RESUMO
Uterine leiomyomas, or fibroids, are the most common benign tumours of the female genital tract. Although uterine fibroids are commonly associated with menorrhagia, dysmenorrhea, symptomatic anaemia, urinary or bowel symptoms and infertility, intra-abdominal haemorrhage is an exceedingly rare complication. Often, the diagnosis is poorly recognizable based on the patient's clinical presentation and alternative diagnoses such as ruptured ectopic pregnancy, ruptured ovarian cyst or perforated viscus are frequently considered. Herein, we describe a case of a 50-year-old perimenopausal woman who presented with acute, lower abdominal pain, evolving anaemia, hypovolaemic shock and haemoperitoneum with no discernable source. Emergency exploratory laparotomy confirmed the source of massive haemoperitoneum arising from a ruptured blood vessel supplying a large subserosal uterine leiomyoma and the patient subsequently underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Given the paucity of publications on this clinical entity, the aim of this report is to highlight a rare complication of uterine leiomyomas, its pathophysiological spectrum and its relevance to emergency physicians, general surgeons and gynaecologists.
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Leiomyomas are the most common solid benign uterine neoplasms; they are usually asymptomatic and are identified incidentally. Yet, responsive to stimulation by estrogens, leiomyomas may expand, potentially outgrowing their blood supply to undergo hemorrhage, fibrosis, calcification, and atrophy. These pathologic mechanisms commonly lead to leiomyomas degeneration, i.e., red, hyaline, cystic, or myxoid. Magnetic resonance (MR) imaging is the most accurate imaging technique for the characterization of leiomyomas. In cases of degeneration, variable features on T2-weighted and contrast-enhanced images can be found. With no recent radiologic pathologic correlation literature available on this matter, herewith, we provide computed tomography (CT)/MR imaging along with histopathological specimens of two young women who were diagnosed with hyaline or hyaline and cyst degeneration of uterine leiomyomas at our university hospital. We report on the imaging features of uterine leiomyomas using CT and MR imaging and discuss the available literature on imaging signs that may be suggestive of hyaline or cyst degeneration using either of the imaging examination methods.
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Leiomyomas (LMs) are the most frequent uterine benign tumors, representing the leading cause of hysterectomy indications worldwide. They are highly associated with women's reproductive complications, and endocrine disruptors may influence their etiology. In this sense, air pollution represents a relevant hormonal disruptor that acts on key signaling pathways, resulting in tumor development and infertility. Our goal was to evaluate submucosal LM samples from patients living in the metropolitan and Sao Paulo city regions, focusing on genes involved in tumor development and infertility features. Twenty-four patients were selected based on their region of residence and clinical information availability. Several genes were differentially expressed between women living in metropolitan areas and Sao Paulo city. Significant associations were observed between BCL-2, DVL1, FGFR3, and WNT5b downregulation and contraceptive use in the samples from women living in Sao Paulo city. ESR1 and HHAT downregulation was associated with ethnicity. WNT5b and GREM were associated with LM treatment and related pathologies, respectively. In the samples from women living in other cities of the metropolitan region, abortion occurrence was associated with BMP4 upregulation. Although further studies may be necessary, our results showed that air pollution exposure influences the expression of genes related to LM development and female reproductive features.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Infertilidade , Leiomioma , Gravidez , Humanos , Feminino , Cidades , Brasil/epidemiologia , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Transcriptoma , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Leiomioma/etiologia , Leiomioma/genéticaRESUMO
