.6% of patients underwent an average of 1.56 revision surgeries. Complete bony integration of the irradiated autografts was achieved in 88.9% of cases after 13.6 months on average. In those cases with successful reintegration, the autograft was shorter (n.s.). Microvascular anastomosis in vascularized fibular strut grafts did not significantly influence the rate of pseudarthrosis. Conclusions the replantation of extracorporeally irradiated bone autografts is an established method for the reconstruction of bone defects after tumor resection. Our rate of complications is comparable to those of other studies and with other methods of bone reconstruction (e.g. prosthesis). In our opinion, this method is especially well suited for younger patients with extraarticular bone tumors that allow for joint preservation. However, these patients should be ready to accept longer treatment periods.

Tenosynovial giant-cell tumor also known as pigmented villonodular synovitis (PVS) is a benign but aggressive synovial proliferative disease most often affecting the knee joint. The mainstay of therapy is surgical resection. Due to a high rate of local recurrence, radiosynoviorthesis (RSO) is used as an adjuvant method in many cases. The aim of this study was to compare local recurrence (LR) rates after surgical synovectomy with and without adjuvant RSO. From 1996 to 2014, 37 surgical interventions were performed in 32 patients with diffuse pigmented villonodular synovitis of the knee. All patients underwent open synovectomy. Adjuvant radiosynoviorthesis (RSO) was applied in 26 cases, the control group consists of 11 cases without RSO. 9 (24%) lesions recurred within a median of 19 months after surgery. Of those 9 recurrences, 3 (17%) were seen in primary disease, 6 (32%) in already recurring cases (n.s.). In 26 RSO treated patients 6 (23%) recurred, in 11 patients of the control group, 3 (27%) recurred (n.s.). RSO is effective in PVS as also shown in some smaller reports in the literature. But surgery is still the mainstay of therapy. RSO is not a method of compensating for an insufficient surgical approach, but it may reduce the high rate of LR in patients with large and even recurrent diffuse forms of the disease.

Introduction Tumors of the scapula are rare representing only 1.6%-2.8% of all skeletal tumor localizations. Wide resection of these tumors is often necessary, and their anatomic location is the most decisive factor for the extent of the resection. Because of the importance of the shoulder girdle for all daily activities, such resections can have major functional consequences. However, only few reports with small numbers of cases are found in the literature. Patients and methods We retrospectively evaluated 31 consecutive patients with scapular tumors treated surgically for aggressive benign or malignant tumors of the scapula. Patients who had received curettage only were excluded. Four of these 31 patients were lost to follow-up. In 7 of the remaining 27 patients, a total scapulectomy had to be performed, whereas all others received a partial resection. In 1 case, a partial resection and replantation after irradiation was performed. Musculoskeletal Tumor Society Scoring System (MSTS) and Toronto Extremity Salvage Score (TESS) scores were evaluated postoperatively at the time of their follow-up. Results In 16 men and 11 women, the median age was 46.2 years and the tumor entities were heterogeneous. The median follow-up time was 71 months. Three patients died during follow-up due to their tumor and 1 due to cardiac disease. We found significantly better functional results in the group with incomplete scapula resections as opposed to the scapulectomy group. We did not see a significant functional difference between the patients with benign and those with malignant lesions. Both the MSTS score with median 83.3% (range between 23% and 100%) and the TESS score with 81.6% (ranging from 20.4% to 100%) were at a satisfactory level. The preservation of the supraspinatus muscle was shown to be advantageous for better shoulder function, and younger patients also tended to have better postoperative results. Conclusion The resection of scapular tumors may lead to a significant functional disability of the shoulder girdle and the affected arm in many cases. However, this is represented neither in the MSTS or TESS score nor in the overall acceptance of the patients. Only 1 patient, an artisan, had to change his job. In total, the clinical results are quite good in short- and long-term follow-up. The score results were comparable to other studies.

