Primary left ventricular leiomyosarcoma: a case report.

Cardiac leiomyosarcomas are a rare subset of the already infrequent, primary malignant cardiac neoplasia spectrum. The most common site for a primary leiomyosarcoma of the ventricle is on the right with fewer than five globally reported cases in the left ventricle. Most present with non-specific symptoms but attention is usually sought after the appearance of compressive symptoms or arrhythmias. We present a case of a left ventricular leiomyosarcoma in a 50-year old female patient that had a delayed diagnosis and its subsequent surgical resection and oncological management with docetaxel and gemcitabine. This case highlights the need for a high index of suspicion for cardiac masses especially if there are competing chronic diseases with similar symptomatology. Given the rare presentation of left ventricular leiomyosarcomas, case reports may provide valuable information that is otherwise unavailable.

Posterior mediastinal leiomyosarcoma: Case report and literature review.

BACKGROUND: Posterior mediastinal leiomyosarcoma is an extremely rare malignant mesenchymal tumor with no special clinical symptoms, which is easily confused with some common tumors in the posterior mediastinum, affecting the accuracy of the first diagnosis by clinicians and delaying the treatment of patients. CASE SUMMARY: We report a 59-year-old woman with a space-occupying lesion in the posterior mediastinum. The patient was mistakenly diagnosed with lumbar muscle or vertebral body lesions due to chest and back pain and underwent conservative treatment, but her symptoms did not improve significantly and she gradually developed pain in both lower limbs. Chest computed tomography (CT) scan indicated the left lower lung paraspinal space and underwent standard single-aperture video-assisted thoracoscopic surgery (VATS), which was pathologically confirmed as posterior mediastinal leiomyosarcoma. CONCLUSION: Complete surgical resection of posterior mediastinal leiomyosarcoma can achieve good clinical results.

A case report of uterine leiomyosarcoma: unusual clinical presentation with unilateral hydronephrosis and importance of an appropriate diagnosis.

Uterine leiomyosarcoma is a rare malignant gynecologic tumor that arises from the myometrial or endometrial stromal precursor cells. This tumor has the highest prevalence in the pre- and post-is more frequent between 40 and 60 years old. It has a very unfavorable prognosis: only early-stage tumors have an acceptable prognosis; unfortunately, it is often diagnosed accidentally, typically on an advanced stage, when hematological metastases have already spread. Surgery is the main treatment strategy, while systemic treatment and radiotherapy are not recommended due to the lack of results. Since metastatization is mainly hematological, lymphadenectomy is not recommended. Recent progresses have been achieved in advanced and recurrent disease, often inoperable, thanks to new chemotherapies, target therapies and immunotherapies. We reported the case of a 51-year-old woman evaluated for lumbar pain in the right region compatible with renal colic. The ultrasound evaluation revealed right hydronephrosis and the presence of a paraovarian or intraligamentary mass compatible with fibroma. The abdominal CT confirmed the presence of a mass with heterogeneous vascularization. Therefore, the patient underwent laparoscopic surgery to remove the lesion which resulted to be a leiomyosarcoma G2. During the following week the patient underwent a laparoscopic hysterectomy. The first step for differential diagnosis consists in the evaluation of clinicopathological features, followed by the analysis of preoperative imaging. Pelvic MRI represents the gold standard, while CT is used to detect metastases. The main issue is that imaging shows limited ability in differential diagnosis between benign and malign smooth muscle tumor. The definitive diagnosis is confirmed by histological analysis; this implies the necessity of improved attentions on the surgical procedure, which is often performed by steps with prolongation of the treatment pathway. To distinguish which fibroids presents a major risk to be misdiagnosed, some risk scores were developed (rPRESS in 2014 and pLMS in 2019), though actually they are not applied in clinical practice. Uterine leiomyosarcoma (uLMS) is rare but causes several deaths in perimenopausal women due to lack of effective treatments, although target therapies represent a future hope. Furthermore, clinical practice needs support through the development and improvement of diagnostic risk scores and their integration into guidelines.

