Search Results (204)

Background/Objectives: There are very few publications on unplanned excisions of great saphenous vein leiomyosarcomas (GSV-LMS), and their impact on the prognosis of the disease is not well known. The objective of this study is to present a series of nine new leiomyosarcomas of the great saphena vein (LMS-GSV) cases, with the aim of increasing diagnostic awareness and proposing guidelines for therapeutic management. Methods: This is a prospective single-centre study of a series of nine GSV-LMS in thigh (stage IIIA AJCC), knee and proximal leg (IB, 1 II and 3 IIIA), and ankle (2 IIIB and 1 II). Eight patients were female, and the mean age was 72 years. All patients were surgically treated. Five (56%) were unplanned excisions. All these patients were reoperated on to attempt wide resection margins. In a patient, an infra-patellar amputation was performed. Another amputation was refused by another patient. Eight patients received adjuvant radiotherapy. Results: One patient died 8 years after amputation for a reason other than LMS. The patient who refused amputation has been alive, disease-free, for 28 months. The mean follow-up of surviving patients was 39 months (6–78 months). In these patients, there were no local recurrences or metastases. The mean functional outcome according to the MSTS score was 28.9 (range: 24–30). Conclusions: Unplanned excision of GSV-LMS can be prevented through clinical and imaging suspicion. Surgery and re-excision in case of inadequate previous margins and adjuvant radiotherapy lead to a good oncological and functional outcome. Full article

Cutaneous leiomyosarcoma is a rare, malignant tumor that arises from smooth muscle cells, accounting for less than 3% of all cutaneous sarcomas. Our case report details a 63-year-old male patient who presented with a rapidly growing, painful nodule in the popliteal region. The patient underwent initial surgical excision in September 2021, followed by three subsequent resections until March 2022 due to local recurrence. Histopathological analysis of all specimens revealed a dermal neoplasm composed of spindle cells arranged in intersecting fascicles with storiform patterns. The immunohistochemistry profile showed strong positivity for the markers SMA and desmin, confirming the diagnosis. Despite early interventions, the deep surgical margins were positive, and further surgeries were required until tumor-free margins were achieved. This case emphasizes the morphological characteristics, clinical behavior, and therapeutic challenges in managing cutaneous leiomyosarcoma. A favorable prognosis is achieved with long-term follow-up and a multidisciplinary approach. Full article

Background/Objectives: Brain metastasis from uterine leiomyosarcoma (ULMS) is an exceptionally rare complication of an aggressive malignancy. With fewer than 40 cases previously documented, a significant knowledge gap exists regarding its clinical course, management, and outcomes. This study provides the largest analysis of ULMS brain metastases to date, integrating a systematic literature review with a novel case report illustrating the disease’s uniquely rapid progression. Methods: Following PRISMA guidelines, we systematically reviewed four major databases to identify all reported cases of intracranial metastasis from ULMS. Data on patient demographics, clinico-radiological features, treatments, and survival were extracted and analyzed. Methodological quality was assessed using a modified Joanna Briggs Institute (JBI) tool. Results: We analyzed 34 studies with 39 individual cases. Additionally, this review was supplemented by one new illustrative case from our institution. The median patient age was 51.5 years, and most presented with focal neurological symptoms. Common imaging findings included hyperdense lesions on CT and homogeneously enhancing, dural-based masses on MRI, which mimic other intracranial pathologies. Though surgery was the most frequent intervention (76.9%), median survival after a brain metastasis diagnosis was a grim 5 months, with no significant difference observed between treatment modalities. Our illustrative case was remarkable for an extremely rapid volumetric doubling time averaging just 7.3 days. Conclusions: Brain metastasis from ULMS is a lethal event with an extremely poor prognosis. Nonspecific imaging features create diagnostic challenges, necessitating histopathological confirmation. Current therapies, including surgery and radiotherapy, offer palliative benefit but do not significantly alter survival. The aggressive biological behavior demonstrated here underscores the urgent need for increased clinical awareness and collaborative research to develop more effective management strategies and improve outcomes for this devastating diagnosis. Full article

