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<b>Introduction:</b> Soft tissue sarcomas (STS) constitute about 1-2% of all malignant tumors, with approximately 10% of them located in the head and neck region.<b>Aim:</b> The aim of this study was the assessment of treatment efficiency in head and neck STS of adult patients of the ENT Department of Medical University of Silesia, treated surgically in the period 1980-2023.<b>Materials and methods:</b> Retrospective analysis of 39 patients with the diagnosis of head and neck STS.<b>Results:</b> Histopathological examination showed 21 different types of STS located most commonly in: paranasal sinuses (13 cases), orbital cavity (6 cases), nasal cavity (3 cases), and larynx (3 cases). Other locations: parapharyngeal space, parotid gland, nasal septum, bridge of the nose, soft and hard palate, mandibular mucosa, tongue, auricle, palatine tonsil, and cheek. All those patients underwent chemoradiation as postoperative treatment. Radical surgical procedure was achieved in 32 patients (82%). However, in 11 patients (28%), microscopic examination did not confirm radical resection (R1 - PSM - positive surgical margin). In 7 patients (18%), the surgical procedure turned out to be not radical on macroscopic examination (R2). Dissemination of neoplasms (distant metastases) was found in 7 patients (18%). Five-year survival time without local recurrence was achieved in 25 patients (64%). The most frequent reason for unsuccessful interventions was local recurrence noted in 18 patients (46%), while distant metastases occurred in 9 patients (23%).<b>Conclusions:</b> The basic procedure in the treatment of STS is radical surgery combined with preoperative or postoperative radiotherapy and/or chemotherapy and, in case of a metastasis, surgical removal thereof. Despite the fact that sarcomas are rare tumors, they remain a challenge for head and neck surgery. Recurrence rates and mortality remain high due to the high degree of malignancy.

Introduction: Soft tissue sarcomas are a group of malignancies that commonly occur in the extremities. As deep lesions may exist within the confines of the muscular fascia, we postulate that local recurrence rates are higher for superficial soft tissue sarcomas managed by the standard of care., Materials and Methods: A retrospective review was performed on 90 patients who underwent surgical resection of soft tissue sarcomas of the extremity from 2007 to 2015. Patients with minimum 2-year follow-up and adequate operative, pathologic, and clinical outcomes data were included., Results: Mean age was 54 ± 18 years with 49 (54.4%) patients being male. Lesions in 77.8% of cases were deep, and 22.2% were superficial to fascia. Following the index surgical resection, a total of 33 (36.7%) patients had positive margins. A total of 17 (18.9%) patients had a local recurrence. Overall, 3-year survival was 92.7%, and 5-year survival was 79.0%. Five-year recurrence-free survival of deep sarcomas was 91.1% versus 58.2% of superficial lesions (p = 0.006). Patients with higher tumor depth had lower odds of experiencing a local recurrence (HR 0.26 [95% CI 0.09-0.72]). Local recurence rates was also associated with positive surgical margins on initial resection (33.3% versus 12.3%) (p = 0.027)., Conclusions: In this series, superficial tumor depth was associated with local recurrence of soft tissue sarcomas of the extremity following surgical resection. Positive surgical margins was also associated with local recurrence., (© 2024. The Author(s).)

The past 25 years have seen significant growth in the role of positron emission tomography/computed tomography (PET/CT) in musculoskeletal oncology. Substantiative advances in technical capability and image quality have been paralleled by increasingly widespread clinical adoption and implementation. It is now recognized that PET/CT is useful in diagnosis, staging, prognostication, response assessment, and surveillance of bone and soft tissue sarcomas, often providing critical information in addition to conventional imaging assessment. As individualized, precision medicine continues to evolve for patients with sarcoma, PET/CT is uniquely positioned to offer additional insight into the biology and management of these tumors., Competing Interests: Disclosure The authors have no relevant financial disclosures or conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Opinion Statement: Soft tissue sarcoma (STS), a substantial group of aggressive and rare tumors with tissue heterogeneity, is infrequently represented in clinical trials with an urgent necessity for newer treatment options. Lurbinectedin, an analog of trabectedin, is currently approved, in various countries, as a single agent, for the treatment of patients with relapsed small cell lung cancer (SCLC). However, preclinical and phase I and phase II trials have demonstrated the efficacy of lurbinectedin in different tumor types, including STS. The better understanding of the pathophysiology and evolution of STS as well as the mechanism of action of lurbinectedin in addition to the available data regarding the activity of this drug in this subset of patients will pave the way to newer therapeutic options and strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mesenchymal tumors with GLI1 fusions or amplifications have recently emerged as a distinctive group of neoplasms. The terms GLI1-altered mesenchymal tumor or GLI1-altered soft tissue tumor serve as a nosological category, although the exact boundaries/criteria require further elucidation. We examined 16 tumors affecting predominantly adults (median age: 40 years), without sex predilection. Several patients had tumors of longstanding duration (>10 years). The most common primary site was soft tissue (n = 9); other sites included epidural tissue (n = 1), vertebra (n = 1), tongue (n = 1), hard palate (n = 1), and liver (n = 1). Histologically, the tumors demonstrated multinodular growth of cytologically uniform, ovoid-to-epithelioid, occasionally short spindled cells with delicate intratumoral vasculature and frequent myxoid stroma. Mitotic activity ranged from 0 to 8 mitoses/2 mm 2 (mean 2). Lymphovascular invasion/protrusion of tumor cells into endothelial-lined vascular spaces was present or suspected in 6 cases. Necrosis, significant nuclear pleomorphism, or well-developed, fascicular spindle-cell growth were absent. Half demonstrated features of the newly proposed subset, "distinctive nested glomoid neoplasm." Tumors were consistently positive for CD56 (n = 5/5). A subset was stained with S100 protein (n = 7/13), SMA (n = 6/13), keratin (n = 2/9), EMA (n = 3/7), and CD99 (n = 2/6). Tumors harbored ACTB::GLI1 (n = 15) or PTCH1::GLI1 (n = 1) fusions. The assays used did not capture cases defined by GLI1 amplification. We also identified recurrent cytogenetic gains (1q, 5, 7, 8, 12, 12q13.2-ter, 21, and X). For patients with available clinical follow-up (n = 8), half were disease free. Half demonstrated distant metastases (lungs, bone, or soft tissue). Of cases without follow-up (n = 8), 2 were known recurrences, and 1 was presumed metastasis. Our results imply a more aggressive biological potential than currently reported. Given the possibility for metastasis and disease progression, even in cytologically bland, nested tumors, close clinical surveillance, akin to that for sarcoma management, may be indicated. The term GLI1-altered mesenchymal tumor with malignant potential is proposed., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Pseudoendocrine sarcoma (PES) is a recently described neoplasm typically arising in paravertebral soft tissues. Histologically, PES resembles well-differentiated neuroendocrine tumors but lacks expression of epithelial/neuroendocrine markers, and most show aberrant nuclear β-catenin positivity. We describe the clinicopathological and molecular features and DNA methylation profile of one PES. A resected paraspinal soft tissue mass in a 52-year-old man showed a neuroendocrine-like neoplasm, negative for keratin, and synaptophysin and showing diffuse nuclear β-catenin expression. Targeted NGS confirmed a CTNNB1 (p.S37C) mutation. Whole genome methylation analysis showed no match to any methylation class in the central nervous system tumor (versions 11b6 and 12b6) or sarcoma classifier (calibrated scores of ≤0.3), but clustered together with a recently reported PES in which methylation analysis was also performed. He remained disease-free for 18 months after surgery, followed by chemoradiation. As more cases are examined, our findings suggest that PES may have a unique methylation profiling signature., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Myxofibrosarcoma is a locally aggressive sarcoma that characteristically arises in the extremities of older patients. Cases arising at a younger age are rare, leading to diagnostic challenges. Our aim was to study the clinicopathologic features of myxofibrosarcoma in patients aged ≤40 years. Cases of myxofibrosarcoma and myxoid malignant fibrous histiocytoma arising in patients aged ≤40 years with clinical follow-up were collected from multiple institutions. Hematoxylin and eosin slides were evaluated for mitoses, necrosis, and epithelioid areas. Seventeen cases were identified (13 females, 4 males; 16-39 years; median 32 years), tumors ranged from 2.2 to 34 cm (median 4.1 cm). Anatomic sites included proximal extremity (9), distal extremity (4), trunk (1), and head/neck (3). Ten were superficial, and 6 were deep-seated. Three cases were predominantly epithelioid. In untreated resection specimens, 6 were FNCLCC grade 1, 4 grade 2, and 2 grade 3. Follow-up (6-204 months, median 36 months) revealed that 2 patients experienced local recurrences, 1 distant metastasis, and 2 patients both. The 5-year overall survival (OS) and event-free survival (EFS) were 84% and 55.9%, respectively. Tumor depth and necrosis were correlated with inferior OS (P = .025, P = .005), while tumor depth was also associated with worse EFS (P = <.001). We conclude that myxofibrosarcomas arising in adolescents and young adults show similar behavior compared to their older adult counterparts. Tumor depth and necrosis are poor prognostic factors in myxofibrosarcoma in this age group. Awareness that myxofibrosarcoma can rarely present in this population is important for accurate diagnosis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Opinion Statement: The therapeutic approach of pleomorphic liposarcoma (PLPS), a rare high-grade subgroup of soft tissue sarcoma, is commonly extrapolated from the management of other LPS subtypes. Only published retrospective data on PLPS currently serve as a guide for oncologists without clear recommendations or specific guidelines. In the advanced setting, specific systemic therapy such as eribulin and trabectedin showed promising activity in comparison to conventional therapy (doxorubicin- and gemcitabine-based protocols), which currently remains the current standard of care at initial stages of the disease. The better understanding of soft tissue sarcoma (STS) pathophysiology and disease course has led to the development of adapted clinical trial designs for rare STS histotypes with specific treatment approach., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bone and soft tissue lesions in the head and neck encompass not only a broad morphologic spectrum but also significant inherent clinicopathologic overlap. Epidemiology, radiology, and location - similar to the diagnostic assessment in other sites - are especially important considerations in the context of an established mesenchymal proliferation. Herein, the approach towards diagnosis is stratified by morphology (spindle, sarcomatoid, epithelioid, round cell), cellular lineage (fibroblastic, nerve sheath, rhabdomyogenic), and tumor grade (benign, low- to high-grade malignant) as the basis of further immunohistochemical or molecular investigation., Competing Interests: Declaration of Competing Interest No conflicts of interest to declare. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article, (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Pleomorphic dermal sarcoma (PDS) is an uncommon cutaneous mesenchymal neoplasm. It is cytomorphologically identical to atypical fibroxanthoma (AFX), but differs due to its invasion beyond the dermis. We undertook an examination of our experience with fine needle aspiration (FNA) biopsy cytology of PDS., Materials and Methods: Our cytopathology files were searched for examples of PDS with concomitant histopathological verification. FNA biopsy smears and cell collection were performed using standard techniques., Results: Seven cases of PDS were retrieved from four different patients (M:F, 1:1; age range: 63-88 years; mean age = 78 years). All patients (57%) presented with a primary tumour with one having an FNA biopsy of two local recurrences and a single distant metastasis. Five aspirates were from the extremities and two from the head/neck. Tumours ranged from 1.0 to 3.5 cm (mean, 2.2 cm). Specific cytological diagnoses were pleomorphic spindle/epithelioid sarcoma (3 cases), PDS (2), AFX (1), and atypical myofibroblastic lesion, query nodular fasciitis (1). Immunohistochemical (IHC) staining from FNA-generated cell blocks in two cases showed non-specific staining with vimentin in both cases; positive CD10, CD68, and INI-1 staining in one case; and smooth muscle actin expression in the other. Multiple negative stains were performed in both of these cases to exclude malignant melanoma, carcinoma, and specific forms of sarcoma. Cytopathology consisted of a mixture of spindle, epithelioid, and bizarre pleomorphic cells., Conclusion: Coupled with ancillary IHC stains, FNA biopsy can help recognise PDS as a sarcomatous cutaneous neoplasm, but is unable to distinguish PDS from AFX., (© 2023 The Authors. Cytopathology published by John Wiley & Sons Ltd.)

