Benign Leiomyoma Research Articles

Mass lesions of the myometrium: interpretation and management of unexpected pathology.

Uterine leiomyomas are the most common benign uterine smooth muscle tumors. On the basis of imaging, these masses are often presumed to be benign conventional leiomyomas and surgical excision is a common treatment choice. After myomectomy or hysterectomy for presumed leiomyomas, the surgical pathology report may reveal an unexpected diagnosis of another type of mesenchymal tumor. These can range from a variant of benign smooth muscle tumors to smooth muscle tumors of uncertain malignant potential to malignant sarcomas. This review describes these variant pathologies and reviews data on recurrence risk and postoperative management. The majority of benign smooth muscle tumors will be classified as leiomyomas. Cellular, bizarre nuclei, mitotically active, epitheliod, myxoid, and dissecting are all terms that describe pathologic variants of benign leiomyomas. Smooth muscle tumors of uncertain malignant potential contain both benign and malignant features and should be referred to Gynecologic Oncology for follow-up. Leiomyosarcomas and low-grade endometrial stromal sarcomas may present preoperatively as benign tumors but are malignant with a high risk of recurrence and should be referred to Gynecologic Oncology. We advocate for the continued benefits of minimally invasive procedures in appropriately selected patients. Despite these measures, unexpected pathologic diagnoses can occur and should be managed appropriately.

1902 Small Bowel Tumor: The Answer to Unexplained Overt Gastrointestinal Bleeding

INTRODUCTION: The rarity of small bowel tumors often makes diagnosis difficult due to nonspecific and variable presenting symptoms. This can result in a delay of diagnosis and consequent poor treatment outcome. Small bowel tumors can be either malignant (adenocarcinomas, lymphomas, sarcomas, and neuroendocrine tumors) or benign (adenomas, leiomyomas, and lipomas). CASE DESCRIPTION/METHODS: We present the case of a 58-year-old male, who presented to the hospital with dizziness, lightheadedness, and dyspnea on exertion for 3 days. History was significant for GERD, and iron deficiency anemia. Recent outpatient evaluation of weakness and fatigue revealed hemoglobin of 10 g/dL, decreased from 16.3 g/dL one year prior. An outpatient colonoscopy was scheduled for the following month but presented to the hospital because of multiple episodes of melenic stools. He denied any hematochezia, abdominal pain, weight loss, dysphagia, nausea, vomiting or hematemesis. He denied any family or personal history of malignancy or inflammatory bowel disease. He was tachycardic on examination. Initial lab work revealed hemoglobin of 8.2 g/dL. During his hospitalization, the patient experienced frank hematochezia and required transfusion of several units of blood due to acute blood loss. The patient underwent endoscopic evaluation, which revealed a small hiatal hernia with normal stomach and normal examined duodenum. A colonoscopy revealed red blood in the entire examined colon as well as the distal ileum. The patient then underwent video capsule endoscopy (VCE), which localized a source of bleeding in the proximal jejunum. A subsequent small bowel enteroscopy revealed a large infiltrative, polypoid, submucosal and ulcerated mass in the proximal jejunum. A CT scan revealed the location of the mass. The patient ultimately went to the operating room. Intraoperative visualization noted the mass to be exophytic, approximately 5 cm in diameter with mild purulence into the peritoneal cavity but without evidence of carcinomatosis. DISCUSSION: Adequate diagnosis of small bowel tumors, which present with varied and nonspecific symptoms, can inform early and appropriate treatment. In this case, endoscopic evaluation with EGD, colonoscopy, and VCE, resulted in the localization of the tumor and facilitated its surgical excision. This case exemplifies a practical algorithmic approach to the evaluation of an unexplained overt gastrointestinal bleed in a patient with nonspecific symptoms.