Deep learning radiomics-based prediction model of metachronous distant metastasis following curative resection for retroperitoneal leiomyosarcoma: a bicentric study.

BACKGROUND: Combining conventional radiomics models with deep learning features can result in superior performance in predicting the prognosis of patients with tumors; however, this approach has never been evaluated for the prediction of metachronous distant metastasis (MDM) among patients with retroperitoneal leiomyosarcoma (RLS). Thus, the purpose of this study was to develop and validate a preoperative contrast-enhanced computed tomography (CECT)-based deep learning radiomics model for predicting the occurrence of MDM in patients with RLS undergoing complete surgical resection. METHODS: A total of 179 patients who had undergone surgery for the treatment of histologically confirmed RLS were retrospectively recruited from two tertiary sarcoma centers. Semantic segmentation features derived from a convolutional neural network deep learning model as well as conventional hand-crafted radiomics features were extracted from preoperative three-phase CECT images to quantify the sarcoma phenotypes. A conventional radiomics signature (RS) and a deep learning radiomics signature (DLRS) that incorporated hand-crafted radiomics and deep learning features were developed to predict the risk of MDM. Additionally, a deep learning radiomics nomogram (DLRN) was established to evaluate the incremental prognostic significance of the DLRS in combination with clinico-radiological predictors. RESULTS: The comparison of the area under the curve (AUC) values in the external validation set, as determined by the DeLong test, demonstrated that the integrated DLRN, DLRS, and RS models all exhibited superior predictive performance compared with that of the clinical model (AUC 0.786 [95% confidence interval 0.649-0.923] vs. 0.822 [0.692-0.952] vs. 0.733 [0.573-0.892] vs. 0.511 [0.359-0.662]; both P < 0.05). The decision curve analyses graphically indicated that utilizing the DLRN for risk stratification provided greater net benefits than those achieved using the DLRS, RS and clinical models. Good alignment with the calibration curve indicated that the DLRN also exhibited good performance. CONCLUSIONS: The novel CECT-based DLRN developed in this study demonstrated promising performance in the preoperative prediction of the risk of MDM following curative resection in patients with RLS. The DLRN, which outperformed the other three models, could provide valuable information for predicting surgical efficacy and tailoring individualized treatment plans in this patient population. TRIAL REGISTRATION: Not applicable.

Novel MIR143HG::PLAG1 gene fusion identified in a rectal myxoid leiomyosarcoma.

Myxoid leiomyosarcoma (MLS) is a rare but well-documented tumor that often portends a poor prognosis compared to the conventional leiomyosarcoma. This rare sarcoma has been reported in the uterus, external female genitalia, soft tissue, and other locations. However, a definite rectal MLS has not been reported. Recently five cases of MLS were reported to harbor PLAG1 fusions (TRPS1::PLAG1, RAD51B::PLAG1, and TRIM13::PLAG1). In this report, we present a case of rectal MLS with a novel MIR143HG::PLAG1 fusion detected by RNA next-generation sequencing.

FOXO3a deregulation in uterine smooth muscle tumors.

OBJECTIVE: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. METHODS: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. RESULTS: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. CONCLUSIONS: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.

Sarcoma of the uterine cervix: experience of a single center.

OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with primary sarcoma of the uterine cervix. METHODS: We identified all patients with primary cervical sarcomas treated at our institution from 2002 to 2020 and analyzed the clinicopathological characteristics and prognosis. RESULTS: 34 patients were identified, 7 (20.6%) patients had leiomyosarcoma, 6 (17.6%) had carcinosarcoma, 5 (14.7%) had Ewing sarcoma, 4 (11.8%) had rhabdomyosarcoma, 4 (11.8%) had undifferentiated sarcoma, 2 (5.9%) had adenosarcoma, 2 (5.9%) had endometrial stromal sarcoma, 1 (2.9%) had dermatofibrosarcoma protuberans, 1 (2.9%) had alveolar soft tissue sarcoma and 2 (5.9%) had sarcoma not otherwise specified. The median age of the whole patients was 43.5 years (range, 13-63). The median age of patients with Ewing sarcoma or rhabdomyosarcoma was 22 years (range, 13-39) and 17 years (range, 13-36 years), respectively. The distribution by stage was: stage I in 21 (61.8%) patients, stage II in 4 (11.8%), stage III in 6 (17.6%) and stage IV in 3 (8.8%). Overall, 30 patients (88.2%) received surgical treatment. The median follow-up was 33.3 months (range 3.6-187.3 months). 11 patients died within 2 years after diagnosis, most of them were patients with carcinosarcoma or undifferentiated sarcoma (45.5%, 5/11). In the entire cohort, 2- and 5-year OS were 67.2% and 56.9%, respectively. 5-year OS was 25.0% for undifferentiated sarcoma, 50.0% for rhabdomyosarcoma, 50.0% for carcinosarcoma, 53.3% for Ewing sarcoma, 57.1% for leiomyosarcoma. CONCLUSION: Cervical sarcomas are rare neoplasms with multiple histological subtypes and follow an aggressive course. Prognosis may be associated with tumor histology and stage.

Tumor nasal de músculo liso de comportamiento maligno incierto: informe de un caso / Nasal smooth muscle tumor of uncertain malignant potential: A case report

Los tumores de músculo liso que no pueden ser clasificados según su histología como leiomiomas o leiomiosarcomas se denominan tumores de músculo liso de comportamiento maligno incierto. La localización nasal de estos tumores es muy infrecuente y la extensión adecuada de la cirugía para tratar estas neoplasias no está bien definida. Se describe el caso clínico de una adolescente de 16 años, que consultó por padecer un tumor de aspecto vascular en la cavidad nasal derecha y que fue tratada con éxito mediante cirugía intranasal. El diagnóstico histológico fue tumor de músculo liso de comportamiento maligno incierto. Por la rareza de estas neoplasias, su infrecuente localización nasal y la falta de evidencia que soporte cuál debe ser la extensión de la cirugía, es relevante la descripción y discusión del caso clínico.

Smooth muscle tumors that cannot be histologically classified as leiomyomas or leiomyosarcomas are defined as smooth muscle tumors of uncertain malignant potential. The location of these tumors in the nose is very rare, and the appropriate surgical extent to manage these neoplasms has not been adequately defined. Here we describe the case of a 16-year-old female adolescent who consulted due to a vascular-like tumor in the right nasal cavity who was successfully treated with intranasal surgery. The histological diagnosis was smooth muscle tumor of uncertain malignant potential. Given that these neoplasms are rare, the uncommon location in the nose, and the lack of evidence indicating the extent of surgery, it is relevant to describe and discuss this clinical case.

Roles of Matrix Metalloproteinases 2 and 9 in Uterine Leiomyosarcoma.

BACKGROUND/AIM: Uterine leiomyosarcoma (uLMS) is a rare, highly malignant, and invasive cancer, with early metastasis. Mismatch repair (MMR) proteins and matrix metalloproteinases (MMPs) are associated with the occurrence, proliferation, and invasion of most malignant cancers; however, their abnormal expression in uLMS remains poorly clarified. PATIENTS AND METHODS: Immunohistochemistry was performed to assess MMR protein and MMP2/9 expression as well as Ki67 marker proliferation in benign and malignant uterine smooth muscle tumors. Data from 28 cases of uterine leiomyoma and 31 cases of uLMS were analyzed. RESULTS: Tumor tissues from patients with uLMS had higher expression levels of MMP2 (p<0.001), MMP9 (p<0.05), and Ki67 (p<0.001) than those from patients with uterine leiomyoma; MMR protein expression showed the opposite trend (p<0.05). uLMS proliferation and metastasis correlated positively with MMP2 (p=0.012 and 0.015, respectively) but negatively with MMP9 (p=0.021 and 0.04, respectively). MMR protein expression did not correlate with uLMS proliferation or metastasis (p>0.05). CONCLUSION: Expression levels of MMP2 and MMP9 were upregulated in malignant uLMS tumors when compared with those in benign uterine leiomyoma tumors. Increased MMP2 expression might promote uLMS invasion and migration. MMP9 overexpression might be related to uLMS occurrence; however, it protects against uLMS invasion and metastasis. MMP2 and MMP9 may be potential predictors of uLMS cell proliferation, metastasis, and prognosis. These findings could be helpful in developing new strategies for diagnosing and treating uLMS.