Background: There is no evidence as to the diagnostic value of the two most frequently used methods of biopsies in sarcomas: Incisional or core needle biopsy. The aim of our study was to evaluate the diagnostic sensitivity of the incisional and the core needle biopsy techniques in the diagnosis of bone and soft tissue sarcomas. Methods: We included 417 patients with a definitive diagnosis of bone or soft tissue sarcoma in whom a total of 472 biopsies had been performed. We correlated the results of the biopsies with the result of the definitive histopathological examination of the resected tumor. Dignity, entity, and grading (whenever possible) of the tissue samples were evaluated. Results: A total of 258 biopsies (55%) were performed in order to diagnose a soft tissue tumor and 351 biopsies (74.4%) were core needle biopsies. The number of repeat core needle biopsies, necessitated because of inconclusive histopathological results, was significantly higher (50 vs. 5, p = 0.003). We observed no significant difference regarding dignity, entity, and grading between the 2 different types of biopsies. Only with regards to the determination of dignity and entity of chondroid tumors, incisional biopsy was superior with statistical significance (p = 0.024). Conclusions: This study represents the largest study on biopsies for bone and soft tissue sarcomas. Based only on our results, we are unable to favor one method of biopsy and found high accuracy with both methods. Considering the potential complications, the added oncological risks of incisional biopsies and the ready availability of core needle biopsies, the latter, in our assessment, represents a valid and favourable method for bone and soft tissue sarcomas.

Simple Summary Soft tissue sarcomas are a group of malignant tumors developing from connective tissues in different parts of the human body. In the face of limited options for systemic therapy, immunotherapeutic approaches are currently being explored. In this context, cancer testis antigens (CTAs) are potential targets for cancer immunotherapy due to tumor-specific patterns of expression and high immunogenicity. We, therefore, aimed to describe the expression of three CTAs, PRAME, NY-ESO-1, and SSX2, and analyze their prognostic value in a large cohort of high-risk soft tissue sarcomas with long-term follow-up. Our results show sarcoma subtype-specific patterns of CTA expression and we demonstrate an association of CTAs with overall survival, especially for PRAME. Our results provide support for future trials investigating CTA-directed immunotherapy in eligible patients with various sarcoma subtypes and they may help establish CTAs as diagnostic tools in soft tissue sarcoma. Abstract (1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 expression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS.

Background In soft tissue sarcomas (STS) radiotherapy (RTx) may be applied pre- or postoperatively with advantages and disadvantages on either side. We examined the effect of preoperative radiation on wound healing in patients with STS of the extremities and the pelvis. Methods Between August 2008 and March 2011, 32 patients with an average of 54 years (SD 18.7) and with STS (all Grade 2 or 3) were treated with a planned wide resection after neoadjuvant RTx leaving a rim of uninvolved soft tissue around the tumor. Preoperative RTx was given at an average dose of 51,5 Gy (SD 4.6) and mean follow up was 12.2 months (SD 9.8). The results were compared to a consecutive series of 60 patients treated later on without neoadjuvant RTx. Results R0 resection were performed in 31 of 32 patients. Impaired wound healing (IWH) occurred in 19 patients (59%), revision surgery had to be performed in 17 patients (53% of total). Four patients had to undergo 2 or more revisions. One patient had to be amputated and one patient died due to septic complications after revision surgery. IWH was seen more frequently in the lower (18 / 28) than in the upper extremities (1 / 4), yet this was not statistically significant in our series (p = 0.223, Fisher’s exact test). Comorbidities were not found to be of influence. In the control group, revision surgery was necessary in 18% of the patients (p = 0.0006). Conclusions Radiotherapy is effective in local tumour control, but causes a high rate of impaired wound healing (59%), if applied prior to surgery. This frequently resulted in one or more revision surgeries delaying the schedule of further therapies. The authors recommend RTx to be applied only in selected cases in a neoadjuvant setting.