2780 A Case of a 20-Year-Old Female With Hereditary Diffuse Gastric Cancer Syndrome With Synchronous Diffuse Gastric Cancer and a Giant Uterine Tumor

INTRODUCTION: Hereditary Diffuse Gastric Cancer (HDGC) is defined by germline autosomal dominant mutation in the CDH1 gene causing an inherited form of diffuse gastric cancer. There are no reported cases of HDCG presenting with a synchronous giant uterine tumor. CASE DESCRIPTION/METHODS: A 20-year-old female with known pathogenic CDH1 mutation presented with 3 days of pelvic pain and a palpable lower abdominal mass. She underwent a CT abdomen/pelvis which revealed a large uterine tumor measuring 16 cm. The patient’s family history is notable for maternal grandmother and maternal uncle who were diagnosed with and died of gastric cancer at 46 and 55, respectively. Her mother, the proband, was diagnosed with stage IV diffuse gastric cancer at age 46, underwent genetic testing and was found to have a pathogenic mutation in the CDH1 gene. The patient’s 42-year-old maternal aunt, who also tested positive, underwent prophylactic gastrectomy. There was no evidence of gastric adenocarcinoma on pathology. The patient also tested positive for CDH1 mutation and was counselled about prophylactic gastrectomy. Given she had just turned 20, the patient was not offered immediate surgery. She underwent a baseline upper endoscopy prior to planned hysterectomy. Random endoscopic biopsies revealed diffuse poorly differentiated carcinoma with signet ring features. Given poor histology and diffuse nature, the patient received 3 cycles of neoadjuvant chemotherapy before undergoing total gastrectomy with Roux-en-Y reconstruction and uterine myomectomy. She opted for myomectomy to preserve fertility. Pathology revealed diffuse pT1aN0M0 poorly differentiated G3, stage IA gastric adenocarcinomaand a benign leiomyoma. DISCUSSION: HDGC is exceedingly rare, accounting for only 1% of all gastric cancers. The median age to develop gastric cancer in pathogenic CDH1 carrier is 33 to 40. The risk of developing gastric cancer is less than 1% in patients under the age of 20. HDGC has penetrance of up to 80%. Our patient’s 42 year old aunt had a pathogenic CDH1 gene; however, her final pathology following prophylactic gastrectomy did not show any evidence of cancer, highlighting the small possibility of having no disease manifestation. Lastly, our patient had a synchronous, yet separate, primary uterine tumor at the time of presentation. In reviewing the literature, there are no other reported HDGC cases with a concurrent separate primary uterine tumor.

CD4 and CD8 but not dn mucosa-associated invariant T cells foster the development of endometriosis: a pilot study

Our study aims to demonstrate the relationship between Mucosa-associated invariant T (MAIT) cells and endometriosis. Case-control study. The study group comprised 32 patients with a diagnosis of endometriosis.18 women with only ovarian benign cysts or uterine leiomyoma who underwent laparoscopy were recruited as control group. Peritoneal fluid (PF) was collected during laparoscopy. Peripheral blood (PB) was obtained shortly before the surgery. We investigated MAIT cells and their different subpopulations in PB and PF from endometriosis (EMS) and control group (CG). MAIT cells were characterized as CD3+CD161+Vα7.2+ cells by flow cytometry. Next based on CD4 and CD8, the cells were divided into three subsets: CD8 MAIT cells, CD4/CD8-/- (double negative, DN) MAIT cells and CD4 MAIT cells. And IL-8, 12, 18, 17, MMP-9, INF-g from the peritoneal fluid and plasma were analyzed by ELISA kit. Our results revealed that there were enrichments of MAIT cells, especially CD4 and CD8 MAIT subset. Moreover, CD8 MAIT cells had a greater activation in EMS group as compared to the results from CG patients. In line with this data, EMS patients produced higher level of IL-8/12/17 as compared to these from controls. On the contrary, control patients exhibited a dramatic upregulation of DN MAIT cells, however, these DN MAIT cells from controls showed a higher expression of PD-1. At the end we performed the relevance analysis, and we discovered that the accumulation of PB MAIT cells correlated with elevated level of serum CA125 production. Our study suggests functional diversities of MAIT cells subsets in the development of endometriosis. CD4 and CD8 MAIT cells could be a promoter in endometriosis, whereas DN MAIT cells might be a protector for the host.