Objectives: To evaluate the performance of machine learning-augmented MRI-based radiomics models for predicting response to neoadjuvant chemotherapy (NAC) in soft tissue sarcomas., Methods: Forty-four subjects were identified retrospectively from patients who received NAC at our institution for pathologically proven soft tissue sarcomas. Only subjects who had both a baseline MRI prior to initiating chemotherapy and a post-treatment scan at least 2 months after initiating chemotherapy and prior to surgical resection were included. 3D ROIs were used to delineate whole-tumor volumes on pre- and post-treatment scans, from which 1708 radiomics features were extracted. Delta-radiomics features were calculated by subtraction of baseline from post-treatment values and used to distinguish treatment response through univariate analyses as well as machine learning-augmented radiomics analyses., Results: Though only 4.74% of variables overall reached significance at p ≤ 0.05 in univariate analyses, Laws Texture Energy (LTE)-derived metrics represented 46.04% of all such features reaching statistical significance. ROC analyses similarly failed to predict NAC response, with AUCs of 0.40 (95% CI 0.22-0.58) and 0.44 (95% CI 0.26-0.62) for RF and AdaBoost, respectively., Conclusion: Overall, while our result was not able to separate NAC responders from non-responders, our analyses did identify a subset of LTE-derived metrics that show promise for further investigations. Future studies will likely benefit from larger sample size constructions so as to avoid the need for data filtering and feature selection techniques, which have the potential to significantly bias the machine learning procedures., (© 2023. The Author(s).)

Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge of its expression patterns in soft tissue tumors is limited. PRAME immunohistochemistry (clone QR005) was assessed on whole tissue sections of 350 soft-tissue tumors and mimics (> 50 histotypes). PRAME immunoreactivity was evaluated as follows: 0 "negative" (0% positive cells); 1+ (1-25% positive cells); 2+ (26-50% positive cells); 3+ (51-75% positive cells), and 4+ "diffuse" (> 75% positive cells). PRAME was expressed in 111 lesions (0 benign, 6 intermediate malignancy, and 105 malignant), including fibrosarcomatous dermatofibrosarcoma protuberans (2/4, 0 diffuse), NTRK-rearranged spindle cell neoplasm (2/4, 0 diffuse), atypical fibroxanthoma (1/7, 0 diffuse), Kaposi sarcoma (1/5, 0 diffuse), myxoid liposarcoma (11/11, 9 diffuse), synovial sarcoma (11/11, 6 diffuse), intimal sarcoma (7/7, 5 diffuse), biphenotypic sinonasal sarcoma (3/3, 1 diffuse), angiosarcoma (10/15, 6 diffuse), malignant peripheral nerve sheath tumor (9/12, 4 diffuse), pleomorphic rhabdomyosarcoma (2/3, 2 diffuse), alveolar rhabdomyosarcoma (2/6, 0 diffuse), embryonal rhabdomyosarcoma (7/7, 4 diffuse), undifferentiated pleomorphic sarcoma (2/12, 1 diffuse), leiomyosarcoma (2/15, 1 diffuse), clear cell sarcoma of soft tissue (1/10, 0 diffuse), low-grade fibromyxoid sarcoma (1/5, 0 diffuse), Ewing sarcoma (2/10, 1 diffuse), CIC-rearranged sarcoma (8/8, 4 diffuse), BCOR-sarcoma (2/5, 1 diffuse), melanoma (20/20, 14 diffuse), and thoracic SMARCA4-deficient undifferentiated tumor (5/5, all diffuse). All tested cases of spindle cell lipoma, dedifferentiated/pleomorphic liposarcoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, inflammatory myofibroblastic tumor, myxoinflammatory fibroblastic sarcoma, nodular fasciitis, myxofibrosarcoma, epithelioid hemangioendothelioma, atypical vascular lesion, hemangioma, lymphangioma, vascular malformation, papillary endothelial hyperplasia, GIST, gastrointestinal clear-cell sarcoma, malignant melanotic nerve sheath tumor, neurofibroma, schwannoma, granular cell tumor, alveolar soft part sarcoma, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma, myoepithelioma, ossifying fibromyxoid tumor, angiomatoid fibrous histiocytoma, PEComa, dermatofibroma, pleomorphic dermal sarcoma, and chordoma were negative. PRAME shows imperfect specificity in soft-tissue pathology but may serve as a diagnostic adjunct in selected differential diagnoses that show contrasting expression patterns., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Non-Diagnostic (ND) biopsies are occasionally encountered during the investigation of soft tissue sarcoma. We performed a retrospective review of all ND soft tissue biopsies discussed at our regional Multi-Disciplinary Team (MDT) meeting between 2004 & 2014 with the aim of establishing the incidence of ND biopsies, identifying predictive factors for repeat biopsies and evaluating the effectiveness of MDT decisions. We identified 80 ND out of 3233 biopsies. Diagnostic Yield (DY) was 97.5%, 76.0% and 77.8% for the first, second and third successive biopsy respectively. With an MDT approach utilising radiological and clinical information, the diagnostic success rate achieved was 98.5%, 82.0% and 77.8% for the first, second and third biopsies respectively. Malignant tumours (sarcoma & carcinoma) were 19 times more likely to undergo an increasing number of biopsies compared to benign lesions (p < 0.01), while repeat biopsies were less useful for suspected benign lesion. Although a repeat biopsy was only performed in 63% of cases, there were no patients originally diagnosed with a benign lesion that re-presented with the same lesion subsequently being malignant throughout the study period. Our study shows that a specialist MDT approach leads to high diagnostic rates and is a safe and effective method of preventing unnecessary, repeat biopsies where the initial biopsy is ND., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: To construct effective prediction models for neoadjuvant radiotherapy (RT) and targeted therapy based on whole-tumor texture analysis of multisequence MRI for soft tissue sarcoma (STS) patients., Methods: Thirty patients with STS of the extremities or trunk from a prospective phase II trial were enrolled for this analysis. All patients underwent pre- and post-neoadjuvant RT MRI examinations from which whole-tumor texture features were extracted, including T 1 -weighted with fat saturation and contrast enhancement (T 1 FSGd), T 2 -weighted with fat saturation (T 2 FS), and diffusion-weighted imaging (DWI) sequences and their corresponding apparent diffusion coefficient (ADC) maps. According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) and non-pCR (N-pCR) groups. pCR was defined as less than 5% of residual tumor cells by postoperative pathology. Delta features were defined as the percentage change in a texture feature from pre- to post-neoadjuvant RT MRI. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance., Results: Five of 30 patients (16.7%) achieved pCR. The Delta&#95;Model (AUC 0.92) had a better predictive ability than the Pre&#95;Model (AUC 0.78) and Post&#95;Model (AUC 0.76) and was better than AJCC staging (AUC 0.52) and RECIST 1.1 criteria (AUC 0.52). The Combined&#95;Model (pre, post, and delta features) had the best predictive performance (AUC 0.95)., Conclusion: Whole-tumor texture analysis of multisequence MRI can well predict pCR status after neoadjuvant RT and targeted therapy in STS patients, with better performance than RECIST 1.1 and AJCC staging., Key Points: • MRI multisequence texture analysis could predict the efficacy of neoadjuvant RT and targeted therapy for STS patients. • Texture features showed incremental value beyond routine clinical factors. • The Combined&#95;Model with features at multiple time points showed the best performance., (© 2022. The Author(s).)

Introduction: Metastatic sarcomas to pleural effusion are extremely rare, accounting for <1% of all malignant pleural effusions. We aim to present our experience with pleural effusion specimens containing metastatic sarcomas over a 10-year period., Methods: We performed a 10-year retrospective search of cytopathology archives to identify all pleural effusions that were involved by metastatic sarcoma. All available cytopathology and surgical pathology specimens were retrieved and reviewed., Results: Twenty-eight pleural fluids from 22 patients with metastatic sarcoma were identified in our search. The patients' ages ranged from 12 to 73 years. The pleural fluid volumes ranged from 10 to 1500 ml. Rhabdomyosarcoma was the most commonly encountered metastatic sarcoma to pleural effusion (n = 7). Other metastatic sarcomas were as follows: epithelioid angiosarcoma (n = 4), Ewing sarcoma (n = 3), clear cell sarcoma (n = 2), high grade conventional osteosarcoma (n = 2), undifferentiated pleomorphic sarcoma (n = 1), epithelioid sarcoma, proximal type (n = 1), dedifferentiated liposarcoma (n = 1), and conventional chondrosarcoma (n = 1). The time between initial diagnosis and effusion varied from 3 months to 25 years. Two patients are alive with disease at 6 and 21 months of follow-up. All other patients were dead of disease and the survival after a malignant pleural effusion ranged from <1 month to 18 months., Conclusions: Metastatic bone and soft tissue sarcomas to pleural effusions are rare and their cytologic features can be mistaken for carcinoma, melanoma, or mesothelioma. Careful review of the patient's medical history, comparison of the previous pathology and the use of ancillary studies are crucial for the evaluation of pleural effusions involved by metastatic sarcomas., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: The fine-needle aspiration (FNA) cytopathology of pleomorphic hyalinizing angiectatic tumor (PHAT) is the subject of a very limited number of reports. We undertook a review of our FNA experience with this neoplasm., Materials and Methods: A search was made of our files for PHAT FNA cases with histopathologic confirmation. FNA biopsy smears and cell blocks were performed and examined using standard techniques., Results: Two primary cases of histologically proven PHAT [both male, ages 56 and 60 years] met study inclusion. FNA sites included buttock and foot. A misdiagnosis of sarcoma was made in each case. Ancillary immunohistochemical testing performed in 1 case suggested angiosarcoma. Cytologic smears showed only modest cellularity with a dual population of bland spindle cells and isolated large pleomorphic cells, many harboring nuclear pseudoinclusions. Smear background was clean, and mitoses absent., Conclusions: The imitative cytopathology of PHAT with a pleomorphic sarcoma remains a pitfall in FNA specimens. Awareness of this entity and its lack of hypercellularity, necrosis, and cohesive groups of atypical cells in smears should assist the cytopathologist in avoiding a misdiagnosis of malignancy., (Copyright © 2022 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Soft-tissue sarcoma is a rare cancer that accounts for approximately 1% of all malignant tumors. Although they occur in various age groups, soft-tissue sarcomas account for 8% of all malignant tumors developing in adolescents and young adults, suggesting that they are not rare in this age group. This study aimed to evaluate the clinical and pathological characteristics of soft-tissue sarcoma in adolescents and young adults. According to the Bone and Soft-Tissue Tumor Registry in Japan, myxoid liposarcoma is the most common type of soft-tissue sarcoma found in adolescents and young adults; alveolar soft part sarcoma, extraskeletal Ewing sarcoma, epithelioid sarcoma, clear cell sarcoma and synovial sarcoma occur predominantly in this age group among soft-tissue sarcomas. The analysis based on this registry demonstrated that age was not a prognostic factor for poor survival of soft-tissue sarcoma, although the prognosis in adolescents and young adults was better than that in older patients in the US and Scandinavia. Adolescent and young adult patients with soft-tissue sarcoma have age-specific problems, and a multidisciplinary approach to physical, psychological, and social issues is necessary to improve the management of these young patients both during and after treatment., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Introduction: Metastasis of sarcomas to lymph nodes is an uncommon event in its natural history. We aimed to present our experience with fine-needle aspiration (FNA) of metastatic sarcomas to lymph nodes over a 10-year period., Material and Methods: The cytopathology archives were searched for FNA of lymph nodes involved by metastatic sarcomas. Available clinicopathologic data were recorded. All slides were retrieved and reviewed., Results: Thirty-three lymph nodes, from 30 patients, with metastatic soft tissue sarcomas were identified. The lymph node metastases occurred in 16 males and 14 females (median age, 56 years). The size of the lymph nodes ranged from 1.2 to 7.5 cm (median size, 2.9 cm). The inguinal lymph nodes were the most commonly involved nodes, followed by thoracic and cervical neck nodes. The most common metastatic soft tissue sarcoma encountered was Kaposi sarcoma (n = 7, 23.3%), followed by angiosarcoma (n = 6, 20%) and rhabdomyosarcoma (n = 6, 20%). The most common site of primary soft tissue sarcoma was the head and neck (n = 8, 26.6%), followed by lower extremity (n = 7, 23.3%). The initial diagnosis of sarcoma was established in 6 cases. Seventen patients had metachronous involvement of lymph nodes, while the remaining patients had synchronous involvement. Seventen patients died of disease, and the survival after lymph node metastasis ranged from 1 to 43 months., Conclusion: FNA is an accurate and effective method in the diagnosis of metastatic sarcoma to lymph nodes. Knowledge of clinical findings and primary tumor diagnosis along with careful assessment of the cytomorphology is extremely helpful for an accurate diagnosis of metastases., (© 2023 S. Karger AG, Basel.)

