Search Results (221)

Background and Clinical Significance: Uterine smooth muscle tumors range from benign leiomyomas to highly aggressive leiomyosarcomas. Smooth muscle tumors of uncertain malignant potential (STUMP) represent an intermediate and diagnostically challenging category defined by borderline or discordant histological features. Their clinical management remains complex due to limited possibilities for reliable preoperative differentiation and the absence of clearly established surveillance protocols. The situation becomes particularly sensitive in postmenopausal patients, in whom tumor growth or abnormal bleeding raises concern for malignancy. Case Presentation: We report a 66-year-old postmenopausal woman presenting with persistent uterine bleeding and interval growth of a previously presumed leiomyoma. Transvaginal ultrasound demonstrated a heterogeneous intramural mass measuring approximately 5–7 cm, while endometrial sampling revealed inactive, atrophic endometrium without evidence of malignancy. Given the patient’s postmenopausal status and progressive symptoms, total abdominal hysterectomy with bilateral adnexectomy was performed. Histopathological examination identified moderate cytological atypia, focal coagulative tumor necrosis, and mitotic activity of up to five mitoses per ten high-power fields, findings insufficient for leiomyosarcoma but exceeding those expected for a benign leiomyoma. A diagnosis of STUMP was established. Postoperative staging showed no residual or metastatic disease, and structured long-term follow-up was initiated. Discussion: This case illustrates the limitations of current preoperative diagnostic tools in distinguishing between benign and borderline or malignant uterine smooth muscle tumors. Clinical presentation, imaging, and endometrial sampling were not predictive of the final diagnosis. In postmenopausal women, enlargement of a presumed leiomyoma should prompt careful evaluation, as histological assessment after complete surgical removal often remains the only reliable method of diagnosis. The unpredictable biological behavior of STUMP and reported cases of late recurrence support the need for prolonged surveillance, even after apparently adequate surgical treatment. Conclusions: STUMP remains primarily a postoperative diagnosis and represents a persistent gray zone in gynecologic oncology. Postmenopausal tumor growth and abnormal bleeding warrant an individualized and cautious approach. Careful histopathological evaluation and long-term follow-up are essential to ensure early detection of possible recurrence and optimal patient management. Full article

Soft tissue sarcomas are rare malignant mesenchymal tumors for which accurate diagnosis, prognostic stratification, and therapeutic decision-making remain challenging. Although histopathology and immunohistochemistry are essential diagnostic tools, they frequently fail to capture the molecular complexity underlying tumor aggressiveness and treatment resistance. In this study, we evaluated the utility of RNA-based next-generation sequencing for the molecular characterization of STS and for elucidating transcriptomic mechanisms associated with aggressive tumor behavior. An observational cohort of 24 patients with histologically confirmed soft tissue sarcomas was analyzed, using adipose and skeletal muscle tissue as controls. RNA was extracted from tumor samples, libraries were prepared with a targeted pan-cancer panel, and sequencing was performed on the Illumina platform, followed by bioinformatic analysis using DRAGEN pipelines and DESeq2. RNA-NGS identified a predominance of single-nucleotide polymorphisms and significant differential gene expression, with overexpression of proliferation-related genes (TOP2A, MKI67, BUB1B), extracellular matrix and microenvironment-associated genes (COL11A1, SPP1), and developmental regulators (HOXD13, MELK). Subgroup analysis revealed a distinct transcriptomic profile in leiomyosarcoma, while gene fusion analysis detected clinically relevant alterations. These findings demonstrate that RNA-NGS provides biologically and clinically meaningful insights into the molecular landscape of soft tissue sarcomas and supports its integration into precision medicine-oriented diagnostic workflows. Full article