How to differentiate uterine leiomyosarcoma from leiomyoma with imaging

Uterine leiomyomas, the most frequent benign myomatous tumors of the uterus, often cannot be distinguished from malignant uterine leiomyosarcomas using clinical criteria. Furthermore, imaging differentiation between both entities is frequently challenging due to their potential overlapping features. Because a suspected leiomyoma is often managed conservatively or with minimally invasive treatments, the misdiagnosis of leiomyosarcoma for a benign leiomyoma could potentially result in significant treatment delays, therefore increasing morbidity and mortality. In this review, we provide an overview of the differences between leiomyoma and leiomyosarcoma, mainly focusing on imaging characteristics, but also briefly touching upon their demographic, histopathological and clinical differences. The main indications and limitations of available cross-sectional imaging techniques are discussed, including ultrasound, computed tomography, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography. A particular emphasis is placed on the review of specific MRI features that may allow distinction between leiomyomas and leiomyosarcomas according to the most recent evidence in the literature. The potential contribution of texture analysis is also discussed. In order to help guide-imaging diagnosis, we provide an MRI-based diagnostic algorithm which takes into account morphological and functional features, both individually and in combination, in an attempt to optimize radiologic differentiation of leiomyomas from leiomyosarcomas.

Unusual FDG PET/CT Uptake in Uterine Tumors in Cancer Survivor

18-Fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT) has become the essential modality of imaging in diagnosis; it is used for assessment of treatment response, after chemotherapy, as well as for prognostic evaluation. Case 1 is a postmenopausal woman treated for the case of Langerhans cell sarcoma; she received chemotherapy; post-chemotherapy PET/CT scan was done to assess the response to chemotherapy with an SUV of 7.1 in the uterus. The rest of the report showed no uptake elsewhere in the body, and hysterectomy with BSO pathological report showed benign leiomyoma. Case 2 is treated for carcinoma thyroid by surgery and radioiodine ablation therapy. She was on regular follow-up, and she is a premenopausal multiparous woman with regular menstruation and on annual PET/CT examination incidentally showed an increased SUV of 8 in the uterus. There was no FDG uptake elsewhere in the body except for uterus. False-positive uptake of 18-FDG PET/CT in uterine tumors can be seen in leiomyoma which has high SUV of more than 6. Surgical management with histopathological confirmation of leiomyoma is needed in cases treated for malignancy elsewhere in the body; we report these two cases hoping to expand the existing knowledge on the topic and highlight the limitation of PET/CT in the diagnosis of leiomyoma.

Identification of a novel diagnostic gene expression signature to discriminate uterine leiomyoma from leiomyosarcoma

Leiomyosarcomas are rare, aggressive tumors, which exhibit a poor prognosis regardless of stage. Pre-operative diagnosis can be difficult as leiomyosarcoma can mimic features of the more common, benign uterine leiomyoma. The goal of this study was to identify specific molecular markers to discriminate between uterine leiomyosarcomas and leiomyomas to facilitate timely, accurate diagnosis and treatment.Gene expression profiles of three leiomyosarcomas, leiomyomas, and normal myometrial tissue samples were analyzed using the Affymetrix Human Gene 1.0 ST Array. GC-robust multiarray average calculation and ANOVA statistical testing were used to identify differentially expressed genes. Sixty genes, with functional roles in tumor progression or suppression, exhibited divergent expression profiles in leiomyosarcomas and leiomyomas, compared to normal myometrium. Differential RNA and protein levels of seven genes, with the most discriminatory expression patterns, were confirmed by RTPCR and immunohistochemistry in an additional 10 leiomyosarcoma and 20 leiomyoma independent samples. CHI3L1, MELK, PRC1, TOP2A, and TPX2 were overexpressed in leiomyosarcomas, while HPGD and TES were overexpressed in leiomyomas. Distinguishing leiomyosarcomas from leiomyomas represents a diagnostic challenge, particularly in the context of minimally invasive surgery. The unique gene expression signatures identified in this study may accurately differentiate between these tumor types at the earliest stage and provides potential prognostic factors and novel therapeutic targets for the treatment of leiomyosarcoma.

