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A solitary fibrous tumor (SFT) is documented in several body sites. However, there are few reports on the radiological and corresponding histopathological, including immunohistochemical, features of SFT in the lower extremities. A 58-year-old male presented with a lump in his right thigh of 6 months duration. Plain radiograph revealed a soft tissue lesion in his right thigh, involving the adjacent mid-diaphysis and showing focal cortical thickening and calcification. Magnetic resonance imaging scans displayed two well-defined, T1-isointense and T2 heterogeneously hyperintense lesions, measuring together 15 cm in the intermuscular plane and the juxtacortical location along the mid-diaphyseal region of the right femur. Radiologically, the differential diagnoses considered were undifferentiated pleomorphic sarcoma and synovial sarcoma. Microscopic examination of the core biopsy and the resected tumor revealed a tumor composed of cells with oval to spindle-shaped nuclei in a variably collagenized stroma, including hyalinized blood vessels and focal dystrophic calcification. Mitotic figures were 4/10 high power fields. Immunohistochemically, the tumor cells were positive for CD34, BCL2, and STAT6. Diagnosis of malignant SFT was offered. The tumor displayed NAB2ex4-STAT6ex2 gene fusion on molecular testing. This constitutes a relatively uncommon case report of a large SFT in the thigh, including its radiological and pathological features, confirmed by STAT6 immunostaining. An SFT should be considered in cases of slow-growing, well-defined soft tissue tumors, which are isointense on T1 and heterogeneously hyperintense on T2-weighted sequences, and display calcification and cortical thickening of the adjacent bones. Various differential diagnoses and their treatment-related implications in such cases are discussed herewith.

Magnetic Resonance Imaging is a fundamental tool in the evaluation of soft tissue sarcoma. Imaging features are relevant for the assessment of treatment strategies, surgical planning and also for patients’ prognosis prediction. Among soft tissue sarcoma and also other malignancies, the size of the mass is usually considered the prognostic key element in diagnostic imaging. Moreover, several other features should be obtained from MRI studies with prognostic implications in all type of soft tissue sarcoma: peritumoral enhancement, signs of necrosis, deep location, ill-defined borders/signs of infiltrations. Focusing on soft tissue sarcoma subtypes, some other magnetic resonance imaging features are more specific and related to prognosis. In myxofibrosarcoma the magnetic resonance imaging “tail sign” and a “water-like” appearance on fluid-sensitive sequences, due to rich myxoid matrix content, are both associated with higher risk of local recurrence after surgical excision; nevertheless, the “tail sign” is also related to a higher risk of distant metastases at diagnosis. The “tail sign” is associated with higher risk of local recurrence after surgical excision in undifferentiated pleomorphic sarcoma as well. In patients affected by synovial sarcoma, the “triple sign” identifiable in magnetic resonance imaging (T2w sequences) is associated with decreased disease-free survival and indicates the simultaneous presence of solid cellular elements (intermediate signal intensity), hemorrhage or necrosis (high signal intensity) and fibrotic regions (low signal intensity). In addition, absence of calcifications are associated with reduced disease-free survival in patients affected by synovial sarcoma. Signal heterogeneity is associated with worst prognosis in all type of soft tissue sarcoma, particularly in myxoid liposarcoma. In recent years, several new quantitative tools applied on magnetic resonance imaging have been proved to predict patients’ prognosis. Above all the new tools, radiomics seems to be one of the most promising, and, has been proved to have the capability in discriminating low-grade from high-grade soft tissue sarcomas. Therefore, magnetic resonance imaging studies in patients with soft tissue sarcoma should be accurately evaluated and their results should be taken into account for prognostic assessment.

ZusammenfassungDas undifferenzierte pleomorphe Sarkom („undifferentiated pleomorphic sarcoma“ [UPS]) gehört zur Gruppe der Weichteilsarkome und macht fast 10 % aller Weichteilsarkome aus. Der Fall eines 49-jährigen Patienten wird vorgestellt, bei dem die kompartmentorientierte Resektion eines primären UPS im linken Musculus gluteus maximus mit adjuvanter Radiotherapie (60 Gy) durchgeführt wurde. Im Rahmen der Tumornachsorge (3 Jahre später) wurde eine lokoregionäre Metastase an einer ungewöhnlichen Lokalisation im M. quadratus femoris festgestellt, welche mittels einer In-toto-Resektion mit intraoperativer Radiotherapie (10 Gy) behandelt wurde. Der intra- und postoperative Verlauf gestalten sich komplikationslos ohne neurologische Defizite. Im Rahmen der Nachtuntersuchung 6 Monate postoperativ war der Patient tumor- und beschwerdefrei.

