Clear Cell Sarcoma Research Articles

Prognostic factors in clear cell sarcoma: an analysis of soft tissue sarcoma in 43 cases.

Clear cell sarcoma (CCS) of tendons and aponeuroses and CCS-like malignant gastrointestinal neuroectodermal tumor/sarcoma (GINET) are characterized by frequent local and distant relapses, alongside with low efficacy of all systemic treatments. We aimed to collect a comprehensive dataset to identify prognostic factors and treatment outcomes. We performed a retrospective single center analysis for diagnosed CCS and GINET on demographic, tumor, treatment and survival data. We identified 43 patients (w:25, m:18) with a median follow-up of 35mo and a 5y-OS-rate of 42%. At diagnosis the median age was 42yrs. Median tumor size was 3.6cm (0.3-11.1cm), and 24/26 (94%) tissues analyzed at our institute were EWSR1::ATF1-translocation-positive. Distant extremities (incl. knee or elbow) were affected in 72.5%. Of note, 79.5% received an excisional biopsy (benign histology suspected in 30.2%) leading to frequent incomplete resection. Final R0 status correlated significantly (p = 0.017) with longer survival rates compared to R + status in localized CCS (N0M0, 5-yr OS 0% vs 64%). Radiation and systemic treatment had limited antitumor effects while isolated limb perfusion was active in some patients. 18.6% of patients showed lymphatic spread and 20.9% distant metastases. Presence of initial M + was associated with a dismal survival of 1.4years (M +) vs 7.1years (M0; p < .001). We here present one of the largest clinical cohorts of patients with CCS/GINET. Our data underscores the exceptional risk of metastatic disease even in small tumors. As systemic treatment and radiation showed limited efficacy, complete resection was the most important treatment option.

Medical imaging for the diagnosis, recurrence and metastasis evaluation of clear cell sarcoma

Clear cell sarcoma (CCS) of soft tissue is extremely rare, accounting for approximately 1% of all soft tissue tumours. It is very difficult to diagnose CCS based on clinical manifestations. Magnetic resonance imaging (MRI) provides high-resolution images of soft tissues and pathological features such as mucus, necrosis, bleeding, and fat through high and low signals on T1 weighted image (T1WI) and T2 weighted image (T2WI). On the other hand, the paramagnetism of melanin in CCS shortens the relaxation time of T1 and T2, and high signal intensity on T1WI and low signal intensity on T2WI can be found. This is different from most other soft tissue sarcomas. At present, the treatment method for CCS is surgical resection. MRI can effectively display the tumour edge, extent of surrounding oedema, and extent of fat involvement, which is highly important for guiding surgical resection and predicting postoperative recurrence. As an invasive sarcoma, CCS has a high risk of metastasis. Regardless of the pathological condition of the resected tumour, MRI or computed tomography (CT) should be performed every 1-2 years to assess recurrence at the primary site and to screen for metastasis in the lungs, liver, and bones. If necessary, PET-CT can be performed to evaluate the overall condition of the patient.

Metastatic clear cell sarcoma of the pancreas: An overview

Clear cell sarcoma (CCS) is a rare soft-tissue sarcoma that accounts for less than 1% of all cases and was originally reported in 1965. The incidence of CCS is estimated to be approximately 0.014/100000 depending on the surveillance, epidemiology and end results databases. CCS is a highly invasive type that mainly metastasizes to the lungs, followed by the bones and brain; however, pancreatic metastasis is relatively rare. It has a high probability of recurrence or metastasis and has a poor prognosis with a high mortality rate. Finally, even after recovery, it is fundamental to keep regular postoperative follow-up for CCS patients.

Solid pancreatic masses: What’s hidden beneath? Insights into rare pancreatic lesions

The diagnostic approach to solid pancreatic masses has significantly evolved from the era when a focal pancreatic mass was almost synonymous to pancreatic ductal adenocarcinoma, to a wide spectrum of pancreatic lesions, some of which have good prognosis. With the advent of advanced diagnostic tools, particularly refined imaging and tissue acquisition techniques, a broader spectrum of differential diagnoses has been recognized, encompassing conditions ranging from neuroendocrine tumors or inflammatory masses, to rare entities like metastatic clear cell sarcoma or solitary fibrous tumors. We herein discuss case reports of some rare pancreatic lesions, which were diagnosed by combining clinical and imaging features and endoscopic ultrasound-guided tissue sampling and confirmed on surgical specimens. Further reports on these rare pancreatic tumors will contribute to a better understanding of their pathogenesis and effective management.

