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Opinion Statement: Over the last decade in soft tissue sarcoma (STS) research, the shifting landscape towards more precise subtype classification and the increasing study of novel therapeutic strategies has prompted a need to highlight current knowledge of effective subtype specific therapies. Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma (MFH), is among the most common subtypes of STS arising in the trunk or extremities of adults. Administration of systemic chemotherapy is the primary management in locally advanced and metastatic UPS. While anthracycline-based chemotherapy continues to be standard of care in this setting, outcomes in locally advanced or metastatic UPS remain poor. Recent studies highlight the unique characteristics of UPS that may contribute to its greater sensitivity to immune checkpoint inhibition (ICI) compared to other STS subtypes. With the promise of benefit from novel therapies, including ICI or ICI plus chemotherapy, for a subset of patients with UPS comes the need to identify biomarkers predictive of response to therapy. Ongoing and future clinical trials should place strong emphasis on correlative biomarker studies to learn more about the unique biology of UPS and to identify patients for whom ICI-based therapy will be effective., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

ATF1, CREB1, and CREM, which encode the CREB family of transcription factors, are fused with EWSR1 or FUS in human neoplasms, such as angiomatoid fibrous histiocytoma. EWSR1/FUS-CREB fusions have recently been reported in a group of malignant epithelioid tumors with a predilection to the peritoneal cavity and frequent cytokeratin expression. Here, we studied 8 cytokeratin-positive abdominal malignancies with these fusions for further characterization. The tumors affected males (15 to 76 y old) and presented as intra-abdominal masses with concurrent or subsequent peritoneal dissemination, ascites, and/or metastases to the liver or lymph nodes. Four patients died of the disease within 18 to 140 months. Cases 1 to 5 showed multinodular growth of monomorphic epithelioid cells with focal serous cysts. Lymphoplasmacytic infiltration was prominent and was associated with systemic inflammatory symptoms. Two patients suffered from membranous nephropathy with nephrosis. The tumors displayed partly overlapping phenotypes with malignant mesothelioma, including diffuse strong expression of AE1/AE3 and WT1 and membranous positivity of sialylated HEG1, although calretinin was negative. Case 6 showed similar histology to cases 1 to 5, but expressed smooth muscle actin diffusely, lacked WT1 and HEG1, and harbored prominent pseudoangiomatous spaces. Cases 7 and 8 displayed dense growth of small oval to short spindle cells, with occasional molding and minor swirling, superficially resembling small cell carcinoma. Lymphoplasmacytic infiltration was not observed. The tumors were positive for AE1/AE3 and CD34 (focal), whereas calretinin, WT1, and HEG1 were negative. The detected fusions were FUS-CREM (n=4), EWSR1-ATF1 (n=2), EWSR1-CREB1 (n=1), and EWSR1-CREM (n=1). We confirmed the prior observation that these tumors do not fit perfectly with known entities and provided additional novel clinicopathologic information. The tumors require wider recognition because of more aggressive behavior than angiomatoid fibrous histiocytoma despite similar genetics, and potential misdiagnosis as unrelated diseases, such as neuroendocrine neoplasms., Competing Interests: Conflicts of Interest and Source of Funding: Supported in part by JSPS Grant-in-Aid for Young Scientists 18K15108 (A.Y.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The purpose of this study was to construct and validate a nomogram for predicting cancer-specific survival (CSS) in undifferentiated pleomorphic sarcoma (UPS) patients at 3, 5, and 8 years after the diagnosis., Methods: Data for UPS patients were extracted from the SEER (Surveillance, Epidemiology, and End Results) database. The patients were randomly divided into a training cohort (70%) and a validation cohort (30%). The backward stepwise Cox regression model was used to select independent prognostic factors. All of the factors were integrated into the nomogram to predict the CSS rates in UPS patients at 3, 5, and 8 years after the diagnosis. The nomogram' s performance was then validated using multiple indicators, including the area under the time-dependent receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, decision-curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification improvement (NRI)., Results: This study included 2,009 UPS patients. Ten prognostic factors were identified after analysis of the Cox regression model in the training cohort, which were year of diagnosis, age, race, primary site, histological grade, T, N, M stage, surgery status, and insurance status. The nomogram was then constructed and validated internally and externally. The relatively high C-indexes and AUC values indicated that the nomogram has good discrimination ability. The calibration curves revealed that the nomogram was well calibrated. NRI and IDI values were both improved, indicating that our nomogram was superior to the AJCC (American Joint Committee on Cancer) system. DCA curves demonstrated that the nomogram was clinically useful., Conclusions: The first nomogram for predicting the prognosis of UPS patients has been constructed and validated. Its usability and performance showed that the nomogram can be applied to clinical practice. However, further external validation is still needed.

Malignant fibrous histiocytoma (MFH) of the chest wall is a rare tumor with poor prognosis. A 70-year-old male was admitted to our hospital because of chest pain and an abnormal shadow on the chest X-ray. He had a right chest wall tumor of 7 cm insize. The tumor was surgically removed completely and the diagnosis of pleomorphic MFH was established pathologically. After surgery, adjuvant radio-chemotherapy was performed. The patient has been followed up for 7 year with no evidence of reccurence.