A study by Tsvetkov et al. recently published a proposed novel form of copper-induced cell death in Science ; however, few studies have looked into the possible mechanism in soft tissue sarcoma (STS). Herein, this study sought to investigate the function of cuproptosis-related genes (CRGs) in the development of tumor-associated immune cells and the prognosis of sarcoma. Herein, this study aimed to explore the role of cuproptosis-related genes (CRGs) in the development, tumor-associated immune cells, and the prognosis of sarcoma., Methods: The prognostic model was established via the least absolute shrinkage and selection operator (LASSO) algorithm as well as multivariate Cox regression analysis. The stromal scores, immune scores, ESTIMA scores, and tumor purity of sarcoma patients were evaluated by the ESTIMATE algorithm. Functional analyses were performed to investigate the underlying mechanisms of immune cell infiltration and the prognosis of CRGs in sarcoma., Results: Two molecular subgroups with different CRG expression patterns were recognized, which showed that patients with a higher immune score and more active immune status were prone to have better prognostic survival. Moreover, GO and KEGG analyses showed that these differentially expressed CRGs were mainly enriched in metabolic/ions-related signaling pathways, indicating that CRGs may have impacts on the immune cell infiltration and prognosis of sarcoma via regulating the bioprocess of mitochondria and consequently affecting the immune microenvironment. The expression levels of CRGs were closely correlated to the immunity condition and prognostic survival of sarcoma patients., Conclusions: The interaction between cuproptosis and immunity in sarcoma may provide a novel insight into the study of molecular mechanisms and candidate biomarkers for the prognosis, resulting in effective treatments for sarcoma patients.

Background: Sarcomas are a heterogeneous group of rare malignant tumors with more than 100 subtypes. Accurate diagnosis remains challenging due to a lack of characteristic molecular or histomorphological hallmarks. A DNA methylation-based tumor profiling classifier for sarcomas (known as sarcoma classifier) from the German Cancer Research Center (Deutsches Krebsforschungszentrum) is now employed in selected cases to guide tumor classification and treatment decisions at our institution. Data on the usage of the classifier in daily clinical routine are lacking., Methods: In this single-center experience, we describe the clinical course of five sarcoma cases undergoing thorough pathological and reference pathological examination as well as DNA methylation-based profiling and their impact on subsequent treatment decisions. We collected data on the clinical course, DNA methylation analysis, histopathology, radiological imaging, and next-generation sequencing., Results: Five clinical cases involving DNA methylation-based profiling in 2021 at our institution were included. All patients' DNA methylation profiles were successfully matched to a methylation profile cluster of the sarcoma classifier's dataset. In three patients, the classifier reassured diagnosis or aided in finding the correct diagnosis in light of contradictory data and differential diagnoses. In two patients with intracranial tumors, the classifier changed the diagnosis to a novel diagnostic tumor group., Conclusions: The sarcoma classifier is a valuable diagnostic tool that should be used after comprehensive clinical and histopathological evaluation. It may help to reassure the histopathological diagnosis or indicate the need for thorough reassessment in cases where it contradicts previous findings. However, certain limitations (non-classifiable cases, misclassifications, unclear degree of sample purity for analysis and others) currently preclude wide clinical application. The current sarcoma classifier is therefore not yet ready for a broad clinical routine. With further refinements, this promising tool may be implemented in daily clinical practice in selected cases., (© 2022. The Author(s).)

Background: According to guidelines, all patients with sarcoma must be managed from initial diagnosis at expert sarcoma centers. However, in everyday practice, the time interval to an expert center visit can be long, which delays presentation to an expert multidisciplinary tumor board and increases the risk of inappropriate management, negatively affecting local tumor control and prognosis. The advent of mobile health offers an easy way to facilitate communication and cooperation between general health care providers (eg, general practitioners and radiologists) and sarcomas experts. We developed a mobile app (Sar'Connect) based on the algorithm designed by radiologists from the French Sarcoma Group. Through a small number of easy-to-answer questions, Sar'Connect provides personalized advice for the management of patients and contact information for the closest expert center., Objective: This retrospective study is the first to assess this mobile app's potential benefits in reducing the time interval for patient referral to an expert center according to the initial clinical characteristics of the soft tissue tumor., Methods: From May to December 2021, we extracted tumor mass data for 78 patients discussed by the multidisciplinary tumor boards at 3 centers of the French Sarcoma Group. We applied the Sar'Connect algorithm to these data and estimated the time interval between the first medical description of the soft tissue mass and the referral to expert center. We then compared this estimated time interval with the observed time interval., Results: We found that the use of Sar'Connect could potentially shorten the time interval to an expert center by approximately 7.5 months (P<.001). Moreover, for half (31/60, 52%) of the patients with a malignant soft tissue tumor, Sar'Connect could have avoided inappropriate management outside of the reference center. We did not identify a significant determinant for shortening the time interval for referral., Conclusions: Overall, promoting the use of a simple mobile app is an innovative and straightforward means to potentially accelerate both the referral and management of patients with soft tissue sarcoma at expert centers., (©Simon Nannini, Nicolas Penel, Emmanuelle Bompas, Thibault Willaume, Jean-Emmanuel Kurtz, Justine Gantzer. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 09.11.2022.)

Spindle cell rhabdomyosarcoma represents a rare neoplasm characterized by monomorphic spindle cells with a fascicular architecture and variable skeletal muscle differentiation. Following incidental identification of a ZFP64::NCOA3 gene fusion in an unclassified spindle cell sarcoma resembling adult-type fibrosarcoma, we performed a retrospective archival review and identified four additional cases with a similar histology and identical gene fusion. All tumors arose in adult males (28-71 years). The neoplasms were found in the deep soft tissues, two were gluteal, and one each arose in the thigh, abdominal wall, and chest wall. Morphologically, the tumors were characterized by spindle cells with a distinctive herringbone pattern and variable collagenous to myxoid stroma. The nuclei were relatively monomorphic with variable mitotic activity. Three tumors had immunoreactivity for MyoD1, and four contained variable expression of desmin and smooth muscle actin. All cases tested for myogenin, CD34, S100, pankeratin, and epithelial membrane antigen were negative. Targeted RNA sequencing revealed a ZFP64::NCOA3 fusion product in all five tumors. Three patients developed distant metastases, and two ultimately succumbed to their disease within 2 years of initial diagnosis. This study suggests ZFP64::NCOA3 fusions define a novel subtype of rhabdomyosarcoma with a spindle cell morphology and aggressive clinical behavior. The potential for morphologic and immunohistochemical overlap with several other sarcoma types underscores the value of molecular testing as a diagnostic adjunct to ensure accurate classification and management of these neoplasms., (© 2022 Wiley Periodicals LLC.)

