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Recently, DNA methylation clocks have been proven to be precise age predictors, and the application of these clocks in cancer tissue has revealed a global age acceleration in a majority of cancer subtypes when compared to normal tissue from the same individual. The polycomb repressor complex 2 plays a pivotal role in the aging process, and its targets have been shown to be enriched in CpG sites that gain methylation with age. This complex is further regulated by the chromatin remodeling complex SWItch/Sucrose Non-Fermentable and its core subunit, notably the tumor suppressor gene SMARCB1, which under physiological conditions inhibits the activity of the polycomb repressor complex 2. Hence, the loss of function of core members of the SWItch/sucrose non-fermentable complex, such as the tumor suppressor gene SMARCB1, results in increased activity of polycomb repressor complex 2 and interferes with the aging process. SMARCB1-deficient neoplasms represent a family of rare tumors, including amongst others malignant rhabdoid tumors, atypical teratoid and rhabdoid tumors, and epithelioid sarcomas. As aging pathways have recently been proposed as therapeutic targets for various cancer types, these tumors represent candidates for testing such treatments. Here, by deriving epigenetic age scores from more than 1000 tumor samples, we identified epigenetic age acceleration as a hallmark feature of epithelioid sarcoma. This observation highlights the potential of targeting aging pathways as an innovative treatment approach for patients with epithelioid sarcoma. [ABSTRACT FROM AUTHOR]

AbstractOur study was carried out to define the efficacy of treatment with sequential chemotherapy lines in patients with epithelioid sarcoma (ES) at referral centres for sarcoma. From 1998 to 2023, 22 patients with ES were treated with chemotherapy and included in the analysis. The median age at the start of palliative treatment was 35 (20–68). The median follow-up was 22.1 months. In the first line, 13 patients (59%) received anthracycline-based chemotherapy and 6 (27%) high-dose ifosfamide. One patient (4.5%) achieved PR, 15 (68%) SD, and 6 (32%) PD as the best response. The median progression-free survival (PFS) in the first line was 6.4 months (95% CI: 3.02–12.9), but 9.7 months (95% CI: 4.37–NR) for chemotherapy based on anthracycline, indicating a more favourable PFS (p = 0.027). Twenty (90%) patients received second-line treatment, and eleven received third-line chemotherapy. The median OS from the start of first-line palliative chemotherapy was 22.1 months (95% CI: 10.5–41.4) and 14.7 months from the beginning of the second line. Perioperatively, patients pretreated with anthracycline had a median PFS of 2.9 months in the M1 setting. Second-line long-time responses were achieved with pazopanib or vincristine with actinomycin D. Despite chemoresistance, an advantage associated with anthracycline-based chemotherapy was confirmed in the ES cohort. Poor responses underscore the need for further research on targeted therapies for ES. Second-line chemotherapy or clinical trials should be offered to all eligible patients. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma (ES) is a rare soft tissue tumor that is commonly misdiagnosed. It is a mesenchymal tumor that shows both mesenchymal and epithelial features. It tends to occur in the distal upper extremity in children and young adults but may appear in any location and any age group. Less than 1% of ES involve the head and neck. Clinically, the tumor can be mistakenly confused with a benign lesion as it can mimic nonspecific ulcers or infected warts. Histologically, ES is characterized by a nodular architecture and epithelioid appearance of cells centered with necrosis, mimicking a granulomatous process. We present the clinical history of a 12-year-old male who presented with an ES of the pretragus with a brief review of the literature to raise awareness on this rare entity and to discuss the challenges in managing histopathological differential diagnosis in front of this unusual clinical presentation. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma (ES) is a rare soft tissue neoplasm with high recurrence rates. Wide surgical resection remains the only potential curative treatment. ES presents most commonly on the fingers, hands and forearm, making light-based cancer cell-targeted therapies such as near-infrared photoimmunotherapy (NIR-PIT) that is target-specific, but with limited penetration depth, suitable for ES treatment. We established that CD44 and EGFR were overexpressed in ES patient samples and in the VA-ES-BJ human ES cell line. NIR-PIT of VA-ES-BJ cells using antibody photosensitizer conjugates, prepared by conjugating a CD44 or EGFR monoclonal antibody to the photosensitizer IR700, confirmed that NIR-PIT with both conjugates resulted in cell death. Neither treatment with NIR light alone nor treatment with the conjugates but without NIR light were effective. CD44-IR700-PIT resulted in greater cell death than EGFR-IR700-PIT, consistent with the increased expression of CD44 by VA-ES-BJ cells. In tumors, EGFR-IR700 exhibited a higher tumor-to-normal ratio, as determined by in vivo fluorescence imaging, and a higher anti-tumor growth effect, compared to CD44-IR700. No antitumor effect of the EGFR antibody or the photosensitizer conjugate alone was observed in vivo. Our data support evaluating the use of EGFR-IR700-PIT in the management of ES for detecting and eliminating ES cells in surgical margins, and in the treatment of superficial recurrent tumors.