CRTC1::TRIM11-fusion tumor with rare sinonasal presentation and locally aggressive disease course

Abstract Introduction/Objective Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT) is a rare dermatological neoplasm that has not yet been formally recognized by the World Health Organization. At present, our knowledge of this disease is limited to single reports and a series 41 cases with limited follow-up information. It is typically described as a skin lesion expressing melanocytic makers, often leading to its misdiagnosis as melanoma or clear cell sarcoma. CMTCT is regarded as an indolent tumor with infrequent recurrence after complete surgical excision. However, we present a case with uncommon sinonasal presentation and metastasis after multiple resections. Methods/Case Report A 23-year-old woman presented with a right nasal vestibule mass, requiring partial rhinectomy in a foreign country, where she subsequently received chemoradiation. Her tumor at the time was diagnosed as a mucosal melanoma. Eleven years following initial presentation, she demonstrated a recurrent right nasal tumor, as well as neck mass, cervical lymphadenopathy, and lung nodules. The patient then underwent a nasal endoscopic resection and modified neck dissection, which demonstrated a high-grade neoplasm with intersecting fascicles of medium-to-large monomorphic cells; whole exome and whole transcriptome sequencing performed on the resected neck mass identified a pathogenic TERT c.-146C&amp;gt;T alteration and CRTC1 exon 1::TRIM11 exon 2 fusion. The patient is currently alive and undergoing post-surgical chemoradiation. Results (if a Case Study enter NA) NA Conclusion This case expands our understanding of CMTCT and emphasizes its potentially aggressive behavior. The sinonasal presentation contrasts the tumor’s typical appearance on the skin and could mimic mucosal melanoma. Of note, our patient developed recurrent disease and distant metastases, thereby emphasizing the possible role of systemic therapy and suggesting that simple surgical excision may not be curative in all cases. Our case illustrates that CMTCT is an uncommon and potentially misidentified neoplasm, but that its proper diagnosis is essential for treatment selection and follow up.

Extra-abdominal and intra-abdominal FET::CREM fusion mesenchymal neoplasms: comparative clinicopathological study of 9 new cases further supporting a distinct potentially aggressive sarcoma and report of novel sites.

With the wide use of RNA sequencing technologies, the family of FET::CREB fusion mesenchymal neoplasms has expanded rapidly to include potentially aggressive neoplasms, not fitting any well established WHO entity. Recently, a group of intra-abdominal FET(EWSR1/FUS)::CREB(CREM/ATF1) fused unclassified neoplasms has been reported followed by recent recognition of an analogous extra-abdominal category of unclassified neoplasms carrying EWSR1::ATF1 fusions. We describe 9 additional tumors (5 extra-abdominal and 4 abdominal) carrying an EWSR1::CREM (n = 8) and FUS::CREM (n = 1) fusion. Patients were 7 females and 2 males aged 10 to 75years (median, 34). Extra-abdominal tumors originated in the head and neck (2 sinonasal, 1 orbital) and soft tissues (1 gluteal, 1 inguinal). Abdominal tumors involved stomach (2), mesentery (1), and kidney (1). Tumor size ranged from 3.5 to 11cm (median, 6). Treatment was radical surgery with (5) or without (2) neo/adjuvant radio/chemotherapy. Extended follow-up of 5 patients (21-52months; median, 24) showed an aggressive course in two (40%); one died of disseminated metastases 52months after several intensified chemotherapy regimens, and one was alive with progressive abdominal disease at 21months. The immunophenotype of the two subcohorts was significantly overlapping with variable expression of EMA (7 of 8), keratin AE1/AE3 (5 of 9), CD99 (4 of 7), MUC4 (2 of 8), ALK (3 of 8), synaptophysin (3 of 9), chromogranin (1 of 8), CD34 (3 of 6), CD30 (1 of 6), PAX8 (1 of 7), and inhibin (1 of 7), but no reactivity with desmin (0 of 8), S100 (0 of 8), and SOX10 (0 of 8). This series further solidifies the notion that FET::CREB fusions are not limited to the triad of angiomatoid fibrous histiocytoma, clear cell sarcoma, and malignant gastrointestinal neuroectodermal tumor, but characterize an emerging family of potentially aggressive neoplasms occurring at both intra- and extra-abdominal sites. These tumors underscore the promiscuity of the FET::CREB fusions and highlight the pivotal role of phenotype-oriented classification of these neoplasms that share the same genotype, still featuring significant biological and behavioral distinctness.