Resection of primary left renal vein leiomyosarcoma with renal preservation following an unusual clinical presentation.

An elderly man was referred to vascular surgery on incidental discovery of a left retroperitoneal mass ultimately found to be of left renal vein (LRV) origin. He initially presented with recurring lower back pain. CT of the abdomen/pelvis showed a 6.0×5.5 cm lobulated retroperitoneal mass anterior to the infrarenal aorta. Resection of the mass necessitated a multidisciplinary team consisting of medical oncologists, radiation oncologists, urologists and vascular surgeons. In efforts to obtain an R0 margin, en-bloc resection of the LRV from its confluence with the inferior vena cava (IVC) was necessary. A primary repair of the IVC was performed with preservation of the left kidney. The patient's back pain has since resolved after the surgery. A literature search found IVC reconstructions to be safe and effective in the removal of vascular leiomyosarcomas.

Leiomyosarcoma of sphenoid sinus- A rare tumor at an unusual site.

Leimyosarcoma (lms) is a malignant soft tissue tumor of smooth muscles. The tumor arises intramuscularly and in subcutaneous locations. It is unusual to encounter lms in head and neck region, even more infrequent to discover lms in nasal and paranasal sinuses. A case of 28 years old male with leiomyosarcoma originating from sphenoid sinus with intracranial extension is being presented with aim to highlight its rarity and to highlight the differential diagnosis and the need for prudent diagnosis in the work-up of the patient.

[A Case of Resection of Leiomyosarcoma Suspected to Originate from the Right Ovarian Vein].

We present a 58-year-old female patient who underwent resection of a leiomyosarcoma arising from the right ovarian vein. She was referred to our hospital because of lower abdominal pain that had been present for 1 month prior to the visit. Ultrasound examination revealed a well-defined, smooth, lobulated, highly vascular mass(57 mm)adjacent to the distal portion of the duodenum. Contrast-enhanced computed tomography revealed the contrast enhancement mass (60 mm)located surround the right ovarian vein. In abdominal magnetic resonance image examination, the mass exhibited isointense signal on T1-weighted images, high signal on T2-weighted images, and restricted diffusion on diffusion- weighted images. We suspected primary leiomyosarcoma of the ovarian vein and proceeded with surgical intervention. On intraoperative findings, the mass was in contact with the duodenum and the inferior vena cava but dissection was easily achieved. We excised the mass together with the right ovarian vein. Pathological findings showed the mass was composed of proliferating spindle-shaped cells arranged in bundles. Some areas showed polygonal nuclear atypia and abnormal mitotic figures. Additional immunostaining showed positive for α-SMA, caldesmon, calponin, and negative for desmin, CD34, CKA1/AE3, S100. Based on the intraoperative findings, we diagnosed it as leiomyosarcoma arising of the right ovarian vein.

Breast lump as the initial presentation of metastatic uterine leiomyosarcoma: a case report and comprehensive literature review.