Abstract Background Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients. Methods We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People’s Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021. Results A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated. Conclusions The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma. Trial registration This study was approved in the Medical Ethics Committee of Peking University People’s Hospital on October 28, 2022 (No.: 2022PHD015-002). The study was registered in Clinicaltrials.gov with identifier no. NCT05656222.

Background: Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients. Methods: We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People's Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021. Results: A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated. Conclusions: The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma. Trial registration: This study was approved in the Medical Ethics Committee of Peking University People's Hospital on October 28, 2022 (No.: 2022PHD015-002). The study was registered in Clinicaltrials.gov with identifier no. NCT05656222. [ABSTRACT FROM AUTHOR]

Background: Patients with neurofibromatosis type I (NF1) have an increased risk of developing soft-tissue sarcomas, particularly those related to the nervous system. Epithelioid sarcoma (ES) is an exceptionally rare subtype of soft-tissue sarcoma, with limited knowledge about its clinical presentation and optimal management in NF1. This report aims to provide insights into the characteristics and outcomes of ES in NF1 patients. Case description: A 37-year-old man with a history of NF1 presented with a progressively worsening mass on his right inner thigh. An MRI scan revealed a well-defined tissue mass originating from the adductor magnus muscle, later confirmed as ES through histopathology and immunohistochemistry. Considering poor local and general prognosis, the multidisciplinary team recommended salvage hip disarticulation, however the patient refused and opted for palliative marginal resection to reduce the tumour size. The patient’s condition declined rapidly, and he succumbed six days after the surgery. Conclusion: This case highlights the rarity of ES in NF1 patients and underscores the potential for malignant tumour development in this population. Further research is needed to improve our understanding and management of sarcomas in the context of NF1.

Epithelioid sarcoma is a rare aggressive soft tissue sarcoma, which can be distal or proximal types. The classic form (distal-type) of epithelioid sarcoma mainly occurs in teenagers and young adults. A rarer form, called large-cell (proximal-type) epithelioid sarcoma, tends to be more aggressive and mainly affects adults. The proximal subtype mostly arises from the proximal pelvis, limbs, and genital tract. We report a case of a 59 -year-old female, presented with a progressively growing mass in the left labia majora. Gynecologic examination revealed a 2 cm mobile and painless mass that was not attached to deep planes. The histological study showed a multinodular tumor was seen comprising sheets of oval to polygonal cells with moderate amount of cytoplasm. Interspersed were larger, rhabdoid cells with abundant eosinophilic cytoplasm and prominent nucleoli. On IHC, the tumor cells showed positivity for EMA and CKAE1/AE3 and do not expressed INI-1 in the nucleus. All tumor cells were negative for S-100 protein and CD34. The histopathological diagnosis was soft tissue of the vulvar region with proximal epithelioid sarcoma. The patient received adjuvant external pelvic radiotherapy and brachytherapy in the vulvar bed. Currently, 3 years after diagnosis, the patient does not present signs of tumor recurrence in her controls. Due to its low incidence, there are no evidence-based diagnostic algorithms or published recommendations for treatment. The prognosis is generally poor. A wide excision with clear margins is imperative with options of post-operative CT/RT in individual cases during a close follow-upbehavior, as seen in our case.

Abstract Background Epithelioid sarcoma (ES) is a rare form of mesenchymal malignancy that rarely occurs in children. Only seven cases of intra-articular epithelioid sarcoma have been reported in the medical literature. Case presentation In this report, we presented the case of a 13-year-old girl with a delayed diagnosis of ES in the left knee. Her initial diagnosis was mistaken for Pigmented Villonodular Synovitis (PVNS) but ruled out later by the first biopsy. However, the lesion rapidly regrew again after arthroscopy, raising suspicions of malignancy. A comprehensive histochemistry examination was conducted again, leading to the diagnosis of INI-1 negative epithelioid sarcoma. Unfortunately, the girl passed away seven months later due to early metastasis of the tumor. Conclusion Careful consideration should be given to the differential diagnosis of pediatric patients presenting with monoarthritis. This report highlights the importance of early and accurate diagnosis and underscores the necessity for effective treatments for epithelioid sarcoma. Surgical resection or radical surgery is recommended, while novel treatment strategies targeting EZH2 show promise.