Myoepithelial carcinoma (MEC) of soft tissue, also known as malignant myoepithelial tumor, is an uncommon malignancy. Cytologic diagnosis of this entity is challenging due to its rarity and heterogeneous morphology. We report a case of MEC in a 22-year-old man, who presented with a 6.5 cm soft tissue mass on his right distal forearm that has been enlarging over the past 3 months. Ultrasound-guided fine-needle aspiration (FNA) revealed abundant isolated neoplastic cells ranging from spindled cells to epithelioid and plasmacytoid morphology in a myxoid background. These cells showed moderate cytologic atypia characterized by high-nuclear/cytoplasmic ratio, irregular nuclear contours, and prominent nucleoli. The cytoplasm varied from dense to vacuolated and occasionally rhabdoid with intracytoplasmic inclusions. Scattered bi- and multinucleated cells were identified. A diagnosis of high-grade malignancy was made with the differential diagnosis including rhabdomyosarcoma and melanoma. A subsequent core biopsy of the tumor showed immunoreactivity for pan-cytokeratins, calponin, p63, and smooth muscle actin. INI-1 was lost. SOX-10 and Melan-A were negative. Molecular studies showed loss of SMARCB1 (INI-1) and CDKN2A. Gene fusion studies did not detect any fusion. A diagnosis of soft tissue MEC was made which is a challenge on FNA due to several cytologic mimickers including rhabdomyosarcoma, epithelioid sarcoma, extrarenal rhabdoid tumor, extra-axial chordoma and melanoma. Recognition of the biphasic cell population in a myxoid background and a battery of immunohistochemical stains are crucial for accurate diagnosis., (© 2022 Wiley Periodicals LLC.)

Undifferentiated mesenchymal neoplasms can be morphologically subclassified based on cell shape; epithelioid tumors may be diagnostically challenging, particularly since they can show morphologic and immunohistochemical overlap with epithelial neoplasms. Following the recent report of an NR1D1::MAML1 gene fusion in an undifferentiated pediatric neoplasm, we performed a retrospective archival review and identified four additional cases of undifferentiated mesenchymal neoplasms with NR1D1-rearrangement. All four tumors occurred in adult women. The tumors involved superficial and/or deep soft tissues of the extremities or abdomen. Morphologically, they showed a spectrum of overlapping features. In addition to epithelioid cells, two cases also had a prominent spindle cell component. Two cases also had admixed polygonal cells containing prominent cytoplasmic vacuoles with amorphous debris. The immunophenotype was nonspecific but all cases had at least focal keratin expression; this was extensive in two tumors. Targeted RNA-sequencing revealed two cases each with NR1D1::MAML1 and NR1D1::MAML2 gene fusions. One patient developed lung and liver metastases, and one patient required amputation due to multifocal disease and underlying bone involvement. This study confirms undifferentiated NR1D1-rearranged sarcoma represents a distinct mesenchymal neoplasm with an epithelioid morphology and potential for aggressive behavior. Further, we offer new insight into the spectrum of clinical, morphologic, immunohistochemical, and molecular findings possible in these rare neoplasms. An awareness of this entity is especially important given the potential for misclassification as a carcinoma., (© 2022 Wiley Periodicals LLC.)

Soft tissue tumors with myxoid components are often a diagnostic challenge for the pathologist. We retrospectively reviewed 41 cases of soft tissue tumors with myxoid components diagnosed in our center over a five-year period. The most frequent diagnoses were myxofibrosarcoma and myxoid liposarcoma, followed by low-grade fibromyxoid sarcoma, low-grade fibromyxoid tumor and myxoid neurofibroma. Other diagnoses included were extraskeletal myxoid chondrosarcoma, myxoinflammatory fibroblastic sarcoma, low-grade myxoliposarcoma, myofibrosarcoma, fibromatosis, solitary fibrous tumor, non-ossifying variant of ossifying fibromyxoid tumor and ancient neurinoma with myxoid degeneration. Immunohistochemical and molecular biology studies contributed significantly to the diagnosis. We highlight the importance of immunohistochemistry for MUC4 in the diagnosis of low-grade fibromyxoid sarcoma, and underscore the need for molecular studies in selected cases. Furthermore, several myxoid neoplasms present specific chromosomal translocations, therefore molecular biology studies to detect fusion genes are usually essential for the diagnosis. When the characteristics of the sample are not adequate for molecular biology, or no specific alterations are described, an in-depth knowledge of the histology of these lesions is still necessary to decide the most accurate diagnosis., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Primary tumor resection is the mainstay of treatment for undifferentiated pleomorphic sarcoma (UPS); however, the necessity of adjuvant chemotherapy has been debated. We aimed to clarify the effect of adjuvant chemotherapy on survival rates in patients with UPS with localized and resectable primary lesions., Methods: This retrospective analysis included data of 2112 patients with localized UPS arising in the extremities and trunk, extracted from a registry in Japan. We estimated overall survival (OS), identified prognostic factors, and adjusted patient characteristics in the two groups treated with or without chemotherapy using propensity score matching (PSM)., Results: The 5-year OS rate was 79.4%. In multivariate OS analysis, adjuvant chemotherapy was a good prognostic factor (hazard ratio 0.65; 95% confidence interval 0.48-0.9, P = 0.009). Large tumor size was the poorest prognostic factor, and OS decreased with the tumor size (P < 0.0001). In all patients, adjuvant chemotherapy prolonged OS (5-year OS: 82.3% vs. 78.6%, P = 0.03). Adjuvant chemotherapy did not affect OS in patients with tumor size < 5 cm; the benefit was strong in patients with tumor size 10 to < 15 cm (5-year OS: 79.5% vs. 66.8%, P = 0.003). Adjuvant chemotherapy efficacy was not pronounced in patients with tumor size 5 to < 10 cm (5-year OS: 87% vs. 80%, P = 0.06) and ≥ 15 cm (5-year OS: 60.7% vs. 49.5%, P = 0.08). After PSM, adjuvant chemotherapy was significantly associated with improved OS (P = 0.02)., Conclusions: In patients with localized UPS, adjuvant chemotherapy tended to improve OS when tumors were ≥ 5 cm, especially when they were 10 to < 15 cm., (© 2021. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Myositis ossificans is a benign, ossifying, soft-tissue pseudotumor that most commonly occurs in men ages 30-40 years after trauma. Myositis ossificans may also occur in children, but it is extremely rare in those younger than 10 years of age. While myositis ossificans can often mimic malignant soft-tissue tumors, it has many unique findings that can aid in diagnostic differentiation. This differentiation is critical to avoid unnecessary risk with potentially harmful procedures. We present a very unusual presentation of myositis ossificans in the immediate post-birth perinatal period, as well as a review of key imaging findings., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The cytopathology of a giant cell tumor of soft tissue (GCT-ST), a fibrohistiocytic neoplasm distinct from other giant cell-rich soft tissue tumors, is rarely reported. The authors report their experience with a series of 4 GCT-ST fine-needle aspiration (FNA) biopsy cases and compare them with a set from giant cell tumors of bone (GCTBs)., Methods: The authors' cytopathology files were searched for GCT-ST examples with histopathologic confirmation. FNA biopsy smears were performed and examined with standard techniques., Results: Four cases of GCT-ST presenting as a primary soft tissue mass from 4 patients (3 males and 1 female; age range, 28-75 years, mean age, 53 years) were retrieved. FNA sites included the anterior tibia, buttock, shoulder, and upper back. Three cases were interpreted as suspicious for sarcoma radiographically. The specific diagnoses were atypical giant cell tumor of tendon sheath, suspicious for GCT-ST, atypical myxoid lesion with giant cells, and benign with osteoclast-like giant cells (OLGCs). No case was interpreted as malignant. Aspirates consisted of mononuclear polygonal cells, spindled fibroblast cell clusters, and large OLGCs to the near exclusion of other cell types. OLGCs possessed 10 or more nuclei per cell. A comparison with GCTB aspirates and single case reports from the literature showed comparable cytomorphology., Conclusions: GCT-ST FNA smears mimic those of GCTBs containing a limited population of uniform spindle cell clusters, single dispersed polygonal cells, and cytologically banal OLGCs. GCT-ST should be considered in the differential diagnosis of aspirates containing numerous osteoclast-like giant cells., (© 2021 American Cancer Society.)