Soft tissue sarcoma (STS) is a heterogeneous family of rare mesenchymal tumors, characterized by histopathological and molecular diversity. Tissue microarray (TMA) is a tool that allows performing research in orphan diseases in a more efficient and cost-effective way. TMAs are paraffin blocks consisting of multiple small representative tissue cores from biological samples, for example, from multiple donors, diverse sites of disease, or multiple different diseases. In 2015, we began constructing TMAs using archival tumor material from STS patients. Specimens were well annotated in terms of histopathological diagnosis, treatment, and clinical follow-up of the tissue donors. Each TMA block contains duplicate or triplicate 1.0–1.5 mm tissue cores from representative tumor areas selected by sarcoma pathologists. The construction of TMAs was performed with TMA Grand Master (3DHistech). So far, we have established disease-specific TMAs from 7 STS subtypes: gastrointestinal stromal tumor (72 cases included in the array), alveolar soft part sarcoma (n = 12 + 47), clear cell sarcoma (n = 22 + 32), leiomyosarcoma (n = 55), liposarcoma (n = 42), inflammatory myofibroblastic tumor (n = 12 + 21), and alveolar rhabdomyosarcoma (n = 24). We also constructed a multisarcoma TMA covering a representative number of important histopathological subtypes on arrays for screening purposes, namely, angiosarcoma, dedifferentiated liposarcoma, pleomorphic liposarcoma, and myxoid liposarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, myxofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma, with 7–11 individual cases per subtype. We are currently expanding the list of TMAs with additional sarcoma entities, considering the heterogeneity of this family of tumors. Our extensive STS TMA platform is suitable for rapid and cost-effective morphological, immunohistochemical, and molecular characterization of the tumor as well as for the identification of potential novel diagnostic markers and drug targets. It is readily available for collaborative projects with research partners.

Introduction: Esophageal carcinosarcoma (ECS) is a rare malignant tumor that often presents as an intraluminal polypoid lesion in the esophageal lumen. Herein we present a case diagnosed as esophageal carcinosarcoma and treated with esophagectomy.Case presentation: A 68-year-old male patient was presented to the thoracic surgery department complaining of dysphagia for about three months. He was diagnosed with ECS and underwent uniport video-assisted thoracic surgery (VATS). Based on the histopathological reports, the patient was finally diagnosed as ECS, clinical T1bN0M0, pathological stage I. 11 days after the surgery, the patient was discharged from the hospital without experiencing any complications.Conclusion: Carcinosarcoma was first described by Virchow in 1865 as a rare malignant neoplasm. The clinical manifestations of ECS includes dysphagia, chest pain and weight loss. IHC analysis indicates carcinoma and the sarcoma occurred independently. Complete resection of the esophagus with lymphadenectomy of locoregional nodes is still recommended as the best potentially curative treatment. For the prognosis of ECS compared to (ESCC), there is a controversy. Here, we reported a case of ECS comprising of squamous cell carcinoma in situ and undifferentiated pleomorphic sarcoma underwent uniport VATS esophagectomy with no serious complications, which indicate that VATS esophagectomy could be applied to ECS patients.

Undifferentiated pleomorphic sarcoma (UPS) is a new disease in the World Health Organization's classification of tumors of soft tissue and bone published in 2013. Primary mediastinal UPS is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, which was initially misdiagnosed as epithelial malignant pleural mesothelioma (MPM). The cytopathological findings of the pleural effusion cell block often contribute to the diagnosis of various malignant tumors. However, these findings may lead to misdiagnosis of highly invasive mediastinal tumors such as UPS. A biopsy for primary mediastinal lesions should be performed because MPM rarely mimics mediastinal tumors with pleural effusion., Mediastinal undifferentiated pleomorphic sarcoma (UPS) is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, cytopathologically mimicking epithelial malignant pleural mesothelioma.

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

Background/aim Sarcomas are considered a heterogeneous disease with incomplete understanding of its molecular basis. In the present study, to further understand general molecular changes in sarcoma, patient-derived xenograft (PDX) mouse models of the three most common soft-tissue sarcomas: myxofibrosarcoma, undifferentiated pleomorphic sarcoma (UPS) and liposarcoma were established and the methylation status of histone H3 lysine marks was studied. Materials and methods Immunoblotting and immunohistochemical staining were used to quantify the extent of methylation of histone H3K4me3 and histone H3K9me3. Results In all 3 sarcoma types in PDX models, histone H3K4me3 and H3K9me3 were found highly over-methylated compared to normal muscle tissue. Conclusion Histone H3 lysine over-methylation may be a general basis of malignancy of the major sarcoma types.

Background: The advantages of methyl-methacrylate sandwich for chest wall reconstruction are controversial. We aimed to report the outcomes of chest wall reconstruction using a methyl-methacrylate sandwich after large tumor resection. Methods: This retrospective research included 30 patients who had chest wall reconstruction after resection of large tumors from January 2010 to December 2018 at a single center. All patients had skeletal reconstruction using a methyl-methacrylate sandwich with a Prolene mesh. Soft-tissue construction was performed with primary closure (n= 12), latissimus dorsi flap (n= 10), local flap (n= 4), and pectoralis muscle flap (n= 4).Results: Male presented 73.3% of the patients (n=22) and the median age was 50 years (range: 20- 75). The pathology of the resected tumors were infiltrating carcinoma of the lung (n= 6; 20%), undifferentiated pleomorphic sarcoma (n= 4; 13.3%), chondrosarcoma (n= 4; 13.3%), infiltrating adenocarcinoma of mesothelial origin (n= 4; 13.3%), adenocarcinoma of lung origin (n= 2; 6.7%), osteochondroma (n= 2; 6.7%), Ewing sarcoma (n= 2; 6.7%), round cell sarcoma (n= 2; 6.7%), sternal sarcoma (n= 2; 6.7%), and chondroma (n= 2; 6.7%). Postoperative complications occurred in 14 patients; atelectasis (n= 2; 13.3%), consolidation (n= 2; 6.7%), wound infection (n= 2; 6.7%), flap seroma (n= 2; 6.7%), acute respiratory distress syndrome (n= 2; 6.7%) and local recurrence (n= 2; 6.7%). We reported two late mortalities because of distant metastasis and sepsis Conclusion: Immediate reconstruction of large chest wall defects following tumor resection could be feasible using methyl-methacrylate filler with synthetic mesh with accepted morbidity and mortality.

