Characterization of the Pathogenesis of Lymphangioleiomyomatosis (LAM)

解释 良性转移性平滑肌瘤和淋巴管肌瘤病(LAM)均以肺内平滑肌样细胞异常增殖为特征。一名32岁的非洲妇女被诊断为LAM，因为肺活检显示平滑肌细胞增殖，对HMB45有局部反应，HMB45是一种识别黑色素瘤抗原gp100的单抗。随后，她因子宫肌瘤接受了子宫肌瘤切除术。患者病情继续发展，胸部X光片可见间质改变。考虑到这种不寻常的病程和表现，进行了重复的肺活检，并做出了良性转移性平滑肌瘤的替代诊断。醋酸亮丙瑞林治疗减少了肺浸润物，改善了肺功能和运动耐量。准确诊断良性转移性子宫肌瘤对临床预后有重要意义。由于其临床表现可能具有误导性，免疫组织化学技术有助于鉴别良性转移性子宫肌瘤和LAM。这一点很重要，因为在BML中，通过抑制性腺类固醇可以减少肿瘤负担和改善肺功能。发现这里描述的病人就是这种情况。 关于肺组织细胞增生症(LCH)和淋巴管肌瘤病(LAM)的诊断工具--支气管肺泡灌洗(BAL)和经支气管肺活检(TBB)的作用，现有的数据有限。本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。我们回顾了452例推定诊断为间质性肺疾病的患者的记录，其中67例临床-放射学诊断为LCH(n=27)或LAM(n=40)。在16例接受BAL的LCH患者中，4例(25%)含有CD1a免疫反应阳性的细胞。在三名BAL液阴性的患者中，有一人的组织诊断为阳性。手术肺活检确诊10例(5例BAL液阴性)。BAL液标准检查对LAM无诊断价值。7例LAM患者中有6例(85%)的TBB活检是诊断性的，没有导致并发症。13例LAM患者接受了外科肺活检，获得了组织病理学诊断。BAL有助于LCH的诊断，而TBB的诊断价值较低。TBB在LAM的诊断中是有用的，因此不需要手术活检。 本研究的目的是确定在淋巴管肌瘤病患者中，基于计算机断层扫描(CT)的评估组织结构的方法是否能显示肺部病变，对其严重程度进行分级，并评估邻近或远离囊肿区的肺组织。对52例患者的326次CT扫描进行了研究。在对肺部进行分割并将图像细分为纹理块后，使用由25个纹理特征组成的多维特征向量对每个纹理块进行区分和分组。包囊轮廓，并分析包囊周围和远离包囊区域的质地。对连续的CT扫描和肺功能检查进行纵向分析，以评估变化趋势。组织病理学检查来自45名患者的活检组织，其中20名是放射学队列的一部分。观察到邻近和远离囊肿区的纹理特征不同。包囊周围区域的包囊评分和总熵与肺功能相关(p&lt；0.0001)。在45例患者中，31例在非囊性区域发现肺气肿样改变。一种利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，并检测囊性区域附近的异常。病理数据也显示了邻近囊肿区的肺损伤。几个纹理特征与肺功能相关。肺功能的下降与质地特征的变化平行。在LAM中，单靠囊性改变可能不能定义肺破坏的程度。胸部CT扫描的正常区域与肺功能和病程相关。

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.