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Seminars in Reproductive Medicine Mar 2017Uterine fibroids, also known as uterine leiomyoma (UL), are monoclonal tumors of the smooth muscle tissue layer (myometrium) of the uterus. Although ULs are considered... (Review)
Review
Uterine fibroids, also known as uterine leiomyoma (UL), are monoclonal tumors of the smooth muscle tissue layer (myometrium) of the uterus. Although ULs are considered benign, uterine fibroids are the source of major quality-of-life issues for approximately 25% of all women, who suffer from clinically significant symptoms of UL. Despite the prevalence of UL, there is no treatment option for UL which is long term, cost-effective, and leaves fertility intact. The lack of understanding about the etiology of UL contributes to the scarcity of medical therapies available. Studies have identified an important role for sex steroid hormones in the pathogenesis of UL, and have driven the use of hormonal treatment for fibroids, with mixed results. Dysregulation of cell signaling pathways, miRNA expression, and cytogenetic abnormalities have also been implicated in UL etiology. Recent discoveries on the etiology of UL and the development of relevant genetically modified rodent models of UL have started to revitalize UL research. This review outlines the major characteristics of fibroids; major contributors to UL etiology, including steroid hormones; and available preclinical animal models for UL.
Topics: Animals; Biomarkers, Tumor; Disease Models, Animal; Female; Genetic Predisposition to Disease; Humans; Leiomyoma; Phenotype; Risk Factors; Signal Transduction; Uterine Neoplasms
PubMed: 28278535
DOI: 10.1055/s-0037-1599090 -
Science Advances Feb 2023Rhabdomyosarcoma (RMS) is a group of pediatric cancers with features of developing skeletal muscle. The cellular hierarchy and mechanisms leading to developmental arrest...
Rhabdomyosarcoma (RMS) is a group of pediatric cancers with features of developing skeletal muscle. The cellular hierarchy and mechanisms leading to developmental arrest remain elusive. Here, we combined single-cell RNA sequencing, mass cytometry, and high-content imaging to resolve intratumoral heterogeneity of patient-derived primary RMS cultures. We show that the aggressive alveolar RMS (aRMS) subtype contains plastic muscle stem-like cells and cycling progenitors that drive tumor growth, and a subpopulation of differentiated cells that lost its proliferative potential and correlates with better outcomes. While chemotherapy eliminates cycling progenitors, it enriches aRMS for muscle stem-like cells. We screened for drugs hijacking aRMS toward clinically favorable subpopulations and identified a combination of RAF and MEK inhibitors that potently induces myogenic differentiation and inhibits tumor growth. Overall, our work provides insights into the developmental states underlying aRMS aggressiveness, chemoresistance, and progression and identifies the RAS pathway as a promising therapeutic target.
Topics: Child; Humans; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma; Muscle, Skeletal; Cell Differentiation; Antineoplastic Agents; Cell Line, Tumor
PubMed: 36753540
DOI: 10.1126/sciadv.ade9238 -
Critical Reviews in Oncology/hematology Apr 2023Leiomyosarcoma (LMS) is a soft tissue sarcoma of smooth muscle origin that can arise in multiple anatomical sites and is broadly classified as extra-uterine LMS or... (Review)
Review
Leiomyosarcoma (LMS) is a soft tissue sarcoma of smooth muscle origin that can arise in multiple anatomical sites and is broadly classified as extra-uterine LMS or uterine LMS. There is substantial interpatient heterogeneity within this histological subtype, and despite multi-modal therapy, clinical management remains challenging with poor patient prognosis and few new therapies available. Here we discuss the current treatment landscape of LMS in both the localised and advanced disease setting. We further describe the latest advances in our evolving understanding of the genetics and biology of this group of heterogeneous diseases and summarise the key studies delineating the mechanisms of acquired and intrinsic chemotherapy resistance in this histological subtype. We conclude by providing a perspective on how novel targeted agents such as PARP inhibitors may usher in a new paradigm of biomarker-driven therapies that will ultimately impact the outcomes of patients with LMS.