Background: Breast sarcomas are extremely rare, can be primary or secondary, pose a high risk of recurrence with an overall poor prognosis. Primary breast sarcomas constitute < 1% of all primary breast malignancies and less than 5% of all sarcomas. Sarcomas arising in phyllodes tumors account for < 6 % of all phyllodes tumors. The most common subtype of both primary and secondary sarcoma is angiosarcoma. Methods: This was a retrospective study of patients diagnosed as sarcoma of breast (excluding malignant phyllodes and metaplastic carcinoma) during the period from January 2016 to July 2019. The demographic and clinical features were noted from the medical records. The details of gross specimens (grossed in strict accordance with CAP protocols) were noted. The haematoxylin and eosin-stained slides along with immunohistochemistry (IHC) (pan cytokeratin, calponin, vimentin, SMA, CD117, Ki 67, desmin, CD10, CK5/6, EMA, p63, CD34, CD56, myogenin, CD99, p16, S100, BCL2, CD31, caldesmon and CD68) were reviewed and categorized according to WHO (2019) criteria. Result: The median age of patients was fifty years. There were fourteen breast sarcomas including one arising in phyllodes tumor during the study period. These included undifferentiated pleomorphic sarcoma (4), liposarcoma (2), myxofibrosarcoma (2), angiosarcoma (2), one each of leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma and stromal sarcoma. Despite using a wide panel of IHC markers, 4/14 (28.57%) sarcomas were classified as undifferentiated pleomorphic sarcoma. Conclusion: Primary breast sarcomas are rare tumors and pose diagnostic challenge. It is important to categorize these entities in view of the differing biologic behavior and molecular profiles. Morphology along with IHC is important for diagnosis, treatment and prognosis.

Objectives: Aberrant expression of neuroendocrine markers has been reported in angiosarcomas and can occasionally result in diagnostic confusion. The aim of this study was to evaluate the expression of insulinoma-associated protein 1 (INSM1), a marker for neuroendocrine differentiation, in angiosarcomas as well as other sarcomas. Methods: Tissue microarrays, including angiosarcoma, Ewing sarcoma, desmoplastic small round cell tumor (DSRCT), clear cell sarcoma, synovial sarcoma, leiomyosarcoma, alveolar soft part sarcoma, epithelioid sarcoma, and undifferentiated pleomorphic sarcoma, were evaluated for expression of INSM1. The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0, no staining; 1+, Results: INSM1 expression was found in a subset of angiosarcomas (n = 24/94, 26%; majority 5+, weak to moderate), as well as DSRCTs (n = 7/62, 11%; 2+, weak to strong) and rarely synovial sarcomas (n = 3/76, 4%; 2+, moderate to strong). No INSM1 expression was detected in the other sarcomas. Conclusions: Aberrant expression of INSM1 can be seen in a subset of angiosarcomas often with diffuse labeling. Other sarcomas that can rarely demonstrate small cell morphology and focal INSM1 expression include DSRCT and synovial sarcoma.

Primary malignant melanoma of the vagina accounts for less than 0.3% of all melanomas and approximately 4% of vaginal malignancies. We present a case of a 61-year-old female who presented with complaints of difficulty in urination and a polyp arising from the vagina. Local examination showed a polyp arising from the lateral vaginal wall and a hymenal tag. Histopathological examination of the polyp showed a neoplasm simulating a leomorphic sarcoma. The hymenal tag showed classical features of malignant melanoma. Immunohistochemistry with S100 and HMB45 confirmed malignant melanoma in the vaginal polyp. We report this case, on account of its rarity and unusual phenotypic profile, which may lead to a delayed or alternate diagnosis. Primary malignant melanoma of the vagina needs early accurate diagnosis and management due to its aggressive nature. Keywords: Vaginal melanoma, Mucosal melanoma, Vaginal polyp, Sarcomatous polyp.

Cardiac myxofibrosarcoma (MFS) is an uncommon entity. It is among the most challenging conditions to diagnose due to its rarity, high variability, and non-specific findings. These tumors often simulate left atrial myxoma or mitral stenosis at clinical presentation. Although, the definitive diagnosis of cardiac tumors depends on histopathological examination, various imaging techniques are also useful to study tumor characteristics to plan an appropriate treatment strategy. Here we highlight a case of primary cardiac MFS of left atrium (LA) showing areas of transition to undifferentiated pleomorphic sarcoma (UPS) with bone or osteoid formation, which is extremely rare and not well described.

