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Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS. [ABSTRACT FROM AUTHOR]

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30‐year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA‐sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis‐free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune‐depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic cardiac sarcomas are extremely rare, highly malignant mesenchymal cardiac neoplasms typically presenting in the sixth decade of life. Here, we have reported a rare case of undifferentiated pleomorphic cardiac sarcoma presenting with dyspnea in a young male. On further evaluations, a large, ill-defined, multilobulated mass was observed in left atrium (LA) with encasement of left circumflex artery, attachment to mitral valve annulus, and invasion through LA wall and pericardium.

A 72 year-old man was referred to our hospital for a detailed examination of a recurrent rectal polyp. He had past histories of surgery and radiation therapy for prostate cancer at the age of 66 and endoscopic excision of a rectal polyp at the age of 70. Colonoscopy revealed a semi-pedunculated lesion surrounded by friable mucosa, which was positive under positron-emission tomography-computed tomography. Histopathological examination of the endoscopically excised polyp revealed proliferation of atypical cells, characterized by strong pleomorphic or spindle morphology, which was immunohistochemically compatible with undifferentiated pleomorphic sarcoma. We diagnosed this case as sarcoma presumably associated with radiation proctitis. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) formerly known as malignant fibrous histiocytoma is a high-grade aggressive soft-tissue sarcoma. UPS is a soft-tissue sarcoma without a definable line of differentiation. Men between the ages of 50 and 70 are frequently affected by it. In adults, the lower extremity and retroperitoneum are the most affected sites, while the paranasal sinus is affected in younger individuals. A 16-year-old male patient reported with swelling in his left posterior maxilla for 2 months. The swelling began quickly and gradually expanded to its current size. On examination, an ill-defined, deep-seated exophytic, ovoid growth was seen on the left maxillary alveolus. Histopathological findings indicated UPS. UPS is a rare malignancy that typically originates in the body’s soft tissues. The treatment for UPS is determined on the site of the cancer, but it typically includes surgery and radiation.

Undifferentiated pleomorphic sarcoma (UPS) is a rare type of tumor, and UPS originating in the adrenal gland is even rarer. Up to now, there have been no reports in English literature of UPS originating from the adrenal gland. This case report presents a 44-year-old female patient with UPS of the adrenal gland, who has shown no signs of recurrence or metastasis half a year after undergoing resection of a left adrenal tumor. A retrospective analysis of the patient’s diagnosis and treatment process is conducted, with the aim of providing a reference for the diagnosis and treatment of adrenal UPS.

Undifferentiated pleomorphic sarcoma (UPS) formerly known as malignant fibrous histiocytoma is a high-grade aggressive soft-tissue sarcoma. UPS is a soft-tissue sarcoma without a definable line of differentiation. Men between the ages of 50 and 70 are frequently affected by it. In adults, the lower extremity and retroperitoneum are the most affected sites, while the paranasal sinus is affected in younger individuals. A 16-year-old male patient reported with swelling in his left posterior maxilla for 2 months. The swelling began quickly and gradually expanded to its current size. On examination, an ill-defined, deepseated exophytic, ovoid growth was seen on the left maxillary alveolus. Histopathological findings indicated UPS. UPS is a rare malignancy that typically originates in the body’s soft tissues. The treatment for UPS is determined on the site of the cancer, but it typically includes surgery and radiation. [ABSTRACT FROM AUTHOR]

We report a case of a 54-year-old female who presents with a gradually expanding mass at the right lateral malleolus. The diagnosis of undifferentiated pleomorphic sarcoma was made after a histopathological examination of the mass following a wide tumor excision. The defected soft tissue area was reconstructed using a local flap, reverse sural artery flap. Following the surgical management, multiple radiotherapy sessions were completed. The patient's follow-up result showed no signs of local recurrence or metastasis, and the wound was well-healed with no complications other than paresthesia in a small area at the posterolateral aspect of the ankle under the lateral malleolus. This case represents a rare form of malignant neoplasm and emphasizes the effectiveness and safety of the reverse sural artery flap reconstruction technique, especially in places where microsurgery is unavailable or when the patient's status does not allow for prolonged anesthesia. [ABSTRACT FROM AUTHOR]