Background: Soft tissue sarcomas (STS) are rare, and little is known about the factors that affect the delays in the initial treatment. The aim of this study is to quantify the period between onset of symptoms and start of treatment of STS and determine the factors affecting delays in initial treatment. Methods: This is a retrospective study of all STS treated in our institution between October 2009 and March 2019. We analysed patient record to determine the period from onset of symptoms to start of initial treatment. We also collected data with regard to patient characteristics and features of the tumour. Tumours were classified into upper extremity, lower extremity, trunk and others based on location of the tumour. Statistical tests were done to identify factors that affected delay in initial treatment. Results: The study included 134 patients (76 male and 58 female) with STS with an average age of 56.6 years. The tumours involved the upper extremity in 20 patients, lower extremity and trunk in 50 patients each and other areas in 14 patients. The most frequent histological subtypes were liposarcomas ( n = 31, 23.5%) and undifferentiated pleomorphic sarcomas ( n = 24, 18.2%). Initial treatment was delayed by an average of 9.9 months for all groups. The period of treatment delay for tumours involving the upper extremity was shorter (7.9 months) and these tumours were smaller at initial presentation (57.6 mm) compared to tumours in other locations ( p < 0.05). Other factors that were positively associated with treatment delays were a history of diabetes mellitus ( p = 0.037) and smoking ( p = 0.026). Conclusion: Patients with upper-extremity STS may have the benefit of a relatively better prognosis as they present earlier and with a smaller tumour. In addition, factors, such as diabetes and smoking, which indicate a low interest in health also influenced the delay in the initial treatment. Level of Evidence: Level III (Therapeutic).

Background and Objectives : Sarcomas are rare malignant tumors of mesenchymal origin. Their low prevalence and histological heterogeneity make their diagnosis a challenging task. To the best of our knowledge, the epidemiology of soft tissue sarcomas (STSs) was not well studied in Jordan. This study thus aimed to determine STS epidemiologic trends at King Abdullah University Hospital (KAUH); a tertiary hospital that provides cancer healthcare for 70% of the population in Irbid Governorate, North Jordan. The findings of this study will provide a good reference point of the burden of STSs in Jordan and the Middle East region. Materials and Methods : All cases with confirmed STS diagnoses who attended KAUH from January 2003 until December 2018 were included in the initial analysis. Bone sarcomas, gastrointestinal stromal tumors and uterine sarcomas were not included in the study. Information collected from the pathology reports and electronic medical records was used to determine STS prevalence, incidence rate, age and gender distributions, histological types and anatomic location. Cases were reviewed by three pathologists with interest in soft tissue tumors. The findings were compared with literature. Results : In total, 157 STS cases were reported (1.9% of cancers diagnosed at KAUH during the 16-year study period). Crude annual incidence rate (IR) per 100,000 person-years ranged from 0.48 in 2015 to 1.83 in 2011 (average = 1.04). Age-standardized IR (ASR) (World &nbsp; WHO &nbsp; 2000-2025) was 1.37. Male:female ratio was 1.3:1. Median age was 39 years. Age ranged from <1 year to 90 years. Overall STS rates increased with age. The most common histological types were liposarcoma (19%), rhabdomyosarcoma (17%) and leiomyosarcoma (10%). The most common anatomic location was the extremity (40.1%), followed by the trunk (14.7%), then head and neck (10.8%). Conclusion : STSs are rare in North Jordan. A slight increase in their incidence was identified during the study period similar to global trends. The collection of relevant data on established risk factors along with a broader scale evaluation of the epidemiology of STS in the Middle East region is recommended to better evaluate disease burden and trends.

Background: The degree of contamination of healthy tissue with tumor cells during a biopsy in bone or soft tissue sarcomas is clearly dependant on the type of biopsy. Some studies have confirmed a clinically relevant contamination of the biopsy tract after incisional biopsies, as opposed to core-needle biopsies. The aim of our prospective study was to evaluate the risk of local recurrence depending on the biopsy type in extremity and pelvis sarcomas., Methods: We included 162 patients with a minimum follow-up of 6 months after wide resection of extremity sarcomas. All diagnostic and therapeutic procedures were performed at a single, dedicated sarcoma center. The excision of the biopsy tract after an incisional biopsy was performed as a standard with all tumor resections. All patients received their follow-up after the conclusion of therapy at our center by means of regional MRI studies and, at a minimum, CT of the thorax to rule out pulmonary metastatic disease. The aim of the study was the evaluation of the influence of the biopsy type and of several other clinical factors on the rate of local recurrence and on the time of local recurrence-free survival., Results: One hundred sixty-two patients with bone or soft tissue tumors of the extremities and the pelvis underwent either an incisional or a core-needle biopsy of their tumor, with 70 sarcomas (43.2%) being located in the bone. 84.6% of all biopsies were performed as core-needle biopsies. The median follow-up time was 55.6 months, and 22 patients (13.6%) developed a local recurrence after a median time of 22.4 months. There were no significant differences between incisional and core-needle biopsy regarding the risk of local recurrence in our subgroup analysis with differentiation by kind of tissue, grading of the sarcoma, and perioperative multimodal therapy., Conclusions: In a large and homogenous cohort of extremity and pelvic sarcomas, we did not find significant differences between the groups of incisional and core-needle biopsy regarding the risk of local recurrence. The excision of the biopsy tract after incisional biopsy in the context of the definitive tumor resection seems to be the decisive factor for this result., (© 2022. The Author(s).)

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.