Non‐osteogenic, non‐Ewing soft‐tissue sarcoma (NONE‐STS) of bone is a rare presentation of primary bone cancers. Optimal treatments and outcomes for this heterogenous group are poorly described. We evaluated the factors associated with long‐term outcomes in patients with this disease. Patients with localized NONE‐STS of bone treated at the Toronto Sarcoma Program from 1987 to 2017 were identified. Clinical characteristics, treatment, and survival information were collected. Kaplan‐Meier (log‐rank) survival estimates from the time of definitive surgery, with uni‐/multivariate analyses (Cox) of sarcoma‐specific survival were performed. A total of 106 patients (60.4% male; median age 46 years) with NONE‐STS of bone were identified. Common histologies included undifferentiated pleomorphic sarcoma [UPS]/malignant fibrous histiocytoma [MFH] (UPS/MFH, 41.5%), leiomyosarcoma (LMS, 20.8%), and fibrosarcoma (FS, 11.3%). Tumors were often high grade (59.4%) and involved the extremities (88.7%), with most receiving chemotherapy (67.9%) with cisplatin/doxorubicin‐based regimens (73.6%). In the full cohort, 10‐year DFS (45.7%, [95%CI: 35.7‐55.8%]), OS (53.4%, [95%CI: 41.7‐62.2%]), and SSS (63.9%, [95%CI: 53.9‐72.5%]) were moderate. Histology specific, 10‐year SSS was 70.7% [95%CI: 56.1‐85.5%] for UPS/MFH, 51.8% [95%CI: 29.8‐73.8%] for LMS, and 72.2% [95%CI: 45.1‐99.2%] for FS. Only UPS/MFH (n = 4) showed sarcoma‐related death >10 years. Multivariate analysis identified axial location (HR = 35.5, [95%CI: 3.4‐369.6]), high grade (HR = 16.9, [95%CI: 1.6‐185.1]), and disease relapse (HR = 485.1, [95%CI: 36.3‐6482.6]) as risk factors for death (p, In patients with Non‐osteogenic, non‐Ewing soft‐tissue sarcoma (NONE‐STS) of bone, long‐term survival is similar to that of osteosarcoma. Patients receiving chemotherapy who demonstrated ≥85% necrosis on pathologic specimens had improved survival, whereas those with UPS/MFH histology experienced sarcoma‐related death beyond 10 years.

Objective Malignant fungating wounds are ulcerating tumors that infiltrate the overlying skin. Little evidence exists regarding the prognosis or treatment of malignant fungating wound in soft tissue sarcoma. This study aimed to reveal the prognosis and outcome of surgical treatment of malignant fungating wound in soft tissue sarcoma. Methods We retrospectively reviewed 26 patients with malignant fungating wound in high-grade soft tissue sarcoma between 2005 and 2018. The patients’ characteristics, treatments, surgical wound complications, local recurrences and prognoses were analyzed. Overall survival was analyzed using the Kaplan–Meier method and compared with that of the control cohort, consisting of 236 consecutive patients with non-malignant fungating wound high-grade soft tissue sarcoma treated during the same period. Results Among the 26 patients, undifferentiated pleomorphic sarcoma was the most common subtype. Twenty-three patients, including 20 (87%) and 3 (13%), underwent limb-salvage surgery and amputation, respectively. Among the 20 patients who underwent limb-salvage surgery, 4 (20%) had surgical wound complications, which required additional surgical procedures. Excluding the patients who underwent palliative surgery, local recurrence occurred in 2 patients (11%). The 5-year overall survival rate for all high-grade malignant fungating wound and non-malignant fungating wound patients was 26.0 and 67.3% (P Conclusions Malignant fungating wounds in soft tissue sarcoma were significantly associated with a poor prognosis; however, the incidence of surgical complications and local recurrence after limb-salvage surgery was comparable to that of general soft tissue sarcoma cases. Limb-salvage surgery should be considered, if possible, to preserve the patient’s quality of life because of the dismal prognosis of patients with malignant fungating wound in soft tissue sarcoma.

A heterogeneous group of CNS tumors are characterized by mixed neuroepithelial and mesenchymal features. Glial tumors manifesting this phenomenon are referred to as gliosarcoma. These tumors are usually mistaken for cerebral metastases or meningioma at operation. Their histological studies have revealed an admixture of gliomatous and sarcomatous tissues, which leads to a biphasic pattern. The mesenchymal component can present in different forms such as fibrosarcoma, undifferentiated pleomorphic sarcoma, chondro-osteogenic, and myogenic differentiation, as well as angiosarcomatous and liposarcomatous types. Squamous differentiation, adenoid formations and glandular structures may also be displayed. Herein, we report a rare case who was admitted to the emergency room with decreased consciousness resembling methadone poisoning. Clinical work-up showed a temporoparietal mass on radiological investigation. Histopathological evaluation of the brain mass revealed a gliosarcoma with adenoid formations and a mesenchymal component, which manifested as chondrosarcomatous differentiation. Immunohistochemical studies confirmed the histologic diagnosis through positivity for EMA, GFAP, S100, and vimentin expression in different components.

ResumoOs sarcomas musculoesqueléticos são doenças raras que exigem atenção. Frequentemente, apresentam alto grau de malignidade ao diagnóstico e se subestimados podem evoluir de forma agressiva local e sistemicamente. Apresentam-se como sarcoma de partes moles e sarcomas ósseos, sendo os de partes moles quatro a cinco vezes mais comuns. A maioria dos sarcomas de partes moles ocorre nos membros. Os subtipos mais comuns nas crianças e adolescentes são o rabdomiossarcoma e o sarcoma sinovial, nos adultos o sarcoma pleomórfico indiferenciado, lipossarcoma, leiomiossarcoma, mixofibrossarcoma e sarcoma sinovial; todos de alto grau de malignidade histológica. Muitos sarcomas de partes moles são confundidos com tumores benignos de partes moles, 100 vezes mais comuns, por isso são ressecados sem o planejamento necessário, acarretando em amputação de um membro que poderia ter sido preservado. Como em todos os cânceres, o fator prognóstico mais importante é a doença metastática. Na sua vigência, a taxa de sobrevida global cai em torno de 20 a 30%. As taxas de sobrevida no geral são parecidas entre os sarcomas ósseos e de partes moles, portanto o sarcoma de partes moles, além de mais prevalente, mostra-se tão agressivo quanto os sarcomas ósseos, por isso merece muita atenção dos ortopedistas que frequentemente são a primeira linha de atendimento dos portadores destes tumores.