Background: Undifferentiated pleomorphic sarcoma (UPS) is a rare malignant tumour of mesenchymal origin, which was conceived following re-classification of malignant fibrous histiocytoma (MFH). The objective of this study is to determine prognostic factors for the outcome of UPS, following multi-modal treatment., Methods: Data of UPS tumours from 1996 to 2016 were collected, totalling 266 unique UPS patients. Median follow-up was 7.8 years. All tumours were retrospectively analysed for prognostic factors of the disease, including local recurrence (LR) and metastatic disease (MD) at diagnosis, tumour size, grade, location and depth, patient age, adjuvant therapy and surgical margin. Overall survival (OS), post-treatment LR and metastatic-free survival were assessed as outcomes., Results: The 5- and 10-year OS rates for all ages were 60% and 48%, respectively, with a median survival time of 10.1 years. Multivariate analysis revealed that the adverse prognostic factors associated with decreased OS were older age (P < 0.001; hazard ratio 1.03) and MD at diagnosis (P = 0.001; 2.89), with upper extremity tumours being favourable (P = 0.043; 2.30). Poor prognosis for post-operative LR was associated with older age (P = 0.046; 1.03) and positive surgical margins (P = 0.028; 2.68). Increased post-treatment MD was seen in patients with large tumours (5-9 cm (P < 0.001; 4.42), ≥10 cm (P < 0.001; 6.80)) and MD at diagnosis (P < 0.001; 3.99), adjuvant therapy was favourable, shown to reduce MD (P < 0.001; 0.34)., Conclusions: UPS is a high-grade soft tissue sarcoma, for which surgery striving for negative margins, with radiotherapy, is the treatment of choice. Older age, lower extremity location, MD at presentation, large size and positive surgical margins, were unfavourable., (© 2019 Royal Australasian College of Surgeons.)

Atypical fibroxanthoma and undifferentiated pleomorphic sarcoma, or pleomorphic dermal sarcoma, are rare malignant cutaneous neoplasms existing along a clinicopathologic spectrum. Although these tumors share many similarities, recognition of distinguishing characteristics may predict differences in clinical behavior and outcomes. Salient features defining atypical fibroxanthoma include superficial tumors with minimal high-risk histologic features. Deeper tumors with high-risk histologic features are often clinically aggressive and should be appropriately designated as pleomorphic dermal sarcoma. Surgery remains gold standard in management; tumor extirpation with complete margin control is critical. In the high-risk tumor cohort, comprehensive evaluation and multidisciplinary management is paramount for optimal outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Undifferentiated pleomorphic sarcoma is a very rare and aggressive type of primary cardiac tumors. Most cardiac sarcomas result in rapid growth and quick death. According to different sources the median survival is typically 6 to 12 months. We are presenting a case of primary cardiac sarcoma with 26 months disease free survival following cytoreductive surgery and chemotherapy., Case Presentation: A 48-year-old woman with progressing symptoms of dyspnea and palpitations for over 2 months was referred to a cardiologist. With the help of echocardiography and cardiovascular magnetic resonance cardiac sarcoma was suspected. Open biopsy and cytoreductive surgery were performed, complete resection of the tumor was not possible. Histology revealed undifferentiated pleomorphic sarcoma. Seven cycles of chemotherapy with Doxorubicine and Ifosfamide were completed. Cardiovascular magnetic resonance revealed a complete response - only signs of fibrosis without any signs of tumor were visible. Follow ups with echocardiography, cardiovascular magnetic resonance and chest, abdomen and pelvic computed tomography is performed every 3 months. Twenty-six months from initial diagnosis the patient is still free of recurrence of tumor with no compromises of the quality of life., Conclusion: Standard chemotherapy together with cytoreductive surgery can have a complete response effect in undifferentiated pleomorphic sarcoma with unusual long-term survival.

Background: As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure., Methods: We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins., Results: 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009)., Conclusions: Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

Purpose: To evaluate the results of an adjuvant contact irradiation using 50kV photons after resection of conjunctival malignancies., Materials and Method: From 2012 to 2014, 14 patients (male: nine; female: five) have been treated by contact irradiation after resection of a malignant tumor of the conjunctiva (melanoma: five patients; malignant fibrous histiocytoma: one patient; carcinoma: eight patients) The treatment was performed using the Papillon 50 machine (Ariane). Three to four sessions were delivered, each giving a dose of 10Gy. The median follow-up in survivors was 33 months., Results: The tolerance was good. A cataract was seen in one patient, and a moderate eye dryness in one. There was no corneal ulcer. One patient died of intercurrent disease. One patient with carcinoma recurred locally., Conclusion: Adjuvant contact radiotherapy provides a good local control after resection of conjunctival malignancies (melanoma, malignant histiocytofibroma, carcinoma). Thanks to its precision, this technique is well tolerated with a low rate of complications. Furthermore, it is delivered on an ambulatory basis., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Opinion Statement: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) tumors share many clinical, etiologic, and histologic features and likely represent components of a tumor spectrum. In dermatologic oncology, differentiating between AFX and PDS is pivotal as tumors with histological features consistent with PDS are more likely to behave in a clinically aggressive manner. Importantly, the term "pleomorphic dermal sarcoma" (PDS) is a more appropriate designation than "undifferentiated pleomorphic sarcoma" (UPS) for describing deeper, more aggressive, histologically high-grade cutaneous tumors that otherwise resemble AFX. Surgery remains the gold standard for treatment. In the setting of AFX, excision with the Mohs micrographic technique appears to offer superior tumor control rates while maintaining greater tissue preservation over wide local excision and should be considered first line. In the setting of PDS, optimal management is less clear given the paucity of available data. However, due to its greater propensity to recur and metastasize, extirpation with complete tumor margin control appears paramount. The roles of imaging and SLNB in management and clinical outcomes of AFX and PDS are unclear given the lack of available data. In reality, these tools are unlikely to be helpful in most cases of AFX. However, in the setting of PDS, emerging literature indicates that these tumors are inherently higher risk, and thus, imaging and SLNB may be helpful in select cases. Additionally, radiation therapy may be of adjuvant benefit for these tumors when clear surgical margins cannot be obtained. While traditional chemotherapy has been largely ineffectual, the recent discovery of key oncogenetic mutations has allowed for the identification of several potential molecular drug targets that may have a therapeutic role with future study. In the unfortunate setting of metastatic disease, a multidisciplinary approach is optimal. Further studies are needed to establish definitive conclusions regarding risk stratification and best management practices.

