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We report on a 14-year-old girl who developed post-transplantation smooth muscle tumours (PTSMT) located in the spleen, lungs, liver, and central nervous system (CNS), 4 years after kidney transplantation. She was asymptomatic, and the disease was detected during the work-up for a urinary tract infection. Diagnosis was performed by the analysis of a tissue specimen, through the biopsy of a lung tumour, which revealed a proliferation of spindle-shaped cells which were positive for actin and vimentin. In situ hybridization studies were positive for Epstein-Barr virus, and her serologic status was negative prior to transplantation. We reduced immunosuppression by stopping mycophenolate and switching tacrolimus for sirolimus. After 18 months of follow-up, she remains asymptomatic, and the CNS tumour reduced its diameter from 24 × 21 mm to 14 × 13 mm. PTSMT should be considered in the differential diagnosis of transplanted patients who develop neoplastic complications associated with immunosuppression., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Differential diagnosis between benign uterine smooth muscle tumors and malignant counterpart is challenging., Objective: To evaluate the accuracy of a clinical and ultrasound based algorithm in predicting mesenchymal uterine malignancies, including smooth muscle tumors of uncertain malignant potential., Study Design: We report the 12-month follow-up of an observational, prospective, single-center study that included women with at least 1 myometrial lesion ≥3 cm on ultrasound examination. These patients were classified according to a 3-class diagnostic algorithm, using symptoms and ultrasound features. "White" patients underwent annual telephone follow-up for 2 years, "Green" patients underwent a clinical and ultrasound follow-up at 6, 12, and 24 months and "Orange" patients underwent surgery. We further developed a risk class system to stratify the malignancy risk., Results: Two thousand two hundred sixty-eight women were included and target lesion was classified as benign in 2158 (95.1%), as other malignancies in 58 (2.6%) an as mesenchymal uterine malignancies in 52 (2.3%) patients. At multivariable analysis, age (odds ratio 1.05 [95% confidence interval 1.03-1.07]), tumor diameter >8 cm (odds ratio 5.92 [95% confidence interval 2.87-12.24]), irregular margins (odds ratio 2.34 [95% confidence interval 1.09-4.98]), color score=4 (odds ratio 2.73 [95% confidence interval 1.28-5.82]), were identified as independent risk factors for malignancies, whereas acoustic shadow resulted in an independent protective factor (odds ratio 0.39 [95% confidence interval 0.19-0.82[). The model, which included age as a continuous variable and lesion diameter as a dichotomized variable (cut-off 81 mm), provided the best area under the curve (0.87 [95% confidence interval 0.82-0.91]). A risk class system was developed, and patients were classified as low-risk (predictive model value <0.39%: 0/606 malignancies, risk 0%), intermediate risk (predictive model value 0.40%-2.2%: 9/1093 malignancies, risk 0.8%), high risk (predictive model value ≥2.3%: 43/566 malignancies, risk 7.6%)., Conclusion: The preoperative 3-class diagnostic algorithm and risk class system can stratify women according to risk of malignancy. Our findings, if confirmed in a multicenter study, will permit differentiation between benign and mesenchymal uterine malignancies allowing a personalized clinical approach., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Uterine smooth muscle neoplasms are a biologically and clinically heterogeneous group of tumors. Morphology is the cornerstone of pathologic diagnosis of these tumors, and most are readily classified as benign or malignant on the basis of routine histologic examination. However, rare subsets-including intravenous leiomyomatosis, benign metastasizing leiomyoma, and disseminated peritoneal leiomyomatosis-have a capacity for extrauterine spread despite benign cytomorphology. A further subset of uterine smooth muscle neoplasms, termed "smooth muscle tumor of uncertain malignant potential (STUMP)," are not readily classified as benign or malignant and carry an intermediate prognosis. STUMP is a protean category, whose precise definition is subject to disagreement among experts. The risk profiles of different STUMP morphotypes remain largely unresolved. Finally, multiple morphology-based systems for risk stratification of uterine leiomyosarcoma have been proposed, though none is widely adopted. Immunohistochemical and molecular prognostic markers for both STUMP and leiomyosarcoma remain in the early phases of adoption in routine diagnostic practice., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMTs) represent a rare category of soft tissue tumors that are predominantly seen in individuals with compromised immune systems. Pathologically, EBV-SMT has malignant potential because of its unpredictable nature. These tumors can manifest at various anatomical sites or even multiple lesions in different locations. Among the various forms of EBV-SMT, individuals with HIV infection or AIDS exhibit the poorest survival outcomes. The efficacy of antiretroviral therapy (ART), either as a standalone treatment or in combination with localized tumor interventions remains uncertain. The highlights of this article are the clinical diversity and various treatment possibilities for multisite AIDS-related EBV-SMT., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with multiple histologic variants and distinct biological behaviors. Pathologic classification (benign, uncertain malignant potential, malignant) relies on the evaluation of mitotic index, necrosis, and degree of cytologic atypia, with different thresholds based on each subtype. Immunohistochemistry and other ancillary studies may be necessary to establish the diagnosis in a subset of cases, given the morphologic overlap with other mesenchymal neoplasms, including low-grade and high-grade endometrial stromal tumors, inflammatory myofibroblastic tumors, and PEComa. Recent advances in molecular diagnostics have refined the classification of smooth muscle tumors, but most cases are diagnosed purely on histologic grounds., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity., Methods: A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n = 95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm., Results: Median age at diagnosis was 58 years (range 22-86), and 74% were male. Ninety-five percent (n = 90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n = 44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day-18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%., Conclusion: In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: The Primary Objective of this study was to analyse reproductive outcomes in patients with STUMP (Smooth Muscle Tumour of Uncertain Potential) or ALM (Atypical Leiomyoma) who underwent fertility-preserving surgeries. Secondary Objectives were to analyse long-term prognosis for these patients and to study the basic demographic and pathological characteristics of patients with STUMP or ALM., Study Design: This retrospective study was conducted at Amrita Institute of Medical Sciences. Cases of STUMP and ALM were retrieved from the hospital medical database between June 2014 and December 2022. Demographic parameters, clinical presentations, pathological features and clinical outcomes were analysed. Categorical variables were expressed in numbers and percentages. Normal distribution data were presented as mean while non-normal distribution was expressed as median and range., Results: Thirty-eight patients were included in the study with a diagnosis of STUMP or ALM in postoperative histology. Seven patients (18.4%) were nulliparous. Myomectomy was performed in 9 (23.6%), while hysterectomy was done in 29 patients (76.3%). Fertility-preserving surgeries were performed on six patients (15.7%). Of these six patients, 4(66.6%) conceived spontaneously and had successful pregnancies. Recurrences were found in 3 patients (7.8%) out of which one had undergone fertility-sparing surgery. All the patients with recurrences had previous history of myomectomies. Morcellation was reportedly done in 2 of these three patients., Conclusion: Good reproductive outcomes have been demonstrated in patients diagnosed with STUMP or ALM and desiring fertility. However, these patients should be kept under follow-up care as they are prone for recurrences. Patients who have undergone morcellation mayhave an increased chance of recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a rare uterine tumor primarily affecting perimenopausal and postmenopausal women, typically aged between 45 and 55 years. Characterized by ambiguous histological features, STUMPs present diagnostic challenges as they cannot be definitively classified as benign or malignant based on morphology alone. This systematic review aims to elucidate the clinical, pathological, immunohistochemical, and treatment-related characteristics of STUMPs through an analysis of the literature from the past 20 years. The study follows PRISMA guidelines, utilizing comprehensive searches of PubMed and Scopus databases, yielding 32 studies that meet the inclusion criteria. From the analysis of these studies, it was revealed that the clinical presentations vary from common symptoms such as abnormal uterine bleeding and pelvic pain to incidental detection of uterine mass. Histologically, STUMPs demonstrate features overlapping with both leiomyomas and leiomyosarcomas, including mild nuclear atypia, low mitotic indices, and focal necrosis. Immunohistochemical markers such as p16 and p53 have been investigated for prognostic significance. Elevated p16 expression, often associated with aggressive behavior, was observed in a subset of STUMPs. Surgical management, typically involving hysterectomy or tumorectomy, is the primary treatment, though the extent of resection is variable. Adjuvant therapies are not routinely recommended, but long-term surveillance is advised, especially for high-risk patients. Recurrence rates for STUMPs are approximately 12%, with factors such as high mitotic counts and coagulative necrosis indicating higher risk. This review highlights the complexity of STUMP diagnosis and management, emphasizing the need for more precise diagnostic criteria and individualized treatment strategies. Understanding the morphological, immunohistochemical, and clinical behavior of STUMPs can improve patient outcomes and guide future research in this diagnostically challenging area.

Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are rare tumors of the uterine myometrium that are often misdiagnosed, owing to limited knowledge of their characteristics on ultrasonography (US) and magnetic resonance imaging (MRI). We report a woman in her mid-30s who was hospitalized because of a pelvic tumor. A 6-cm mass was found in her lower left abdomen. US and MRI revealed a well-demarcated mass in the left adnexal area, with both cystic and solid elements, visible blood flow within the septa, a strong signal across >50% of the volume on T2-weighted imaging (T2WI), and a strong signal on diffusion-weighted imaging (DWI). After hysterectomy and bilateral salpingectomy, immunohistochemical examination confirmed STUMP. A review of the literature revealed characteristic imaging features of STUMP. Ultrasonography reveals STUMP as a solitary, well-circumscribed lesion with isoechoic or mixed echogenicity, the absence of posterior shadowing, and variations in blood flow. STUMP is characterized by strong signal intensity on T2WI, small areas of strong signal on T1WI, and non-enhancing cystic areas on contrast-enhanced MRI scans. Early diagnosis is crucial for the management and treatment of STUMP, and here we have summarized the imaging features of the lesion, thereby providing a valuable diagnostic reference., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients., Methods: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival., Results: Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up., Conclusion: PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Epstein-Barr virus, a herpesvirus, has been associated with a variety of cancers, including Burkitt, Hodgkin, and non-Hodgkin lymphomas; posttransplant lymphoproliferative disorders; gastric carcinoma; and nasopharyngeal carcinoma, in both immunocompetent and immunocompromised individuals. Previous studies have established a connection between Epstein-Barr virus and the development of smooth-muscle tumors. Smooth-muscle tumors of the brain are very rare and are often misdiagnosed as meningiomas on imaging. To our knowledge, advanced imaging findings such as MR perfusion of smooth-muscle tumors of the brain have never been reported. We describe the radiologic and pathologic features of the Epstein-Barr virus-associated smooth-muscle tumors of the brain in a person with newly diagnosed advanced HIV., (© 2024 by American Journal of Neuroradiology.)