1778P Clear cell sarcomas (CCS) express Gp100: A novel immune target for a bispecific T cell engager

1778P Clear cell sarcomas (CCS) express Gp100: A novel immune target for a bispecific T cell engager

Foot Tumor: Comprehensive Collation and Evaluation

Background: Considerable evidence showed that foot tumors can cause severe harm to people across various age groups, though they have relatively low incidence rate. Currently, substantial research articles provide thorough discoveries among diagnosis, treatment, reconstruction, and other related areas. However, a comprehensive literature evaluation of current study findings is required. Methods: A search approach implementing the PICOS principle was utilized to acquire the literature from mainly three databases—PubMed, NCBI and SpringerLink. All the included studies underwent independent screening and evaluations of quality and risk of bias. The outcomes covered evaluation and comparison of various tumor kinds, diagnostic techniques, treatment modalities, and reconstructive procedures. Results: The location of the foot is characterized by the presence of three primary bone tumor types — osteosarcoma (OS), chondrosarcoma (CDS) and Ewing sarcoma (ES)— and four forms of soft tissue tumor—Synovial sarcoma (SS), epithelioid sarcoma (EPS), clear cell (CC) sarcoma and melanoma. Diagnosis involves the utilization of four approaches—CT, MRI, X-ray and biopsy, either singly or in combination. Out of all the options, biopsy is the most effective and accurate. Surgery and immunotherapy are widely used to treat foot tumor. The advancement of immunotherapy can significantly improve the efficiency and effectiveness of foot tumor treatment due to its specific targets and better established adjustment mechanism. Combining various types of immunotherapy with additional medicines such as chemotherapy and radiotherapy can help improve the progression of foot tumor treatment. For the reconstruction methods, Structural allograft Plastic surgery is widely used for bone tumor and soft tissue sarcoma respectively. Conclusion: The clinical significance of foot tumors is attributed to their infrequency, resulting high possibility of delayed detection and difficulties in proper treatment. The text that provides a comprehensive discussion and analysis of the diagnostic, therapeutic tactics, and repair approaches for the foot tumor can be highly beneficial to the development of foot tumor in the medical area. The methodical collation on characteristics, data of foot tumor categories is therefore equally significant. By obtaining and analyzing such information, researchers and physicians can better identify certain pattern in foot tumor. For the treatment, Immunotherapy stands out among the existing methods since it has the highest potential to selectively target certain types of foot tumors depending on their distinct needs. The evaluation of immunotherapy and reconstruction methods still contain some limitations due to the lack of the latest and adequate research.

53820 14 Cases of Clear Cell Sarcoma of Soft Tissue: Comparative Analysis of Cutaneous Type versus Tendon and Aponeurosis Type

53820 14 Cases of Clear Cell Sarcoma of Soft Tissue: Comparative Analysis of Cutaneous Type versus Tendon and Aponeurosis Type

Clear cell sarcoma in Japan: an analysis of the population-based cancer registry in Japan.

Clear cell sarcoma is rare, so no reports have previously characterized its national profiles. We examined the nationwide epidemiology and clinical outcomes of patients with clear cell sarcoma based on the National Cancer Registry in Japan. Overall, 23 522 patients with soft tissue sarcoma-entered in the National Cancer Registry in 2016-2019 using the International Classification of Diseases for Oncology, Third Edition cancer topography and morphology codes-were enrolled in either the clear cell or the non-clear cell sarcoma group. Data extracted included: demographics (sex and age), tumor details (reason for diagnosis, tumor location, histology and stage), hospital volume and facility type, treatment and prognosis for each patient. Of 23 522 soft tissue sarcoma patients, 122 were enrolled in the clear cell sarcoma group and 23 400 in the non-clear cell sarcoma group. The incidence of clear cell sarcoma was 0.52% of all soft tissue sarcoma, with an age-adjusted incidence of 0.024/100 000/year. The age at diagnosis was significantly younger, and more tumors were at the localized stage in the clear cell than the non-clear cell sarcoma group. In addition, the overall survival in the clear cell group was worse than in the non-clear cell group (P<0.001). Of 122 patients with clear cell sarcoma, the localized stage, surgical treatment and treatment without chemotherapy were associated with better overall survival in the univariate analyses. The present study is the first to have clarified the epidemiology, clinical features, treatment, prognosis and significant factors affecting the prognosis of patients with clear cell sarcoma in Japan.