Rationale: Malignant fibrous histiocytoma (MFH), primary presented in liver, was very rare and displayed a poor prognosis because of high aggression. As a few of cases had been reported merely, we shared the case of primary hepatic MFH combined with invasion of inferior vena cava (IVC)., Patients Concerns: A 69-year-old women presented with abdominal pain., Diagnoses: Abdominal computed tomography and magnetic resonance imaging indicated a soft mass about 5.4 × 4.2 cm in the caudate lobe, accompanied with IVC invaded., Interventions: After the multidisciplinary consultation, laparotomy was performed, followed by chemotherapy and radiotherapy. Primary hepatic MFH was demonstrated pathologically. Till now, the patient was alive for >22 months after surgery and no evidence of recurrence or distant metastasis was suspected., Outcomes: We discussed the integrated procedure of diagnosis and treatment, combined with data from literature review., Lessons: To our knowledge, the primary hepatic MFH combined with invasion of IVC was hardly reported. Despite the poor prognosis, the comprehensive treatment integrating the surgery, chemotherapy, and radiotherapy showed the satisfactory disease-free and overall survival. However, further investigations are definitely warranted.

Background: There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas., Methods: Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed., Results: In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively., Conclusions: Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

A 68-year-old gentleman presented with a lesion that resembled a pyogenic granuloma in his inferior fornix. The lesion was excised and biopsy demonstrated a proliferation of malignant spindle cells. Three weeks following initial excision, the lesion recurred and was removed via wedge excision of the eyelid. Definitive clearance was achieved through Mohs micrographic surgery. The patient received adjuvant postoperative radiotherapy and remains disease-free. This case demonstrates the need to consider sinister pathology in the setting of recurrent periocular lesions.

Background: Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of intermediate biologic potential. Because of its rarity and nonspecific radiological and diverse pathological findings, AFH is often clinically misdiagnosed. However, few clinical reports have described this tumor. As reported herein, we analyzed the clinical and radiological features and clinical outcomes of AFH., Methods: We retrospectively reviewed the medical records of seven cases histopathologically diagnosed as AFH. We examined clinical features, MRI findings, histopathological diagnoses, treatments, and outcomes., Results: These seven cases comprised five male and two female patients with ages ranging from 8 to 50 years old. The primary locations included upper extremities in 2, lower extremities in 4, and the inguinal region in one patient. Of the tumors, 4 occurred in subcutaneous tissues and 3 occurred in deep tissues. No cases were diagnosed as AFH from MRI and needle biopsy results. All cases were diagnosed histopathologically after excision. After treatment, 2 patients (29%) had tumor recurrence and metastasis, one of whom died from disease progression. These 2 aggressive cases involved both EWSR1 and CREB1 gene rearrangements as determined by FISH. The other patients were alive and well without recurrence or metastasis., Conclusion: AFH is a rare tumor that is difficult to diagnose. Therefore, it tends to be misdiagnosed and to be treated inadequately by referring physicians. Surgeons must therefore be mindful of the presence of AFH, learn about appropriate treatment necessary for this tumor, and conduct careful follow-up because AFH can engender poor outcomes.

Objectives: This study aims to evaluate patients diagnosed with malignant fibrous histiocytoma and investigate the possible prognostic factors associated with duration of survival., Patients and Methods: The study, which was conducted between May 1994 and September 2013, included 14 patients diagnosed as malignant fibrous histiocytoma (12 males, 2 females; median age 48 years; range 17 to 64 years). We evaluated patients' demographic features, location of the pathology, histological findings, surgical margins, and treatment modalities and investigated the effects of these parameters on survival., Results: Femur was the most frequently involved bone, followed by tibia and humerus. The median follow-up duration of the patients was 129 months. We performed limb salvage surgeries in 13 patients and amputation in one patient. Surgical margins were marginal in three patients and postoperative radiotherapy was performed for local control of the disease. Although there was no local recurrence in these patients, distant metastasis developed in two patients, indicating the importance of surgical margin as a significant factor on survival. Five-year survival rate was 81.9% in patients with wide surgical margins and 33.3% in patients with marginal margins., Conclusion: Surgical excision with wide margins and adjuvant chemotherapy provided adequate control of the disease and longer survival. The only prognostic factor statistically significantly associated with duration of survival was surgical margins. Neoadjuvant chemotherapy may be used when there is a suspicion of not obtaining adequately wide surgical margin perioperatively due to close association with neurovascular structures.