Synovial sarcoma is a high-grade soft tissue sarcoma that occurs primarily in the deep soft tissue of extremities, and primary colorectal synovial sarcoma is extremely rare. In this report, we present a synovial sarcoma mostly located within the mucosa of the sigmoid colon. The patient was a man in his forties with a germline deletion in the MSH2 gene. He had experienced undifferentiated pleomorphic sarcoma of the left forearm 7 years before and adenocarcinoma of the transverse colon 6 years before, both of which were successfully treated and exhibited no recurrence to date. A surveillance colonoscopy for Lynch syndrome revealed the tumor which had a submucosal tumor-like appearance with central erosion and endoscopic resection was performed. Histologically, it was composed of monotonous proliferation of spindle cells arranged in cellular fascicles; these findings were compatible with monophasic fibrous synovial sarcoma. In the tumor cells, the presence of the SS18-SSX1 fusion gene was confirmed. Protein expression of mismatch repair genes was intact in the tumor cells, indicating the association between microsatellite instability and synovial sarcoma was weak. The present case highlights a rare primary site of synovial sarcoma in a patient with Lynch syndrome.

Purpose: Nanoparticle-encapsulated drug formulations can improve responses to conventional chemotherapy by increasing drug retention within the tumor and by promoting a more effective antitumor immune response than free drug. New drug delivery modalities are needed in sarcomas because they are often chemoresistant cancers, but the rarity of sarcomas and the complexity of diverse subtypes makes it challenging to investigate novel drug formulations. Experimental Design: New drug formulations can be tested in animal models of sarcomas where the therapeutic response of different formulations can be compared using mice with identical tumor-initiating mutations. Here, using Cre/loxP and CRISPR/Cas9 techniques, we generated two distinct mouse models of Pten-deleted soft-tissue sarcoma: malignant peripheral nerve sheath tumor (MPNST) and undifferentiated pleomorphic sarcoma (UPS). We used these models to test the efficacy of chimeric polypeptide doxorubicin (CP-Dox), a nanoscale micelle formulation, in comparison with free doxorubicin. Results: The CP-Dox formulation was superior to free doxorubicin in MPNST models. However, in UPS tumors, CP-Dox did not improve survival in comparison with free doxorubicin. While CP-Dox treatment resulted in elevated intratumoral doxorubicin concentrations in MPNSTs, this increase was absent in UPS tumors. In addition, elevation of CD8+ T cells was observed exclusively in CP-Dox–treated MPNSTs, although these cells were not required for full efficacy of the CP nanoparticle–based chemotherapy. Conclusions: These results have important implications for treating sarcomas with nanoparticle-encapsulated chemotherapy by highlighting the tumor subtype–dependent nature of therapeutic response.

Highlights • Metastatic undifferentiated pleomorphic sarcoma (Malignant Fibrous Histiocytoma) is a rare entity in the visceral organs. • We report a case of a metastatic primary cardiac undifferentiated pleomorphic sarcoma which presented with a recurrent small bowel intussusception in a young man. • Laparotomy by a small midline incision performed on the same day identified an intussusception of a 15-cm section of small intestine caused by a 4-cm intraluminal metastasis from undifferentiated pleomorphic sarcoma. • Metastasis intussusception in the small intestine is a very rare condition and they are part of differential diagnosis in patient with a history of tumor who present with intussusception., Introduction Undifferentiated metastatic pleomorphic sarcoma (Malignant Fibrous Histiocytoma) is a rare entity in the small intestine, especially when the primary tumor is of cardiac origin. Case Report We report a case of metastatic intestinal undifferentiated pleomorphic sarcoma in a young patient with a history of primary cardiac tumor in the left atrium and recurrent small bowel intussusception. He was admitted for abdominal pain and constipation. A segmental resection of the small intestine was performed with side-to-side entero-enteroic anastomosis. Discussion Intussusception of the small bowel is rare in adults and it represents about 1–3% of intestinal obstructions. It mainly affects the fifth decade with a male/female ratio of 1:5 More than 60% of patients with intussusception have a tumor with 50% being malignant. This type of intussusception can be diagnosed on the CT abdominalscan. Radiological features include a typical “target” sign with overdistention of the proximal intestine and air-fluid levels, but the diagnosis of certainty is made by exploratory laparotomy. Conclusion The metastatic tumors that cause intussusception represent a rare clinical condition in adult patients, but much more common than primary ones. Metastasis to the small intestine are part of differential diagnosis in patient with a history of tumor who present with intussusception.

Background and aim Soft tissue sarcomas are exceptionally located in the elbow region. The aim of this work was to study the soft tissue sarcomas of the elbow region, their epidemiological and histopathological characteristics, anatomical features, the treatment performed, and the results obtained, in a unit of musculoskeletal tumours. Methods Retrospective review of ten patients with a mean follow-up of 65.0 ± 11.9 (range 21-132) months with soft tissue sarcomas located in the elbow region operated in our centre between 2008 and 2016. Results Mean age was 60.8 ± 6.7 years. Undifferentiated pleomorphic sarcoma was the most frequent histological diagnosis. Limb preservation surgery was performed in 90% of patients. Three patients were previously operated without following surgical oncology guidelines in another hospital, and this was statistically related to the need for more than one surgery to control the disease. R1 margin was obtained in 5 patients and R0 in another 5. Adjuvant radiotherapy was used in 7 cases. In 4 patients, subsequent surgery was performed for local or systemic control of the disease. Local recurrence occurred in 3 cases and in 5 there was distant disease. Conclusion The elbow region presents difficulty in achieving wide margins due to the proximity of neurovascular structures, adjuvant and / or neoadjuvant therapies could play an important role in performing limb preservation surgery. It would be advisable to refer these tumours to specialized units with multidisciplinary teams.