Topics: Female; Humans; Leiomyosarcoma; Sarcoma; Antineoplastic Agents; Uterine Neoplasms; Biology
PubMed: 36893945
DOI: 10.1016/j.critrevonc.2023.103955 -
African Journal of Paediatric Surgery :... 2022Rhabdomyosarcoma (RMS) is one of the common malignant soft-tissue sarcomas affecting children. It originates from the embryonic mesenchyme precursor of striated muscle...
Rhabdomyosarcoma (RMS) is one of the common malignant soft-tissue sarcomas affecting children. It originates from the embryonic mesenchyme precursor of striated muscle and is frequently seen in the head-and-neck region, genitourinary system and extremities. Occasionally, it arises from the retroperitoneum, biliary tract and abdomen and is rarely seen in the sacrococcygeal area. A 4-month-male child presented with a nodule over the sacrum. Based on histopathology and immunohistochemical marker studies, a final diagnosis of RMS was rendered. There was no evidence of any teratomatous elements.
Topics: Child; Humans; Male; Rhabdomyosarcoma; Sacrococcygeal Region; Soft Tissue Neoplasms; Teratoma
PubMed: 36018208
DOI: 10.4103/ajps.ajps_69_21 -
Ear, Nose, & Throat Journal Sep 2021
Topics: Adolescent; Child; Female; Head and Neck Neoplasms; Humans; Male; Medical Illustration; Myofibroblasts; Neoplasms, Muscle Tissue; Young Adult
PubMed: 31760795
DOI: 10.1177/0145561319890165 -
Modern Pathology : An Official Journal... Jan 2018Mesenchymal tumors of the prostate are rare but often cause considerable diagnostic difficulty when encountered. These may be either benign or malignant and can arise... (Review)
Review
Mesenchymal tumors of the prostate are rare but often cause considerable diagnostic difficulty when encountered. These may be either benign or malignant and can arise within the prostate gland or in adjacent tissues. This review covers prostatic stromal proliferations (prostatic stromal tumor of uncertain malignant potential and stromal sarcoma), solitary fibrous tumor, myofibroblastic proliferations, smooth muscle neoplasms (leiomyoma and leiomyosarcoma), gastrointestinal stromal tumor, schwannoma, rhabdomyosarcoma, sarcomatoid carcinoma, postradiation sarcoma, and mixed epithelial stromal tumor of the seminal vesicle. Differential diagnostic considerations are emphasized, including descriptions of helpful histological and/or clinical clues and the use of adjuvant diagnostic techniques.
Topics: Diagnosis, Differential; Gastrointestinal Stromal Tumors; Humans; Male; Mesoderm; Neoplasms, Connective Tissue; Neurilemmoma; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Rhabdomyosarcoma; Smooth Muscle Tumor; Solitary Fibrous Tumors
PubMed: 29297486
DOI: 10.1038/modpathol.2017.155 -
BMJ Case Reports Nov 2014We report a case of synchronous, multicentric low-grade myofibroblastic sarcoma presenting in a 62-year-old man. He initially presented with inflammatory symmetric...
We report a case of synchronous, multicentric low-grade myofibroblastic sarcoma presenting in a 62-year-old man. He initially presented with inflammatory symmetric polyarthritis and adhesive capsulitis of his shoulder and hips bilaterally and did not respond to a trial of disease modifying antirheumatic drugs. Over a period of several years he developed progressive restriction of both knees and nodules on his hands, both knees and back. A biopsy of the nodule on his back was inconclusive and subsequent biopsies on his left and then right knee revealed a spindle cell neoplasm with an infiltrative growth pattern, mitotic figures, positive immunostaining for smooth muscle actin and focal myxoid change consistent with myofibroblastic sarcoma. While myofibroblastic sarcoma has been known to metastasise, to our knowledge, a multifocal presentation of this tumour has not been described previously.
Topics: Fibrosarcoma; Humans; Male; Middle Aged; Myofibroblasts; Myosarcoma; Neoplasm Recurrence, Local; Neoplasms, Muscle Tissue; Soft Tissue Neoplasms
PubMed: 25368122
DOI: 10.1136/bcr-2013-201666 -
Archives of Pathology & Laboratory... Aug 2022Rhabdomyosarcoma, the most common soft tissue sarcoma of children, is currently classified into the following 4 subtypes: embryonal rhabdomyosarcoma, alveolar... (Review)
Review
CONTEXT.—
Rhabdomyosarcoma, the most common soft tissue sarcoma of children, is currently classified into the following 4 subtypes: embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, spindle cell/sclerosing rhabdomyosarcoma, and pleomorphic rhabdomyosarcoma, based on recent molecular genetic knowledge and morphologic features.