Background: Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The purpose of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes., Methods: A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA, and outcome., Results: At a median follow-up of 3.9 years (9 years for survivors), 5-year disease-specific survival (DSS) was 63 %. Clinical variables associated with improved DSS included age <61 years, tumor size <10 cm, margin-negative resection, and sporadic-tumor status. At the protein level, loss of cyclin D1 (p = 0.06), pEGFR (p = 0.023), pIGF-1R (p = 0.022), and PTEN (p < 0.001) and overexpression of AXL (p = 0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA, and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS), whereas RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R., Discussion: Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions.

Background: Racial disparities in access and survival have been reported in a variety of cancers. These issues, however, have yet to be explored in detail in patients with soft-tissue sarcomas (STS). The purpose of this paper was to investigate the independent role of race with respect to survival outcomes in STS., Methods: A total of 7601 patients were evaluated in this study. A SEER registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009 (n=7225) was performed. Survival outcomes were analyzed after patients were stratified by race. Multivariable survival models were used to identify independent predictors of sarcoma-specific death. The Wilcoxon rank-sum test was used to compare continuous variables. Statistical significance was maintained at P<0.05., Results: This study showed that African American patients were more likely to die of their STS. They were younger at presentation (P=0.001), had larger tumors (P<0.001), had less surgery (P=0.002), received radiotherapy less frequently (P=0.024), had higher family income (P<0.001), and were less likely to be married (P<0.001). African American race by itself was not an independent predictor of death., Conclusions: African Americans encounter death due to STS at a much larger proportion and faster rate than their respective white counterparts. African Americans frequently present with a larger size tumor, do not undergo surgical resection, or receive radiation therapy as frequently as compared with their white peers. Barriers to timely and appropriate care should be further investigated in this group of at-risk patients.

We present the case of a 74-year-old man with Stage IV metastatic, multifocal, malignant fibrous histiocytoma (T2b, N1, M1, G4) invading the proximal area of the left lower extremity and resulting in intractable neuropathic pain along the distribution of the femoral nerve. He described the pain as being so severe to cause inability to ambulate without assistance or to sleep in a supine or prone position. After a spinal cord stimulation trial and a trial of intrathecal (IT) hydromorphone, both performed at an outside institution, had failed to achieve adequate pain relief, we decided to perform a femoral nerve chemical neurolysis with phenol under ultrasound (US) guidance. The intervention provided 6 months of almost complete pain relief. With the tumor spreading in girth distally and proximally to the scrotal and pelvic areas as well as to the lungs, and pain returning back to baseline, we proceeded with a second femoral nerve chemical neurolysis. Unfortunately we were not able to achieve adequate pain relief. Therefore we opted to proceed with a diagnostic injection of local anesthetic under fluoroscopic guidance at the left L2, L3, and L4 nerve roots level. This intervention provided 100% pain relief and was followed, a few days later, by chemical neurolysis with phenol 3%. The patient reported complete pain relief with the procedure and no sensory-motor related side effects or complications. He was able to enjoy the last 6 weeks of life with his wife and family, pain-free. With this report we add to the limited literature available regarding the management of intractable cancer pain with chemical neurolysis in and around the epidural space.

We hereby present a case of pre-treated unresectable sarcoma recurrence of the trunk which showed an excellent response to concomitant tri-modal therapy, consisting of re-irradiation, chemotherapy and regional hyperthermia even with a strong compromised re-irradiation dose. No significant toxicity of the combined therapy and fast achievement of the pain and neurological symptoms relief are reported. The case shows that concurrent tri-modality treatment can be considered as a therapeutic option for the management of pre-treated unresectable recurrence even in there-irradiation setting.

Background and Objectives: In 2002, with the advent of better classification techniques, the World Health Organization declassified malignant fibrous histiocytoma (MFH) as a distinct histological entity in favor of the reclassified entity high-grade undifferentiated pleomorphic sarcoma (HGUPS). To date, no study has evaluated comparative outcomes between patients designated historically in the MFH group and those classified in the new HGUPS classification. Our goal was to determine the presence of clinical prognostic implications that have evolved with this new nomenclature., Methods: Sixty-eight patients were retrospectively evaluated between January 1998 and December 2007. Forty-five patients diagnosed with MFH between 1998 and 2003 were compared to 23 patients in the HGUPS group, from 2004 to 2007. Primary prognostic outcomes assessed included overall survival, metastatic-free, and local recurrence-free survival., Results: Five-year survivorship between MFH and HGUPS populations, using Kaplan-Meier or competing risk methods, did not show statistical difference for overall survival (60% vs. 74%, P=0.36), 5-year metastasis-free survival (31% vs. 26%, P=0.67), or local recurrence-free survival (13% vs. 16%, P=0.62)., Conclusion: Despite new classification nomenclature, there appears to be no identifiable prognostic implications for sarcomas that remain in the unclassifiable HGUPS group, as compared to the previously accepted MFH group., (© 2014 Wiley Periodicals, Inc.)