Primary cardiac sarcomas are rare and sometimes difficult to discern from benign tumors and intracardiac thrombi. We describe the ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a case of left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation, presenting with severe mitral regurgitation and pulmonary hypertension. The tumor presented as a broad-base mass protruding into the cardiac lumen, accompanied by punctate calcification-like high attenuation on CT. 18F-FDG PET/CT revealed high 18F-FDG uptake in the mass. Severe mitral regurgitation, a rare manifestation, was caused by tumor extension to the mitral valve leaflets and subvalvular tissue, which was best visualized on transesophageal echocardiography. This case illustrates the importance of multimodal diagnostic approaches including 18F-FDG PET/CT, which can facilitate accurate diagnosis and timely initiation of curative treatment, ultimately saving the patient's life. Firstly, cardiac sarcomas, particularly those with calcification/ossification, are rare and may mimic benign tumors and chronic intracardiac thrombi. Multimodal imaging approach, including 18F-FDG PET/CT, may be helpful in the accurate diagnosis of malignancies. Second, left atrial undifferentiated pleomorphic sarcoma has the potential to extensively spread along the endocardium and can extend to involve the valve leaflets, resulting in mitral regurgitation and pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Background Cardiac masses encompass a wide differential including primary and secondary malignancies and can present with a variety of symptoms, many of which are non-specific. Early identification and classification are important, particularly for cardiac malignancies such as sarcomas as these are aggressive tumours with exceptionally poor prognoses when metastases are present at diagnosis. Case summary We report two cases of patients who presented with dyspnoea and were diagnosed with cardiac sarcomas; the former a primary sarcoma (undifferentiated pleomorphic subtype) and the latter a secondary sarcoma (round cell myxoid liposarcoma) that serve as comparisons for presentation and management of different types of this disease. Computed Tomography (CT) and echocardiography imaging findings are demonstrated showing the typical location and morphology of each subtype. Discussion Cardiac sarcomas are the most common primary cardiac malignancy, of which undifferentiated pleomorphic sarcoma is a common subtype. Undifferentiated pleomorphic sarcomas are aggressive, have a tendency to arise in the left atrium, and can appear similar to benign cardiac masses. Round cell myxoid liposarcomas by contrast are rare causes of secondary cardiac malignancies, metastasizing to the heart from soft tissues. Both diagnoses carry poor prognoses and although rare, are important to recognize as timely intervention with surgery, radiotherapy, and consideration of chemotherapy is key to maximizing survival. [ABSTRACT FROM AUTHOR]

Malignant transformation of chronic burn scars are usually toward cutaneous lineages, including squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Sarcomas are less common. Undifferentiated pleomorphic sarcoma(UPS) is a subtype of soft tissue sarcoma with storiform-pleomorphic cells of uncertain origin, and has sparingly been reported to arise from burn scars. The majority are localized lesions probably due to the spatial distance of mesenchymal cells from the epithelium. The authors describe a rare case of UPS of the chronic burn scar of his knee with ipsilateral femoral and external iliac lymph node metastasis. [ABSTRACT FROM AUTHOR]

A 52-year-old male had pain in the right back and right hypochondrium, and an abdominal CT scan revealed a 49-mm tumor in the right upper perirenal space. Additional MRI and PET-CT suggested that the tumor may be a primary adrenal carcinoma and could invade the liver and diaphragmatic leg. The tumor was completely removed by laparotomy and histopathologically diagnosed as retroperitoneal primary undifferentiated pleomorphic sarcoma. The patient has remained recurrence-free for 1.5 years after the surgery.

Undifferentiated pleomorphic sarcoma is an extremely rare malignant thyroid tumor. Thyroid sarcoma differs from common malignant thyroid tumors, such as thyroid follicular cell carcinoma. It is usually highly malignant, progresses rapidly, and is prone to remote metastasis. Currently, there is no standard protocol for the treatment of thyroid sarcomas, and most treatment effects are unsatisfactory. Argon-helium cryoablation is an important method of local treatment that is widely used in patients with unresectable advanced tumors. However, owing to the low incidence of thyroid sarcomas, there are no relevant literature reports on the treatment of thyroid sarcomas using cryoablation in China. This study reports the case of a patient with undifferentiated pleomorphic sarcoma of the thyroid gland who was treated with argon-helium cryoablation, and the immediate outcome was good. Based on a review of relevant literature, we discussed the effectiveness and safety of argon-helium cryoablation treatment to provide clinical guidance and references for the treatment of patients with thyroid sarcoma.

Primary laryngeal sarcomas are rare. Their nomenclature and classification are similar to soft tissue counterparts; however, there are notable differences between clinical presentation, behavior, treatment, and follow-up. There is sparse information regarding the clinical features, biologic behavior, and treatment modalities of laryngeal sarcomas. To increase our understanding about these tumors, we describe herein an additional series of four cases of different pathologic types of laryngeal sarcomas, including low-grade chondrosarcoma, leiomyosarcoma, well-differentiated liposarcoma, and undifferentiated pleomorphic sarcoma. Our main aim is to upsurge awareness about the morphologic variations of laryngeal sarcomas, to avoid potential pitfalls during histopathologic examination. It is essential to ensure that correct diagnosis, subclassification, and grading are achieved for proper guidance of treatment and clinical follow-up at multidisciplinary team meetings.

Abstract Background Undifferentiated pleomorphic sarcoma is an uncommon sarcoma and its presence in the spleen is even rarer, with only a handful of cases reported in English literature. It is typically only diagnosed following histological analysis. Its rarity also means that there is little consensus over ideal management. Case presentation This report presents a case of a 40-year-old Caucasian male who was found to have a splenic mass after presenting with non-specific abdominal pain and generalized malaise. Numerous imaging modalities were used which demonstrated a large partially solid and partially cystic lesion in spleen with no evidence of metastasis. As core biopsies were undiagnostic, he was planned for a diagnostic and therapeutic splenectomy. However, despite magnetic resonance imaging 11 days prior to his operation showed no evidence of liver metastasis, a massive splenic tumour with hepatic metastases was identified intraoperatively. An open splenectomy, distal pancreatectomy and liver metastasectomy was hence carried out. Histological analysis confirmed liver metastasis secondary to a splenic undifferentiated pleomorphic sarcoma. The patient recovered well and was discharged home. He presented again three weeks after his operation with lower back pain, abdominal pain and fever. Computed tomography demonstrated extensive recurrent disease burden in the peritoneum and liver. The patient passed away a month after surgery. Conclusion Splenic undifferentiated pleomorphic sarcoma is a rare tumour which may pose a significant diagnostic challenge on both clinical and histopathological grounds. Following diagnosis and treatment, its aggressive nature often results in a poor prognosis. Current literature fails to delineate any superior management strategy to increase survival.