Benign soft tissue lesions are 300 times as common as soft tissue sarcomas; hence, the likelihood of confusion is high. Lesions that are larger than 5 cm, deep, show infiltrative growth, or recur despite benign histology are suspicious for soft tissue sarcoma. The biopsy incision must be carefully chosen; in large lipomas, atypical lipomatous tumor should be considered in the differential diagnosis. Lymphomas can be misdiagnosed and treated as undifferentiated soft tissue sarcoma. Vascular tumors and epithelioid lesions require more attention in histopathologic diagnostics and staging. Inflammatory lesions and aggressive fibromatosis (desmoid tumor) should also be borne in mind. In general, staging should be adapted to the underlying tumor biology. Neoadjuvant and adjuvant multimodal therapy must be discussed with the patient and used in a targeted manner. Superficial infiltrating sarcomas are prone to intralesional resection and may require intraoperative frozen section histology. If plastic reconstruction is necessary, a two-step procedure after proven tumor-free margins can be beneficial. Cavities and seromas, tight sutures, and closing the wound with clips are particularly critical. Wound drains at the thigh, pelvis, and groin should be left longer. Early revision in cases of hematoma or critical wound healing have proven beneficial. Adjuvant therapies are best planned before discharge from hospital. Overall, tumor-specific follow-up can significantly reduce the disadvantages of a recurrence resection.

(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2, p = 0.019), higher TIL counts (p = 0.033), expression of PD1 (p = 0.046), PDL1 (p = 0.031), and CD3+ (p = 0.023). In patients without CD3+ TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (p = 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (p = 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA+ tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.

Background Pharmacologic options for treatment of osteolytic diseases especially in children are limited. Although not licensed for use, denosumab, a fully humanized antibody to RANKL, is used in children with good effects. Among others, one possible indication are giant cell tumors and aneurysmatic bone cysts. However, there are reports of severe hypercalcemia during weeks to months after termination of denosumab, that are rarely seen in adults. Methods We collected data of four patients, aged 6–17 years, who experienced severe hypercalcemia after completion of treatment with denosumab for unresectable giant cell tumors of bone or aneurysmal bone cysts and methods of their treatment. The detailed case information were described. Results One patient was treated with long-term, high-dose steroid therapy, leading to typical Cushing’s syndrome. Another patient was restarted on denosumab repeatedly due to relapses of hypercalcemia after every stop. Finally, in two patients, hypercalcemia ceased definitely after treatment with bisphosphonates. However, several applications were necessary to stabilize calcium levels. Conclusions There is a considerable risk of hypercalcemia as an adverse effect after denosumab treatment in children. Therapeutic and, preferably, preventive strategies are needed. Bisphosphonates seem to be an option for both, but effective proceedings still remain to be established.

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future., In this Expert Consensus, Grünwald et al. summarize their recommendations for the diagnosis and treatment of patients with renal cell carcinoma and metastasis to the bone. They also outline current challenges and unmet patient needs that should be addressed in the future.

Weichteilsarkome stellen Behandler aufgrund ihrer Seltenheit und Vielgestaltigkeit vor grose Herausforderungen — sowohl hinsichtlich der Diagnostik als auch der Therapie. Lesen Sie im folgende Beitrag, wie Hochrisiko-Weichteilsarkome vor der Operation behandelt werden sollten.

Benigne Knochenlasionen wie einige Tumoren oder nichtneoplastische Lasionen besitzen in bestimmten Fallen ein nicht unerhebliches Risiko einer malignen Entartung. Das Wissen um dieses ist wesentlich, da die Patientenberatung und -fuhrung entsprechend angepasst werden muss. Ziel dieser Arbeit ist es, die typischen Lasionen aufzuzeigen sowie das relative Risiko und den potenziellen Verlauf darzustellen. Aus der vorhandenen Literatur und der klinischen Erfahrung wurden jene Knochenlasionen benannt, bei denen ein Potenzial zur sekundaren Malignisierung besteht oder vermutet wird. Dieses wurde dann in einer dezidierten Literaturrecherche evaluiert. Belege fur die Dedifferenzierung oder sekundare Malignitat fanden sich fur kartilaginare Exostosen, Enchondromatose, Morbus Paget, fibrose Dysplasie, osteofibrose Dysplasie, Knocheninfarkt, Osteomyelitis und die synoviale Chondromatose. Fur den notochordalen Tumor, das Osteoblastom und die aneurysmale Knochenzyste ist die Datenlage zu gering, um eine solche zu postulieren. Es gibt benigne Lasionen, die in einer Inzidienz von bis zu 40 % in ein sekundares Malignom ubergehen konnen. Dieses muss in der Patientenberatung vermittelt werden. Geeignete Vorsorgeuntersuchungen, wie z. B. das Ganzkorper-MRT bei den multiplen chondroiden Lasionen, sind aufwendig, in diesen Fallen jedoch auch zu rechtfertigen.