La léiomyomatose extra-utérine : revue de la littérature

Extra-uterine leiomyomatosis is a rare pathology defined by the presence of benign smooth uterine muscle cells in unusual localizations, including different entities. It mainly affects premenopausal women with a medical history of uterine myoma with or without surgical treatment. Three main types are discribed: intraveinous leiomyomatosis, benign metastatisizing leiomyoma and leiomyomatosis peritonealis disseminata. The diagnosis may be complex with many differential diagnosis, and relies on histology. The treatment depends on multiple factors such as age, localization, size, symptoms and associated comorbidities. It is based on surgical resection and hormonal privation, surgical (adnexectomy) or medical (hormonotherapy). There is a high risk of recurrence. Some malignant evolutions have been reported, mostly leiomyosarcoma following peritoneal disseminated leiomyomatosis. Long term follow-up of these patients is mandatory. A particular manifestation of extra-uterine leiomyomatosis is the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. It is an autosomal dominant disorder which confers an increased risk of cutaneous and uterine leiomyomas and renal cell cancer, with a poor prognosis due to the urologic tumor.

PD-L1 Expression and Tumor-infiltrating Lymphocytes in Uterine Smooth Muscle Tumors: Implications for Immunotherapy.

Immunotherapies targeting the PD-1/PD-L1 checkpoint axis are of growing interest for the treatment of mesenchymal neoplasms. However, PD-L1 expression and tumor-associated lymphocytes have not been well-investigated in uterine smooth muscle tumors. Forty-nine uterine smooth muscle tumors (23 leiomyosarcomas, 8 smooth muscle tumors of uncertain malignant potential [STUMP], 7 atypical leiomyomas, and 11 benign leiomyomas) were evaluated for tumoral and tumor-associated immune PD-L1 expression and tumor-associated T-cell infiltration. ALK immunohistochemistry was performed to exclude inflammatory myofibroblastic tumors. Tumor PD-L1 expression was seen in 70% of leiomyosarcomas and 14% of atypical leiomyomas; no cases of STUMP or benign leiomyoma demonstrated tumoral PD-L1. PD-L1 positivity was seen in tumor-associated immune cells in 78% of leiomyosarcomas, 25% of STUMP, no cases of atypical leiomyomas, and 9% of benign leiomyomas. Of the 23 leiomyosarcomas, 15 (65%) had a combined positive score ≥1, while of the 26 other uterine smooth muscle tumors, only 2 (8%) had a combined positive score ≥1. Tumor-associated CD8+ cells were highest among leiomyosarcomas (mean: 87/high-power fields vs. 17/high-power fields for nonleiomyosarcomas), and were significantly associated with PD-L1 expression. One PD-L1, CD8-enriched leiomyosarcoma showed an ALK overexpression suggesting possible classification as inflammatory myofibroblastic tumor, but otherwise lacked morphologic features of this entity. Leiomyosarcomas demonstrate significantly higher PD-L1 expression and cytotoxic T-cell infiltration when compared with other uterine smooth muscle tumors. These data suggest the possibility that treatment with targeted immunotherapy may be appropriate in a selected population of patients with leiomyosarcoma and, potentially, in related tumors bearing ALK rearrangements.