Background: Sarcoma surveillance guidelines still apply uniform imaging intervals based on tumor grade and stage that ignore histotype-specific metastatic behavior. We prospectively analyzed metastatic timing, organ tropism, and lesion burden across a real-world sarcoma cohort to generate an evidence base for risk-adapted follow-up and treatment stratification. Methods: In a prospective multicenter study, 1850 patients with suspected sarcoma were screened. SHAPEHub, a real-world-time data warehouse, captured clinicopathological variables and imaging. Adults with histologically confirmed soft-tissue or bone sarcoma (n = 295) formed the analytic cohort. Metastases were classified as synchronous (≤6 months) or metachronous (>6 months), lung-only versus multi-organ, and oligometastatic (≤5 lesions, ≤2 organs) versus polymetastatic. TTME was illustrated with Kaplan–Meier curves for the full cohort (descriptive); where subgroup comparisons are shown, log-rank tests are reported. Results: Ninety-three patients (31.5%) developed metastases after a median follow-up of 20.9 months. Metastatic risk was front-loaded: 36.6% were synchronous, and 67.8% of metachronous events occurred within year 1. The lung was the initial site in 62.4% of events, bone in 18.3%, and liver in 11.8%. Half of the lung-metastatic patients remained pulmonary-confined; the remainder followed a multi-organ route involving bone and lymph nodes. Oligometastatic spread predominated in the lung-only subgroup (61%) versus multi-organ (28%). Histotype influenced both timing and tropism: angiosarcoma and Ewing sarcoma metastasized earliest (median 3.7 and 5.0 months) and multi-organ; leiomyosarcoma and UPS were lung-dominant; Ewing sarcoma and epithelioid haemangioendothelioma were bone-tropic; and angiosarcoma was liver-tropic. Conclusions: Metastatic sarcoma displays three intersecting dimensions—early versus late onset, organ-specific tropism, and oligo- versus polymetastatic burden—none of which are addressed by the current “one-size-fits-all” surveillance. Recognizing these patterns delineates windows for tailored imaging and stratified therapy selection (e.g., local ablation for oligometastatic lung disease, intensified systemic regimens for early, polymetastatic spread). These findings lay the groundwork for precision-adapted surveillance and treatment protocols. Pattern-stratified trials and health-economic evaluations are now needed to assess whether this approach improves outcomes and optimizes resource allocation. Full article

Background: Vulvar leiomyosarcoma (VLMS) is a rare and aggressive soft tissue malignancy arising from smooth muscle cells, comprising less than 3% of vulvar cancers. Its clinical resemblance to benign vulvar lesions often leads to delayed diagnosis. Despite surgical resection and adjuvant therapy, VLMS is associated with high recurrence rates and a poor prognosis, and due to its rarity, there is no standardized management or surveillance protocol. Case Report: We present a case of high-grade VLMS in a postmenopausal woman, initially diagnosed in 2020 and managed with surgical excision and adjuvant radiotherapy. The primary tumor was a 10 cm solid, lobulated mass involving the mons pubis, with histology confirming high-grade leiomyosarcoma based on marked cellular atypia, high mitotic activity, and smooth muscle differentiation. Immunohistochemistry was positive for SMA, vimentin, and CD34, and negative for S100 and MyoD1. Five years later, the patient developed a local recurrence with an enlarged inguinal lymph node. She underwent complete tumor resection and bilateral inguinal lymphadenectomy. Histology of the recurrent lesion mirrored the initial findings, with no lymph node metastases. This case highlights the aggressive nature and potential for late recurrence in vulvar leiomyosarcoma, underscoring the importance of long-term surveillance. Conclusions: High-grade VLMS is a rare malignancy with a high recurrence risk. This case highlights the importance of early diagnosis, radical surgical treatment, and long-term surveillance. Although recurrence occurred five years after the initial treatment, timely surgical intervention led to a favorable postoperative course. Multidisciplinary management and individualized follow-up strategies remain key to improving outcomes in these rare gynecologic sarcomas. Full article

