Smooth Muscle Tumors Research Articles

Leiomyoma of the prostate: A case report and literature review.

Prostate leiomyoma is a rare condition globally, often challenging to diagnose preoperatively, with most cases being definitively identified through postoperative pathology. This benign tumor generally has a good prognosis and is primarily treated with transurethral resection of the prostate in clinical settings. However, there are no established guidelines or therapeutic protocols for managing this disease. The patient was admitted to our hospital's Department of Urology with complaints of hematuria, urinary frequency, and urgency for 1 month. Pelvic computed tomography revealed an irregular, mass-like high-density shadow posterior to the bladder, indistinctly separated from the prostate. The patient had been diagnosed with renal insufficiency during a physical examination 4 years prior but had not received standardized treatment. Six years ago, the patient underwent electrocision of the prostate at our hospital, and postoperative pathology indicated prostate leiomyoma. Postoperative pathology confirmed a diagnosis of prostate leiomyoma. The patient presented with an enlarged prostate and preoperative hematuria. Holmium laser enucleation of the prostate (HoLEP) was performed. The Foley catheter was removed on the second postoperative day, and the patient was discharged 3 days after surgery. Following discharge, the patient was instructed to undergo reexaminations every 6 months. Current follow-up indicates the patient is in good health, with no recurrence of the mass observed. Prostate leiomyoma is an extremely rare condition, and the current primary approach for managing prostate smooth muscle tumors involves active patient monitoring, regular evaluations, and timely surgical intervention if clinical symptoms emerge. In this study, we present a new case report of prostatic smooth muscle tumor and review the existing literature to explore treatment options for prostate leiomyoma within this field.

The impact and correlation of lymphadenectomy with outcomes in patients with uterine sarcoma: A systematic review

Background: Sarcomas are an uncommon type of smooth muscle tumors in the uterus. The most popular form of treatment for uterine sarcomas is surgery. There is disagreement, nonetheless, over the best course of action for initial surgery. The aim of this systematic review was to examine the potential association between patient outcomes and the effects of LAD in individuals diagnosed with uterine sarcoma. Method: We conducted a comprehensive search of the PubMed database to identify publications assessing the impact of LAD on patients with uterine sarcoma that were published between 2009 and 2024. Based on the references in the studies that we included, we also conducted a search of the PubMed database. To find more relevant studies, the bibliographies of each pertinent paper were thoroughly reviewed. This review only includes studies that were published in English. Results: We included 7 papers in this systematic review, totaling 7896 patients. Four publications examined ESS, four studies examined LMS, two articles examined adenosarcoma, one study examined carcinosarcoma, and one study examined rhabdomyosarcoma. For individuals with low-grade ESS or adenosarcoma, LAD was not linked to a better prognosis. The survival rate was lower for patients with leiomyosarcoma who had LAD. Those who had LAD and had high-grade undifferentiated ESS fared better. LAD did not significantly correlate with RFS or OS in uterine sarcoma patients. Conclusion: Resection of lymph nodes or LAD has minimal potential benefit in terms of prognosis and clinical value.

Challenges Associated with Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) Management—A Case Report with Comprehensive Literature Review

Background: Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a poorly studied neoplasm that does not fulfill the definition of either leiomyoma or leiomyosarcoma. STUMP symptoms are indistinguishable from those of benign lesions; it has no specific biochemical markers or ultrasound presentations. The management of this type of tumor is particularly challenging due to significant heterogeneity in its behavior and the lack of clear guidelines; moreover, the lesion may recur after excision. Case Report: We report on a case of a 42-year-old patient diagnosed with a STUMP. The preliminary diagnosis was a submucous leiomyoma, which was removed hysteroscopically due to menorrhagia resulting in anemia. The histopathological examination of the resected myoma pointed to the diagnosis of STUMP. The hysterectomy was performed as the patient had completed her reproductive plans. There were no complications. The patient is currently recurrence-free after a 9-month follow-up. Discussion and Conclusions: The care of a patient diagnosed with STUMP requires a personalized approach and the cooperation of various medical disciplines, including molecular diagnostics, imaging techniques, and minimally invasive surgery. Management of STUMP must consider the patient’s plans for childbearing. All cases of tumors with “uncertain malignant potential” are a challenge in the context of patient-physician communication.

