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Concept: Myometrium

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Purpose: Imaging features and clinical characteristics of degenerated leiomyoma in patients referred for uterine fibroid embolization (UFE) were analyzed to assess the incidence of degenerated leiomyoma. Materials and Methods: Patients referred for UFE between 2008 and 2009 were retrospectively analyzed (n=276). Patients ranged in age from 27 to 51 years (mean 38.0 years). All patients underwent screening MRI with contrast enhancement. Medical histories and clinical symptoms were evaluated. Results: Among the 276 patients who underwent MRI, 14 (5.1%) showed degenerated leiomyomas. Symptoms were abdominal pain (n=4, 26.7%), menorrhagia (n=5, 35.7%) and bulk-related symptoms (n=5, 35.7%) and no symptoms (n=5, 35.7%). Of the 14 patients with degenerated leiomyomas, 5 (42.9%) had a history of pregnancy in the past two years. For T1-weighted imaging (T1WI), a high signal intensity (SI) of the leiomyoma was the most common finding (n=9, 64.3%) and a hyperintense rim (n=4, 28.6%) was the second most common. On T2-weighted imaging (T2WI), a low SI of the leiomyoma was found in six patients (42.9%), a high SI in four (28.6%) and a heterogeneous SI in four (28.6%) patients. Conservative management was performed in 11 (78.6%) patients, surgery in 3 (21.4%) and uterine artery embolization in one (7.1%) patient. Conclusion: The incidence of degeneration of leiomyoma in patients referred for UFE was 5.1%. Patients presented with variable clinical symptoms with or without a history of pregnancy. MR imaging showed a high SI on T1WI and various SIs on T2WI without contrast enhancement. An understanding of the degeneration of leiomyomata is essential when considering UFE.

Concepts: Uterus, Anatomical pathology, Radiology, Gynecology, Uterine fibroids, Leiomyoma, Myometrium, Uterine artery embolization

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Five samples of human midterm fetal uterus and fallopian tube (four donor bodies) were used to assess whether or not processes of angiogenesis are guided by endothelial tip cells (ETCs), and if cytokine-receptors, such as CD117/c-kit and PDGFR-α, are expressed in the microenvironment of the endothelial tubes. CD34 labeled microvessels in the uterine wall (myometrium and endometrium) and in the wall of the uterine (fallopian) tube, and accurately identified ETCs in both organs. We conclude that sprouting angiogenesis in the developing human female tract is guided by ETCs. Moreover, CD117/c-kit antibodies labeled mural networks of pericytes, α-SMA-positive and desmin-negative, related to the endometrial (but not myometrial) microvessels, and similar labeling was identified in the wall of the uterine tube. PDGFR-α positive labeling, stromal and pericytary, was also found. Thus, sprouting angiogenesis in human fetal genital organs appears to be guided by tip cells and is influenced by tyrosine kinase receptor signaling.

Concepts: Signal transduction, Embryo, Uterus, Endometrium, Fallopian tube, Myometrium

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Adenomyosis is a common benign uterine pathology that is defined by the presence of islands of ectopic endometrial tissue within the myometrium. It is asymptomatic in one third of cases, but when there are clinical signs they remain non-specific. It can often be misdiagnosed on sonography as it may be taken to be multiple uterine leiomyomata or endometrial thickening, both of which have a different prognosis and treatment. Adenomyosis is often associated with hormone-dependent pelvic lesions (myoma, endometriosis, or endometrial hyperplasia). It is less commonly connected to infertility or obstetrical complications and indeed any direct relationship remains controversial. The purpose of imaging is to make the diagnosis, to determine the extent of spread (focal or diffuse, superficial or deep adenomyosis, adenomyoma), and to check whether there is any associated disease, in particular endometriosis. The aim of this article is to provide assistance in recognising adenomyosis on imaging and to identify the pathologies that are commonly associated with it in order to guide the therapeutic management of symptomatic patients. Pelvic ultrasonography is the first line investigation. Sonohysterography can assist with diagnosis in some cases (pseudothickening of the endometrium seen on sonography). MRI may be used in addition to sonography to back up the diagnosis and to look for any associated disease.