Background: Bladder leiomyosarcoma is an extremely rare non-urothelial malignancy, accounting for less than 0.1% of all bladder tumors. It presents significant diagnostic and therapeutic challenges due to its aggressive nature and the absence of standardized treatment protocols. Case presentation: We report the case of a 61-year-old woman who presented with hematuria, dysuria, and suprapubic pain. Imaging revealed a large, locally invasive bladder mass, and histopathological examination following transurethral resection confirmed leiomyosarcoma. The patient underwent radical cystectomy with resection of adjacent bowel segments and urinary diversion. Histology showed a high-grade leiomyosarcoma (pT3N0) with extensive necrosis and a high mitotic index. Two months postoperatively, peritoneal dissemination was detected. Systemic chemotherapy with dacarbazine and doxorubicin initially led to the regression of metastases, but disease progression occurred within months, including lung, liver, and bone metastases. Palliative radiotherapy and second-line chemotherapy were initiated. As of now, 16 months have elapsed since surgery. Conclusions: This case underscores the aggressive clinical course of bladder leiomyosarcoma despite multimodal therapy and the urgent need for individualized management strategies. Given its rarity, this case contributes to the limited literature and highlights the importance of vigilant follow-ups and further studies to establish evidence-based treatment protocols. Full article

Uterine leiomyomas (ULM) and uterine leiomyosarcomas (ULMS) represent smooth muscle tumors with similar initial presentations but drastically different outcomes. This literature review analyzes the similarities and differences in their epigenetic profiles to identify diagnostic biomarkers and potential therapeutic targets that could improve clinical management. Both tumor types exhibit mostly distinct epigenetic signatures while sharing key pathway dysregulations. ULMS demonstrates global DNA hypomethylation, increased histone acetyltransferase activity, elevated Histone Deacetylase (HDAC) class I expression, and characteristic microRNA profiles. ULM displays focal methylation patterns and specific microRNA alterations that promote extracellular matrix accumulation. Despite these differences in epigenetic mechanisms, both tumors converge on dysregulation of signaling pathways including PI3K/AKT/mTOR, Wnt/β-catenin, and Transforming Growth Factor beta (TGF-β) signaling, suggesting common downstream effects from distinct epigenetic origins. Understanding the shared and distinct epigenetic landscape between ULM and ULMS will enhance our insights into tumor pathogenesis and may offer promising biomarkers and therapeutic targets. Full article

High-grade sarcomas often lack typical morphological features and exhibit no clear differentiation, often leading to a diagnosis of undifferentiated sarcoma (US). Pleomorphic leiomyosarcoma (PLMS) is a high-grade sarcoma consisting of a typical leiomyosarcoma (LMS) component alongside dedifferentiated high-grade areas. A few decades ago, PLMS was regarded as a subtype of high-grade sarcoma previously referred to as malignant fibrous histiocytoma; it is now classified as a variant of LMS. The mechanisms underlying myogenic differentiation and their relevance to the pathological diagnosis of high-grade sarcomas remain poorly understood. To investigate the gene expression networks associated with myogenic differentiation, we employed Cap Analysis of Gene Expression (CAGE) to distinguish PLMS from other high-grade sarcoma subtypes. We analyzed 27 frozen high-grade sarcoma samples, comprising 10 PLMSs, 11 high-grade myxofibrosarcomas, 3 dedifferentiated liposarcomas, 2 USs, and 1 high-grade sarcoma not otherwise specified, using CAGE profiling. Hierarchical clustering based on differentially expressed genes identified by CAGE separated 7 of the 10 PLMSs from other high-grade sarcomas, while the remaining 3 PLMSs clustered with a single US case. CAGE analysis also revealed that the myostatin (MSTN) promoter (false discovery rate [FDR] < 0.05) was more strongly activated in the high-grade sarcoma group lacking morphological and immunohistochemical smooth muscle differentiation than in the PLMS group, whereas the alpha smooth muscle actin (ACTA2) promoter (FDR < 0.05) was more prominently activated in the PLMS group. Immunohistochemical analysis showed reduced or absent myostatin expression in PLMSs, in contrast to diffuse myostatin expression in other high-grade sarcomas. Smooth muscle actin, encoded by ACTA2, was expressed in all 10 PLMS cases but only in 11 of 17 other high-grade sarcomas. Furthermore, both conventional immunohistochemistry and double immunostaining revealed that myostatin and myogenic markers exhibited largely mutually exclusive expression patterns within these tumors. A validation study was performed using 59 soft tissue sarcoma cases, including 27 PLMSs and 16 LMSs. Loss or reduction in myostatin expression was confirmed in both LMS and PLMS, and the ratio of myostatin loss was comparable (62.5% in LMS vs. 63% in PLMS). Collectively, these findings suggest that myostatin contributes to smooth muscle differentiation in high-grade sarcomas and has potential utility as a diagnostic marker. Full article

Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, BUB1 was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high BUB1 expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas. Full article