Background: Rare primary malignant bone sarcomas (RPMBS) account for 5%–10% of primary high‐grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO‐B.O.S.S) is presented. Methods: Inclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high‐grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m2, ifosfamide 9 g/m2, and cisplatin 90 mg/m2; postoperative methotrexate 8 g/m2 was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan–Meier curves, log‐rank tests, and univariate Cox regression models were used. Results: In total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40–66 years), and 67 patients were men. Eighty‐eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty‐three of 113 tumors were located in the extremities. Ninety‐five of 113 patients presented with no evidence of metastases. After a median follow‐up of 6.8 years (interquartile range [IQR], 3.5–9.8 years), the 5‐year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%–77.5%), and it was 71.7% (IQR, 58.1%–81.6%) for patients with UPS and 54.9% (IQR, 29.5%–74.5%) for patients with leiomyosarcoma. Grade III–IV hematologic toxicity was reported in 81% patients; 23% had grade II–III neurotoxicity, and 37.5% had grade I–II nephrotoxicity. Five‐year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities. Conclusions: The survival of patients who had RPMBS in the current series was similar to that of age‐matched patients who had high‐grade osteosarcoma treated according to the same protocol. An osteosarcoma‐like chemotherapy may be proposed in patients who have RPMBS. Rare and ultra‐rare primary malignant bone sarcomas, namely, undifferentiated pleomorphic sarcomas, leiomyosarcomas, fibrosarcomas, and angiosarcomas, are usually diagnosed in adult and elderly patients and represent a treatment challenge. This study demonstrates that a clinical trial might be run within a European network in the setting of rare cancers and that a combination of surgery and age‐adjusted osteosarcoma regimen might be proposed for these patients, possibly representing a benchmark for future histology‐driven approaches. [ABSTRACT FROM AUTHOR]

Background: To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). Methods: All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005‐2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan–Meier curves for overall survival and disease‐free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. Results: Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT‐RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p =.09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT‐RT, whereas RECIST response was. Conclusion: In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT. A correlation between response and outcome was found in patients with myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities or trunk wall who received preoperative therapies. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is a malignant soft tissue tumor that occurs primarily in the extremities and very rarely originates from the rectum. Here we report a 20-year-old male who presented with features of large gut obstruction. On digital rectal examination, a proliferative growth was felt at 4 cm from anal verge occupying whole of rectal lumen causing luminal narrowing. Computed tomography (CT) abdomen/pelvis revealed dilated colon secondary to a large, asymmetrical, lobulated, polypoidal enhancing lesion in rectum starting just above anal verge occupying and distending the whole rectum. Exploratory laparotomy with assessment of growth and sigmoid loop colostomy was performed under general anesthesia. Operative findings were a rectosigmoid growth with ascites. However, there were no distant metastasis in abdominal cavity. Proctoscopic biopsy was taken and came out to be pleomorphic sarcoma (undifferentiated) with positive vimentin and KI 67 on immunohistochemistry. Ultra-low anterior resection of tumor with closure of anal canal and end colostomy was performed. Histopathology of specimen confirmed undifferentiated pleomorphic sarcoma invading serosa (pT2a) with all 22 lymph nodes negative for tumor (N0). Patient is doing well after 14 months of surgery and has received 30 cycles (60 Gy) of radiotherapy and four cycles of chemotherapy. Undifferentiated pleomorphic sarcoma in the rectum is a rare malignant tumor with a poor prognosis. The main treatment for undifferentiated pleomorphic sarcoma is early complete resection. Adjuvant radiotherapy or chemotherapy can be attempted; however, till date, no data is available to support their role. [ABSTRACT FROM AUTHOR]

Background: Undifferentiated pleomorphic sarcoma is an uncommon sarcoma and its presence in the spleen is even rarer, with only a handful of cases reported in English literature. It is typically only diagnosed following histological analysis. Its rarity also means that there is little consensus over ideal management. Case presentation: This report presents a case of a 40-year-old Caucasian male who was found to have a splenic mass after presenting with non-specific abdominal pain and generalized malaise. Numerous imaging modalities were used which demonstrated a large partially solid and partially cystic lesion in spleen with no evidence of metastasis. As core biopsies were undiagnostic, he was planned for a diagnostic and therapeutic splenectomy. However, despite magnetic resonance imaging 11 days prior to his operation showed no evidence of liver metastasis, a massive splenic tumour with hepatic metastases was identified intraoperatively. An open splenectomy, distal pancreatectomy and liver metastasectomy was hence carried out. Histological analysis confirmed liver metastasis secondary to a splenic undifferentiated pleomorphic sarcoma. The patient recovered well and was discharged home. He presented again three weeks after his operation with lower back pain, abdominal pain and fever. Computed tomography demonstrated extensive recurrent disease burden in the peritoneum and liver. The patient passed away a month after surgery. Conclusion: Splenic undifferentiated pleomorphic sarcoma is a rare tumour which may pose a significant diagnostic challenge on both clinical and histopathological grounds. Following diagnosis and treatment, its aggressive nature often results in a poor prognosis. Current literature fails to delineate any superior management strategy to increase survival. [ABSTRACT FROM AUTHOR]