Research Question: What is the expression pattern of Raf kinase inhibitory protein (RKIP) in different subtypes of leiomyoma (usual type, cellular, apoplectic or haemorrhagic leiomyoma, leiomyoma with bizarre nuclei and lipoleiomyoma) and leiomyosarcoma specimens, and what is its biological role in leiomyosarcoma cells?, Design: Leiomyoma and leiomyosarcoma specimens underwent immunohistochemistry staining. Leiomyosarcoma SK-LMS-1 cell line was RKIP knocked down and RKIP overexpressed, and cell viability, wound healing migration and clonogenicity assays were carried out., Results: A higher immunohistochemical expression of RKIP was observed in bizarre leiomyomas, than in usual-type leiomyomas. Decreased expression was also found in cellular leiomyoma, with generally absent staining in leiomyosarcomas. Upon RKIP expression manipulation in SK-LMS-1 cell line, no major differences were observed in cell viability and migration capacity over time. RKIP knockout, however, resulted in a significant increase in the cell's ability to form colonies (P = 0.011)., Conclusion: RKIP distinct expression pattern among leiomyoma histotype and leiomyosarcoma, and its effect on leiomyosarcoma cells on colony formation, encourages further studies of RKIP in uterine smooth muscle disorders., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior omental smooth muscle tumor case in an adult male patient., Case Presentation: A 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up., Discussion and Conclusion: We encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare no conflict of interest and funding disclosures., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

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., (Sociedad Argentina de Pediatría.)

Purpose: To evaluate the magnetic resonance imaging (MRI) features that may help distinguish leiomyosarcomas from atypical leiomyomas (those presenting hyperintensity on T2-W images equal or superior to 50% compared to the myometrium)., Materials and Methods: The authors conducted a retrospective single-centre study that included a total of 57 women diagnosed with smooth muscle tumour of the uterus, who were evaluated with pelvic MRI, between January 2009 and March 2020. All cases had a histologically proven diagnosis (31 Atypical Leiomyomas-ALM; 26 Leiomyosarcomas-LMS). The MRI features evaluated in this study included: age at presentation, dimension, contours, intra-tumoral haemorrhagic areas, T2-WI heterogeneity, T2-WI dark areas, flow voids, cyst areas, necrosis, restriction on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) values, signal intensity and heterogeneity after contrast administration in T1-WI, presence and location of unenhanced areas. The association between the MRI characteristics and the histological subtype was evaluated using Chi-Square and ANOVA tests., Results: The MRI parameters that showed a statistically significance correlation with malignant histology and thus most strongly associated with LMS were found to be: irregular contours (p < 0.001), intra-tumoral haemorrhagic areas (p = 0.028), T2-WI dark areas (p = 0.016), high signal intensity after contrast administration (p = 0.005), necrosis (p = 0.001), central location for unenhanced areas (p = 0.026), and ADC value lower than 0.88 × 10 -3 mm 2 /s (p = 0.002)., Conclusion: With our work, we demonstrate the presence of seven MRI features that are statistically significant in differentiating between LMS and ALM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inflammatory rhabdomyoblastic tumor is a recently introduced name for neoplasms currently included in the World Health Organization classification of soft tissue tumors under the rubric inflammatory leiomyosarcoma. Inflammatory rhabdomyoblastic tumor is an excellent example of how surgical pathologists working in conjunction with tumor biologists can greatly improve tumor classification to the benefit of patients. Over the last 28 years, understanding of this entity has undergone a fascinating evolution. This review serves as a summary of the latest findings in inflammatory rhabdomyoblastic tumor research and a diagnostic manual for the practicing surgical pathologist., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types., Methods: This was a retrospective, multicenter study that included 285 patients diagnosed with uterine smooth muscle tumors (50 leiomyosarcomas, 35 smooth muscle tumors of uncertain malignant potential, and 200 leiomyomas). The patients were divided into three groups based on the histological type of their tumors, and the groups were compared according to the variables collected., Results: Leiomyosarcomas were more common in older and post-menopausal women. Compared with leiomyomas, smooth muscle tumors of uncertain malignant potential and leiomyosarcomas had similar ultrasound features such as absence of normal myometrium, multilocular appearance, hyper-echogenicity in case of uniform echogenicity, absence of posterior shadows, echogenic areas, and hyperechoic rim. Leiomyosarcomas were larger, had more cystic areas, and were associated with a higher prevalence of pelvic free fluid. Smooth muscle tumors of uncertain malignant potential were characterized by a higher frequency of International Federation of Gynecology and Obstetrics (FIGO) type 6-7, the absence of internal shadows, and, in the case of cystic area, the presence of a regular internal wall. Tumor outline varied among the three histological types. A color score of 1 was typical of leiomyoma, a color score 2 was mainly observed in leiomyomas and smooth muscle tumors of uncertain malignant potential, a color score 3 did not differ among the tumors, while a color of score 4 was related to leiomyosarcomas. When combining color scores 3 and 4, leiomyosarcomas and smooth muscle tumors of uncertain malignant potential showed a high percentage of both circumferential and intra-lesional vascularization. A cooked appearance was not statistically different among the tumors., Conclusions: Based on our findings, specific ultrasonographic features as well as age and menopausal status are associated with different uterine smooth muscle tumor types. Integration of these data can help the pre-operative assessment of these lesions for proper management., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: Epstein-Barr Virus-Associated Smooth Muscle Tumor (EBV-SMT) is a rare tumor with a higher rate of occurrence in unusual locations in the setting of immunodeficiency. In this study, we evaluated a cohort of ordinary leiomyosarcomas (LMS) for the presence of EBV and described the clinicopathological features deviating from routinely diagnosed cases of EBV-SMT., Material and Method: The sections of tissue microarrays including 93 classical LMS occurring in various locations were hybridized with EBER and stained for LMP1 antibody using the Leica Bond Autostainer. EBV real-time PCR assay was performed in 2 EBER-positive cases., Results: Among the 93 LMS cases, 2 non-uterine cases (2.2%) were positive for EBER and negative for LMP1, and were referred to as `EBV-positive LMS`. Both were females in their 6th decade without immunosuppression. EBV real-time PCR assay revealed the presence of EBV in one of the cases. Tumors were located in the pancreas and chest wall. Morphologically, tumors were rather myxoid, multinodular, and composed of long fascicles of spindle cells with intermediate- to high-grade features. High mitotic activity and focal necrosis were present, whereas no accompanying lymphocytes were detected. One of the patients developed metastatic disease after 3 years., Conclusion: EBV-positive LMS occurring in immunocompetent patients has features distinct from classical EBV-SMT seen in immunosuppressed patients.