Background: Epithelioid sarcoma (ES) is a rare form of mesenchymal malignancy that rarely occurs in children. Only seven cases of intra-articular epithelioid sarcoma have been reported in the medical literature. Case presentation: In this report, we presented the case of a 13-year-old girl with a delayed diagnosis of ES in the left knee. Her initial diagnosis was mistaken for Pigmented Villonodular Synovitis (PVNS) but ruled out later by the first biopsy. However, the lesion rapidly regrew again after arthroscopy, raising suspicions of malignancy. A comprehensive histochemistry examination was conducted again, leading to the diagnosis of INI-1 negative epithelioid sarcoma. Unfortunately, the girl passed away seven months later due to early metastasis of the tumor. Conclusion: Careful consideration should be given to the differential diagnosis of pediatric patients presenting with monoarthritis. This report highlights the importance of early and accurate diagnosis and underscores the necessity for effective treatments for epithelioid sarcoma. Surgical resection or radical surgery is recommended, while novel treatment strategies targeting EZH2 show promise. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma (ES) is a rare soft tissue sarcoma subtype, predominantly occurring in children and young adults. Despite optimal management of localized disease, approximately 50% of patients develop advanced disease. The management of advanced ES remains challenging due to limited response to conventional chemotherapy and despite novel oral EZH2 inhibitors that have better tolerability but similar efficacy to chemotherapy. We performed a literature review using the PubMed (MEDLINE) and Web of Science databases. We have focused on the role of chemotherapy, targeted agents such as EZH2 inhibitors, potential new targets and immune checkpoint inhibitors and combinations of therapies currently undergoing clinical investigation. ES is a soft tissue sarcoma with a heterogeneous pathological, clinical, and molecular presentation. In the current era of precision medicine, more trials with targeted therapies and a combination of chemotherapy or immunotherapy with targeted therapies are required to establish optimal treatment for ES. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma is a rare and aggressive mesenchymal tumour, the genetic hallmark of which is the loss of expression of SMARCB1, a key member of the SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin remodelling complex. Hampered by its rarity, epithelioid sarcoma has received little research attention and therapeutic options for this disease remain limited. SMARCB1‐deficient tumours also include malignant rhabdoid tumour, atypical teratoid and rhabdoid tumour, epithelioid malignant peripheral nerve sheath tumour, and poorly differentiated chordoma. Histologically, it can be challenging to distinguish epithelioid sarcoma from malignant rhabdoid tumour and other SMARCB1‐deficient tumours, whereas methylation profiling shows that they represent distinct entities and facilitates their classification. Methylation studies on SMARCB1‐deficient tumours, although not including epithelioid sarcomas, reported methylation subgroups which resulted in new clinical stratification and therapeutic approaches. In addition, emerging evidence indicates that immunotherapy, including immune checkpoint inhibitors, represents a promising therapeutic strategy for SMARCB1‐deficient tumours. Here, we show that some epithelioid sarcomas share methylation patterns of malignant rhabdoid tumours indicating that this could help to distinguish these entities and guide treatment. Using gene expression data, we also showed that the immune environment of epithelioid sarcoma is characterised by a predominance of CD8+ lymphocytes and M2 macrophages. These findings have potential implications for the management of patients with epithelioid sarcoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epithelioid fibrous histiocytoma is a rare morphologic variant of benign fibrous histiocytoma. Most commonly it presents in the lower limbs of young adults as a well-defined nodular lesion. Microscopically due to its epithelioid-like morphology, it has multiple differential diagnosis. CLINICAL CASE: A 43-year-old male presented an ovoid, exophytic lesion in the knee, clinically compatible with dermatofibroma. Surgical resection was performed without recurrences to date. Histopathologic findings showed distinctive hallmarks such as well-formed epidermal collarette and pleomorphic appearance cells. CONCLUSIONS: It is important to recognize histopathologically this variant of benign fibrous histiocytoma and differentiate it from neoplastic processes with similar epithelioid morphology, both benign such as Spitz nevus and malignant like amelanotic melanoma and epithelioid sarcoma. [ABSTRACT FROM AUTHOR]

Abstract Objective The prognostic factors for patients with epithelial sarcoma remain unclear. The study aims to develop a practical clinical nomogram that predicts prognosis in patients with ES using the Surveillance, Epidemiology, and End Results (SEER) database. Methods We extracted clinical data from 2004 to 2015 from the SEER database about patients with ES. All patients were randomly divided into training cohort and validation cohort. Kaplan–Meier analyses were used to compare outcomes between different subgroups. In order to estimate the chance of survival for patients with ES, we developed a nomogram. Nomogram performance was evaluated by discrimination and calibration. Additionally, an analysis of decision curves was conducted to evaluate the clinical usefulness of this newly developed model. Results In the primary cohort,320 met the inclusion criteria to be entered into this study. The median OS was 66.000 months (range 34.704 to 94.296 months), and the 1‐, 3‐, and 5‐year OS rates were 70.7%, 56.1%, and 50.4%, respectively. For the validation cohort, we studied 136 consecutive patients. Age, primary site, grade, AJCC (American Joint Committee on Cancer) T, AJCC M, and surgery were included in the nomogram. The C‐index values for the training set and validation set were 0.817 and 0.832, respectively. The calibration plots showed good agreement between the prediction and the observation. Based on the clinical decision curve, the model has a good clinical net benefit for ES patients. Conclusions It is the first study that developed an effective survival prediction model for patients with ES. Using this nomogram can assist in clinical decision‐making as it has satisfactory accuracy. Even so, additional external validation is needed.