OBJECTIVE.—
To highlight the most recent advances of molecular genetic alterations, and to familiarize pathologists with most recent genotype and phenotype correlation in rhabdomyosarcoma.
DATA SOURCES.—
Data were derived from the World Health Organization Classification of Soft Tissue and Bone Tumors, fifth edition, recently published literature (PubMed), and clinical practice experience.
CONCLUSIONS.—
Current classification has been significantly impacted by genotype and phenotype correlation, especially with PAX-FOXO1 fusion-positive rhabdomyosarcoma versus fusion-negative rhabdomyosarcoma, and with the emergence of 3 distinct new subtypes of spindle cell/sclerosing rhabdomyosarcoma. Although all rhabdomyosarcomas were considered a single diagnostic entity in the past, they are now considered to be a group of histologically similar but biologically diverse entities because their clinical behavior and underlying molecular alterations dramatically differ. This review outlines recent molecular genetic developments, corresponding morphologic features, and current challenges faced by pathologists in daily practice.
Topics: Humans; Mutation; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Soft Tissue Neoplasms; World Health Organization
PubMed: 35051261
DOI: 10.5858/arpa.2021-0183-RA -
Advances in Clinical and Experimental... Oct 2023Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and represents a high-grade neoplasm of skeletal myoblast-like cells. About 40% of all... (Review)
Review
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and represents a high-grade neoplasm of skeletal myoblast-like cells. About 40% of all registered soft tissue tumors are RMSs. This paper describes our current understanding of the RMS subtypes (alveolar (ARMS), embryonic (ERMS), pleomorphic (PRMS), and spindle cell/sclerosing (s/scRMS)), diagnostic methods, molecular bases, and characteristics. We also present the currently used treatment methods and the potential use of natural substances in the treatment of this type of cancer. Natural cytotoxic substances are compounds that have been the subject of numerous studies and discussions in recent years. Since anti-cancer therapies are often limited by a low therapeutic index and cancer resistance to pharmacotherapy, it is very important to search for new, effective compounds. Additionally, compounds of a natural origin are usually readily available and have a reduced cytotoxicity. Thus, the undiscovered potential of natural anti-cancer compounds makes this field of research a very important area. The introduction of model species into research examining the use of natural cytostatic therapies for RMS will allow for further assessment of the effects of these compounds on cancerous and healthy tissues.
Topics: Child; Humans; Cytostatic Agents; Rhabdomyosarcoma; Sarcoma; Soft Tissue Neoplasms
PubMed: 36920267
DOI: 10.17219/acem/161165 -
Advances in Respiratory Medicine 2018Inflammatory myofibroblastic tumors (IMT) of the lung, first reported in 1939, are considered a subset of inflammatory pseudo -tumors. They are a distinctive lesions... (Review)
Review
Inflammatory myofibroblastic tumors (IMT) of the lung, first reported in 1939, are considered a subset of inflammatory pseudo -tumors. They are a distinctive lesions composed of myofibroblastic spindle cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils. IMTs may be benign, invade surrounding structures, undergo malignant transformation, recur or may even metastasize. They can occur due to a genetic mutation or can occur secondary to infectious or autoimmune diseases. Patients may be asymptomatic, or present with cough, hemoptysis, dyspnea, pleuritic pain, constitutional symptoms or pneumonia. In this article we review the pathophysiology, genetics, clinical presentation, imaging findings of IMT of the lung. We also discuss the various surgical and non-surgical treatment options and the prognosis associated with this disease.
Topics: Cough; Diagnosis, Differential; Humans; Lung Neoplasms; Myofibroblasts; Neoplasms, Muscle Tissue; Pneumonia; Rare Diseases
PubMed: 29490419
DOI: 10.5603/ARM.2018.0007