Treatment of highly malignant soft tissue sarcomas (STSs) requires multicomponent therapy including surgery, radiotherapy, and chemotherapy. Despite the advancements in targeted cancer therapies, cytostatic drug combinations remain the gold standard for STS chemotherapy. The lack of algorithms for personalized selection of STS chemotherapy leads to unhelpful treatment of chemoresistant tumors, causing severe side effects in patients. The goal of our study is to assess the applicability of in vitro chemosensitivity/resistance assays (CSRAs) in predicting STS chemoresistance. Primary cell cultures were obtained from 148 surgery samples using enzymatic and mechanical disaggregation. CSRA was performed using resazurin-based metabolic activity measurement in cells cultured with doxorubicin, ifosfamide, their combination and docetaxel, gemcitabine, and also their combination for 7 days. Both the clinical data of patients and the CSRA results demonstrated a higher resistance of some cancer histotypes to specific drugs and their combinations. The correlation between the CSRA results for doxorubicin and ifosfamide and clinical responses to the combination chemotherapy with these drugs was demonstrated via Spearman rank order correlation. Statistically significant differences in recurrence-free survival were also shown for the groups of patients formed, according to the CSRA results. Thus, CSRAs may help both practicing physicians to avoid harmful and useless treatment, and researchers to study new resistance markers and to develop new STS drugs. [ABSTRACT FROM AUTHOR]

MYC amplifications have been frequently detected in radiation (RT)‐associated angiosarcomas (ASs) by low‐resolution molecular methods. However, large‐scale next‐generation sequencing (NGS) studies to investigate the genomic landscape of RT‐AS are scarce, particularly compared with other RT‐associated sarcomas. We performed a detailed comparative genomic investigation of RT‐AS versus other RT‐associated histotypes, as well as sporadic sarcomas with similar histologies. Our institutional targeted DNA‐NGS assay database was searched for RT‐associated sarcomas. Clinical outcome data, pathologic diagnosis, and the types and frequencies of genomic alterations, including single nucleotide variants (SNVs) and copy number alterations (CNAs), were analyzed. The cohort consisted of 82 patients, 68 (83%) females and 14 (17%) males, aged 37–88 (mean 64) years. Forty‐four RT‐ASs (38 from breast) and 38 RT sarcomas of other histologies, including 12 malignant peripheral nerve sheath tumors (RT‐MPNSTs), 14 undifferentiated pleomorphic sarcomas (RT‐UPSs), and 12 osteosarcomas (RT‐OSs), were included. Median time intervals from radiation to initial diagnosis in RT‐AS (8.0 years) were significantly lower than those in RT‐MPNST and RT‐UPS (12.5 and 18.5 years), respectively. Each RT‐sarcoma histotype harbored distinct mutations and CNAs. RT‐associated AS had more frequent MYC, FLT4, CRKL, HRAS, and KMT2D alterations than sporadic AS (enriched in TP53, KDR, ATM, ATRX), whereas the mutational landscapes of MPNST, UPS, and OS were similar in both RT and non‐RT settings. CDKN2A/B deletions and TP53 alterations were infrequent in RT‐AS compared with other RT sarcomas. Among RT sarcomas, RT‐AS harbored the lowest fraction of genome altered (FGA), while RT‐MPNST showed the highest FGA. RT‐AS had the lowest insertion:SNV and deletion:SNV ratios, while RT‐UPS had the highest. The predominant mutational signatures were associated with errors in DNA repair and replication. In conclusion, RT‐AS has a distinct genomic landscape compared with other RT sarcomas and sporadic AS. Potential molecular targets for precision medicine may be histotype‐dependent. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Purpose: Undifferentiated pleomorphic sarcoma (UPS) is associated with poor prognosis. Recently, signal regulatory protein alpha (SIRPα), which is the immune checkpoint of macrophages, and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), which is the immune checkpoint of T cells and natural killer cells, have been considered as potential targets for cancer immunotherapy. This study aimed to assess the value of SIRPα and TIGIT as prognostic factors of UPS. Materials and methods: The cBio Cancer Genomics Portal was used to analyze mRNA expression data of 50 UPS cases in the Cancer Genome Atlas. We retrieved 49 UPS cases and performed immunohistochemistry (IHC) to detect programmed death ligand 1 (PD-L1), SIRPα, CD68, CD163, TIGIT, CD155, and CD8. Results: SIRPα was positively associated with CD163 (Pearson's r = 0.51, p = 0.0002) as per open access data and IHC of the cohort (p = 0.002), which revealed that SIRPα-positive macrophage infiltration was higher in UPS cells with ≥ 1% PD-L1 expression than that in UPS cells with < 1% PD-L1 expression (p = 0.047). TIGIT was positively correlated with PD-L1 (r = 0.54, p < 0.0001) and CD8A (r = 0.98, p < 0.0001). In 35 of 49 cases, IHC revealed high levels of TIGIT expression on tumor cells. Furthermore, TIGIT expression on tumor cells was negatively correlated with CD155-positive (p = 0.0144) and CD8-positive (p = 0.0487) cell infiltration. Survival analysis showed that the high degree of SIRPα-positive macrophage infiltration was associated with poor overall survival and metastasis (p < 0.0001, p = 0.0006, respectively). Conclusion: SIRPα-positive macrophages infiltrated UPS cells, which predicted poor prognosis. High TIGIT expression on tumor cells was associated with decreased levels of tumor-infiltrating macrophages in UPS. [ABSTRACT FROM AUTHOR]