Smooth Muscle Tumor of Uncertain Malignant Potential: An Unexpected Diagnosis in a Young Female

Smooth Muscle Tumor of Uncertain Malignant Potential: An Unexpected Diagnosis in a Young Female

SUCCESSFUL CONCEPTION AND FIRST PREGNANCY IN A 28-YEAR-OLD WOMAN WITH CERVICAL UTERINE MYOMA AND TOTAL PLACENTA PREVIA: A CASE REPORT

Background: Placenta previa is a major pregnancy complication associated with life-threatening hemorrhage. Cervical Uterine Myomas, benign smooth muscle tumors, increase the risk of placenta previa by two to three times, contributing to adverse pregnancy outcomes such as infection, urinary retention, preterm labor, and bleeding. Understanding the interaction between Cervical Uterine Myomas and placenta previa is crucial for optimizing care in high-risk pregnancies and improving maternal and fetal outcomes. Case Description: A 28-year-old primigravida (G1P0A0) patient was diagnosed with a breech presentation, Cervical Uterine Myoma, and total placenta previa at Klungkung Regional Hospital. The patient had a regular menstrual cycle and no history of comorbid conditions. The patient's management includes hospitalization with strict bed rest, followed by a scheduled elective cesarean section (CS). Fluid therapy will be administered using Ringer's lactate, and preoperative prophylactic antibiotics will be provided. Discussion: Cervical Uterine Myoma, particularly cervical myomas, can significantly impact pregnancy outcomes, with a prevalence of 1.6% to 10.7%. These fibroids, particularly large ones, increase the risk of placenta previa, a condition where the placenta partially or completely covers the cervix. The combination presents significant risks for both the obstetrician and the patient, including urinary retention, myoma degeneration, preterm labor, obstructed labor, and postpartum hemorrhage. Careful surgical planning and management strategies are crucial. Conclusion: A 28-year-old primigravida with breech presentation, Cervical Uterine Myoma, and total placenta previa was admitted after three days of abdominal pain and scheduled for an elective cesarean section at 36 weeks. The cesarean successfully delivered a healthy male infant, and a 10 x 10 cm cervical myoma was identified without complications. Postoperatively, the patient had a normal recovery with well-healing surgical wounds and was discharged in stable condition with appropriate medications.

Solitary fibrous tumor of the stomach

Abstract Introduction/Objective Solitary fibrous tumor (SFT) is an uncommon fibroblastic tumor that originates from the mesenchymal tissue. It has been rarely reported within the stomach. None of these reported tumors have occurred in a background of autoimmune atrophic gastritis as was seen in our patient. Methods/Case Report Case report Results (if a Case Study enter NA) An 85-year-old female with history of anemia and autoimmune atrophic gastritis presented with two-month history of dysphagia and abdominal discomfort. Upper gastrointestinal endoscopy showed a 1 cm subepithelial lesion in the gastric body along the greater curvature. Upper endoscopic ultrasound showed mildly hypoechoic lesion in the submucosa of the stomach with the differential of leiomyoma, neuroendocrine tumor, gastrointestinal stromal tumor, and an atypical looking lipoma. The entire gastric lesion was lifted with submucosal saline injection and then resected using cap endoscopic mucosal resection (EMR) snare cautery. Gross examination showed a well-circumscribed lesion with firm, tan-white cut surface. On microscopy, a bland appearing spindle cell proliferation within a collagenous stroma was seen with alternating hypercellular and hypocellular areas and few dilated vessels. No significant mitosis, nuclear pleomorphism or necrosis was identified. Immunohistochemical stains were performed and the lesional cells were positive for STAT6. Markers for gastrointestinal stromal tumor (CD117, DOG1), smooth muscle tumor (desmin, smooth muscle actin) and schwannoma (S100, SOX10) were negative. Nuclear staining for STAT6 is a sensitive and specific marker for SFTs. This particular SFT was considered to be of low risk and non-malignant considering its small size, lack of mitotic activity and tumor necrosis. The etiology for SFT is not entirely clear but molecular studies have shown that the NAB2::STAT6 translocation in a spindle cell neoplasm is a diagnostic hallmark for SFTs. Conclusion Solitary fibrous tumors have been rarely reported within the stomach. Complete surgical resection with negative margins is the mainstay of treatment as they may recur after an incomplete resection.