Background: Diverse lesions ranging from infective, inflammatory to neoplastic can occur in the hand. Almost all lesions that occur elsewhere in the body can affect the hand as well. Methods: This was a hospital-based retrospective study of 5 years done between January 2016 and December 2020. We enumerated the clinical and histopathological spectrum of lesions of the hand. The details were collected from the patient requisition forms and pathology records. Results: Of the 80 cases seen during the study period, 25 (31.3%) were non-neoplastic and 55 (68.8%) were neoplastic; male: female ratio was 0.95:1. The most frequent lesions identified were ganglion cysts (n = 13), followed by giant cell tumour (GCT) of tendon sheath (n = 11). Common non-neoplastic lesions included were ganglion cyst (n = 13), pyogenic granuloma (n = 3); epidermoid cyst, fungal granuloma, pigmented seborrhoeic keratosis (n = 2 each) and cutaneous horn, molluscum contagiosum and granulomatous inflammation. Amongst neoplastic lesions, mesenchymal lesions were 49 (89.1%) and epithelial lesions were 6 (10.9%); they were GCT of tendon sheath 11 (22.4%) lipomas and nerve sheath tumours 9 (18.36%) cases each, arteriovenous malformations/haemangiomas 5 (10.2%), fibromas 2 (4.08%) and one (2.04%) case each of myolipoma, fibrolipoma, benign fibrous histiocytoma, calcifying aponeurotic fibroma and benign spindle cell tumour, palmar fibromatosis. Malignant mesenchymal neoplasms included synovial sarcoma (n = 3), epithelioid sarcoma, malignant peripheral nerve sheath tumour and high-grade spindle cell sarcoma (n = 1 each). Amongst epithelial, benign lesions were 2, malignant lesions were 4, of which 3 were squamous cell carcinoma and one was melanoma and the two benign lesions were skin adnexal tumours, of which one was a case of eccrine poroma and the other was pilomatrixoma. Conclusions: In patients presenting with lumps and bumps on the hand, common non-neoplastic lesions included ganglion cyst and pyogenic granuloma. Amongst neoplastic lesions, mesenchymal lesions and epithelial lesions were most commonly seen.

Epithelioid sarcoma (ES) is a very rare sarcoma characterized by loss of INI1. Enzinger first described ES in 1970, but the histopathologic differential diagnosis of ES remains challenging. There are two ES subtypes, the classical type with spindle epithelioid to the central pseudogranulomatous cells, and the proximal type, which is predominantly composed of epithelioid and rhabdoid cells. ES symptoms and signs are not specific and depend on tumor localization. The only treatment for ES is radical excision with a microscope-radical margin. In general, the best treatment for ES in extremes is radical resection with a wide margin or amputation with or without lymph node dissection. Surgery may be followed by adjuvant chemotherapy and/or radiation therapy. Referral of patients with ES to a sarcoma center that offers hypofractionation RT trials and multidisciplinary clinical trials should be considered upfront. Neoadjuvant chemotherapy with ifosfamide and doxorubicin with / or without radiation therapy must be used after a multidisciplinary team discussion. On 23 January 2020, the US Food and Drug Administration (FDA) first approved tazemetostat – an inhibitor of zeste homolog 2 enhancer – therapy for metastatic ES or locally advanced ES not eligible for radical resection. [ABSTRACT FROM AUTHOR]

Background: Diverse lesions ranging from infective, inflammatory to neoplastic can occur in the hand. Almost all lesions that occur elsewhere in the body can affect the hand as well. Methods: This was a hospital-based retrospective study of 5 years done between January 2016 and December 2020. We enumerated the clinical and histopathological spectrum of lesions of the hand. The details were collected from the patient requisition forms and pathology records. Results: Of the 80 cases seen during the study period, 25 (31.3%) were non-neoplastic and 55 (68.8%) were neoplastic; male: female ratio was 0.95:1. The most frequent lesions identified were ganglion cysts (n = 13), followed by giant cell tumour (GCT) of tendon sheath (n = 11). Common non-neoplastic lesions included were ganglion cyst (n = 13), pyogenic granuloma (n = 3); epidermoid cyst, fungal granuloma, pigmented seborrhoeic keratosis (n = 2 each) and cutaneous horn, molluscum contagiosum and granulomatous inflammation. Amongst neoplastic lesions, mesenchymal lesions were 49 (89.1%) and epithelial lesions were 6 (10.9%); they were GCT of tendon sheath 11 (22.4%) lipomas and nerve sheath tumours 9 (18.36%) cases each, arteriovenous malformations/haemangiomas 5 (10.2%), fibromas 2 (4.08%) and one (2.04%) case each of myolipoma, fibrolipoma, benign fibrous histiocytoma, calcifying aponeurotic fibroma and benign spindle cell tumour, palmar fibromatosis. Malignant mesenchymal neoplasms included synovial sarcoma (n = 3), epithelioid sarcoma, malignant peripheral nerve sheath tumour and high-grade spindle cell sarcoma (n = 1 each). Amongst epithelial, benign lesions were 2, malignant lesions were 4, of which 3 were squamous cell carcinoma and one was melanoma and the two benign lesions were skin adnexal tumours, of which one was a case of eccrine poroma and the other was pilomatrixoma. Conclusions: In patients presenting with lumps and bumps on the hand, common non-neoplastic lesions included ganglion cyst and pyogenic granuloma. Amongst neoplastic lesions, mesenchymal lesions and epithelial lesions were most commonly seen. [ABSTRACT FROM AUTHOR]