Leiomyosarcoma with adipocytic differentiation or lipoleiomyosarcoma is an uncommon sarcoma of the female genital tract with only a few individual reports in the literature. We therefore performed a morphologic, immunohistochemical, MDM2 gene amplification and RNA and DNA sequencing analysis of a series of gynecologic lipoleiomyosarcoma to better define the clinicopathologic spectrum. Six tumors from 6 patients were identified and classified as spindled lipoleiomyosarcoma (n = 2), mixed spindled and myxoid lipoleiomyosarcoma (n = 1), epithelioid lipoleiomyosarcoma with focal myxoid features (n = 1) and mixed spindled and epithelioid lipoleiomyosarcoma (n = 2). Patient age ranged from 41 to 64 years (mean: 49; median: 50). Primary location included uterine corpus (3), uterine corpus/cervix (2) and broad ligament (1). Tumor size ranged from 4.5 to 22 cm (mean: 11.2; median: 9.8). Four patients had metastasis at presentation or subsequently developed recurrent or distant disease. Patient status was known for 5: 2 dead of disease, 2 alive with disease and 1 alive without evidence of disease. Immunohistochemical expression of smooth muscle markers, ER, PR and WT-1 showed patterns similar to non-adipocytic gynecologic leiomyosarcomas. MDM2 amplification fluorescence in situ hybridization performed on 2 tumors was negative in 1 and equivocal in 1. Sequencing studies performed on 3 tumors found TP53 mutations in 3, with 1 tumor also having an ATRX alteration. No gene fusions were identified. Although lipoleiomyosarcomas have a diverse morphologic spectrum, our findings suggest the smooth muscle component shares morphologic and immunohistochemical features with female genital tract non-adipocytic leiomyosarcomas. Lipoleiomyosarcomas also have genetic alterations associated with non-adipocytic gynecologic leiomyosarcomas., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pulmonary nodules are a common complication in solid organ transplant recipients, and may have various underlying causes, with Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) being one of them. Given the rarity of this entity, we describe the diagnosis and therapeutic interventions for post-transplant EBV-SMT in two individuals. Both cases involved female patients who were diagnosed with multiple pulmonary nodules 60 months and 116 months, respectively, after receiving living-related kidney transplantation. Pathological examination revealed a spindle cell tumor, with immunophenotype and EBV in situ hybridization supporting the diagnosis of EBV-SMT. After diagnosis, these two patients underwent intervention by decreasing their intake of immunosuppressants. As of the latest follow-up, the patients' lesion size remained stable, and their overall condition was favorable. We also reviewed literature about the morphological and molecular pathological features of EBV-SMT and highlighted the diagnosis and differential diagnosis of pulmonary spindle cell lesions especially in the setting of immunosuppression.

Objectives: The present study aimed to analyze of uterine smooth muscle tumors of uncertain malignant potential (STUMP) and the outcomes of patients with STUMP., Material and Methods: In this retrospective study, the data of patients diagnosed with STUMP in a single tertiary center between January 2005-January 2020 were reviewed. We assessed the demographic variables, treatment outcomes, time until recurrence, disease-free and overall survival of the patients., Results: Twenty-five patients diagnosed with STUMP were included in the study. The mean age of the patients was 43.2 ± 10.3 years. Thirteen of the 25 patients (52%) were treated by myomectomy, others received diagnoses following hysterectomy. The median follow-up time was 45.2 months. Recurrence was observed in three cases (12%), two of which were followed up without hysterectomy, and the third patient died by peritonitis carcinomatosa 60 months after diagnosis although she received cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment., Conclusions: This study evaluates the data of patients with STUMP. Our results reveal a STUMP recurrence of 12%, like those previously reported in the literature. Despite the possibility of malignant recurrence, fertility-preserving treatment with close follow-up should be tried, because of the relatively early age at diagnosis.