Leiomyoma with bizarre nuclei occurring post hysterectomy mimicking malignancy: a rare case report

Abstract Introduction/Objective Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, represents a rare subtype of benign uterine smooth muscle neoplasm. Histologically, it is characterized by significant cytological atypia in a typical leiomyoma background with rare mitoses and without tumor necrosis. Methods/Case Report We report a case of a 48-year-old woman, status post hysterectomy for symptomatic fibroids, with imaging showing multiple contiguous pelvic masses extending from the pelvis to the upper abdomen and displacing the colon laterally and small bowel posteriorly. The findings were highly suspicious for ovarian malignancy. A bilateral salpingo-oophorectomy and a partial colectomy were performed with tumor debulking and omentectomy. Grossly, multiple well-circumscribed soft masses ranging in size from 1.5-16 cm, in contiguity with pericolonic mesentery with a smooth fleshy cut surface and cystic changes were found. Bilateral ovaries were unremarkable. Microscopically the larger masses were composed of spindle cells with bizarre nuclei throughout, while smaller masses showed foci of bizarrely shaped-spindle cells with bizarre nuclei in a background of a typical leiomyoma. Mono- and multinucleated cells with smudged chromatin were also seen. The mitotic index was low confirmed with a low Ki-67 proliferation index (< 5%). Immunohistochemical stainings showed that the neoplastic cells were positive for desmin, SMA, and caldesmon; and negative for CD10, with a wild type p53 expression. Fumarate hydratase immunostain was retained. MDM2 amplification was not detected by FISH. The morphology and immunohistochemical findings were compatible with LBN. Results (if a Case Study enter NA) NA Conclusion In summary, this is a rare and challenging case of multiple LBN developed years post hysterectomy and clinically mimicking a malignancy.

A Case Report of Inflammatory Myofibroblastic Tumor Mimicking Leiomyosarcoma of the Uterus

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare entity that presents significant diagnostic challenges due to its infrequency and has the potential for being misdiagnosed as a leiomyoma, endometrial stromal tumor, or myxoid leiomyosarcoma, resulting in undertreatment or overtreatment. Methods/Case Report We present a case report of a 50-year-old woman with a history of anemia due to heavy menstruation caused by fibroids, who underwent hysterectomy. The concurrent pelvic wash cytology raised suspicious for myxoid leiomyosarcoma. Results (if a Case Study enter NA) Macroscopic examination revealed both well and poorly circumscribed nodules, ranging upto 4.7 cm in maximum dimension. Cut surfaces exhibited a spectrum of appearances, including tan-pink, whorled and rubbery, as well as soft, hemorrhagic, edematous, and mucinous areas with necrosis. Microscopically, the tumor exhibited myxoid spindle cell proliferation, in the background of lymphoplasmacytic inflammatory infiltrates. She was diagnosed with IMT metastasis to left fallopian tube, ovary, and omentum. Immunohistochemical (IHC) analysis further confirmed the diagnosis, showing strong and diffuse cytoplasmic positivity for ALK (anaplastic lymphoma kinase), caldesmon, and smooth muscle actin. This case underscores the critical importance of accurate diagnosis in guiding appropriate treatment strategies. Moreover, given the morphological overlap with other uterine tumors, the identification of ALK rearrangement emerges as a pivotal diagnostic marker, distinguishing IMT from its mimics such as leiomyoma, leiomyosarcoma and smooth muscle tumor of uncertain malignant potential (STUMP). Enhancing our understanding of the histomorphological features and ALK immunostaining of uterine IMT is essential for optimizing patient management and outcomes. Conclusion IMT in the female genital tract can mimic other more common benign and malignant tumors like leiomyoma, leiomyosarcoma, and endometrial stromal sarcoma. Familiarity with clinical and histologic features and the use of ALK immunostaining can be critical for correct diagnosis.

