Smooth Muscle Tumors Of Uncertain Malignant Potential Research Articles

Uterine smooth muscle tumors of uncertain malignant potential: a retrospective evaluation of clinical pathology and immunohistochemistry features

BackgroundUterine smooth muscle tumor of uncertain malignant potential (STUMP) is a group of uterine smooth muscle tumors which cannot be classified as a subtype of leiomyoma or leiomyosarcoma. Diagnosis, prognosis, and treatment of these tumors are challenging due to recurrence, potential of malignancy, and metastasis.MethodsA retrospective cohort study was conducted in southern Iran during 2011 to 2020. We included records of 21 patients with STUMP and 24 patients with leiomyoma by simple randomized sampling in the tertiary health care centers in Shiraz, southern Iran. Slides were reviewed by an expert pathologist for examining mitosis, necrosis, and atypia, and also proper blocks were selected for immunohistochemistry (IHC) staining.ResultsFrom 45 participants, 21 (46.7%) and 24 (53.3%) patients were in the STUMP and normal leiomyoma groups, respectively. Odds ratio and 95% confidence interval (OR (95% C.I)) of pathologic size in the range of 5–10 cm was significantly higher in the STUMP group compared with normal leiomyoma. (CI: 7.22 (1.44–36.22)). Additionally, hyaline necrosis 0.05 (0.0-0.91), mild to moderate atypia 0.02 (0.0-0.4), moderate to severe atypia 0.01 (0.0-0.22), focal atypia 0.01 (0-0.26) and diffuse atypia 0.01 (0-0.26) were significantly fewer in normal leiomyoma compared to the STUMP group. Negative P16 0.01 (0.0007-0.24) and negative Bcl2 0.22 (0.06–0.81) were significantly higher in the normal leiomyoma group compared with the STUMP group. The cut-off points for predicting STUMP were 2.5% (sensitivity = 62% and specificity = 100%) and 45% (sensitivity = 43% and specificity = 96%) for P16 and bcl2, respectively.ConclusionThe category and management of STUMP continues to progress. The diagnosis for STUMP mainly depends on the histopathological manifestations. No single IHC marker such as P53, P16, and Bcl-2 has proved robust enough in separating STUMP from other leiomyoma variants; however, according to our study, we suggest combination use of P16 and Bcl-2 (cut off 2.5 and 45%, respectively) to distinguish equivocal cases of STUMP.

A Rare Case of Recurrent Vulvovaginal Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP)

Smooth muscle tumours are the most common mesenchymal tumors of the vulva and vagina, yet their infrequency is demonstrated by the prevalence of published reports as individual cases or small case series. This article reports a case of a 42-year-old woman who presented with apparently recurrent vulvovaginal leiomyoma and a past history of surgical excisions. Histopathology revealed Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP).

Low-Grade Uterine Leiomyosarcoma Is Highly Sensitive to Hormonal Treatment.

According to the World Health Organization classification system, uterine leiomyosarcomas (ULMS) are high-grade. A diagnosis of smooth-muscle tumors of uncertain malignant potential (STUMP) is made when Stanford Criteria for ULMS are not met. When a STUMP recurs, the tumor is diagnosed as ULMS and medical treatment is the same as for ULMS. In recent years, some sarcoma centers valued the less aggressive clinical behavior of several recurring STUMP and, given their expression of estrogen and progesterone receptors, started to treat them with hormonal therapy. This was a retrospective cohort analysis conducted at three referral centers joining the Leiomyosarcoma Foundation Roundtable. We selected all cases of uterine smooth muscle tumors consistent with STUMP and treated with hormonal therapy. 27 consecutive patients were identified. Median age at diagnosis was 43 years. Stage was IA-IB in more than 70% of patients. In these patients, median time to relapse was 62 months. Sites of first relapses were mostly pelvis and peritoneum (76%). After a median follow-up of 49 months, 14 patients (52%) had a partial response while 10 (37%) had a minor response or stable disease. Median time to progression was not reached. We observed a response or long-term stability rate on hormonal therapy in the 90% range; in all cases the time to relapse was significantly longer than in ULMS and in most cases the relapse was abdominal. On the basis of these findings, we conclude that a proportion of patients with uterine smooth muscle neoplasms actually present with a "low-grade ULMS."

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Comprehensive Multidisciplinary Update.