ERBB2/ ERBB3-mutated S100/ SOX10-positive unclassified high-grade uterine sarcoma: first detailed description of a novel entity.

With the increasing use of innovative next generation sequencing (NGS) platforms in routine diagnostic and research settings, the genetic landscape of uterine sarcomas has been dynamically evolving during the last two decades. Notably, the majority of recently recognized genotypes in uterine sarcomas represent gene fusions, while recurrent oncogene mutations of diagnostic and/ or therapeutic value have been rare. Recently, a distinctive aggressive uterine sarcoma expressing S100 and SOX10, but otherwise lacking diagnostic morphological, immunophenotypic and molecular features of other uterine malignancies has been presented in a scientific abstract form (USCAP, 2023), but detailed description and delineation of the entity is still missing. We herein describe two high-grade unclassified uterine sarcomas characterized by spindle to round cell morphology and diffuse expression of S100 and SOX10, originating in the uterine body and cervix of 53- and 45-year-old women and carrying an ERBB3 (p.Glu928Gly) and an ERBB2 (p.Val777Leu) mutation, respectively. Both tumors harbored in addition genomic HER2 amplification, ATRX mutation and CDKN2A deletion. Methylation studies revealed a methylome most similar to MPNST-like tumors, but distinct from melanoma, MPNST, clear cell sarcoma, and endometrial stromal sarcoma. Case 1 died of progressive peritoneal metastases after multiple trials of chemotherapy 47months after diagnosis. Case 2 is a recent case who presented with a cervical mass, which was biopsied. This study defines a novel heretofore unrecognized aggressive uterine sarcoma with unique phenotypic and genotypic features. Given the potential value of targeting HER2, recognizing this tumor type is mandatory for appropriate therapeutic strategies and for better future delineation of the entity.

Unusual Clinical Presentation of Clear Cell Sarcoma Masquerading as Cutaneous Lymphoma, in a Young Male

Background: Clear cell sarcoma of soft tissue is an exceedingly rare tumor that originates from the neural crest cells. These tumors are histologically characterized by the presence of clear cells that contain accumulated glycogen. Clear cell sarcomas share histological and immunohistochemical features with malignant melanoma. They commonly arise from tendinous sheaths and aponeuroses, with the lower limbs, particularly around the ankles, being the most common site. Tumors arising in the upper extremities are rare, and very few primary clear cell sarcoma cases have been described in the chest wall and scapular soft tissues. They usually present as a solitary mass. Materials and Methods: Here we are reporting a case of clear cell sarcoma in a young boy, presenting with multifocal lesions involving the trunk, both upper and lower extremities, lymph nodes, bone marrow, and many internal viscera. Results: The case described an unusual presentation of clear cell sarcoma with multifocal involvement, which is rare compared to the typical presentation as a solitary mass. Conclusion: The reported case demonstrates a very unusual presentation of clear cell sarcoma involving multiple sites, highlighting the importance of considering a wide differential diagnosis when encountering multifocal soft tissue lesions.

Real-world efficacy, safety data and predictive clinical parameters for treatment outcomes in advanced soft tissue sarcoma treated with combined immunotherapy and antiangiogenic therapy