Smooth muscle tumors are the most common mesenchymal tumors of the female genital tract, including the vulva. Since vulvar smooth muscle tumors are rare, our understanding of them compared to their uterine counterparts continues to evolve. Herein, we present two cases of morphologically distinct myxoid epithelioid smooth muscle tumors of the vulva with novel MEF2D::NCOA2 gene fusion. The tumors involved 24 and 37-year-old women. Both tumors presented as palpable vulvar masses that were circumscribed, measuring 2.8 and 5.1 cm in greatest dimension. Histologically, they were composed of epithelioid to spindle-shaped cells with minimal cytologic atypia and prominent myxoid matrix. Rare mitotic figures were present (1-3 mitotic figures per 10 high-power field (HPF)), and no areas of tumor necrosis were identified. By immunohistochemistry, the neoplastic cells strongly expressed smooth muscle actin, calponin, and desmin, confirming smooth muscle origin. Next-generation sequencing identified identical MEF2D::NCOA2 gene fusions. These two cases demonstrate that at least a subset of myxoid epithelioid smooth muscle tumors of the vulva represent a distinct entity characterized by a novel MEF2D::NCOA2 gene fusion. Importantly, recognition of the distinct morphologic and genetic features of these tumors is key to understanding the biological potential of these rare tumors., (© 2023 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

A 48-year-old woman underwent total abdominal hysterectomy and right salpingo-oophorectomy and was initially diagnosed with a uterine leiomyoma and right ovarian cystadenoma. After 4 years, multiple pulmonary metastases were identified, and treatment with gonadotropin-releasing hormone agonists was started, but stopped later due to disease progression. The patient developed dyspnea and underwent right upper lobectomy. The histopathological findings were consistent with those of pulmonary metastases secondary to a uterine smooth muscle tumor of uncertain malignant potential. Slow disease progression after a poor response to adriamycin and hormone receptor positivity led to the start of letrozole. Letrozole induced spontaneous regression of the pulmonary metastases, and about 2 years into the treatment, sustained response was achieved with minimal side effects. This may be the first case supporting the long-term efficacy and safety of letrozole in the management of adriamycin-resistant lung metastases of uterine smooth muscle tumors of uncertain malignant potential., (© 2023 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), both uterine mesenchymal tumors, are distinguished by the number of cells exhibiting mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiating between benign and malignant tumors, is difficult. For example, cotyledonoid dissecting leiomyoma (CDL) or uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which a differential diagnosis is challenging. To date, a standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of CDL or STUMP in the differential diagnosis have not been defined. Several clinical studies have reported that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The immunohistochemical biomarkers reported so far cannot effectively help determine the malignant potential of CDL or STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by using next-generation molecular techniques can facilitate disease prediction, diagnosis, treatment, and prognosis. We examined the oncological properties of STUMP in adults using molecular pathological techniques on tissue excised from patients with uterine mesenchymal tumor. In a clinical study conducted by our medical team, the results of gene expression profiling indicated factors that may be associated with malignancy of uterine mesenchymal tumors. We herein describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies. It is expected that the establishment of a diagnostic method targeting the characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Background: EBV-associated smooth muscle tumors (EBV-SMTs) are rare and typically develop in individuals with a compromised immune system, particularly those who have acquired immunodeficiency syndrome (AIDS) or who have undergone organ transplants., Methods: We document a case of EBV-SMT in an HIV-positive 25-year-old man. The lesion was incised and assessed histologically and a panel of immune markers were performed. EBV association was demonstrated by in situ hybridization for EBV-encoded RNA (EBER-ISH)., Results: Microscopically, the tumor composed of mildly pleomorphic, ovoid to spindled cells with numerous slit-like vascular channels. The tumor cells exhibited diffuse and strong immunoreactivity for smooth muscle actin (SMA) and focal positivity for h-caldesmon. EBER-ISH of the tumor cells revealed strong positive nuclear signals., Conclusion: The histopathological features of EBV-SMT do not conform to either benign or malignant SMTs and it has a peculiar predilection to develop at sites unusual for leiomyoma or leiomyosarcoma. The key diagnostic features of EBV-SMT include history of immunosuppression, histologic evidence of primitive and mildly pleomorphic cells maintaining blunt nuclear features in most areas, and positivity for EBER-ISH., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