Background: Fibroid is the most prevalent benign tumor of the female genital tract. Intravenous and intracardiac leiomyomatosis (IVL and ICLM, respectively) are rare complications that present with symptoms of pulmonary thromboembolism and heart failure and whose etiology, despite controversial, is a direct vascular invasion by a primary uterine leiomyoma. Case presentation: We present the case of a 31-year-old female patient with a previous history of pelvic pain and dysmenorrhea, whose ultrasound showed an enlarged and heterogeneous uterus. Complete hysterectomy was performed, and the anatomopathological examination showed leiomyomas without evidence of malignancy. One month later, the patient manifested dyspnea and chest pain. A neoplastic thrombus was identified, extending from the inferior vena cava to the right atrium, for which we proceeded with cavo-atrial thrombectomy under Normothermic Cardiopulmonary Bypass (CPB) with Warm Blood Cardioplegia (WBC). A metastatic lung injury of non-malignant histology was also detected. Discussion: Uterine leiomyoma is a very common benign tumor of the female genital tract. IVL with ICLM are rare and difficult-to-treat complications, whose etiology is a direct vascular invasion by a primary uterine leiomyoma, although it is still controversial. The incidence of ICLM is 10 to 30% of IVL cases. The main symptoms of ICLM are dyspnea, syncope, edema of the lower extremities and palpitations. Treatment is based on complete surgical removal of the tumor thrombus. Studies demonstrated that the one-stage procedure is safer from the patient's perspective and that CPB with WBC reduced intraoperative blood loss and total operative time, ensuring a less traumatic postoperative. Conclusions: Most patients with uterine leiomyoma are asymptomatic and acute complications are rare. In ICLM clinical manifestations are related to heart failure and flow obstruction. Because of the severity of the condition and the curative potential of treatment, surgery is morbid but highly recommended. The use of CPB with WBC improved the postoperative period and increased the patient's quality of life.
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The present narrative review is aimed to rekindle discussion regarding whether and how uterine leiomyoma and pregnancy may impact each other. Although fibroids are hormone-dependent lesions, their growth during pregnancy seems to have a nonlinear trend. Besides placental estrogens and progesterone, an array of endocrine and paracrine factors affect fibroid blood supply, growth rate, and risk of degeneration along the gestational and puerperal periods. According to current evidence, the presence of leiomyomas might increase the risk of some adverse pregnancy outcomes. Although a causative relation between fibroids and spontaneous abortion is questionable, the presence of multiple submucosal lesions in certain populations, such as infertile women, may increase the risk of pregnancy loss. Slightly increased risks of placenta previa, placental abruption and fetal malpresentation may occur, mainly due to the mechanical influence of multiple and large fibroids. Cesarean section and preterm birth rates are also probably increased in the presence of fibroids. The risk associations are based on meta-analyses of cohort studies (level of evidence 2a), retrospective cohort studies (2b), case-control (3a), and cross-sectional studies (3b), but with a predominantly low risk of bias. For evaluating the growth pattern of leiomyomas and their real influence on obstetric outcomes, future studies should enroll women with fibroids diagnosed prior to pregnancy and follow them prospectively throughout the gestation and puerperium.
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Aborto Espontâneo , Infertilidade Feminina , Leiomioma , Complicações Neoplásicas na Gravidez , Nascimento Prematuro , Neoplasias Uterinas , Cesárea/efeitos adversos , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Infertilidade Feminina/etiologia , Leiomioma/patologia , Placenta/patologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: Angiotensin-converting-enzyme 2 (ACE2), the cell surface receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is found in a variety of reproductive tissues. The present study evaluated whether uterine fibroids and normal myometrium express ACE2 and, if so, at which tissue compartments. METHODS: We included 13 premenopausal women (age range 33-50 years, median 40 years) with uterine fibroids undergoing elective hysterectomy or myomectomy. Samples of leiomyoma (n = 12) and normal myometrial tissue (n = 8) were analyzed by immunohistochemistry for protein localization or by real time PCR for mRNA detection. RESULTS: In normal myometrium, ACE2 immunoreactivity was localized in smooth muscle fibers, arteriolar walls, and endothelial cells. In uterine leiomyoma, ACE2 staining was more intense in smooth muscle cells than in the extracellular matrix, and was also present in vascular endothelium. ACE2 mRNA was detected in myometrium as well as in fibroid samples. CONCLUSION: Human myometrium and uterine leiomyoma express ACE2 mRNA and have abundant distribution of ACE2 protein in their smooth muscle cells and microvasculature.