The purpose of this study is to evaluate the effectiveness and safety of a computed tomography (CT)-guided, multidisciplinary, minimally invasive approach to the treatment of patients with large, refractory malignant fibrous histiocytoma. This approach includes microwave ablation and absolute alcohol therapy combined with 125I seed implantation. Seven patients (5 males and 2 females, 26-78 years old, mean 49.7 years old) with large, refractory malignant fibrous histiocytoma participated in this study. The tumors had an average maximum diameter of 14.1 cm (10.0-19.0 cm). Follow-up was conducted for an average of 35.7 months to determine the local control rate, overall survival rate, and clinical complications. Follow-up times ranged from 2 to 45 months. Pain was significantly relieved in patients treated with multidisciplinary, minimally invasive approach. Complete response was achieved in 5 patients (71.4%), partial response in the other 2 patients (28.6%). The response rate of this treatment was 100%. The median survival time was 35.7 months. All patients were alive in 2 years after the treatment. Five patients were still alive after 3 years. The 3 year survival rate was 71.4%. The long-term complications included hyperpigmentation at the operative sites (n = 5) and insensible feeling at the ablation sites (n = 3).This CT-guided multidisciplinary, minimally invasive approach is an effective, safe, and feasible means of treating large, refractory malignant fibrous histiocytoma with minimal damage and few complications, but large-scale randomized clinical trials are necessary to confirm this assessment., (© The Author(s) 2014.)

Background: Histologic response to chemotherapy has been shown to be an independent prognostic factor in patients with osteosarcoma and Ewing sarcoma. However, in patients with soft tissue sarcoma (STS), the prognostic impact of histologic response to chemotherapy is less clear. In the current study, the authors sought to determine the prognostic significance of treatment-induced pathologic necrosis in patients receiving neoadjuvant chemoradiotherapy for STS., Methods: Between 1989 and 2011, a total of 113 patients with grade 2 or 3 (graded according to the National Cancer Institute grading system using 3 tiers) extremity or truncal STS were identified who received neoadjuvant interdigitated chemoradiotherapy according to protocol followed by surgery. The extent of tumor necrosis in the resected specimens was quantified and correlated with outcome., Results: The median tumor necrosis rate was 90%, and 103 patients (91%) received all 3 cycles of planned neoadjuvant chemotherapy. The likelihood of achieving ≥95% necrosis was not related to the number of preoperative cycles of chemotherapy received but was found to be related to tumor histology (62% for malignant fibrous histiocytoma vs 0% for synovial sarcoma [P<.001]; 56% for myxoid liposarcoma vs 0% for synovial sarcoma [P = .002]). At a median follow-up of 6 years, there were no statistically significant differences noted in the 5-year local control, disease-specific survival, and overall survival rates for patients with ≥95% necrosis (50 patients; 44%) and <95% necrosis (63 patients; 56%), even when stratifying by histology., Conclusions: In a homogeneous population of patients with high-grade extremity and truncal STS who were treated with neoadjuvant chemoradiotherapy, the extent of pathologic tumor necrosis did not correlate with outcome., (© 2014 American Cancer Society.)

The aim of this study was to assess the management of myxofibrosarcoma in a single specialist centre, and examine factors contributing to local recurrence, metastasis and patient survival. Retrospective analysis of the referral, diagnosis, and management were obtained. Outcome measures including local recurrence, metastasis and death were recorded. 30 patients (mean age of 65.8 years) were treated for myxofibrosarcoma with limb salvage surgery between January 2003 and July 2012. 25 patients were treated for primary disease. Mean follow-up was 49 months (range 10-122). Larger tumours were most likely to metastasise (p = 0.041). Tumour size, resection margin and grade did not predict local recurrence or death. Local recurrence developed in eight patients (26.7%) with six subsequently requiring amputation, and four patients (16.7%) developed metastasis. Our results regarding local control and patient survival compare with that of the literature regarding limb salvage for primary disease, but amputation may be required for recurrent disease.

Sarcomas are relatively resistant because of hypoxia. We previously demonstrated that the transcutaneous CO(2) therapy reduced hypoxic conditions in human malignant fibrous histiocytoma (MFH). Therefore, we hypothesized that transcutaneous CO(2) therapy could enhance the antitumor effect of radiation therapy in human MFH. Our purpose was to evaluate the effects of transcutaneous CO(2) therapy on the antitumor efficacy of X-ray irradiation using MFH. First, in an in vitro study, we assessed apoptotic activity and reactive oxygen species (ROS) production using flow cytometric and immunoblot analysis at 24 h after X-ray irradiation under three different oxygen conditions (normoxic, reoxygenated and hypoxic). In addition, in the in vivo study, 24 male athymic BALB/c nude mice with MFH tumors that were inoculated in the dorsal subcutaneous area were randomized into four groups: control, CO(2), X-ray irradiation and combination (CO(2) and X-ray irradiation). Treatments were performed twice weekly for 2 weeks, four times in total. Tumor volume was calculated. All tumors were excised and apoptotic activity, ROS production, related proteins and HIF-1α expression were assessed using flow cytometric and immunoblot analysis. The in vitro study revealed that X-ray irradiation induced increased apoptosis and ROS production in MFH cells under normoxic and reoxygenated conditions relative to hypoxic conditions (P<0.01). In the in vivo study, tumor volume in the combination group was reduced to 28, 42 and 47% of that in the control, CO(2), and X-ray groups, respectively (P<0.05). Apoptotic activity and ROS production in the combination group were strongly increased with decreasing HIF-1α expression relative to the control, CO(2) and X-ray groups. The transcutaneous CO(2) system enhanced the antitumor action of X-ray irradiation and could be a novel therapeutic tool for overcoming radio-resistance in human malignancies.