Proximal-type epithelioid sarcoma of the perineum is a rare soft-tissue malignancy, and only 55 cases have been reported in the English literature to date. This tumor has an indetectable early symptom and frequent recurrences. Here, we present the case of a 31-year-old man with proximal-type epithelioid sarcoma of the perineum who underwent wide excision. Further, we reviewed the current literature regarding differential diagnosis and management of this disease. [ABSTRACT FROM AUTHOR]

Primary soft-tissue sarcomas of the paratesticular region are uncommon tumors comprising 1% of all adult sarcomas. Paratesticular epithelioid sarcoma (ES) is a rare subtype. Here, we report the case of a 68-years-old male with scrotal swelling who underwent high inguinal exploration and right orchidectomy. Histopathology and immunohistochemistry revealed paratesticular ES. Very few cases of paratesticular ES have been reported so far in the literature. Clinical presentation, investigations, treatment interventions, and prognosis have been discussed. As it can be confused with other benign and malignant conditions, diagnosis is often made on histopathological evaluation.

BackgroundData on the clinical features, optimal treatment and outcomes of paediatric patients with epithelioid sarcoma (ES) are limited and mostly retrospective.MethodsA subset analysis of ES patients

Objective: The prognostic factors for patients with epithelial sarcoma remain unclear. The study aims to develop a practical clinical nomogram that predicts prognosis in patients with ES using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We extracted clinical data from 2004 to 2015 from the SEER database about patients with ES. All patients were randomly divided into training cohort and validation cohort. Kaplan–Meier analyses were used to compare outcomes between different subgroups. In order to estimate the chance of survival for patients with ES, we developed a nomogram. Nomogram performance was evaluated by discrimination and calibration. Additionally, an analysis of decision curves was conducted to evaluate the clinical usefulness of this newly developed model. Results: In the primary cohort,320 met the inclusion criteria to be entered into this study. The median OS was 66.000 months (range 34.704 to 94.296 months), and the 1‐, 3‐, and 5‐year OS rates were 70.7%, 56.1%, and 50.4%, respectively. For the validation cohort, we studied 136 consecutive patients. Age, primary site, grade, AJCC (American Joint Committee on Cancer) T, AJCC M, and surgery were included in the nomogram. The C‐index values for the training set and validation set were 0.817 and 0.832, respectively. The calibration plots showed good agreement between the prediction and the observation. Based on the clinical decision curve, the model has a good clinical net benefit for ES patients. Conclusions: It is the first study that developed an effective survival prediction model for patients with ES. Using this nomogram can assist in clinical decision‐making as it has satisfactory accuracy. Even so, additional external validation is needed. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma is a rare but aggressive soft tissue sarcoma that presents a significant diagnostic and management challenge to clinicians. We report a 31-year-old female who presented with a non-healing ulcer of three years' duration on her left thumb after a burn. Examination revealed an ulcerative tumour invading the bone with areas of haemorrhage. Microscopic examination showed an epithelioid neoplasm with central necrosis. The neoplastic cells formed dyscohesive sheets, slit-like channels, and pseudovascular spaces. Erythrocytes were frequently observed in these areas. The neoplastic malignant cells were diffusely positive for cytokeratin AE1/AE3, EMA, vimentin, Fli-1; while focally positive for CD34 and CD31. The morphology and immunophenotype overlap with a vascular neoplasm. Additional immunohistochemical stain revealed loss of SMARCB1/INI1 expression supporting the diagnosis of epithelioid sarcoma of distal type, angiomatoid variant. We present a distinctive case of angiomatoid epithelioid sarcoma that developed in a burn ulcer and highlight pathological characteristics that distinguish it from epithelioid vascular neoplasms. [ABSTRACT FROM AUTHOR]

Poorly differentiated chordoma is an exceedingly rare, aggressive subtype of chordoma. These tumors typically arise in the axial skeleton of young patients, most commonly the skull base, followed by the cervical spine. Herein, we present a 60-year-old patient with longstanding knee pain and nondiagnostic imaging, initially thought to be due to osteoarthritis. No discrete mass-forming lesion was identified by radiology. Synovial histology at the time of arthroplasty revealed a multinodular proliferation of epithelioid-to-histiocytoid cells with a moderate amount of eosinophilic-to-clear, vacuolated cytoplasm. Scattered cells with high-grade nuclear atypia were present. A diagnosis of metastatic carcinoma was considered due to immunohistochemical positivity for keratin and GATA3. However, a diagnosis of epithelioid sarcoma was rendered based on clinical context, morphology, and loss of immunohistochemical expression for SMARCB1 (INI1). However, upon re-review of the tumor, brachyury was retrospectively added to the immunohistochemistry panel and showed strong positivity, thus prompting amendment of the initial diagnosis of epithelioid sarcoma to extra-axial poorly differentiated chordoma. Given the rarity of this diagnosis, molecular testing was performed which revealed a unique SMARCB1 molecular profile with a single-nucleotide variant in addition to the commonly reported loss of chromosome 22q. This report of an ultra-rare sarcoma in an uncommon anatomic site highlights multiple potential pitfalls in the diagnosis of poorly differentiated chordoma, emphasizes the importance of brachyury immunohistochemistry in rendering a correct interpretation, and underscores an opportunity for further molecular analysis to better define the molecular profile of this entity. [ABSTRACT FROM AUTHOR]