Leiomyomas of the Gastrointestinal Tract: A Clinicopathologic Review

Abstract Introduction/Objective Leiomyomas are benign smooth muscle tumors that can be found anywhere along the gastrointestinal tract (GIT). We undertook a retrospective study to investigate the incidence of GIT leiomyomas and to gain better understanding of their clinicopathologic characteristics. Methods/Case Report The surgical pathology files at our institution were searched for GIT leiomyomas encountered between 07/1994 and 12/2023. The clinical and histopathological findings were recorded. Results (if a Case Study enter NA) 74 leiomyomas were identified in various GIT locations, including esophagus (8), stomach (20), duodenum (3), colon (37) and rectum (6). There were 40 females and 34 males, with an average age of 61.5 years. Esophageal leiomyomas showed a mean size of 2.2 cm. 5/8 patients had synchronous adenocarcinomas of gastroesophageal junction and 1/8 patient had synchronous squamous cell carcinoma of esophagus. Gastric leiomyomas showed a mean size of 2.0 cm. 6/20 patients had synchronous and 4/20 patients had metachronous GIT cancers. 2/6 patients who had leiomyomas with synchronous GIT cancers also presented with gastrointestinal stromal tumors (GIST). Duodenal leiomyomas showed a mean size of 0.7 cm. 1/3 patient had synchronous pancreatic adenocarcinoma. Colonic leiomyomas showed a mean tumor size of 0.6 cm. 2/37 patients had synchronous and 6/37 patients had metachronous GIT cancers. Rectal leiomyomas showed a mean tumor size of 0.9 cm. 1/6 patient had metachronous non-GIT sarcoma. Adenomatous polyps coexisted with 10/37 colonic leiomyomas, 2/6 rectal leiomyomas and 1/20 gastric leiomyoma. Immunohistochemical stains (αSMA, Desmin, CD117, DOG-1, CD34) were consistently utilized in diagnosis to exclude GIST. Conclusion Leiomyomas were most frequently found in the colon (50.0%), followed by the stomach (27.0%). Esophageal and gastric leiomyomas showed larger sizes (averaged 2.2 and 2.0 cm respectively) than duodenal, colonic, and rectal counterparts (averaged 0.7, 0.6, and 1 cm, respectively). This suggests an association between tumor locations and clinical features. Synchronous malignancies occurred in 20.2% of cases, mainly gastroesophageal/colonic adenocarcinomas. Metachronous malignancies were noted in 14.8% of cases. Given the high incidence of synchronous/metachronous malignancies (35.1%) in the gastrointestinal tract, close clinical surveillance is warranted for these patients.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Fifteen lesions (3-42mm) were identified, predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AML contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four AL contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included ulceration, thrombosis, inflammation, myxoid change, senescent nuclei, and extramedullary hematopoiesis; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin, desmin, and/or caldesmon) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AML. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

Uterine mesenchymal tumours harboring the KAT6B/A::KANSL1 gene fusion represent a distinct type of uterine sarcoma based on DNA methylation profiles.

Uterine mesenchymal tumours harboring KAT6B/A::KANSL1 gene fusions typically exhibit histological and immunophenotypic overlap with endometrial stromal and smooth muscle tumours. To date it remains uncertain whether such neoplasms should be regarded as variants of smooth muscle or endometrial stromal neoplasm, or if they constitute a distinct tumour type. In this study we investigated DNA methylation patterns and copy number variations (CNVs) in a series of uterine tumours harboring KAT6B/A::KANSL1 gene fusions in comparison to other mesenchymal neoplasms of the gynecological tract. Unsupervised hierarchical clustering and t-SNE analysis of DNA methylation data (Illumina EPIC array) identified a distinct cluster for 8/13 KAT6B/A::KANSL1 tumours (herein referred to as core cluster). The other 5 tumours (herein referred to as outliers) did not assign to the core cluster but clustered near various other tumour types. CNV analysis did not identify significant alterations in the core cluster. In contrast, various alterations, including deletions at the CDKN2A/B and NF1 loci were identified in the outlier group. Analysis of the DNA methylation clusters in relation to histological features revealed that while tumours in the core KAT6B/A::KANSL1 cluster were histologically bland, outlier tumours frequently exhibited "high-grade" histologic features in the form of significant nuclear atypia, increased mitotic activity and necrosis. Three of the five patients with outlier tumours died from their disease while clinical follow-up in the remaining two patients was limited (less than 12months). In comparison, none of the 7 out of 8 patients with tumors in the core KAT6B/A::KANSL1 sarcoma cluster, where follow-up was available, died from disease. Furthermore, only 1 out of 7 patients recurred (mean follow-up of 30months). In conclusion, KAT6B/A::KANSL1 uterine sarcoma is a molecularly unique type of uterine tumour that should be recognized as a distinct entity. These tumors typically exhibit low-grade histologic features but are occasionally morphologically high-grade; the latter have a DNA methylation profile different from the typical low-grade neoplasms and may be associated with aggressive behaviour.