Background: Extremity sarcoma national guidelines offer several stage-specific treatment options; therefore, treatment approaches are not standardized. Our objectives were to examine multimodality treatment trends, practice patterns, and factors associated with neoadjuvant or postoperative adjuvant therapy utilization., Methods: Using the National Cancer Data Base (2000-2009), treatment of non-metastatic extremity sarcoma was examined. Regression models were developed to identify factors associated with neoadjuvant or postoperative adjuvant therapy receipt and treatment sequence., Results: Twenty-two thousand fifty-one patients underwent resection (stage I: 45.2%, stage II: 27.7%, stage III: 27.1%). Over 10 years, neoadjuvant radiation (6.4-11.6%, P < 0.001) and chemotherapy utilization (1.4-1.8%, P = 0.037) increased, while postoperative radiation (34.3-29.2%, P = 0.023) and trimodality therapy decreased (10.5-9.6%, P = 0.002). After adjusting for age, comorbidities, and histology, patients with large high-grade tumors treated at high-volume academic centers were more likely to receive neoadjuvant therapy (all P < 0.001). Postoperative chemotherapy utilization was associated with younger age, synovial histology, high grade, and surgical margins (all P < 0.001)., Conclusions: Utilization of neoadjuvant therapy for extremity sarcoma has increased over time. Practice patterns are not only related to tumor size, grade, histology, and margins but also hospital type. Opportunities remain to better define the most effective multimodality treatment for extremity sarcoma., (© 2013 Wiley Periodicals, Inc.)

Background: Soft-tissue sarcomas are rare tumors with the incidence of multiple metachronous or synchronous lesions in the extremities being even more uncommon. In effort to preserve the function of upper extremities, limb-salvage surgery became the treatment of choice for soft-tissue sarcomas. Subsequent adjuvant chemotherapy, as well as radiotherapy, is believed to decrease local recurrence rates, however, their effect on overall survival remains unclear., Case: We report herein a case of symmetrical bilateral metachronous malignant fibrous histiocytomas of the shoulder. A 19-year-old patient presented with stiffness and pain in the right shoulder. The same symptoms developed 1.5 years later in the other shoulder. The culprit tumors are reported metachronous with regard to the succession in the onset of symptoms. Wide tumor resection was performed in both shoulders, and postoperative radiotherapy was then conducted. Chemotherapy was not indicated after the first surgery; whereas, in the second case it was the patient who refused the recommended adjuvant chemotherapy., Conclusion: The phenomenon of either metachronous or synchronous incidence of multiple soft tissue sarcomas is very rare and systematic reporting of every new case in the literature could contribute to further knowledge of tumors unique behavior.Key words: malignant fibrous histiocytoma - radiotherapy - upper extremity - neoplasms - multiple primary.

Background: The purpose of this study was to evaluate the survival impact and prognostic factors of pulmonary metastasectomy in patients with pulmonary metastasis from head and neck cancer., Methods: A retrospective study of 69 patients was analyzed. Twenty-four patients (35%) underwent pulmonary metastasectomy, and the remaining 45 patients (65%) were treated with chemotherapy or best supportive care., Results: The 1-year overall survival (OS) of 69 patients was 28%. Pulmonary metastasectomy (p = .01) and histology (p < .001) had a significant impact on the prognosis. One-year OS of patients who underwent metastasectomy and those who did not was 90% and 35%, respectively. In the metastasectomy group, recurrence of primary ahead of lung metastasis (p = .006) and disease-free interval (DFI; ≤21.4 months; p = .046) were significant negative prognostic factors., Conclusion: Pulmonary metastasectomy has an impact on survival in carefully selected patients, especially for those with a long DFI and with no recurrence of primary cancer ahead of lung metastasis., (Copyright © 2012 Wiley Periodicals, Inc., A Wiley Company.)

