肺类癌型微小瘤的临床病理及其形态发生分析

Analysis of clinicopathologic features and morphogenesis of carcinoid tumorlets in the lung with bronchiectasis

目的 描述肺类癌型微小瘤的病理特征和免疫表型 ,探讨其发生的形态学基础。方法 对 3例支气管扩张症 (支扩 )伴发微小瘤进行临床病理学观察 ,另 11例支扩和 2例正常肺作对照 ;应用免疫组织化学EnVision法检测其特异性标志物和标记气道上皮内神经内分泌细胞 (NECs)。结果 肺类癌型微小瘤多为散发多灶性镜下结节 ,呈簇状、巢状或索团状 ,分布于支扩受损的支气管壁旁、细小支气管周围和瘢痕化的组织中 ;由短梭形或小圆形细胞构成 ,核呈圆形、椭圆或长椭圆形 ,染色深 ;胞质弱嗜酸性 ;细胞嗜银性强 ;强表达神经元特异性烯醇化酶 (NSE)、嗜铬素、降钙素、胃泌素等神经内分泌性标志物 ,小灶性表达绒毛膜促性腺激素 (HCG)、促肾上腺皮质激素 (ACTH)、5 羟色胺(5 HT) ,弱表达细胞角蛋白 (CK)、上皮膜抗原 (EMA)、S 10 0。微小瘤旁气道黏膜上皮NECs明显增生 ,比不伴微小瘤的支扩肺和正常肺气道黏膜上皮内NECs计数的差异均具有统计学意义 (P值均 <0 .0 0 1)。结论 肺微小瘤具有周围型典型性类癌的病理特征和免疫表型 ,可能是典型性类癌发生的早期阶段。

Objective To describe the clinicopathologic features and immunophenotypes of carcinoid tumorlets in the lung with bronchiectasis, and to study the morphogenesis of these tiny tumors. Methods The histopathologic characteristics of 3 bronchiectasis cases with carcinoid tumorlets, 11 bronchiectasis and 2 normal lungs were studied. Specific markers of the tiny tumors and the number of neuroendocrine cells (NECs) in the airway mucosa were immunohistochemically detected by EnVision method. Results The tumorlets in the lungs presented as multi-focal nodules and most were displayed only under microscopy. These cells were arranged in clusters and foci of fascicles which were situated in the surrounding bronchial wall and bronchioles adjacent to bronchiectatic lesion, or in the scar tissues. The tiny tumors were consisted of short fusiform cells and small ovoid cells. Their nuclei were circular, oval or long fusiform and the cells were strongly argyrophilic on Grimelius staining. Intensive positive immunostaining for calcitonin, chromogranin A, NSE and gastrin were detected. Weak positive for CK, EMA, S-100 and focal positive for HC, ACTH, 5-HT were also observed. Proliferative NECs in airway mucosa adjacent to the tiny tumors increased significantly in number, compared with those in the airway mucosa of bronchiectasis without tumorlets and normal lungs (P<0.001, respectively). Conclusions The clinicopathologic features and immunophenotypes of carcinoid tumorlets resemble carcinoid tumors. They are the early stage of carcinoid development. Their development may be related to the chronic pulmonary damage resulting in hypoxia and stimulating the proliferation of NECs. These pulmonary carcinoid tumorlets can be used as a model to study the tumorigenesis of carcinoid carcinoma of the lung.