Lung cysts in Birt-Hogg-Dubé syndrome: Histopathological characteristics and aberrant sequence repeats
Article first published online: 24 SEP 2009
© 2009 The Authors. Journal compilation © 2009 Japanese Society of Pathology
Volume 59, Issue 10, pages 720–728, October 2009
How to Cite
Koga, S., Furuya, M., Takahashi, Y., Tanaka, R., Yamaguchi, A., Yasufuku, K., Hiroshima, K., Kurihara, M., Yoshino, I., Aoki, I. and Nakatani, Y. (2009), Lung cysts in Birt-Hogg-Dubé syndrome: Histopathological characteristics and aberrant sequence repeats. Pathology International, 59: 720–728. doi: 10.1111/j.1440-1827.2009.02434.x
- Issue published online: 24 SEP 2009
- Article first published online: 24 SEP 2009
- Received 2 April 2009. Accepted for publication 8 June 2009.
- alveolar cysts;
- Birt-Hogg-Dubé syndrome;
- sequence repeat
Birt-Hogg-Dubé (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.