Background: Vascular leiomyosarcoma (LMS) is an exceptionally rare and aggressive soft tissue sarcoma arising from the smooth muscle cells of the vascular wall. They account for approximately 0.5–2% of adult soft-tissue sarcomas and are the most frequent primary malignancy of vascular origin. Among venous sites, the inferior vena cava (IVC) is the most frequently involved, accounting for more than half of reported vascular LMS cases, with rarer occurrences in peripheral veins, including the internal saphenous vein and the external iliac vein. Case Presentation: We report a case series comprising two distinct presentations of vascular LMS involving the internal saphenous vein and the inferior vena cava, respectively. Each case highlights unique clinical manifestations, radiologic features, histopathologic diagnosis, and therapeutic challenges inherent to the involved vascular territory. Surgical resection with clear margins was the primary treatment modality, complemented by adjuvant therapies tailored according to tumor grade and extent. Literature Review: An updated literature review contextualizes these findings, detailing epidemiology, diagnostic challenges, prognostic factors, and current management approaches. It emphasizes the rarity of leiomyosarcomas originating from major venous pathways and highlights variability in clinical presentation, tumor size, growth patterns, and outcomes. Achieving complete surgical removal with negative margins continues to be the primary treatment goal and the most significant prognostic factor. Conclusions: Given the paucity of cases, our series contributes valuable insights into the clinical spectrum and multidisciplinary approach necessary for optimal outcomes in vascular LMS. Early recognition and aggressive treatment remain paramount to improving survival in this rare malignancy. Full article

Background: Retroperitoneal leiomyosarcomas are aggressive malignancies. Complete surgical resection with negative margins is crucial to decrease the risk of recurrence but can be risky due to vascular involvement. The aim of our study was to evaluate the different approaches to IVC and renal vein management and their impact on postoperative complications. Methods: We performed a retrospective review of patients who underwent surgery for retroperitoneal leiomyosarcoma with IVC and/or renal vein involvement at our institution from 2016 to 2024. Patients were stratified by intraoperative vascular management, including ligation only versus varying forms of vascular reconstruction. Postoperative complications, including bleeding, transfusions, the need for acute and chronic hemodialysis, and thromboembolic events, were recorded. Chi-squared tests were used to compare rates of postoperative complications by vascular management. A p-value of 0.05 was considered statistically significant. Results: We identified 60 patients at our institution who underwent surgery for leiomyosarcoma with IVC and/or renal vein involvement. Ten patients underwent IVC ligation alone due to thrombosis, thirty-six had IVC replacement, and fourteen had patch angioplasty. In the entire cohort, twenty-six patients (43.3%) experienced an adverse event after surgery. When looking at postoperative adverse events by IVC management, we did not find any statistically significant differences among rates of adverse events by group. There were also no statistically significant differences in complications following renal vein ligation versus renal vein reconstruction. Conclusions: Patients with leiomyosarcoma with IVC and/or renal vein involvement have several options for intraoperative vascular management. Our data demonstrates that there are no statistically significant differences in rates of complications among the different groups. Full article

Uterine smooth muscle tumors (USMTs) represent a diagnostically and clinically challenging subset of uterine mesenchymal neoplasms. Up to 5% of these tumors exhibit ambiguous histological features that preclude definitive classification as either benign leiomyomas or malignant leiomyosarcomas. This review provides a comprehensive synthesis of the evolving diagnostic criteria, histopathological variants, and recent advancements in immunohistochemical and molecular profiling of smooth muscle tumors with uncertain malignant potential (STUMPs). The review traces the historical development of diagnostic criteria, from the original mitotic thresholds to the “Stanford criteria,” which incorporate mitotic index, cytological atypia, and tumor cell necrosis. Contemporary WHO guidelines largely uphold these principles, with nuanced refinements for spindle, myxoid, and epithelioid subtypes. However, recent studies suggest additional morphologic indicators, such as atypical mitoses, infiltrative margins, and vascular invasion, may provide prognostic insight. Notably, necrosis remains the most reliable histologic predictor of recurrence, while mitotic activity and atypia, though important, are less specific. In conclusion, STUMPs represent a heterogeneous group with unpredictable behavior that requires long-term clinical follow-up. While existing histological and molecular tools aid classification, definitive prognostic markers remain elusive. Further studies integrating histopathology, immunohistochemistry, and molecular biology are essential to refine diagnosis and improve therapeutic decision-making in this diagnostically ambiguous group of uterine tumors. Full article

