Lung cysts in Birt-Hogg-Dube syndrome: Histopathological characteristics and aberrant sequence repeats
Lung cysts in Birt-Hogg-Dube syndrome: Histopathological characteristics and aberrant sequence repeats
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DOI：
10.1111/j.1440-1827.2009.02434.x
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发表时间：
2009-10-01
影响因子：
2.2
通讯作者：
Nakatani, Yukio
中科院分区：
文献类型：
--
作者：
Koga, Shunsuke;Furuya, Mitsuko;Nakatani, Yukio
Birt-Hogg-Dube（BHD）综合征是一种罕见的常染色体显性遗传疾病。受影响的患者易患皮肤纤维毛囊瘤、肾细胞瘤和肺囊肿，并伴有复发性气胸。与皮肤和肾脏中的肿瘤事件相反，肺囊肿经常与非肿瘤性变化（如水泡或大疱）混淆。本文报告一例多发性肺囊肿合并BHD综合征。病变的详细组织病理学特征也给出了。肺囊肿与周围小叶间隔、脏层胸膜或间隔胸膜交界区关系密切。这些囊肿部分邻接肺泡结构，并内衬一层肺泡上皮。这些独特的显微镜特征支持了BHD肺病变与其他类型的大疱性病变不同的观点。基因组DNA分析表明，一个异常的序列重复，造成移码突变。免疫组织化学显示，在患者和正常对照组的肺巨噬细胞和上皮细胞中，BHD基因编码蛋白滤泡素的定位。卵泡素的单倍不足可能导致肺泡发育紊乱，导致异常的囊性肺泡形成。BHD综合征患者的异常重复序列的独特突变模式也进行了审查。
Birt-Hogg-Dube (BHD) syndrome is a rare disorder inherited in an autosomal dominant manner. The affected patients are predisposed to cutaneous fibrofolliculomas, renal cell tumors and lung cysts with recurrent pneumothorax. Contrary to neoplastic events in the skin and the kidney, the lung cysts have frequently been confused with non-neoplastic changes such as blebs or bullae. Herein is reported a case of multiple lung cysts associated with BHD syndrome. Detailed histopathological characteristics of the lesion are also given. The lung cysts were closely associated with the peripheral interlobular septum, visceral pleura or septal-pleural junctional region. These cysts were partly abutting alveolar structures, and lined by a layer of alveolar epithelium. These unique microscopic features supported the notion that the BHD lung lesions are distinct from other types of bullous changes. Genomic DNA analysis indicated an aberrant sequence repeat that caused frameshift mutation. Immunohistochemistry showed the localization of folliculin, the BHD gene-encoding protein, in macrophages and epithelial cells in the patient's and normal control's lungs. Haploinsufficiency of folliculin may cause deranged alveolar development, leading to the aberrant cystic alveolar formation. The unique mutation patterns of abnormal sequence repeats in patients with BHD syndrome are also reviewed.