Concepts: Pregnancy, Uterus, Medical diagnosis, Gynecology, Endometrium, Endometriosis, Adenomyosis, Myometrium

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Context:Uterine leiomyomas (fibroids or myomas) are benign tumors of the uterus and are clinically apparent in up to 25% of reproductive-age women. Heavy or abnormal uterine bleeding, pelvic pain or pressure, infertility, and recurrent pregnancy loss are generally associated with leiomyoma. Although surgical and radiological therapies are frequently used for the management of this tumor, medical therapies are considered the first-line treatment of leiomyoma.Evidence Acquisition and Synthesis:A review was conducted of electronic and print data comprising both original and review articles on pathophysiology and medical treatments of uterine leiomyoma retrieved from the PubMed or Google Scholar database up to June 2012. These resources were integrated with the authors' knowledge of the field.Conclusion:To date, several pathogenetic factors such as genetic factors, epigenetic factors, estrogens, progesterone, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in leiomyoma development and growth. On the basis of current hypotheses, several medical therapies have been investigated. GnRH agonist has been approved by US Food and Drug Administration for reducing fibroid volume and related symptoms. In addition, the FDA also approved an intrauterine device, levonorgestrel-releasing intrauterine system (Mirena), for additional use to treat heavy menstrual bleeding in intrauterine device users only. Currently, mifepristone, asoprisnil, ulipristal acetate, and epigallocatechin gallate have been shown to be effective for fibroid regression and symptomatic improvement which are all in clinical trial. In addition, some synthetic and natural compounds as well as growth factor inhibitors are now under laboratory investigation, and they could serve as future therapeutic options.

Concepts: Immune system, Medicine, Pregnancy, Uterus, Hormonal contraception, Endometrium, Progesterone, Myometrium

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The objective of this study was to analyze the clinical and pathologic factors in patients with uterine serous carcinoma confined to the endometrium. A total of 236 uterine serous carcinoma patients from the pathology databases of 4 large academic institutions were included in the study. Clinical and pathologic variables were analyzed, including patient demographics, tumor size (≤2 vs. >2 cm), myometrial invasion, lymphovascular invasion, lymph node status, tumor location (endometrium vs. polyp), cervical involvement, lower uterine segment involvement, FIGO stage, pelvic washings, recurrence, overall survival, and progression-free survival. Of 236 patients, 55 (23%) had tumors limited to the endometrium. Forty-four patients (80%) had Stage IA tumors. The tumor was confined to a polyp in 17 (30.9%) patients. Twenty patients (36.4%) had tumor sizes >2 cm and 12 (21.8%) exhibited lymphovascular invasion. Only 3 patients (5.4 %) had cervical stromal involvement. Thirty-three (66%) patients underwent pelvic and para-aortic lymphadenectomy with 2 positive para-aortic lymph nodes identified. Seven (12.7%) patients had positive washings, whereas 8 patients (14.5 %) had disease recurrence. At a median follow-up of 46 months, there was no difference in overall survival (P=0.216) or progression-free survival (P=0.063) between patients with tumors confined to a polyp, patients with tumors confined to the endometrium, and patients with tumors present in both polyp and the endometrium. Uterine serous carcinoma with only endometrial involvement, even when confined to a polyp, can be associated with poor prognosis, further stressing the importance of complete surgical staging and adjuvant treatment in this setting.

Concepts: Cancer, Lymph node, Endometrium, Lymph, Myometrium, Paraaortic lymph node

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The human uterus is composed of the endometrial lining and the myometrium. The endometrium, in particular the functionalis layer, regenerates and regresses with each menstrual cycle under hormonal control. A mouse xenograft model has been developed in which the functional changes of the endometrium are reproduced. The myometrium possesses similar plasticity, critical to permit the changes connected with uterine expansion and involution associated with pregnancy. Regeneration and remodeling in the uterus are likely achieved through endometrial and myometrial stem cell systems. Putative stem/progenitor cells in humans and rodents recently have been identified, isolated and characterized. Their roles in endometrial physiology and pathophysiology are presently under study. These stem/progenitor cells ultimately may provide a novel means by which to produce tissues and organs in vitro and in vivo.