Background and Objectives: This study aimed to describe the clinical characteristics and survival outcomes of three representative complex karyotype soft tissue sarcoma (STS) subtypes—undifferentiated sarcoma (US, primarily undifferentiated pleomorphic sarcoma (UPS)), myxofibrosarcoma (MFS), and leiomyosarcoma of soft tissue (LMS-ST)—using data from a single-institution cohort. Materials and Methods: A retrospective review of 124 patients treated at a single tertiary referral center between 2002 and 2024 was conducted. Clinicopathologic characteristics and survival outcomes were analyzed. Kaplan–Meier methods were used to estimate overall survival (OS). Cox proportional hazards regression models were applied to identify independent prognostic factors for survival, incorporating variables such as age, sex, tumor stage, and treatment modality. Results: The cohort comprised 36 cases of US, 64 of MFS, and 24 of LMS-ST. OS and survival after cohort enrollment (S-NCC) were evaluated both by subtype and across the entire cohort to assess potential differences across tumor subgroups. In both univariable and multivariable analyses, US subtypes showed poorer survival than MFS and LMS-ST. FNCLCC grade 3 emerged as a significant adverse prognostic factor for survival across all three subtypes. For FNCLCC grade 3 patients, the presence of benign prostatic hyperplasia (BPH) was significantly associated with an increased risk of death. Conclusions: Among the three subtypes, US demonstrated the most aggressive clinical course, MFS was notable for frequent local recurrence but relatively favorable survival, and LMS-ST showed intermediate outcomes. These findings highlight the clinical heterogeneity of complex karyotype STS and provide a foundation for future studies integrating molecular and multi-omics data to refine risk stratification and therapeutic strategies. Full article

Background: Leiomyosarcomas are an aggressive soft-tissue sarcoma that arise from smooth muscle, have a high metastatic potential and account for 10–20% of soft-tissue sarcomas. Despite decades of research, the first-line treatment remains unresolved due to the absence of direct comparative trials, heterogeneous study designs, and trade-offs between efficacy and toxicity. This systematic review evaluates the optimal therapeutic systemic chemotherapy regimens in the first-line setting, specifically gemcitabine- and doxorubicin-based regimens, including associated toxicities. Methods: A systematic search in MEDLINE (Ovid), Embase (Ovid), and Cochrane Library (Wiley) identified studies of first-line gemcitabine- or doxorubicin-based chemotherapy for leiomyosarcoma. The review protocol was registered in PROSPERO (CRD420261280028). Of the 3092 articles screened, 11 articles were eligible for inclusion, comprising results from 1225 patients. Eligible studies were in English and included ≥10 patients with advanced/metastatic leiomyosarcoma reporting on LMS-specific outcomes and no prior systemic therapy. This qualitative systematic review synthesizes prospective and retrospective evidence without quantitative meta-analysis. Results: The review included two phase 3 trials, six phase 2 trials, one phase 1b trial, and two retrospective studies. While there was no direct comparison in this setting, doxorubicin-based combinations consistently reported higher objective response rates, progression-free survival, and overall survival. The most favorable outcomes were observed in the LMS04 trial with doxorubicin plus trabectedin followed by surgery and trabectedin maintenance, yielding a median progression-free survival of 12 months, overall survival of 33 months, and objective response rate of 36%. This regimen also had the highest grade 3–4 toxicity. Conclusions: Doxorubicin-based regimens remain the most active first-line option for leiomyosarcoma, although treatment practices remain heterogeneous. Full article