Pseudomyogenic hemangioendothelioma (PMHE), a rare soft tissue tumor predominantly affecting young adults, often presents as multiple nodules in various tissue planes of a limb. Malignant transformation and metastatic disease are unusual and pose diagnostic and therapeutic challenges. A 17-year-old patient from Western India, with a history of recurrent excisions for a toe swelling presented to our center for evaluation and management. A below-knee amputation was performed, and histopathology revealed PMHE. Adjuvant therapy was deemed unnecessary given the borderline nature of the tumor. Shortly thereafter, he developed features of local recurrence and underwent above-knee amputation. An expert histopathological review confirmed the diagnosis and noted features of malignant transformation–progression to a higher grade with greater cytological atypia, confluent growth, and increased mitotic activity over time. Upon further distant progression in the lung, he was started on a palliative regimen of weekly paclitaxel, vinblastine, and propranolol but eventually succumbed to his illness. In contrast to conventional descriptions of low mitotic activity, minimal nuclear atypia, and absence of necrosis, our patient exhibited increased mitotic rates, nuclear atypia, and evolving necrosis in serial histopathological evaluations. The fulminant clinical progression within a short interval was also atypical. Our patient's clinical course underscores the need for meticulous histopathological and molecular characterization and vigilant clinical surveillance after resection in patients with PMHE. Providing the standard of care for malignant disease in the adjuvant setting is challenging owing to the rarity and the lack of treatment guidelines. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma (ES) is a very rare mesenchymal malignancy. Its oncogenesis remains unknown, and few therapies are available for advanced patients. Improved therapies, such as combined therapies, are urgently needed for the treatment of advanced ES. To identify precision drugs for advanced ES patients, the sensitivity of the drugs must be screened and evaluated before they are used for treatment. In the present study, tumour tissue from an ES patient was subjected to NGS sequencing, cell culture and the construction of a PDX model. Using the early generations of tumour-derived cells, we performed a screen and found that the combined drugs ADM and trametinib exhibited coefficiency in tumour inhibition. This conclusion was further confirmed in experiments with later generations of cells and PDX models. Therefore, we suggest that early generations of tumour-derived cells be used to test the sensitivity of ES tumours to candidate drugs. Moreover, we speculate that trametinib may be combined with chemotherapy in ES patients to prolong the duration of the chemotherapeutic response. • Establishment of an epithelioid sarcoma PDCs and PDX. • PDX was used to test the sensitivity of ES tumours to candidate drugs. • Trametinib combined with chemotherapy may be better for ES patients. [ABSTRACT FROM AUTHOR]

Aims: SMARCB1 (INI‐1)‐deficient vulvar neoplasms comprise a group of rare tumours that include epithelioid sarcoma (ES), myoepithelial carcinoma (MEC), the recently described myoepithelioma‐like tumour of the vulvar region (MELTVR), and sarcomas that are difficult to classify. It has been suggested that so‐called vulvar yolk sac tumours (YST) may represent morphologic variants of SMARCB1‐deficient tumours; thus, we investigated the immunoreactivity of germ cell markers in SMARCB1‐deficient vulvar neoplasms. Methods and results: Ten SMARCB1‐deficient vulvar neoplasms were stained with germ cell tumour markers (SALL4, glypican‐3, OCT3/4, and AFP) and re‐reviewed for morphologic features. The tumours occurred in adult females (median age 41 years) and included ES (n = 7), MELTVR (n = 2), and MEC (n = 1). All cases showed loss of SMARCB1 expression. Four cases (40%) were focally positive for SALL4 in areas with morphology of typical‐appearing ES. One of these cases also showed focal staining for OCT3/4. One ES showed a transition from typical‐appearing ES to YST‐like morphology, with diffuse expression of SALL4 and glypican‐3, and focal expression of AFP, in these latter areas. All other tested cases were negative for AFP. Conclusion: Our study reveals that SALL4, glypican‐3, and OCT3/4 are positive in a subset of SMARCB1‐deficient vulvar neoplasms, which may pose a diagnostic challenge and result in consideration of a germ cell tumour. We also highlight a case with transition from ES to YST‐like morphology, lending further support that YSTs of the vulva are somatically derived SMARCB1‐deficient neoplasms and do not represent true germ‐cell neoplasia. [ABSTRACT FROM AUTHOR]