Positive regulatory domain member (PRDM) proteins play a critical role in the transmission of signals that control cell proliferation and differentiation, and neoplastic transformation. Positive regulatory domain member 10 (tristanin) is a poorly studied member of PRDM protein family. Gene fusion transcripts containing PRDM10 were recently identified in low-grade undifferentiated pleomorphic sarcomas (UPS), and associated with pleomorphic morphology and low mitotic index. The aim of this study was to investigate the immunohistochemical staining of PRDM10 in a larger sample of soft tissue sarcomas. Therefore, the study included 118 soft tissue sarcomas from different classes, and PRDM10 antibody was applied to all of them. Immuno-histochemically, staining was observed in 22 (19%) cases, while 96 (81%) showed no staining. When PRDM10 expression was compared with clinico-pathological features, there was a statistically significant correlation between PRDM10 expression and myxoid changes, multi-nucleated giant cells, and surgical margin (p = 0.017, p = 0.034, p = 0.032, respectively). No statistically significant association was found between PRDM10 expression and other parameters. Based on the obtained data, it can be said that PRDM10-positive-stained tumors (tumors with PDRM10 expression) are mostly myxoid, containing multi-nucleated giant cells, and can be removed with well-circumscribed margins.

Abstract Background Undifferentiated pleomorphic sarcoma (UPS) in the esophagus is extremely rare. Therefore, there are few reports of UPS in the esophagus (UPSE). We present a case of UPSE after multiple cancer treatments. Case presentation A 73-year-old man with a history of cancer treatment, including distal gastrectomy, transverse colectomy, and chemoradiotherapy, was diagnosed with an elevated lesion such as a submucosal tumor in the lower esophagus by regular endoscopy. A boring biopsy was performed, and the specimen showed features of sarcoma. The patient underwent a partial esophagectomy without lymph node dissection. Histopathological findings confirmed an undifferentiated pleomorphic sarcoma. Adjuvant therapy was not administered, and the patient survived without recurrence 1 year after surgery. Conclusions Currently, complete resection is the only treatment option for UPSE. An optimal treatment strategy using chemotherapy or radiotherapy should be established.

Abstract Background Undifferentiated pleomorphic sarcoma (UPS) is considered one of the most common types of soft tissue sarcoma (STS). Current studies have shown that the prognosis of UPS is related to some of its clinical characteristics, but no survival prediction model for the overall survival (OS) of UPS patients has been reported. The purpose of this study is to construct and validate a nomogram for predicting OS in UPS patients at 3, 5 years after the diagnosis. Methods According to the inclusion and exclusion criteria, 1079 patients with UPS were screened from the SEER database and randomly divided into the training cohort (n = 755) and the validation cohort (n = 324). Patient demographic and clinicopathological characteristics were first described, and the correlation between the two groups was compared, using the Kaplan–Meier method and Cox regression analysis to determine independent prognostic factors. Based on the identified independent prognostic factors, a nomogram for OS in UPS patients was established using R language. The nomogram’s performance was then validated using multiple indicators, including the area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA). Results Both the C-index of the OS nomogram in the training cohort and the validation cohort were greater than 0 .75, and both the values of AUC were greater than 0.78. These four values were higher than their corresponding values in the TNM staging system, respectively. The calibration curves of the Nomogram prediction model and the TNM staging system were well fitted with the 45° line. Decision curve analysis showed that both the nomogram model and the TNM staging system had clinical net benefits over a wide range of threshold probabilities, and the nomogram had higher clinical net benefits than the TNM staging system as a whole. Conclusion With good discrimination, accuracy, and clinical practicability, the nomogram can individualize the prediction of 3-year and 5-year OS in patients with UPS, which can provide a reference for clinicians and patients to make better clinical decisions.