Background: Sarcomas are rare, aggressive malignancies with limited therapeutic options in advanced stages. This is the first real-world study in the MENA region evaluating the clinical utility of Next-Generation Sequencing (NGS) in guiding sarcoma treatment and improving outcomes. Methods: We retrospectively reviewed sarcoma patients who underwent NGS at a major referral center (2021–2024), comparing clinical and molecular outcomes between those who received NGS-based treatment adjustments (NBTA) and those who did not. Results: Seventy-eight patients were included (60% male; median age 44 years). Soft tissue sarcomas accounted for 70.5% of cases (n = 55), while bone sarcomas represented 29.5% (n = 23). Prior to NGS, 64.1% of patients had received a median of one line of systemic therapy. NGS was performed late in the disease course in 73% of cases. At least one mutation was detected in 87% (median 3 mutations). Targetable alterations were identified in 33% at the time of testing, rising to 42% with updated genomic knowledge and therapeutic advances. Overall, 20.5% received NBTA. Among non-NBTA patients, 67% had no actionable targets, 17% had no detectable mutations, and 16% were ineligible due to cost, limited access, or clinical deterioration. Tumor Mutational Burden was low in 79%, intermediate in 19%, and high in 2%, and all tumors were microsatellite stable. Patients receiving NBTA had a longer median Progression-Free Survival (9 vs. 2 months; p = 0.023). Median Overall Survival was longer in the NBTA group (74 vs. 48 months), though not statistically significant (p = 0.207). Genomic alterations were subtype-specific: EWSR1 rearrangements (Ewing and Desmoplastic small round cell tumors), CDK4 and MDM2 amplifications (Liposarcoma and Osteosarcoma), TP53 and RB1 mutations (Leiomyosarcoma), CDKN2A/B deletions (Undifferentiated Pleomorphic Sarcoma and Chondrosarcoma), and SS18 rearrangements (Synovial Sarcoma). Conclusions: Genomics-guided therapy in sarcoma is feasible and impactful. Expanding timely access to molecular profiling is essential for advancing precision oncology in the MENA region. Full article

Uterine mesenchymal tumors encompass a diverse and diagnostically challenging group of neoplasms, including smooth muscle tumors, endometrial stromal tumors (ESS), perivascular epithelioid cell tumors (PEComas), inflammatory myofibroblastic tumors (IMTs), uterine tumor resembling ovarian sex cord tumor (UTROSCT), along with many other relatively rare entities. Traditionally classified by histomorphology and immunophenotype, these tumors are now increasingly defined by recurrent genetic alterations that refine diagnosis and elucidate tumorigenesis. For example, leiomyosarcomas display complex genomic instability with frequent TP53, RB1, and ATRX mutations. Low grade-ESS are characterized by JAZF1::SUZ12 and other related fusions, whereas high-grade tumors harbor YWHAE::NUTM2 or ZC3H7B::BCOR fusions, and BCOR internal tandem duplication (ITD) alterations. PEComas frequently contain TSC1 or TSC2 mutations, leading to aberrant activation of the mTOR pathway. Beyond their diagnostic utility, these molecular signatures increasingly inform prognosis and highlight potential therapeutic targets, including CDK4/6 inhibition, PI3K/AKT/mTOR blockade, and immunotherapy. This review summarizes the evolving molecular landscape of uterine mesenchymal tumors, underscoring the value of integrating molecular testing into clinical practice to enhance diagnostic precision and enable personalized management of these rare yet clinically significant neoplasms. Full article