Introduction: Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few studies that attempt to correlate histopathologic response to NRT with oncologic outcomes in patients with STS., Methods: Using our institutional database, we identified 58 patients who received NRT followed by surgical resection for primary intermediate or high-grade STS and 34 patients who received surgical resection without NRT but did receive adjuvant radiation therapy or did not receive any radiation therapy. We analyzed four histologic parameters of response to therapy: residual viable tumor, fibrosis/hyalinization, necrosis, and infarction (each ratiometrically determined). Data were stratified into two binary groups. Unadjusted, 5- and 10-year overall survival, and relapsed-free survival (RFS) were calculated using the Kaplan-Meier method., Results: Analysis of pathologic characteristics showed that patients treated with NRT demonstrate significantly higher tumor infarction, higher tumor fibrosis/hyalinization, and a lower percent viable tumor compared with patients not treated with NRT (p < 0.0001). Based on Kaplan-Meier curve analysis and multivariate cox proportional hazard model for OS and RFS, patients treated with NRT and showing >12.5% tumor fibrosis/hyalinization have significantly higher overall survival and recurrence-free survival at 5 and 10 years., Discussion and Conclusion: We have identified three histopathologic characteristics-fibrosis, hyalinization, and infarction-that may serve as predictive biomarkers of response to NRT for STS patients. Future prospective studies will be needed to confirm this association., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Small round cell sarcomas (SRCSs) account for most solid malignancies in the pediatric age group and are a part of group of malignant tumors characterized by heterogenous clinical presentation and overlapping microscopic features of small, round, primitive cells. In addition to the recently established certain genetically defined subset of undifferentiated round cell sarcomas of soft tissue and bone, this group of sarcomas include desmoplastic small round cell tumor, poorly differentiated synovial sarcoma, alveolar rhabdomyosarcoma, mesenchymal chondrosarcoma, and small cell osteosarcoma. Although, those entities share clinical and cytomorphologic features and cannot be unequivocally classified based on clinical presentation and morphology alone. Most of SRCSs characterizes of particular patterns of protein expression or genetic changes and ancillary tests remain necessary to confirm or rule out a specific diagnosis. Subtle but occasionally distinctive cytologic features narrows the number of differential diagnoses and helps to select appropriate ancillary tests necessary for the final diagnosis. Thus, when adequate fine needle aspiration (FNA) biopsy specimen is combined with ancillary tests, a specific histologic diagnosis can be made in almost all cases. However, due to complex cytologic features of SRCS as well as various quality and diversity of FNA smears, there are cases in that cytologic features which do not entirely match the known diagnostic criteria., Summary: The aim of this review was to summarize cytomorphologic criteria and to present rare and divergent cytological features of SRCSs. Careful assessment of clinical presentation, cytological features, immunohistochemical patterns, and molecular alternations is necessary for an accurate diagnosis. Knowing of rare and divergent microscopic findings that does not fit with the known cytological criteria will help to avoid misdiagnosis., Key Messages: The role of FNA biopsies diagnosing soft tissue and bone tumors has been increasing because of the ability of ancillary tests to assist in the diagnosis of specific tumors. SRCSs may be diagnosed accurately in cytology specimens. Access to clinical and radiographic presentation, utility of ancillary tests, understanding complexity of cytological features, and awareness of the rare cytologic findings that differ from that of the established diagnostic criteria are essential to make correct diagnosis., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Purpose: A prior phase I study showed that the neo-adjuvant combination of pazopanib and radiotherapy was well tolerated, and induced promising pathological responses in soft-tissue sarcoma patients. Results of the subsequent prospective, multicenter phase II, PASART-2 trial are presented here, further investigating the efficacy and safety of this combination., Patients and Methods: Patients with high-risk, localized soft-tissue sarcoma received neo-adjuvant radiotherapy, 50 Gy in 25 fractions (PASART-2A) or with a subsequent dose de-escalation to 36 Gy in 18 fractions (PASART-2B). This was combined with 800 mg once daily pazopanib, which started one week before radiotherapy and finished simultaneously. After an interval of 4-8 weeks, surgical resection was performed. The primary endpoint was the rate of pathological complete responses (pCR), defined as ≤5% viable cells., Results: 25 patients were registered in the study, 21 in PASART-2A and 4 in PASART-2B. After central pathology review, the combination treatment led to a pCR in 5 patients (20%). 17 patients (68%) experienced grade 3+ toxicities during neo-adjuvant treatment, of which the most common were alanine aminotransferase (ALT) elevation, aspartate aminotransferase (AST) elevation, and hypertension, all asymptomatic. Grade 3+ acute post-operative toxicities occurred in 5 patients (20%), of which the most common was wound infection. All patients completed the full radiotherapy regimen and underwent surgery. Pazopanib was discontinued before completion in 9 patients (36%), due to elevated ALT and/or AST, and shortly interrupted in 2 patients (8%), due to hypertension., Conclusion: Apart from asymptomatic hepatotoxicity, the study regimen was well tolerated. Although the pre-specified efficacy endpoint (30% pCR) was not met, a more than doubling of historical pCR rates after neo-adjuvant radiotherapy alone was observed, which warrants further investigation.

Background: The literature on bone and soft tissue sarcomas (BSTSs) involving effusions and cerebrospinal fluid (CSF) is very limited., Methods: A computerized search for fluid cytology with a sarcoma diagnosis from 2000 to 2020 was performed. All available cases, including the clinical follow-up, were reviewed., Results: A total of 57 fluids specimens from 36 BSTSs were identified (9 rhabdomyosarcomas, 6 angiosarcomas, 5 epithelioid hemangioendotheliomas, 3 dedifferentiated liposarcomas, 2 chondrosarcomas, 1 extraskeletal myxoid chondrosarcoma, 3 Ewing sarcomas, 2 undifferentiated sarcomas, 3 osteosarcomas, 1 synovial sarcoma, and 1 hybrid low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma). There were 22 males and 14 females. The age range was 4 to 82 years (median, 45 years). Sites of involvement included pleural fluid (n = 38), peritoneal fluid (n = 14), and CSF (n = 5). Twenty-four cytology cases were available for review. The cytologic features were nonspecific and ranged from dyshesive to clusters of round, epithelioid, pleomorphic, and occasionally spindle-shaped malignant cells that could easily mimic other non-BSTS malignant tumors. The diagnosis of BSTS was made by comparison with a prior specimen and/or ancillary studies (molecular or immunohistochemical stains). The prognosis was poor because 95% of the patients died of their disease., Conclusions: The incidence of BSTS in fluid cytology is extremely rare, and it can have cytologic features similar to those of non-BSTS malignancies. Although, in most cases, a comparison with a prior known BSTS specimen may suffice, the use of ancillary studies is extremely helpful in arriving at the correct diagnosis. However, in cases with no known prior malignancy, including BSTS in the differential diagnosis is prudent for preventing misdiagnosis., (© 2021 American Cancer Society.)

Introduction: Solitary fibrous tumor (SFT), a fibroblastic neoplasm characterized by a specific genetic alteration (NAB2-STAT6 fusion) and relatively specific immunohistochemical profile (STAT6/CD34 positivity), is seldom the subject of cytopathology data. We report our experience with scrape smears and fine-needle aspiration (FNA) biopsies of SFT in a large patient cohort., Materials and Methods: A search was made of our cytopathology and surgical pathology databases for cases diagnosed as solitary fibrous tumor (SFT). FNA biopsy smears, imprint smears, and cell blocks were performed and examined using standard technique., Results: Thirty-four cases from 30 patients (M:F = 1.1:1; age range: 24-86 years, x = 58 years) met inclusion criteria for this study. All patients had prior or subsequent tissue confirmation of SFT. Twenty-seven (79%) specimens were FNAs, and 7 (21%) were scrape smears. Most cases (29, 85%) represented primary tumors, 4 (12%) were metastatic deposits, and 1 (3.5%) was a locally recurrent neoplasm. Sites included: pleura/lung 9 (26%), head/neck 8 (24%), lower extremity 7 (21%), trunk 4 (12%), intra-abdominal 3 (9%), upper extremity 2 (7%), and mediastinum 1 (4%). Mean tumor size was 7.2 cm (range: 1.5-19 cm). Three (9%) cases were diagnosed specifically as SFT. Remaining diagnoses were spindle cell neoplasm/proliferation 14 (41%), nondiagnostic 5 (15%), specific type of sarcoma 3 (9%), malignant round cell tumor 2 (6%), sarcoma 2 (6%), malignant tumor 2 (6%) and single cases of melanoma, pleomorphic adenoma, and mesenchymal tumor. Immunohistochemical (IHC) testing was performed in 7 of 27 (26%) cell blocks., Conclusion: SFT FNA cytopathology is morphologically ambiguous, overlapping with a broad array of other spindle cell proliferations. A specific diagnosis is only possible with added staining of STAT6 coupled with a set of other IHC markers., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Diagnosing bone and soft tissue neoplasms remains challenging because of the large number of subtypes, many of which lack diagnostic biomarkers. DNA methylation profiles have proven to be a reliable basis for the classification of brain tumours and, following this success, a DNA methylation-based sarcoma classification tool from the Deutsches Krebsforschungszentrum (DKFZ) in Heidelberg has been developed. In this study, we assessed the performance of their classifier on DNA methylation profiles of an independent data set of 986 bone and soft tissue tumours and controls. We found that the 'DKFZ Sarcoma Classifier' was able to produce a diagnostic prediction for 55% of the 986 samples, with 83% of these predictions concordant with the histological diagnosis. On limiting the validation to the 820 cases with histological diagnoses for which the DKFZ Classifier was trained, 61% of cases received a prediction, and the histological diagnosis was concordant with the predicted methylation class in 88% of these cases, findings comparable to those reported in the DKFZ Classifier paper. The classifier performed best when diagnosing mesenchymal chondrosarcomas (CHSs, 88% sensitivity), chordomas (85% sensitivity), and fibrous dysplasia (83% sensitivity). Amongst the subtypes least often classified correctly were clear cell CHSs (14% sensitivity), malignant peripheral nerve sheath tumours (27% sensitivity), and pleomorphic liposarcomas (29% sensitivity). The classifier predictions resulted in revision of the histological diagnosis in six of our cases. We observed that, although a higher tumour purity resulted in a greater likelihood of a prediction being made, it did not correlate with classifier accuracy. Our results show that the DKFZ Classifier represents a powerful research tool for exploring the pathogenesis of sarcoma; with refinement, it has the potential to be a valuable diagnostic tool., (© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

