Characterization of the Pathogenesis of Lymphangioleiomyomatosis (LAM)

淋巴管平滑肌瘤病 (LAM) 发病机制的特征

• 批准号: 8557920
• 负责人: Joel Moss
• 金额: $ 317.45万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8557920
• 关键词: Abdomen; Affect; African; Angiomyolipoma; Antigens; Appearance; Area; Benign; Biological Markers; Biological Process; Biopsy; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Cell Count; Cell Proliferation; Cell Size; Cells; Chest; Clinical; Computing Methodologies; Cyst; Cystic Lesion; Data; Diagnosis; Diagnostic; Disease; Disease Progression; Disease susceptibility; Entropy; Evaluation; Exercise Tolerance; Genes; Genetic; Goals; Gonadal Steroid Hormones; Growth; Hereditary Disease; High Resolution Computed Tomography; Histocompatibility Testing; Image; Imaging Techniques; Immunohistochemistry; Interstitial Lung Diseases; Langerhans-Cell Histiocytosis; Leiomyoma; Lesion; Leuprolide Acetate; Loss of Heterozygosity; Lung; Lung Lymphangioleiomyomatosis; Lung diseases; Lung nodule; Lymphangioleiomyomatosis; Lymphangiomyoma; Lymphatic; Methods; Molecular Target; Monoclonal Antibodies; Mutation; Neoplasm Metastasis; Operative Surgical Procedures; Organ; Outcome; Pathogenesis; Pathology; Patients; Pattern; Pelvis; Pharmaceutical Preparations; Proteins; Pulmonary Embolism; Pulmonary Emphysema; Pulmonary function tests; Quality of life; Records; Reporting; Respiratory physiology; Role; Scanning; Severities; Sirolimus; Smooth Muscle; Smooth Muscle Myocytes; Smooth Muscle Tumor; Specimen; Structure; Structure of parenchyma of lung; Sum; Symptoms; Syndrome; TSC1 gene; TSC2 gene; Techniques; Texture; Therapy Clinical Trials; Thoracic Radiography; Tissues; Treatment Protocols; Tuberous sclerosis protein complex; Tumor Burden; Uterine Fibroids; Uterine myomectomy; Uterus; Woman; X-Ray Computed Tomography; aged; base; cohort; double-blind placebo controlled trial; drug withdrawal; effective therapy; effusion; immunoreactivity; improved; interstitial; longitudinal analysis; mTOR protein; melanoma; neoplastic cell; pulmonary function; reproductive; tool; trend; tumor; vector

Explanation Benign metastasizing leiomyoma and lymphangioleiomyomatosis (LAM) are both characterized by abnormal proliferation of smooth muscle-like cells in the lung. A 32 year-old African woman was given a diagnosis of LAM based on a lung biopsy showing proliferation of smooth muscle cells with focal reactivity to HMB45, a monoclonal antibody that recognizes gp100, a melanoma antigen. She subsequently underwent myomectomy for uterine fibroids. The patients disease continued to progress, with an interstitial pattern seen on chest X-ray. Given the unusual course and presentation, a repeat lung biopsy was performed and an alternative diagnosis of benign metastasizing leiomyoma was made. Treatment with leuprolide acetate decreased pulmonary infiltrates and improved lung function and exercise tolerance. Accurately diagnosing benign metastasizing leiomyoma has important implications for clinical outcome. Since its clinical presentation may be misleading, immunohistochemistry techniques may assist in differentiating benign metastasizing leiomyoma from LAM. This is important because in BML, reduced tumor burden and improved pulmonary function may be achieved by suppressing gonadal steroids. This was found to be the case with the patient described here. Limited data are available regarding the role of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) as diagnostic tools in pulmonary Langerhans Cell Histiocytosis (LCH) and lymphangioleiomyomatosis (LAM). The aim of this study was to assess the value of these two techniques in the diagnosis of these cystic lung diseases. Records of 452 patients with the presumptive diagnosis of interstitial lung disease were reviewed; 67 had a clinical-radiological diagnosis of either LCH (n=27) or LAM (n= 40). Of 16 patients with LCH who underwent BAL, four specimens (25%) contained cells which had positive immunoreactivity for CD1a. Of three patients with negative BAL fluid who had TBB, one had a positive tissue diagnosis. Surgical lung biopsy was diagnostic in ten patients (5 with negative BAL fluid). Standard examination of BAL fluid was of no diagnostic value in LAM. TBB biopsies in six of seven LAM patients (85%) were diagnostic and did not result in complications. In thirteen LAM patients who underwent surgical lung biopsies, a histopathologic diagnosis was obtained. BAL may assist in the diagnosis of LCH whereas TBB has less value. TBB is useful in the diagnosis of LAM, thus avoiding the need for surgical biopsy. The aim of this study was to determine whether a computed tomography (CT)-based method assessing tissue texture demonstrates lung lesions, grades their severity, and evaluates lung tissue in areas adjacent to or remote from cysts, in patients with lymphangioleiomyomatosis. 326 CT scans from 52 patients were studied. After segmenting the lungs and subdividing images into texture blocks, a multi-dimensional feature vector composed of 25 texture features was used to differentiate and group each texture block. Cysts were outlined, and texture around the cysts and in regions away from cysts, was analyzed. Longitudinal analysis was conducted on the sequential CT scans and the pulmonary function tests to assess the trend of change. Histopathological examination was performed on biopsies from 45 patients, 20 of whom were part of the radiologic cohort. Differences in texture features between areas adjacent to and remote from the cysts were observed. Cyst score and sum entropy in areas around the cysts correlated with lung function (p<0.0001). Emphysematous-like changes in non-cystic areas were identified in lung tissue from 31 of 45 patients. A computational method that uses texture analysis and feature correlation, can identify and quantify cystic areas where LAM exists, and detect abnormalities in areas near cysts. Pathological data also demonstrate lung damage in areas adjacent to cysts. Several texture features correlate with lung function. Decline in lung function paralled changes in texture features. In LAM, cystic changes alone may not define the extent of lung destruction. Normal-appearing areas of the chest CT scan correlate with pulmonary function and course of disease.