Background and Objectives: The uterine smooth muscle tumors of uncertain malignant potential (STUMP) are tumors with pathological characteristics similar to leiomyosarcoma, but that do not satisfy histological criteria for leiomyoma. These are problematic lesions with intermediate morphologic features; thus, diagnosis and treatment are difficult. This narrative review aims to review data in the literature about STUMPs, particularly focusing on management and therapeutic options and strategies for women who desire to preserve fertility. Material and Methods: authors searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed and Scopus databases, from 2000 to March 2023. Pertinent articles were obtained in full-text format and screened for additional references. Only articles in English language were included. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: The median age was 43 years old. Symptoms are similar to those of leiomyomas, with a mean diameter of 8.0 cm. Total hysterectomy with or without bilateral salpingo-oophorectomy is the standard care for women if fertility desire is satisfied. Myomectomy alone can be considered for young patients. Although these tumors have not a high malignant potential, several studies described recurrence and metastases. Conclusions: STUMPs are complex uterine smooth muscle tumors, with a rare but reasoned clinical-diagnostic management. Considering the high clinical and histological complexity of these tumors, high level of expertise is mandatory.

Uterine smooth muscle tumors with uncertain malignant potential: analysis following fertility-saving procedures

ObjectiveThe 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...

Smooth muscle tumor of uncertain malignant potential (STUMP): a case-based analysis.

The present study aimed to analyze of uterine smooth muscle tumors of uncertain malignant potential (STUMP) and the outcomes of patients with STUMP. 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. 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. 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.

Uterine inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is recognized as a true neoplasm of unknown etiology, but its pathogenesis is related to abnormalities in the ALK gene. This is an uncommon tumor with a wide anatomic distribution and often constitutes a challenging diagnosis owing to its histological similarities with other tumors. Uterine IMTs are rare and their detailed characteristics should be described based on case reports and small case series. Thus, we performed a comprehensive review of the literature showing that uterine IMTs show a wide range of age at diagnosis (median, 39 years), and a symptomatology similar to that of common leiomyomas, only rarely presenting with inflammatory manifestations. IMTs represent 0.1% of "leiomyomas," an estimate that increases to 10% for pregnant women and to 14% for the smooth muscle tumors of uncertain malignant potential (STUMP) category of tumors, implying that tumors excised during pregnancy, STUMPs, and leiomyosarcomas should be systematically screened with ALK immunohistochemistry, as this is a targetable abnormality. Most reported cases are ALK-positive; the fusion partners vary, but in pregnancy-associated tumors, TIMP3 prevails. Almost 25% of the patients will show an aggressive course, and this is associated with older age, non-pregnancy-associated tumors, larger tumors, infiltrative tumor border, absence of abundant inflammation, atypia, important mitotic activity, and necrosis.

Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1)

ObjectiveGynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus...

Molecular-Based Immunohistochemical Algorithm for Uterine Leiomyosarcoma Diagnosis

The morphologic assessment of uterine leiomyosarcoma (LMS) may be challenging, and diagnostic immunohistochemical (IHC) analysis is currently lacking. We evaluated the genomic landscape of 167 uterine LMS by targeted next-generation sequencing (NGS) to identify common genomic alterations. IHC analyses corresponding to these genomic landmarks were applied to a test cohort of 16 uterine LMS, 6 smooth muscle tumors of uncertain malignant potential (STUMP), and 6 leiomyomas with NGS data and a validation cohort of 8 uterine LMS, 12 STUMP, 21 leiomyomas and leiomyoma variants, 7 low-grade endometrial stromal sarcomas, and 2 diagnostically challenging uterine smooth muscle tumors. IHC results were individually interpreted by 3 pathologists blinded to NGS data. Overall, 94% of LMS showed ≥1 genomic alteration involving TP53, RB1, ATRX, PTEN, CDKN2A, or MDM2, with 80% showing alterations in ≥2 of these genes. In the test cohort, an initial panel of p53, Rb, PTEN, and ATRX was applied, followed by a panel of DAXX, MTAP, and MDM2 in cases without abnormalities. Abnormal p53, Rb, PTEN, and ATRX IHC expression was seen in 75%, 88%, 44%, and 38% of LMS, respectively, in the test cohort. Two or more abnormal IHC results among these markers were seen in 81% of LMS. STUMPs demonstrated only 1 IHC abnormality involving these markers. No IHC abnormalities were seen in leiomyomas. In the validation cohort, abnormal p53, Rb, and PTEN IHC results were seen in LMS, whereas rare STUMP or leiomyomas with bizarre nuclei showed IHC abnormalities involving only 1 of the markers. Abnormalities in ≥2 markers were present in both diagnostically challenging smooth muscle tumors, confirming LMS. Concordance was excellent among pathologists in the interpretation of IHC (κ = 0.97) and between IHC and NGS results (κ = 0.941). Uterine LMS exhibit genomic landmark alterations for which IHC surrogates exist, and a diagnostic algorithm involving molecular-based IHC may aid in the evaluation of unusual uterine smooth muscle tumors.