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Abstract Uterine leiomyoma is themost prevalent benign type of gynecological tumor. It affects more than 80% of women worldwide and, within this group, more than 50% may be asymptomatic. However, large fibroid volumes may be associated with symptoms of extrinsic compression, and most of the cases do not present atypical cells. We present the case of a 49-year-old woman who underwent a total abdominal hysterectomy of a 13.5-kg uterine leiomyoma with no malignancies at histopathology and review the literature about giant uterine leiomyomas and their clinical repercussion. We concluded that large volumes do not always pose a threat regarding malignancy; however, future molecular studies are needed to investigate giant uterine fibroids.
Resumo Leiomioma uterino é o tumor benigno ginecológico de maior prevalência. Ele afeta mais de 80% das mulheres no mundo e, deste grupo, mais de 50% podem ser assintomáticas. Contudo, miomas de grande volume podem ser associados com sintomas de compressão extrínseca, e a maioria dos casos não apresentam células atípicas. Nós apresentamos o caso de uma mulher de 49 anos que foi submetida a histerectomia total abdominal de um espécime de 13,5 quilos sem malignidades ao exame histopatológico. Também revisamos a literatura sobre leiomiomas uterinos de grande volume e sua repercussão clínica. Concluímos que grandes volumes nem sempre representam um risco relacionado à malignidade; contudo, estudos moleculares futuros são necessários para investigar leiomiomas uterinos gigantes.
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Humanos , Feminino , Neoplasias Uterinas/diagnóstico , Leiomioma/diagnóstico , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/patologia , Histerectomia , Leiomioma/cirurgia , Leiomioma/patologia , Pessoa de Meia-IdadeRESUMO
Extraintestinal pathogenic Escherichia coli (ExPEC) is a highly diverse pathotype of E. coli which colonizes the intestine, and it is considered an important etiological agent associated with bacteremia and other systemic infections, among them urinary tract infection. Retrospective studies evaluating morbidity and mortality of nondomestic felids have demonstrated that urinary tract diseases are among the main causes of death for geriatric animals. Also, mesenchymal neoplasms of the uterus are common in wild felids, and they possess variable morphologic characteristics related to invasiveness and malignancy. This report describes a case of bilateral pyelonephritis due to extraintestinal uropathogenic E. coli infection in a captive jaguar (Panthera onca). The diagnosis was confirmed through pathological, bacterial and immunohistochemical findings. According to molecular analysis, this E. coli strain was classified in the phylogroup F, possessing the following virulence-associated genes: usp, cnf-1, hlyA, papC and sfa. Additionally, this E. coli was highly resistant to beta-lactams and first-generation cephalosporin. This jaguar also presented a uterine leiomyoma with distinct distribution, and severe degenerative articular disease, both of them described as frequently seen lesions in geriatric animals from the Panthera genus.(AU)
Escherichia coli extraintestinal patogênica (ExPEC) é um patotipo altamente diverso de E. coli que coloniza o intestino e é considerada um agente etiológico importante, associado com bacteremia e outras infecções sistêmicas, dentre elas infecções do trato urinário. Estudos retrospectivos avaliando morbidade e mortalidade de felídeos não domésticos demostram que doenças do trato urinário estão entre as principais causas de morte de animais geriátricos. Ainda, neoplasias mesenquimais uterinas são comuns em felídeos de cativeiro e possuem características morfológicas variáveis relacionadas a invasividade e malignidade. Neste relato é descrito um caso de pielonefrite bilateral por E. coli extraintestinal uropatogênica em uma onça-pintada de cativeiro (Panthera onca). O diagnóstico foi confirmado através dos achados patológicos, bacteriológicos e imuno-histoquímicos. A partir da análise molecular, esta cepa de E. coli foi classificada no filogrupo F, possuindo os seguintes genes associados a virulência: usp, cnf-1, hlyA, papC and sfa. Adicionalmente, a bactéria isolada foi altamente resistente a ß-lactâmicos e cefalosporinas de primeira geração. Foi observado ainda um leiomioma uterino com distribuição distinta e doença articular degenerativa severa, ambas descritas na literatura como comumente observadas em animais geriátricos do gênero Panthera.(AU)