The purpose of this study was to distinguish leiomyosarcomas/smooth muscle tumors of uncertain malignant potential (STUMP) from leiomyomas with high signal intensity (SI) on T2-weighted imaging (T2WI) using quantitative MR texture analysis combined with patient characteristics and visual assessment. Thirty-one leiomyomas, 2 STUMPs, and 6 leiomyosarcomas showing high SI on T2WI were included. First, we searched for differences in patient characteristics and visual assessment between leiomyomas and leiomyosarcomas/STUMPs. We also compared the MR texture on T2WI and the apparent diffusion coefficient (ADC) to identify differences between leiomyomas and leiomyosarcomas/STUMPs. In the univariate analysis, significant differences between leiomyomas and leiomyosarcomas/STUMPs were observed in age, menopausal status, margin, hemorrhage, long diameter, T2-variance, T2-volume, ADC-variance, ADC-entropy, ADC-uniformity, ADC-90th and 95th percentile values, and ADC-volume (P < .05, respectively). There were significantly more postmenopausal patients with leiomyosarcomas/STUMPs than with leiomyomas, and leiomyosarcomas/STUMPs had more irregular margins, more frequent presence of hemorrhage and exhibited larger tumor diameters, T2-volume, T2-variance, ADC-volume, ADC-variance, ADC-entropy, and higher ADC-90th and 95th percentile values but lower ADC-uniformity. Multivariate analyses revealed that the independent differentiators were menopausal status, hemorrhage and ADC-entropy (P < .05, respectively). The area under the curve obtained by combining the 3 items was 0.980. The best cutoff value for ADC-entropy was 9.625 (sensitivity: 100%, specificity: 58%). The combination of menopausal status, hemorrhage, and ADC-entropy can help accurately distinguish leiomyosarcomas/STUMPs from leiomyomas with high SI on T2WI; however, external validation in a larger population is required because of the small sample size of our study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Leiomyomas are smooth muscle tumors of the uterus and are the most common uterine neoplasm. Although leiomyomas are usually asymptomatic, they can manifest with symptoms such as pain or uterine bleeding. Leiomyomas are classified on the basis of their anatomic location and morphology. Localization of leiomyomas relative to the endometrium, myometrium, and uterine serosa with use of the International Federation of Gynecology and Obstetrics (FIGO) classification system is helpful for guiding management in symptomatic patients. The FIGO system is a practical and universally accepted approach for classifying leiomyomas to guide radiologists and clinicians in deciding management. The MRI appearance of conventional leiomyomas is related to their tissue contents of smooth muscle and fibrous tissue and is well established. The MRI features of some leiomyoma subtypes and forms of degeneration also have been described. Other smooth muscle tumors of the uterus recognized in the 2020 World Health Organization classification system include intravenous leiomyomatosis, smooth muscle tumors of uncertain malignant potential, and metastasizing leiomyoma. At the far end of the spectrum are leiomyosarcomas, which are frankly malignant and therefore must be managed accordingly. Although MRI features that suggest a diagnosis of leiomyosarcoma have been proposed, these features overlap with those of some leiomyoma subtypes and degeneration. © RSNA, 2023 See the invited commentary by Fennessy and Gargiulo in this issue. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

Epstein-Barr virus (EBV)-associated smooth muscle tumors (EBV-SMTs) are rare smooth muscle neoplasms exclusively associated with immunosuppression, such as in patients with HIV/AIDS, posttransplant, and congenital immunodeficiency. However, the genomic landscape of EBV-SMTs is poorly understood. Leiomyosarcomas harbor genomic instability and multiple recurrent DNA copy number alterations, whereas leiomyomas lack such changes. Thus, this study aimed to fill this knowledge gap by characterizing copy number alterations in EBV-SMTs and correlating this information with clinicopathologic characteristics. Our study investigated and compared the pathologic characteristics and copy number profiles of 9 EBV-SMTs (from 7 post-transplant and AIDS patients), 6 leiomyomas, and 7 leiomyosarcomas, using chromosomal microarray platforms. Our results showed a lower copy number alteration burden in EBV-SMTs and leiomyoma than in leiomyosarcoma. This contrast in the molecular profile between EBV-SMTs and leiomyosarcoma is concordant with the different clinical behaviors and pathologic characteristics exhibited by these tumors. Despite having an overall copy number alteration profile closer to leiomyoma, recurrent copy number gain of oncogenes, such as RUNX1, CCND2, and ETS2, was found in EBV-SMTs. Epigenetic alterations may play an important role in tumorigenesis as recurrent copy number gains were found in histone deacetylases. A gene enrichment analysis also demonstrated enrichment of genes involved in the host response to viral infection, suggesting that the tumor immune microenvironment may play an important role in EBV-SMT tumorigenesis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to analyze the clinical and reproductive outcomes of patients treated with myomectomy who were histologically diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP)., Methods: Patients who were diagnosed with STUMP and underwent a myomectomy at our institution between October 2003 and October 2019 were identified. Variables of interest obtained from the institution's database included patient age, relevant medical history, pre-operative appearance of the tumor on ultrasound, parameters of the surgical procedure, histopathological analysis of the tumor, post-operative clinical course, and course of follow-up, including reinterventions and fertility outcomes., Results: There were a total of 46 patients that fulfilled the criteria of STUMP. The median patient age was 36 years (range, 18-48 years) and the mean follow-up was 47.6 months (range, 7-149 months). Thirty-four patients underwent primary laparoscopic procedures. Power morcellation was used for specimen extraction in 19 cases (55.9% of laparoscopic procedures). Endobag retrieval was used in nine patients and six procedures were converted to an open approach due to the suspicious peri-operative appearance of the tumor. Five patients underwent elective laparotomy due to the size and/or number of tumors; three patients had vaginal myomectomy; two patients had the tumor removed during planned cesarean section; and two underwent hysteroscopic resection.There were 13 reinterventions (five myomectomies and eight hysterectomies) with benign histology in 11 cases and STUMP histology in two cases (4.3% of all patients). We did not observe any recurrence as leiomyosarcoma or other uterine malignancy. We did not observe any deaths related to the diagnosis. Twenty-two pregnancies were recorded among 17 women, which resulted in 18 uncomplicated deliveries (17 by cesarean section and one vaginal), two missed abortions, and two pregnancy terminations., Conclusions: Our study found that uterus-saving procedures and fertility-preservation strategies in women with STUMP are feasible, safe, and seem to be associated with a low risk of malignant recurrence, even while maintaining the mini-invasive laparoscopic approach., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