BackgroundThe combination of immunotherapy and antiangiogenic therapy has shown potential in the treatment of numerous malignant tumors, but limited evidence was available for soft tissue sarcomas (STS). Therefore, the aim of the present study is to assess the efficacy and safety of immunotherapy in conjunction with antiangiogenic therapy in patients diagnosed with advanced STS (aSTS).MethodsThe study enrolled patients with aSTS from January 2014 to October 2022. Eligible participants had previously received anthracycline-based chemotherapy, presented with an anthracycline-resistant sarcoma subtype, or were ineligible for anthracycline treatment due to medical conditions. Following enrollment, these patients received a combination of immunotherapy and antiangiogenic therapy. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS), while the secondary endpoints included the disease control rate (DCR), overall survival (OS), and the incidence of adverse events.ResultsFifty-one patients were included in this cohort study. The median duration of follow-up was 15.8 months. The ORR and DCR were 17.6%, and 76.5%, respectively. The median PFS (mPFS) was 5.8 months (95% CI: 4.8–6.8) for all patients, and the median OS had not been reached as of the date cutoff. Multivariate analysis indicated that Eastern Cooperative Oncology Group performance status of 0–1 and ≤ second-line treatment were positive predictors for both PFS and OS. Patients with alveolar soft part sarcoma or clear cell sarcoma had longer mPFS (16.2 months, 95% CI: 7.8–25.6) when compared to those with other subtypes of STS (4.4 months, 95% CI: 1.4–7.5, P < 0.001). Among the observed adverse events, hypertension (23.5%), diarrhea (17.6%), and proteinuria (17.6%) were the most common, with no treatment-related deaths reported.ConclusionThe combination of immunotherapy and antiangiogenic agents showed promising efficacy and acceptable toxicity in patients with aSTS, especially those with alveolar soft part sarcoma or clear cell sarcoma.

Contemporary surgical management of pediatric non-rhabdomyosarcoma soft tissue sarcoma.

Non-rhabdomyosarcoma soft tissue sarcoma (STS) comprises most STS in pediatric patients. It is a diverse set of over 30 histologic subtypes. Treatment is based on risk group determined by tumor size, grade, and the presence of metastases. Surgical resection is a cornerstone of therapy, as tumors are often resistant to chemotherapy or radiation. While patients with isolated tumors less than 5cm may undergo upfront resection, strong consideration should be given to neoadjuvant chemoradiotherapy to ensure negative margins at surgical resection and optimal outcomes. Sentinel lymph node biopsy is strongly recommended for clear cell and epithelioid sarcomas. The most common metastatic site is the lung, and metastases should be resected at the end of therapy, when feasible. Unfortunately, many high-risk patients progress on therapy, and alternative strategies including earlier metastatic control require investigation.

Rib tumors: A ten-year institutional study

Objectives The primary aim of this study was to study the demography and frequency distribution of the various rib tumors. The treatment modality offered and patient outcomes were also recorded wherever available. Material and Methods A ten year data was retrieved from the hospital registry from 2011-2021. Inclusion criteria were all patients with any tumors in the rib. Those patients who did not have a histological diagnosis and those having a chest wall mass and secondary involvement of the ribs were excluded. Results Out of 72 cases of rib tumors, 25 were diagnosed as Ewing Sarcoma, 22 Chondrosarcoma cases, 10 Multiple myeloma/plasmacytoma cases, 9 Osteosarcoma cases, rest 1 case each of Non Hodgkin Lymphoma, Brown tumor, Enchondroma, Osteochondroma, Clear cell sarcoma and metastases. Conclusion In this study the most common primary malignant tumor of the ribs in adults was Chondrosarcoma (41.1%) and in pediatric &amp; young adolescent age group (upto 18yrs) it was Ewing sarcoma (76.1%)

Efficacy and safety of nivolumab monotherapy in patients with unresectable clear cell sarcoma and alveolar soft part sarcoma (OSCAR Trial/NCCH1510).

Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune-checkpoint inhibitors (ICIs) are effective in these tumors. The authors conducted a phase 2 trial to evaluate the efficacy and safety of nivolumab for CCS and ASPS. The number of patients expected to be enrolled was 15-25 and was determined based on the Bayesian design. The primary end point was the confirmed objective response rate (ORR) according to the central review and the secondary end points included ORR, progression-free survival (PFS), overall survival (OS), and safety. A total of 26 patients (CCS, 12; ASPS, 14) were enrolled. Efficacy and safety were analyzed on 25 and 26 patients, respectively. The minimum number of responses required for a positive conclusion regarding the efficacy was four. However, only one patient (4.0%) with ASPS had a partial response. Complete response, stable disease, progression disease, and not evaluable were 0%, 60%, 32%, and 4.0%, respectively. Adverse events of grade 3 or 4 occurred in 57.7% (15 of 26). The median PFS was 4.9 months (95% confidence interval [CI], 3.7-8.6 months) and the median OS was 15.8 months (95% CI, 8.2-not reached). The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS.

Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR).

The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.

EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms.

With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.