Different methylation levels in the KLF4, ATF3 and DLEC1 genes in the myometrium and in corpus uteri mesenchymal tumours as assessed by MS-HRM

Mesenchymal tumours of the corpus uteri comprise common benign lesions – leiomyomas and very rare malignant variants – sarcomas. It can be difficult to distinguish between the particular types of mesenchymal tumours pre-surgically. Primarily, leiomyomas and the very aggressive leiomyosarcomas can be easily misdiagnosed when using only imaging devices. Therefore, a reliable non-invasive marker for these tumour types would provide greater certitude for patients that the lesion remains benign. Our collection comprises 76 native leiomyomas, an equal number of healthy myometrium samples and 49 FFPE samples of various types of sarcomas. The methylation level was assessed by MS-HRM method and we observed differences in the methylation level between healthy, benign and (semi)malignant tissues in the KLF4 and DLEC1 genes. The mean methylation levels of leiomyomas compared to myometrium and leiomyosarcomas were 70.7% vs. 6.5% vs. 39.6 % (KLF4) and 66.1% vs. 14.08% vs. 37.5% (DLEC1). The ATF3 gene was differentially methylated in leiomyomatous and myometrial tissues with 98.1% compared to 76.6%. The AUC values of the predictive logistic regression model for discrimination between leiomyomas and leiomyosarcomas based on methylation levels were 0.7829 (KLF4) and 0.7719 (DLEC1). Finally, our results suggest that there should be distinct models for the methylation events in benign leiomyomas and sarcomas, and that the KLF4 and DLEC1 genes can be considered potential methylation biomarkers for uterine leiomyomas.

Fully Human Tumor-based Matrix in Three-dimensional Spheroid Invasion Assay.

Two-dimensional cell culture-based assays are commonly used in in vitro cancer research. However, they lack several basic elements that form the tumor microenvironment. To obtain more reliable in vitro results, several three-dimensional (3D) cell culture assays have been introduced. These assays allow cancer cells to interact with the extracellular matrix. This interaction affects cell behavior, such as proliferation and invasion, as well as cell morphology. Additionally, this interaction could induce or suppress the expression of several pro- and anti-tumorigenic molecules. Spheroid invasion assay was developed to provide a suitable 3D in vitro method to study cancer cell invasion. Currently, animal-derived matrices, such as mouse sarcoma-derived matrix (MSDM) and rat tail type I collagen, are mainly used in the spheroid invasion assays. Taking into consideration the differences between the human tumor microenvironment and animal-derived matrices, a human myoma-derived matrix (HMDM) was developed from benign uterus leiomyoma tissue. It has been shown that HMDM induces migration and invasion of carcinoma cells better than MSDM. This protocol provided a simple, reproducible, and reliable 3D human tumor-based spheroid invasion assay using the HMDM/fibrin matrix. It also includes detailed instructions on imaging and analysis. The spheroids grow in a U-shaped ultra-low attachment plate within the HMDM/fibrin matrix and invade through it. The invasion is daily imaged, measured, and analyzed using ilastik and Fiji ImageJ software. The assay platform was demonstrated using human laryngeal primary and metastatic squamous cell carcinoma cell lines. However, the protocol is suitable also for other solid cancer cell lines.

The Use of Smoothelin and Other Antibodies in the Diagnosis of Uterine and Soft Tissue Smooth Muscle Tumors.

Smoothelin is a cytoplasmic protein expressed in differentiated smooth muscle cells. Immunohistochemical evaluation of smoothelin has previously been reported in gastrointestinal (GI) smooth muscle tumors, but has yet to be studied in smooth muscle tumors of uterine and other soft tissue origin. DOG1 expression is reported to be specific for GI stromal tumors; however, variable expression has been reported in leiomyosarcomas (LMS) depending on site of origin. Overexpression of p16 is common in LMS of uterine and other sites of origin, but has not been correlated with tumor grade. This study explores the differential expression of these markers, as well as caldesmon, in LMS cases to assess diagnostic utility. Using tissue microarrays and cases from Tulane Medical Center and Medical College of Wisconsin, expression of smoothelin, DOG1, caldesmon, and p16 was evaluated by immunohistochemistry in 87 cases of LMS. The cases were subdivided by location of origin into uterine (N=31) and nonuterine (N=56) with 10 of the nonuterine of GI origin, as well as by grade into low grade (N=27) and intermediate and high grade (N=60). Differential expression among different grades and locations was evaluated. The same markers were evaluated in atypical leiomyoma cases (N=4) and 1 smooth muscle tumor of uncertain malignant potential case (N=1). Smoothelin expression was also assessed in 20 benign uterine leiomyomas. Weak DOG1 expression is rare but possible in extrauterine LMS. Expression of p16 is common in both uterine and extrauterine LMS, and more frequent in higher grades. Expression of smoothelin in this study differed depending on tumor type, grade, and site of origin. All leiomyomas and most atypical leiomyomas showed cytoplasmic positivity for smoothelin, whereas only 5% of LMS had cytoplasmic expression. The study suggests smoothelin may be downregulated in the cytoplasm of malignant smooth muscle tumor cells and may serve as a supportive aid in the distinction of LMS from benign smooth muscle tumors in cases where it is difficult by morphology alone.

