Birt-Hogg-Dubé syndrome: a literature review and case study of a Chinese woman presenting a novel FLCN mutation

Abstract

Background: The Birt-Hogg-Dubé (BHD) syndrome is a very rare autosomal dominant form of genodermatosis caused by germline mutations in the folliculin (FLCN) gene, which is mapped to the p11.2 region in chromosome 17. BHD commonly presents cutaneous fibrofolliculomas, pulmonary cysts, renal cell carcinoma, and recurrent pneumothoraxes. The disease is easily ignored or misdiagnosed as pneumothorax, pulmonary lymphangiomyomatosis (LAM), or emphysema. Follow-up and guidelines for managing recurrent pneumothoraxes in these patients are lacking.

Case presentation: We reported the case of a 56-year-old Chinese woman who presented skin lesions, multiple lung bubblae, recurrent pneumothoraxes, thyroid nodules, and pulmonary inflammatory pseudotumors (PITs). The patient had a family history of pneumothoraxes and renal tumor. The BHD diagnosis was confirmed by genetic testing, which revealed a novel FLCN mutation in exon 14. Furthermore, the patient underwent a bullectomy because of recurrent pneumothorax 6 years ago.

Conclusion: To our knowledge, the novel mutation in exon 14 and the manifestation of PIT in the present case have never been reported for BHD. The patient underwent a bullectomy previously with no relapse at the last follow-up before the preparation of this report, thereby suggesting that thoracotomy with bullectomy may be a possible therapeutic approach for some BHD patients with recurrent pneumothorax.

Keywords: Birt–Hogg–Dubé syndrome; Lung bubblae; Mutation; Pneumothorax; Treatment.

Fig. 1

Multiple pale and dome-shaped macules over the patient’s face, which are characteristic skin lesions of BHD syndrome

Fig. 2

Histopathological features of the resected lung specimens from the patient 6 years ago. Cysts are indicated by stars. a These cysts are incorporated with interstitial stroma of the interlobular septum or pleura (hematoxylin–eosin–safranin staining). Cysts lined by b CK7⁺ and c TTF-1⁺ pneumocytes. d D2-40 is negative in the lining (thin arrows) but positive in lymphatics (thick arrow)

Fig. 3

Postoperative changes are shown in the right lung. a, c The previous CT scan shows numerous cysts in the lung bases; one dominant cyst measures 8.4 cm × 5.1 cm in the right lung and contains some liquid; another huge cyst is anterior to the heart (white arrow). b, d The right lung expanded well after the operation with no obvious scar or atelectasis. Some cysts remained stable (black arrow) or became even smaller (white arrow). However, more cysts appeared in the lung bases (thick arrow)

Fig. 4

Chest CT scan with pulmonary pseudotumor. a Previous CT scan shows a fibrous change in the same slice. b The present CT scan shows a 2.8 cm × 2.3 cm pulmonary solid lesion with irregular margins and adjacent pleural thickness. c, d Corresponding mediastinal window

Fig. 5

Ultrosound-guided needle biopsy of the lung lesion with immunohistochemistry showed that it is positive for an inflammatory pesudotumor with a extensively hyperplasic fibrous and inflammatory cell infiltration, and b necrosis lung tissues

Fig. 6

Identification of a germline heterozygous FLCN mutation in the patients. The result showed a heterozygous mutation in exon 14 resulting in an animo acid transformation of phenylalanine into serine (p.Phe766Ser)