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Animais , Feminino , Pielonefrite/etiologia , Neoplasias Uterinas/veterinária , Panthera , Infecções por Escherichia coli/veterinária , Escherichia coli Extraintestinal Patogênica , Leiomioma/veterinária , Animais de ZoológicoRESUMO
OBJECTIVE: Despite the high prevalence of uterine fibroids, the psychosocial impact of fibroids has not been evaluated across different quality of life indicators and compared with other chronic conditions. Here, we rigorously analyzed available evidence pertaining to the psychosocial burden of uterine fibroids in premenopausal women and compared validated quality of life and symptom scores before and after treatment. DATA SOURCES: We searched PubMed, PsycINFO, ClinicalTrials.gov, Embase, and Cochrane Library for publications from January 1990 to January 2020. STUDY ELIGIBILITY CRITERIA: We considered English-language publications that evaluated the association between uterine fibroids diagnosed by imaging studies in premenopausal women and quality of life by standardized and validated questionnaires at baseline and after treatment. We used a detailed list of terms related to quality of life, questionnaires, and uterine fibroids to conduct the search. METHODS: Three reviewers screened titles and abstracts and then obtained full-text articles for further analysis. The reviewers assessed risk of bias using established Cochrane and Newcastle-Ottawa Scale guidelines. The quality of life scores of premenopausal women with fibroids were reviewed at baseline and compared with those of published quality of life scores in other disease populations in addition to after fibroid treatment. RESULTS: A total of 57 studies were included in the review: 18 randomized controlled trials and 39 observational studies. Of note, the 36-Item Short Form Survey and European Quality of Life Five-Dimension Scale questionnaires both indicated a diagnosis of uterine fibroids to have a disability score that was similar to or exceeded (was a greater psychosocial stressor) a diagnosis of heart disease, diabetes mellitus, or breast cancer. Quality of life scores were lower at baseline than after treatment in all instruments measuring these variables in women with uterine fibroids, indicating significantly impaired psychosocial functioning. Uterine fibroids were associated with significant patient-reported health disabilities related to bodily pain, mental health, social functioning, and satisfaction with sex life. CONCLUSION: A diagnosis of uterine fibroids was a significant psychosocial stressor among women at baseline and relative to other diseases. Validated quality of life instruments indicated therapeutic success and the improvement of both physical and emotional symptoms after treatment.
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Leiomioma/psicologia , Saúde Mental , Qualidade de Vida , Saúde Sexual , Participação Social , Neoplasias Uterinas/psicologia , Contraceptivos Hormonais/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Histerectomia , Leiomioma/fisiopatologia , Leiomioma/terapia , Pré-Menopausa , Embolização da Artéria Uterina , Miomectomia Uterina , Neoplasias Uterinas/fisiopatologia , Neoplasias Uterinas/terapiaRESUMO
BACKGROUND: Uterine leiomyoma has been reported to be a worse problematic disease for African American than Caucasian women in the US. Data are almost non-existent for other populations of African ancestry. Our aim was to investigate the hypothesis of an equivalent influence of ethnicity on uterine leiomyomas for women of a French African-Caribbean population. BASIC PROCEDURES: Retrospective analysis of hysterectomies performed from 2010 to 2015 at the teaching hospital of Guadeloupe (French West Indies), where most inhabitants are of West African origin, was carried out. Data of the 899 hysterectomies, including those for malignancy, were collected, in particular, uterine weight. MAIN FINDINGS: The indications were leiomyoma in 66.5 % of cases and leiomyomas were found in 91 % of all cases. The mean age and uterine weight were 51.7 years and 464 g for the entire population, 50.2 years and 488 g for the population without malignancies, and 47.0 years and 567 g for the population with leiomyomas. PRINCIPAL CONCLUSIONS: The data were compared to those reported in the literature for several populations, notably African Americans and Caucasians in the US and mainland France. This comparison supports the hypothesis that Guadeloupean women, an African-Caribbean population, have characteristics in terms of uterine leiomyoma that are close to those of African Americans. Although confirmation is required, these results highlight the need for specific research, therapeutic approaches, and improved early management of these populations.