Histopathological Spectrum of Leiomyoma of the Uterus with an Emphasis on Pathological Technique to Avoid the Misdiagnosis: A Single Tertiary Centre Experience

Background: The most typical uterine tumour that develops from smooth muscle is a leiomyoma. It might be challenging to provide an accurate diagnosis when it exhibits abnormal gross features or artefacts. The fixation, grossing, taking sections, tissue processing, sectioning and staining are all aspects that might alter the histological spectrum, which varies from benign to malignant. Therefore, careful consideration must be given to all advantages and disadvantages in specimen handling, processing, evaluating gross examination and obtaining sections to arrive at a definitive diagnosis. Aims: To identify the pathological factors that affect the diagnostic accuracy in resection specimen of uterine mass, clinico-radiologically suggestive leiomyoma. Patients: All female patients (352) who underwent surgery for clinically suggestive uterine leiomyoma in a period of two years were included in the study. Materials and Methods: It was a retrospective observational study in a tertiary care centre that spanned 2 years, from January 2019 to January 2021. All patients who had undergone surgery for leiomyoma in this duration were included. All big specimens underwent customised pathology techniques. Results: A total of 352 cases, including 348 leiomyomas, three uterine smooth-muscle tumours of uncertain malignant potential (STUMP) and one case of leiomyosarcoma, were studied. A majority of patients were in the age group of 36–45 years (49.04%). Total hysterectomy was the most common type of surgery performed for leiomyoma (62.06% cases). The most common site of occurrence is intramural. The average size of leiomyoma was 4.72 cm. A majority (88.21%) of leiomyomas were of typical type without any degeneration or variation in histology. Hyalinised collagen (5.75%) is the most frequent finding encountered as a histopathological variant, followed by myxoid change (1.43%). Associated pathology with leiomyoma was adenomyoma (10.91%), followed by uterine malignancy. Adopting the pathology techniques, three cases of uterine smooth-muscle tumours of uncertain malignant potential (STUMP) and one case of leiomyosarcoma could be identified. Conclusion: A pathologist needs to be skilled in troubleshooting lacunae, whether they are caused by fixing the gross or by cutting sections and staining tissue processing. These variables affect the accuracy of the diagnostic process.

Smooth muscle tumor of uncertain malignant potential (STUMP)

Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor belonging to a group of smooth muscle tumor that possess both benign and malignant features, complicating the diagnosis. STUMP is a rare uterine tumor with a paucity of literature available regarding management and subsequent malignant potential. A 22-year-old unmarried lady presented as uterine fibroids with 24 weeks size uterus. There was one intramural and another subserosal mass both of which revealed smooth muscle tumor of uncertain malignant potential in histopathology.

Smooth muscle tumor of uncertain malignant potential (STUMP) of Vulva

A 30-years old nulliparous lady presented with apparently recurrent leiomyoma of vulva and past history of repeated resections. She had firm bilobed non-tender vulval lump and underwent partial vulvectomy. Histopathology revealed Smooth muscle tumor of uncertain malignant potential (STUMP).
 Conclusion: Vulvar leiomyoma is fairly uncommon and can often be misdiagnosed. Surgical excision and histopathological analysis is helpful/ recommended for final diagnosis of Vulvar STUMP.

Review of: "Changelles in identifying biomarkers for Smooth muscle tumours of uncertain malignant potential (STUMP)"

Review of: "Changelles in identifying biomarkers for Smooth muscle tumours of uncertain malignant potential (STUMP)"

Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) Treated with Conservative Surgery: Systematic Review of Reproductive Outcomes