Aim: Histopathologic diagnosis of a subset of uterine smooth muscle tumors is challenging. We report a critical review regarding the clinicopathological point of view of 62 cases of subsequently recurred or metastasized leiomyoma., Methods: Medical records and glass slides of 62 cases of uterine smooth muscle tumor diagnosed as leiomyoma, which subsequently recurred or metastasized, were critically reviewed by pathologists specializing in gynecologic pathology and oncology., Results: In 47 (75.8%) of 62 cases, the diagnosis of leiomyoma was confirmed, including 11 intravascular leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML). In 29 cases (46.8%) laparoscopic surgery was performed, of which morcellator without a bag was employed in 23 cases. Fifteen cases (24.2%) appeared to be underestimated and were re-classified as smooth muscle tumor of uncertain malignant potential (STUMP), leiomyosarcoma, or other malignant mesenchymal tumors. Recurrences in seven cases (11.3%) were interpreted to be a malignant transformation, and one STUMP recurred as STUMP., Conclusion: The recurrence or metastasis in cases of "leiomyoma" is attributed to iatrogenic or under-evaluation of primary tumors, although a subset of cases is a rare example of biological progression., (© 2022 Japan Society of Obstetrics and Gynecology.)

Leiomyoma with bizarre nuclei (LM-BN) is a rare variant of leiomyoma with overall benign clinical course. It has histologic features showing focal or diffuse nuclear atypia surrounded by usual type leiomyoma. Uterine leiomyosarcomas (LMS) are a group of rare and aggressive malignancies with limited treatment options available. The potential association between LM-BN with LMS is largely unknown. In this study, we report 2 cases of uterine smooth muscle tumor with typical histologic and molecular evidence of LM-BN, which are associated with its progression to the malignant counterpart of LMS. We summarize the detailed histologic, morphologic, and genomic characteristics of these 2 sets of cases. Our findings suggest that LMS progressing from preexisting LM-BN can be one of the tumor pathogenesis pathways in uterine leiomyosarcomas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.

Objective: To correlate the ultrasound appearance of highly vascularized uterine myomas with their histopathological diagnosis., Methods: This was a prospective observational study of patients with a preoperative ultrasound diagnosis of a highly vascularized uterine myoma (color score of 3 or 4, according to the Morphological Uterus Sonographic Assessment (MUSA) criteria), characterized by circumferential and intralesional vascular pattern, who underwent myomectomy or hysterectomy. For each patient, ultrasound characteristics were recorded at baseline, including the number of lesions, the size, echogenicity and border regularity of the lesion, presence of cystic areas and shadowing within the myoma, and visualization of the endometrium. Ultrasound features were correlated with the definitive histological diagnosis. Ultrasound features were then compared between malignant and benign lesions., Results: We included 70 patients with highly vascularized uterine myomas on power/color Doppler. Their mean age was 46.5 ± 11.4 years and 13 (18.6%) were postmenopausal. At histological examination, 65 (92.9%) uterine myomas were benign lesions, comprising 32 typical leiomyomas, 29 leiomyoma variants and four adenomyomas. The remaining five (7.1%) uterine myomas were malignant masses, comprising two uterine sarcomas, one leiomyosarcoma, one neuroendocrine tumor and one uterine smooth muscle tumor of uncertain malignant potential (STUMP). The mean age of patients with a malignant lesion was significantly higher than the age of those with a benign lesion (64.8 ± 16.0 vs 42.4 ± 5.1; P < 0.001). Four out of five patients with a malignant lesion were over 45 years old. Ultrasound demonstrated cystic areas within the lesion in 10/32 (31.3%) typical leiomyomas, 16/29 (55.2%) leiomyoma variants, all four adenomyomas and in the cases of STUMP and leiomyosarcoma. Lesion borders were regular in 64/65 (98.5%) benign lesions and 2/5 (40%) malignant lesions (P < 0.05). No significant differences were observed between benign and malignant lesions with respect to echogenicity, presence of shadowing and size. The endometrium was visible in 55/65 women with benign lesions and in 2/5 with malignant lesions (P = 0.03)., Conclusions: Our results showed that ultrasound features of uterine myomas, such as circumferential and intralesional vascularity, cystic areas and lesion borders, are important parameters for differential diagnosis, especially when combined with the patient's age. Such features could be useful to differentiate typical myomas from benign variants and malignant lesions in a preoperative setting and to select patients that may benefit from conservative management rather than surgery. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Epstein-Barr virus (EBV) can infect smooth muscle cells causing smooth muscle tumors (SMTs) or leiomyoma. Here, we report a patient with a heterozygous 22q11.2 deletion/DiGeorge syndrome who developed a unique, broad, and lethal susceptibility to EBV characterized by EBV-infected T and B cells and disseminated EBV+SMT. The patient also harbored a homozygous missense mutation (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection. We show that wild-type CD137L was up-regulated on activated monocytes and dendritic cells, EBV-infected B cells, and SMT. The CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells. Therefore, these results highlight the critical role of the CD137-CD137L pathway in anti-EBV immunity, in particular in the control of EBV+SMT., (© 2022 Fournier et al.)

Competing Interests: The authors declare no conflict of interest.