Diagnostic value of 3 T MR spectroscopy, diffusion-weighted MRI, and apparent diffusion coefficient value for distinguishing benign from malignant myometrial tumours

To further verify the effectiveness of diffusion-weighted (DWI) magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopy (MRS) using a 3 T MRI system to differentiate benign leiomyomas from uterine sarcoma; to investigate the benefit of adding MRS to the apparent diffusion coefficient (ADC) for improving the specificity of the benign/malignant classification. The dataset included 21 uterine sarcoma from 14 patients and 84 benign leiomyomas from 51 patients. T1-and T2-weighted images as well as DWI were obtained using a 3-T MRI system. Approximately 60% of patients also underwent MRS. The chi-square test was used to compare the percentage of malignant lesions that showed choline peaks, lipid peaks, and restricted diffusion to the corresponding percentage of benign masses. Using the area under a receiver operating characteristic (AUC) curve, the efficacy of different parameters for distinguishing uterine sarcomas from leiomyomas was measured. The visual assessment of DWI images showed that 100% of malignant lesions exhibited restricted diffusion while the corresponding figure for benign leiomyomas was only 5%. The mean ADC of malignant tumours differed significantly from that of benign ones (p<0.001). The percentage of malignant lesions for which choline and lipid peaks were present was significantly higher than that of benign lesions. By combining the ADC and MRS findings, an accuracy of 98.3 (95.1-100) was achieved. The findings suggested that a combination of DWI and MRS could be useful in the preoperative assessment of uterine masses to differentiate benign leiomyomas from leiomyosarcoma.

Uterine sarcoma: a clinical case and a literature review.

Uterine sarcomas are rare gynaecologic tumours representing 3-7% of all uterine malignancies. The aetiology of sarcomas is still unclear: it is thought, that chromosomal translocations have influence on wide histological variety of sarcomas. Presenting symptoms are vague and nonspecific. Usually sarcoma causes abnormal vaginal bleeding, can cause abdominal or pelvic pain, or manifests as a rapidly growing uterine tumour. The diagnosis of sarcoma is often made retrospectively after surgical removal of a presumed benign uterine neoplasm, because imaging modalities such as ultrasound, computed tomography, or magnetic resonance imaging cannot yet accurately and reliably distinguish between benign leiomyoma and malignant pathology. If there are certain clinical features that raise a suspicion of malignancy in the uterus, it is recommended to avoid the use of power morcellation through laparoscopic surgery in order to prevent disease dissemination. We present a clinical case of a 64-year-old patient, who was referred to hospital due to abdominal pain and tenesmus that lasted for two days. From a past medical history it was known that previously the patient had been diagnosed with uterine myoma. Transvaginal ultrasonography showed a 10.4 cm × 9.8 cm uterine tumour of nonhomogeneous structure with signs of necrosis and good vascularization. The patient refused urgent hysterectomy, that was advised to her. The patient was operated on one month later and total hysterectomy with bilateral salpingooforectomy was performed. Postoperative histological evaluation showed undifferentiated sarcoma uterus pT1b L/V0. Imaging modalities were made to evaluate possible dissemination of the disease. In the absence of signs of disease progression, the patient received radiotherapy and brachytherapy and was followed-up by doctors. Uterine sarcomas are highly malignant tumours that originate from smooth muscles and connective tissue elements of the uterus and make up 1% of all malignant gynaecological tumours and about 3-7% of all malignant uterine tumours. Imaging modalities cannot yet reliably distinguish benign myomas from malignant sarcomas. It is important not to damage the wholeness of uterus during operation in order to prevent dissemination of the disease in the abdominal cavity. The low-grade endometrial stromal sarcoma has the best survival prognosis, while carcinosarcoma and undifferentiated uterine sarcoma have the lowest survival rates.