Aortic spindle cell sarcoma is a rare neoplasm with poor prognosis that is often found incidentally due to its adverse effects. CT and MRI with contrast are useful imaging modalities, but a tissue biopsy is the gold standard for diagnosis. Tumor resection is the ultimate treatment followed by chemotherapy. Our case was an adult female who presented mainly for shortness of breath, and further imaging workup demonstrated a soft tumor juxtaposed to a major vein with compressive effect. The patient’s tumor was resected, and the pathology result confirmed undifferentiated aortic sarcoma. The patient’s condition improved and she was discharged with outpatient oncology follow-up and possible treatment.

Undifferentiated pleomorphic sarcoma (UPS) is a high-grade neoplasm that is usually located in the extremities and retroperitoneum. In the past, UPS was considered the most common soft tissue sarcoma in adults; due to improvements in diagnostic techniques, most cases have been reclassified as other lineage-specific tumors. Gnathic bones are rarely affected, and the clinicopathological characteristics of this neoplasm when diagnosed in the jaw remain to be better described. In this report, we present a rare case of mandibular UPS affecting an 88-year-old female who demonstrated a painful swelling on the right side of the mandible that was accompanied by a pathological fracture. Microscopic examination revealed a pleomorphic spindle-cell neoplasm with mitotic figures and necrosis. The patient underwent surgery and adjuvant radiotherapy but experienced metastasis after 12 months of follow-up and died. Diagnosis of UPS is challenging, and oral pathologists must be aware of this entity when dealing with aggressive undifferentiated neoplasms.

Background Limited information exists on the influence of demographics, tumor characteristics, and treatment on survival in cutaneous pleomorphic sarcoma (CPS). Objective To describe incidence rates and prognostic factors affecting survival in CPS. Methods National Cancer Institute's Surveillance, Epidemiology, and End Results data (1972-2013) was analyzed for 2423 patients with CPS diagnoses. Results The age-adjusted incidence rate was 0.152 cases/100,000 person-years and was 4.5-fold higher in male than female patients. Male sex, white race, and increasing age >40 years were significantly associated with decreased overall survival. Head and neck tumors, tumors >15 mm, and tumors with grade III or IV histology were associated with significantly decreased survival. Surgical excision had a survival benefit compared with no treatment. Radiation therapy did not provide a survival benefit. Patients with localized disease had the greatest survival followed by regional and distant disease. Limitations Surveillance, Epidemiology, and End Results data might not be reflective of all CPS patients. Recurrences, restaging, or other nonmortality events over time were not tracked. Conclusion Tumor size, grade, sex, age at diagnosis, and race appear to influence survival as prognostic factors in CPS. Surgical tumor extirpation provides a survival benefit over no treatment whereas primary or adjuvant radiation does not provide a survival benefit.

A 77-year-old woman with heart failure was admitted to our hospital. Computed tomography (CT) of the chest revealed an anterior mediastinal tumor. CT-guided biopsy revealed a malignant nonepithelial tumor of unknown origin. She was not treated with chemotherapy or radiotherapy because of her poor clinical condition. She died 33 days after admission. Following autopsy, we confirmed that the mediastinal tumor had infiltrated the large blood vessels. After final histological examination, undifferentiated pleomorphic sarcoma was diagnosed. Primary mediastinal sarcomas are very rare; clinicians should be aware of their possibility because some cases may progress rapidly as evidenced in this case., EXCLI Journal; 19:Doc1161; ISSN 1611-2156

Sarcomas are malignancies arising from mesenchymal (nonepithelial) tissue and are broadly classified into sarcomas of soft tissue and bone. Soft tissue sarcomas of the head and neck are rare; they comprise

IntroductionNeurotrophic receptor tyrosine kinase fusions cause overexpression or activation of kinase and are believed to confer oncogenic potential in some non-rhabdomyosarcoma soft tissue sarcomas. TRK inhibitors have recently been shown to induce responses in these tumours though current experience with these agents is still limited.Case reportWe report a case of an adolescent with treatment-refractory non-rhabdomyosarcoma soft tissue sarcomas, carrying a novel DCTN1–NTRK1 gene fusion whose progressive disease was treated with multi-kinase and TRK inhibitors. Management and outcome: Our patient was started on pan-TRK inhibitor larotrectinib, as his disease progressed after chemotherapy, radiation therapy and surgery, based on next-generation sequencing test showing DCTN1–NTRK1 gene fusion. He responded quickly to larotrectinib with the improvement of symptoms and reduction of masses. However, this response was short-lived due to the development of acquired solvent front resistance mutation. This patient did not respond to next-generation TRK inhibitor selitrectinib and eventually succumbed to his disease.DiscussionThe initial rapid and drastic response of our patient to larotrectinib was not sustained due to the development of acquired resistance. This case emphasizes the need for upfront and periodic next-generation sequencing testing to guide treatment of patients with refractory non-rhabdomyosarcoma soft tissue sarcomas.