Aims: The treatment of pelvic soft tissue sarcomas (STS) presents one of the most challenging problems in musculoskeletal oncology because of the complex anatomy of the pelvis, late diagnosis and large tumor size. Our study was designed to determine the outcome and prognostic factors for survival and local recurrence in patients with pelvic STS located deep to the fascia and deemed suitable for curative surgical treatment., Patients and Methods: Ninety consecutive pelvic STS patients with at least 5-year possible follow-up from diagnosis were studied. Mean age at diagnosis was 54 years. Mean follow-up and tumor size were 69 months and 13 cm, respectively. Histological grades were grade 3 in 51, grade 2 in 22 and grade 1 in 17 patients. Tumor locations were extra-pelvic or outside pelvic brim (n=67), intra-pelvic or within pelvic brim (n=10), and combined or involving both outside and within pelvic brim (n=13)., Result: Surgical treatment was excision in 84 patients and hindquarter amputation in 6 patients. In 84 patients who underwent excision, surgical margin was wide in 21 patients, marginal in 33, and intralesional in 30. Radiotherapy was used for all high grade tumors. Disease-specific survival was 53.3% at 5 years. Local recurrence occurred in 23%. Development of local recurrence was related to surgical margin (p=0.03). Local recurrence, tumor histological grade and metastasis at diagnosis independently influenced disease-specific survival (p=0.0008, p<0.0001, p=0.02, respectively)., Conclusion: The patients with high grade tumors and positive surgical margins represent a particular group with high risk of local recurrence even with radiotherapy., (Copyright © 2012. Published by Elsevier Ltd.)

Objective: To overcome the therapeutic limitations of malignant fibrous histiocytoma (MFH), we evaluated human adipose tissue-derived mesenchymal stromal cells (MSCs) that secrete tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on metastatic MFH., Background: MFH is a highly malignant and metastatic type of sarcoma but surgical removal is the only effective method for treating MFH. MSCs are easily transduced to express a high level of transgene and can migrate toward cancer. For this reason, MSCs are a promising candidate for metastatic MFH therapies., Methods: In vitro sustainability of MSC-TRAIL against MFH-ino was analyzed by apoptosis assay. For preclinical study, anti-MFH effects of MSC-TRAILs were validated in murine models for local tumorigenesis and metastasis. Furthermore, a time-interval metastasis model of MFH was applied to confirm antimetastatic ability of MSC-TRAIL for preestablished metastatic MFH., Results: We found that MFH-ino is highly susceptible to recombinant TRAIL and MSC-TRAIL, which selectively induce apoptosis via caspase-8 activation in vitro. Moreover, not only MFH-ino but xenograft explants were also significantly inhibited by MSC-TRAIL in local tumorigenesis. In particular, the metastatic ability of MFH-ino was considerably reduced by MSC-TRAIL in metastasis murine model, particularly for preestablished metastatic MFH., Conclusions: These results suggest that MSC-TRAIL is sufficiently effective in inhibiting MFH-ino metastasis and the application using MSC-TRAIL could be extended to other sarcomas and recurrent metastatic cancers for cell-mediated cancer therapy.

Aims and Background: Adult sarcomas of the head and neck region (HNSs) are considered a rare clinicopathological entity. They account for only 2-15% of all adult sarcomas and for less than 1% of all head and neck malignancies. The preferred initial treatment option is wide surgical excision. Whenever surgery is considered infeasible, a frontline combined-modality approach including radiotherapy and chemotherapy might be proposed. We here report on a case of localized sarcoma of the maxillary sinus treated with induction chemotherapy and subsequent intensity-modulated radiation therapy (IMRT), achieving a persistent complete remission status., Methods: A 66-year-old man was referred to our institution hospital for left-sided facial pain with swollen left cheek and ipsilateral facial palsy. Magnetic resonance imaging showed a mass within the left maxillary sinus extending to the orbital floor and adjacent alveolar bones. Histological examination of the biopsy specimen demonstrated a myxofibrosarcoma. The patient underwent induction chemotherapy with gemcitabine 900 mg/m2 (days 1-8) and taxotere 80 mg/m2 every 3 weeks for 3 cycles and sequential simultaneous integrated boost (SIB) IMRT up to a total dose of 70 Gy/35 fractions to the macroscopic disease with 59.5 Gy/35 fractions to the level IB-II lymph nodes in the left neck., Results: Treatment was well tolerated with mild acute toxicity. Complete remission was achieved at restaging MRI 6 months after the end of the combined modality approach. The patient remains in complete, unmaintained clinical and instrumental complete remission 18 months after treatment, with no late side effects., Conclusion: Combination therapy with induction chemotherapy and sequential SIB-IMRT could therefore be a promising modality for head and neck sarcomas, allowing for simultaneous tumor control and normal tissue sparing.