Background: Sarcomas are a rare and biologically diverse group of malignant tumors that originate from mesenchymal tissues. They are characterized by a broad range of histopathological subtypes, varying clinical courses, and differing responses to treatment. This study seeks to clarify the clinicopathological and molecular predictors of recurrence in leiomyosarcomas, carcinosarcomas, and endometrial stromal sarcomas to enhance our understanding, thereby improving clinical knowledge, consultation practices, and the overall benefit for patients. Methods: A literature search was conducted utilizing PubMed/MEDLINE, Embase, Cochrane Library, and Scopus to execute a comprehensive structured narrative review of articles published up to 31 March 2025. Results: We summarize existing evidence on the clinical, histological, and molecular predictors of recurrence and poor prognosis for leiomyosarcomas, carcinosarcomas, and endometrial stromal sarcomas. While the stage, grade, tumor size, and novel molecular biomarkers are crucial high-risk parameters that have been associated with recurrence, existing data demonstrate contradictory results, indicating the need for further research. Conclusions: Recent advancements in next-generation sequencing have facilitated the identification of women at increased risk of recurrence, poor disease-free survival, and overall adverse prognosis. Stratifying this risk requires a comprehensive understanding of the clinical, histological, and molecular risk factors involved. Understanding these underlying factors is essential for effectively addressing the initial consultation, guiding management, and—considering the novel treatment modalities—individualizing the care provided to the affected women. Full article

Purpose: We present our single-institution experience of sarcomatous brain metastasis patients who underwent stereotactic radiosurgery (SRS) over the past 35 years. Methods: In total, 31 patients (16 males) who underwent SRS for sarcoma brain metastases were identified. Median age at presentation to SRS was 47 (range: 4–78) months. Common histopathologies included leiomyosarcoma (eight patients), osteosarcoma (six patients), alveolar sarcoma (three patients), Ewing sarcoma (three patients), and undifferentiated/unclassified sarcoma (three patients). The median Karnofsky Performance Score (KPS) was 90. Nine patients underwent pre-SRS craniotomy. The median dose prescribed was 18 Gy. The median cumulative tumor volume was 1.4 cc. Results: Median patient overall survival (OS) after SRS was 7 (range: 0–155) months. Local tumor control (LTC) was achieved in 105 out of 113 tumors, at a median time of 3 (range: 0–17) months between SRS and progression. LTC rates per patient and per tumor were 74.2% and 92.9%, respectively. Following SRS, 10 patients (32.3%) developed new tumors at a median time of 6 (range: 1–25) months. Four patients experienced adverse radiation effects (AREs). At the last follow-up, all patients died, one patient from intracranial progression, 27 from systemic disease progression, and the remaining from unrelated medical conditions. Conclusions: Given high LTC and low ARE rates, this suggests SRS as a strong candidate for the non-invasive management of sarcomatous brain metastases, which typically present late following initial presentation of the primary disease. Full article

Objectives: To evaluate the clinical heterogeneity of sarcomas by examining associations between histological subtypes, metastatic patterns, treatment modalities, and survival outcomes. Methods: We analyzed data from 97,062 adult patients diagnosed with sarcoma between 2000 and 2020, using the Surveillance, Epidemiology, and End Results (SEER) database. Fourteen histological subtypes were included. Propensity score matching (PSM) was employed to adjust for baseline differences, and Cox proportional hazards models were used to identify prognostic variables. Results: The most prevalent subtypes were sarcoma not otherwise specified (31.9%), leiomyosarcoma (17.1%), and liposarcoma (13.9%). Metastatic patterns differed significantly by subtype; liver metastases were most common in sarcomas with small blue round cell (SBRC) features (8.9%) and stromal sarcoma (6.1%), while lung metastases were frequently observed in Ewing sarcoma (10.0%) and rhabdomyosarcoma (9.7%). Median overall survival (mOS) varied widely, ranging from 234 months in chondrosarcoma to 16–20 months in rhabdomyosarcoma and SBRC sarcoma. Overall, patients with primary sarcoma had significantly better survival than those with treatment-related disease (119.0 vs. 45.0 months, p < 0.0001), with this trend consistent across most subtypes. Treatment responses were subtype- and size-dependent. For instance, surgery plus radiotherapy improved outcomes in giant cell sarcoma regardless of tumor size, whereas chemotherapy provided benefit only in tumors larger than 5 cm. Combined surgery and radiotherapy offered additional survival benefit in select subtypes, including chordoma, leiomyosarcoma (>5 cm), and synovial sarcoma (<5 cm). Conclusions: Sarcomas exhibit substantial clinical and prognostic heterogeneity across histological subtypes. These findings underscore the importance of subtype-specific, individualized treatment strategies in optimizing patient outcomes. Full article