Uterine leiomyosarcoma (uLMS) is a rare but aggressive cancer with a high metastatic potential and an unfavorable prognosis. A 54-year-old woman with a history of uterine fibroids clinically presented with a painless, palpable left breast mass measuring 20 mm. A core biopsy of the breast mass demonstrated a cellular spindle cell neoplasm (a potentially malignant smooth muscle neoplasm; B4). A wide local breast-mass excision was performed, revealing grade-2 leiomyosarcoma. A re-review of the uterine fibroids revealed that the largest one (200 × 130 mm), initially diagnosed as symplastic leiomyoma, was morphologically identical to the breast lesion. Additional diagnostic work-up revealed multiple liver and pulmonary metastases with a suspected metastatic sclerotic lesion in the L3 projection. The patient was subsequently treated with chemotherapy protocol for metastatic uLMS. The latest follow-up in September 2023 confirmed stable disease. This case highlights the importance of considering unusual metastatic patterns when evaluating breast masses, particularly in patients with a history of non-specific uterine conditions. Comprehensive diagnostic work-up, including imaging and histopathologic examinations, is crucial for an accurate diagnosis of uLMS and appropriate treatment selection. Further studies are needed to better understand the underlying mechanisms and optimal management strategies for metastatic uLMS.

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor With Sarcomatous Transformation: Clinicopathologic and Molecular Analysis of 4 Cases.

Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described adipocytic tumor predominantly affecting the subcutaneous soft tissues of adults. Previous studies have shown that ASPLT follows a benign clinical course with a 4% to 12% local recurrence rate and no risk of dedifferentiation. Herein, we describe the clinicopathologic and molecular findings of 4 cases of ASPLT showing unequivocal sarcomatous transformation. Three patients were male and one was female, aged 65, 70, 74, and 78 years. Two cases presented as mass-forming lesions, while 1 case was incidentally discovered. The tumors measured 30, 55, 80, and 110 mm and occurred in the chest wall (n = 2) or arm (n = 2); all were subcutaneous. Microscopically, they showed a biphasic appearance comprising a low-grade ASPLT component and a high-grade sarcomatous component. The low-grade components showed features in the spectrum of either atypical pleomorphic lipomatous tumor (n = 2) or atypical spindle cell lipomatous tumor (n = 2). The high-grade components displayed leiomyosarcoma-like (n = 2), pleomorphic liposarcoma-like (n = 1) or undifferentiated sarcoma-like (n = 1) morphology. On immunohistochemistry, tumors were negative for MDM2 and showed loss of RB1 expression. In addition, the leiomyosarcoma-like areas seen in 2 cases were positive for smooth muscle actin and H-caldesmon. Single-nucleotide polymorphism array, performed in 3 cases, showed deletions of TP53, RB1, and flanking genes in both components. In contrast, the sarcomatous components showed more complex genomic profiles with rare segmental gains and recurrent loss of PTEN (n = 3), ATM (n = 2), and CDKN2A/B (n = 2) among other genes. Whole exome sequencing identified a TP53 variant in one case and an ATRX variant in another, each occurring in both tumor components. Limited clinical follow-up showed no recurrence or metastasis after 1 to 13 months (median, 7.5 months) postsurgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offer insights into the molecular mechanisms underlying this event.

Uterine leiomyosarcoma cell-derived extracellular vesicles induce the formation of cancer-associated fibroblasts.

OBJECTIVE: Uterine leiomyosarcoma (ULMS) is a rare malignant tumor, which is aggressive, and has a poor prognosis even during its early stages. Extracellular vesicles (EVs) carry cargo, such as microRNAs (miRNAs), which are involved in intercellular communication in the tumor microenvironment and other processes. Because there are no studies on EV-related miRNAs in ULMS, we identified EV-related miRNAs in ULMS and examined their function. METHODS: Small EVs (sEVs) and medium/large EVs (m/lEVs) were extracted from ULMS cells by ultracentrifugation and their basic characteristics were evaluated. Then, small RNA sequencing was done to obtain EV-related miRNA profiles. Next, miRNA expression levels in sera and tissues of ULMS patients were compared with those of myoma patients. RESULTS: miR-654-3p and miR-369-3p were indicated to be highly expressed in both sera and tissues of ULMS patients. These two miRNAs are also highly expressed in ULMS cell lines and ULMS-derived EVs. Some cancer-associated fibroblast (CAF) markers were increased when fibroblasts were treated with ULMS-derived EVs. Furthermore, fibroblasts took up EVs derived from ULMS as determined by confocal laser microscopy. In addition, the transfection of the two candidate miRNAs into fibroblasts significantly increased some CAF markers, particularly ACTA2. CONCLUSION: miR-654-3p and miR-369-3p are highly expressed in ULMS-derived EVs, indicating that these EV-related miRNAs induce the formation of cancer-associated fibroblasts.