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Negro ou Afro-Americano/etnologia , Histerectomia , Leiomioma/etnologia , Leiomioma/cirurgia , Neoplasias Uterinas/etnologia , Neoplasias Uterinas/cirurgia , Adulto , África/etnologia , Região do Caribe/etnologia , Feminino , França/etnologia , Guadalupe/etnologia , Humanos , Estudos Retrospectivos , Estados Unidos/etnologia , População Branca/etnologiaRESUMO
ABSTRACT: Extraintestinal pathogenic Escherichia coli (ExPEC) is a highly diverse pathotype of E. coli which colonizes the intestine, and it is considered an important etiological agent associated with bacteremia and other systemic infections, among them urinary tract infection. Retrospective studies evaluating morbidity and mortality of nondomestic felids have demonstrated that urinary tract diseases are among the main causes of death for geriatric animals. Also, mesenchymal neoplasms of the uterus are common in wild felids, and they possess variable morphologic characteristics related to invasiveness and malignancy. This report describes a case of bilateral pyelonephritis due to extraintestinal uropathogenic E. coli infection in a captive jaguar (Panthera onca). The diagnosis was confirmed through pathological, bacterial and immunohistochemical findings. According to molecular analysis, this E. coli strain was classified in the phylogroup F, possessing the following virulence-associated genes: usp, cnf-1, hlyA, papC and sfa. Additionally, this E. coli was highly resistant to -lactams and first-generation cephalosporin. This jaguar also presented a uterine leiomyoma with distinct distribution, and severe degenerative articular disease, both of them described as frequently seen lesions in geriatric animals from the Panthera genus.
RESUMO: Escherichia coli extraintestinal patogênica (ExPEC) é um patotipo altamente diverso de E. coli que coloniza o intestino e é considerada um agente etiológico importante, associado com bacteremia e outras infecções sistêmicas, dentre elas infecções do trato urinário. Estudos retrospectivos avaliando morbidade e mortalidade de felídeos não domésticos demostram que doenças do trato urinário estão entre as principais causas de morte de animais geriátricos. Ainda, neoplasias mesenquimais uterinas são comuns em felídeos de cativeiro e possuem características morfológicas variáveis relacionadas a invasividade e malignidade. Neste relato é descrito um caso de pielonefrite bilateral por E. coli extraintestinal uropatogênica em uma onça-pintada de cativeiro (Panthera onca). O diagnóstico foi confirmado através dos achados patológicos, bacteriológicos e imuno-histoquímicos. A partir da análise molecular, esta cepa de E. coli foi classificada no filogrupo F, possuindo os seguintes genes associados a virulência: usp, cnf-1, hlyA, papC and sfa. Adicionalmente, a bactéria isolada foi altamente resistente a -lactâmicos e cefalosporinas de primeira geração. Foi observado ainda um leiomioma uterino com distribuição distinta e doença articular degenerativa severa, ambas descritas na literatura como comumente observadas em animais geriátricos do gênero Panthera.
