Characterization of the Pathogenesis of Lymphangioleiomyomatosis (LAM)

解释 良性转移性平滑肌瘤和淋巴管平滑肌瘤病（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，其诊断基于肺活检，肺活检显示平滑肌细胞增殖，对HMB 45具有局部反应性，HMB 45是一种识别gp100的单克隆抗体，一种黑色素瘤抗原。她随后接受了子宫肌瘤切除术。 患者的疾病继续进展，胸部X线检查显示间质性模式。由于不寻常的过程和表现，再次肺活检和良性转移平滑肌瘤的替代诊断。 醋酸亮丙瑞林治疗减少了肺浸润，改善了肺功能和运动耐量。正确诊断良性转移性平滑肌瘤对临床预后有重要意义。 由于其临床表现可能是误导，免疫组化技术可能有助于区分良性转移平滑肌瘤LAM。 这一点很重要，因为在BML中，可以通过抑制性腺类固醇来降低肿瘤负荷和改善肺功能。 这就是这里描述的病人的情况。 关于支气管肺泡灌洗（BAL）和经支气管肺活检（TBB）作为肺朗格汉斯细胞组织细胞增生症（LCH）和淋巴管平滑肌瘤病（LAM）诊断工具的作用，数据有限。 本研究的目的是评估这两种技术在这些囊性肺疾病的诊断价值。回顾了452例间质性肺疾病的假定诊断患者的记录; 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例标本（25%）含有CD1a免疫反应阳性的细胞。在3例BAL液阴性的TBB患者中，1例组织诊断阳性。 10例患者（5例BAL液阴性）进行了手术肺活检诊断。BAL液的标准检查对LAM没有诊断价值。7例LAM患者中有6例（85%）的TBB活检是诊断性的，未导致并发症。在13例接受手术肺活检的LAM患者中，获得了组织病理学诊断。BAL有助于LCH的诊断，TBB的诊断价值较低。 TBB在LAM的诊断中是有用的，从而避免了手术活检的需要。 本研究的目的是确定是否计算机断层扫描（CT）为基础的方法评估组织纹理显示肺病变，分级其严重程度，并评估肺组织在邻近或远离囊肿，在淋巴管平滑肌瘤病患者。对52例患者的326次CT扫描进行了研究。在对肺部图像进行分割和纹理块细分后，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。 概述囊肿，并分析囊肿周围和远离囊肿的区域的纹理。 对连续CT扫描和肺功能检查进行纵向分析，以评估变化趋势。 对45例患者的活检进行组织学检查，其中20例为放射学队列的一部分。邻近和远离囊肿的区域之间的纹理特征的差异进行了观察。囊肿周围区域的囊肿评分和总熵与肺功能相关（p <0.0001）。45例患者中有31例在肺组织中发现了非囊性区域的肺气肿样改变。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LAM存在的囊性区域，并检测囊肿附近区域的异常。病理学数据也显示囊肿附近区域的肺损伤。一些纹理特征与肺功能相关。肺功能的下降与纹理特征的变化并行。在LAM中，单纯的囊性改变可能不能定义肺破坏的程度。胸部CT扫描的正常表现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.