Retroperitoneal sarcomas (RPS) are rare tumours, primarily treated with surgical resection. However, recurrences are frequent. Combining clinical factors with CT-derived radiomic features could enhance treatment stratification and personalization. This study aims to assess whether radiomic features provide additional prognostic value beyond clinicopathological features in patients with high-risk RPS treated with preoperative radiotherapy. This retrospective study included patients aged 18 or older with non-recurrent and non-metastatic RPS treated with preoperative radiotherapy between 2008 and 2016. Hazard ratios (HR) were calculated using Cox proportional hazards regression to assess the impact of clinical and radiomic features on time to event outcomes. Predictive accuracy was assessed with c-statistics. Radiomic analysis was performed on the high-risk group (undifferentiated pleomorphic sarcoma, well-differentiated/de-differentiated liposarcoma or grade 2/3 leiomyosarcoma). Seventy-two patients were included, with a median follow-up of 3.7 years, the 5-year overall survival (OS) was 67%. Multivariable analysis showed older age (HR: 1.3 per 5-year increase, p = 0.04), grade 3 (HR: 180.3, p = 0.02), and larger tumours (HR: 4.0 per 10 cm increase, p = 0.02) predicted worse OS. In the higher-risk group, the c-statistic for the clinical model was 0.59 (time to distant metastasis (TDM)) and 0.56 (OS). Among 27 radiomic features, kurtosis improved OS prediction (c-statistic 0.69, p = 0.013), and Neighbourhood Gray-Tone Difference Matrix (NGTDM) busyness improved it to 0.73 (p = 0.036). Kurtosis also improved TDM prediction (c-statistic 0.72, p = 0.023). Radiomic features may complement clinicopathological factors in predicting overall survival and time to distant metastasis in high-risk retroperitoneal sarcoma. These exploratory findings warrant validation in larger, multi-institutional studies. Full article

Uterine angiomyolipoma (AML) is an exceptionally rare mesenchymal tumor of the perivascular epithelioid cell tumor (PEComa) family. Most cases are benign and exhibit a triphasic histologic pattern. Although extragenital PEComas typically show strong, diffuse HMB-45 reactivity, uterine AMLs/PEComas often exhibit weak or negative staining, thereby introducing diagnostic uncertainty. We describe a rare case of uterine AML with diffuse nuclear atypia in a postmenopausal woman, which mimicked a degenerative leiomyoma or leiomyosarcoma. A 49-year-old postmenopausal woman presented with the rapid enlargement of a uterine mass that had been followed for four years as a presumed leiomyoma. Imaging revealed a well-circumscribed uterine mass with heterogeneous enhancement, cystic degeneration, and restricted diffusion on MRI. A total hysterectomy was performed. Grossly, the tumor measured 8 cm. Microscopically, it consisted of pleomorphic epithelioid cells (70%), mature adipose tissue (20%), and thick-walled vessels. Immunohistochemistry revealed diffuse smooth muscle actin (SMA) positivity, while Human Melanoma Black (HMB)-45 and Melan-A were negative. Only one mitosis per 50 HPF was identified, with no atypical mitoses or necrosis, and the Ki-67 index was low (<5%). The patient has remained disease-free for 56 months post-surgery. This case represents the first documented HMB-45-negative uterine angiomyolipoma with diffuse nuclear atypia, characterized by a low mitotic index, low Ki-67 proliferation rate, and a benign 56-month follow-up. It broadens the morphologic spectrum of uterine AML, demonstrating that diffuse nuclear atypia can occur in HMB-45-negative tumors with benign behavior, and that atypia alone should not be interpreted as evidence of malignancy. Recognition of this rare variant is essential to avoid misdiagnosing it as leiomyosarcoma. Full article

Uterine leiomyosarcoma (uLMS) is a rare, highly aggressive malignancy of uterine smooth muscle, associated with early metastasis, frequent recurrence, and poor prognosis. Accurate preoperative diagnosis remains difficult given that clinical and radiologic features often overlap with benign leiomyomas, and no reliable biomarkers are currently available. This review summarizes recent evidence on the role of microRNAs (miRNAs) in the biology and clinical management of uLMS. Literature from molecular and translational studies was examined to identify dysregulated miRNAs, their target pathways, and potential diagnostic and therapeutic applications. uLMS displays a characteristic miRNA profile, including downregulation of tumor-suppressive miRNAs such as the miR-29 and miR-200 families and upregulation of oncogenic miRNAs including miR-21 and the miR-183~96~182 cluster, leading to activation of PI3K/AKT/mTOR signaling and epithelial–mesenchymal transition (EMT). Circulating and tissue miRNAs show promise as minimally invasive biomarkers for differentiating uLMS from leiomyomas, predicting prognosis, and guiding therapy. Emerging therapeutic approaches aim to restore the tumor-suppressive miRNAs or inhibit oncogenic ones using mimics or antagomiRs. Overall miRNAs represent critical regulators of uLMS pathogenesis and hold significant potential for precision diagnosis, prognostication, and targeted therapy, though larger validation studies and improved delivery systems are required before clinical translation. Full article

