Cool Carlyne D, Groshong Steve D, Rai Pradeep R, Henson Peter M, Stewart J Scott, Brown Kevin K
Departments of Medicine and Pathology, University of Colorado Health Sciences Center; and Interstitial Lung Disease Program, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Am J Respir Crit Care Med. 2006 Sep 15;174(6):654-8. doi: 10.1164/rccm.200602-205OC. Epub 2006 Jun 23.
Usual interstitial pneumonia (UIP), the pathologic correlate of idiopathic pulmonary fibrosis, contains characteristic discrete areas of fibroblasts, myofibroblasts, and newly formed collagen, termed "fibroblast foci." These lesions are argued to represent isolated sites of recurrent acute lung injury and suggested to be the mechanism of disease progression. We hypothesized that, rather than isolated, these lesions are part of an organized neoplasm.
Morphometric analysis of pentachrome-stained histologic sections of UIP was performed. Using point-counting technique on serial sections, fibroblast foci, arteries, and macrophage clusters were identified and we determined their individual "connectiveness" by estimating the Euler number. Two-dimensional micrographs were collated into a three-dimensional array from which a visual three-dimensional reconstruction could be constructed. Clonality analysis was performed using human androgen receptor gene methylation assay.
Blood vessels show significant connectivity with a Euler number of 2, whereas macrophage clusters exhibited no connectivity. The fibroblast foci showed a high level of interconnection with Euler numbers ranging from 19 to 39. The computer generated three-dimensional models provide a visual confirmation of this connectiveness. Human androgen receptor gene methylation assay analysis of the foci showed balanced methylation consistent with polyclonality.
The fibroblast foci of UIP are the leading edge of a complex reticulum that is highly interconnected and extends from the pleura into the underlying parenchyma. It is a reactive, rather than a malignant, process.
普通型间质性肺炎（UIP）是特发性肺纤维化的病理对应物，包含成纤维细胞、肌成纤维细胞和新形成的胶原蛋白的特征性离散区域，称为“成纤维细胞灶”。这些病变被认为代表反复发生的急性肺损伤的孤立部位，并被认为是疾病进展的机制。我们假设，这些病变并非孤立存在，而是一个有组织的肿瘤的一部分。
对UIP的五染色组织切片进行形态计量分析。使用连续切片的点计数技术，识别成纤维细胞灶、动脉和巨噬细胞簇，并通过估计欧拉数来确定它们各自的“连通性”。将二维显微照片整理成三维阵列，从中构建可视化的三维重建。使用人类雄激素受体基因甲基化检测进行克隆性分析。
血管显示出显著的连通性，欧拉数为2，而巨噬细胞簇没有连通性。成纤维细胞灶显示出高度的相互连接，欧拉数范围为19至39。计算机生成的三维模型直观地证实了这种连通性。对这些病灶的人类雄激素受体基因甲基化检测分析显示甲基化平衡，与多克隆性一致。
UIP的成纤维细胞灶是一个复杂网状结构的前沿，该网状结构高度相互连接，从胸膜延伸至下方的实质组织。这是一个反应性过程，而非恶性过程。