Background: Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a rare tumor that represent a diagnostic challenge to both clinicians and pathologists. Hysterectomy is considered the definitive treatment in women who don’t desire to conceive anymore; while myomectomy is suggested in young women who desire to preserve their fertility. The aim of this review is to evaluate the reproductive outcomes in patients submitted to fertility sparing treatment and with a diagnosis of STUMP at the definitive pathological evaluation. Methods: We searched among electronic databases from inception of them through January 2022. The research was conducted using meshes created by the combination of relevant heading term, key words, and word variants for: “uterine smooth muscle tumor of uncertain malignant potential”, “fertility”, “pregnancy”. Results: Seven retrospective studies including 80 women desirous of conceiving after a diagnosis of STUMP were included in this systematic review. Among these, 33 (41.25%) women got pregnant at least once and we recorded a total number of pregnancies of thirty-nine. Almost all deliveries were performed by caesarean section. Two (6.1%) relapses were diagnosed. Patients were submitted to hysterectomy and STUMP was confirmed as the final pathological diagnosis. The median follow-up in patients who delivered live babies was 61 months after surgery. At the last follow-up, all patients were alive without evidence of disease. Conclusions: This review shows that pregnacy seems to be possible and safe after the diagnosis of STUMP. These women should undergo rigorous follow-up and consider hysterectomy after completion of their reproductive plan. This review could be a useful tool for the counseling and the management of women with STUMP who desire to keep their fertility.

Leiomyoma with Bizarre Nuclei: A Current Update.

Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, is a histological subtype of benign leiomyoma with bizarre cells and nuclear atypia. Differentiating LBN from other benign leiomyoma subtypes, uterine smooth muscle tumors of uncertain malignant potential (STUMP), or leiomyosarcoma (LMS) can be diagnostically challenging owing to overlapping features in clinical presentation and pathologic morphological analysis. The difficulty of distinguishing LBN from other lesions, especially from LMS, and the potential of LBN for subsequent malignant transformation make LBN an important topic of research. Herein, we review the definition, diagnosis, treatment, and prognosis of LBN. Histopathological examination is essential for distinguishing LBN from other diseases. Pathology sampling and morphological examination remain the key to diagnosis. The newly established ancillary immunohistochemical (IHC) and molecular genetic analysis can be useful tools for differential diagnosis. Furthermore, serum biomarkers and imaging examination may also be useful diagnostic tools. Attention should be paid to the differentiation between LBN and LMS because morphological diagnosis may still be challenging in some cases. Some IHC markers of LBN have been identified, which may be helpful for differential diagnosis. Furthermore, the use of IHC panels as diagnostic markers may be advocated. Molecular genetic studies suggest that some genes can aid with the differential diagnosis between LBN and LMS. However, increasing evidence support the idea that LBN and LMS are molecularly related, indicating that LBN may represent a potentially malignant stage of precancerous progression. At present, conservative treatment is recommended for primary LBN, especially for patients desiring to retain fertility, but close follow-up with imaging examinations is required.

Retrospective Analysis on Characteristics of Uterine Smooth Muscle Tumors of Uncertain Malignant Potential—13 Years' Experience

Background: Benign leiomyomas (LM) and malignant leiomyosarcomas (LMS) can be distinguished by increased cellularity with mitotic activity. Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are a group of rare tumors in between, for which there is still no standardized classification, nor any definitive preoperative imaging or laboratory investigations regarding the possible inclusion of STUMP in the differential diagnosis. Methods: In this study, we retrospectively reviewed 6 cases of STUMP, and assessed their pathogenesis, risk factors, and prognostic features. Results: The mean age of STUMP patients was 40.6 years old. No recurrence has been reported in all six cases after more than 3.6 years of follow-up. The mean tumor size was 9.44 cm (range 6.14–12.21). 4 cases (66.7%) with <5 mitoses, 1 case (16.7%) with 5–9 mitoses, and 1 case (16.7%) with >10 mitoses per 10 high-power fields. Immunohistochemical staining for cyclin dependent kinase nhibitor 2A (p16), tumor protein p53 (p53), and Antigen KI-67 (Ki-67) was 100% positive (2/2, 6/6, and 6/6, respectively). The estrogen receptor (ER) expression rate was 50.0% (3/6), and the progesterone receptor (PR) was 33.3% (1/3). There was no correlation between the expression of these biomarkers and mitotic counts or recurrence. Conclusions: The current immunohistochemical biomarkers are ineffective in determining the probability of malignancy in STUMP patients with desire of further fertility. Detection of gene expression profiles or variants using next-generation molecular techniques may aid in disease prediction, diagnosis, treatment, and prognosis.

A critical review of “uterine leiomyoma” with subsequent recurrence or metastasis: A multicenter study of 62 cases

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. 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. 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. 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.