Background/Objectives: The prognostic associations of tumor genomics and metastatic patterns remain incompletely defined in leiomyosarcoma (LMS). We investigated the association between tumor mutations, sites of metastasis, and survival in patients with LMS. Methods: This single-center retrospective cohort study evaluated 110 patients with biopsy-proven LMS who underwent genomic testing between January 2009 and May 2023. Associations between tumor mutations, metastatic sites, and uterine vs. non-uterine LMS were assessed using χ² or Fisher’s exact test. Progression-free survival/recurrence-free survival (PFS/RFS) and overall survival (OS) were estimated with the Kaplan–Meier method and compared using the log-rank test, and subsequent Cox proportional hazards regression examined associations of OS and PFS/RFS with tumor mutations and metastatic sites. Results: The study included 110 subjects (F/M: 81/29; median age, 57 years; 25/110 with metastatic disease). Overall, the most common mutations were in TP53 (74/110, 67%) and RB1 (24/110, 22%), and the most common metastatic sites were the lungs (79/99, 80%) and liver (37/99, 37%). In terms of metastatic patterns, peritoneal (24/50, 48%), pelvic (23/50, 46%), and pleural (9/50, 18%) metastases were more common in the uLMS group (p = 0.001, 0.01, and 0.04, respectively), whereas liver (27/60, 45%) and retroperitoneal (15/60, 25%) metastases were more common in the nuLMS group (p = 0.03 and 0.04, respectively). ATRX mutations (17/110, 15%) and pleural metastases (11/99, 11%) were independently associated with lower OS. Predictive survival models were generated, demonstrating variable interdependent associations between genomic alterations, metastatic sites, and outcomes (OS and PFS/RFS). Post hoc analysis of an independent cohort (N = 2606) demonstrated that ATRX mutations were similarly associated with lower OS (28.95 vs. 33.86 months; p = 0.006). Conclusions: Our study identifies differences in metastatic patterns between uterine and non-uterine LMS and highlights the adverse prognostic association of ATRX mutations and pleural metastases in a leiomyosarcoma-specific cohort. Full article

Uterine leiomyomas are a heterogenous group of benign mesenchymal tumours. While diagnosis is usually achieved through clinical assessment and pelvic ultrasound (PU), atypical subtypes are not as easily recognisable and can be mistaken for malignant tumours such as leiomyosarcoma or ovarian carcinoma. We describe the case of a 41-year-old patient who presented with increasing bulk symptoms, urinary frequency and growth of a hydropic leiomyoma (HLM) of the left lateral and posterior uterine wall that had been known for 10 years, confirmed with previous biopsy. The tumour filled the entire pelvic cavity in PU and was increasingly difficult to delineate; therefore an abdominal hysterectomy without oophorectomy was performed. Gross tissue examination showed an irregularly enlarged, asymmetric uterus with an intrauterine subserosal mass and an extrauterine papillary tumour arising from the right and posterior uterine wall. The tumour measured 20 × 17 × 10 cm in size. Numerous smooth muscle nodules were observed within the uterus and extending into the extrauterine component in a continuous transition, exhibiting a benign, bland appearance. The nodules were separated by abundant edematous connective tissue with increased vascularization. Histopathological analysis revealed low mitotic activity with no evidence of nuclear atypia, pleomorphism, or necrosis. Immunohistochemical staining confirmed the diagnosis of a benign smooth muscle tumour. Our findings confirm a rare, benign smooth muscle neoplasm with both intrauterine and extrauterine involvement, and add to the existing literature regarding presentation, diagnostic and therapeutic challenges associated with HLM. Full article

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