Surgical principles in sarcoma are a wide resection, including surrounding tissues and maximisation of the function of the affected limb. Rotator cuff muscles are biomechanically important structures acting as a force couple in movement of the shoulder joint. Thus, conjoined tendons are essential for motion capability in absence of the supraspinatus muscle. This article reports a case of a large undifferentiated pleomorphic sarcoma (UPS) at the suprascapular fossa in a 78-year-old man. After diagnosis of sarcoma, he underwent wide, en-bloc excision preserving conjoined tendons of rotator cuff muscles and low-dose radiation therapy for surveillance of local recurrence. All dissection was performed to avoid contaminating the tumour and involved the whole supraspinatus except the conjoined tendons. We report a case of UPS at the suprascapular fossa, which showed a good result after a wide resection preserving conjoined tendons of rotator cuff muscles. Level of Evidence: Level V (Therapeutic) [ABSTRACT FROM AUTHOR]

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) can be considered as a spectrum of the same disease entity, representing one of the most common adult soft tissue sarcoma (STS) of the extremities. While MFS is rarely metastasizing, it shows an extremely high rate of multiple frequent local recurrences (50–60% of cases). On the other hand, UPS is an aggressive sarcoma prone to distant recurrence, which is correlated to a poor prognosis. Differential diagnosis is challenging due to their heterogeneous morphology, with UPS remaining a diagnosis of exclusion for sarcomas with unknown differentiation lineage. Moreover, both lesions suffer from the unavailability of diagnostic and prognostic biomarkers. In this context, a genomic approach combined with pharmacological profiling could allow the identification of new predictive biomarkers that may be exploited for differential diagnosis, prognosis and targeted therapy, with the aim to improve the management of STS patients. RNA-Seq analysis identified the up-regulation of MMP13 and WNT7B in UPS and the up-regulation of AKR1C2, AKR1C3, BMP7, and SGCG in MFS, which were confirmed by in silico analyses. Moreover, we identified the down-regulation of immunoglobulin genes in patient-derived primary cultures that responded to anthracycline treatment compared to non-responder cultures. Globally, the obtained data corroborated the clinical observation of UPS as an histotype refractory to chemotherapy and the key role of the immune system in determining chemosensitivity of these lesions. Moreover, our results confirmed the validity of genomic approaches for the identification of predictive biomarkers in poorly characterized neoplasms as well as the robustness of our patient-derived primary culture models in recapitulating the chemosensitivity features of STS. Taken as a whole, this body of evidence may pave the way toward an improvement of the prognosis of these rare diseases through a treatment modulation driven by a biomarker-based patient stratification. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive soft tissue tumor with a high degree of malignancy and rapid progression, usually occurring in the extremities, retroperitoneum, and abdomen, whereas it rarely arises in the mediastinum, and is treated mainly by surgical resection. The prognosis of patients with advanced sarcoma is poor, and doxorubicin monotherapy is the standard first-line chemotherapy for most advanced soft tissue sarcomas (STS), but the prognosis is generally unsatisfactory. Immune checkpoint inhibitors (ICIs) have been established as therapies for many solid cancers in recent years; however, evidence on the efficacy of ICIs in undifferentiated sarcoma is scarce, mostly consisting of small studies, and no ICIs are currently approved for use in sarcomas. We report a case of a middle-aged man with primary mediastinal UPS with high PD-L1 expression (TPS was approximately 80%) and TLS positive. The patient was treated with sequential tislelizumab monotherapy maintenance after 6 cycles of tislelizumab combined with epirubicin, efficacy evaluation was partial remission (PR), progression-free survival (PFS) was 8.5 months, and grade 1 fatigue was identified as an adverse event. [ABSTRACT FROM AUTHOR]

Purpose: Primary breast sarcomas are extraordinary rare, in particular undifferentiated pleomorphic sarcoma (UPS). UPS with neoplastic fever (UPS-NF) of the breast has not been reported yet. Here, we present an extended UPS-NF of the breast including its comprehensive molecular workup. Methods: A 58-year-old female presented with general malaise, fever spikes, weight loss, and a massively swollen left breast. C-reactive protein and blood leucocytes were significantly increased. However, repeated blood cultures and smears were all sterile. Histopathology of the abscess-forming tumor revealed an undifferentiated malignancy with numerous of tumor giant cells as well as spindle-shaped cells with nuclear pleomorphism and hyperchromasia. Immunohistochemistry demonstrated partial, patchy desmin staining and weak heterogonous neuron-specific enolase immunoreactivity of tumor cells, but a focal staining for Melan-A. Results: Neither common melanoma driver mutations nor an ultraviolet mutational signature was detected by whole genome sequencing. Using FISH and RT-PCR we also excluded translocations characteristic for clear cell sarcoma. Thus, the diagnosis of inflammatory UPS-NF of the breast was considered highly probable. Despite a complete mastectomy, the tumor recurred after only three months. This recurrence was treated with a combination of ipilimumab and nivolumab based on the primary tumor's TPS score for PD-L1 of 30%. After an initial response, however, the tumor was progressive again. Conclusion: We describe here the first case of UPS-NF of the breast, which shows great clinical and histopathologic resemblances to previously reported UPS-NF of other anatomic localizations. [ABSTRACT FROM AUTHOR]