Sarcomas of the head, neck, and skull base represent a heterogeneous group of tumors with distinct prognostic features. There have been significant improvements in characterizing these sarcomas using traditional morphologic assessments and more recent immunohistochemical analysis. Surgery is the mainstay of treatment followed by radiation therapy. Treatment modalities have changed in select pediatric sarcomas, for which new chemotherapeutic combinations have improved survival statistics. The high rate of distant failure emphasizes the need for novel systemic and directed molecular therapies. Tumor grade, size, and margin status are key factors in survival., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: The study objective is to evaluate the clinical features and outcomes of patients treated for head and neck malignant fibrous histiocytoma at a tertiary care medical facility., Materials and Methods: This is a retrospective case series of 17 adult subjects with malignant fibrous histiocytoma of the head and neck who were treated between January 1, 1965, and December 31, 2010. This study was conducted using patient charts at a tertiary medical center. Subject selection was conducted using Current Procedural Terminology numbers; International Classification of Diseases, Ninth Revision, codes; and a search of the tumor registry., Results: Chart review of the 17 identified subjects revealed an overwhelming male predominance (88%) with an overall mean age of 69 years(52-87 years). Thirteen patients (78%) underwent some form of surgical resection, 6 patients (35%) received radiation therapy, and 6 (35%) were given chemotherapy over the course of treatment. Nine tumors (53%) had a cutaneous origin, whereas 8 lesions (47.1%) were found in the soft tissue of the head and neck region. The local recurrence rate following a single resection was 46%. Overall median survival following diagnosis was found to be 65 months, with a 5-year survival rate of 52%. Median disease-free survival was 20 months, with a 5-year disease-free survival rate of 37%. Overall median and 5-year survival rates were found to increase with clear surgical margins, as was 5-year survival., Conclusions: Aggressive surgical management to achieve clear margins is central to the effective treatment of malignant fibrous histiocytoma of the head and neck. Metastatic disease portends a dismal prognosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Malignant fibrous histiocytoma (MFH) is a rare neoplasm exhibiting a propensity for aggressive clinical behavior. This review seeks to provide the practicing dermatologist with a contemporary understanding of MFH in order to guide management decisions. An extensive review of the literature was conducted using PubMed and OVID databases, searching for articles regarding MFH and undifferentiated pleomorphic sarcoma. The modern conception of MFH has changed extensively from clinical and pathologic standpoints. Limitations of the study included the reliability of past studies given the changing nature of MFH as a diagnostic entity. MFH represents an aggressive neoplasm with unique molecular, immunohistochemical, and behavioral characteristics. Practicing clinicians would benefit from a contemporary understanding of these tumors, particularly as a discussion of advances in the conception of MFH is largely absent in the dermatologic literature., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

This article concentrates on the less-common cutaneous malignancies such as merkel cell, atypical fibroxanthoma, malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, microcystic adnexal carcinoma, and sebaceous carcinoma. The clinical and histopathologic descriptions of each, most current and emerging etiologies, diagnosis, staging, treatment, and prognosis are discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Takayasu arteritis (TA) is a type of systemic large-vessel vasculitis that usually affects the aorta and its major branches. It remains unrecognized owing to delayed diagnosis (Boltin et al. in Rheumatol Int 27(10):985-987, 2007) and non-characteristic clinical features. It has been described in association with many autoimmune diseases, such as inflammatory digestive tract diseases. However, report of TA associated with tumors, especially malignant tumors, are rare. We here presented a case diagnosed by both Takayasu arteritis and malignant fibrous histiocytoma, from which we learned not only clinical lessons, but also consensus of relationships between these two diseases.

A 67-year-old female who was diagnosed with ulcerative colitis in 2001, presented with a soft tissue mass in the middle of her back of 4 months duration in April 2011. It was excised; however it recurred at the same site in September 2011. Wide excision of the mass was done. Pathology revealed T1aNxM0 pleomorphic malignant fibrous histiocytoma or undifferentiated pleomorphic sarcoma. Whole body bones scan and staging CT scan of the chest, abdomen and pelvis was negative for distant metastasis. She received local radiotherapy at the site of excision. No chemotherapy was given.

Although the incidence of malignant tumors in patients undergoing total hip arthroplasties (THAs) is known to be lower than the general population, there exist several reports on the development of malignant tumors at the site of THAs. We report another case of malignant fibrous histiocytoma at the site of a THA, which was developed in an older patient who presented a cystic mass around the total hip prosthesis using a ceramic-on-ceramic bearing system, even without evidence of osteolysis or loosening of implants. This is the second case associated with an aluminum oxide prosthesis in English literature., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Pleomorphic sarcoma, widely known as malignant fibrous histiocytoma (MFH), is a soft tissue sarcoma. The occurrence of this malignancy in the mediastinum is rare. To our knowledge, only 13 cases of MFH of the mediastinum have been previously reported. Furthermore, only three cases of MFH in patients infected with human immunodeficiency virus (HIV) have been previously described. Here we present a 44-year-old African-American male who complained of epigastric pain radiating to the right chest. On admission, a chest radiograph revealed a widened mediastinum, and chest computerized tomography (CT) identified a large mass in the posterior mediastinum. Histologic diagnosis revealed a high-grade MFH. He was also incidentally diagnosed with HIV infection. The rarity of this malignancy and uncommon site of presentation in association with an immunodeficient state makes this case unique. This is the first report in the literature of an HIV-infected patient presenting with this uncommon tumor in the mediastinum.

Malignant fibrous histiocytoma (MFH) is the most common soft-tissue sarcoma of late adult life occurring predominantly in the extremities and the retroperitoneum. MFH of the ovary is very rare, with only six cases previously reported. A 67-year-old woman with a right pelvic tumor highly suspicious of ovarian carcinoma was submitted to exploratory laparotomy. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, pelvic and paraaortic lymphadenectomy with right hemicolectomy along with permanent cutaneous ileostomy were performed. Since a storiform-pleomorphic type of MHF was diagnosed from histopathological and immunohistochemical findings, chemotherapy was proposed as the postoperative treatment. Despite extensive surgery with negative surgical margins, the patient had recurrence of the tumor within four months, and was submitted to secondary surgery. A combination of chemo- and radiotherapy was performed postoperatively, but the patient developed respiratory problems and died one year later from the primary diagnosis.