This manuscript examines the role of artificial intelligence (AI) in the diagnosis and treatment of uterine fibroids and uterine sarcomas, offering a comprehensive assessment of AI-supported diagnostic and therapeutic techniques. Through the use of radiomics, machine learning, and deep neural network models, AI shows promise in identifying benign and malignant uterine lesions, directing therapeutic decisions, and improving diagnostic accuracy. It also demonstrates significant capabilities in the timely detection of fibroids. Additionally, AI improves surgical precision, real-time structure detection, and patient outcomes by transforming surgical techniques such as myomectomy, robot-assisted laparoscopic surgery, and High-Intensity Focused Ultrasound (HIFU) ablation. By helping to forecast treatment outcomes and monitor progress during procedures like uterine fibroid embolization, AI also offers a fresh and fascinating perspective for improving the clinical management of these conditions. This review critically assesses the current literature, identifies the advantages and limitations of various AI approaches, and provides future directions for research and clinical implementation. Full article

This retrospective, single-center study investigates the association between PET parameters and pathological response or disease recurrence in patients with soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy (NACT). The maximum standardized uptake value (SUVmax_BL), metabolic tumor volume (MTV_BL), and total lesion glycolysis (TLG_BL) were measured at baseline [¹⁸F]FDG PET/CT and the change in percentage (ΔSUVmax, ΔMTV, ΔTLG) from baseline to early evaluation [¹⁸F]FDG PET/CT was calculated. The optimal cutoff values of the different PET parameters for pathological response, defined as <10% residual viable tumor (RVT) or >15% fibrosis/hyalinization, and recurrence-free survival were obtained for analysis. Forty-two patients who underwent baseline [¹⁸F]FDG PET/CT and NACT followed by surgery were included between January 2015 and January 2023. The primary diagnoses were angiosarcoma (n = 15), leiomyosarcoma (n = 15), sarcoma not otherwise specified (n = 9) and synovial sarcoma (n = 3). Twenty-eight (66.6%) patients underwent an early evaluation PET/CT. MTV_BL, TLG_BL, and ΔSUVmax (p = 0.024; p = 0.042, p = 0.009, respectively) values above the cutoff were associated with a pathological response based on RVT. ΔSUVmax, ΔMTV, and ΔTLG (p = 0.002; p = 0.019; p = 0.039, respectively) values above the cutoff were positively related to >15% fibrosis/hyalinization. MTV_BL, TLG_BL, and ΔMTV (p = 0.014; p = 0.022; p = 0.034, respectively) values above the cutoff were prognostic for the recurrence of disease. [¹⁸F]FDG PET/CT has a promising role in STS patients treated with NACT. Full article

Background: Serum biomarkers such as Carcinoma Antigen 125 (CA125) and Human Epididymis Protein 4 (HE4) are widely used in the diagnosis and prognosis of gynecological malignancies. Serum biomarkers such as CA125 and HE4 represent essential tools in improving early detection, risk stratification, and therapeutic decision-making for gynecological malignancies. However, their role in identifying uterine sarcomas remains debated. This systematic review and case series aims to examine the diagnostic and prognostic significance of CA125 and HE4 in uterine sarcomas. Methods: A systematic review was performed on studies investigating serum CA125 and HE4 levels in uterine sarcomas. A case series of all uterine sarcomas treated at the Campus Bio-Medico Gynecology Unit of Rome from 2010 to 2020 was analyzed. Results: The analysis of the 11 selected studies allowed us to investigate the role of CA125 in uterine sarcomas. No studies analyzing the role of HE4 in monitoring the disease were found. A total of 16 patients with confirmed uterine leiomyosarcoma were included in our case series. Conclusions: Neither CA125 nor HE4 can currently be considered definitive biomarkers for the diagnosis of uterine leiomyosarcomas. However, they may serve as useful adjuncts in the differential diagnosis between leiomyomas and leiomyosarcomas, particularly in reproductive-age patients. Full article