解释 良性转移平滑肌瘤和淋巴血管瘤瘤病（L​​AM）的特征都以肺中平滑肌样细胞的异常增殖。 一名32岁的非洲妇女基于肺活检，显示出对平滑肌细胞的扩散，对HMB45的反应性（一种识别GP100，一种黑色素瘤抗原）的局灶性反应性。随后，她接受了子宫肌瘤的肌瘤切除术。 患者疾病继续进展，胸部X射线上看到了间隙模式。考虑到异常的过程和表现，进行了重复的肺活检，并进行了良性转移平滑肌瘤的替代诊断。 用乙酸亮油乙酸盐治疗可降低肺浸润，并提高肺功能和运动耐受性。准确诊断良性转移平滑肌瘤对临床结果具有重要意义。 由于其临床表现可能具有误导性，因此免疫组织化学技术可能有助于区分良性转移平滑肌瘤和LAM。 这很重要，因为在BML中，可以通过抑制性腺类固醇来实现肿瘤负担减轻和改善的肺功能。 发现此处描述的患者是这种情况。 关于支气管肺泡灌洗（BAL）和经支气管肺活检（TBB）作为肺Langerhans细胞组织（LCH）和淋巴结杆菌病（LAM）中的诊断工具的作用有限。 这项研究的目的是评估这两种技术在诊断这些囊性肺疾病中的价值。审查了452例假定诊断性质肺疾病的患者的记录； 67具有LCH（n = 27）或LAM（n = 40）的临床放射学诊断。在接受BAL的16例LCH患者中，有4个标本（25％）包含CD1A免疫反应阳性的细胞。在三名患有TBB的BAL流体负液的患者中，一名患有阳性组织诊断。 手术肺活检在十名患者中诊断为诊断（5例巴尔液负液）。 BAL流体的标准检查在LAM中无诊断值。七名LAM患者中有六名（85％）的TBB活检是诊断性的，没有导致并发症。在接受手术肺活活检的13名LAM患者中，获得了组织病理学诊断。 BAL可能有助于诊断LCH，而TBB的价值较小。 TBB可用于诊断LAM，因此避免了需要手术活检。 这项研究的目的是确定评估组织纹理的计算机断层扫描（CT）方法是否证明了肺部病变，逐渐严重，并评估淋巴结瘤病患者的肺部组织的肺部组织，并远离囊肿或远离囊肿的区域。研究了52例患者的326次CT扫描。将肺部和细分图像分割成纹理块后，使用由25种纹理特征组成的多维特征向量进行区分和分组每个纹理块。 概述了囊肿，并分析了囊肿周围和远离囊肿区域的质地。 对顺序CT扫描和肺功能测试进行了纵向分析，以评估变化的趋势。 对45例患者的活检进行了组织病理学检查，其中20例是放射线队列的一部分。观察到与囊肿相邻的区域之间的纹理特征差异。囊肿周围区域的囊肿评分和熵与肺功能相关（p <0.0001）。从45例患者中有31例，在肺组织中鉴定出非囊肿区域的过滤样变化。一种使用纹理分析和特征相关性的计算方法，可以识别和量化存在LAM的囊性区域，并检测囊肿附近区域的异常。病理数据还证明了与囊肿相邻区域的肺损伤。几种纹理特征与肺功能相关。肺功能下降与纹理特征的变化相位。在LAM中，仅囊性变化可能无法定义肺部破坏的程度。胸部CT扫描的正常表现区域与肺功能和疾病病程相关。