unilayered or multilayered groups of cells. CK5/6 was heterogeneously positive, frequently in luminal cells. P63 was negative in the NEH tumorlets and foci (including in luminal cells). Lymphocytes were detected at proximity for some of the NEH lesions. Of interest would be the heterogeneous expression of CK5/6 in the chromogranin-positive and TTF1-positive NEH foci. The expression of CK5/6 in luminal cells, as compared with the normal expression pattern in basal cells of normal bronchial-type epithelia (Supplementary Fig. 1, Supplemental Digital Content 1, http://links.lww.com/AIMM/A246), suggested that the chromogranin-positive hyperplastic or proliferative cells (negative for CK5/6) develop extraluminally, toward the alveolar septum tissue rather than toward the lumina, possibly “pushing” luminally the CK5/6-positive cells. Interestingly, p63 was negative in these foci, including in luminal cells, whereas it was positive in the adjacent bronchiolar or bronchiolar-metaplasia– type epithelium. The presence of chromograninpositive NEH lesions in alveolar septa suggest a multistep process, of bronchiolar metaplasia of the alveoli, undergoing a second change, that of NEH. In conclusion, NEH foci may show CK5/6 immunohistochemical heterogeneity, suggesting an origin from bronchiolar-metaplasia epithelia besides that from the bronchiolar epithelium.

中文翻译：

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HER2阳性转移性黑色素瘤

单层或多层细胞群。CK5/6 呈异质性阳性，常在腔细胞中。P63 在 NEH 小瘤和病灶（包括管腔细胞）中呈阴性。在一些NEH病变附近检测到淋巴细胞。感兴趣的是 CK5/6 在嗜铬粒蛋白阳性和 TTF1 阳性 NEH 病灶中的异质表达。与正常支气管型上皮细胞基底细胞中正常表达模式相比，CK5/6 在腔细胞中的表达（补充图 1，补充数字内容 1，http://links.lww.com/AIMM/A246 )，表明嗜铬粒蛋白阳性增生或增殖细胞（CK5/6 阴性）在腔外发育，朝向肺泡间隔组织而不是朝向腔，可能“推动”腔内 CK5/6 阳性细胞。有趣的是，p63 在这些病灶中呈阴性，包括在管腔细胞中，而在相邻的细支气管或细支气管-化生型上皮细胞中呈阳性。肺泡间隔中嗜铬粒蛋白阳性 NEH 病变的存在表明肺泡细支气管化生的多步骤过程，经历了第二个变化，即 NEH。总之，NEH 病灶可能显示 CK5/6 免疫组织化学异质性，表明除了来自细支气管上皮外，还来自细支气管 - 化生上皮。