Clinical and Histopathological Predictors of Recurrence in Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Multicenter Retrospective Cohort Study of Tertiary Centers

BackgroundThe term uterine smooth muscle tumor of uncertain malignant potential (STUMP) indicates a rare, equivocal entity between benign leiomyomas and leiomyosarcomas. In the present study, we evaluated a comprehensive range of clinical, surgical, and pathological features in a large multicenter series of patients with STUMP to identify risk factors for recurrence.MethodsThis is a retrospective study performed by collecting consecutive cases diagnosed between January 2000 and December 2020 in five tertiary centers. Associations between STUMP recurrence and clinicopathological characteristics as well as surgical treatment modality were investigated.ResultsEighty-seven patients affected by STUMP were considered. Of them, 18 cases (20.7%) recurred: 11 as leiomyosarcoma (LMS) and 7 as STUMP. The mean time to recurrence was 79 months. We found that fragmentation/morcellation, epithelioid features, high mitotic count, Ki-67 value > 20%, progesterone receptor (PR) < 83%, and p16 diffuse expression were associated with higher risk of recurrence and shorter recurrence-free survival (RFS). Furthermore, morcellation/fragmentation and mitotic count remained independent risk factors for recurrence and shorter RFS after multivariate analysis, while the presence of epithelioid features was an independent risk factor for recurrence only.ConclusionsOur results suggest that morcellation is associated with risk of recurrence and shorter RFS, thus it should be avoided if a STUMP is suspected preoperatively. Epithelioid features, high proliferation activity, low PR expression, and diffuse p16 expression are also unfavorable prognostic factors, so patients presenting these features should be closely followed up.

ASO Author Reflections: Surgical Management and Histopathological Predictors of Recurrence in Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): New Insights.

ASO Author Reflections: Surgical Management and Histopathological Predictors of Recurrence in Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): New Insights.

Proteomic analysis of uterine smooth muscle tumors and rare uterine fibroid variants (120)

<b>Objectives:</b> Uterine leiomyoma (ULM) variants, such as smooth muscle tumors of uncertain malignant potential (STUMP), may represent pre-malignant tumors that can lead to the development of malignant neoplasms, such as uterine leiomyosarcomas (LMS). Here we performed in-depth global proteomic analyses of archival ULM, STUMP, and LMS tissues from >60 patients to explore the relationship of protein expression among these tumor types. <b>Methods:</b> Diagnosis-confirmed, formalin-fixed, paraffin-embedded tissues corresponding to ULM (<i>n</i>=25), STUMP (<i>n</i>=16), and LMS (<i>n</i>=27) were obtained from the Joint Pathology Center. Whole tumor collections employing laser microdissection were trypsin digested and analyzed by multiplexed, mass spectrometry-based quantitative proteomics. Differential expression analysis was performed using commercial and in-house bioinformatic pipelines. <b>Results:</b> Global proteomic analysis of ULM, STUMP, and LMS tumor tissues quantified 7,090 unique proteins. Principle component analysis of 187 variably abundant proteins (median absolute deviation > 1) accounted for 32.6% and 12.6% of the variance observed between these tumor groups. Differential analysis of STUMP, LMS, and ULM tumors revealed 30 proteins significantly co-altered across samples (LIMMA adjusted p < 0.05). Many of these proteins exhibited progressively increasing abundance trends across ULM to STUMP to LMS tumors and correlated with enrichment of DNA replication and cell proliferation signaling pathways. Comparison of proteins co-altered in LMS versus STUMP and LMS versus ULM tumors further revealed enrichment of cellular pathways regulating cell proliferation as well as vasculogenesis signaling in LMS tumors. Additional investigation of proteins uniquely elevated in LMS tumors identified several candidates involved in regulating cellular metabolism and are targetable by small molecule inhibitors. <b>Conclusions:</b> Quantitative proteomic analysis of uterine smooth muscle tumors reveals distinct changes in the proteomes of ULM, STUMP, and LMS tumors, including increased tumor cell proliferation signaling in LMS compared with ULM. These data also identify discrete alterations correlating with the transition of ULM to STUMP to LMS tumors that may contribute to the molecular evolution from ULM to STUMP tumors and drive LMS to be aggressive, treatment-resistant, and deadly. The comparative analysis further revealed insights into enriched cellular pathways, and protein alterations uniquely elevated in LMS tumors, further correlating with vasculogenesis signaling and cellular metabolism that are putative therapeutic targets. This study provides insights into the disease biology underlying the development of ULM, STUMP, and LMS tumors that may lead to the development of diagnostic and treatment strategies toward improved management of these increasingly prevalent gynecologic conditions.Fig. 1