Objectives: To determine the clinicopathological features of epithelioid sarcoma presenting in head and neck region (HNES) and elucidate diagnostic key points and treatment options for HNES. Materials and Methods: A total of 12 HNES cases were collected in our department from 2010 to 2020. Their clinical information and pathological features were documented, and relevant follow‐up was performed. Immunohistochemistry was carried to analyze the protein markers of HNES. Results: Of the 12 HNES cases, 10 were primary tumors and 2 were metastasized from foot and shoulder, respectively. The patients with primary tumors were significantly younger than those with metastasized ones (22.7 vs 41.5, p =.0157), and male patients outnumbered female patients (3:1). Of all HNES cases, 9 were classic subtype, and 3 were proximal subtype. HNES patients had a poor prognosis, with 5‐year overall survival of 41.5% and 5‐year relapse‐free survival of 22.5%. A loss of INI1 was identified as the hallmark of HNES with 83.3% (10/12) of HNES cases presenting as EZH2 positive. Conclusions: HNES is more prevalent at younger ages and in males, has a poor prognosis, and exhibits a greater proportion of classic subtype than proximal subtype. EZH2 inhibitor has therapeutic potential in HNES. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma (ES) is a very rare and aggressive mesenchymal tumor of unclear origin and uncertain lineage characterized by a prevalent epithelioid morphology. The only recurrent genetic alteration reported in ES as yet is the functional inactivation of SMARCB1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1), a key component of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes. How SMARCB1 deficiency dictates the clinicopathological characteristics of ES and what other molecular defects concur to its malignant progression is still poorly understood. This review summarizes the recent findings about ES pathobiology, including defects in chromatin remodeling and other signaling pathways and their role as therapeutic vulnerabilities. [ABSTRACT FROM AUTHOR]

Poorly differentiated chordoma is an exceedingly rare, aggressive subtype of chordoma. These tumors typically arise in the axial skeleton of young patients, most commonly the skull base, followed by the cervical spine. Herein, we present a 60-year-old patient with longstanding knee pain and nondiagnostic imaging, initially thought to be due to osteoarthritis. No discrete mass-forming lesion was identified by radiology. Synovial histology at the time of arthroplasty revealed a multinodular proliferation of epithelioid-to-histiocytoid cells with a moderate amount of eosinophilic-to-clear, vacuolated cytoplasm. Scattered cells with high-grade nuclear atypia were present. A diagnosis of metastatic carcinoma was considered due to immunohistochemical positivity for keratin and GATA3. However, a diagnosis of epithelioid sarcoma was rendered based on clinical context, morphology, and loss of immunohistochemical expression for SMARCB1 (INI1). However, upon re-review of the tumor, brachyury was retrospectively added to the immunohistochemistry panel and showed strong positivity, thus prompting amendment of the initial diagnosis of epithelioid sarcoma to extra-axial poorly differentiated chordoma. Given the rarity of this diagnosis, molecular testing was performed which revealed a unique SMARCB1 molecular profile with a single-nucleotide variant in addition to the commonly reported loss of chromosome 22q. This report of an ultra-rare sarcoma in an uncommon anatomic site highlights multiple potential pitfalls in the diagnosis of poorly differentiated chordoma, emphasizes the importance of brachyury immunohistochemistry in rendering a correct interpretation, and underscores an opportunity for further molecular analysis to better define the molecular profile of this entity., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Epithelioid sarcoma (ES) is a rare tumor hallmarked by the loss of INI1/SMARCB1 expression. Apart from this alteration, little is known about the biology of ES. Despite recent advances in treatment, the prognosis of ES remains unsatisfactory. To elucidate the molecular underpinnings of ES, and to identify diagnostic biomarkers and potential therapeutic vulnerabilities, we performed an integrated omics profiling (RNA sequencing and methylation array) of 24 primary, untreated ESs. Transcriptome and methylome analysis identified two distinct molecular clusters that essentially corresponded to the morphologic variants of ES, classic ES (C-ES) and the more aggressive proximal ES (P-ES). The P-ES group was characterized by hyperactivation of GATA3 and MYC pathways, with extensive epigenetic rewiring associated with EZH2 overexpression. Both DNA methylation and gene expression analysis indicated a striking similarity with the "MYC subgroup" of ATRT, another SMARCB1-deficient tumor, implying a shared molecular background and potential therapeutic vulnerabilities. Conversely, the C-ES group exhibited an endothelial-like molecular profile, with expression of vascular genes and elevated pro-angiogenic SOX17 signaling. Immunohistochemistry validated the overexpression of the chromatin regulators GATA3 (9/12 vs. 0/16) and EZH2 (7/7 vs. 2/6) in P-ESs, and of the vascular factors SOX17 (8/8 vs. 1/10) and N-cadherin (5/9 vs 0/10) in C-ESs. Therefore, these molecules emerge as potential diagnostic tools to fill the gap represented by the lack of ES subtype-specific biomarkers. In summary, our study shows that P-ES and C-ES represent distinct molecular entities defined by MYC/GATA3 and SOX17/endothelial molecular traits, respectively. Besides providing insights into the biology of ES, our study pinpoints subtype-specific biomarkers and potential therapeutic vulnerabilities., (Copyright © 2024 THE AUTHORS. Published by Elsevier Inc. All rights reserved.)