7908 GPNMB Promotes Tumor Growth And Is A Biomarker For Lymphangioleiomyomatosis (LAM)

Abstract Disclosure: E. Gibbons: None. M. Taya: None. H. Wu: None. S. Lopa: None. J. Moss: None. E.P. Henske: None. F.X. McCormack: None. S.R. Hammes: None. Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB’s unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here we establish that GPNMB regulates TSC2-null tumor cell invasion as well as TSC2-null xenograft tumor growth, and that GPNMB expression is dependent on mTORC1 signaling. Further, we show that GPNMB’s ectodomain is released from the cell surface of TSC2-null cells by ADAM10 and 17 proteases, and we identify the protease target sequence on GPNMB. In fact, mutating this cleavage sequence so that the GPNMB ectodomain can no longer be shed results in cessation of TSC2-null tumor growth. Finally, we demonstrate that GPNMB’s ectodomain is present at higher levels in LAM patient serum compared to healthy controls, and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker. Presentation: 6/3/2024

7908 GPNMB Promotes Tumor Growth and is a Biomarker for Lymphangioleiomyomatosis (LAM)

Abstract Disclosure: E. Gibbons: None. M. Taya: None. H. Wu: None. S. Lopa: None. J. Moss: None. E.P. Henske: None. F.X. McCormack: None. S.R. Hammes: None. Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB’s unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here we establish that GPNMB regulates TSC2-null tumor cell invasion as well as TSC2-null xenograft tumor growth, and that GPNMB expression is dependent on mTORC1 signaling. Further, we show that GPNMB’s ectodomain is released from the cell surface of TSC2-null cells by ADAM10 and 17 proteases, and we identify the protease target sequence on GPNMB. In fact, mutating this cleavage sequence so that the GPNMB ectodomain can no longer be shed results in cessation of TSC2-null tumor growth. Finally, we demonstrate that GPNMB’s ectodomain is present at higher levels in LAM patient serum compared to healthy controls, and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker. Presentation: 6/3/2024

9308 GPNMB Promotes Tumor Growth And Is A Biomarker For Lymphangioleiomyomatosis (LAM)

Abstract Disclosure: E. Gibbons: None. M. Taya: None. H. Wu: None. S. Lopa: None. J. Moss: None. E.P. Henske: None. F.X. McCormack: None. S.R. Hammes: None. Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB’s unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here we establish that GPNMB regulates TSC2-null tumor cell invasion as well as TSC2-null xenograft tumor growth, and that GPNMB expression is dependent on mTORC1 signaling. Further, we show that GPNMB’s ectodomain is released from the cell surface of TSC2-null cells by ADAM10 and 17 proteases, and we identify the protease target sequence on GPNMB. In fact, mutating this cleavage sequence so that the GPNMB ectodomain can no longer be shed results in cessation of TSC2-null tumor growth. Finally, we demonstrate that GPNMB’s ectodomain is present at higher levels in LAM patient serum compared to healthy controls, and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker. Presentation: 6/3/2024

Tumeurs mésenchymateuses utérines associées à translocation : du nouveau sans oublier l’ancien. Une approche diagnostique intégrée

This review focuses on uterine mesenchymal tumors that are defined on a molecular level by a single and unique genetic alteration, that is somehow necessary and sufficient to allow tumor growth and progression. Although diverse from a clinical, morphological and immunohistochemical point of view, the different entities we are going to talk about share both a simple genomic profile with a low number of chromosomal alterations observed by CGH Array (few deletions, gains or amplifications...) and a low mutational burden observed by sequencing technics. Some of these entities are already well known and described in the literature when found outside of the uterus and gynecological tract. It remains intriguing that uterine mesenchymal pathology has been lagging behind when compared to its extrauterine counterpart. How can we explain that when it comes to inflammatory myofibroblastic tumors, abundant numbers of articles have been published since the 70's, but it was only in the early 2000s that the first relevant descriptions of this tumor in the uterus emerged? Certainly, the increased accuracy, availability, and use of molecular biology technics and in particular RNA sequencing in the area of uterine pathology can partly explain the reduction of the gap between soft tissue and uterine pathology we currently observe. Other reasons explaining this gap may be the high prevalence of smooth muscle tumors in the uterus and the abounding diversity of their morphological aspects, which may have partly eclipsed the array of differential diagnoses. Last but not least, one can hypothesize that the relative "simplicity" of hysterectomy procedures, referring to their safety and accessibility, has cured most of the lesions and partly clouded our knowledge regarding the biological potential and natural history of these newly described entities. As a consequence of this situation, our reader will often encounter the wording "uncertain malignant potential", as for some of these rare entities, evidence to establish reliable prognostic variables is still insufficient. We hope this review to be a useful tool to guide pathologists through the diversity and complexity of uterine mesenchymal tumors. As a scientific and medical community, sharing this knowledge will help us to collectively raise our vigilance and awareness by expanding the array of our differential diagnoses. We hope this will lead to more cases being accurately diagnosed, and ultimately, to a deeper knowledge regarding the biological potential and clinical evolution of these tumors. From a therapeutical point of view, the consequences of an accurate diagnosis for the patient are already appreciable through the use of targeted therapy. Examples include: ALK inhibitors in inflammatory myofibroblastic tumor, tyrosine-kinase inhibitors in COL1A::PDGFB rearranged sarcomas or mTOR inhibitors in PEComa.