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Resumen ANTECEDENTES: Los leiomiomas uterinos son los tumores benignos ginecológicos más frecuentes en las mujeres en edad reproductiva; por tanto, son extremadamente raros en las adolescentes (menos de 1%) y solo se encuentran reportes de caso en la bibliografía. CASO CLÍNICO: Paciente de 16 años, con tumor suprapúbico de rápido crecimiento, acompañado de dolor abdominal generalizado, enviada a la unidad médica con diagnóstico de miomatosis uterina para descartar su malignidad. El ultrasonido pélvico reportó múltiples lesiones hipoecoicas diseminadas en el miometrio, similares a metástasis. La tomografía abdomino-pélvica informó hepatomegalia, a expensas del lóbulo izquierdo y leiomiomas intramurales de medianos y grandes elementos; los marcadores tumorales se encontraron en límites normales. En la laparotomía se encontró una tumoración interligamentaria izquierda de 25 cm; el estudio histopatológico reportó: leiomioma uterino de patrón histológico convencional. CONCLUSIONES: El cuadro clínico de los leiomiomas en adolescentes representa un reto clínico por la edad, signos, síntomas y necesidad de preservación de la función reproductiva, aspectos decisivos a la hora de decidir el tratamiento.
Abstract BACKGROUND: The uterine leiomyomas are the most common gynecological benign tumors in fertile females; however, they are very rare in adolescents (less than 1%) and there are only a few reports in the literature. CLINICAL CASE: A 16-year-old patient with a fast-growing suprapubic tumor, accompanied by generalized abdominal pain, sent to the hospital with diagnosis of pelvic tumor probable uterine miomatosis, to rule out malignant tumor. Pelvic ultrasound was performed with a report of multiple disseminated hypoechoic lesions in myometrium giving appearance of metastasis, without being the characteristic images of myomas, pelvic abdominal tomography reported hepatomegaly of the left lobe, intramural leiomyomas of medium and large elements, tumor markers within normal limits. The laparotomy was performed, left intraligamentary myoma of giant elements was located; and the histopathological study reported uterine leiomyoma of conventional histological pattern. CONCLUSIONS: The clinical of leiomyomas in adolescent patients represents a challenge for the gynecologist. The age, symptomatology, and preservation of reproductive function are important aspects to decide the therapeutic regimen.
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Introducción: El síndrome de Meigs consiste en la asociación de tumor benigno de ovario tipo fibroma con ascitis e hidrotórax, que se resuelven tras la extirpación del tumor. El síndrome de pseudo-Meigs secundario al leiomioma uterino es una entidad rara. Presentación de caso: Mujer de 68 años que presentó una historia de un mes con sensación de opresión torácica y disnea. La radiografía de tórax reveló derrame pleural derecho. En la tomografía axial computarizada de abdomen y región pelviana se aprecia ascitis y un gran mioma uterino subseroso. Se sometió a una histerectomía abdominal total con salpingo-ooforectomía bilateral. Conclusiones: La ascitis y el derrame pleural desaparecieron rápidamente en el postoperatorio. Tras 20 meses de seguimiento, no hay recidiva de la enfermedad(AU)
Introduction: Meigs syndrome consists of the association of a benign tumor of the ovary "fibroma type" with ascites and hydrothorax, which resolve after the tumor is removed. The pseudo-Meigs syndrome secondary to uterine leiomyoma is a rare entity. Case report: A 68-year-old woman refered having a month with a sensation of chest tightness and dyspnea. Chest X-ray revealed right pleural effusion. Computed axial tomography of the abdomen and pelvic region shows ascites and a large subserous uterine myoma. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Conclusions: Ascites and pleural effusion disappeared rapidly in the postoperative period. After 20 months of follow-up, there is no recurrence(AU)
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Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Uterinas/diagnóstico por imagem , Leiomioma/diagnóstico por imagem , Síndrome de Meigs/diagnóstico , Síndrome de Meigs/epidemiologiaRESUMO
The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.