[A rare malignant tumor of the renal vein]. / Une tumeur maligne rare de la veine rénale.

The renal vein is an exceptional location for leiomyosarcoma, an aggressive malignant tumor of smooth-muscle origin with a poor prognosis. We report the case of a 55-year-old female patient who consulted for left flank pain that had been present for 6 months. A CT scan revealed a 9.4cm left retroperitoneal mass in contact with the psoas muscle, left kidney, stomach, spleen, left colon and extending up to the pancreas, raising the suspicion of a tumour originating in the retroperitoneal tissues. A biopsy revealed a smooth-muscle cell tumour with a degree of malignancy difficult to define. The patient underwent a monobloc left compartmentectomy, which led to the diagnosis of leiomyosarcoma of the left renal vein. A review of the literature on these rare tumours in this location is presented.

A novel nomogram and recursive partitioning analysis for predicting cancer-specific survival of patients with subcutaneous leiomyosarcoma.

Accurately predicting prognosis subcutaneous leiomyosarcoma (LMS) is crucial for guiding treatment decisions in patients. The objective of this study was to develop prediction models for cancer-specific survival (CSS) in patients with subcutaneous LMS. The collected cases of diagnosed subcutaneous LMS were randomly divided into a training cohort and a validation cohort at a 6:4 ratio based on tumor location and histological code. The X-tile program was utilized to determine the optimal cutoff points for age index. Univariate and Cox multivariate regression analyses were conducted to identify independent risk factors for subcutaneous LMS patients. Nomograms were constructed to predict CSS, and their performance was assessed using C-index and calibration plots. Additionally, a decision tree model was established using recursive partitioning analysis to determine the total score for CSS prediction in subcutaneous LMS patients based on the nomogram model. A total of 1793 patients with subcutaneous LMS were found. X-tile software divides all patients into ≤ 61 years old, 61-82 years old, and ≥ 82 years old. The most important anatomical sites were the limbs (including the upper and lower limbs, 48.0%). Only 6.2% of patients received chemotherapy, while 44% had a history of radiotherapy and 92.9% underwent surgery. The independent risk factors for patients with subcutaneous LMS were age, summary stage, grade, and surgery. CSS was significantly decreased in patients with distant metastases, which showed the highest independent risk predictor (HR 4.325, 95% CI 3.010-6.214, p < 0.001). The nomogram prediction model of LMS was constructed based on four risk factors. The C-index for this model was 0.802 [95% CI 0.781-0.823] and 0.798 [95% CI 0.768-0.829]. The training cohort's 3-, 5-, and 10-year AUCs for CSS in patients with subcutaneous LMS were 0.833, 0.830, and 0.859, and the validation cohort's AUC for predicting CSS rate were 0.849, 0.830, and 0.803, respectively. Recursive segmentation analysis divided patients into 4 risk subgroups according to the total score in the nomogram, including low-risk group < 145, intermediate-low-risk group ≥ 145 < 176, intermediate-high-risk group ≥ 176 < 196, and high-risk group ≥ 196; The probability of the four risk subgroups is 9.1%, 34%, 49%, and 79% respectively. In this retrospective study, a novel nomogram or corresponding risk classification system for patients with subcutaneous LMS were developed, which may assist clinicians in identifying high-risk patients and in guiding the clinical decision.

Conjunctival leiomyosarcoma: A clinico-pathological study with in deep molecular characterization.