Sarcoma comprises a group of malignancies that includes over 100 individual disease entities. Type-specific genetic events initiate each tumor, occurring within a specific cellular context or circumstance. All sarcomas share a relationship with mesenchymal tissues of origin. Conceptual models for each specific route towards sarcomagenesis have developed over the years as clinical, cellular, and increasingly molecular observations have advanced hypotheses to be tested in the forward or reverse direction in experimental systems, often genetically engineered model organisms. This review considers the history of these discoveries in the context of technologies available at the time each was made and provides a comprehensive summary of the current knowledge of sarcoma genetics, including characteristic translocations, oncogene activation and loss of tumor suppressor gene events, and their putative cells of origin. Also considered are the interrelatedness of molecular clinical observations and genetic experiments in model systems to move this field of knowledge forward, as well as their implications for diagnostic and therapeutic paradigms for sarcoma. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Epithelioid sarcoma (ES) of the hand is a rare, aggressive cutaneous malignancy with high rates of recurrence, metastases and mortality. With an incidence rate of 0.4 cases/y per one million population, which compromise for approximately 1-1.4% of all soft tissue sarcoma, ES accounts for 10% of soft tissues sarcomas of the hand and foot. Its aggressiveness and propensity to spread and metastases without being noticed, makes it unique and potentially lethal. Missed or delayed diagnosis are often encountered as this tumor can mimic variety of different entities and due to the infrequent nature of this lesion, treatment options are still controversial. The authors provide systemic review of the current literature on epidemiology, etiology, pathogenesis, management and outcomes of this disease as well as a case presentation and a proposed treatment algorithm. The choice of treatment option depends on disease characteristics, staging at presentation, regional lymph node involvement, comorbidities and performance status of the patient. Emphasis on a multidisciplinary coordinated care is crucial as early diagnosis and treatment can decrease morbidity and mortality rates.

Objectives: The objectives of this study included utilising a large database from a diagnostic laboratory to identify any breed, sex or age predilections for cutaneous and subcutaneous soft tissue sarcomas (STSs), and the most common anatomical locations. The second aim was to obtain clinical outcomes and to assess histological features of those tumours to identify any potentially useful prognostic indicators and propose a grading system., Methods: Records from the laboratory were searched for feline submissions received from January 2012 to December 2013 diagnosed with STSs; the breed, age, sex and neuter status of the cat and anatomical location of the tumour were recorded. Clinical outcomes were acquired using a questionnaire to submitting practices, and histological features of tumours from patients with known outcomes were assessed., Results: No sex, neuter status or breed predispositions were found. Most STSs arise in middle-aged and older cats, and the most common anatomical location was the trunk. Forty-seven cases had a known clinical outcome and archived tissues allowing for histological assessment of the tumour. Significant differences in median survival time (MST), mitotic index and histological score were detected between those cats that died of tumour-related disease and those that did not. A novel grading system applied to these tumours produced significant differences in MST between cats with low (MST = 900.5 days), intermediate (MST = 514 days) and high grade tumours (MST = 283 days)., Conclusions and Relevance: This is the first study applying a histological grading system to these common tumours. Local recurrence is often the cause of a poor outcome, with metastatic disease apparently rare. The proposed grading system incorporates features that can be assessed on routine haematoxylin and eosin-stained sections; in this small study, the histological grade of the tumour appears to be associated with survival time.

Background: IL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited., Methods: This study investigated the immunohistochemical expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. Immunohistochemical staining for IL4Rα and IL13Rα1 were scored according to a combination of staining intensity and staining area in tissue microarray samples. Positivity for the immunohistochemical expression of IL4Rα and IL13Rα1 were determined using receiver operating curve analysis. Statistical analysis was performed using regression analysis and a chi-square test., Results: In human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p < 0.001) of soft-tissue sarcoma patients. Moreover, the co-expression pattern of nuclear IL4Rα and IL13Rα1 was an independent indicator of shorter survival of soft-tissue sarcoma patients (overall survival; overall p < 0.001, relapse-free survival; overall p < 0.001)., Conclusions: This study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.

The most widely used patient-reported outcome (PRO) measure for soft tissue sarcoma (STS) patients is the Toronto Extremity Salvage Score (TESS). The aim of the study was to validate and test the reliability of the TESS for patients with lower extremity STS based on Finnish population data. Patients were assessed using the TESS, the QLQ-C30 Function and Quality of life (QoL) modules, the 15D and the Musculoskeletal tumour Society (MSTS) score. The TESS was completed twice with a 2- to 4-week interval. The intraclass correlation coefficient (ICC) was used for test-retest reliability. Construct validity was tested for structural validity and convergent validity. Altogether 136 patients completed the TESS. A ceiling effect was noted as 21% of the patients scored maximum points. The ICC between first and second administration of the TESS was 0.96. The results of exploratory factor analysis together with high Cronbach's alpha (0.98) supported a unidimensional structure. The TESS correlated moderately with the MSTS score (rho = 0.59, p< 0.001) and strongly with the mobility dimension in the 15D HRQL instrument (rho = 0.76, p < 0.001) and the physical function in QLQ-C30 (rho = 0.83, p< 0.001). The TESS instrument is a comprehensive and reliable PRO measure. The TESS may be used as a validated single index score, for lower extremity STS patients for the measurement of a functional outcome. The TESS seems to reflect patients' HRQoL well after the treatment of lower extremity soft tissue sarcomas., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Biphenotypic sinonasal sarcoma is an anatomically restricted low-grade malignant neoplasm with dual neural and myogenic differentiation composed of a monotonous population of spindled cells with herringbone/fascicular architecture. These tumors demonstrate a unique immunoprofile with relatively consistent S100-protein and actin expression in conjunction with more variable desmin, myogenin and myoD1 staining. SOX10 is uniformly negative. Genetically, the majority of tumors harbor PAX3-MAML3 fusions, with alternate PAX3 partners including FOXO1, NCOA1, NCOA2 and WWTR1. Although the differential diagnosis of BSNS is broad, careful morphologic inspection together with targeted ancillary studies is often sufficient to arrive at the correct diagnosis. As these tumors have significant local recurrence rates but lack metastatic potential, awareness and accurate diagnosis of this rare and newly described neoplasm is critical for appropriate management.