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Animais , Feminino , Ratos , Neoplasias Uterinas/tratamento farmacológico , Extratos Vegetais/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Curcuma/química , Rizoma/química , Leiomioma/tratamento farmacológico , Fatores de Transcrição , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Radioimunoensaio , Ratos Sprague-Dawley , Análise de Sequência com Séries de Oligonucleotídeos , Modelos Animais de Doenças , Leiomioma/genética , Leiomioma/metabolismoRESUMO
PURPOSE: Pulmonary benign metastasizing leiomyoma (PBML), a rare condition of smooth muscle tumor, originates from women with a history of uterine leiomyoma (LM). Numerous genetic studies of uterine LM have been reported; however, there are few cytogenetic and molecular descriptions of PBML. Therefore, molecular subtyping is necessary to understand the pathogenesis of metastasizing sites. METHODS: Driver gene exon-capture sequencing was performed on one patient's peripheral blood, paraffin samples from primary uterine LM, and lung metastasizing leiomyoma 8 years later. RESULTS: The results showed that the same missense mutations of BLMH, LRP2, MED12, SMAD2, and UGT1A8 were concurrently mutated in the primary uterine LM and the PBML. Moreover, a splice mutation of PTEN (c.492+1G>A) was uniquely identified in the lung metastasis of the patient. CONCLUSION: This study indicates that the metastatic lung lesions were derived from the same malignant cell clone of uterine LMs and later acquired the novel driver mutations in the evolution of the tumor. In addition, driver gene sequencing can discriminate somatic driver mutations as biological indicators of potential malignant leiomyoma and can identify pathogenic variation driver mutations, which could be used for individualized therapy.
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Biomarcadores Tumorais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leiomioma/patologia , Neoplasias Pulmonares/secundário , Mutação , Neoplasias Uterinas/patologia , Feminino , Testes Genéticos , Humanos , Leiomioma/genética , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Prognóstico , Neoplasias Uterinas/genéticaRESUMO
Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium. Compared to myometrium, uterine leiomyoma cells showed an increase in PRT mRNA expression when treated with E2, and increase in PRB mRNA expression when treated with E2 and P4. Treatment with mifepristone had no significant impact on mRNA expression in these cells. The HDAC activity was higher in uterine leiomyoma compared to myometrial cells after treatment with E2 and E2 + P4 + mifepristone. HAT activity was barely detectable. Our results suggest that ovarian steroid hormones modulate PR, and mifepristone was unable to decrease PRT and PRB mRNA. The higher activity of HDAC leiomyoma cells could be involved in transcriptional repression of genes implicated in normal myometrium cell function, contributing to the maintenance and growth of uterine leiomyoma.
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Estrogênios/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Leiomioma/metabolismo , Miométrio/efeitos dos fármacos , Progestinas/farmacologia , Receptores de Progesterona/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Células Cultivadas , Estradiol/metabolismo , Estradiol/farmacologia , Estrogênios/metabolismo , Feminino , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Antagonistas de Hormônios/farmacologia , Humanos , Leiomioma/enzimologia , Leiomioma/patologia , Pessoa de Meia-Idade , Mifepristona/farmacologia , Miométrio/citologia , Miométrio/metabolismo , Miométrio/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Progesterona/metabolismo , Progesterona/farmacologia , Progestinas/metabolismo , Receptores de Progesterona/genética , Células Tumorais Cultivadas , Neoplasias Uterinas/enzimologia , Neoplasias Uterinas/patologiaRESUMO
MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. They play a key role in several biological processes. Their abnormal expression may lead to malignant cell transformation. This study aimed to evaluate the expression profile of 84 miRNAs involved in tumorigenesis in immortalized cells of myometrium (MM), uterine leiomyoma (ULM), and uterine leiomyosarcoma (ULMS). Specific cell lines were cultured and qRT-PCR was performed. Thirteen miRNAs presented different expression profiles in ULM and the same thirteen in ULMS compared to MM. Eight miRNAs were overexpressed, and five were underexpressed in ULM. In ULMS cells, five miRNAs exhibited an overexpression and eight were down-regulated. Six miRNAs (miR-1-3p, miR-130b-3p, miR-140-5p, miR-202-3p, miR-205-5p, and miR-7-5p) presented a similar expression pattern in cell lines compared to patient samples. Of these, only three miRNAs showed significant expression in ULM (miR-1-3p, miR-140-5p, and miR-7-5p) and ULMS (miR-1-3p, miR-202-3p, and miR-7-5p). Our preliminary approach identified 24 oncomirs with an altered expression profile in ULM and ULMS cells. We identified four differentially expressed miRNAs with the same profile when compared with patients' samples, which strongly interacted with relevant genes, including apoptosis regulator (BCL2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), insulin like growth factor 1 receptor (IGF1R),serine/threonine kinase (RAF1), receptor tyrosine kinase (MET), and bHLH transcription factor (MYCN). This led to alterations in their mRNA-target.