Mesenchymal and mixed uterine tumors : Current overview and practical aspects

Benign leiomyomas are the most frequent mesenchymal tumors of the uterus. In contrast, uterine sarcomas are very rare. Leiomyosarcomas are the most frequent sarcomas followed by endometrial stromal sarcomas (ESS). Leiomyosarcomas are characterized by marked nuclear atypia and high mitotic count and may also show tumor cell necrosis and myometrial and vascular invasion. For cases of diagnostic uncertainty, the category of smooth muscle tumor of uncertain malignant potential (STUMP) may be considered but should be rarely used. Besides low-grade ESS and stromal nodules, acategory of high-grade ESS was reconsidered by the WHO in 2014. High-grade ESS are characterized by fibromyxoid and round cell histology, myoinvasive growth, and immunoreactivity for cyclin D1 and BCOR and distinct gene fusions involving YWHAE and BCOR, respectively. The very rare undifferentiated uterine sarcomas need to be redefined due to overlap with high-grade ESS. Uterine tumors resembling ovarian sex cord tumors (UTROSCT) rarely behave malignant, but need to be distinguished from endometrial carcinomas. Mixed epithelial and mesenchymal tumors of the uterus are rare with carcinosarcomas occurring more frequently than adenosarcomas. For prognosis of adenosarcomas the recognition of sarcomatous overgrowth is crucial. Carcinosarcomas are histologically heterogeneous although genetically clonal; biologically they are considered as undifferentiated carcinomas. There will be an increasing importance of molecular pathology for the classification of rare and unusual mesenchymal uterine tumors.

Machine Learning to Differentiate T2-Weighted Hyperintense Uterine Leiomyomas from Uterine Sarcomas by Utilizing Multiparametric Magnetic Resonance Quantitative Imaging Features

Uterine leiomyomas with high signal intensity on T2-weighted imaging (T2WI) can be difficult to distinguish from sarcomas. This study assessed the feasibility of using machine learning to differentiate uterine sarcomas from leiomyomas with high signal intensity on T2WI on multiparametric magnetic resonance imaging. This retrospective study included 80 patients (50 with benign leiomyoma and 30 with uterine sarcoma) who underwent pelvic 3 T magnetic resonance imaging examination for the evaluation of uterine myometrial smooth muscle masses with high signal intensity on T2WI. We used six machine learning techniques to develop prediction models based on 12 texture parameters on T1WI and T2WI, apparent diffusion coefficient maps, and contrast-enhanced T1WI, as well as tumor size and age. We calculated the areas under the curve (AUCs) using receiver-operating characteristic analysis for each model by 10-fold cross-validation and compared these to those for two board-certified radiologists. The eXtreme Gradient Boosting model gave the highest AUC (0.93), followed by the random forest, support vector machine, multilayer perceptron, k-nearest neighbors, and logistic regression models. Age was the most important factor for differentiation (leiomyoma 44.9 ± 11.1 years; sarcoma 58.9 ± 14.7 years; p < 0.001). The AUC for the eXtreme Gradient Boosting was significantly higher than those for both radiologists (0.93 vs 0.80 and 0.68, p = 0.03 and p < 0.001, respectively). Machine learning outperformed experienced radiologists in the differentiation of uterine sarcomas from leiomyomas with high signal intensity on T2WI.

A Benign Uterine Leiomyoma with Disturbing Appearance.

