대한흉부영상의학회 Weekly Chest Cases

Case No : 699 Date 2011-03-22

Courtesy of Hwan-Seok Yong, Eun-Young Kang, Yun Kyoung Kim. / Korea University Guro Hospital
Age/Sex 54 / F
Chief ComplaintDyspnea, cough and chest pain

Figure 1
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Fig.1

Diagnosis With Brief Discussion

Diagnosis: Birt-Hogg-Dube (BHD) syndrome
Radiologic Findings: Chest CT scan after closed thoracostomy revealed multiple thin-walled cysts and bullae in both lungs (Figs. 1-3). They were round or oval shaped and some of them showed lobulating contour. The intervening lung parenchyma between the cysts was normal without any evidence of pulmonary nodule or fibrosis. She had a history of closed thoracostomy due to right pneumothorax 35 years ago. She had multiple whitish papules measuring 2-3 mm on her cheek, and punch biopsy was performed. The pathologic result was perifollicular fibrosis, consistent with histologic diagnosis of fibrofolliculoma. Ultrasonography of the kidneys did not show any abnormality.
Brief Review: Birt-Hogg-Dube (BHD) syndrome is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal tumors, and multiple lung cysts with or without spontaneous pneumothorax (1-3). Fibrofolliculomas usually appear as multiple, dome-shaped, whitish papules in the face (4, 5). Patients with BHD syndrome have a 7-fold increased risk of developing renal neoplasm and the most life-threatening complication of BHD syndrome is renal cancer (4, 6). More than 80% of adult patients with BHD syndrome have multiple lung cysts. Despite the presence of multiple lung cysts, lung function is usually unaffected (7). The histology of pleuropulmonary lesions include intraparenchymal collections of air surrounded by normal parenchyma or a thin fibrous wall and blebs within the pleura (8). Patients with BHD syndrome have a 50-fold increased risk of spontaneous pneumothorax (6).
Clinical diagnosis of BHD syndrome requires a fulfillment of one major or two minor criteria. Major criteria include: 1) at least five fibrofolliculomas, at least one histologically confirmed; 2) pathogenic FLCN germline mutation. Minor criteria include: 1) multiple lung cysts, bilateral basally located, with or without spontaneous pneumothorax; 2) renal cancer, early onset (<50 years) or multifocal or bilateral; 3) a first-degree relative with BHD syndrome (5).
In the analysis of thin-section CT findings of pulmonary cysts in 12 patients with genetically diagnosed BHD syndrome, multiple, irregular-shaped cysts of various sizes with lower medial lung zone predominance were characteristic for BHD syndrome. In addition, cysts abutting or including the proximal portions of lower pulmonary arteries or veins were found in all patients (9).
References: 1. Birt AR, Hogg GR, Dube WJ. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol 1977;113:1674-1677
2. Schmidt LS, Warren MB, Nickerson ML, Weirich G, Matrosova V, Toro JR, et al. Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet 2001;69:876-882
3. Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, et al. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell 2002;2:157-164
4. Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, et al. Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube syndrome. Am J Hum Genet 2005;76:1023-1033
5. Menko FH, van Steensel MA, Giraud S, Friis-Hansen L, Richard S, Ungari S, et al. Birt-Hogg-Dube syndrome: diagnosis and management. Lancet Oncol 2009;10:1199-1206
6. Zbar B, Alvord WG, Glenn G, Turner M, Pavlovich CP, Schmidt L, et al. Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dube syndrome. Cancer Epidemiol Biomarkers Prev 2002;11:393-400
7. Toro JR, Pautler SE, Stewart L, Glenn GM, Weinreich M, Toure O, et al. Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dube syndrome. Am J Respir Crit Care Med 2007;175:1044-1053
8. Butnor KJ, Guinee DG Jr. Pleuropulmonary pathology of Birt-Hogg-Dube syndrome. Am J Surg Pathol 2006;30:395-399
9. Tobino K, Gunji Y, Kurihara M, Kunogi M, Koike K, Tomiyama N, et al. Characteristics of pulmonary cysts in Birt-Hogg-Dube syndrome: Thin-section CT findings of the chest in 12 patients. Eur J Radiol Forthcoming 2009
Keywords: Lung, Multiple organ, Interstitial lung disease, Genetic disorder, ILD,

No. of Applicants : 120

▶ Correct Answer : 24/120, 20.0%

- Oita University, Faculty of Medicine , Japan Fumito Okada
- Yokohama-asahi-chuo-general hospital , Japan Kyoko Nagai
- Okayama University , Japan Akihiro Tada
- Saga University , Japan Ryoko Egashira
- Youngdong Hospital , Korea (South) Sang Min Lee
- Shiga university of medical science , Japan Akitoshi Inoue
- m2comm , Korea (South) admin master
- Ishikawa Matto Central Hospital , Japan Manabu Akimoto
- Diskapi Yildirim Beyazit Hospital, Ankara , Turkey Meric Tuzun
- IRSA La Rochelle France , France Denis Chabassiere
- HSC , Brazil Diogo Pinheiro
- Kobe City Medical Center General Hospital , Japan Hitomi Nagano
- All India Institute of Medical Sciences , India Ashish Gupta
- Okayama university , Japan Mayu Uka
- , Korea (South) sang young oh
- CH de la C�te Basque , France Paul ARDILOUZE
- Toyama University Hospital, Laboratory of Pathology , Japan TOMONORI TANAKA
- Onomichi municipal hospital , Japan Ryotaro Kishi
- nipppon medical school musashikosugi hospital , Japan saiko isshiki
- SAISEIKAI KURIHASHI HOSPITAL , Japan YASUO OOKUBO
- IRCCS Istituto Oncologico - Bari , Italy Carlo Florio
- McGill University Health Center , Canada Alexandre Semionov
- Saint Malo , France jean-baptiste Noel
- Asan Medial center , Korea (South) Chae Lim

▶ Correct Answer as Differential Diagnosis : 10/120, 8.3%

- Fukuyama daiichi Hospital , Japan Mototsugu Saeki
- Onomichi municipal hospital , Japan Hirofumi Mifune
- Az Osp Santa Maria , Italy angelo carloni
- Osaka University , Japan Hiromitsu Sumikawa
- University of British Columbia , Canada Amr Ajlan
- Gifu Chuo Hospital , Japan Yo Kaneko
- Radiology , Korea (South) YOONAH SONG
- Hanyang University Hospital , Korea (South) Jina Park
- Mallinckrodt Institute of Radiology , United States Naganathan Mani
- Hospital Sotiria, Athens, Greece , Greece Vasilios Tzilas

대한흉부영상의학회 Korean Society of Thoracic Radiology

Archive of Old Cases

Case No : 699 Date 2011-03-22

Discussion

No. of Applicants : 120