Superficial CD34-positive fibroblastic tumor (SCPFT) is a fibroblastic/myofibroblastic soft tissue tumor of rarely metastasizing intermediate malignancy. Some recent studies have described a relationship between SCPFT and PRDM10-rearranged soft tissue tumor (PRT) based on SynCAM3 and PRDM10 expression on immunohistochemistry. We performed CD34, cytokeratin AE1/AE3, SynCAM3, and PRDM10 immunohistochemistry in SCPFT and its histological mimics, including myxoinflammatory fibroblastic sarcoma (MIFS), superficially localized myxofibrosarcoma (MFS), and undifferentiated pleomorphic sarcoma. We also examined cyclin D1 expression because it is expressed in MIFS and MFS. We conducted fluorescence in situ hybridization (FISH) of PRDM10 rearrangement in SCPFT cases. On immunohistochemistry, only SCPFT showed strong and diffuse SynCAM3 expression. SCPFT also exhibited strong nuclear and weak cytoplasmic cyclin D1 expression, which was similar to that observed in MIFS. Two of five SCPFT cases exhibited nuclear PRDM10 expression. FISH revealed PRDM10 split signals in 44% and 24% of tumor cells in two SCPFT cases showing nuclear PRDM10 expression on immunohistochemistry, respectively. A minority of non-SCPFT cases showed focal SynCAM3 expression, but a combination of SynCAM3 and cyclin D1 in addition to CD34 and cytokeratin AE1/AE3 may be useful for the differential diagnosis of SCPFT and its histological mimics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Undifferentiated Pleomorphic Sarcoma (UPS) is a common soft tissue sarcoma that can develop in various organs, but lung involvement is usually due to metastasis. UPS originating primarily in the lungs is called primary pulmonary undifferentiated pleomorphic Sarcoma (PPUPS) and is exceptionally rare. It is a high-grade pleomorphic neoplasm with no identifiable lines of differentiation. Thus, it is essentially a diagnosis of exclusion that requires extensive clinical, radiographic and histopathological evaluation. Herein we report the case of a 49-year-old gentleman who presented with anemia and weight loss and was found to have a large right lung mass. The lesion was diagnosed as PPUPS after detailed histopathological, immunohistochemical and molecular analysis and exclusion of a possible extrapulmonary origin. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma is uncommonly seen and can be present in soft tissue as a slow‐growing and painless mass. The usual presenting symptoms of these tumors are swelling, pain, and constitutional symptoms. However, an initial presentation of pleomorphic sarcoma as an embolic stroke is rarely seen. We report a patient who presented with cerebellar stroke and had widespread pulmonary nodules on chest X‐ray. The Computed Tomography (CT)‐guided biopsy of the pulmonary nodules revealed a diagnosis of undifferentiated pleomorphic sarcoma. These findings prompted a thorough physical examination in search of malignancy. Unfortunately, the patient was found to have left leg swelling, which was missed on the initial exam, delaying diagnosis and management. Additionally, the patient was found to have a patent foramen ovale (PFO) on transesophageal echocardiogram (TEE). However, no source of emboli was found. [ABSTRACT FROM AUTHOR]

We are going to present a case of malignant fibrous histiocytoma in the right atrium, which is a very rare entity. The patient had a right atrial mass, which prolapsed through the tricuspid valve into the right ventricle, causing functional tricuspid valve stenosis. The tumor was completely resected and the patient had an uneventful postoperative period. Histopathological examination reported malignant fibrous histiocytoma. The patient presented to the emergency department five weeks after discharge with dyspnea and palpitation. Echocardiography and magnetic resonance imaging revealed recurrent right atrial tumor mass. His clinical status has worsened, with syncope and acute renal failure. On the repeated echocardiography, suspected tumor recurrence was observed in left atrium, which probably caused systemic embolization. Considering the aggressive nature of the tumor and systemic involvement, our Heart Council decided to provide palliative treatment by nonsurgical management. His status deteriorated for the next few days and the patient succumbed to a cardiac arrest on the 4th day.

Undifferentiated pleomorphic sarcoma is a common soft tissue sarcoma. Unfortunately, any attempt to describe the line of differentiation fails. It represents a final common pathway in tumors that undergoes progression towards dedifferentiation. We report a man with an undifferentiated pleomorphic sarcoma presenting as an exophytic pedunculated tumor of the left scapula. Histopathology analysis revealed spindle-shaped cells with great pleomorphism and numerous mitoses. Immunohistochemistry showed diffuse expression of vimentin. Wide local excision was performed after an oncology consultation. After two-years of follow-up, the patient has shown no evidence of recurrence or metastases.

Atypical fibroxanthoma (AFX) is a rare cutaneous fibrohistiocytic tumor that typically arises on chronically sun-damaged skin, such as the head and neck, as a nondescript ulcerated papule, nodule, or tumor. The clinical prognosis is usually favorable and metastasis is rare. Pleomorphic dermal sarcoma (PDS), or undifferentiated pleomorphic sarcoma, is a recently introduced diagnostic moniker for AFX-like tumors with more aggressive clinical and histologic features such as necrosis and vascular invasion. The exact relationship between AFX and PDS has been debated. Diagnosis of these tumors is generally based on immunohistochemical staining to exclude other mimics. A wholly specific marker for this tumor does not exist, leading to diagnostic ambiguity in certain cases. Herein, we present a case of pleomorphic dermal sarcoma in a 53-year-old man with human immunodeficiency virus that displayed patchy S100 staining concerning for melanoma upon hospital pathology review. Next-generation sequencing analysis confirmed a mutation pattern consistent with published molecular signatures of AFX/PDS. In discussing this case, we review the current understanding of AFX/PDS and discuss diagnostic pitfalls, as well as emphasize on how next-generation sequencing techniques might improve accuracy in the diagnosis of tumors in the spectrum of AFX/PDS.