The 2020 WHO Classification defines the spindle cell, epithelioid, and myxoid variants as subtypes of uterine leiomyosarcomas (LMS). Presence of cellular atypia (size variation of polymorphic nuclei > 2-3:1), tumor cell necroses, and mitotic count (usually ≥ 10 MF/10 HPF) are still the key features for diagnostic separation from uterine leiomyomas. Preanalytic variables, staining quality, as well as intralesional geographic distribution may affect the mitotic count. Smooth muscle tumors of uncertain malignant potential (STUMP) still exist as a not yet well-characterized diagnostic entity. Immunohistochemical stains against p16, p53, Ki-67, and WT‑1 may aid differential diagnosis in selected cases. Diagnostic molecular pathology is not yet relevant for diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

BACKGROUND Mixed endometrial stromal and smooth muscle tumors (MESSMT) of the uterus are rare disease entities. The histogenesis is unclear, but its clinical manifestations are similar to those of other mesenchymal tumors. This unique uterine tumor was originally reported as having ultrastructural characteristics of both endometrial stromal and smooth muscle cells. Subsequently, MESSMT was defined as having at least 30% of each component present. Here we present an MESSMT with unusual features in a nulliparous woman and describe its morphological and immunohistochemical characteristics. CASE REPORT A 35-year-old nulliparous woman presented with menorrhagia for 2 months. Transvaginal ultrasonography and magnetic resonance imaging revealed an enlarged uterus with a 6.0×5.5×4.5 cm mass and cystic degeneration. The patient underwent abdominal mass excision. Microscopically, the tumor consisted of 3 distinct components. The outermost area consisted of smooth muscle cells. Well-differentiated endometrial stromal cells that were centrally located showed irregular borders and were merged with smooth muscle cells. In addition, the endometrial stromal component showed focal sex-cord-like differentiation. Morphological and immunohistochemical evaluations were performed, and a MESSMT with focal sex-cord-like differentiation was diagnosed. The patient's postoperative course was uneventful for 29 months. CONCLUSIONS The diagnosis of MESSMT is challenging due to its many overlapping features with other mesenchymal uterine tumors. Although this rare tumor was histologically and clinically consistent with low-grade endometrial stromal sarcoma, it can cause recurrence and metastasis. Therefore, regular follow-up with radiologic examination is essential for the timely detection of local recurrence and distant metastasis.

Epithelioid leiomyosarcoma of the uterus is rare and poorly understood. Herein, we characterize a large institutional series of epithelioid leiomyosarcomas aiming to define outcome-determinant diagnostic pathologic features. We also retrieved epithelioid smooth muscle tumors of unknown malignant potential and evaluated a consecutive cohort of leiomyomas for epithelioid subtypes. Of a total of 1177 uterine leiomyosarcomas, 81 (7%) were categorized as epithelioid after review. Epithelioid leiomyosarcoma was strictly defined as having round to polygonal cells with visible pink cytoplasm and round to ovoid nuclei in ≥50% of the tumor volume. Average age was 55 years (range: 26 to 81 y). Median tumor size was 11 cm; tumor was >5 cm in 93% of subjects; 47% were stage 1 at presentation. An infiltrative tumor border was observed, grossly and/or microscopically, in 89% of cases; necrosis was noted in 80%, and vascular invasion in 47%. Mitotic count in 2.4 mm2 (totalling 10 high-power fields, each field 0.55 mm in diameter) ranged from 3 to 100 (median: 26). All cases had moderate, severe or highly pleomorphic atypia. All cases had 2 or 3 of the following: necrosis, at least moderate atypia and ≥4 mitoses in 2.4 mm2. Immunohistochemistry revealed frequent expression of smooth muscle markers including SMA (96%), desmin (95%), and caldesmon (81%). HMB45 and Melan-A were negative in 92% and 100% of cases, respectively. Estrogen and progesterone receptors were expressed by 65% and 54% of tumors, respectively. Follow-up information was available in 68 subjects (median: 23 mo, range: 1 to 254); cancer-related death occurred in 63%, and an additional 15% had recurrent or metastatic disease at last follow-up. Disease-specific survival was shorter in epithelioid leiomyosarcoma patients (median: 44  mo; 35% at 5-y) than in a matched cohort of nonepithelioid leiomyosarcoma (median: 55 mo; 46% at 5-y) (P=0.03). Three epithelioid smooth muscle tumors of unknown malignant potential were evaluated, all <5 cm in size and with atypia and/or irregular borders but mitotic count below the threshold for malignancy. Two of these had follow-up available, which was uneventful. Of 142 consecutive leiomyomas assessed, none had epithelioid morphology as defined. Epithelioid leiomyosarcoma is an aggressive neoplasm, sometimes with a remarkably low mitotic count. In the setting of an epithelioid smooth muscle tumor of the uterus, we postulate that the diagnosis of malignancy is made in the presence of ≥2 of the following: moderate or severe atypia, ≥4 mitoses/2.4 mm2 and tumor cell necrosis. In their absence, the finding of tumor size ≥5 cm, vascular invasion, infiltrative edges or atypical mitoses should be treated with caution, and designation as of at least uncertain malignant potential is warranted., Competing Interests: Conflicts of Interest and Source of Funding: D.B.C. work is supported by the Ovarian Cancer Research Alliance (Ann Schreiber Mentored Investigator Award; grant number 650320). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)