Background Undifferentiated pleomorphic sarcomas are one of the most common subtypes of soft tissue sarcomas. These are aggressive mesenchymal tumors and are devoid of the major known biomarkers except vimentin. Our objective was to establish and characterize a primary cell population from a mandibular UPS specimen. Methods The tumor was surgically removed from the right mandible of a 24‐year‐old male with IRB approved signed consent. Tumor was dissected, cultured ex vivo, and a cell population, MUPS‐1, were isolated from outgrowths. Gene and protein expression profiles of both the primary tumor and the derived there from cells were obtained by quantitative RT‐PCR and immunohistochemistry and included markers of epithelial, endothelial, and mesenchymal differentiation. To better define potential biomarkers, MUPS‐1 cells were additionally characterized by RNA sequencing analysis. Results Pathological analysis of primary tumor tissue revealed a sarcoma demonstrating multiple pathways of differentiation simultaneously with myxoid, fibrous, and osseous tissue. The isolated cells had a spindle cell‐like morphology, were maintained in culture for greater than 20 passages, and formed colonies in soft agar indicating tumorigenicity. The cells, similar to the primary tumor, were strongly positive for vimentin and moderately expressed alkaline phosphatase. RNA‐seq analysis revealed the tumor over‐expressed several genes compared to normal tissue, including components of the Notch signaling pathway, NOTCH3 and JAG1. Conclusions We have successfully established an undifferentiated pleomorphic sarcoma cell population, which will provide a valuable resource for studying fundamental processes and potentially serving as a platform for exploring therapeutic strategies for sarcomas.

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization and next-generation sequencing confirmed that a significant fraction of MFS and UPS patient samples (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray analysis identified a correlation between absent Rb and p53 expression and positive expression of Skp2. Downregulation of Skp2 or treatment with the Skp2-specific inhibitor C1 revealed that Skp2 drives proliferation of patient-derived MFS/UPS cell lines deficient in both Rb and p53 by degrading p21 and p27. Inhibition of Skp2 using the neddylation-activating enzyme inhibitor pevonedistat decreased growth of Rb/p53-negative patient-derived cell lines and mouse xenografts. These results demonstrate that loss of both Rb and p53 renders MFS and UPS dependent on Skp2, which can be therapeutically exploited and could provide the basis for promising novel systemic therapies for MFS and UPS. Significance: Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies. See related commentary by Lambert and Jones, p. 2437

Introduction Prostate sarcoma is an extremely rare disease with a poor prognosis. Undifferentiated pleomorphic sarcoma has never been described in the prostate.Case presentation: A 27-year-old man complained of frequent urination and dysuria for several years. Various examinations were suggestive of prostate sarcoma. The pathological diagnosis was confirmed as prostate sarcoma via ultrasound-guided transrectal needle biopsy. Because the location of the tumor in the prostate was confirmed by magnetic resonance imaging, we performed robot-assisted radical prostatectomy. The final pathological diagnosis was undifferentiated pleomorphic sarcoma. Local recurrence occurred at the front of the rectum 2 months after surgery. Although chemotherapy and radiotherapy were initially effective, he died 18 months after surgery. Conclusion Undifferentiated pleomorphic sarcoma of the prostate is believed to have a poor prognosis. When selecting the surgical procedure, functionality should be considered for individual cases with complete resection.

Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in several solid tumor types and hematological malignancies. Data related to their activity in soft-tissue sarcomas (STS) are scarce.We performed a pooled analysis of clinical trials investigating a PD1 or PD-L1 antagonist in patients with advanced STS. Three hundred eighty-four patients were included in the pooled analysis; of those, 153 (39.8%) received a PD1/PD-L1 antagonist as a single agent. In patients treated with anti-PD1/PDL1 as a single agent, the overall response rate (ORR) and non-progression rate (NPR) were 15.1% and 58.5% respectively. In patients treated with a combination regimen, the ORR and NPR were 13.4% and 55.8% respectively. Analysis by histological subtype revealed that patients with alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma exhibited the highest response rates and leiomyosarcoma the lowest. PD-L1 expression rate was low and inconsistently associated with objective response.PD-1/PD-L1 antagonists have limited activity in unselected STS. Future studies should implement histology and immune-based stratification of STS in their design as well as sequential blood and tissue sampling to better understand the mechanisms of resistance and response given sarcomas inherent heterogeneity.

Background Reports of metastatic sarcoma to the pancreas are limited. We reviewed the clinicopathologic characteristics of such cases. Methods We reviewed 124 cases of metastatic tumors to the pancreas diagnosed at Asan Medical Center between 2000 and 2017. Results Metastatic tumors to the pancreas consisted of 111 carcinomas (89.5%), 12 sarcomas (9.6%), and one melanoma (0.8%). Primary sarcoma sites were bone (n = 4); brain, lung, and soft tissue (n = 2 for each); and the uterus and pulmonary vein (n = 1 for each). Pathologically, the 12 sarcomas comprised 2 World Health Organization grade III solitary fibrous tumors/hemangiopericytomas, and one case each of synovial sarcoma, malignant solitary fibrous tumor, undifferentiated pleomorphic sarcoma, osteosarcoma, mesenchymal chondrosarcoma, intimal sarcoma, myxofibrosarcoma, myxoid liposarcoma, rhabdomyosarcoma, subtype uncertain, and high-grade spindle-cell sarcoma of uncertain type. The median interval between primary cancer diagnosis and pancreatic metastasis was 28.5 months. One case manifested as a solitary pancreatic osteosarcoma metastasis 15 months prior to detection of osteosarcoma in the femur and was initially misdiagnosed as sarcomatoid carcinoma of the pancreas. Conclusions The metastatic sarcoma should remain a differential diagnosis when spindle-cell malignancy is found in the pancreas, even for solitary lesions or in patients without prior history.