Undifferentiated pleomorphic sarcoma (UPS) previously called as malignant fibrous histiocytoma comprises a group of high-grade pleomorphic sarcomas that cannot be otherwise classified and considered as a diagnosis of exclusion. In the head neck region, UPS is extremely rare and accounts for 3% of all the undifferentiated pleomorphic sarcomas. Some of the reported sites include maxilla, mandible, buccal mucosa, temperomandibular fossa, tongue, gingiva, paranasal sinuses, salivary glands, and retro-orbital soft tissue. Undifferentiated pleomorphic sarcoma of the floor of the mouth is very rare. To our knowledge, only one case has been reported earlier. We report the second case of undifferentiated pleomorphic sarcoma of the floor of mouth. [ABSTRACT FROM AUTHOR]

Introduction: Soft tissue sarcomas (STS) are highly metastatic, connectivetissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS). Materials and Results: A single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation. Discussion: These data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas. [ABSTRACT FROM AUTHOR]

Introduction Retroperitoneal tumors with endocrine abnormalities are suspected to be functional adrenal tumors. Retroperitoneal soft tissue sarcomas are rare tumors, without endocrine potential. Case presentation A 60‐year‐old male was referred for a 15 cm mass in the left suprarenal space. His plasma cortisol and catecholamine levels were elevated. He underwent open left adrenalectomy with radical nephrectomy and his endocrinological abnormalities were improved. Pathological findings suggested that it had originated from the retroperitoneal fat tissue, and a diagnosis of undifferentiated pleomorphic sarcoma was made based on the results of immunohistochemical analysis and fluorescence in situ hybridization. Interestingly, neither cortisol nor catecholamine was elevated when, 6 months after surgery, local recurrence developed. Conclusion This is the first reported case of undifferentiated pleomorphic sarcoma accompanied by high levels of cortisol and catecholamine. We should keep in mind the possibility of tumors like retroperitoneal soft tissue sarcomas inducing endocrine abnormalities.

Abstract Background Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma (MFH), hardly originates from the colorectum. Case presentation We reported a 65-year-old female presented with UPS in the descending colon. Computed tomography (CT) revealed an irregularly thickened descending colon. On colonoscopy examination, an ulcerative tumour was identified. The patient received radical resection of the left colon and partial enterectomy. The resected tumor was ulcerative, 10 cm × 8 cm × 5 cm in size, and infiltrated the serosa layer. Postsurgical pathology showed that the tumor was high-graded UPS in the colon with large amounts of necrotic tissues. Conclusions UPS in the large intestine is a rare malignant tumor with a poor prognosis and unknown pathogenesis. The main treatment for UPS is early complete resection. Postsurgery adjuvant radiotherapy or chemotherapy can be attempted.

Abstract Background Primary undifferentiated pleomorphic sarcoma (UPS) of the pancreas is an exceedingly rare malignant tumor, with only 15 cases have been reported in the medical literature. At present, clinicians have poor recognition of the tumor, the epidemiology, diagnosis, and treatment of this disease have yet not been established. Case presentation In this report, we depict the clinical and imaging characteristics of a 37-year-old man presenting with a primarily cystic UPS. The patient complained of epigastric pain and distention over 20 days. Abdominal CT and pancreatic magnetic resonance imaging revealed cystic and cystic solid masses in the pancreatic body and tail. An abdominal ultrasound echogram revealed the mass in the body of the pancreas to be cystic with separation echo inside, and the wall was thick, not smooth. Besides, a hypoechoic mass was seen in the tail area of the pancreas with an inhomogeneous echoic pattern, containing small patches of no echo zone in the central. Microscopically, spindle fibroblast-like cells are arranged in a characteristic storiform pattern with pleomorphic and multinucleated cells. Immunohistochemically, tumor cells were positive for CD68 and vimentin. Seven months postoperatively, he was diagnosed with pulmonary lymph node metastasis and died 5 months later. Combined with this case report, we also reviewed the literature regarding UPS of the pancreas. Conclusions As we know, this is the first report on ultrasonography findings of pancreatic UPS. Despite there are no distinctive manifestation of UPS, a solid cystic lesion on ultrasonography or a hypodense area in the lesion on T2-weighted imaging, should be considered for differential diagnosis with pancreatic UPS. We believe this article may add some ideas into the diagnosis and therapy of patients with this tumor.

Undifferentiated pleomorphic sarcoma (UPS), once termed as malignant fibrous histiocytoma, has always been diagnosed exclusively in clinical practice because it lacks any defined resemblance to normal mesenchymal tissue. Although myxofibrosarcoma (MFS) has been separated from UPS due to its fibroblastic differentiation with myxoid stroma, UPS and MFS are still identified as a sarcoma group in terms of molecular landscapes. In this review article, we will describe the associated genes and signaling pathways involved in the process of sarcoma genesis and make a summary of conventional management, targeted therapy, immunotherapy, and some novel potential treatments of UPS/MFS. With the progressive advancements in medical technology and a better understanding about the pathogenic mechanism of UPS/MFS in the coming decades, new lights will be shed on the successful management of UPS/MFS.