Assuntos
Perfilação da Expressão Gênica , Leiomiossarcoma/genética , MicroRNAs/genética , Neoplasias Uterinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Análise por Conglomerados , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-IdadeRESUMO
Abstract Introduction Intravenous leiomyomatosis is a benign and rare condition that can result in cardiac events with fatal outcomes when left untreated. Intravenous leiomyomatosis is probably underestimated because the diagnosis is easily missed. We present a case of an intravenous leiomyomatosis without extra-pelvic involvement, with a brief review of this pathology. Case Report 46-year-old woman submitted to hysterectomy and bilateral adnexectomy because of a pelvic mass detected in ultrasound. During the surgery, intravenous leiomyomatosis diagnosis was suspected. Pathological analysis confirmed this suspicion. Further imaging exams were performed without detecting any anomalies related to this condition. The patient remained with no evidence of disease after one year of follow-up. Conclusion Intravenous leiomyomatosis is a rare condition that can lead to serious complications. Early diagnosis followed by an appropriate treatment is very important to patient outcome, and underdiagnoses can be counteracted if the gynecologist is aware of this entity.
Resumo Introdução A leiomiomatose intravenosa é uma condição benigna, rara, que pode resultar em eventos cardíacos, podendo ser fatal quando não tratada. Esta patologia está provavelmente subestimada, uma vez que facilmente não é diagnosticada. Neste artigo, apresentamos um caso de leiomiomatose intravenosa sem envolvimento extrapélvico, com uma breve revisão da patologia. Relato de Caso Mulher de 46 anos de idade, submetida a histerectomia e anexectomia bilateral após detecção ecográfica de massa pélvica. Durante a cirurgia, houve a suspeita de leiomiomatose intravenosa, e o exame anátomo-patológico confirmou o diagnóstico. A paciente foi submetida a outros exames de imagem, não sendo detectada qualquer anomalia relacionada com a patologia. Após um ano de followup, a paciente manteve-se sem evidência de doença. Conclusão A leiomiomatose intravenosa é uma condição rara que pode levar a complicações graves. O diagnóstico precoce e o tratamento adequado são muito importantes para o prognóstico da paciente, e os subdiagnósticos podem ser evitados se o ginecologista estiver ciente dessa entidade.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Leiomiomatose , Ovário/irrigação sanguínea , Útero/irrigação sanguínea , Neoplasias Vasculares , Leiomiomatose/patologia , Leiomiomatose/cirurgia , Neoplasias Vasculares/patologia , Neoplasias Vasculares/cirurgiaRESUMO
Uterine leiomyoma (UL) is the most commonly occurring benign tumor that affects women of reproductive ages. Studies strongly suggest that ULs are hormonally dependent and that genes acting in estrogen metabolism might be involved in their development. The focus of this case-control study was to determine whether the Leucine432Valine single-nucleotide polymorphism (SNP) in the gene encoding cytochrome P450 1B1 (CYP1B1) was associated with an increased risk of UL in Black Barbadian women. The investigation comprised 37 women clinically diagnosed with UL and 52 controls. The CYP1B1 Leu432Val polymorphism (Leu/Val) was analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. The homozygous Valine432 variant (Val/Val) was predominant in both cases and controls for this population (89 and 83 %, respectively). The odds ratio for risk of developing the disease was 1.33, but this was not statistically significant. We discuss a possible protective function for CYP1B1 based on the high prevalence of this mutant SNP and its lack of association with UL.