Concepts: Pregnancy, Embryo, Uterus, Menopause, Menstrual cycle, Endometrium, Menstruation, Myometrium

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The human uterus mainly consists of two layers: an inner endometrium and an outer layer, the myometrium, made of smooth muscle. The uterus is characterized by its unique capacity for regeneration. This capacity permits cyclical regeneration and remodeling of the tissue over the course of a woman’s reproductive life. During each menstrual cycle, the endometrium regenerates, and the uterus enlarges to make room for fetal growth. This cyclic physiologic pattern suggests that myometrial stem/progenitor cells are present in the tissue and play a role in myometrial functions. Our group (and others) recently characterized and isolated putative stem/progenitor cells in the myometrium. These findings are permitting a better understanding of myometrial physiology and pathology. We review current studies of myometrial stem/progenitor cells and suggestions that, in combination with hypoxia, these cells may contribute to uterine remodeling during pregnancy and the formation of myomas.

Concepts: Pregnancy, Embryo, Uterus, Menopause, Menstrual cycle, Female reproductive system, Endometrium, Myometrium

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Fibroids or myomas involve large proportion of women of reproductive age. The myoma formation starts from the transformation of the myometrium, causing the progressive formation of a pseudocapsule, which is made of compressed muscle fibers. Numerous studies investigated on myoma pseudocapsule anatomy, discovering many neurotransmitters and neuropeptides, as a neurovascular bundle, influencing myometrial physiology. These substances have a positive impact on wound healing and muscular restoring, also playing a role in sexual and reproductive function. Based on investigations, a distinct surgical technique evolved, called “intracapsular myomectomy”, meaning myoma removal from its pseudocapsule, which enables protection of the myoma pseudocapsule, containing neuropeptides and neurofibers involved in physiological myometrial healing. This technique, performed by a gentle myoma enucleating by stretching from myometrium and sparing pseudocapsule, reduces surgical trauma caused by iatrogenic myoma pseudocapsule damage. Intracapsular myomectomy meets the basic surgical anatomy principle: myoma is removed by a bloodless, precise and careful dissection sparing myometrium, as much as possible. The rationale of intracapsular myomectomy should be applied to all myoma removals; therefore, it has been used for both laparoscopic and laparotomic myomectomy, as well as for cesarean myomectomy. Scientific research is still seeks to clarify some reports of myomas with infertility, especially in the case of intramural myomas, but it is clear that in the case of performing myomectomy, it must do by the described intracapsular technique. This enables myometrial preservation, especially peripherally to myoma bed, promoting myometrial healing after myoma removal.

Concepts: Medicine, Wound healing, Uterus, Physiology, Surgery, Muscle, Leiomyoma, Myometrium

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Background Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. Methods We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. Results Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. Conclusions Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. (Funded by the Academy of Finland Center of Excellence program and others.).

Concepts: Gene, Cancer, Oncology, Anatomical pathology, Benign tumor, Tumor, Leiomyoma, Myometrium

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Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome secondary to germline fumarate hydratase (FH) mutation presents with cutaneous and uterine leiomyomas, and a distinctive aggressive renal carcinoma. Identification of HLRCC patients presenting first with uterine leiomyomas may allow early intervention for renal carcinoma. We reviewed the morphology and immunohistochemical (IHC) findings in patients with uterine leiomyomas and confirmed or presumed HLRCC. IHC was also performed on a tissue microarray of unselected uterine leiomyomas and leiomyosarcomas. FH-deficient leiomyomas underwent Sanger and massively parallel sequencing on formalin-fixed paraffin-embedded tissue. All 5 patients with HLRCC had at least 1 FH-deficient leiomyoma: defined as completely negative FH staining with positive internal controls. One percent (12/1152) of unselected uterine leiomyomas but 0 of 88 leiomyosarcomas were FH deficient. FH-deficient leiomyoma patients were younger (42.7 vs. 48.8 y, P=0.024) and commonly demonstrated a distinctive hemangiopericytomatous vasculature. Other features reported to be associated with FH-deficient leiomyomas (hypercellularity, nuclear atypia, inclusion-like nucleoli, stromal edema) were inconstantly present. Somatic FH mutations were identified in 6 of 10 informative unselected FH-deficient leiomyomas. None of these mutations were found in the germline. We conclude that, while the great majority of patients with HLRCC will have FH-deficient leiomyomas, 1% of all uterine leiomyomas are FH deficient usually due to somatic inactivation. Although IHC screening for FH may have a role in confirming patients at high risk for hereditary disease before genetic testing, prospective identification of FH-deficient leiomyomas is of limited clinical benefit in screening unselected patients because of the relatively high incidence of somatic mutations.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Concepts: Genetics, Cancer, Mutation, Renin, Renal cell carcinoma, Leiomyoma, Myometrium, Creative Commons