BCOR overexpression in pediatric sarcomas- a morphologic continuum of mixed round and spindle cell tumors

Objectives The vast majority of BCOR (BCL6 corepressor) sarcomas occur in the pediatric population and include different clinico-pathologic entities. This study evaluates morphology, immunohistochemistry and clinical outcome in pediatric BCOR sarcomas. Material and Methods Children, aged ≤ 18yrs, diagnosed to have translocation negative Ewing-like sarcoma, clear cell sarcoma of the kidney and primitive myxoid mesenchymal tumor of infancy, over a period of five years were included. Immunohistochemical staining for BCOR antibody was done and the cases with BCOR overexpression were subjected to a further immunopanel comprising of special AT-rich sequence-binding protein 2 (SATB2), Transducin-Like enhancer of split-1 (TLE1), Cyclin D1 and NKX2.2. The clinical outcome of patients with BCOR overexpression was assessed. Results BCOR overexpression was seen in 16/42 cases; Five were primary soft tissue tumors, three were primary bone tumors, seven were clear cell sarcoma of the kidney and one primary renal sarcoma. The median age of this group was 3.5 years (range 2–18 years) with male predominance (75%). All the BCOR positive tumors showed statistically significant morphological and immunohistochemical overlap. 4/16 did not take treatment at our center. Of the 12 who received treatment, 8 are in Complete Remission 1 (CR1). The mean event-free survival (EFS) and overall survival (OS) were 51.89 months (95% CI: 37.36-66.42) and 62.08 months (95% confidence interval (CI): 52.85-71.30) respectively. Conclusion BCOR sarcomas did not show any statistically significant histological and immunohistochemical differences, thus reiterating the morphologic continuum of these clinically distinct tumors.

Outcomes of children with clear cell sarcoma of kidney following NWTS strategies in Shanghai China (2003-2021).

Although clear cell sarcoma of kidney (CCSK) is rare, it is the second most common renal tumor in children after Wilms' tumor. NWTS and SIOP are two major groups which had made tremendous efforts on renal tumors, but the strategies are different, for NWTS follows the upfront surgery principle providing definite pathology and the SIOP follows the upfront chemotherapy principle, each has its own advantages. Here we aimed to evaluate the outcomes of CCSK in China following NWTS strategies to analyze the prognostic factors. For this multicenter retrospective study, a total of 54 patients were enrolled from three children's hospitals, between April 2003 and December 2021. Treatment comprised upfront radical nephrectomy, followed by radiotherapy and intensive chemotherapy. Clinical records were regularly updated. Prognostic factors and survival rates were evaluated. The 54 enrolled patients had a median age of 37 months (range, 4 months to 11.4 years). The stage distribution was 16% stage I (n = 9), 30% stage II (n = 16), 39% stage III (n = 21), and 15% stage IV (n = 8). Among stage IV, metastasis sites included the lung (n = 6), bone (n = 1), and intra-orbital/cervical lymph node (n = 1). After a median follow-up of 5.6 years, the 5-year event-free survival (EFS) was 82.4±5.4%, and overall survival was 88.1±4.6%. The EFS was 100% for stage I, 93.8 ±6.1% for stage II, 71.1±10.0% for stage III, and 68.6±18.6% for stage IV. Univariate analysis revealed that staging (III/IV), tumor rupture, and inferior vena cava tumor thrombus were inferior prognostic factors. Multivariate analysis revealed that tumor rupture was independent poor prognostic factor (P = 0.01, HR 5.9). Among relapsed patients, relapse occurred a median of 11 months after diagnosis (range, 4-41 months), and 50% (4/8) achieved a second complete remission after multiple treatment. None of the six lung metastasis patients received lung RT, only one patient developed a relapse and was salvaged by RT after relapse. Tumor rupture was independent poor prognostic factor. Upfront surgery of NWTS strategies can make a definite pathology diagnosis, but how to reduce tumor rupture during surgery is important especially in developing countries. The outcomes of patients with stage I-III CCSK in China were comparable to findings in other developed countries. Better outcomes were achieved in stage IV CCSK by using an intensive chemotherapy regimen including carboplatin, which require further confirmation by AREN0321. Lung RT may be safely omitted in selected patients who achieve a compete radiographic response after 6 weeks of systemic treatment (including surgery). Treatment should be encouraged even in CCSK cases with metastasis and relapse.