BACKGROUND: Primary and metastatic leiomyosarcomas (LMS) involving the orbital region are well known to occur however, the conjunctiva represents an extremely rare site of occurrence. METHODS: A 97-year-old male was referred to the Ocular Oncology Unit due to a rapidly growing painful mass (16×12×20 mm) in the nasal conjunctiva of his left eye. Wide excision followed by radiotherapy was performed. RESULTS: Based on the microscopic features (hypercellular neoplasm composed of spindle cells with cigar shaped and blunt ended nuclei with brightly eosinophilic fibrillary cytoplasm) and immunohistochemical findings (positive staining for Vimentin, Desmin, Caldesmon, and SMA and negative staining for AE1/AE3, EMA, CD117, S100, MelanA, SOX10, HMB45, TLE1, CD99, EMA and AE1 / AE3) the final diagnosis of grade 2 leyomiosarcoma was rendered. Moreover, 'in deep' DNA sequencing (>500 genes analysis) revealed a neoplasm with high TMB: 64 muts/Mb and numerous VUS and several pathogenic/oncogenic molecular alterations, including CNV loss or gain in > 10 genes. At the last follow-up visit, residual disease was observed in the superior fornix, at the nasal limbus and the cornea. At the time of writing, after a follow-up of 2 month the patients is still alive without evidence of metastatic disease. CONCLUSION: An uncommon molecular finding observed in our case was the presence of TSC1 gene mutation usually associated with soft tissue and gynecological PEComas. Our finding may harbor important therapeutic implications since the inactivation of the tumor suppressor genes TSC1 and TSC2 lead to upregulation of mTOR signaling, providing the rationale for target therapy with mTOR inhibitors. Additional studies on larger series are needed to validate our findings.

Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft-tissue Sarcomas: Clinical Outcomes and Biological Correlates.

PURPOSE: Eribulin modulates the tumor-immune microenvironment via cGAS-STING signaling in preclinical models. This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft-tissue sarcomas (STS). PATIENTS AND METHODS: Patients enrolled in one of three cohorts: leiomyosarcoma (LMS), liposarcomas (LPS), or other STS that may benefit from PD-1 inhibitors, including undifferentiated pleomorphic sarcoma (UPS). Eribulin was administered at 1.4 mg/m2 i.v. (days 1 and 8) with fixed-dose pembrolizumab 200 mg i.v. (day 1) of each 21-day cycle, until progression, unacceptable toxicity, or completion of 2 years of treatment. The primary endpoint was the 12-week progression-free survival rate (PFS-12) in each cohort. Secondary endpoints included the objective response rate, median PFS, safety profile, and overall survival (OS). Pretreatment and on-treatment blood specimens were evaluated in patients who achieved durable disease control (DDC) or progression within 12 weeks [early progression (EP)]. Multiplexed immunofluorescence was performed on archival LPS samples from patients with DDC or EP. RESULTS: Fifty-seven patients enrolled (LMS, n = 19; LPS, n = 20; UPS/Other, n = 18). The PFS-12 was 36.8% (90% confidence interval: 22.5-60.4) for LMS, 69.6% (54.5-89.0) for LPS, and 52.6% (36.8-75.3) for UPS/Other cohorts. All 3 patients in the UPS/Other cohort with angiosarcoma achieved RECIST responses. Toxicity was manageable. Higher IFNα and IL4 serum levels were associated with clinical benefit. Immune aggregates expressing PD-1 and PD-L1 were observed in a patient that completed 2 years of treatment. CONCLUSIONS: The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.

Elevated 68 Ga-FAPI Activity in Leiomyosarcoma.

ABSTRACT: Leiomyosarcoma is an aggressive subtype of soft tissue sarcoma with frequent metastatic relapse after curative surgery. Herein, we report the 68 Ga-FAPI PET/CT findings in a 45-year-old woman with leiomyosarcoma. 68 Ga-FAPI-04 PET/CT detected increased FAPI uptake in abdominal leiomyosarcoma and liver metastases. The positive findings of 68 Ga-FAPI in this case highlighted that 68 Ga-FAPI may have potential value in the evaluation of leiomyosarcoma.