Intravenous leiomyomatosis: A rare case report

Introduction: Intravascular leiomyomatosis (IVL) is a rare histological benign tumor without invading the tissue of the venous vessels themselves. It is characterized by continuous intraluminal growth of benign smooth muscle tumor cells along with the uterine vein to the pelvic and abdominal venous systems, including the iliac vein and inferior vena cava, and even to the right atrium of the heart and pulmonary artery, leading to life-threatening complications. This case report describes a 43-year-old female patient with IVL who underwent four myomectomy surgeries. Case Report: A 43-year-old female patient with rare IVL was admitted after four myomectomy surgeries. After preoperative evaluation by color Doppler ultrasound, cardiac ultrasound, chest and abdominal computed tomography (CT) scans, this patient underwent total hysterectomy, bilateral salpingectomy, and complete resection of the entire intravascular leiomyoma. This article discusses the characteristics, diagnosis, treatment, and especially surgical precautions of IVL. In addition to surgical resection, this article also discusses other treatment options for IVL. Conclusion: Intravascular leiomyomatosis has unique biological characteristics and clinical manifestations. Through accurate diagnosis and timely complete tumor resection, as well as regular follow-up after surgery, most IVL patients can achieve good long-term prognosis and quality of life. However, further research is needed on the etiology and pathogenesis of IVL.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Fifteen lesions (3 to 42 mm) were identified predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AMLs contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four ALs contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included surface ulceration, vascular thrombosis, chronic inflammation, and myxoid change; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin and/or desmin) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AMLs. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Systematic Review of the Literature in the Last 20 Years.

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.

Epstein-Barr virus-associated post-transplant smooth muscle tumours in a kidney transplant patient.

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.

Immunohistochemical Expression of Lymphoid Enhancer-binding Factor 1 in Low-grade Endometrial Stromal Tumors.

Endometrial stromal tumors (ESTs) are uncommon uterine mesenchymal lesions. Nuclear expression of β-catenin, an indication of activated Wnt/β-catenin signaling pathway, was described in 50% to 92% of low-grade ESTs, including endometrial stromal nodule and low-grade endometrial stromal sarcoma. Activation of the Wnt/β-catenin signaling pathway leads to the translocation of β-catenin into the nucleus and interaction with the T-cell factor/lymphoid enhancer-binding factor-1 (LEF1) family of transcription factors to regulate cell proliferation, differentiation, migration, and survival. Immunohistochemical analysis of β-catenin and LEF1 was performed in 2 endometrial stromal nodules and 20 low-grade endometrial stromal sarcomas and demonstrated 90.9% and 81.8% positive rates for β-catenin and LEF1, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of β-catenin and LEF1 were 90.9% versus 81.8%, 81.0% versus 85.7%, 83.3% versus 85.7%, 89.5% versus 81.8%, respectively, in the diagnosis of low-grade ESTs. There is no statistical significance of the performance of β-catenin and LEF1 in all ESTs ( P = 0.664) or in primary or metastatic/recurrent settings ( P = 0.515 and 0.999, respectively). Only 3 smooth muscle tumors showed focal and weak positivity for LEF1. Our results indicate LEF1 can be a useful marker in aiding a diagnosis of low-grade EST and differentiating from smooth muscle tumors alone or in combination with β-catenin.