Simple Summary High-risk soft tissue sarcomas (HR-STS) account for less than 1% of all malignancies in adults. Despite optimal local treatment, almost half of patients will die within five years of their diagnosis. Chemoresistance is a major responsible mechanism for treatment failure in advanced tumor stages. In contrast to other cancer types, molecular predictors of response to chemotherapy and survival have not been identified and put into clinical practice by now. We analyzed the predictive value of two molecules involved in the working and resistance mechanisms to doxorubicin, TOP2A and SIRT1, in a large cohort of locally advanced HR-STS who underwent a neoadjuvant anthracycline-based chemotherapy with a long-term follow-up. Our results show sarcoma subtype-specific patterns of TOP2A and SIRT1 expression. We demonstrate significant differences in overall survival according to the TOP2A and SIRT1 expression status. Both markers can be used as clinically significant predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy. Abstract Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A (“Top survivors”) significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the “Top survivor” biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy.

Intraarticular benign tumors are rare lesions in many cases seen as incidental findings. One of the typical lesions is the diffuse or nodular form of pigmented villonodular synovitis, which needs a complete surgical removal. Magnetic Resonance Imaging (MRI) is diagnostic in most of the cases because of the intracellular iron content which shows an at least in some parts dark T2-sequence. Adjuvant therapies as radiosynoviorthesis should be considered in diffuse or recurrent lesions. Synovial Chondromatosis represents a metaplastic disorder of the synovial membrane resulting in the production of loose cartilage bodies. Also in this dissease synovectomy or, in late cases, removal of the loose bodies only, is recommended. Synovial hemangiomas are hamartomas which may lead to pain or restriction of movement. In these cases total or partial resection is justified. Alternative treatment options such as laserablation may be possible. Lipoma arborescens represents a proliferative lipoid lesion of the subsynovial region leading to villonodular synovial proliferation. If clinically symptomatic, resection by arthroscopic or open synovectomy is recommented.

To report our experience with EBRT combined with limb-sparing surgery in elderly patients (>70 years) with primary extremity soft tissue sarcomas (STS). Retrospectively analyzed were 35 patients (m:f 18:17, median 78 years) who all presented in primary situation without nodal/distant metastases (Charlson score 0/1 in 18 patients; ≥2 in 17 patients). Median tumor size was 10 cm, mainly located in lower limb (83%). Stage at presentation (UICC7th) was Ib:3%, 2a:20%, 2b:20%, and 3:57%. Most lesions were high grade (97%), predominantly leiomyosarcoma (26%) and undifferentiated pleomorphic/malignant fibrous histiocytoma (23%). Limb-sparing surgery was preceded (median 50 Gy) or followed (median 66 Gy) by EBRT. Median follow-up was 37 months (range 1–128 months). Margins were free in 26 patients (74%) and microscopically positive in 9 (26%). Actuarial 3‑ and 5‑year local control rates were 88 and 81% (4 local recurrences). Corresponding rates for distant control, disease-specific survival, and overall survival were 57/52%, 76/60%, and 72/41%. The 30-day mortality was 0%. Severe postoperative complications were scored in 8 patients (23%). Severe acute radiation-related toxicity was observed in 2 patients (6%). Patients with Charlson score ≥2 had a significantly increased risk for severe postoperative complications and acute radiation-related side effects. Severe late toxicities were found in 7 patients (20%), including fractures in 3 (8.6%). Final limb preservation rate was 97%. Combination of EBRT and limb-sparing surgery is feasible in elderly patients with acceptable toxicities and encouraging but slightly inferior outcome compared to younger patients. Comorbidity correlated with postoperative complications and acute toxicities. Late fracture risk seems slightly increased.