Background and aim Cardiac sarcoma is a rare condition and may mimic atrial myxoma. We present a case report of a man with a cardiac sarcoma. Method Case report presentation. Results A 68-year-old man with a permanent pacemaker presented to us with a 4-month history of breathlessness. Echocardiography revealed a large right atrial mass adherent to the pacemaker lead and a provisional diagnosis of atrial myxoma was made based on echocardiographic appearance. A 60 x 30 x 30 mm irregular lobulated tumour was surgically resected from the right atrium. Upon histopathologic examination, the tumour was consistent with an undifferentiated pleomorphic sarcoma. Conclusion Cardiac sarcomas have an extremely poor prognosis and more unfortunately this man developed a surgical site infection and died of acute mediastinitis. We discuss the presentation, imaging and current surgical approaches to cardiac sarcoma. Curative treatment is currently limited for this disease.

Undifferentiated pleomorphic sarcoma (UPS) was previously known as malignant fibrous histiocytoma (MFH). This sarcoma occurs preferentially in the extremities and retroperitoneal space; primary pulmonary UPS/MFH is rare. We report a 52-year-old woman referred to our hospital with dyspnea and severe cough. Chest computed tomography (CT) revealed a pulmonary mass in the left upper lobe and pleural effusion. Cytology of the effusion showed no malignancy; however, the tumor increased rapidly in size, and the patient’s respiratory symptoms worsened. The tumor occupied almost all of the left upper lobe and involved the adjacent pericardium. She underwent left upper lobectomy with pericardial resection and reconstruction. Postoperative pathology of the resected specimen showed undifferentiated pulmonary sarcoma, pT4N0M1a stage IV A, and genetic analyses revealed the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. The patient’s dyspnea recurred 1 month postoperatively, and CT showed marked pleural effusion. An 18F-fluorodeoxyglucose positron emission tomography demonstrated abnormal diffuse accumulation of 18F-fluorodeoxyglucose in the left pleural cavity. We initiated five cycles of chemotherapy with doxorubicin and ifosfamide, and the patient has been well without recurrence for 24 months after multidisciplinary treatment with surgery followed by systemic combination chemotherapy. We successfully treated our patient with primary pulmonary UPS/MFH using a multidisciplinary approach, even though this sarcoma carries a poor prognosis and is insensitive to both chemotherapy and radiotherapy.

STAT6 stain has proved to be a good surrogate marker for the genetic alteration (NAB2-STAT6 gene fusion) in solitary fibrous tumor (SFT). This study aims to validate the use of STAT6 rabbit monoclonal antibody in differentiating SFT from its histologic mimics. Forty-five cases of SFT and 110 cases from 9 other spindle cell tumors were collected for STAT6 immunostaining. Positive nuclear STAT6 staining was present in all 45 SFT cases (100% sensitivity). No nuclear staining was identified in other spindle cell neoplasms (0/13, dedifferentiated liposarcoma; 0/17, synovial sarcoma; 0/16, malignant peripheral nerve sheath tumors; 0/25, undifferentiated pleomorphic sarcoma; 0/10, dermatofibrosarcoma protuberans; 0/9, low-grade fibromyxoid sarcoma; 0/6, angiofibroma; 0/5, deep fibromatosis; 0/9, gastrointestinal tumor). The STAT6 staining in SFT was usually diffuse (5+ in 19 cases; 4+ in 17 cases) and strong (40 cases). Monoclonal STAT6 stain is highly sensitive and specific for SFTs and particularly useful in the diagnosis of difficult SFT cases.

Context.—Undifferentiated pleomorphic sarcoma (UPS) of soft tissue is defined as a sarcoma with no recognizable line of differentiation. During the past few decades, advances in ancillary studies and review of prior UPS diagnoses have narrowed the category of UPS by excluding more-specific malignancies. However, few of those studies have specifically targeted pleomorphic hematolymphoid neoplasms.Objective.—To determine what fraction of UPS cases are misclassified pleomorphic hematolymphoid neoplasms, such as anaplastic large cell lymphoma, diffuse large B-cell lymphoma, histiocytic sarcoma (HS), myeloid sarcoma, and follicular dendritic cell sarcoma.Design.—Sixty-one UPS cases were screened by tissue microarray and an immunostain panel with subsequent analysis on whole block sections for suspicious cases.Results.—Five of 61 tumors (8%) were suggestive of HS based on the screening panel and were further evaluated with additional immunostains (PU.1, CD45, CD163) using whole sections. The 5 candidate HS cases were only focally positive for at most one stain with most staining in smaller, less-pleomorphic cells. Ultimately, no UPS met criteria for anaplastic large cell lymphoma, diffuse large B-cell lymphoma, myeloid sarcoma, follicular dendritic cell sarcoma, or HS.Conclusions.—Our results suggest that a UPS of somatic soft tissue is unlikely to represent a misclassified hematopoietic malignancy. Exclusion of HS is most challenging, but immunostaining for PU.1, a nuclear transcription factor, may be easier to interpret in this context.

BACKGROUND AND OBJECTIVES Malignant fibrous histiocytoma (MFH) of bone, now known as undifferentiated pleomorphic sarcoma of bone, is a rare neoplasm that accounts for less than 2% of all primary malignant bone tumors. The objective of the current study was to evaluate prognosis and survival for MFH of bone. METHODS The 2004 to 2016 National Cancer Database was queried to identify patients with a primary MFH of bone. Kaplan-Meier survival and Cox regression analyses were used to analyze overall survival and risk factors associated with overall mortality. RESULTS The overall 5-year and 10-year survival rates were 38.3% and 30.5%, respectively. Increasing stage and metastatic disease at presentation were associated with poor overall survival (P