Epithelioid sarcoma (ES) is a rare soft tissue tumor that is commonly misdiagnosed. It is a mesenchymal tumor that shows both mesenchymal and epithelial features. It tends to occur in the distal upper extremity in children and young adults but may appear in any location and any age group. Less than 1% of ES involve the head and neck. Clinically, the tumor can be mistakenly confused with a benign lesion as it can mimic nonspecific ulcers or infected warts. Histologically, ES is characterized by a nodular architecture and epithelioid appearance of cells centered with necrosis, mimicking a granulomatous process. We present the clinical history of a 12-year-old male who presented with an ES of the pretragus with a brief review of the literature to raise awareness on this rare entity and to discuss the challenges in managing histopathological differential diagnosis in front of this unusual clinical presentation., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Aim: Clinicopatholgical findings and outcomes in epithelioid sarcoma (ES) patients. Materials & methods: ES patients registered in sarcoma clinic from 2015 to 2021. Results: There were 20 patients with median age of 26 years. Majority had distal ES (70%) and advanced disease (85%). In patients with advanced disease lymph nodes were involved in 65%, lungs in 58% and others in 35%. Among 14 patients who underwent biopsy outside our institute, nine (64.2 %) had been initially misdiagnosed. Response rates to doxorubicin (n = 12), pazopanib (n = 6), gemcitabine/docetaxel (n = 5), tazemetostat (n = 3) and immunotherapy (n = 2) used in various lines were 16, 16, 20, 33 and 0%, respectively. Conclusion: Our patients had an advanced-stage and distal ES, with a modest response to chemotherapy.

Background: Metastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat. Methods: In order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next‐generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance. Results: Other biologically inspired functional interrogations of EPS cultures using gene knockdown or chemical probes demonstrated only limited to modest efficacy in vitro. However, our molecular studies uncovered distinguishing features (including retained dysfunctional SMARCB1 expression and elevated GLI3, FYN and CXCL12 expression) of distal, paediatric/young adult‐associated EPS versus proximal, adult‐associated EPS. Conclusions: Overall results highlight the complexity of the disease and a limited chemical space for therapeutic advancement. However, subtle differences between the two EPS subtypes highlight the biological disparities between younger and older EPS patients and emphasise the need to approach the two subtypes as molecularly and clinically distinct diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Epithelioid sarcoma most frequently occurs in the dermal or subcutaneous area of the distal extremities. To date, there have been three cases of primary pulmonary epithelioid sarcoma reported. We report a case of epithelioid sarcoma that is considered a primary lung tumor. Case presentation A 65-year-old asymptomatic Asian male patient underwent chest radiography during a routine health examination, and an abnormal mass was detected. His past medical history was unremarkable. He smoked 40 cigarettes every day and had slightly obstructive impairment on spirometry. He worked as an employee of a company and had no history of asbestos exposure. He underwent partial resection of the right lung by thoracoscopy. A histological examination of the tumor revealed a cellular nodule of epithelioid and spindle-shaped cells. Some of the tumor cells displayed rhabdoid features and reticular arrangement in a myxomatous stroma. Immunohistochemically, the tumor cells were positive for vimentin, smooth muscle actin (SMA), CD34, and epithelial membrane antigen (EMA); loss of the BAF47/INI1 protein in the tumor cells was also confirmed. A diagnosis of epithelioid sarcoma was established. Careful screening by whole-body positron emission tomography for another primary lesion after surgery did not detect any possible lesion. He had no cutaneous disease. Conclusion To our knowledge, this is the fourth case of a proximal-type epithelioid sarcoma considered as a primary lung tumor.

Abstract Background Epithelioid sarcomas and rhabdoid tumors are rare, aggressive malignancies with poor prognosis. Both are characterized by INI1 alterations and deregulation of growth factor receptors albeit their interaction has not been elucidated. Methods In this study, we investigated the activity of a panel of epigenetic modulators and receptor tyrosine kinase inhibitors in vitro on respective cell lines as well as on primary patient-derived epithelioid sarcoma cells, and in vivo on xenografted mice. Focusing on histone deacetylase (HDAC) inhibitors, we studied the mechanism of action of this class of agents, its effect on growth factor receptor regulation, and changes in epithelial-to-mesenchymal transition by using cell- and RT-qPCR-based assays. Results Pan-HDAC inhibitor panobinostat exhibited potent anti-proliferative activity at low nanomolar concentrations in A204 rhabdoid tumor, and VAESBJ/GRU1 epithelioid sarcoma cell lines, strongly induced apoptosis, and resulted in significant tumor growth inhibition in VAESBJ xenografts. It differentially regulated EGFR, FGFR1 and FGFR2, leading to downregulation of EGFR in epithelioid sarcoma and to mesenchymal-to-epithelial transition whereas in rhabdoid tumor cells, EGFR was strongly upregulated and reinforced the mesenchymal phenotype. All three cell lines were rendered more susceptible towards combination with EGFF inhibitor erlotinib, further enhancing apoptosis. Conclusions HDAC inhibitors exhibit significant anticancer activity due to their multifaceted actions on cytotoxicity, differentiation and drug sensitization. Our data suggest that the tailored, tissue-specific combination of HDAC inhibitors with therapeutics which target cellular salvage mechanisms might increase their therapeutic relevance.

Epithelioid sarcoma (ES) is a rare, clinically polymorphic tumor that afflicts the dermal and subcutaneous region of distal extremity of young adults. In the distal extremity, the involvement of pubic and inguinal region is very rare. We present a case of an epithelioid sarcoma of the pubic region, which was managed, with a combination of upfront surgery and adjuvant therapy, and is presently disease free 5 years after completion of treatment.