Herein, we described a 53-year-old woman who underwent laparoscopic uterine myomectomy. The cut surface of the leiomyoma showed a grain appearance, instead of a whorled feature. The disturbing appearance was an unexpected surprise to the surgeon. The diagnosis of benign uterine leiomyoma was established through intraoperative frozen section and was identical to the subsequent permanent pathology.

Uterine smooth muscle tumor of uncertain malignant potential

Uterine smooth muscle tumor of uncertain malignant potential (STUMP) are uterine neoplasms with mesenchymal characteristics between benign leiomyomas and malignant leiomyosarcomas. A 41-year-old patient sought the Gynecology and Obstetrics Service of the Federal University of the Triângulo Mineiro for parous myoma and severe anemia.The patient underwent abdominal hysterectomy and the anatomicopathologic results showed mild nuclear atypia, hypercellularity, and foci of necrosis, which confirmed the diagnosis of STUMP. The patient was followed up for 45 months without recurrence of the disease.

Smooth muscle tumors of uncertain malignant potential

To investigate microsatellite instability in smooth muscle tumors of uncertain malignant potential and to compare the results with clinical and morphological data. Histological and immunohistochemical studies were conducted in 26 patients aged 30-63 years (mean age, 37 years) with leiomyomatosis; which revealed intravenous leiomyomatosis in 20 cases, metastasizing leiomyoma in 2, disseminated peritoneal leiomyomatosis in 3, and smooth muscle tumor of uncertain malignant potential in 1 case. Microsatellite instability was studied by fragment analysis on a genetic analyzer using a test system of six markers: D10S1146, D10S218, D10S24, D10S1213, D3S1295, and D9S942. Microsatellite repeat changes characteristic of leiomyosarcomas (heterozygosity loss and/or microsatellite instability in at least one locus studied) were found in 6 patients; all were clinically and morphologically diagnosed as having intravenous leiomyomatosis. In 3 of these 6 cases, leiomyomatosis was accompanied by metastases to the lungs and spread to the peritoneum; heart damage was noted in 2 cases. The data analysis did not allow identification of any significant clinical and morphological criteria for this group. Leiomyomatosis is not a transitional form from benign leiomyoma to leiomyosarcoma, as evidenced by the difference in the status of molecular markers. Analysis of molecular genetic changes in DNA from tumor tissue samples cannot categorically clarify the nature of the disease by identifying the signs of genetic instability; however, there is a need for further accumulation of experience in studying tumors of this group and in identifying the possible association with disease prognosis.

Factors targeting MED12 to drive tumorigenesis?

Mediator Complex Subunit 12 (MED12) is part of the transcriptional preinitiation machinery. Mutations of its gene predominantly occur in two types of highly frequent benign tumors, uterine leiomyomas and fibroadenomas of the breast, where they apparently act as driver mutations. Nevertheless, their presence is not restricted to benign tumors having been found at considerable frequencies in uterine leiomyosarcomas, malignant phyllodes tumors, and chronic lymphocytic leukemia also. Most of the mutations are located within exon 2 of the gene but in rare cases the intron 1/exon 2 boundary or exon 1 are affected. As to their type, predominantly single nucleotide exchanges with a hotspot in one codon are found, but small deletions clustering around that hotspot also are not uncommon. These latter deletions are leaving the open reading frame intact. As to the types of mutations, so far no apparent differences between the tumor entities affected have emerged. Interestingly, this pattern with small deletions clustered around the hotspot of single nucleotide exchanges resembles that seen as a result of targeted gene editing. In contrast to other driver mutations the percentage of MED12-mutation positive tumors of independent clonal origin increases with the number of tumors per patient suggesting unknown etiological factors supporting site specific mutagenesis. These factors may act by inducing simultaneous site-specific double strand breaks the erroneous repair of which may lead to corresponding mutations. As inducers of DNA damage and its repair such as foreign nucleic acids of the microbiome displaying sequence homology to the putative target site might play a role. Interestingly, a 16 base pair homology of the hotspot to a putative terminator base-paired hairpin sequence of a Staphylococcus aureus tRNA gene cluster has been noted which might form R-loop like structures with its target sequence thus inducing said changes.